Michele G. Sullivan

Two simple recommendations for older patients with asthma – keeping medication in the bathroom and integrating its use into a daily routine – can significantly improve adherence to inhaled corticosteroids.

When patients consistently did either of those, adherence rose threefold, compared with patients who didn’t, Dr. Alex Federman and his associates wrote in the August issue of the Journal of Internal Medicine.

The findings suggest that clinicians might help improve adherence by suggesting that their patients store the medication in their bathroom cabinet, and take it, for example, when they brush their teeth every day.

©CandyBoxImages/thinkstockphotos.com

"Because adherence strategies are modifiable, the findings in this study may provide clinicians and care coaches with straightforward and useful messages to help older patients improve their medication adherence," wrote Dr. Federman of Icahn School of Medicine at Mount Sinai, New York, and his coauthors (J. Intern. Med. 2014 Aug. 5 [doi:10.1007/s11606-014-2940-8]).

The team investigated adherence to inhaled corticosteroids among 358 elderly patients with asthma. They were a mean of 67 years old, with 31% older than 70 years. Most (84%) were women and many were Latino (38%). Black patients comprised 31% of the cohort and the others were non-Hispanic whites.

The majority had a low monthly income ($1,350 or less), and 25% were not fully literate in English. Many had comorbid psychological conditions, including depression (20%) and anxiety (21%).

Low health literacy was common (34%), although most (71%) did understand that they would always have asthma and that it could not be cured (81%) But half believed that they only had the disease when they were symptomatic. In a survey of medication beliefs, most did believe that the steroids were good for them and that their benefits outweighed the risks.

However, only 37% of the cohort reported good medication adherence. This proportion was significantly worse among blacks and Hispanics; those with lower incomes and lower education; those born in Puerto Rico and the Dominican Republic; and those with poor physical health, anxiety, or depression.

The authors identified six medication adherence strategies among the group: keeping the medication in a usual location (44%); integrating it into their daily routine (33%); taking it at a specific time of day (22%); taking it with other medications (13%); using it only when needed; (13%) and using other reminders (12%). Less than 2% reported using written notes as a reminder or having someone else remind them; 4% had no specific strategy.

The most common places to keep medicine were at the bedside (20%) and in the bathroom (9%). Those who integrated taking it with other daily routines did in the morning (12%) and at bedtime (8%).

Only three of the strategies were significantly associated with good adherence: keeping medication in the bathroom (16% adherent vs. 5% nonadherent); integrating it into a daily routine (morning 25% vs. 5%; evening 13% vs. 6%); and taking it at a specific time of day (29% vs. 17%).

Courtesy Emily Goodman

Taking the medication only when needed was associated with significantly worse adherence.

After controlling for other variables, only leaving the medication in the bathroom significantly predicted good adherence (odds ratio 3), compared with those who kept it somewhere else).

Those who integrated medication into other daily routines were also significantly more likely to be adherent (OR 3.7) in a partially adjusted model, but not in a fully adjusted model. Still, the authors noted, this recommendation would be a good suggestion toward improving adherence.

Patients who used these two strategies were more likely to be white, have at least a partial education, and to have been born in the United States. Low income, limited English proficiency, low health literacy, poor physical and psychological health, and erroneous beliefs about asthma predicted poor adherence.

The team postulated that there are two types of nonadherence: simple forgetfulness or lack of understanding about its importance and deliberate nonadherence.

"The bathroom and daily routine strategies may address forgetful nonadherence. ... Taking the medication only as needed, on the other hand, may indicate faulty disease or medication beliefs. ... Taken together, these findings provide further evidence of the value of patient-centered care: Clinicians need to understand why patients do not use their medications appropriately before counseling patients on ways to improve adherence."

The study was supported by a grant from the National Heart, Lung, and Blood Institute. None of the authors had any financial disclosures.

[email protected]

Two simple recommendations for older patients with asthma – keeping medication in the bathroom and integrating its use into a daily routine – can significantly improve adherence to inhaled corticosteroids.

When patients consistently did either of those, adherence rose threefold, compared with patients who didn’t, Dr. Alex Federman and his associates wrote in the August issue of the Journal of Internal Medicine.

The findings suggest that clinicians might help improve adherence by suggesting that their patients store the medication in their bathroom cabinet, and take it, for example, when they brush their teeth every day.

©CandyBoxImages/thinkstockphotos.com

"Because adherence strategies are modifiable, the findings in this study may provide clinicians and care coaches with straightforward and useful messages to help older patients improve their medication adherence," wrote Dr. Federman of Icahn School of Medicine at Mount Sinai, New York, and his coauthors (J. Intern. Med. 2014 Aug. 5 [doi:10.1007/s11606-014-2940-8]).

The team investigated adherence to inhaled corticosteroids among 358 elderly patients with asthma. They were a mean of 67 years old, with 31% older than 70 years. Most (84%) were women and many were Latino (38%). Black patients comprised 31% of the cohort and the others were non-Hispanic whites.

The majority had a low monthly income ($1,350 or less), and 25% were not fully literate in English. Many had comorbid psychological conditions, including depression (20%) and anxiety (21%).

Low health literacy was common (34%), although most (71%) did understand that they would always have asthma and that it could not be cured (81%) But half believed that they only had the disease when they were symptomatic. In a survey of medication beliefs, most did believe that the steroids were good for them and that their benefits outweighed the risks.

However, only 37% of the cohort reported good medication adherence. This proportion was significantly worse among blacks and Hispanics; those with lower incomes and lower education; those born in Puerto Rico and the Dominican Republic; and those with poor physical health, anxiety, or depression.

The authors identified six medication adherence strategies among the group: keeping the medication in a usual location (44%); integrating it into their daily routine (33%); taking it at a specific time of day (22%); taking it with other medications (13%); using it only when needed; (13%) and using other reminders (12%). Less than 2% reported using written notes as a reminder or having someone else remind them; 4% had no specific strategy.

The most common places to keep medicine were at the bedside (20%) and in the bathroom (9%). Those who integrated taking it with other daily routines did in the morning (12%) and at bedtime (8%).

Only three of the strategies were significantly associated with good adherence: keeping medication in the bathroom (16% adherent vs. 5% nonadherent); integrating it into a daily routine (morning 25% vs. 5%; evening 13% vs. 6%); and taking it at a specific time of day (29% vs. 17%).

Courtesy Emily Goodman

Taking the medication only when needed was associated with significantly worse adherence.

After controlling for other variables, only leaving the medication in the bathroom significantly predicted good adherence (odds ratio 3), compared with those who kept it somewhere else).

Those who integrated medication into other daily routines were also significantly more likely to be adherent (OR 3.7) in a partially adjusted model, but not in a fully adjusted model. Still, the authors noted, this recommendation would be a good suggestion toward improving adherence.

Patients who used these two strategies were more likely to be white, have at least a partial education, and to have been born in the United States. Low income, limited English proficiency, low health literacy, poor physical and psychological health, and erroneous beliefs about asthma predicted poor adherence.

The team postulated that there are two types of nonadherence: simple forgetfulness or lack of understanding about its importance and deliberate nonadherence.

"The bathroom and daily routine strategies may address forgetful nonadherence. ... Taking the medication only as needed, on the other hand, may indicate faulty disease or medication beliefs. ... Taken together, these findings provide further evidence of the value of patient-centered care: Clinicians need to understand why patients do not use their medications appropriately before counseling patients on ways to improve adherence."

The study was supported by a grant from the National Heart, Lung, and Blood Institute. None of the authors had any financial disclosures.

[email protected]

Two simple recommendations for older patients with asthma – keeping medication in the bathroom and integrating its use into a daily routine – can significantly improve adherence to inhaled corticosteroids.

When patients consistently did either of those, adherence rose threefold, compared with patients who didn’t, Dr. Alex Federman and his associates wrote in the August issue of the Journal of Internal Medicine.

The findings suggest that clinicians might help improve adherence by suggesting that their patients store the medication in their bathroom cabinet, and take it, for example, when they brush their teeth every day.

©CandyBoxImages/thinkstockphotos.com

"Because adherence strategies are modifiable, the findings in this study may provide clinicians and care coaches with straightforward and useful messages to help older patients improve their medication adherence," wrote Dr. Federman of Icahn School of Medicine at Mount Sinai, New York, and his coauthors (J. Intern. Med. 2014 Aug. 5 [doi:10.1007/s11606-014-2940-8]).

The team investigated adherence to inhaled corticosteroids among 358 elderly patients with asthma. They were a mean of 67 years old, with 31% older than 70 years. Most (84%) were women and many were Latino (38%). Black patients comprised 31% of the cohort and the others were non-Hispanic whites.

The majority had a low monthly income ($1,350 or less), and 25% were not fully literate in English. Many had comorbid psychological conditions, including depression (20%) and anxiety (21%).

Low health literacy was common (34%), although most (71%) did understand that they would always have asthma and that it could not be cured (81%) But half believed that they only had the disease when they were symptomatic. In a survey of medication beliefs, most did believe that the steroids were good for them and that their benefits outweighed the risks.

