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Modifiable risk factors account for most of the dementia risk imposed by low socioeconomic status
LONDON – Twelve modifiable risk factors appear to account for more than half of the variation in dementia risk associated with socioeconomic status.
When integrated into an 18-point risk score, dubbed the “Lifestyle for Brain Health” (LIBRA) index, they accurately predicted dementia risk in more than 6,300 subjects who were followed for 7 years: Dementia risk increased by 30% for every 1-point increase on the LIBRA score, Sebastian Koehler, PhD, said at the Alzheimer’s Association International Conference.
According to Public Health England, 52% of citizens choose dementia prevention as a top health priority, but almost the same number believe that “there is nothing anyone can do to reduce their risk of getting dementia.” The LIBRA score could be employed as a public health measure to counteract that misunderstanding, he said.
“We can reduce the gap in risk that’s related to low socioeconomic status by improving health in that group. But we know that public health measures and messages are taken up much better by those with higher socioeconomic status. We think the first step is to raise awareness among this group that there is something we can do about dementia risk. And then we can reach out to this vulnerable group and design measures and messages that speak to both their needs and their resources.”
The 12 risk and protective factors were originally identified by epidemiologist Kay Deckers of Maastricht University, who drew them from a large meta-analysis published in 2015 (Int J Geriatr Psychiatry. 2015 Mar;30[3]:234-46).
They are the following:
• Diabetes.
• Hypertension.
• High cholesterol.
• Smoking.
• Obesity.
• Physical inactivity.
• Depression.
• Coronary heart disease.
• Kidney disease.
• Diet.
• Alcohol.
• Mental activity.
Dr. Koehler and his colleagues used them to create the weighted LIBRA score, which computes an 18-point risk level ranging from –5.9 (lower risk) to 12.7 (higher risk). Among the factors that reduce dementia risk are high cognitive activity, healthy diet or Mediterranean diet, and low-moderate alcohol intake. The others all increased risk. Each of the factors was assigned a point value based on its percentage of risk reduction or increase. For example, high cognitive activity reduced risk by more than 3 points, but depression increased it by 2 points. The investigators then validated this score on 6,346 participants in the English Longitudinal Study of Ageing, who were followed for up to 7 years.
Dr. Koehler’s study, however, was not just a LIBRA validation study. He wanted to correlate these protective and endangering factors with each subject’s socioeconomic status, and determine how much of the risk difference generally accredited to wealth was related to the LIBRA factors.
After 7 years, about 9% of the study sample developed incident dementia. These subjects were significantly older than those who didn’t (77 vs. 64 years). They were more likely to have lower education attainment (58% vs. 37%), and more likely to be poor (44% vs. 29%).
On the LIBRA risk factors, the participants who developed dementia were significantly more likely to have heart disease, diabetes, hypercholesterolemia, hypertension, and depression, although not significantly more likely to be obese or to smoke.
On the LIBRA protective factors, they were significantly less likely to be low-moderate alcohol users (37% vs. 57%), to have high cognitive activity (17% vs. 45%), and significantly more likely to be physically inactive (59% vs. 24%).
Two survival curves compared the incidence of dementia related to wealth and LIBRA score. Subjects of low socioeconomic status experienced an increase in dementia risk very similar to those with high LIBRA scores. Dr. Koehler also conducted three analyses that examined the effects of wealth on dementia risk: the total effect of wealth, the direct effect of wealth, and what he called the “indirect wealth effect.” This examined the impact of wealth on LIBRA scores, followed by the effect of these scores on dementia risk.
This final model concluded that 56% of the risk imposed by low socioeconomic status was actually attributable to LIBRA scores. In other words, low socioeconomic status was directly tied to both increases in physical and mental risk factors, and decreases in physical and mental protective factors.
“Health inequalities influencing dementia risk exist because of socioeconomic differences between people,” Dr. Koehler said. “People with less wealth have a higher frequency of being exposed to risk factors for dementia that are potentially treatable.”
The LIBRA study is part of a larger dementia prevention study called Innovative, Midlife Intervention for Dementia Deterrence (In-MINDD). Dr. Koehler had no financial disclosures.
[email protected]
On Twitter @alz_gal
LONDON – Twelve modifiable risk factors appear to account for more than half of the variation in dementia risk associated with socioeconomic status.
When integrated into an 18-point risk score, dubbed the “Lifestyle for Brain Health” (LIBRA) index, they accurately predicted dementia risk in more than 6,300 subjects who were followed for 7 years: Dementia risk increased by 30% for every 1-point increase on the LIBRA score, Sebastian Koehler, PhD, said at the Alzheimer’s Association International Conference.
According to Public Health England, 52% of citizens choose dementia prevention as a top health priority, but almost the same number believe that “there is nothing anyone can do to reduce their risk of getting dementia.” The LIBRA score could be employed as a public health measure to counteract that misunderstanding, he said.
“We can reduce the gap in risk that’s related to low socioeconomic status by improving health in that group. But we know that public health measures and messages are taken up much better by those with higher socioeconomic status. We think the first step is to raise awareness among this group that there is something we can do about dementia risk. And then we can reach out to this vulnerable group and design measures and messages that speak to both their needs and their resources.”
The 12 risk and protective factors were originally identified by epidemiologist Kay Deckers of Maastricht University, who drew them from a large meta-analysis published in 2015 (Int J Geriatr Psychiatry. 2015 Mar;30[3]:234-46).
They are the following:
• Diabetes.
• Hypertension.
• High cholesterol.
• Smoking.
• Obesity.
• Physical inactivity.
• Depression.
• Coronary heart disease.
• Kidney disease.
• Diet.
• Alcohol.
• Mental activity.
Dr. Koehler and his colleagues used them to create the weighted LIBRA score, which computes an 18-point risk level ranging from –5.9 (lower risk) to 12.7 (higher risk). Among the factors that reduce dementia risk are high cognitive activity, healthy diet or Mediterranean diet, and low-moderate alcohol intake. The others all increased risk. Each of the factors was assigned a point value based on its percentage of risk reduction or increase. For example, high cognitive activity reduced risk by more than 3 points, but depression increased it by 2 points. The investigators then validated this score on 6,346 participants in the English Longitudinal Study of Ageing, who were followed for up to 7 years.
Dr. Koehler’s study, however, was not just a LIBRA validation study. He wanted to correlate these protective and endangering factors with each subject’s socioeconomic status, and determine how much of the risk difference generally accredited to wealth was related to the LIBRA factors.
After 7 years, about 9% of the study sample developed incident dementia. These subjects were significantly older than those who didn’t (77 vs. 64 years). They were more likely to have lower education attainment (58% vs. 37%), and more likely to be poor (44% vs. 29%).
On the LIBRA risk factors, the participants who developed dementia were significantly more likely to have heart disease, diabetes, hypercholesterolemia, hypertension, and depression, although not significantly more likely to be obese or to smoke.
On the LIBRA protective factors, they were significantly less likely to be low-moderate alcohol users (37% vs. 57%), to have high cognitive activity (17% vs. 45%), and significantly more likely to be physically inactive (59% vs. 24%).
Two survival curves compared the incidence of dementia related to wealth and LIBRA score. Subjects of low socioeconomic status experienced an increase in dementia risk very similar to those with high LIBRA scores. Dr. Koehler also conducted three analyses that examined the effects of wealth on dementia risk: the total effect of wealth, the direct effect of wealth, and what he called the “indirect wealth effect.” This examined the impact of wealth on LIBRA scores, followed by the effect of these scores on dementia risk.
This final model concluded that 56% of the risk imposed by low socioeconomic status was actually attributable to LIBRA scores. In other words, low socioeconomic status was directly tied to both increases in physical and mental risk factors, and decreases in physical and mental protective factors.
“Health inequalities influencing dementia risk exist because of socioeconomic differences between people,” Dr. Koehler said. “People with less wealth have a higher frequency of being exposed to risk factors for dementia that are potentially treatable.”
The LIBRA study is part of a larger dementia prevention study called Innovative, Midlife Intervention for Dementia Deterrence (In-MINDD). Dr. Koehler had no financial disclosures.
[email protected]
On Twitter @alz_gal
LONDON – Twelve modifiable risk factors appear to account for more than half of the variation in dementia risk associated with socioeconomic status.
When integrated into an 18-point risk score, dubbed the “Lifestyle for Brain Health” (LIBRA) index, they accurately predicted dementia risk in more than 6,300 subjects who were followed for 7 years: Dementia risk increased by 30% for every 1-point increase on the LIBRA score, Sebastian Koehler, PhD, said at the Alzheimer’s Association International Conference.
According to Public Health England, 52% of citizens choose dementia prevention as a top health priority, but almost the same number believe that “there is nothing anyone can do to reduce their risk of getting dementia.” The LIBRA score could be employed as a public health measure to counteract that misunderstanding, he said.
“We can reduce the gap in risk that’s related to low socioeconomic status by improving health in that group. But we know that public health measures and messages are taken up much better by those with higher socioeconomic status. We think the first step is to raise awareness among this group that there is something we can do about dementia risk. And then we can reach out to this vulnerable group and design measures and messages that speak to both their needs and their resources.”
The 12 risk and protective factors were originally identified by epidemiologist Kay Deckers of Maastricht University, who drew them from a large meta-analysis published in 2015 (Int J Geriatr Psychiatry. 2015 Mar;30[3]:234-46).
They are the following:
• Diabetes.
• Hypertension.
• High cholesterol.
• Smoking.
• Obesity.
• Physical inactivity.
• Depression.
• Coronary heart disease.
• Kidney disease.
• Diet.
• Alcohol.
• Mental activity.
Dr. Koehler and his colleagues used them to create the weighted LIBRA score, which computes an 18-point risk level ranging from –5.9 (lower risk) to 12.7 (higher risk). Among the factors that reduce dementia risk are high cognitive activity, healthy diet or Mediterranean diet, and low-moderate alcohol intake. The others all increased risk. Each of the factors was assigned a point value based on its percentage of risk reduction or increase. For example, high cognitive activity reduced risk by more than 3 points, but depression increased it by 2 points. The investigators then validated this score on 6,346 participants in the English Longitudinal Study of Ageing, who were followed for up to 7 years.
Dr. Koehler’s study, however, was not just a LIBRA validation study. He wanted to correlate these protective and endangering factors with each subject’s socioeconomic status, and determine how much of the risk difference generally accredited to wealth was related to the LIBRA factors.
After 7 years, about 9% of the study sample developed incident dementia. These subjects were significantly older than those who didn’t (77 vs. 64 years). They were more likely to have lower education attainment (58% vs. 37%), and more likely to be poor (44% vs. 29%).
On the LIBRA risk factors, the participants who developed dementia were significantly more likely to have heart disease, diabetes, hypercholesterolemia, hypertension, and depression, although not significantly more likely to be obese or to smoke.
On the LIBRA protective factors, they were significantly less likely to be low-moderate alcohol users (37% vs. 57%), to have high cognitive activity (17% vs. 45%), and significantly more likely to be physically inactive (59% vs. 24%).
Two survival curves compared the incidence of dementia related to wealth and LIBRA score. Subjects of low socioeconomic status experienced an increase in dementia risk very similar to those with high LIBRA scores. Dr. Koehler also conducted three analyses that examined the effects of wealth on dementia risk: the total effect of wealth, the direct effect of wealth, and what he called the “indirect wealth effect.” This examined the impact of wealth on LIBRA scores, followed by the effect of these scores on dementia risk.
This final model concluded that 56% of the risk imposed by low socioeconomic status was actually attributable to LIBRA scores. In other words, low socioeconomic status was directly tied to both increases in physical and mental risk factors, and decreases in physical and mental protective factors.
“Health inequalities influencing dementia risk exist because of socioeconomic differences between people,” Dr. Koehler said. “People with less wealth have a higher frequency of being exposed to risk factors for dementia that are potentially treatable.”
The LIBRA study is part of a larger dementia prevention study called Innovative, Midlife Intervention for Dementia Deterrence (In-MINDD). Dr. Koehler had no financial disclosures.
[email protected]
On Twitter @alz_gal
AT AAIC 2017
Key clinical point:
Major finding: The factors accounted for 56% of the risk imposed by low SES.
Data source: The LIBRA validation study comprised more than 6,300 subjects.
Disclosures: The LIBRA study is part of a larger dementia prevention study called In-MINDD. Dr. Koehler had no financial disclosures.
Racial differences in dementia risk persist from midlife to oldest old
LONDON – The racial and ethnic patterns of dementia risk seen in older adults appear to hold steady even in the oldest old, with blacks about 30% more likely than are whites to develop the disorder even well into their 90s.
The magnitude of disparity remained consistent even after researchers controlled for traditional risk factors such as access to health care, cardiovascular risk, stroke, and education, Maria Corrada, ScD, said at the Alzheimer’s Association International Conference.
“These are the first estimates of dementia in a diverse cohort of subjects 90 years or older,” said Dr. Corrada, a professor of epidemiology at the University of California, Irvine. “The racial and ethnic differences in dementia incidence didn’t appear to be due to these factors that we have come to expect. These estimates can provide us with an important foundation for understanding the burden of racial disparities in the oldest old, which is the fastest-growing segment of our population in the U.S. and in many other countries.”
Most of the cohort (72%) was white; blacks comprised 16%, Latinos 4%, and Asians 7%. Not surprisingly, most were women (65%). The mean age at baseline was 93 years. Overall, 50% had at least a high school education, but that percentage was higher in whites (56%) and lower in blacks and Latinos (33% and 24%, respectively).
Midlife obesity was present in 42% overall, but this was significantly higher in blacks and Latinos (63%), and lower in whites and Asians (38% and 24%). Midlife hypertension was present in 38% overall. This was highest in blacks (63%), followed by Latinos (42%) and whites (35%). Only 7% of Asians had high blood pressure in midlife. About 40% of each group had experienced a late-life stroke, with the exception of Asians, with a stroke incidence of just 7%. Diabetes was present in 24% overall, in 20% of whites, and about a third of the other groups.
Over the follow-up period, dementia developed in 33% of subjects, at a mean age of 95 years, which did not vary among groups. The incidence of dementia was lowest in whites (32%) and Asians (31%). It was most frequent in blacks (39%), followed by Latinos (35%). The age-adjusted, 5-year incidence rate was 10% overall. It was lowest in Asians (9%) and whites (9.7%), followed by Latinos (10.6%); it was highest in blacks (12%).
Dr. Corrada then conducted a series of five multivariate regression analyses to examine the effect of various risk factors on dementia. The first three controlled for age alone; for age and education; and for age, education, and midlife risk factors of obesity, hypertension, and cholesterol levels. In every model, blacks were 30% more likely to develop dementia over the follow-up period than were whites. Model 4 controlled for age, education, and the late-life risk factors of stroke, depression, ischemic heart disease, heart failure, and heart attack. Model 5 controlled for age, education, and both the late- and midlife risk factors.
Again, no matter which model was used, blacks faced the same 30% increased risk, compared with whites. “The differences remained very consistent,” Dr. Corrada said. “The patterns of racial and ethnic disparity seen in younger elderly continued well after age 90.”
Dr. Corrada had no financial conflicts of interest.
[email protected]
On Twitter @alz_gal
LONDON – The racial and ethnic patterns of dementia risk seen in older adults appear to hold steady even in the oldest old, with blacks about 30% more likely than are whites to develop the disorder even well into their 90s.
The magnitude of disparity remained consistent even after researchers controlled for traditional risk factors such as access to health care, cardiovascular risk, stroke, and education, Maria Corrada, ScD, said at the Alzheimer’s Association International Conference.
“These are the first estimates of dementia in a diverse cohort of subjects 90 years or older,” said Dr. Corrada, a professor of epidemiology at the University of California, Irvine. “The racial and ethnic differences in dementia incidence didn’t appear to be due to these factors that we have come to expect. These estimates can provide us with an important foundation for understanding the burden of racial disparities in the oldest old, which is the fastest-growing segment of our population in the U.S. and in many other countries.”