However, only 37% of the cohort reported good medication adherence. This proportion was significantly worse among blacks and Hispanics; those with lower incomes and lower education; those born in Puerto Rico and the Dominican Republic; and those with poor physical health, anxiety, or depression.

The authors identified six medication adherence strategies among the group: keeping the medication in a usual location (44%); integrating it into their daily routine (33%); taking it at a specific time of day (22%); taking it with other medications (13%); using it only when needed; (13%) and using other reminders (12%). Less than 2% reported using written notes as a reminder or having someone else remind them; 4% had no specific strategy.

The most common places to keep medicine were at the bedside (20%) and in the bathroom (9%). Those who integrated taking it with other daily routines did in the morning (12%) and at bedtime (8%).

Only three of the strategies were significantly associated with good adherence: keeping medication in the bathroom (16% adherent vs. 5% nonadherent); integrating it into a daily routine (morning 25% vs. 5%; evening 13% vs. 6%); and taking it at a specific time of day (29% vs. 17%).

Courtesy Emily Goodman

Taking the medication only when needed was associated with significantly worse adherence.

After controlling for other variables, only leaving the medication in the bathroom significantly predicted good adherence (odds ratio 3), compared with those who kept it somewhere else).

Those who integrated medication into other daily routines were also significantly more likely to be adherent (OR 3.7) in a partially adjusted model, but not in a fully adjusted model. Still, the authors noted, this recommendation would be a good suggestion toward improving adherence.

Patients who used these two strategies were more likely to be white, have at least a partial education, and to have been born in the United States. Low income, limited English proficiency, low health literacy, poor physical and psychological health, and erroneous beliefs about asthma predicted poor adherence.

The team postulated that there are two types of nonadherence: simple forgetfulness or lack of understanding about its importance and deliberate nonadherence.

"The bathroom and daily routine strategies may address forgetful nonadherence. ... Taking the medication only as needed, on the other hand, may indicate faulty disease or medication beliefs. ... Taken together, these findings provide further evidence of the value of patient-centered care: Clinicians need to understand why patients do not use their medications appropriately before counseling patients on ways to improve adherence."

The study was supported by a grant from the National Heart, Lung, and Blood Institute. None of the authors had any financial disclosures.

[email protected]

Elderly patients who report poor sleep quality face a significantly increased risk of suicide for up to a decade, whether or not depression is also present.

Even after controlling for comorbid depression, investigators found that impaired sleep was associated with a 20% increased risk of suicide in these patients.

Results of the prospective observational study suggest that regularly asking about sleep quality might help improve suicide risk assessment, Rebecca A. Bernert, Ph.D., and her colleagues reported online Aug. 13 in JAMA Psychiatry (doi: 10.1001/jamapsychiatry.2014.1126).

Older adults tend to seek more physician care in the final weeks and months before a suicide than do other at-risk populations (73% and 45%, respectively).

"Furthermore, at least one psychological autopsy study indicates that disturbed sleep is visible to friends and family members in the weeks and months preceding death," wrote Dr. Bernert of Stanford (Calif.) University and her coauthors. "Targeting disturbed sleep as a visible warning sign of suicide may, in this way, constitute a novel opportunity for improved risk detection; this more narrowed, demographic focus may specifically inform intervention among a group at heightened risk for suicide."

The cohort comprised 420 subjects who were a subpopulation of the Established Populations for Epidemiologic Studies of the Elderly study. This project followed 14,500 older adults from 1981 to 1993; its purpose was to identify predictors of mortality, hospitalization, and placement in long-term care facilities and to investigate risk factors for chronic diseases and loss of function.

From this group, 400 controls were matched to 20 subjects who had committed suicide.

Sleep was evaluated with a five-item Sleep Quality Index (SQI) constructed by the investigators. Other measures included assessments of depression, cognition, and physical function.

Subjects were a mean of 75 years old at baseline; 60% were white, 19% were African American, and 1% were Asian, American Indian, or Hispanic. The methods of suicide included firearm (62%), cutting (10%), hanging (9%), poisoning (5%), drowning (5%), lethal jump (5%), and suffocation (5%).

The mean SQI scores were significantly higher among those who committed suicide than among the controls (10 vs. 8). Individuals who committed suicide also reported higher scores on all of the SQI subsets: difficulty falling asleep, difficulty staying asleep, early morning awakening, daytime sleepiness, and nonrestorative sleep.

In the univariate analysis, the total sleep score was a significant predictor of suicide (higher score odds ratio, 1.39) over the 10-year follow-up period. Difficulty falling asleep and nonrestorative sleep also were significant predictors (OR, 2.24 and 2.17, respectively).

After controlling for the presence of baseline comorbid depression, the investigators found that the relationship between overall sleep quality and suicide remained significant (OR, 1.2). Difficulty falling asleep and nonrestorative sleep lost their significance in the multivariate analysis.

The authors proposed that sleep-related deficits in cognitive and emotional processing might be a key factor in suicide among such patients.

"Research indicates that sleep fragmentation results in increased emotional reactivity, intensifying negative emotional responses while blunting positive affect," they noted. "Similarly, sleep deprivation among healthy adults is associated with amplification of amygdala activation, as well as increased reactivity to negative emotions such as anger and fear. Notably, a night of recovery sleep following sleep deprivation reverses this effect, decreasing amygdala activation and reducing such emotional reactivity.

"We propose that such deficits may lower the threshold for suicidal behaviors by impairing the processing of emotionally salient information and associated neural circuitry."

The authors cited several limitations of their study. For example, the measures of sleep quality were self-reported rather than measured objectively. Also, diagnostic information that might influence sleep quality, such as chronic pain and substance use, was not included. Finally, the results are not generalizable to the larger population because 19 of the 20 decedents in the current study were male. "Although this reflects national rates and statistics, the present results should be interpreted as primarily applicable to men and chiefly white men," Dr. Bernert and her associates wrote.

The study was sponsored by the National Institutes of Health and the Centers for Disease Control and Prevention. Neither Dr. Bernert nor her coauthors reported any financial conflicts.

Elderly patients who report poor sleep quality face a significantly increased risk of suicide for up to a decade, whether or not depression is also present.

Even after controlling for comorbid depression, investigators found that impaired sleep was associated with a 20% increased risk of suicide in these patients.

Results of the prospective observational study suggest that regularly asking about sleep quality might help improve suicide risk assessment, Rebecca A. Bernert, Ph.D., and her colleagues reported online Aug. 13 in JAMA Psychiatry (doi: 10.1001/jamapsychiatry.2014.1126).

Older adults tend to seek more physician care in the final weeks and months before a suicide than do other at-risk populations (73% and 45%, respectively).

"Furthermore, at least one psychological autopsy study indicates that disturbed sleep is visible to friends and family members in the weeks and months preceding death," wrote Dr. Bernert of Stanford (Calif.) University and her coauthors. "Targeting disturbed sleep as a visible warning sign of suicide may, in this way, constitute a novel opportunity for improved risk detection; this more narrowed, demographic focus may specifically inform intervention among a group at heightened risk for suicide."

The cohort comprised 420 subjects who were a subpopulation of the Established Populations for Epidemiologic Studies of the Elderly study. This project followed 14,500 older adults from 1981 to 1993; its purpose was to identify predictors of mortality, hospitalization, and placement in long-term care facilities and to investigate risk factors for chronic diseases and loss of function.

From this group, 400 controls were matched to 20 subjects who had committed suicide.

Sleep was evaluated with a five-item Sleep Quality Index (SQI) constructed by the investigators. Other measures included assessments of depression, cognition, and physical function.

Subjects were a mean of 75 years old at baseline; 60% were white, 19% were African American, and 1% were Asian, American Indian, or Hispanic. The methods of suicide included firearm (62%), cutting (10%), hanging (9%), poisoning (5%), drowning (5%), lethal jump (5%), and suffocation (5%).

The mean SQI scores were significantly higher among those who committed suicide than among the controls (10 vs. 8). Individuals who committed suicide also reported higher scores on all of the SQI subsets: difficulty falling asleep, difficulty staying asleep, early morning awakening, daytime sleepiness, and nonrestorative sleep.

In the univariate analysis, the total sleep score was a significant predictor of suicide (higher score odds ratio, 1.39) over the 10-year follow-up period. Difficulty falling asleep and nonrestorative sleep also were significant predictors (OR, 2.24 and 2.17, respectively).

After controlling for the presence of baseline comorbid depression, the investigators found that the relationship between overall sleep quality and suicide remained significant (OR, 1.2). Difficulty falling asleep and nonrestorative sleep lost their significance in the multivariate analysis.

The authors proposed that sleep-related deficits in cognitive and emotional processing might be a key factor in suicide among such patients.

"Research indicates that sleep fragmentation results in increased emotional reactivity, intensifying negative emotional responses while blunting positive affect," they noted. "Similarly, sleep deprivation among healthy adults is associated with amplification of amygdala activation, as well as increased reactivity to negative emotions such as anger and fear. Notably, a night of recovery sleep following sleep deprivation reverses this effect, decreasing amygdala activation and reducing such emotional reactivity.