Most of the cohort (72%) was white; blacks comprised 16%, Latinos 4%, and Asians 7%. Not surprisingly, most were women (65%). The mean age at baseline was 93 years. Overall, 50% had at least a high school education, but that percentage was higher in whites (56%) and lower in blacks and Latinos (33% and 24%, respectively).
Midlife obesity was present in 42% overall, but this was significantly higher in blacks and Latinos (63%), and lower in whites and Asians (38% and 24%). Midlife hypertension was present in 38% overall. This was highest in blacks (63%), followed by Latinos (42%) and whites (35%). Only 7% of Asians had high blood pressure in midlife. About 40% of each group had experienced a late-life stroke, with the exception of Asians, with a stroke incidence of just 7%. Diabetes was present in 24% overall, in 20% of whites, and about a third of the other groups.
Over the follow-up period, dementia developed in 33% of subjects, at a mean age of 95 years, which did not vary among groups. The incidence of dementia was lowest in whites (32%) and Asians (31%). It was most frequent in blacks (39%), followed by Latinos (35%). The age-adjusted, 5-year incidence rate was 10% overall. It was lowest in Asians (9%) and whites (9.7%), followed by Latinos (10.6%); it was highest in blacks (12%).
Dr. Corrada then conducted a series of five multivariate regression analyses to examine the effect of various risk factors on dementia. The first three controlled for age alone; for age and education; and for age, education, and midlife risk factors of obesity, hypertension, and cholesterol levels. In every model, blacks were 30% more likely to develop dementia over the follow-up period than were whites. Model 4 controlled for age, education, and the late-life risk factors of stroke, depression, ischemic heart disease, heart failure, and heart attack. Model 5 controlled for age, education, and both the late- and midlife risk factors.
Again, no matter which model was used, blacks faced the same 30% increased risk, compared with whites. “The differences remained very consistent,” Dr. Corrada said. “The patterns of racial and ethnic disparity seen in younger elderly continued well after age 90.”
Dr. Corrada had no financial conflicts of interest.
[email protected]
On Twitter @alz_gal
LONDON – The racial and ethnic patterns of dementia risk seen in older adults appear to hold steady even in the oldest old, with blacks about 30% more likely than are whites to develop the disorder even well into their 90s.
The magnitude of disparity remained consistent even after researchers controlled for traditional risk factors such as access to health care, cardiovascular risk, stroke, and education, Maria Corrada, ScD, said at the Alzheimer’s Association International Conference.
“These are the first estimates of dementia in a diverse cohort of subjects 90 years or older,” said Dr. Corrada, a professor of epidemiology at the University of California, Irvine. “The racial and ethnic differences in dementia incidence didn’t appear to be due to these factors that we have come to expect. These estimates can provide us with an important foundation for understanding the burden of racial disparities in the oldest old, which is the fastest-growing segment of our population in the U.S. and in many other countries.”
Most of the cohort (72%) was white; blacks comprised 16%, Latinos 4%, and Asians 7%. Not surprisingly, most were women (65%). The mean age at baseline was 93 years. Overall, 50% had at least a high school education, but that percentage was higher in whites (56%) and lower in blacks and Latinos (33% and 24%, respectively).
Midlife obesity was present in 42% overall, but this was significantly higher in blacks and Latinos (63%), and lower in whites and Asians (38% and 24%). Midlife hypertension was present in 38% overall. This was highest in blacks (63%), followed by Latinos (42%) and whites (35%). Only 7% of Asians had high blood pressure in midlife. About 40% of each group had experienced a late-life stroke, with the exception of Asians, with a stroke incidence of just 7%. Diabetes was present in 24% overall, in 20% of whites, and about a third of the other groups.
Over the follow-up period, dementia developed in 33% of subjects, at a mean age of 95 years, which did not vary among groups. The incidence of dementia was lowest in whites (32%) and Asians (31%). It was most frequent in blacks (39%), followed by Latinos (35%). The age-adjusted, 5-year incidence rate was 10% overall. It was lowest in Asians (9%) and whites (9.7%), followed by Latinos (10.6%); it was highest in blacks (12%).
Dr. Corrada then conducted a series of five multivariate regression analyses to examine the effect of various risk factors on dementia. The first three controlled for age alone; for age and education; and for age, education, and midlife risk factors of obesity, hypertension, and cholesterol levels. In every model, blacks were 30% more likely to develop dementia over the follow-up period than were whites. Model 4 controlled for age, education, and the late-life risk factors of stroke, depression, ischemic heart disease, heart failure, and heart attack. Model 5 controlled for age, education, and both the late- and midlife risk factors.
Again, no matter which model was used, blacks faced the same 30% increased risk, compared with whites. “The differences remained very consistent,” Dr. Corrada said. “The patterns of racial and ethnic disparity seen in younger elderly continued well after age 90.”
Dr. Corrada had no financial conflicts of interest.
[email protected]
On Twitter @alz_gal
AT AAIC 2017
Key clinical point:
Major finding: Blacks were 30% more likely to develop dementia than were whites, even after researchers controlled for age, education, and mid- and late-life health–related risk factors.
Data source: The 5-year prospective study comprised more than 2,000 subjects aged 90 years and older.
Disclosures: The presenter had no financial disclosures.
Life-long risk reduction could cut late-life dementia by up to 35%
LONDON – As many as a third of dementia cases could be prevented worldwide if society could adopt a life course–focused approach of supporting brain health with mostly common-sense measures.
Improving childhood education, controlling blood pressure and cholesterol, keeping socially and intellectually active, exercising, and ceasing tobacco use are among the recommendations to reduce the incidence of dementia made by a worldwide panel of expert clinicians and researchers.
The findings are part of an exhaustive report commission by The Lancet and released at the Alzheimer’s Association International Conference. The report has concluded that nine lifestyle factors, most of which are modifiable from childhood though middle age, account for 35% of dementia that strikes elderly persons, Gillian Livingston, MD, said at the conference. The report was simultaneously published.
Being homozygous for the ApoE4 allele confers about an immutable 7% increased chance of developing Alzheimer’s disease. But two of the other factors identified in the Lancet report, low education in childhood and hearing loss at middle age, confer even higher individual risks of 8% and 9%. And when combined with other mid-life risks of hypertension and obesity, and late-life risks imposed by smoking, depression, inactivity, social isolation, and diabetes, these factors not only dwarf the potential impact of ApoE4, but offer a lifelong chance to forestall or even prevent dementia.
The findings, all gathered from an exhaustive literature review, bolster the notion that public health interventions could block the tsunami of dementia cases that threaten to overwhelm the world’s health care resources by 2050, Dr. Livingston said.
“While public health interventions won’t prevent or cure all potentially modifiable dementia, intervention for cardiovascular risk factors, mental health, and hearing may push back the onset in many people for years. Even if only some of this promise is realized, it could make a huge difference. We have, in fact, already seen that in some populations dementia is being delayed for years. If we could achieve an overall delay of onset by 5 years, we could cut the global prevalence by half.”
The Lancet commissioned the panel of global dementia experts to review the extant literature and construct a lifespan-focused risk model. In addition to examining risk and making recommendations to ameliorate it, the panel issued recommendations about treating cognition and psychiatric and behavioral problems; protecting dementia patients in both home and long-term care settings; supporting the family members who provide most of the care for dementia patients; and helping patients and families navigate end-of-life situations.
The literature review identified nine modifiable risk factors that account for 35% of dementia risk worldwide:
• Education in youth. Less education in childhood, which the commission identified as a lack of secondary schooling, increased the risk of dementia by 8%. Improving education at this age would remove this portion of the population attributable risk factor (PAF), Dr. Livingston said.
This finding represents an enormous opportunity for improvement: The decline in dementia incidence seen in some populations occurs mostly among the better-educated. “The mechanism of prevention here appears to be increasing brain resilience,” said Lon Schneider, MD, a member of the Lancet panel.
Tackling poor childhood education is a daunting task and requires commitment from both public and private sectors, the report noted, but its importance cannot be overstated.
• Hearing loss at mid-life. This emerged as the most powerful risk factor in the analysis, conferring an independent 9% increased risk of dementia, “a relatively new idea that has not been included in previous calculations of population attributable factors,” the commission wrote. The mechanism of increased risk isn’t clear, but may be a combination of neurodegeneration and social isolation imposed by being shut out of easy communication. It’s unclear whether hearing aids can mitigate the effects of hearing loss on dementia risk, the report noted.
• Hypertension, obesity, and diabetes. Respectively, these accounted for 2%, 1%, and 1% of the PAF. Obesity is linked to prediabetes and diabetes, which are in turn linked to insulin resistance, decreased brain amyloid clearance, high blood glucose, and inflammation – all risks for Alzheimer’s disease.
The report recommends that anyone aged 45-65 years who has hypertension should be actively treated for the disorder.
• Smoking. At 5%, smoking posted the third-highest PAF. The risk is probably mediated through smoking’s detrimental effects on cardiovascular health. But the report noted that tobacco smoke contains known neurotoxins as well.
Preventing the smoking/dementia connection is simple, Dr. Livingston said. “Simply stop smoking. If you’re smoking, just stop. Please.”
• Depression. Depression in late life imposed a 4% PAF. The evidence reviewed suggested that depression is not, in fact, linked to dementia when experienced at mid-life. But late-life depression may be a prodromal symptom of dementia and biologically linked to increased stress hormones, decreased neuronal growth factors, and decreased hippocampal volume. The commission noted animal models that suggest some antidepressants, including citalopram, decrease amyloid progression.
• Social isolation. Associated with a 2% PAF, social isolation may, like depression, be a prodromal symptom. But, the report said, there is growing evidence that it actually is an independent risk factor as well. It has been shown to also increase the risk of hypertension, cardiovascular disease, and depression, all dementia risk factors in their own right.
Longitudinal studies suggest that social activities and personal connections may prevent or delay dementia, although top-grade evidence is lacking. Still, maintaining a rich social network not only reduces the chance of isolation, but helps prevent depression as well.
• Physical inactivity. Sedentary lifestyle carried a 3% PAF for dementia. Older adults who maintain physical activity are more likely to remain cognitively intact. Physical exercise improves mood, reduces the risk of falls, and maintains normal physical function. The report cited a meta-analysis of 16 studies and almost 164,000 participants without dementia; it concluded that those in the highest level of activity had a 25% decreased risk of all-cause dementia and a 45% decreased risk of Alzheimer’s disease.
The strongest evidence for exercise’s benefit on cognition may be from the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER). Patients with a high risk of dementia who completed the lifestyle modification program of healthy diet cognitive training, vascular risk factor management, and aerobic exercise showed a slowing of cognitive decline and improvements in executive function and processing speed.
Becoming aware of the risk factors is one thing, the report said. Doing something about them is another. In general, the first step is to “be ambitious” about prevention.
“Prevention is always better than treatment,” Dr. Livingston said in an interview. “We need to start thinking about dementia not as something that simply happens outside our control, but as something that we can have an effect on.”
The Lancet commissioned the report. Dr. Livingston did not have any financial declarations but many of the other authors reported multiple relationships with pharmaceutical companies.
[email protected]
On Twitter @alz_gal
LONDON – As many as a third of dementia cases could be prevented worldwide if society could adopt a life course–focused approach of supporting brain health with mostly common-sense measures.
Improving childhood education, controlling blood pressure and cholesterol, keeping socially and intellectually active, exercising, and ceasing tobacco use are among the recommendations to reduce the incidence of dementia made by a worldwide panel of expert clinicians and researchers.
The findings are part of an exhaustive report commission by The Lancet and released at the Alzheimer’s Association International Conference. The report has concluded that nine lifestyle factors, most of which are modifiable from childhood though middle age, account for 35% of dementia that strikes elderly persons, Gillian Livingston, MD, said at the conference. The report was simultaneously published.
Being homozygous for the ApoE4 allele confers about an immutable 7% increased chance of developing Alzheimer’s disease. But two of the other factors identified in the Lancet report, low education in childhood and hearing loss at middle age, confer even higher individual risks of 8% and 9%. And when combined with other mid-life risks of hypertension and obesity, and late-life risks imposed by smoking, depression, inactivity, social isolation, and diabetes, these factors not only dwarf the potential impact of ApoE4, but offer a lifelong chance to forestall or even prevent dementia.
The findings, all gathered from an exhaustive literature review, bolster the notion that public health interventions could block the tsunami of dementia cases that threaten to overwhelm the world’s health care resources by 2050, Dr. Livingston said.
“While public health interventions won’t prevent or cure all potentially modifiable dementia, intervention for cardiovascular risk factors, mental health, and hearing may push back the onset in many people for years. Even if only some of this promise is realized, it could make a huge difference. We have, in fact, already seen that in some populations dementia is being delayed for years. If we could achieve an overall delay of onset by 5 years, we could cut the global prevalence by half.”
The Lancet commissioned the panel of global dementia experts to review the extant literature and construct a lifespan-focused risk model. In addition to examining risk and making recommendations to ameliorate it, the panel issued recommendations about treating cognition and psychiatric and behavioral problems; protecting dementia patients in both home and long-term care settings; supporting the family members who provide most of the care for dementia patients; and helping patients and families navigate end-of-life situations.
The literature review identified nine modifiable risk factors that account for 35% of dementia risk worldwide:
• Education in youth. Less education in childhood, which the commission identified as a lack of secondary schooling, increased the risk of dementia by 8%. Improving education at this age would remove this portion of the population attributable risk factor (PAF), Dr. Livingston said.
This finding represents an enormous opportunity for improvement: The decline in dementia incidence seen in some populations occurs mostly among the better-educated. “The mechanism of prevention here appears to be increasing brain resilience,” said Lon Schneider, MD, a member of the Lancet panel.
Tackling poor childhood education is a daunting task and requires commitment from both public and private sectors, the report noted, but its importance cannot be overstated.
• Hearing loss at mid-life. This emerged as the most powerful risk factor in the analysis, conferring an independent 9% increased risk of dementia, “a relatively new idea that has not been included in previous calculations of population attributable factors,” the commission wrote. The mechanism of increased risk isn’t clear, but may be a combination of neurodegeneration and social isolation imposed by being shut out of easy communication. It’s unclear whether hearing aids can mitigate the effects of hearing loss on dementia risk, the report noted.
• Hypertension, obesity, and diabetes. Respectively, these accounted for 2%, 1%, and 1% of the PAF. Obesity is linked to prediabetes and diabetes, which are in turn linked to insulin resistance, decreased brain amyloid clearance, high blood glucose, and inflammation – all risks for Alzheimer’s disease.
The report recommends that anyone aged 45-65 years who has hypertension should be actively treated for the disorder.
• Smoking. At 5%, smoking posted the third-highest PAF. The risk is probably mediated through smoking’s detrimental effects on cardiovascular health. But the report noted that tobacco smoke contains known neurotoxins as well.
Preventing the smoking/dementia connection is simple, Dr. Livingston said. “Simply stop smoking. If you’re smoking, just stop. Please.”
• Depression. Depression in late life imposed a 4% PAF. The evidence reviewed suggested that depression is not, in fact, linked to dementia when experienced at mid-life. But late-life depression may be a prodromal symptom of dementia and biologically linked to increased stress hormones, decreased neuronal growth factors, and decreased hippocampal volume. The commission noted animal models that suggest some antidepressants, including citalopram, decrease amyloid progression.
• Social isolation. Associated with a 2% PAF, social isolation may, like depression, be a prodromal symptom. But, the report said, there is growing evidence that it actually is an independent risk factor as well. It has been shown to also increase the risk of hypertension, cardiovascular disease, and depression, all dementia risk factors in their own right.