"We propose that such deficits may lower the threshold for suicidal behaviors by impairing the processing of emotionally salient information and associated neural circuitry."

The authors cited several limitations of their study. For example, the measures of sleep quality were self-reported rather than measured objectively. Also, diagnostic information that might influence sleep quality, such as chronic pain and substance use, was not included. Finally, the results are not generalizable to the larger population because 19 of the 20 decedents in the current study were male. "Although this reflects national rates and statistics, the present results should be interpreted as primarily applicable to men and chiefly white men," Dr. Bernert and her associates wrote.

The study was sponsored by the National Institutes of Health and the Centers for Disease Control and Prevention. Neither Dr. Bernert nor her coauthors reported any financial conflicts.

Elderly patients who report poor sleep quality face a significantly increased risk of suicide for up to a decade, whether or not depression is also present.

Even after controlling for comorbid depression, investigators found that impaired sleep was associated with a 20% increased risk of suicide in these patients.

Results of the prospective observational study suggest that regularly asking about sleep quality might help improve suicide risk assessment, Rebecca A. Bernert, Ph.D., and her colleagues reported online Aug. 13 in JAMA Psychiatry (doi: 10.1001/jamapsychiatry.2014.1126).

Older adults tend to seek more physician care in the final weeks and months before a suicide than do other at-risk populations (73% and 45%, respectively).

"Furthermore, at least one psychological autopsy study indicates that disturbed sleep is visible to friends and family members in the weeks and months preceding death," wrote Dr. Bernert of Stanford (Calif.) University and her coauthors. "Targeting disturbed sleep as a visible warning sign of suicide may, in this way, constitute a novel opportunity for improved risk detection; this more narrowed, demographic focus may specifically inform intervention among a group at heightened risk for suicide."

The cohort comprised 420 subjects who were a subpopulation of the Established Populations for Epidemiologic Studies of the Elderly study. This project followed 14,500 older adults from 1981 to 1993; its purpose was to identify predictors of mortality, hospitalization, and placement in long-term care facilities and to investigate risk factors for chronic diseases and loss of function.

From this group, 400 controls were matched to 20 subjects who had committed suicide.

Sleep was evaluated with a five-item Sleep Quality Index (SQI) constructed by the investigators. Other measures included assessments of depression, cognition, and physical function.

Subjects were a mean of 75 years old at baseline; 60% were white, 19% were African American, and 1% were Asian, American Indian, or Hispanic. The methods of suicide included firearm (62%), cutting (10%), hanging (9%), poisoning (5%), drowning (5%), lethal jump (5%), and suffocation (5%).

The mean SQI scores were significantly higher among those who committed suicide than among the controls (10 vs. 8). Individuals who committed suicide also reported higher scores on all of the SQI subsets: difficulty falling asleep, difficulty staying asleep, early morning awakening, daytime sleepiness, and nonrestorative sleep.

In the univariate analysis, the total sleep score was a significant predictor of suicide (higher score odds ratio, 1.39) over the 10-year follow-up period. Difficulty falling asleep and nonrestorative sleep also were significant predictors (OR, 2.24 and 2.17, respectively).

After controlling for the presence of baseline comorbid depression, the investigators found that the relationship between overall sleep quality and suicide remained significant (OR, 1.2). Difficulty falling asleep and nonrestorative sleep lost their significance in the multivariate analysis.

The authors proposed that sleep-related deficits in cognitive and emotional processing might be a key factor in suicide among such patients.

"Research indicates that sleep fragmentation results in increased emotional reactivity, intensifying negative emotional responses while blunting positive affect," they noted. "Similarly, sleep deprivation among healthy adults is associated with amplification of amygdala activation, as well as increased reactivity to negative emotions such as anger and fear. Notably, a night of recovery sleep following sleep deprivation reverses this effect, decreasing amygdala activation and reducing such emotional reactivity.

"We propose that such deficits may lower the threshold for suicidal behaviors by impairing the processing of emotionally salient information and associated neural circuitry."

The authors cited several limitations of their study. For example, the measures of sleep quality were self-reported rather than measured objectively. Also, diagnostic information that might influence sleep quality, such as chronic pain and substance use, was not included. Finally, the results are not generalizable to the larger population because 19 of the 20 decedents in the current study were male. "Although this reflects national rates and statistics, the present results should be interpreted as primarily applicable to men and chiefly white men," Dr. Bernert and her associates wrote.

The study was sponsored by the National Institutes of Health and the Centers for Disease Control and Prevention. Neither Dr. Bernert nor her coauthors reported any financial conflicts.

The addition of a gut microbiome analysis to fecal occult blood testing improved the accuracy of standard colorectal cancer screening by more than 50-fold.

The expanded analysis not only differentiated healthy subjects from those with lesions, it also separated those with adenomas from those with invasive cancers, Dr. Joseph Zackular and colleagues reported in the Aug. 7 issue of Cancer Research and Prevention (Canc. Prev. Res. 2014 Aug. 7 [doi:10.1158/1940-6207.CAPR-14-0129]).

"We found that failure to detect at least one of the [strains measured] served as a signal of the presence of adenoma. The probability of having an adenoma rose more than 50-fold with this added information about microbiome," wrote Dr. Zackular of the University of Michigan, Ann Arbor, and his coauthors.

The investigators used gene sequencing to identify bacterial strains in the fresh stool of 90 subjects: 30 healthy controls, 30 with colorectal adenomas, and 30 with invasive colorectal cancers.

They established a microbiome signature for each group, and striking differences quickly emerged.

Compared with healthy subjects, those with adenomas had a greater abundance of strains of Ruminococcaceae, Clostridium, Pseudomonas, and Porphyromonadaceae.

They also had a lower relative abundance of strains affiliated with Bacteroides, Lachnospiraceae, and Clostridiales; and greater abundances of strains associated with Fusobacterium, Porphyromonas, Lachnospiraceae, and Enterobacteriaceae.

The microbiome composition also differentiated those with adenoma and carcinoma. Compared with those with adenomas, subjects with carcinomas had higher abundances of strains associated with Fusobacterium, Bacteroides, Phascolarctobacterium, and Porphyromonas. Those with adenomas had higher abundances of strains affiliated with Blautia, Ruminococcus, Clostridium, and Lachnospiraceae.

The research team then selected specific strains to include in a logistic regression model to differentiate healthy subjects from those with disease. This they compared with a model consisting of the clinical characteristics that best differentiated the groups.

For adenoma, a model that included the five strains most common in healthy subjects, plus the risk factors of age and race, improved the sensitivity by 4.5-fold above that of age and race alone.

For carcinoma, a model that included age, race, body mass index, and six bacterial strains improved the probability of detecting carcinoma by 5.4-fold over the clinical risk factor model alone.

The model that best differentiated adenomas from carcinomas included body mass index and four bacterial strains. It also significantly improved the sensitivity of the clinical characteristic–only model.

Dr. Zackular and his associates also compared the predictive value of their microbiome-driven risk models with that of the standard fecal occult blood test.

When comparing the clinical risk model alone with the fecal occult blood test alone in the adenoma and carcinoma groups, the odds ratio for carcinoma was 3.76; that test carried a positive predictive value of 61%.

The microbiome analysis alone carried a positive predictive value of 95%. When that was added to a combination model of the fecal test and BMI, the positive predictive value rose to 97%.

Finally, the authors validated the combination model against the age-specific rates of colorectal cancer extracted from the Surveillance, Epidemiology, and End Results (SEER) cancer database.

"Because likely candidates for colorectal cancer screening would target identification of early-stage disease (adenoma), we designed a preliminary screening test based on the five [strains] which were enriched in healthy subjects," Dr. Zackular and his associates explained.

Those who had any detectable level of the five strains were more likely to have a healthy colon and these tests were read as negative. They also calculated the sensitivity and specificity of the test in each 4-year age group ranging from 35 to 85 years old – the sensitivity for any lesion with the combination test was 23% and specificity 100%.

"When we applied the [microbiome] test to [the total] age group, the probability of adenoma was 10.67% ... (1 in 9 chance of having an adenoma). For people 50 years of age, the results suggest a 1 in 26 chance of having an adenoma with a positive test, and for adults 80 years of age, a positive test yielded a 1 in 5 chance of having an adenoma."

The fecal occult blood test alone, however, was much less accurate, with a 6.5% probability of adenoma in those aged 65 years – a 1 in 15 chance of having an adenoma – compared with the 10.7% probability and 1 in 9 chances in the same patient using the microbiome test.

"This [test] has considerable importance in secondary prevention because screening for early-stage colorectal cancer hinges on the ability to detect early pathologic changes," they noted. "The probability of having an adenoma rose more than 50-fold with this added information about microbiome."

The findings not only suggest that the composition of the microbiome can predict the presence of precancerous colon lesions, but that it might, in itself, be functionally related to their development.