Longitudinal studies suggest that social activities and personal connections may prevent or delay dementia, although top-grade evidence is lacking. Still, maintaining a rich social network not only reduces the chance of isolation, but helps prevent depression as well.
• Physical inactivity. Sedentary lifestyle carried a 3% PAF for dementia. Older adults who maintain physical activity are more likely to remain cognitively intact. Physical exercise improves mood, reduces the risk of falls, and maintains normal physical function. The report cited a meta-analysis of 16 studies and almost 164,000 participants without dementia; it concluded that those in the highest level of activity had a 25% decreased risk of all-cause dementia and a 45% decreased risk of Alzheimer’s disease.
The strongest evidence for exercise’s benefit on cognition may be from the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER). Patients with a high risk of dementia who completed the lifestyle modification program of healthy diet cognitive training, vascular risk factor management, and aerobic exercise showed a slowing of cognitive decline and improvements in executive function and processing speed.
Becoming aware of the risk factors is one thing, the report said. Doing something about them is another. In general, the first step is to “be ambitious” about prevention.
“Prevention is always better than treatment,” Dr. Livingston said in an interview. “We need to start thinking about dementia not as something that simply happens outside our control, but as something that we can have an effect on.”
The Lancet commissioned the report. Dr. Livingston did not have any financial declarations but many of the other authors reported multiple relationships with pharmaceutical companies.
[email protected]
On Twitter @alz_gal
LONDON – As many as a third of dementia cases could be prevented worldwide if society could adopt a life course–focused approach of supporting brain health with mostly common-sense measures.
Improving childhood education, controlling blood pressure and cholesterol, keeping socially and intellectually active, exercising, and ceasing tobacco use are among the recommendations to reduce the incidence of dementia made by a worldwide panel of expert clinicians and researchers.
The findings are part of an exhaustive report commission by The Lancet and released at the Alzheimer’s Association International Conference. The report has concluded that nine lifestyle factors, most of which are modifiable from childhood though middle age, account for 35% of dementia that strikes elderly persons, Gillian Livingston, MD, said at the conference. The report was simultaneously published.
Being homozygous for the ApoE4 allele confers about an immutable 7% increased chance of developing Alzheimer’s disease. But two of the other factors identified in the Lancet report, low education in childhood and hearing loss at middle age, confer even higher individual risks of 8% and 9%. And when combined with other mid-life risks of hypertension and obesity, and late-life risks imposed by smoking, depression, inactivity, social isolation, and diabetes, these factors not only dwarf the potential impact of ApoE4, but offer a lifelong chance to forestall or even prevent dementia.
The findings, all gathered from an exhaustive literature review, bolster the notion that public health interventions could block the tsunami of dementia cases that threaten to overwhelm the world’s health care resources by 2050, Dr. Livingston said.
“While public health interventions won’t prevent or cure all potentially modifiable dementia, intervention for cardiovascular risk factors, mental health, and hearing may push back the onset in many people for years. Even if only some of this promise is realized, it could make a huge difference. We have, in fact, already seen that in some populations dementia is being delayed for years. If we could achieve an overall delay of onset by 5 years, we could cut the global prevalence by half.”
The Lancet commissioned the panel of global dementia experts to review the extant literature and construct a lifespan-focused risk model. In addition to examining risk and making recommendations to ameliorate it, the panel issued recommendations about treating cognition and psychiatric and behavioral problems; protecting dementia patients in both home and long-term care settings; supporting the family members who provide most of the care for dementia patients; and helping patients and families navigate end-of-life situations.
The literature review identified nine modifiable risk factors that account for 35% of dementia risk worldwide:
• Education in youth. Less education in childhood, which the commission identified as a lack of secondary schooling, increased the risk of dementia by 8%. Improving education at this age would remove this portion of the population attributable risk factor (PAF), Dr. Livingston said.
This finding represents an enormous opportunity for improvement: The decline in dementia incidence seen in some populations occurs mostly among the better-educated. “The mechanism of prevention here appears to be increasing brain resilience,” said Lon Schneider, MD, a member of the Lancet panel.
Tackling poor childhood education is a daunting task and requires commitment from both public and private sectors, the report noted, but its importance cannot be overstated.
• Hearing loss at mid-life. This emerged as the most powerful risk factor in the analysis, conferring an independent 9% increased risk of dementia, “a relatively new idea that has not been included in previous calculations of population attributable factors,” the commission wrote. The mechanism of increased risk isn’t clear, but may be a combination of neurodegeneration and social isolation imposed by being shut out of easy communication. It’s unclear whether hearing aids can mitigate the effects of hearing loss on dementia risk, the report noted.
• Hypertension, obesity, and diabetes. Respectively, these accounted for 2%, 1%, and 1% of the PAF. Obesity is linked to prediabetes and diabetes, which are in turn linked to insulin resistance, decreased brain amyloid clearance, high blood glucose, and inflammation – all risks for Alzheimer’s disease.
The report recommends that anyone aged 45-65 years who has hypertension should be actively treated for the disorder.
• Smoking. At 5%, smoking posted the third-highest PAF. The risk is probably mediated through smoking’s detrimental effects on cardiovascular health. But the report noted that tobacco smoke contains known neurotoxins as well.
Preventing the smoking/dementia connection is simple, Dr. Livingston said. “Simply stop smoking. If you’re smoking, just stop. Please.”
• Depression. Depression in late life imposed a 4% PAF. The evidence reviewed suggested that depression is not, in fact, linked to dementia when experienced at mid-life. But late-life depression may be a prodromal symptom of dementia and biologically linked to increased stress hormones, decreased neuronal growth factors, and decreased hippocampal volume. The commission noted animal models that suggest some antidepressants, including citalopram, decrease amyloid progression.
• Social isolation. Associated with a 2% PAF, social isolation may, like depression, be a prodromal symptom. But, the report said, there is growing evidence that it actually is an independent risk factor as well. It has been shown to also increase the risk of hypertension, cardiovascular disease, and depression, all dementia risk factors in their own right.
Longitudinal studies suggest that social activities and personal connections may prevent or delay dementia, although top-grade evidence is lacking. Still, maintaining a rich social network not only reduces the chance of isolation, but helps prevent depression as well.
• Physical inactivity. Sedentary lifestyle carried a 3% PAF for dementia. Older adults who maintain physical activity are more likely to remain cognitively intact. Physical exercise improves mood, reduces the risk of falls, and maintains normal physical function. The report cited a meta-analysis of 16 studies and almost 164,000 participants without dementia; it concluded that those in the highest level of activity had a 25% decreased risk of all-cause dementia and a 45% decreased risk of Alzheimer’s disease.
The strongest evidence for exercise’s benefit on cognition may be from the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER). Patients with a high risk of dementia who completed the lifestyle modification program of healthy diet cognitive training, vascular risk factor management, and aerobic exercise showed a slowing of cognitive decline and improvements in executive function and processing speed.
Becoming aware of the risk factors is one thing, the report said. Doing something about them is another. In general, the first step is to “be ambitious” about prevention.
“Prevention is always better than treatment,” Dr. Livingston said in an interview. “We need to start thinking about dementia not as something that simply happens outside our control, but as something that we can have an effect on.”
The Lancet commissioned the report. Dr. Livingston did not have any financial declarations but many of the other authors reported multiple relationships with pharmaceutical companies.
[email protected]
On Twitter @alz_gal
AT AAIC 2017
Amyloid PET imaging impacts diagnoses, management for those with MCI and dementia
LONDON – A study to prove the practical clinical utility of amyloid PET scanning appears to be doing just that: The knowledge of patients’ brain amyloid status changed clinical management for 68% of those who had the imaging done.
Interim results of the Imaging Dementia–Evidence for Amyloid Scanning (IDEAS) study far exceeded the 30% change rate that investigators hoped to see, Gil Rabinovici, MD, said at the Alzheimer’s Association International Conference. Not only did many patients receive a more suitable care plan, the scans actually changed diagnoses in three-quarters of those who tested positive, said Dr. Rabinovici of the University of California, San Francisco.
The U.S.-wide, open-label study is being conducted in Medicare beneficiaries who have been diagnosed with mild cognitive impairment (MCI) or dementia of uncertain cause. Its two goals are to show that amyloid PET imaging affects a patient’s care plan within 3 months of the scan and to show an impact on major medical outcomes 12 months later. In diagnostically uncertain cases, investigators theorized, amyloid PET imaging would lead to significant changes in patient management, which would then translate into improved medical outcomes.
At the meeting, Dr. Rabinovici discussed the preplanned interim analysis of 3-month care plan changes. After the scan was completed, physicians related the results to patients and recommended any appropriate management changes. At the 90-day post-scan visit, physicians documented how any changes had been implemented. Data on the 12-month outcomes have not been announced on any portion of the cohort.
The patients were a mean of 76 years old; 64% had a diagnosis of MCI and 36% a diagnosis of dementia. Alzheimer’s disease was the suspected etiology in 74% of the MCI group and in 80% of the dementia group. About one-third of MCI patients and two-thirds of dementia patients were taking Alzheimer’s medications at enrollment.
The scans were positive in 54% of the MCI patients and in 70% of dementia patients. In amyloid-positive patients, the rate of Alzheimer’s diagnosis increased from 78% to 85%. In amyloid-negative patients, the rate of Alzheimer’s diagnosis decreased from 73% to 14%.
More than two-thirds of patients in both groups experienced a change in management after the scans were read. Changes in Alzheimer’s drugs occurred in 48% of both groups, while changes in non-Alzheimer’s drugs occurred in 36% of the MCI group and 32% of the dementia group. In amyloid-positive patients, use of Alzheimer’s drugs increased from 51% to 84%. In amyloid-negative patients, the use of Alzheimer’s drugs decreased from 39% to 31%.
Patient counseling also changed in 24% of the MCI group and 16% of the dementia group.
Dr. Rabinovici was cautiously optimistic about the interim results. “The study has two aims, and Medicare has made it clear that we need to complete both before they will consider covering the scans. I hope they understand that these changes in management are incredibly important, but they also want to see that they result in improved outcomes. That will take a year from when we enroll our last patient.”
Although the study is designed to show change in clinical outcomes, it’s also changing something less tangible, but no less important: patients’ understanding of their situation.
“We may be looking at objective changes in management, but we are also seeing that patients really want to know what’s going on in their brain, what the cause of their cognitive impairment is. They don’t want to be told that it’s normal aging, because they know it isn’t. There is a real value to getting that diagnosis, even if it’s the bad news that there are amyloid plaques in the brain. It leads to a clear plan in terms of what drugs to use, the possibility of enrolling in clinical trials, and getting some clarity about what’s going on. A lot of times, the certainty is better than the uncertainty.”
As of June, IDEAS had recruited 12,484 patients and completed 11,712 amyloid PET scans. Dr. Rabinovici hopes the recruitment will be completed by late this year, or early 2018.
IDEAS is being funded by the Centers for Medicare & Medicaid Services, Avid Radiopharmaceuticals/Eli Lilly, GE Healthcare, Piramal Imaging, the Alzheimer’s Association, and the American College of Radiology. Dr. Rabinovici has received honoraria or consulting fees from Eisai, Genentech, Lundbeck, Merck, Putnam, and Roche.
[email protected]
On Twitter @alz_gal
LONDON – A study to prove the practical clinical utility of amyloid PET scanning appears to be doing just that: The knowledge of patients’ brain amyloid status changed clinical management for 68% of those who had the imaging done.
Interim results of the Imaging Dementia–Evidence for Amyloid Scanning (IDEAS) study far exceeded the 30% change rate that investigators hoped to see, Gil Rabinovici, MD, said at the Alzheimer’s Association International Conference. Not only did many patients receive a more suitable care plan, the scans actually changed diagnoses in three-quarters of those who tested positive, said Dr. Rabinovici of the University of California, San Francisco.
The U.S.-wide, open-label study is being conducted in Medicare beneficiaries who have been diagnosed with mild cognitive impairment (MCI) or dementia of uncertain cause. Its two goals are to show that amyloid PET imaging affects a patient’s care plan within 3 months of the scan and to show an impact on major medical outcomes 12 months later. In diagnostically uncertain cases, investigators theorized, amyloid PET imaging would lead to significant changes in patient management, which would then translate into improved medical outcomes.
At the meeting, Dr. Rabinovici discussed the preplanned interim analysis of 3-month care plan changes. After the scan was completed, physicians related the results to patients and recommended any appropriate management changes. At the 90-day post-scan visit, physicians documented how any changes had been implemented. Data on the 12-month outcomes have not been announced on any portion of the cohort.
The patients were a mean of 76 years old; 64% had a diagnosis of MCI and 36% a diagnosis of dementia. Alzheimer’s disease was the suspected etiology in 74% of the MCI group and in 80% of the dementia group. About one-third of MCI patients and two-thirds of dementia patients were taking Alzheimer’s medications at enrollment.
The scans were positive in 54% of the MCI patients and in 70% of dementia patients. In amyloid-positive patients, the rate of Alzheimer’s diagnosis increased from 78% to 85%. In amyloid-negative patients, the rate of Alzheimer’s diagnosis decreased from 73% to 14%.
More than two-thirds of patients in both groups experienced a change in management after the scans were read. Changes in Alzheimer’s drugs occurred in 48% of both groups, while changes in non-Alzheimer’s drugs occurred in 36% of the MCI group and 32% of the dementia group. In amyloid-positive patients, use of Alzheimer’s drugs increased from 51% to 84%. In amyloid-negative patients, the use of Alzheimer’s drugs decreased from 39% to 31%.
Patient counseling also changed in 24% of the MCI group and 16% of the dementia group.
Dr. Rabinovici was cautiously optimistic about the interim results. “The study has two aims, and Medicare has made it clear that we need to complete both before they will consider covering the scans. I hope they understand that these changes in management are incredibly important, but they also want to see that they result in improved outcomes. That will take a year from when we enroll our last patient.”
Although the study is designed to show change in clinical outcomes, it’s also changing something less tangible, but no less important: patients’ understanding of their situation.
“We may be looking at objective changes in management, but we are also seeing that patients really want to know what’s going on in their brain, what the cause of their cognitive impairment is. They don’t want to be told that it’s normal aging, because they know it isn’t. There is a real value to getting that diagnosis, even if it’s the bad news that there are amyloid plaques in the brain. It leads to a clear plan in terms of what drugs to use, the possibility of enrolling in clinical trials, and getting some clarity about what’s going on. A lot of times, the certainty is better than the uncertainty.”
As of June, IDEAS had recruited 12,484 patients and completed 11,712 amyloid PET scans. Dr. Rabinovici hopes the recruitment will be completed by late this year, or early 2018.
IDEAS is being funded by the Centers for Medicare & Medicaid Services, Avid Radiopharmaceuticals/Eli Lilly, GE Healthcare, Piramal Imaging, the Alzheimer’s Association, and the American College of Radiology. Dr. Rabinovici has received honoraria or consulting fees from Eisai, Genentech, Lundbeck, Merck, Putnam, and Roche.
[email protected]
On Twitter @alz_gal
LONDON – A study to prove the practical clinical utility of amyloid PET scanning appears to be doing just that: The knowledge of patients’ brain amyloid status changed clinical management for 68% of those who had the imaging done.
Interim results of the Imaging Dementia–Evidence for Amyloid Scanning (IDEAS) study far exceeded the 30% change rate that investigators hoped to see, Gil Rabinovici, MD, said at the Alzheimer’s Association International Conference. Not only did many patients receive a more suitable care plan, the scans actually changed diagnoses in three-quarters of those who tested positive, said Dr. Rabinovici of the University of California, San Francisco.
The U.S.-wide, open-label study is being conducted in Medicare beneficiaries who have been diagnosed with mild cognitive impairment (MCI) or dementia of uncertain cause. Its two goals are to show that amyloid PET imaging affects a patient’s care plan within 3 months of the scan and to show an impact on major medical outcomes 12 months later. In diagnostically uncertain cases, investigators theorized, amyloid PET imaging would lead to significant changes in patient management, which would then translate into improved medical outcomes.