Both adenoma and carcinoma were associated with a "dramatic loss" of strains of Clostridium, Bacterioides, and Lachnospiraceae. "Each of these bacterial taxa is a well-known producer of short-chain fatty acids in the colon. The fatty acids are important microbial metabolites that supply nutrients to colonocytes and help maintain epithelial health and homeostasis," Dr. Zackular and his associates said.

One of these fatty acids, butyrate, displays antitumorigenic properties, including inhibiting tumor cell proliferation, initiating tumor cell apoptosis, and mediating T-regulatory cell homeostasis.

"Loss of these important bacterial populations in concert with an enrichment of pathogenic populations likely plays a synergistic role in potentiating tumorigenesis," they wrote.

The study was funded by the National Institutes of Health. Neither Dr. Zackular nor his colleagues had any financial disclosures.

[email protected]

The addition of a gut microbiome analysis to fecal occult blood testing improved the accuracy of standard colorectal cancer screening by more than 50-fold.

The expanded analysis not only differentiated healthy subjects from those with lesions, it also separated those with adenomas from those with invasive cancers, Dr. Joseph Zackular and colleagues reported in the Aug. 7 issue of Cancer Research and Prevention (Canc. Prev. Res. 2014 Aug. 7 [doi:10.1158/1940-6207.CAPR-14-0129]).

"We found that failure to detect at least one of the [strains measured] served as a signal of the presence of adenoma. The probability of having an adenoma rose more than 50-fold with this added information about microbiome," wrote Dr. Zackular of the University of Michigan, Ann Arbor, and his coauthors.

The investigators used gene sequencing to identify bacterial strains in the fresh stool of 90 subjects: 30 healthy controls, 30 with colorectal adenomas, and 30 with invasive colorectal cancers.

They established a microbiome signature for each group, and striking differences quickly emerged.

Compared with healthy subjects, those with adenomas had a greater abundance of strains of Ruminococcaceae, Clostridium, Pseudomonas, and Porphyromonadaceae.

They also had a lower relative abundance of strains affiliated with Bacteroides, Lachnospiraceae, and Clostridiales; and greater abundances of strains associated with Fusobacterium, Porphyromonas, Lachnospiraceae, and Enterobacteriaceae.

The microbiome composition also differentiated those with adenoma and carcinoma. Compared with those with adenomas, subjects with carcinomas had higher abundances of strains associated with Fusobacterium, Bacteroides, Phascolarctobacterium, and Porphyromonas. Those with adenomas had higher abundances of strains affiliated with Blautia, Ruminococcus, Clostridium, and Lachnospiraceae.

The research team then selected specific strains to include in a logistic regression model to differentiate healthy subjects from those with disease. This they compared with a model consisting of the clinical characteristics that best differentiated the groups.

For adenoma, a model that included the five strains most common in healthy subjects, plus the risk factors of age and race, improved the sensitivity by 4.5-fold above that of age and race alone.

For carcinoma, a model that included age, race, body mass index, and six bacterial strains improved the probability of detecting carcinoma by 5.4-fold over the clinical risk factor model alone.

The model that best differentiated adenomas from carcinomas included body mass index and four bacterial strains. It also significantly improved the sensitivity of the clinical characteristic–only model.

Dr. Zackular and his associates also compared the predictive value of their microbiome-driven risk models with that of the standard fecal occult blood test.

When comparing the clinical risk model alone with the fecal occult blood test alone in the adenoma and carcinoma groups, the odds ratio for carcinoma was 3.76; that test carried a positive predictive value of 61%.

The microbiome analysis alone carried a positive predictive value of 95%. When that was added to a combination model of the fecal test and BMI, the positive predictive value rose to 97%.

Finally, the authors validated the combination model against the age-specific rates of colorectal cancer extracted from the Surveillance, Epidemiology, and End Results (SEER) cancer database.

"Because likely candidates for colorectal cancer screening would target identification of early-stage disease (adenoma), we designed a preliminary screening test based on the five [strains] which were enriched in healthy subjects," Dr. Zackular and his associates explained.

Those who had any detectable level of the five strains were more likely to have a healthy colon and these tests were read as negative. They also calculated the sensitivity and specificity of the test in each 4-year age group ranging from 35 to 85 years old – the sensitivity for any lesion with the combination test was 23% and specificity 100%.

"When we applied the [microbiome] test to [the total] age group, the probability of adenoma was 10.67% ... (1 in 9 chance of having an adenoma). For people 50 years of age, the results suggest a 1 in 26 chance of having an adenoma with a positive test, and for adults 80 years of age, a positive test yielded a 1 in 5 chance of having an adenoma."

The fecal occult blood test alone, however, was much less accurate, with a 6.5% probability of adenoma in those aged 65 years – a 1 in 15 chance of having an adenoma – compared with the 10.7% probability and 1 in 9 chances in the same patient using the microbiome test.

"This [test] has considerable importance in secondary prevention because screening for early-stage colorectal cancer hinges on the ability to detect early pathologic changes," they noted. "The probability of having an adenoma rose more than 50-fold with this added information about microbiome."

The findings not only suggest that the composition of the microbiome can predict the presence of precancerous colon lesions, but that it might, in itself, be functionally related to their development.

Both adenoma and carcinoma were associated with a "dramatic loss" of strains of Clostridium, Bacterioides, and Lachnospiraceae. "Each of these bacterial taxa is a well-known producer of short-chain fatty acids in the colon. The fatty acids are important microbial metabolites that supply nutrients to colonocytes and help maintain epithelial health and homeostasis," Dr. Zackular and his associates said.

One of these fatty acids, butyrate, displays antitumorigenic properties, including inhibiting tumor cell proliferation, initiating tumor cell apoptosis, and mediating T-regulatory cell homeostasis.

"Loss of these important bacterial populations in concert with an enrichment of pathogenic populations likely plays a synergistic role in potentiating tumorigenesis," they wrote.

The study was funded by the National Institutes of Health. Neither Dr. Zackular nor his colleagues had any financial disclosures.

[email protected]

The addition of a gut microbiome analysis to fecal occult blood testing improved the accuracy of standard colorectal cancer screening by more than 50-fold.

The expanded analysis not only differentiated healthy subjects from those with lesions, it also separated those with adenomas from those with invasive cancers, Dr. Joseph Zackular and colleagues reported in the Aug. 7 issue of Cancer Research and Prevention (Canc. Prev. Res. 2014 Aug. 7 [doi:10.1158/1940-6207.CAPR-14-0129]).

"We found that failure to detect at least one of the [strains measured] served as a signal of the presence of adenoma. The probability of having an adenoma rose more than 50-fold with this added information about microbiome," wrote Dr. Zackular of the University of Michigan, Ann Arbor, and his coauthors.

The investigators used gene sequencing to identify bacterial strains in the fresh stool of 90 subjects: 30 healthy controls, 30 with colorectal adenomas, and 30 with invasive colorectal cancers.

They established a microbiome signature for each group, and striking differences quickly emerged.

Compared with healthy subjects, those with adenomas had a greater abundance of strains of Ruminococcaceae, Clostridium, Pseudomonas, and Porphyromonadaceae.

They also had a lower relative abundance of strains affiliated with Bacteroides, Lachnospiraceae, and Clostridiales; and greater abundances of strains associated with Fusobacterium, Porphyromonas, Lachnospiraceae, and Enterobacteriaceae.

The microbiome composition also differentiated those with adenoma and carcinoma. Compared with those with adenomas, subjects with carcinomas had higher abundances of strains associated with Fusobacterium, Bacteroides, Phascolarctobacterium, and Porphyromonas. Those with adenomas had higher abundances of strains affiliated with Blautia, Ruminococcus, Clostridium, and Lachnospiraceae.

The research team then selected specific strains to include in a logistic regression model to differentiate healthy subjects from those with disease. This they compared with a model consisting of the clinical characteristics that best differentiated the groups.

For adenoma, a model that included the five strains most common in healthy subjects, plus the risk factors of age and race, improved the sensitivity by 4.5-fold above that of age and race alone.

For carcinoma, a model that included age, race, body mass index, and six bacterial strains improved the probability of detecting carcinoma by 5.4-fold over the clinical risk factor model alone.

The model that best differentiated adenomas from carcinomas included body mass index and four bacterial strains. It also significantly improved the sensitivity of the clinical characteristic–only model.

Dr. Zackular and his associates also compared the predictive value of their microbiome-driven risk models with that of the standard fecal occult blood test.

When comparing the clinical risk model alone with the fecal occult blood test alone in the adenoma and carcinoma groups, the odds ratio for carcinoma was 3.76; that test carried a positive predictive value of 61%.

The microbiome analysis alone carried a positive predictive value of 95%. When that was added to a combination model of the fecal test and BMI, the positive predictive value rose to 97%.

Finally, the authors validated the combination model against the age-specific rates of colorectal cancer extracted from the Surveillance, Epidemiology, and End Results (SEER) cancer database.

"Because likely candidates for colorectal cancer screening would target identification of early-stage disease (adenoma), we designed a preliminary screening test based on the five [strains] which were enriched in healthy subjects," Dr. Zackular and his associates explained.