At the meeting, Dr. Rabinovici discussed the preplanned interim analysis of 3-month care plan changes. After the scan was completed, physicians related the results to patients and recommended any appropriate management changes. At the 90-day post-scan visit, physicians documented how any changes had been implemented. Data on the 12-month outcomes have not been announced on any portion of the cohort.
The patients were a mean of 76 years old; 64% had a diagnosis of MCI and 36% a diagnosis of dementia. Alzheimer’s disease was the suspected etiology in 74% of the MCI group and in 80% of the dementia group. About one-third of MCI patients and two-thirds of dementia patients were taking Alzheimer’s medications at enrollment.
The scans were positive in 54% of the MCI patients and in 70% of dementia patients. In amyloid-positive patients, the rate of Alzheimer’s diagnosis increased from 78% to 85%. In amyloid-negative patients, the rate of Alzheimer’s diagnosis decreased from 73% to 14%.
More than two-thirds of patients in both groups experienced a change in management after the scans were read. Changes in Alzheimer’s drugs occurred in 48% of both groups, while changes in non-Alzheimer’s drugs occurred in 36% of the MCI group and 32% of the dementia group. In amyloid-positive patients, use of Alzheimer’s drugs increased from 51% to 84%. In amyloid-negative patients, the use of Alzheimer’s drugs decreased from 39% to 31%.
Patient counseling also changed in 24% of the MCI group and 16% of the dementia group.
Dr. Rabinovici was cautiously optimistic about the interim results. “The study has two aims, and Medicare has made it clear that we need to complete both before they will consider covering the scans. I hope they understand that these changes in management are incredibly important, but they also want to see that they result in improved outcomes. That will take a year from when we enroll our last patient.”
Although the study is designed to show change in clinical outcomes, it’s also changing something less tangible, but no less important: patients’ understanding of their situation.
“We may be looking at objective changes in management, but we are also seeing that patients really want to know what’s going on in their brain, what the cause of their cognitive impairment is. They don’t want to be told that it’s normal aging, because they know it isn’t. There is a real value to getting that diagnosis, even if it’s the bad news that there are amyloid plaques in the brain. It leads to a clear plan in terms of what drugs to use, the possibility of enrolling in clinical trials, and getting some clarity about what’s going on. A lot of times, the certainty is better than the uncertainty.”
As of June, IDEAS had recruited 12,484 patients and completed 11,712 amyloid PET scans. Dr. Rabinovici hopes the recruitment will be completed by late this year, or early 2018.
IDEAS is being funded by the Centers for Medicare & Medicaid Services, Avid Radiopharmaceuticals/Eli Lilly, GE Healthcare, Piramal Imaging, the Alzheimer’s Association, and the American College of Radiology. Dr. Rabinovici has received honoraria or consulting fees from Eisai, Genentech, Lundbeck, Merck, Putnam, and Roche.
[email protected]
On Twitter @alz_gal
AT AAIC 2017
Key clinical point:
Major finding: Amyloid status changed clinical management in 68% of patients diagnosed with mild cognitive impairment or dementia.
Data source: An interim analysis of 4,000 out of 18,500 planned for enrollment in the IDEAS study.
Disclosures: IDEAS is being funded by the Centers for Medicare & Medicaid Services, Avid Radiopharmaceuticals/Eli Lilly, GE Healthcare, Piramal Imaging, the Alzheimer’s Association, and the American College of Radiology. Dr. Rabinovici has received honoraria or consulting fees from Eisai, Genentech, Lundbeck, Merck, Putnam, and Roche.
New classification system for systemic lupus erythematosus moves forward
MADRID – A proposed classification scheme for systemic lupus erythematosus (SLE) relies on a combination of antinuclear antibody titer and the weighted scoring of signs and symptoms in seven clinical and three immunologic domains.
Anyone with an ANA titer of at least 1:80 on immunofluorescence and 84 points accumulated from the domains can be classified as having the disease, according to the proposed system. An international collaboration between the American College of Rheumatology and the European League Against Rheumatism, the system is the first classification scheme update since 2012, said Sindhu Johnson, MD, PhD, who discussed it during the European Congress of Rheumatology.
[polldaddy:9802068]
The proposed system is not intended to be a diagnostic tool, Dr. Johnson said in an interview. Rather, it’s meant to better stratify patients into research studies. “The prior criteria were missing patients. And, since classification criteria are used to decide whether patients can get into a clinical trial, we all felt that we were doing patients an injustice if the criteria were excluding some and denying them an opportunity to receive a novel therapy.”
There are currently two classification criteria in use: the 1982 American College of Rheumatology criteria and the Systemic Lupus International Collaborating Clinics Criteria (SLICC 2012). New understandings of SLE pathogenesis have rendered the 1982 ACR criteria outdated, according to a recently published paper (Arthritis Care Res. 2017 July 10. doi: 10.1002/acr.23317). While the SLICC 2012 criteria incorporated some of the new concepts and have increased sensitivity, compared with the 1982 ACR criteria, their specificity actually declined, partially because the document assigned equal weight to each of the clinical and immunologic criteria. The ACR/EULAR project takes a different tack. Criteria are weighted to reflect the clinical impact of different signs and symptoms, Dr. Johnson said.
“In clinical practice, if someone has class III/IV lupus nephritis, that’s a very different patient than someone who has leukopenia. As clinicians, we weight things differently, and so do these criteria, putting more weight on serious or internal organ manifestations of SLE.”
The ACR/EULAR criteria begin with a confirmed ANA titer of at least 1:80. “This has never been a requirement before, but the consensus now is that you need to have a positive ANA to be classified.”
Once that baseline is established, patients can be assessed in seven clinical domains and three immunologic domains. Each contains a subgroup of weighted signs and symptoms. These are ordered from those with least impact to those with most impact. Within each domain, only the highest-scoring criterion is counted toward the total score. When assessing, clinicians should not score any symptom if a cause other than SLE is more likely. The symptoms are not time-bound either, Dr. Johnson said. A symptom may have occurred only one time in the past, and that’s sufficient to earn a score. At least one clinical criterion must be present to be classified as SLE-positive.
The clinical domains
Constitutional: Fever (13 points). The only symptom in this domain, it’s never before been assessed in SLE criteria, Dr. Johnson said. “Our inclusion of fever is new, but our work in phase 1 of this project found that fever is a feature that can distinguish early lupus from mimickers. We want to identify patients as early in the disease course as possible so we can intervene, and fever appears to improve the ability to detect those patients.”
Cutaneous: Nonscarring alopecia (13), oral ulcers (14), subacute cutaneous or discoid lupus (29), and acute cutaneous lupus (38).
“Skin has long been recognized as an important part of lupus, but it got a lot of weight that some people felt was inappropriate. These criteria still include skin, but a patient can’t be classified on skin findings alone. There is concern that skin findings by themselves may not be lupus but something else, and some people even consider that cutaneous and systemic lupus are two different things.”
Arthritis: Synovitis in at least two joints (34).
Neurologic: Delirium (12), psychosis (20), and seizure (34).
Serositis: Pleural or pericardial effusion (34) and acute pericarditis (38).
Hematologic: Leukopenia (12), thrombocytopenia (26), and autoimmune hemolysis (28).
Renal: Proteinuria more than 0.5 g/24 hours (27), renal biopsy with class II or V lupus nephritis (55), and renal biopsy with class III or IV lupus nephritis (74).
The immunologic domains
Antiphospholipid antibodies: Anticardiolipin immunoglobulin G more than 40 GPL units, anti-beta2GP1 IgG more than 40 units, or lupus anticoagulant positive (13).
Complement proteins: Low C3 or low C4 (19) and low C3 and low C4 (27).
Highly specific antibodies: Anti-dsDNA antibody (38) and anti-Smith antibody (40).
Moving forward
Screening 10 domains with their attendant components may seem a bit clunky now, Dr. Johnson noted, but the final iteration should be more streamlined. Plus, she said, the system will be presented on a computer application that makes calculation much easier. “We’re aiming for feasibility and simplicity, but, at the same time, when you have a complex disease, you don’t want oversimplification. You may lose sensitivity and specificity.”
After further streamlining, Dr. Johnson said, the next step will be validating in a large retrospective patient cohort. “Right now, we are still collecting data for the validation cohort, which will be drawn from 36 centers. We’ll analyze sensitivity and specificity, comparing this system with the other two. We hope to present all these data at the ACR meeting in the fall.”
While research classification is the system’s raison d’être, it will undoubtedly influence diagnosis and clinical assessment as well, Dr. Johnson said. “ACR and EULAR are very clear that they only support the validation of classification criteria. The diagnosis of SLE is still within the hands of the physician. But, we know that classification criteria do inform our concept of the disease, so it’s likely these will shift the way we think about diagnosing lupus as well. We do hope to identify patients with earlier disease, so they have the opportunity to be involved in research” that may modify their disease course and, ultimately, prevent permanent damage and improve quality of life.
Dr. Johnson had no disclosures related to the development of the classification criteria.
[email protected]
On Twitter @alz_gal
This joint ACR/EULAR effort is very large, involving over 40 international SLE experts and centers, including many Systemic Lupus International Collaborating Clinics Criteria members. The goals are to develop new criteria that will be both sensitive and specific for SLE, which is a very heterogeneous and often elusive disease, using newer rigorous expert opinion–based and data-driven methodologies (as has been accomplished recently for rheumatoid arthritis, scleroderma, and gout).
This is a tall order! While genetic and cytokine-based biomarkers are being developed for the identification of SLE, unfortunately, we were not able incorporate them as they are not available for routine use at this time. The SLE classification criteria are used worldwide for inclusion in clinical trials and studies.
The work has been preceding in phases: phase 1, item generation; phase 2, item reduction and definition of criteria; phase 3, multicriteria decision analysis and threshold identification; and phase 4, validation. Phases 1-3 involved many iterative, group discussions, data collection and review, and novel “forced choice” methodologies for arriving at group consensus. In phase 4 (validation), the goal is to compare classification using these criteria with the existing ACR and SLICC criteria, as well as SLE expert physician diagnosis. We will see how they do after all this effort!
Karen H. Costenbader, MD, is the lupus program director at Brigham and Women’s Hospital, Boston. She is a member of the classification criteria steering committee and is the senior author on a paper describing the process to develop the draft classification criteria (Arthritis Care Res. 2017 July 10. doi: 10.1002/acr.23317).
This joint ACR/EULAR effort is very large, involving over 40 international SLE experts and centers, including many Systemic Lupus International Collaborating Clinics Criteria members. The goals are to develop new criteria that will be both sensitive and specific for SLE, which is a very heterogeneous and often elusive disease, using newer rigorous expert opinion–based and data-driven methodologies (as has been accomplished recently for rheumatoid arthritis, scleroderma, and gout).
This is a tall order! While genetic and cytokine-based biomarkers are being developed for the identification of SLE, unfortunately, we were not able incorporate them as they are not available for routine use at this time. The SLE classification criteria are used worldwide for inclusion in clinical trials and studies.
The work has been preceding in phases: phase 1, item generation; phase 2, item reduction and definition of criteria; phase 3, multicriteria decision analysis and threshold identification; and phase 4, validation. Phases 1-3 involved many iterative, group discussions, data collection and review, and novel “forced choice” methodologies for arriving at group consensus. In phase 4 (validation), the goal is to compare classification using these criteria with the existing ACR and SLICC criteria, as well as SLE expert physician diagnosis. We will see how they do after all this effort!
Karen H. Costenbader, MD, is the lupus program director at Brigham and Women’s Hospital, Boston. She is a member of the classification criteria steering committee and is the senior author on a paper describing the process to develop the draft classification criteria (Arthritis Care Res. 2017 July 10. doi: 10.1002/acr.23317).
This joint ACR/EULAR effort is very large, involving over 40 international SLE experts and centers, including many Systemic Lupus International Collaborating Clinics Criteria members. The goals are to develop new criteria that will be both sensitive and specific for SLE, which is a very heterogeneous and often elusive disease, using newer rigorous expert opinion–based and data-driven methodologies (as has been accomplished recently for rheumatoid arthritis, scleroderma, and gout).
This is a tall order! While genetic and cytokine-based biomarkers are being developed for the identification of SLE, unfortunately, we were not able incorporate them as they are not available for routine use at this time. The SLE classification criteria are used worldwide for inclusion in clinical trials and studies.
The work has been preceding in phases: phase 1, item generation; phase 2, item reduction and definition of criteria; phase 3, multicriteria decision analysis and threshold identification; and phase 4, validation. Phases 1-3 involved many iterative, group discussions, data collection and review, and novel “forced choice” methodologies for arriving at group consensus. In phase 4 (validation), the goal is to compare classification using these criteria with the existing ACR and SLICC criteria, as well as SLE expert physician diagnosis. We will see how they do after all this effort!
Karen H. Costenbader, MD, is the lupus program director at Brigham and Women’s Hospital, Boston. She is a member of the classification criteria steering committee and is the senior author on a paper describing the process to develop the draft classification criteria (Arthritis Care Res. 2017 July 10. doi: 10.1002/acr.23317).
MADRID – A proposed classification scheme for systemic lupus erythematosus (SLE) relies on a combination of antinuclear antibody titer and the weighted scoring of signs and symptoms in seven clinical and three immunologic domains.
Anyone with an ANA titer of at least 1:80 on immunofluorescence and 84 points accumulated from the domains can be classified as having the disease, according to the proposed system. An international collaboration between the American College of Rheumatology and the European League Against Rheumatism, the system is the first classification scheme update since 2012, said Sindhu Johnson, MD, PhD, who discussed it during the European Congress of Rheumatology.
[polldaddy:9802068]
The proposed system is not intended to be a diagnostic tool, Dr. Johnson said in an interview. Rather, it’s meant to better stratify patients into research studies. “The prior criteria were missing patients. And, since classification criteria are used to decide whether patients can get into a clinical trial, we all felt that we were doing patients an injustice if the criteria were excluding some and denying them an opportunity to receive a novel therapy.”
There are currently two classification criteria in use: the 1982 American College of Rheumatology criteria and the Systemic Lupus International Collaborating Clinics Criteria (SLICC 2012). New understandings of SLE pathogenesis have rendered the 1982 ACR criteria outdated, according to a recently published paper (Arthritis Care Res. 2017 July 10. doi: 10.1002/acr.23317). While the SLICC 2012 criteria incorporated some of the new concepts and have increased sensitivity, compared with the 1982 ACR criteria, their specificity actually declined, partially because the document assigned equal weight to each of the clinical and immunologic criteria. The ACR/EULAR project takes a different tack. Criteria are weighted to reflect the clinical impact of different signs and symptoms, Dr. Johnson said.
“In clinical practice, if someone has class III/IV lupus nephritis, that’s a very different patient than someone who has leukopenia. As clinicians, we weight things differently, and so do these criteria, putting more weight on serious or internal organ manifestations of SLE.”
The ACR/EULAR criteria begin with a confirmed ANA titer of at least 1:80. “This has never been a requirement before, but the consensus now is that you need to have a positive ANA to be classified.”
Once that baseline is established, patients can be assessed in seven clinical domains and three immunologic domains. Each contains a subgroup of weighted signs and symptoms. These are ordered from those with least impact to those with most impact. Within each domain, only the highest-scoring criterion is counted toward the total score. When assessing, clinicians should not score any symptom if a cause other than SLE is more likely. The symptoms are not time-bound either, Dr. Johnson said. A symptom may have occurred only one time in the past, and that’s sufficient to earn a score. At least one clinical criterion must be present to be classified as SLE-positive.
The clinical domains
Constitutional: Fever (13 points). The only symptom in this domain, it’s never before been assessed in SLE criteria, Dr. Johnson said. “Our inclusion of fever is new, but our work in phase 1 of this project found that fever is a feature that can distinguish early lupus from mimickers. We want to identify patients as early in the disease course as possible so we can intervene, and fever appears to improve the ability to detect those patients.”
Cutaneous: Nonscarring alopecia (13), oral ulcers (14), subacute cutaneous or discoid lupus (29), and acute cutaneous lupus (38).
“Skin has long been recognized as an important part of lupus, but it got a lot of weight that some people felt was inappropriate. These criteria still include skin, but a patient can’t be classified on skin findings alone. There is concern that skin findings by themselves may not be lupus but something else, and some people even consider that cutaneous and systemic lupus are two different things.”
Arthritis: Synovitis in at least two joints (34).
Neurologic: Delirium (12), psychosis (20), and seizure (34).
Serositis: Pleural or pericardial effusion (34) and acute pericarditis (38).
Hematologic: Leukopenia (12), thrombocytopenia (26), and autoimmune hemolysis (28).
Renal: Proteinuria more than 0.5 g/24 hours (27), renal biopsy with class II or V lupus nephritis (55), and renal biopsy with class III or IV lupus nephritis (74).
The immunologic domains
Antiphospholipid antibodies: Anticardiolipin immunoglobulin G more than 40 GPL units, anti-beta2GP1 IgG more than 40 units, or lupus anticoagulant positive (13).
Complement proteins: Low C3 or low C4 (19) and low C3 and low C4 (27).
Highly specific antibodies: Anti-dsDNA antibody (38) and anti-Smith antibody (40).
Moving forward
Screening 10 domains with their attendant components may seem a bit clunky now, Dr. Johnson noted, but the final iteration should be more streamlined. Plus, she said, the system will be presented on a computer application that makes calculation much easier. “We’re aiming for feasibility and simplicity, but, at the same time, when you have a complex disease, you don’t want oversimplification. You may lose sensitivity and specificity.”
After further streamlining, Dr. Johnson said, the next step will be validating in a large retrospective patient cohort. “Right now, we are still collecting data for the validation cohort, which will be drawn from 36 centers. We’ll analyze sensitivity and specificity, comparing this system with the other two. We hope to present all these data at the ACR meeting in the fall.”
While research classification is the system’s raison d’être, it will undoubtedly influence diagnosis and clinical assessment as well, Dr. Johnson said. “ACR and EULAR are very clear that they only support the validation of classification criteria. The diagnosis of SLE is still within the hands of the physician. But, we know that classification criteria do inform our concept of the disease, so it’s likely these will shift the way we think about diagnosing lupus as well. We do hope to identify patients with earlier disease, so they have the opportunity to be involved in research” that may modify their disease course and, ultimately, prevent permanent damage and improve quality of life.
Dr. Johnson had no disclosures related to the development of the classification criteria.
[email protected]
On Twitter @alz_gal
MADRID – A proposed classification scheme for systemic lupus erythematosus (SLE) relies on a combination of antinuclear antibody titer and the weighted scoring of signs and symptoms in seven clinical and three immunologic domains.
Anyone with an ANA titer of at least 1:80 on immunofluorescence and 84 points accumulated from the domains can be classified as having the disease, according to the proposed system. An international collaboration between the American College of Rheumatology and the European League Against Rheumatism, the system is the first classification scheme update since 2012, said Sindhu Johnson, MD, PhD, who discussed it during the European Congress of Rheumatology.
[polldaddy:9802068]
The proposed system is not intended to be a diagnostic tool, Dr. Johnson said in an interview. Rather, it’s meant to better stratify patients into research studies. “The prior criteria were missing patients. And, since classification criteria are used to decide whether patients can get into a clinical trial, we all felt that we were doing patients an injustice if the criteria were excluding some and denying them an opportunity to receive a novel therapy.”
There are currently two classification criteria in use: the 1982 American College of Rheumatology criteria and the Systemic Lupus International Collaborating Clinics Criteria (SLICC 2012). New understandings of SLE pathogenesis have rendered the 1982 ACR criteria outdated, according to a recently published paper (Arthritis Care Res. 2017 July 10. doi: 10.1002/acr.23317). While the SLICC 2012 criteria incorporated some of the new concepts and have increased sensitivity, compared with the 1982 ACR criteria, their specificity actually declined, partially because the document assigned equal weight to each of the clinical and immunologic criteria. The ACR/EULAR project takes a different tack. Criteria are weighted to reflect the clinical impact of different signs and symptoms, Dr. Johnson said.
“In clinical practice, if someone has class III/IV lupus nephritis, that’s a very different patient than someone who has leukopenia. As clinicians, we weight things differently, and so do these criteria, putting more weight on serious or internal organ manifestations of SLE.”
The ACR/EULAR criteria begin with a confirmed ANA titer of at least 1:80. “This has never been a requirement before, but the consensus now is that you need to have a positive ANA to be classified.”
Once that baseline is established, patients can be assessed in seven clinical domains and three immunologic domains. Each contains a subgroup of weighted signs and symptoms. These are ordered from those with least impact to those with most impact. Within each domain, only the highest-scoring criterion is counted toward the total score. When assessing, clinicians should not score any symptom if a cause other than SLE is more likely. The symptoms are not time-bound either, Dr. Johnson said. A symptom may have occurred only one time in the past, and that’s sufficient to earn a score. At least one clinical criterion must be present to be classified as SLE-positive.
The clinical domains
Constitutional: Fever (13 points). The only symptom in this domain, it’s never before been assessed in SLE criteria, Dr. Johnson said. “Our inclusion of fever is new, but our work in phase 1 of this project found that fever is a feature that can distinguish early lupus from mimickers. We want to identify patients as early in the disease course as possible so we can intervene, and fever appears to improve the ability to detect those patients.”
Cutaneous: Nonscarring alopecia (13), oral ulcers (14), subacute cutaneous or discoid lupus (29), and acute cutaneous lupus (38).
“Skin has long been recognized as an important part of lupus, but it got a lot of weight that some people felt was inappropriate. These criteria still include skin, but a patient can’t be classified on skin findings alone. There is concern that skin findings by themselves may not be lupus but something else, and some people even consider that cutaneous and systemic lupus are two different things.”
Arthritis: Synovitis in at least two joints (34).
Neurologic: Delirium (12), psychosis (20), and seizure (34).
Serositis: Pleural or pericardial effusion (34) and acute pericarditis (38).
Hematologic: Leukopenia (12), thrombocytopenia (26), and autoimmune hemolysis (28).
Renal: Proteinuria more than 0.5 g/24 hours (27), renal biopsy with class II or V lupus nephritis (55), and renal biopsy with class III or IV lupus nephritis (74).
The immunologic domains
Antiphospholipid antibodies: Anticardiolipin immunoglobulin G more than 40 GPL units, anti-beta2GP1 IgG more than 40 units, or lupus anticoagulant positive (13).
Complement proteins: Low C3 or low C4 (19) and low C3 and low C4 (27).
Highly specific antibodies: Anti-dsDNA antibody (38) and anti-Smith antibody (40).
Moving forward
Screening 10 domains with their attendant components may seem a bit clunky now, Dr. Johnson noted, but the final iteration should be more streamlined. Plus, she said, the system will be presented on a computer application that makes calculation much easier. “We’re aiming for feasibility and simplicity, but, at the same time, when you have a complex disease, you don’t want oversimplification. You may lose sensitivity and specificity.”
After further streamlining, Dr. Johnson said, the next step will be validating in a large retrospective patient cohort. “Right now, we are still collecting data for the validation cohort, which will be drawn from 36 centers. We’ll analyze sensitivity and specificity, comparing this system with the other two. We hope to present all these data at the ACR meeting in the fall.”
While research classification is the system’s raison d’être, it will undoubtedly influence diagnosis and clinical assessment as well, Dr. Johnson said. “ACR and EULAR are very clear that they only support the validation of classification criteria. The diagnosis of SLE is still within the hands of the physician. But, we know that classification criteria do inform our concept of the disease, so it’s likely these will shift the way we think about diagnosing lupus as well. We do hope to identify patients with earlier disease, so they have the opportunity to be involved in research” that may modify their disease course and, ultimately, prevent permanent damage and improve quality of life.
Dr. Johnson had no disclosures related to the development of the classification criteria.
[email protected]
On Twitter @alz_gal
AT THE EULAR 2017 CONGRESS
Hospitalizations may speed up cognitive decline in older adults
LONDON – Older adult patients who already had cognitive decline when they were admitted to a hospital often left with a significantly accelerated rate of decline, according to findings from a large longitudinal cohort study.
The study found up to a 62% acceleration of prehospital cognitive decline after any hospitalization. Urgent or emergency hospitalizations exacted the biggest toll on cognitive health, Bryan James, PhD, said at the Alzheimer’s Association International Conference.
Cognitive decline after hospitalization in older patients is a common occurrence but still poorly understood, he said. “Some data suggest this could actually be seen as a public health crisis since 40% of all hospitalized patients in the U.S. are older than 65, and the risk of past-hospitalization cognitive impairment rises with age.
“Given the risk to cognitive health, older patients, families, and physicians require information on when to admit to the hospital,” Dr. James said. “We wondered if those who decline rapidly after the hospital admission were already declining before. Our second question was whether elective hospital admissions are associated with the same negative cognitive outcomes as nonelective (emergent or urgent) admissions.”
To examine this, Dr. James and his colleagues used patient data from the Rush Memory and Aging Project, which provides each participant with an annual cognitive assessment consisting of 19 neuropsychological tests. They linked these data to each patient’s Medicare claims record, allowing them to assess cognitive function both before and after the index hospitalization.
The cohort comprised 930 patients who were followed for a mean of 5 years. Hospitalized patients were older (81 vs. 79 years). Most patients in both groups had at least one medical condition, such as hypertension, heart disease, diabetes, cancer, thyroid disease, head injury, or stroke. Cognition was already impaired in many of the hospitalized patients; 62% had mild cognitive impairment (MCI) and 35% had dementia. Among the nonhospitalized subjects, 49% had MCI and 24% had dementia.
Of the cohort, 66% experienced a hospitalization during follow-up. Most hospitalizations (57%) were either for urgent or emergency problems. The rest were elective admissions. The main outcome was change in global cognition – an averaged z-score of all 19 tests of working memory, episodic memory, semantic memory, visuospatial processing, and perceptual speed.
Elective admissions were mostly planned surgeries (94%), and unplanned surgeries occurred in 64% of the nonelective admissions. Most of the elective admissions (81%) involved anesthesia, compared with 32% of the nonelective admissions. About 40% of each group required a stay in the intensive care unit. Around 11% in each group had a critical illness – a stroke, hemorrhage, or brain trauma in about 6% of each group.
A multivariate analysis looked at the change in cognition during two time points: 2 years before the index hospitalization and up to 8 years after it. As could be expected of aged subjects in a memory study cohort, most patients experienced a decline in cognition over the study period. However, nonhospitalized patients continued on a smooth linear slope of decline. Hospitalized patients experienced a significant 62% increased rate of decline, even after controlling for age, education, comorbidities, depression, Activities of Daily Living disability, and physical activity.
Visuospatial processing was the only domain not significantly affected by a hospital admission. All of the memory domains, as well as perceptual speed, declined significantly faster after hospitalization than before.
The second analysis examined which type of admission was most dangerous for cognitive health. This controlled for even more potential confounding factors, including length of stay, surgery and anesthesia, Charlson comorbidity index, critical illness, brain injury, and number of hospitalizations during the follow-up period.
Urgent and emergency admissions drove virtually all of the increase in decline, Dr. James said, with a 60% increase in the rate of decline, compared with the prehospitalization rate. Patients who had elective admissions showed no variance from their baseline rate of decline, and, in fact, followed the same slope as nonhospitalized patients. Again, change was seen in the global score and in all the memory domains and perceptual speed. Only visuospatial processing was unaffected.
“It’s unclear why the urgent and emergent admissions drove this finding, even after we controlled for illness and injury severity and other factors,” Dr. James said. “Obviously, we need more research in this area.”
He had no financial disclosures.
[email protected]
On Twitter @alz_gal
LONDON – Older adult patients who already had cognitive decline when they were admitted to a hospital often left with a significantly accelerated rate of decline, according to findings from a large longitudinal cohort study.
The study found up to a 62% acceleration of prehospital cognitive decline after any hospitalization. Urgent or emergency hospitalizations exacted the biggest toll on cognitive health, Bryan James, PhD, said at the Alzheimer’s Association International Conference.
Cognitive decline after hospitalization in older patients is a common occurrence but still poorly understood, he said. “Some data suggest this could actually be seen as a public health crisis since 40% of all hospitalized patients in the U.S. are older than 65, and the risk of past-hospitalization cognitive impairment rises with age.
“Given the risk to cognitive health, older patients, families, and physicians require information on when to admit to the hospital,” Dr. James said. “We wondered if those who decline rapidly after the hospital admission were already declining before. Our second question was whether elective hospital admissions are associated with the same negative cognitive outcomes as nonelective (emergent or urgent) admissions.”
To examine this, Dr. James and his colleagues used patient data from the Rush Memory and Aging Project, which provides each participant with an annual cognitive assessment consisting of 19 neuropsychological tests. They linked these data to each patient’s Medicare claims record, allowing them to assess cognitive function both before and after the index hospitalization.
The cohort comprised 930 patients who were followed for a mean of 5 years. Hospitalized patients were older (81 vs. 79 years). Most patients in both groups had at least one medical condition, such as hypertension, heart disease, diabetes, cancer, thyroid disease, head injury, or stroke. Cognition was already impaired in many of the hospitalized patients; 62% had mild cognitive impairment (MCI) and 35% had dementia. Among the nonhospitalized subjects, 49% had MCI and 24% had dementia.
Of the cohort, 66% experienced a hospitalization during follow-up. Most hospitalizations (57%) were either for urgent or emergency problems. The rest were elective admissions. The main outcome was change in global cognition – an averaged z-score of all 19 tests of working memory, episodic memory, semantic memory, visuospatial processing, and perceptual speed.
Elective admissions were mostly planned surgeries (94%), and unplanned surgeries occurred in 64% of the nonelective admissions. Most of the elective admissions (81%) involved anesthesia, compared with 32% of the nonelective admissions. About 40% of each group required a stay in the intensive care unit. Around 11% in each group had a critical illness – a stroke, hemorrhage, or brain trauma in about 6% of each group.
A multivariate analysis looked at the change in cognition during two time points: 2 years before the index hospitalization and up to 8 years after it. As could be expected of aged subjects in a memory study cohort, most patients experienced a decline in cognition over the study period. However, nonhospitalized patients continued on a smooth linear slope of decline. Hospitalized patients experienced a significant 62% increased rate of decline, even after controlling for age, education, comorbidities, depression, Activities of Daily Living disability, and physical activity.
Visuospatial processing was the only domain not significantly affected by a hospital admission. All of the memory domains, as well as perceptual speed, declined significantly faster after hospitalization than before.
The second analysis examined which type of admission was most dangerous for cognitive health. This controlled for even more potential confounding factors, including length of stay, surgery and anesthesia, Charlson comorbidity index, critical illness, brain injury, and number of hospitalizations during the follow-up period.
Urgent and emergency admissions drove virtually all of the increase in decline, Dr. James said, with a 60% increase in the rate of decline, compared with the prehospitalization rate. Patients who had elective admissions showed no variance from their baseline rate of decline, and, in fact, followed the same slope as nonhospitalized patients. Again, change was seen in the global score and in all the memory domains and perceptual speed. Only visuospatial processing was unaffected.
“It’s unclear why the urgent and emergent admissions drove this finding, even after we controlled for illness and injury severity and other factors,” Dr. James said. “Obviously, we need more research in this area.”
He had no financial disclosures.