Those who had any detectable level of the five strains were more likely to have a healthy colon and these tests were read as negative. They also calculated the sensitivity and specificity of the test in each 4-year age group ranging from 35 to 85 years old – the sensitivity for any lesion with the combination test was 23% and specificity 100%.

"When we applied the [microbiome] test to [the total] age group, the probability of adenoma was 10.67% ... (1 in 9 chance of having an adenoma). For people 50 years of age, the results suggest a 1 in 26 chance of having an adenoma with a positive test, and for adults 80 years of age, a positive test yielded a 1 in 5 chance of having an adenoma."

The fecal occult blood test alone, however, was much less accurate, with a 6.5% probability of adenoma in those aged 65 years – a 1 in 15 chance of having an adenoma – compared with the 10.7% probability and 1 in 9 chances in the same patient using the microbiome test.

"This [test] has considerable importance in secondary prevention because screening for early-stage colorectal cancer hinges on the ability to detect early pathologic changes," they noted. "The probability of having an adenoma rose more than 50-fold with this added information about microbiome."

The findings not only suggest that the composition of the microbiome can predict the presence of precancerous colon lesions, but that it might, in itself, be functionally related to their development.

Both adenoma and carcinoma were associated with a "dramatic loss" of strains of Clostridium, Bacterioides, and Lachnospiraceae. "Each of these bacterial taxa is a well-known producer of short-chain fatty acids in the colon. The fatty acids are important microbial metabolites that supply nutrients to colonocytes and help maintain epithelial health and homeostasis," Dr. Zackular and his associates said.

One of these fatty acids, butyrate, displays antitumorigenic properties, including inhibiting tumor cell proliferation, initiating tumor cell apoptosis, and mediating T-regulatory cell homeostasis.

"Loss of these important bacterial populations in concert with an enrichment of pathogenic populations likely plays a synergistic role in potentiating tumorigenesis," they wrote.

The study was funded by the National Institutes of Health. Neither Dr. Zackular nor his colleagues had any financial disclosures.

[email protected]

COPENHAGEN – More than 1 in 10 community-dwelling dementia patients had firearms in their homes, and many of those patients suffered from delusions, hallucinations, or depression, a study of nearly 500 Midwestern patients revealed.

"This combination of a growing elderly population and guns presents some very concerning public health issues," said study investigator Jason Hsieh, a fourth-year medical student at Cleveland Clinic Lerner College of Medicine. "First and foremost, they have the highest suicide rate of any population segment, and a firearm in the home is the most common method of carrying out that act. Dementia patients are also victims of a high rate of homicide, most committed by family members or caregivers."

The inexorable personality changes that develop as disease progresses – aggression, hallucinations, and paranoid delusions – also make the combination of dementia and a loaded weapon an extraordinarily bad one, Mr. Hsieh said.

National statistics already identify gun ownership as fairly high among U.S. elders: As many as 27% own at least one. And those who do have a firearm at home are likely to have more than one – up to six, in fact, according to the National Rifle Association. But a not-insignificant proportion of those senior citizens also have diagnosed dementia disorders, and this combination should be ringing a very loud alarm bell for doctors, families, and communities, Mr. Hsieh said at the Alzheimer’s Association International Conference 2014.

Mr. Hsieh and his colleagues conducted a chart review of 495 patients who underwent initial evaluation for cognitive impairment at an outpatient memory clinic at the Cleveland Clinic. Of these, 89 (18%) lived in a home with a gun; 70% of that group (62) had a formal diagnosis of Alzheimer’s or another dementia disorder.

Associated mental disorders were common in the group with dementia. More than half (33) had delusions, 15 had hallucinations, and nearly all (57) had a diagnosed depression or endorsed depressive symptoms during their evaluation.

The delusions and hallucinations were likely to be paranoid (73% and 47%, respectively). Charts also included descriptions of aggressive behavior – some of which included firing weapons in the house and through open windows. Family members also reported some patients who repeatedly asked for their gun in order to commit suicide.

The unsettling combination is a difficult knot for U.S. doctors, Mr. Hsieh said.

"Doctors have no legal right here to remove weapons from the home," he said. "The only thing we can do is try to identify if one exists and encourage family members and carers to consider removing it or at least store it locked and unloaded in an inaccessible location."

Mr. Hsieh had no financial disclosures.

[email protected]

On Twitter @alz_gal

COPENHAGEN – More than 1 in 10 community-dwelling dementia patients had firearms in their homes, and many of those patients suffered from delusions, hallucinations, or depression, a study of nearly 500 Midwestern patients revealed.

"This combination of a growing elderly population and guns presents some very concerning public health issues," said study investigator Jason Hsieh, a fourth-year medical student at Cleveland Clinic Lerner College of Medicine. "First and foremost, they have the highest suicide rate of any population segment, and a firearm in the home is the most common method of carrying out that act. Dementia patients are also victims of a high rate of homicide, most committed by family members or caregivers."

The inexorable personality changes that develop as disease progresses – aggression, hallucinations, and paranoid delusions – also make the combination of dementia and a loaded weapon an extraordinarily bad one, Mr. Hsieh said.

National statistics already identify gun ownership as fairly high among U.S. elders: As many as 27% own at least one. And those who do have a firearm at home are likely to have more than one – up to six, in fact, according to the National Rifle Association. But a not-insignificant proportion of those senior citizens also have diagnosed dementia disorders, and this combination should be ringing a very loud alarm bell for doctors, families, and communities, Mr. Hsieh said at the Alzheimer’s Association International Conference 2014.

Mr. Hsieh and his colleagues conducted a chart review of 495 patients who underwent initial evaluation for cognitive impairment at an outpatient memory clinic at the Cleveland Clinic. Of these, 89 (18%) lived in a home with a gun; 70% of that group (62) had a formal diagnosis of Alzheimer’s or another dementia disorder.

Associated mental disorders were common in the group with dementia. More than half (33) had delusions, 15 had hallucinations, and nearly all (57) had a diagnosed depression or endorsed depressive symptoms during their evaluation.

The delusions and hallucinations were likely to be paranoid (73% and 47%, respectively). Charts also included descriptions of aggressive behavior – some of which included firing weapons in the house and through open windows. Family members also reported some patients who repeatedly asked for their gun in order to commit suicide.

The unsettling combination is a difficult knot for U.S. doctors, Mr. Hsieh said.

"Doctors have no legal right here to remove weapons from the home," he said. "The only thing we can do is try to identify if one exists and encourage family members and carers to consider removing it or at least store it locked and unloaded in an inaccessible location."

Mr. Hsieh had no financial disclosures.

[email protected]

On Twitter @alz_gal

COPENHAGEN – More than 1 in 10 community-dwelling dementia patients had firearms in their homes, and many of those patients suffered from delusions, hallucinations, or depression, a study of nearly 500 Midwestern patients revealed.

"This combination of a growing elderly population and guns presents some very concerning public health issues," said study investigator Jason Hsieh, a fourth-year medical student at Cleveland Clinic Lerner College of Medicine. "First and foremost, they have the highest suicide rate of any population segment, and a firearm in the home is the most common method of carrying out that act. Dementia patients are also victims of a high rate of homicide, most committed by family members or caregivers."

The inexorable personality changes that develop as disease progresses – aggression, hallucinations, and paranoid delusions – also make the combination of dementia and a loaded weapon an extraordinarily bad one, Mr. Hsieh said.

National statistics already identify gun ownership as fairly high among U.S. elders: As many as 27% own at least one. And those who do have a firearm at home are likely to have more than one – up to six, in fact, according to the National Rifle Association. But a not-insignificant proportion of those senior citizens also have diagnosed dementia disorders, and this combination should be ringing a very loud alarm bell for doctors, families, and communities, Mr. Hsieh said at the Alzheimer’s Association International Conference 2014.

Mr. Hsieh and his colleagues conducted a chart review of 495 patients who underwent initial evaluation for cognitive impairment at an outpatient memory clinic at the Cleveland Clinic. Of these, 89 (18%) lived in a home with a gun; 70% of that group (62) had a formal diagnosis of Alzheimer’s or another dementia disorder.

Associated mental disorders were common in the group with dementia. More than half (33) had delusions, 15 had hallucinations, and nearly all (57) had a diagnosed depression or endorsed depressive symptoms during their evaluation.

The delusions and hallucinations were likely to be paranoid (73% and 47%, respectively). Charts also included descriptions of aggressive behavior – some of which included firing weapons in the house and through open windows. Family members also reported some patients who repeatedly asked for their gun in order to commit suicide.

The unsettling combination is a difficult knot for U.S. doctors, Mr. Hsieh said.

"Doctors have no legal right here to remove weapons from the home," he said. "The only thing we can do is try to identify if one exists and encourage family members and carers to consider removing it or at least store it locked and unloaded in an inaccessible location."

Mr. Hsieh had no financial disclosures.

[email protected]

On Twitter @alz_gal

COPENHAGEN – A new study revealing the presence of firearms in the homes of more than 12% of community-dwelling dementia patients in the Midwest highlights a difficult situation for physicians treating such patients.

"Doctors have no legal right here to remove weapons from the home," noted study investigator Jason Hsieh, a fourth-year medical student at Cleveland Clinic Lerner College of Medicine. "The only thing we can do is try to identify if one exists, and encourage family members and caregivers to consider removing it or at least store it locked and unloaded in an inaccessible location."

In a video interview at the Alzheimer’s Association International Conference 2014, Mr. Hsieh discussed the study’s findings and the strategies physicians might use to keep their community-dwelling patients with dementia safe.

[email protected]

On Twitter @alz_gal

COPENHAGEN – A new study revealing the presence of firearms in the homes of more than 12% of community-dwelling dementia patients in the Midwest highlights a difficult situation for physicians treating such patients.

"Doctors have no legal right here to remove weapons from the home," noted study investigator Jason Hsieh, a fourth-year medical student at Cleveland Clinic Lerner College of Medicine. "The only thing we can do is try to identify if one exists, and encourage family members and caregivers to consider removing it or at least store it locked and unloaded in an inaccessible location."

In a video interview at the Alzheimer’s Association International Conference 2014, Mr. Hsieh discussed the study’s findings and the strategies physicians might use to keep their community-dwelling patients with dementia safe.

[email protected]

On Twitter @alz_gal

COPENHAGEN – A new study revealing the presence of firearms in the homes of more than 12% of community-dwelling dementia patients in the Midwest highlights a difficult situation for physicians treating such patients.

"Doctors have no legal right here to remove weapons from the home," noted study investigator Jason Hsieh, a fourth-year medical student at Cleveland Clinic Lerner College of Medicine. "The only thing we can do is try to identify if one exists, and encourage family members and caregivers to consider removing it or at least store it locked and unloaded in an inaccessible location."

In a video interview at the Alzheimer’s Association International Conference 2014, Mr. Hsieh discussed the study’s findings and the strategies physicians might use to keep their community-dwelling patients with dementia safe.

[email protected]

On Twitter @alz_gal

COPENHAGEN – Almost half of patients with mild cognitive impairment progressed to dementia within 1 year of undergoing either arthroplasty or coronary angiography, according to a small Australian study.

Baseline cognitive impairment appeared to be the main driver of progression, increasing the risk more than sevenfold – significantly more than age or heart attack, Lisbeth Evered, Ph.D., said at the annual Alzheimer’s Association International Conference.

"After 12 months, 42% met the criteria for dementia," said Dr. Evered, a researcher at the University of Melbourne. "The expected annual progression from mild cognitive impairment [MCI] to dementia would be about 10%-12% per year."

Her study included 67 patients with a mean age of 70 years. All had MCI at baseline, with a mean score of 23 on the Mini-Mental State Exam (MMSE). They underwent either arthroplasty (26 patients) or coronary angiography (41 patients).

A year after surgery, about 34% of the arthroplasty patients and 46% of the angiography patients had progressed to dementia. Baseline cognitive impairment was the only factor significantly associated with the change.

Postsurgical cognitive decline, both transient and long lasting, is a well-documented phenomenon, with studies going back to the late 1800s. Although the causative link isn’t entirely clear, anesthetics have long been implicated, said Dr. Evered. In animal models, some anesthesia drugs do seem to precipitate an Alzheimer’s-like amyloidosis and tau hyperphosphorylation.

More recent animal data suggest that inflammation might be a powerful influence.

"When a patient has surgery with a general anesthetic, they experience peripheral inflammation," Dr. Evered explained. "In a healthy normal brain, there’s plenty of cognitive reserve, and although there might be some cognitive decline afterward, the person won’t really notice and will certainly recover."

In a vulnerable brain, however, the inflammation may be amplified and may cause significant collateral damage that accelerates cognitive decline. "The problem is, we don’t know why they are vulnerable or what we might do about it," she noted.

The best approach now is to routinely assess cognition before surgery and monitor it afterward, Dr. Evered explained. "Then, the perioperative period is not something occurring in isolation," she noted. "We will be better able to identify those at risk and implement strategies to improve their outcomes."

In a video interview, Dr. Evered and Dr. Brendan Silbert of St. Vincent’s Hospital, Melbourne, discuss the study and its implications.

Dr. Evered had no financial disclosures

[email protected]

On Twitter @alz_gal

COPENHAGEN – Almost half of patients with mild cognitive impairment progressed to dementia within 1 year of undergoing either arthroplasty or coronary angiography, according to a small Australian study.

Baseline cognitive impairment appeared to be the main driver of progression, increasing the risk more than sevenfold – significantly more than age or heart attack, Lisbeth Evered, Ph.D., said at the annual Alzheimer’s Association International Conference.

"After 12 months, 42% met the criteria for dementia," said Dr. Evered, a researcher at the University of Melbourne. "The expected annual progression from mild cognitive impairment [MCI] to dementia would be about 10%-12% per year."

Her study included 67 patients with a mean age of 70 years. All had MCI at baseline, with a mean score of 23 on the Mini-Mental State Exam (MMSE). They underwent either arthroplasty (26 patients) or coronary angiography (41 patients).

A year after surgery, about 34% of the arthroplasty patients and 46% of the angiography patients had progressed to dementia. Baseline cognitive impairment was the only factor significantly associated with the change.

Postsurgical cognitive decline, both transient and long lasting, is a well-documented phenomenon, with studies going back to the late 1800s. Although the causative link isn’t entirely clear, anesthetics have long been implicated, said Dr. Evered. In animal models, some anesthesia drugs do seem to precipitate an Alzheimer’s-like amyloidosis and tau hyperphosphorylation.

More recent animal data suggest that inflammation might be a powerful influence.

"When a patient has surgery with a general anesthetic, they experience peripheral inflammation," Dr. Evered explained. "In a healthy normal brain, there’s plenty of cognitive reserve, and although there might be some cognitive decline afterward, the person won’t really notice and will certainly recover."

In a vulnerable brain, however, the inflammation may be amplified and may cause significant collateral damage that accelerates cognitive decline. "The problem is, we don’t know why they are vulnerable or what we might do about it," she noted.

The best approach now is to routinely assess cognition before surgery and monitor it afterward, Dr. Evered explained. "Then, the perioperative period is not something occurring in isolation," she noted. "We will be better able to identify those at risk and implement strategies to improve their outcomes."

In a video interview, Dr. Evered and Dr. Brendan Silbert of St. Vincent’s Hospital, Melbourne, discuss the study and its implications.

Dr. Evered had no financial disclosures

[email protected]

On Twitter @alz_gal

COPENHAGEN – Almost half of patients with mild cognitive impairment progressed to dementia within 1 year of undergoing either arthroplasty or coronary angiography, according to a small Australian study.

Baseline cognitive impairment appeared to be the main driver of progression, increasing the risk more than sevenfold – significantly more than age or heart attack, Lisbeth Evered, Ph.D., said at the annual Alzheimer’s Association International Conference.

"After 12 months, 42% met the criteria for dementia," said Dr. Evered, a researcher at the University of Melbourne. "The expected annual progression from mild cognitive impairment [MCI] to dementia would be about 10%-12% per year."

Her study included 67 patients with a mean age of 70 years. All had MCI at baseline, with a mean score of 23 on the Mini-Mental State Exam (MMSE). They underwent either arthroplasty (26 patients) or coronary angiography (41 patients).

A year after surgery, about 34% of the arthroplasty patients and 46% of the angiography patients had progressed to dementia. Baseline cognitive impairment was the only factor significantly associated with the change.

Postsurgical cognitive decline, both transient and long lasting, is a well-documented phenomenon, with studies going back to the late 1800s. Although the causative link isn’t entirely clear, anesthetics have long been implicated, said Dr. Evered. In animal models, some anesthesia drugs do seem to precipitate an Alzheimer’s-like amyloidosis and tau hyperphosphorylation.

More recent animal data suggest that inflammation might be a powerful influence.

"When a patient has surgery with a general anesthetic, they experience peripheral inflammation," Dr. Evered explained. "In a healthy normal brain, there’s plenty of cognitive reserve, and although there might be some cognitive decline afterward, the person won’t really notice and will certainly recover."

In a vulnerable brain, however, the inflammation may be amplified and may cause significant collateral damage that accelerates cognitive decline. "The problem is, we don’t know why they are vulnerable or what we might do about it," she noted.

The best approach now is to routinely assess cognition before surgery and monitor it afterward, Dr. Evered explained. "Then, the perioperative period is not something occurring in isolation," she noted. "We will be better able to identify those at risk and implement strategies to improve their outcomes."

In a video interview, Dr. Evered and Dr. Brendan Silbert of St. Vincent’s Hospital, Melbourne, discuss the study and its implications.

Dr. Evered had no financial disclosures

[email protected]

On Twitter @alz_gal

COPENHAGEN – Once more, an antiamyloid antibody has failed to live up to hopes for the treatment of Alzheimer’s disease.

Roche’s contender, crenezumab, faltered on all of the primary endpoints of its phase II clinical trial, dubbed ABBY. The drug delivered no overall benefit over placebo in measures of both cognition and function, except in a small, unplanned subanalysis, Dr. Jeffrey Cummings said at the Alzheimer’s Association International Conference 2014.