[email protected]
On Twitter @alz_gal
LONDON – Older adult patients who already had cognitive decline when they were admitted to a hospital often left with a significantly accelerated rate of decline, according to findings from a large longitudinal cohort study.
The study found up to a 62% acceleration of prehospital cognitive decline after any hospitalization. Urgent or emergency hospitalizations exacted the biggest toll on cognitive health, Bryan James, PhD, said at the Alzheimer’s Association International Conference.
Cognitive decline after hospitalization in older patients is a common occurrence but still poorly understood, he said. “Some data suggest this could actually be seen as a public health crisis since 40% of all hospitalized patients in the U.S. are older than 65, and the risk of past-hospitalization cognitive impairment rises with age.
“Given the risk to cognitive health, older patients, families, and physicians require information on when to admit to the hospital,” Dr. James said. “We wondered if those who decline rapidly after the hospital admission were already declining before. Our second question was whether elective hospital admissions are associated with the same negative cognitive outcomes as nonelective (emergent or urgent) admissions.”
To examine this, Dr. James and his colleagues used patient data from the Rush Memory and Aging Project, which provides each participant with an annual cognitive assessment consisting of 19 neuropsychological tests. They linked these data to each patient’s Medicare claims record, allowing them to assess cognitive function both before and after the index hospitalization.
The cohort comprised 930 patients who were followed for a mean of 5 years. Hospitalized patients were older (81 vs. 79 years). Most patients in both groups had at least one medical condition, such as hypertension, heart disease, diabetes, cancer, thyroid disease, head injury, or stroke. Cognition was already impaired in many of the hospitalized patients; 62% had mild cognitive impairment (MCI) and 35% had dementia. Among the nonhospitalized subjects, 49% had MCI and 24% had dementia.
Of the cohort, 66% experienced a hospitalization during follow-up. Most hospitalizations (57%) were either for urgent or emergency problems. The rest were elective admissions. The main outcome was change in global cognition – an averaged z-score of all 19 tests of working memory, episodic memory, semantic memory, visuospatial processing, and perceptual speed.
Elective admissions were mostly planned surgeries (94%), and unplanned surgeries occurred in 64% of the nonelective admissions. Most of the elective admissions (81%) involved anesthesia, compared with 32% of the nonelective admissions. About 40% of each group required a stay in the intensive care unit. Around 11% in each group had a critical illness – a stroke, hemorrhage, or brain trauma in about 6% of each group.
A multivariate analysis looked at the change in cognition during two time points: 2 years before the index hospitalization and up to 8 years after it. As could be expected of aged subjects in a memory study cohort, most patients experienced a decline in cognition over the study period. However, nonhospitalized patients continued on a smooth linear slope of decline. Hospitalized patients experienced a significant 62% increased rate of decline, even after controlling for age, education, comorbidities, depression, Activities of Daily Living disability, and physical activity.
Visuospatial processing was the only domain not significantly affected by a hospital admission. All of the memory domains, as well as perceptual speed, declined significantly faster after hospitalization than before.
The second analysis examined which type of admission was most dangerous for cognitive health. This controlled for even more potential confounding factors, including length of stay, surgery and anesthesia, Charlson comorbidity index, critical illness, brain injury, and number of hospitalizations during the follow-up period.
Urgent and emergency admissions drove virtually all of the increase in decline, Dr. James said, with a 60% increase in the rate of decline, compared with the prehospitalization rate. Patients who had elective admissions showed no variance from their baseline rate of decline, and, in fact, followed the same slope as nonhospitalized patients. Again, change was seen in the global score and in all the memory domains and perceptual speed. Only visuospatial processing was unaffected.
“It’s unclear why the urgent and emergent admissions drove this finding, even after we controlled for illness and injury severity and other factors,” Dr. James said. “Obviously, we need more research in this area.”
He had no financial disclosures.
[email protected]
On Twitter @alz_gal
AT AAIC 2017
Key clinical point:
Major finding: Urgent or emergency admissions accelerated the rate of cognitive decline by 60%, compared with the prehospitalization rate. Elective admissions did not change the rate of cognitive decline.
Data source: The 930 patients were drawn from the Rush Memory and Aging Project.
Disclosures: The presenter had no financial disclosures.
Small brain infarcts’ cognitive impact equals that of large infarcts
LONDON – Small infarct-like brain lesions have long been ignored in both research and clinical settings, but an ongoing analysis of an observational cohort shows that they can be just as cognitively damaging as large infarcts. Having both is a serious one-two punch to thinking and memory.
At less than 3 mm, infarct-like lesions (ILL) may be tiny, but, over 20 years, they exerted exactly the same deleterious effect on cognition as lesions 3 mm or larger, Beverly Gwen Windham, MD, said at the Alzheimer’s Association International Conference.
When neuroradiologists began to look at brain infarcts several decades ago, they used then state-of-the-art 1.5 Tesla MRI. As infarct description and classification evolved, anything measuring smaller than 3 mm was classified as an infarct-like lesion and anything 3 mm or larger as a large infarct. There was some concern that readers would confuse the ILLs with perivascular spaces and flag these normal voids as pathological changes, Dr. Windham said. As a result, research studies have always excluded them. Since they’re usually associated with silent events, without any clinical signs or symptoms, they’ve been clinically disregarded as well, adding to the perception that they have little long-term impact.
However, in 2015, Dr. Windham and her team proved this perception incorrect, at least when it came to stroke and stroke mortality. Using the large Atherosclerosis Risk in Communities (ARIC) Study cohort, they showed that ILLs alone tripled the risk of both a stroke and stroke mortality. Patients who had both ILLs and large infarcts were nine times more likely to have a stroke and seven times more likely to die from a stroke than were patients who had no lesions.
Dr. Windham used the same ARIC cohort in the 20-year cognition study. Begun in 1987, ARIC enrolled 15,800 middle-aged adults who have been followed regularly with physical and neurocognitive testing. Its goals are largely to investigate the natural history and multiple risk factors of cardiovascular and cerebrovascular disease. In 1993, subjects who had not experienced a stroke also had a brain MRI to add more detail to the study. The investigators also have performed cognitive assessments of a large number of participants five times since 1993 on measures of delayed word recall, digit symbol substitution, and word fluency. The outcome was the change in the composite Z-score over time.
The cognition study comprised 1,881 who had brain MRI and the full five cognitive assessments over a 20-year period. The participants were stratified as having no infarcts (1,611), only ILLs (50) or large infarcts (185), or both lesions (35).
At baseline, these subjects had a mean age of 63 years, 17% had diabetes, and 48% had hypertension. About one-third were positive for an ApoE e4 allele. The mean white matter intensity score was 1.4.
“In general, everyone in the cohort had some decline in cognitive function as they got older,” Dr. Windham said. But, a striking observation was that those with ILLs only and those with large lesions only had virtually identical decline slopes over the 20-year follow-up. The change from baseline in global Z-score was 0.18 standard deviations for the ILL-only group and 0.24 standard deviations for the large infarct group. For those with both lesions, the change from baseline was 0.62.
“At the end of 20 years, those with no lesion burden declined 1.3 standard deviations from baseline, those with only ILLs declined 1.5 standard deviations, and those with large infarcts, 1.6 standard deviations,” Dr. Windham said. “But, subjects who had both lesions declined 2.5 standard deviations from baseline. This is equivalent to adding 27 years of aging. The effect of having both was nearly four times greater than [that of] having only large lesions, which, up until now, have been the only ones read on MRI in either clinical practice or in research. Overall, our findings confirm that the relationship of ILLs to cognition is very similar that of large infarcts.
“The presence of midlife ILLs appears to amplify the effect of large infarcts on cognition, and we hypothesize that this process may represent vascular disease at midlife. We may also be able to identify people at high risk of cognitive decline or even dementia at midlife. I also think that we need to be rethinking how we read MRIs. Stopping at the 3-mm threshold may be too conservative. We should be looking at other studies on the consequences of these small lesions,” she said.
Dr. Windham had no financial disclosures.
[email protected]
On Twitter @alz_gal
Virtually every time researchers look for an effect of brain vascular health on cognition, they find it. Not only do these data reveal a surprisingly large effect of a previously ignored type of brain lesion on cognition, they also highlight that poor management of vascular risk factors in midlife may lead to dementia decades later. This suggests we need more research to understand the long-term impact of these small lesions on brain health and the development of Alzheimer’s disease.
Keith Fargo, PhD, is the Alzheimer’s Association’s director of scientific programs and outreach.
Virtually every time researchers look for an effect of brain vascular health on cognition, they find it. Not only do these data reveal a surprisingly large effect of a previously ignored type of brain lesion on cognition, they also highlight that poor management of vascular risk factors in midlife may lead to dementia decades later. This suggests we need more research to understand the long-term impact of these small lesions on brain health and the development of Alzheimer’s disease.
Keith Fargo, PhD, is the Alzheimer’s Association’s director of scientific programs and outreach.
Virtually every time researchers look for an effect of brain vascular health on cognition, they find it. Not only do these data reveal a surprisingly large effect of a previously ignored type of brain lesion on cognition, they also highlight that poor management of vascular risk factors in midlife may lead to dementia decades later. This suggests we need more research to understand the long-term impact of these small lesions on brain health and the development of Alzheimer’s disease.
Keith Fargo, PhD, is the Alzheimer’s Association’s director of scientific programs and outreach.
LONDON – Small infarct-like brain lesions have long been ignored in both research and clinical settings, but an ongoing analysis of an observational cohort shows that they can be just as cognitively damaging as large infarcts. Having both is a serious one-two punch to thinking and memory.
At less than 3 mm, infarct-like lesions (ILL) may be tiny, but, over 20 years, they exerted exactly the same deleterious effect on cognition as lesions 3 mm or larger, Beverly Gwen Windham, MD, said at the Alzheimer’s Association International Conference.
When neuroradiologists began to look at brain infarcts several decades ago, they used then state-of-the-art 1.5 Tesla MRI. As infarct description and classification evolved, anything measuring smaller than 3 mm was classified as an infarct-like lesion and anything 3 mm or larger as a large infarct. There was some concern that readers would confuse the ILLs with perivascular spaces and flag these normal voids as pathological changes, Dr. Windham said. As a result, research studies have always excluded them. Since they’re usually associated with silent events, without any clinical signs or symptoms, they’ve been clinically disregarded as well, adding to the perception that they have little long-term impact.
However, in 2015, Dr. Windham and her team proved this perception incorrect, at least when it came to stroke and stroke mortality. Using the large Atherosclerosis Risk in Communities (ARIC) Study cohort, they showed that ILLs alone tripled the risk of both a stroke and stroke mortality. Patients who had both ILLs and large infarcts were nine times more likely to have a stroke and seven times more likely to die from a stroke than were patients who had no lesions.
Dr. Windham used the same ARIC cohort in the 20-year cognition study. Begun in 1987, ARIC enrolled 15,800 middle-aged adults who have been followed regularly with physical and neurocognitive testing. Its goals are largely to investigate the natural history and multiple risk factors of cardiovascular and cerebrovascular disease. In 1993, subjects who had not experienced a stroke also had a brain MRI to add more detail to the study. The investigators also have performed cognitive assessments of a large number of participants five times since 1993 on measures of delayed word recall, digit symbol substitution, and word fluency. The outcome was the change in the composite Z-score over time.
The cognition study comprised 1,881 who had brain MRI and the full five cognitive assessments over a 20-year period. The participants were stratified as having no infarcts (1,611), only ILLs (50) or large infarcts (185), or both lesions (35).
At baseline, these subjects had a mean age of 63 years, 17% had diabetes, and 48% had hypertension. About one-third were positive for an ApoE e4 allele. The mean white matter intensity score was 1.4.
“In general, everyone in the cohort had some decline in cognitive function as they got older,” Dr. Windham said. But, a striking observation was that those with ILLs only and those with large lesions only had virtually identical decline slopes over the 20-year follow-up. The change from baseline in global Z-score was 0.18 standard deviations for the ILL-only group and 0.24 standard deviations for the large infarct group. For those with both lesions, the change from baseline was 0.62.
“At the end of 20 years, those with no lesion burden declined 1.3 standard deviations from baseline, those with only ILLs declined 1.5 standard deviations, and those with large infarcts, 1.6 standard deviations,” Dr. Windham said. “But, subjects who had both lesions declined 2.5 standard deviations from baseline. This is equivalent to adding 27 years of aging. The effect of having both was nearly four times greater than [that of] having only large lesions, which, up until now, have been the only ones read on MRI in either clinical practice or in research. Overall, our findings confirm that the relationship of ILLs to cognition is very similar that of large infarcts.
“The presence of midlife ILLs appears to amplify the effect of large infarcts on cognition, and we hypothesize that this process may represent vascular disease at midlife. We may also be able to identify people at high risk of cognitive decline or even dementia at midlife. I also think that we need to be rethinking how we read MRIs. Stopping at the 3-mm threshold may be too conservative. We should be looking at other studies on the consequences of these small lesions,” she said.
Dr. Windham had no financial disclosures.
[email protected]
On Twitter @alz_gal
LONDON – Small infarct-like brain lesions have long been ignored in both research and clinical settings, but an ongoing analysis of an observational cohort shows that they can be just as cognitively damaging as large infarcts. Having both is a serious one-two punch to thinking and memory.
At less than 3 mm, infarct-like lesions (ILL) may be tiny, but, over 20 years, they exerted exactly the same deleterious effect on cognition as lesions 3 mm or larger, Beverly Gwen Windham, MD, said at the Alzheimer’s Association International Conference.
When neuroradiologists began to look at brain infarcts several decades ago, they used then state-of-the-art 1.5 Tesla MRI. As infarct description and classification evolved, anything measuring smaller than 3 mm was classified as an infarct-like lesion and anything 3 mm or larger as a large infarct. There was some concern that readers would confuse the ILLs with perivascular spaces and flag these normal voids as pathological changes, Dr. Windham said. As a result, research studies have always excluded them. Since they’re usually associated with silent events, without any clinical signs or symptoms, they’ve been clinically disregarded as well, adding to the perception that they have little long-term impact.
However, in 2015, Dr. Windham and her team proved this perception incorrect, at least when it came to stroke and stroke mortality. Using the large Atherosclerosis Risk in Communities (ARIC) Study cohort, they showed that ILLs alone tripled the risk of both a stroke and stroke mortality. Patients who had both ILLs and large infarcts were nine times more likely to have a stroke and seven times more likely to die from a stroke than were patients who had no lesions.
Dr. Windham used the same ARIC cohort in the 20-year cognition study. Begun in 1987, ARIC enrolled 15,800 middle-aged adults who have been followed regularly with physical and neurocognitive testing. Its goals are largely to investigate the natural history and multiple risk factors of cardiovascular and cerebrovascular disease. In 1993, subjects who had not experienced a stroke also had a brain MRI to add more detail to the study. The investigators also have performed cognitive assessments of a large number of participants five times since 1993 on measures of delayed word recall, digit symbol substitution, and word fluency. The outcome was the change in the composite Z-score over time.
The cognition study comprised 1,881 who had brain MRI and the full five cognitive assessments over a 20-year period. The participants were stratified as having no infarcts (1,611), only ILLs (50) or large infarcts (185), or both lesions (35).
At baseline, these subjects had a mean age of 63 years, 17% had diabetes, and 48% had hypertension. About one-third were positive for an ApoE e4 allele. The mean white matter intensity score was 1.4.
“In general, everyone in the cohort had some decline in cognitive function as they got older,” Dr. Windham said. But, a striking observation was that those with ILLs only and those with large lesions only had virtually identical decline slopes over the 20-year follow-up. The change from baseline in global Z-score was 0.18 standard deviations for the ILL-only group and 0.24 standard deviations for the large infarct group. For those with both lesions, the change from baseline was 0.62.