The subanalysis of patients who were the least impaired – with scores of 22-26 on the Mini-Mental State Exam (MMSE) – showed a significant 35% reduction in cognitive decline (P = .036) and a nonsignificant 19.6% reduction in global functional decline (P = .42) after 68 weeks of treatment, said Dr. Cummings, a primary investigator on the study and director of Cleveland Clinic’s Lou Ruvo Center for Brain Health in Las Vegas.

The news is a blow to researchers, who hoped crenezumab might break the string of antiamyloid antibody failures that has hampered immunotherapy clinical trials in Alzheimer’s. The drug’s early promise secured Roche $100 million in federal funds to help launch the first-ever Alzheimer’s primary prevention study.

The Alzheimer’s Prevention Initiative Autosomal Dominant Alzheimer’s Disease Treatment Trial is recruiting Colombian families who carry the presenilin 1 mutation – a virtual guarantee of early-onset Alzheimer’s disease. It was set to randomize cognitively healthy subjects to placebo or to 300 mg subcutaneous crenezumab – the dose that showed absolutely no efficacy signal in ABBY.

The trial’s future seems uncertain now, Dr. Cummings said at the meeting.

"These data require interpretation and then, proper ethical application in that study," he said. "Exactly what the outcome of that decision process will be, I don’t know."

ABBY enrolled 431 patients with mild to moderate Alzheimer’s disease (MMSE 18-26). They were randomized to two placebo-controlled arms: subcutaneous crenezumab 300 mg once every 2 weeks (low dose) or a matching placebo and intravenous crenezumab 15 mg/kg once every 4 weeks (high dose) or a matching placebo. The trial included a 68-week treatment period and a 4-week washout period.

The subjects had a mean age of 70 years and a mean MMSE of 21. Most of the low- and high-dose group included homozygous carriers of the apolipoprotein epsilon-4 allele (65% and 70%, respectively).

For either dosage arm, there were no significant differences in any of the co–primary endpoints, which included a reduction in cognitive decline on the Alzheimer’s Disease Assessment Scale-cognitive domain (ADAS-cog), the Clinical Dementia Rating Scale sum of boxes (CDR-SOB), or in the secondary endpoint of change in the Alzheimer’s Disease Cooperative Study Activities of Daily Living Inventory scores (ADCS-ADL). In a prespecified subgroup analysis of patients with milder disease (MMSE 20-26), the high-dose intravenous arm experienced a 24% reduction in cognitive decline relative to placebo, but this was not statistically significant (P = .15).

However, the encouraging trend prompted the additional subgroup analysis of some patients with even milder disease (MMSE 22-26). Here there was a significant 35% reduction in cognitive decline (P = .036) and a nonsignificant 19.6% reduction in global functional decline (P = .42).

Crenezumab was safe and generally well tolerated. The 25% discontinuation rate was consistent in each treatment group as well as the placebo groups. There was one case of asymptomatic amyloid-related imaging abnormalities (ARIA) in a patient taking high-dose crenezumab.

There were three deaths: one from disease progression, one from respiratory failure, and one from pneumonia; none were considered related to the study drug.

Roche and its subsidiary Genentech sponsored the study. Dr. Cummings has received financial remuneration from the company.

[email protected]

On Twitter @alz_gal

COPENHAGEN – Once more, an antiamyloid antibody has failed to live up to hopes for the treatment of Alzheimer’s disease.

Roche’s contender, crenezumab, faltered on all of the primary endpoints of its phase II clinical trial, dubbed ABBY. The drug delivered no overall benefit over placebo in measures of both cognition and function, except in a small, unplanned subanalysis, Dr. Jeffrey Cummings said at the Alzheimer’s Association International Conference 2014.

The subanalysis of patients who were the least impaired – with scores of 22-26 on the Mini-Mental State Exam (MMSE) – showed a significant 35% reduction in cognitive decline (P = .036) and a nonsignificant 19.6% reduction in global functional decline (P = .42) after 68 weeks of treatment, said Dr. Cummings, a primary investigator on the study and director of Cleveland Clinic’s Lou Ruvo Center for Brain Health in Las Vegas.

The news is a blow to researchers, who hoped crenezumab might break the string of antiamyloid antibody failures that has hampered immunotherapy clinical trials in Alzheimer’s. The drug’s early promise secured Roche $100 million in federal funds to help launch the first-ever Alzheimer’s primary prevention study.

The Alzheimer’s Prevention Initiative Autosomal Dominant Alzheimer’s Disease Treatment Trial is recruiting Colombian families who carry the presenilin 1 mutation – a virtual guarantee of early-onset Alzheimer’s disease. It was set to randomize cognitively healthy subjects to placebo or to 300 mg subcutaneous crenezumab – the dose that showed absolutely no efficacy signal in ABBY.

The trial’s future seems uncertain now, Dr. Cummings said at the meeting.

"These data require interpretation and then, proper ethical application in that study," he said. "Exactly what the outcome of that decision process will be, I don’t know."

ABBY enrolled 431 patients with mild to moderate Alzheimer’s disease (MMSE 18-26). They were randomized to two placebo-controlled arms: subcutaneous crenezumab 300 mg once every 2 weeks (low dose) or a matching placebo and intravenous crenezumab 15 mg/kg once every 4 weeks (high dose) or a matching placebo. The trial included a 68-week treatment period and a 4-week washout period.

The subjects had a mean age of 70 years and a mean MMSE of 21. Most of the low- and high-dose group included homozygous carriers of the apolipoprotein epsilon-4 allele (65% and 70%, respectively).

For either dosage arm, there were no significant differences in any of the co–primary endpoints, which included a reduction in cognitive decline on the Alzheimer’s Disease Assessment Scale-cognitive domain (ADAS-cog), the Clinical Dementia Rating Scale sum of boxes (CDR-SOB), or in the secondary endpoint of change in the Alzheimer’s Disease Cooperative Study Activities of Daily Living Inventory scores (ADCS-ADL). In a prespecified subgroup analysis of patients with milder disease (MMSE 20-26), the high-dose intravenous arm experienced a 24% reduction in cognitive decline relative to placebo, but this was not statistically significant (P = .15).

However, the encouraging trend prompted the additional subgroup analysis of some patients with even milder disease (MMSE 22-26). Here there was a significant 35% reduction in cognitive decline (P = .036) and a nonsignificant 19.6% reduction in global functional decline (P = .42).

Crenezumab was safe and generally well tolerated. The 25% discontinuation rate was consistent in each treatment group as well as the placebo groups. There was one case of asymptomatic amyloid-related imaging abnormalities (ARIA) in a patient taking high-dose crenezumab.

There were three deaths: one from disease progression, one from respiratory failure, and one from pneumonia; none were considered related to the study drug.

Roche and its subsidiary Genentech sponsored the study. Dr. Cummings has received financial remuneration from the company.

[email protected]

On Twitter @alz_gal

COPENHAGEN – Once more, an antiamyloid antibody has failed to live up to hopes for the treatment of Alzheimer’s disease.

Roche’s contender, crenezumab, faltered on all of the primary endpoints of its phase II clinical trial, dubbed ABBY. The drug delivered no overall benefit over placebo in measures of both cognition and function, except in a small, unplanned subanalysis, Dr. Jeffrey Cummings said at the Alzheimer’s Association International Conference 2014.

The subanalysis of patients who were the least impaired – with scores of 22-26 on the Mini-Mental State Exam (MMSE) – showed a significant 35% reduction in cognitive decline (P = .036) and a nonsignificant 19.6% reduction in global functional decline (P = .42) after 68 weeks of treatment, said Dr. Cummings, a primary investigator on the study and director of Cleveland Clinic’s Lou Ruvo Center for Brain Health in Las Vegas.

The news is a blow to researchers, who hoped crenezumab might break the string of antiamyloid antibody failures that has hampered immunotherapy clinical trials in Alzheimer’s. The drug’s early promise secured Roche $100 million in federal funds to help launch the first-ever Alzheimer’s primary prevention study.

The Alzheimer’s Prevention Initiative Autosomal Dominant Alzheimer’s Disease Treatment Trial is recruiting Colombian families who carry the presenilin 1 mutation – a virtual guarantee of early-onset Alzheimer’s disease. It was set to randomize cognitively healthy subjects to placebo or to 300 mg subcutaneous crenezumab – the dose that showed absolutely no efficacy signal in ABBY.

The trial’s future seems uncertain now, Dr. Cummings said at the meeting.

"These data require interpretation and then, proper ethical application in that study," he said. "Exactly what the outcome of that decision process will be, I don’t know."

ABBY enrolled 431 patients with mild to moderate Alzheimer’s disease (MMSE 18-26). They were randomized to two placebo-controlled arms: subcutaneous crenezumab 300 mg once every 2 weeks (low dose) or a matching placebo and intravenous crenezumab 15 mg/kg once every 4 weeks (high dose) or a matching placebo. The trial included a 68-week treatment period and a 4-week washout period.