“At the end of 20 years, those with no lesion burden declined 1.3 standard deviations from baseline, those with only ILLs declined 1.5 standard deviations, and those with large infarcts, 1.6 standard deviations,” Dr. Windham said. “But, subjects who had both lesions declined 2.5 standard deviations from baseline. This is equivalent to adding 27 years of aging. The effect of having both was nearly four times greater than [that of] having only large lesions, which, up until now, have been the only ones read on MRI in either clinical practice or in research. Overall, our findings confirm that the relationship of ILLs to cognition is very similar that of large infarcts.
“The presence of midlife ILLs appears to amplify the effect of large infarcts on cognition, and we hypothesize that this process may represent vascular disease at midlife. We may also be able to identify people at high risk of cognitive decline or even dementia at midlife. I also think that we need to be rethinking how we read MRIs. Stopping at the 3-mm threshold may be too conservative. We should be looking at other studies on the consequences of these small lesions,” she said.
Dr. Windham had no financial disclosures.
[email protected]
On Twitter @alz_gal
AT AAIC 2017
Key clinical point:
Major finding: A composite cognitive measure showed a decline of 1.5 standard deviations from baseline in patients with only infarct-like lesions, 1.6 standard deviations in those with large infarcts, and 2.5 standard deviations in subjects who had both lesions.
Data source: The ARIC substudy comprised 1,881 subjects followed for 20 years.
Disclosures: Dr. Windham had no financial disclosures.
Stressful life events take greater cognitive toll on African Americans than whites
LONDON – African Americans not only report experiencing more stressful experiences across their lifespans than do whites, but they have more cognitive consequences from them as well, new research suggests.
In fact, the weight of these experiences affected cognition even more than traditional risk factors like genetic status and even age, Megan Zuelsdorff, PhD, said at the Alzheimer’s Association International Conference.
Racial disparities have long been evident in the development and progression of dementia, Dr. Zuelsdorff said. Socioeconomic factors are also important players in this scenario. Stress, likewise, has long been linked to poorer cognitive health. “But, there are still significant gaps in our knowledge of stress and cognition. The contribution of stress to well-established socioeconomic impacts on health is unclear, and the research focus here has always been on events happening in midlife and onward. But, it’s crucial to expand this window of time backward to include earlier years. If we look at a graph of cognitive function across the lifespan, the rate of decline doesn’t vary much. What we do see is that blacks, starting at midlife, are closer to the clinical threshold of cognitive impairment and may reach the threshold at an earlier age. What this said to me is that we needed to look at these earlier life factors that could bring someone to this state of lower cognitive function in midlife.”
Dr. Zuelsdorff and her colleagues analyzed data from the Wisconsin Registry for Alzheimer’s Prevention to examine this question. The observational study comprises 1,500 adults being followed for 15-20 years and is enriched for those with a family history of Alzheimer’s disease. The main goal of WRAP is to understand the biological, medical, environmental, and lifestyle factors that increase a person’s risk of developing Alzheimer’s disease.
Subjects have a study visit every 2-4 years that includes a full physical and cognitive workup. At one visit, Dr. Zuelsdorff said, they were asked to complete a questionnaire concerning 27 different stressful life events. These experiences were deeply disturbing and potentially life altering. They included childhood experiences, such as parental abuse, alcoholism, and flunking out of school, and adult experiences, such as combat experience, bankruptcy, or the death of a child. She then analyzed how the total number of stressful events in a person’s life changed that person’s risk of developing dementia.
Of the entire WRAP cohort, 1,314 completed the stress questionnaire and had sufficient cognitive data. These subjects were largely white (1,232). Only 82 were African American, a weakness of the study, Dr. Zuelsdorff noted, but a reflection of Wisconsin’s racial makeup.
They were similar in a number of important ways, including age (mean, 58 years), proportion of apolipoprotein E4 (APOE4) allele carriers (38%), and years of education (mean, 16). African Americans had higher body mass index (33.3 vs. 28.8 kg/m2), reported less physical activity, were more often current smokers (22% vs. 6%), and had a lower-quality education despite similar time in the classroom.
On average, African Americans reported a mean of 4.5 stressful life events – a significant, 60% increase over the 2.8 reported by whites. The experience of stressful events directly influenced a subject’s performance in the speed and flexibility domain of executive function and in working memory, Dr. Zuelsdorff said.
“We saw a substantial 13.5% attenuation of performance on speed and flexibility, but we also saw attenuation in working memory. That told us something else was going on – that it wasn’t just the accumulation of stressful events but that there was a differential vulnerability. The negative association between lifetime stressful events and the cognitive domains was much stronger in blacks than in whites.”
She then conducted a risk analysis to determine the impact of stress. “Stress was right at the top for blacks. It tended to be one of the most important predictors of cognitive function. The only other one that came out as significant was quality of education. The social environment in this sample was more important than the traditional risk factors of genetics and chronological age.”
The study barely scratches the surface of the stress/cognition conundrum, Dr. Zuelsdorff said. “We would like to look at the timing next and see if there is some critical window that is especially influencing to cognitive health. We then need to target both interventions and effect modifiers, such as social, community, and financial resources that might buffer the effects of this negative stress.”
She had no financial disclosures.
[email protected]
On Twitter @alz_gal
LONDON – African Americans not only report experiencing more stressful experiences across their lifespans than do whites, but they have more cognitive consequences from them as well, new research suggests.
In fact, the weight of these experiences affected cognition even more than traditional risk factors like genetic status and even age, Megan Zuelsdorff, PhD, said at the Alzheimer’s Association International Conference.
Racial disparities have long been evident in the development and progression of dementia, Dr. Zuelsdorff said. Socioeconomic factors are also important players in this scenario. Stress, likewise, has long been linked to poorer cognitive health. “But, there are still significant gaps in our knowledge of stress and cognition. The contribution of stress to well-established socioeconomic impacts on health is unclear, and the research focus here has always been on events happening in midlife and onward. But, it’s crucial to expand this window of time backward to include earlier years. If we look at a graph of cognitive function across the lifespan, the rate of decline doesn’t vary much. What we do see is that blacks, starting at midlife, are closer to the clinical threshold of cognitive impairment and may reach the threshold at an earlier age. What this said to me is that we needed to look at these earlier life factors that could bring someone to this state of lower cognitive function in midlife.”
Dr. Zuelsdorff and her colleagues analyzed data from the Wisconsin Registry for Alzheimer’s Prevention to examine this question. The observational study comprises 1,500 adults being followed for 15-20 years and is enriched for those with a family history of Alzheimer’s disease. The main goal of WRAP is to understand the biological, medical, environmental, and lifestyle factors that increase a person’s risk of developing Alzheimer’s disease.
Subjects have a study visit every 2-4 years that includes a full physical and cognitive workup. At one visit, Dr. Zuelsdorff said, they were asked to complete a questionnaire concerning 27 different stressful life events. These experiences were deeply disturbing and potentially life altering. They included childhood experiences, such as parental abuse, alcoholism, and flunking out of school, and adult experiences, such as combat experience, bankruptcy, or the death of a child. She then analyzed how the total number of stressful events in a person’s life changed that person’s risk of developing dementia.
Of the entire WRAP cohort, 1,314 completed the stress questionnaire and had sufficient cognitive data. These subjects were largely white (1,232). Only 82 were African American, a weakness of the study, Dr. Zuelsdorff noted, but a reflection of Wisconsin’s racial makeup.
They were similar in a number of important ways, including age (mean, 58 years), proportion of apolipoprotein E4 (APOE4) allele carriers (38%), and years of education (mean, 16). African Americans had higher body mass index (33.3 vs. 28.8 kg/m2), reported less physical activity, were more often current smokers (22% vs. 6%), and had a lower-quality education despite similar time in the classroom.
On average, African Americans reported a mean of 4.5 stressful life events – a significant, 60% increase over the 2.8 reported by whites. The experience of stressful events directly influenced a subject’s performance in the speed and flexibility domain of executive function and in working memory, Dr. Zuelsdorff said.
“We saw a substantial 13.5% attenuation of performance on speed and flexibility, but we also saw attenuation in working memory. That told us something else was going on – that it wasn’t just the accumulation of stressful events but that there was a differential vulnerability. The negative association between lifetime stressful events and the cognitive domains was much stronger in blacks than in whites.”
She then conducted a risk analysis to determine the impact of stress. “Stress was right at the top for blacks. It tended to be one of the most important predictors of cognitive function. The only other one that came out as significant was quality of education. The social environment in this sample was more important than the traditional risk factors of genetics and chronological age.”
The study barely scratches the surface of the stress/cognition conundrum, Dr. Zuelsdorff said. “We would like to look at the timing next and see if there is some critical window that is especially influencing to cognitive health. We then need to target both interventions and effect modifiers, such as social, community, and financial resources that might buffer the effects of this negative stress.”
She had no financial disclosures.
[email protected]
On Twitter @alz_gal
LONDON – African Americans not only report experiencing more stressful experiences across their lifespans than do whites, but they have more cognitive consequences from them as well, new research suggests.
In fact, the weight of these experiences affected cognition even more than traditional risk factors like genetic status and even age, Megan Zuelsdorff, PhD, said at the Alzheimer’s Association International Conference.
Racial disparities have long been evident in the development and progression of dementia, Dr. Zuelsdorff said. Socioeconomic factors are also important players in this scenario. Stress, likewise, has long been linked to poorer cognitive health. “But, there are still significant gaps in our knowledge of stress and cognition. The contribution of stress to well-established socioeconomic impacts on health is unclear, and the research focus here has always been on events happening in midlife and onward. But, it’s crucial to expand this window of time backward to include earlier years. If we look at a graph of cognitive function across the lifespan, the rate of decline doesn’t vary much. What we do see is that blacks, starting at midlife, are closer to the clinical threshold of cognitive impairment and may reach the threshold at an earlier age. What this said to me is that we needed to look at these earlier life factors that could bring someone to this state of lower cognitive function in midlife.”
Dr. Zuelsdorff and her colleagues analyzed data from the Wisconsin Registry for Alzheimer’s Prevention to examine this question. The observational study comprises 1,500 adults being followed for 15-20 years and is enriched for those with a family history of Alzheimer’s disease. The main goal of WRAP is to understand the biological, medical, environmental, and lifestyle factors that increase a person’s risk of developing Alzheimer’s disease.
Subjects have a study visit every 2-4 years that includes a full physical and cognitive workup. At one visit, Dr. Zuelsdorff said, they were asked to complete a questionnaire concerning 27 different stressful life events. These experiences were deeply disturbing and potentially life altering. They included childhood experiences, such as parental abuse, alcoholism, and flunking out of school, and adult experiences, such as combat experience, bankruptcy, or the death of a child. She then analyzed how the total number of stressful events in a person’s life changed that person’s risk of developing dementia.
Of the entire WRAP cohort, 1,314 completed the stress questionnaire and had sufficient cognitive data. These subjects were largely white (1,232). Only 82 were African American, a weakness of the study, Dr. Zuelsdorff noted, but a reflection of Wisconsin’s racial makeup.
They were similar in a number of important ways, including age (mean, 58 years), proportion of apolipoprotein E4 (APOE4) allele carriers (38%), and years of education (mean, 16). African Americans had higher body mass index (33.3 vs. 28.8 kg/m2), reported less physical activity, were more often current smokers (22% vs. 6%), and had a lower-quality education despite similar time in the classroom.
On average, African Americans reported a mean of 4.5 stressful life events – a significant, 60% increase over the 2.8 reported by whites. The experience of stressful events directly influenced a subject’s performance in the speed and flexibility domain of executive function and in working memory, Dr. Zuelsdorff said.
“We saw a substantial 13.5% attenuation of performance on speed and flexibility, but we also saw attenuation in working memory. That told us something else was going on – that it wasn’t just the accumulation of stressful events but that there was a differential vulnerability. The negative association between lifetime stressful events and the cognitive domains was much stronger in blacks than in whites.”
She then conducted a risk analysis to determine the impact of stress. “Stress was right at the top for blacks. It tended to be one of the most important predictors of cognitive function. The only other one that came out as significant was quality of education. The social environment in this sample was more important than the traditional risk factors of genetics and chronological age.”
The study barely scratches the surface of the stress/cognition conundrum, Dr. Zuelsdorff said. “We would like to look at the timing next and see if there is some critical window that is especially influencing to cognitive health. We then need to target both interventions and effect modifiers, such as social, community, and financial resources that might buffer the effects of this negative stress.”
She had no financial disclosures.
[email protected]
On Twitter @alz_gal
AT AAIC 2017
Key clinical point:
Major finding: African Americans reported 60% more stressful life events than whites, which were tied to a 13% decrease in the speed and flexibility domain of executive function.
Data source: The observational cohort study comprised 1,314 subjects.
Disclosures: Dr. Zuelsdorff had no financial disclosures.
ANCA-associated vasculitis appears to increase risk of stroke, death
MADRID – Small-vessel vasculitis associated with antineutrophil cytoplasmic autoantibodies (ANCAs) appears to increase the risk of stroke and overall mortality, results of a French retrospective study suggest.
Patients with ANCA-associated vasculitis (AAV) were twice as likely as those without to experience a stroke over 7.5 years, Grégory Pugnet, MD, reported at the European Congress of Rheumatology. Their all-cause mortality was also significantly higher, with 30% of the deaths attributed to cardiovascular causes, said Dr. Pugnet of the Internal Medicine Service at Purpan Hospital in Toulouse, France.
“We think this [shows that it] is very important to monitor [these patients] and to be vigilant in our search for cardiovascular complications and cardiovascular risk factors in this population,” he said.
Dr. Pugnet and his colleagues conducted a retrospective study of 125 patients with AAV who were diagnosed in a teaching hospital between 1981 and 2015. He compared cardiovascular outcomes and mortality between this cohort and two French regional registries: the Midi-Pyrénées County Mortality and Acute Myocardial Infarction Registry and the Dijon Stroke Registry. Outcomes were the date of first acute myocardial infarction, date of first stroke, and date of death; the mean follow-up was about 90 months.
Of the 125 patients with AAV, 99 had granulomatosis with polyangiitis, and 26 had microscopic polyangiitis. Preexisting cardiovascular disease was present in 23. Patients were a mean of 61 years old. Hypertension, peripheral artery disease, and coronary artery disease were all more common among those with cardiovascular disease. These patients were also more likely to smoke.
Over the follow-up period, there were 10 acute myocardial infarctions for an incidence of 8.5 per 1,000 person-years. The MI incidence in the Midi-Pyrénées registry was 2.2 per 1,000 person-years, which was a significant difference in an unadjusted analysis. But after adjusting for age, AAV patients were not significantly more likely to experience a heart attack than were those in the registry.
There were nine strokes during the follow-up period for an incidence of 10.2 per 1,000 person-years. After adjusting for age, this was more than three times higher than the rate of 1.9 per 1,000 person-year in the Dijon Stroke Registry – a significant difference.
A total of 22 AAV patients died during the follow-up period, translating to a mortality of 22.5 per 1,000 person-years. Mortality in the stroke registry was 1.9 per 1,000 person-years. An age-adjusted analysis found that AAV patients were about 1.6 times more likely to die than were those in the Midi-Pyrénées registry.
A multivariate regression analysis identified some factors that were independently associated with the outcomes. Smoking almost quadrupled the risk of having any cardiovascular event (hazard ratio, 3.7), and having had a plasma exchange tripled it (HR, 2.9). Smoking and a history of coronary artery disease were significant risk factors for myocardial infarction (HRs of 8.8 and 10.3, respectively). Dr. Pugnet and his associates didn’t find any significant independent risk factors for stroke. Age was not independently associated with any of the outcomes.
Dr. Pugnet reported receiving travel support from AbbVie and Actelion, fees for serving on an advisory board from Grifols, and lecture fees from AbbVie.
[email protected]
On Twitter @alz_gal
MADRID – Small-vessel vasculitis associated with antineutrophil cytoplasmic autoantibodies (ANCAs) appears to increase the risk of stroke and overall mortality, results of a French retrospective study suggest.
Patients with ANCA-associated vasculitis (AAV) were twice as likely as those without to experience a stroke over 7.5 years, Grégory Pugnet, MD, reported at the European Congress of Rheumatology. Their all-cause mortality was also significantly higher, with 30% of the deaths attributed to cardiovascular causes, said Dr. Pugnet of the Internal Medicine Service at Purpan Hospital in Toulouse, France.
“We think this [shows that it] is very important to monitor [these patients] and to be vigilant in our search for cardiovascular complications and cardiovascular risk factors in this population,” he said.
Dr. Pugnet and his colleagues conducted a retrospective study of 125 patients with AAV who were diagnosed in a teaching hospital between 1981 and 2015. He compared cardiovascular outcomes and mortality between this cohort and two French regional registries: the Midi-Pyrénées County Mortality and Acute Myocardial Infarction Registry and the Dijon Stroke Registry. Outcomes were the date of first acute myocardial infarction, date of first stroke, and date of death; the mean follow-up was about 90 months.
Of the 125 patients with AAV, 99 had granulomatosis with polyangiitis, and 26 had microscopic polyangiitis. Preexisting cardiovascular disease was present in 23. Patients were a mean of 61 years old. Hypertension, peripheral artery disease, and coronary artery disease were all more common among those with cardiovascular disease. These patients were also more likely to smoke.
Over the follow-up period, there were 10 acute myocardial infarctions for an incidence of 8.5 per 1,000 person-years. The MI incidence in the Midi-Pyrénées registry was 2.2 per 1,000 person-years, which was a significant difference in an unadjusted analysis. But after adjusting for age, AAV patients were not significantly more likely to experience a heart attack than were those in the registry.
There were nine strokes during the follow-up period for an incidence of 10.2 per 1,000 person-years. After adjusting for age, this was more than three times higher than the rate of 1.9 per 1,000 person-year in the Dijon Stroke Registry – a significant difference.
A total of 22 AAV patients died during the follow-up period, translating to a mortality of 22.5 per 1,000 person-years. Mortality in the stroke registry was 1.9 per 1,000 person-years. An age-adjusted analysis found that AAV patients were about 1.6 times more likely to die than were those in the Midi-Pyrénées registry.
A multivariate regression analysis identified some factors that were independently associated with the outcomes. Smoking almost quadrupled the risk of having any cardiovascular event (hazard ratio, 3.7), and having had a plasma exchange tripled it (HR, 2.9). Smoking and a history of coronary artery disease were significant risk factors for myocardial infarction (HRs of 8.8 and 10.3, respectively). Dr. Pugnet and his associates didn’t find any significant independent risk factors for stroke. Age was not independently associated with any of the outcomes.
Dr. Pugnet reported receiving travel support from AbbVie and Actelion, fees for serving on an advisory board from Grifols, and lecture fees from AbbVie.
[email protected]
On Twitter @alz_gal
MADRID – Small-vessel vasculitis associated with antineutrophil cytoplasmic autoantibodies (ANCAs) appears to increase the risk of stroke and overall mortality, results of a French retrospective study suggest.
Patients with ANCA-associated vasculitis (AAV) were twice as likely as those without to experience a stroke over 7.5 years, Grégory Pugnet, MD, reported at the European Congress of Rheumatology. Their all-cause mortality was also significantly higher, with 30% of the deaths attributed to cardiovascular causes, said Dr. Pugnet of the Internal Medicine Service at Purpan Hospital in Toulouse, France.
“We think this [shows that it] is very important to monitor [these patients] and to be vigilant in our search for cardiovascular complications and cardiovascular risk factors in this population,” he said.
Dr. Pugnet and his colleagues conducted a retrospective study of 125 patients with AAV who were diagnosed in a teaching hospital between 1981 and 2015. He compared cardiovascular outcomes and mortality between this cohort and two French regional registries: the Midi-Pyrénées County Mortality and Acute Myocardial Infarction Registry and the Dijon Stroke Registry. Outcomes were the date of first acute myocardial infarction, date of first stroke, and date of death; the mean follow-up was about 90 months.
Of the 125 patients with AAV, 99 had granulomatosis with polyangiitis, and 26 had microscopic polyangiitis. Preexisting cardiovascular disease was present in 23. Patients were a mean of 61 years old. Hypertension, peripheral artery disease, and coronary artery disease were all more common among those with cardiovascular disease. These patients were also more likely to smoke.
Over the follow-up period, there were 10 acute myocardial infarctions for an incidence of 8.5 per 1,000 person-years. The MI incidence in the Midi-Pyrénées registry was 2.2 per 1,000 person-years, which was a significant difference in an unadjusted analysis. But after adjusting for age, AAV patients were not significantly more likely to experience a heart attack than were those in the registry.
There were nine strokes during the follow-up period for an incidence of 10.2 per 1,000 person-years. After adjusting for age, this was more than three times higher than the rate of 1.9 per 1,000 person-year in the Dijon Stroke Registry – a significant difference.
A total of 22 AAV patients died during the follow-up period, translating to a mortality of 22.5 per 1,000 person-years. Mortality in the stroke registry was 1.9 per 1,000 person-years. An age-adjusted analysis found that AAV patients were about 1.6 times more likely to die than were those in the Midi-Pyrénées registry.
A multivariate regression analysis identified some factors that were independently associated with the outcomes. Smoking almost quadrupled the risk of having any cardiovascular event (hazard ratio, 3.7), and having had a plasma exchange tripled it (HR, 2.9). Smoking and a history of coronary artery disease were significant risk factors for myocardial infarction (HRs of 8.8 and 10.3, respectively). Dr. Pugnet and his associates didn’t find any significant independent risk factors for stroke. Age was not independently associated with any of the outcomes.
Dr. Pugnet reported receiving travel support from AbbVie and Actelion, fees for serving on an advisory board from Grifols, and lecture fees from AbbVie.
[email protected]
On Twitter @alz_gal
AT THE EULAR 2017 CONGRESS
Key clinical point:
Major finding: AAV patients were twice as likely as those without the vasculitis to experience a stroke over 7.5 years.
Data source: A retrospective comparison of 125 AAV patients and patients from two French regional registries: the Midi-Pyrénées County Mortality and Acute Myocardial Infarction Registry and the Dijon Stroke Registry.
Disclosures: Dr. Pugnet reported receiving travel support from AbbVie and Actelion, fees for serving on an advisory board from Grifols, and lecture fees from AbbVie.
Sustained remission on biologics bodes well for children with JIA
MADRID – Many children with juvenile idiopathic arthritis (JIA) who do well on biologics for a prolonged period will stay in remission after the medication is withdrawn, some new real-world data suggest.
A database review found that 70% of those in remission for at least 1.5 years remained in remission after stopping their biologic agent. Patients taking tocilizumab had the best outcomes, with 8 months of sustained, drug-free remission and only a 12% rate of disease flare, Ekaterina Alexeeva, MD, reported at the European Congress of Rheumatology.
“Prolonged therapy with biologic agents may cause adverse events which lead to the necessity of discontinuation of therapy in patients once complete disease quiescence has been achieved,” she said. While long-term drug studies do offer some glimpse into the stability of remission after drug discontinuation, these data don’t often reflect real-world experience.
“Clinical trials are made up of highly selected participants in contorted conditions with limited duration. Real-word data, collected under real-life practical circumstances, provide additional characteristics of patient populations, information on the effectiveness and safety of treatment over time, and the outcomes we can achieve under real-world conditions,” Dr. Alexeeva said.
She plumbed a national JIA database to find 83 patients who had achieved longstanding clinical remission on a biologic therapy, then either rapidly discontinued treatment (61) or went through a tapering protocol (22), according to their doctors’ decision. These children were a mean of 11 years old, with mean disease duration of 2 years before the initiation of a biologic treatment. Systemic JIA was present in 40%; 22% had oligoarthritis, and 38% had polyarthritis.
All of the patients with systemic JIA were taking tocilizumab, although only 25% took it as monotherapy. Other medications being used were methotrexate (42%), cyclosporine (15%), glucocorticoids (15%), and leflunomide (3%).
For those with oligo- and polyarthritis, etanercept was the most commonly employed biologic (70%), followed by adalimumab (30%). Most (68%) were on monotherapy with their agent; however, 18% of those taking etanercept and 14% of those taking adalimumab were also taking methotrexate.
Before discontinuing their medication, the systemic JIA patients taking tocilizumab had a mean 43 months of inactive disease and a mean 37 months of remission. Among those taking adalimumab, the mean period of inactive disease was 48 months and the mean remission was 40 months. Among those taking etanercept, the mean period of inactive disease was 40 months and the mean remission was 34 months.
After discontinuing the biologic, the mean overall remission length was 6 months for all patients. However, this varied considerably with diagnosis and medication, Dr. Alexeeva noted. For systemic JIA patients taking tocilizumab, remission ranged from a minimum of 1 month to a maximum of 48 months. For those taking adalimumab, remission ranged from 4 to 38 months. Remission ranged from 1 to 20 months among those taking etanercept.
Disease flare occurred in 12% of those taking tocilizumab, at a mean of 8 months after discontinuation; 31% of those taking etanercept at a mean of 5.5 months; and 60% of those taking adalimumab at a mean of 4 months. Time to flare was longest among those taking tocilizumab (6-18 months), followed by etanercept (1.5-12 months) and adalimumab (1-13 months).
Dr. Alexeeva disclosed research funding and support from numerous pharmaceutical companies.
[email protected]
On Twitter @alz_gal
MADRID – Many children with juvenile idiopathic arthritis (JIA) who do well on biologics for a prolonged period will stay in remission after the medication is withdrawn, some new real-world data suggest.
A database review found that 70% of those in remission for at least 1.5 years remained in remission after stopping their biologic agent. Patients taking tocilizumab had the best outcomes, with 8 months of sustained, drug-free remission and only a 12% rate of disease flare, Ekaterina Alexeeva, MD, reported at the European Congress of Rheumatology.
“Prolonged therapy with biologic agents may cause adverse events which lead to the necessity of discontinuation of therapy in patients once complete disease quiescence has been achieved,” she said. While long-term drug studies do offer some glimpse into the stability of remission after drug discontinuation, these data don’t often reflect real-world experience.
“Clinical trials are made up of highly selected participants in contorted conditions with limited duration. Real-word data, collected under real-life practical circumstances, provide additional characteristics of patient populations, information on the effectiveness and safety of treatment over time, and the outcomes we can achieve under real-world conditions,” Dr. Alexeeva said.
She plumbed a national JIA database to find 83 patients who had achieved longstanding clinical remission on a biologic therapy, then either rapidly discontinued treatment (61) or went through a tapering protocol (22), according to their doctors’ decision. These children were a mean of 11 years old, with mean disease duration of 2 years before the initiation of a biologic treatment. Systemic JIA was present in 40%; 22% had oligoarthritis, and 38% had polyarthritis.
All of the patients with systemic JIA were taking tocilizumab, although only 25% took it as monotherapy. Other medications being used were methotrexate (42%), cyclosporine (15%), glucocorticoids (15%), and leflunomide (3%).
For those with oligo- and polyarthritis, etanercept was the most commonly employed biologic (70%), followed by adalimumab (30%). Most (68%) were on monotherapy with their agent; however, 18% of those taking etanercept and 14% of those taking adalimumab were also taking methotrexate.
Before discontinuing their medication, the systemic JIA patients taking tocilizumab had a mean 43 months of inactive disease and a mean 37 months of remission. Among those taking adalimumab, the mean period of inactive disease was 48 months and the mean remission was 40 months. Among those taking etanercept, the mean period of inactive disease was 40 months and the mean remission was 34 months.
After discontinuing the biologic, the mean overall remission length was 6 months for all patients. However, this varied considerably with diagnosis and medication, Dr. Alexeeva noted. For systemic JIA patients taking tocilizumab, remission ranged from a minimum of 1 month to a maximum of 48 months. For those taking adalimumab, remission ranged from 4 to 38 months. Remission ranged from 1 to 20 months among those taking etanercept.
Disease flare occurred in 12% of those taking tocilizumab, at a mean of 8 months after discontinuation; 31% of those taking etanercept at a mean of 5.5 months; and 60% of those taking adalimumab at a mean of 4 months. Time to flare was longest among those taking tocilizumab (6-18 months), followed by etanercept (1.5-12 months) and adalimumab (1-13 months).
Dr. Alexeeva disclosed research funding and support from numerous pharmaceutical companies.
[email protected]
On Twitter @alz_gal
MADRID – Many children with juvenile idiopathic arthritis (JIA) who do well on biologics for a prolonged period will stay in remission after the medication is withdrawn, some new real-world data suggest.
A database review found that 70% of those in remission for at least 1.5 years remained in remission after stopping their biologic agent. Patients taking tocilizumab had the best outcomes, with 8 months of sustained, drug-free remission and only a 12% rate of disease flare, Ekaterina Alexeeva, MD, reported at the European Congress of Rheumatology.
“Prolonged therapy with biologic agents may cause adverse events which lead to the necessity of discontinuation of therapy in patients once complete disease quiescence has been achieved,” she said. While long-term drug studies do offer some glimpse into the stability of remission after drug discontinuation, these data don’t often reflect real-world experience.
“Clinical trials are made up of highly selected participants in contorted conditions with limited duration. Real-word data, collected under real-life practical circumstances, provide additional characteristics of patient populations, information on the effectiveness and safety of treatment over time, and the outcomes we can achieve under real-world conditions,” Dr. Alexeeva said.
She plumbed a national JIA database to find 83 patients who had achieved longstanding clinical remission on a biologic therapy, then either rapidly discontinued treatment (61) or went through a tapering protocol (22), according to their doctors’ decision. These children were a mean of 11 years old, with mean disease duration of 2 years before the initiation of a biologic treatment. Systemic JIA was present in 40%; 22% had oligoarthritis, and 38% had polyarthritis.
All of the patients with systemic JIA were taking tocilizumab, although only 25% took it as monotherapy. Other medications being used were methotrexate (42%), cyclosporine (15%), glucocorticoids (15%), and leflunomide (3%).
For those with oligo- and polyarthritis, etanercept was the most commonly employed biologic (70%), followed by adalimumab (30%). Most (68%) were on monotherapy with their agent; however, 18% of those taking etanercept and 14% of those taking adalimumab were also taking methotrexate.
Before discontinuing their medication, the systemic JIA patients taking tocilizumab had a mean 43 months of inactive disease and a mean 37 months of remission. Among those taking adalimumab, the mean period of inactive disease was 48 months and the mean remission was 40 months. Among those taking etanercept, the mean period of inactive disease was 40 months and the mean remission was 34 months.
After discontinuing the biologic, the mean overall remission length was 6 months for all patients. However, this varied considerably with diagnosis and medication, Dr. Alexeeva noted. For systemic JIA patients taking tocilizumab, remission ranged from a minimum of 1 month to a maximum of 48 months. For those taking adalimumab, remission ranged from 4 to 38 months. Remission ranged from 1 to 20 months among those taking etanercept.
Disease flare occurred in 12% of those taking tocilizumab, at a mean of 8 months after discontinuation; 31% of those taking etanercept at a mean of 5.5 months; and 60% of those taking adalimumab at a mean of 4 months. Time to flare was longest among those taking tocilizumab (6-18 months), followed by etanercept (1.5-12 months) and adalimumab (1-13 months).
Dr. Alexeeva disclosed research funding and support from numerous pharmaceutical companies.
[email protected]
On Twitter @alz_gal
AT THE EULAR 2017 CONGRESS
Key clinical point:
Major finding: Overall, 70% of those who were in remission for at least 1.5 years remained in remission after stopping their biologic.
Data source: A database review comprising 83 children.
Disclosures: Dr. Alexeeva disclosed research and grant support from numerous pharmaceutical companies.