The subjects had a mean age of 70 years and a mean MMSE of 21. Most of the low- and high-dose group included homozygous carriers of the apolipoprotein epsilon-4 allele (65% and 70%, respectively).

For either dosage arm, there were no significant differences in any of the co–primary endpoints, which included a reduction in cognitive decline on the Alzheimer’s Disease Assessment Scale-cognitive domain (ADAS-cog), the Clinical Dementia Rating Scale sum of boxes (CDR-SOB), or in the secondary endpoint of change in the Alzheimer’s Disease Cooperative Study Activities of Daily Living Inventory scores (ADCS-ADL). In a prespecified subgroup analysis of patients with milder disease (MMSE 20-26), the high-dose intravenous arm experienced a 24% reduction in cognitive decline relative to placebo, but this was not statistically significant (P = .15).

However, the encouraging trend prompted the additional subgroup analysis of some patients with even milder disease (MMSE 22-26). Here there was a significant 35% reduction in cognitive decline (P = .036) and a nonsignificant 19.6% reduction in global functional decline (P = .42).

Crenezumab was safe and generally well tolerated. The 25% discontinuation rate was consistent in each treatment group as well as the placebo groups. There was one case of asymptomatic amyloid-related imaging abnormalities (ARIA) in a patient taking high-dose crenezumab.

There were three deaths: one from disease progression, one from respiratory failure, and one from pneumonia; none were considered related to the study drug.

Roche and its subsidiary Genentech sponsored the study. Dr. Cummings has received financial remuneration from the company.

[email protected]

On Twitter @alz_gal

COPENHAGEN – When it comes to beta-amyloid plaques, the eyes may be more than a poetic window to the soul – they also may be mirrors of pathology developing in the brain.

It turns out that the eye, as a virtual extension of the brain itself, accumulates the same amyloid pathology that damages the brain when Alzheimer’s disease strikes. Visualizing these plaques in the retina and in the lens may eventually become a low-cost, noninvasive screening tool for early disease, according to research presented at the Alzheimer’s Association International Conference 2014.

"Our first 45 subjects showed a strong correlation between retinal amyloid and brain plaques," said Shaun Frost of the Commonwealth Scientific and Industrial Research Organisation (CSIRO) in Australia. "In fact, we had 100% sensitivity and no false positives, something that’s critical for an Alzheimer’s test, because we don’t want to leave anyone behind when it comes to early signs."

Curcumin, an extract of the spice turmeric, is the fluorescent agent in the test. Mr. Frost said investigators were first drawn to it because some studies suggest a lower rate of Alzheimer’s in India, where turmeric is a common seasoning.

Paul Hartung, president of Cognoptix in Acton, Mass., said his company focuses on lens amyloid, which shows a correlation to brain plaques. Cognoptix is accumulating data on a device that identifies plaques using dynamic light scattering and a fluorescent molecule delivered in an ophthalmic ointment.

In the phase II study he presented, the test differentiated 20 people with Alzheimer’s from 20 healthy controls with an 85% sensitivity and 95% specificity. It also correlated significantly with brain plaques seen on PET amyloid imaging.

A phase III trial is in the works, after which Cognoptix intends to seek approval from the Food and Drug Administration. Mr. Hartung hopes the device could be marketed by 2016.

The lens amyloid trial is a collaboration between CSIRO; Edith Cowan University in Mt. Lawley, Australia; the McCusker Alzheimer’s Research Foundation; California-based NeuroVision Imaging; and the Australian Imaging, Biomarker & Lifestyle Flagship Study of Ageing. Mr. Frost had no financial disclosures. Mr. Hartung is a full-time employee of Cognotpix, which is developing the test for commercial use.

[email protected]

On Twitter @alz_gal

COPENHAGEN – When it comes to beta-amyloid plaques, the eyes may be more than a poetic window to the soul – they also may be mirrors of pathology developing in the brain.

It turns out that the eye, as a virtual extension of the brain itself, accumulates the same amyloid pathology that damages the brain when Alzheimer’s disease strikes. Visualizing these plaques in the retina and in the lens may eventually become a low-cost, noninvasive screening tool for early disease, according to research presented at the Alzheimer’s Association International Conference 2014.

"Our first 45 subjects showed a strong correlation between retinal amyloid and brain plaques," said Shaun Frost of the Commonwealth Scientific and Industrial Research Organisation (CSIRO) in Australia. "In fact, we had 100% sensitivity and no false positives, something that’s critical for an Alzheimer’s test, because we don’t want to leave anyone behind when it comes to early signs."

Curcumin, an extract of the spice turmeric, is the fluorescent agent in the test. Mr. Frost said investigators were first drawn to it because some studies suggest a lower rate of Alzheimer’s in India, where turmeric is a common seasoning.

Paul Hartung, president of Cognoptix in Acton, Mass., said his company focuses on lens amyloid, which shows a correlation to brain plaques. Cognoptix is accumulating data on a device that identifies plaques using dynamic light scattering and a fluorescent molecule delivered in an ophthalmic ointment.

In the phase II study he presented, the test differentiated 20 people with Alzheimer’s from 20 healthy controls with an 85% sensitivity and 95% specificity. It also correlated significantly with brain plaques seen on PET amyloid imaging.

A phase III trial is in the works, after which Cognoptix intends to seek approval from the Food and Drug Administration. Mr. Hartung hopes the device could be marketed by 2016.

The lens amyloid trial is a collaboration between CSIRO; Edith Cowan University in Mt. Lawley, Australia; the McCusker Alzheimer’s Research Foundation; California-based NeuroVision Imaging; and the Australian Imaging, Biomarker & Lifestyle Flagship Study of Ageing. Mr. Frost had no financial disclosures. Mr. Hartung is a full-time employee of Cognotpix, which is developing the test for commercial use.

[email protected]

On Twitter @alz_gal

COPENHAGEN – When it comes to beta-amyloid plaques, the eyes may be more than a poetic window to the soul – they also may be mirrors of pathology developing in the brain.

It turns out that the eye, as a virtual extension of the brain itself, accumulates the same amyloid pathology that damages the brain when Alzheimer’s disease strikes. Visualizing these plaques in the retina and in the lens may eventually become a low-cost, noninvasive screening tool for early disease, according to research presented at the Alzheimer’s Association International Conference 2014.

"Our first 45 subjects showed a strong correlation between retinal amyloid and brain plaques," said Shaun Frost of the Commonwealth Scientific and Industrial Research Organisation (CSIRO) in Australia. "In fact, we had 100% sensitivity and no false positives, something that’s critical for an Alzheimer’s test, because we don’t want to leave anyone behind when it comes to early signs."

Curcumin, an extract of the spice turmeric, is the fluorescent agent in the test. Mr. Frost said investigators were first drawn to it because some studies suggest a lower rate of Alzheimer’s in India, where turmeric is a common seasoning.

Paul Hartung, president of Cognoptix in Acton, Mass., said his company focuses on lens amyloid, which shows a correlation to brain plaques. Cognoptix is accumulating data on a device that identifies plaques using dynamic light scattering and a fluorescent molecule delivered in an ophthalmic ointment.

In the phase II study he presented, the test differentiated 20 people with Alzheimer’s from 20 healthy controls with an 85% sensitivity and 95% specificity. It also correlated significantly with brain plaques seen on PET amyloid imaging.

A phase III trial is in the works, after which Cognoptix intends to seek approval from the Food and Drug Administration. Mr. Hartung hopes the device could be marketed by 2016.

The lens amyloid trial is a collaboration between CSIRO; Edith Cowan University in Mt. Lawley, Australia; the McCusker Alzheimer’s Research Foundation; California-based NeuroVision Imaging; and the Australian Imaging, Biomarker & Lifestyle Flagship Study of Ageing. Mr. Frost had no financial disclosures. Mr. Hartung is a full-time employee of Cognotpix, which is developing the test for commercial use.

[email protected]

On Twitter @alz_gal

COPENHAGEN – The incidence of Alzheimer’s disease appears to be declining in the United States and may be following a similar positive trend in Germany as well.

An analysis of the ongoing Framingham Heart Study suggests that the disease has declined by 44% since 1978 in the United States, Claudia Satizabal, Ph.D., said at the Alzheimer’s Association International Conference 2014. Better management of cardiovascular risk factors and a generally higher education level seem to be driving the change.

"There has been a progressive decrease over that period," Dr. Satizabal of Boston University said during a press briefing. "Our results are in line with other studies from developed countries, and offer cautious hope that some cases might be preventable by managing risk – especially hypertension – and continuing to improve educational status."

She divided the Framingham study period into four epochs, beginning in 1978, 1989, and 1996, and finally, running from 2006 to 2013. She then calculated the 5-year incidence of Alzheimer’s disease in each of those periods, and according to gender and age of onset.

Using epoch 1 as the baseline, Dr. Satizabal found that overall incidence had decreased 22% by epoch 2. From epoch 2 to 3, she found a total decrease of 38% from baseline. From epoch 3 to 4, the total overall decrease was 44% from baseline.

The incidence reduction was somewhat greater in women, dropping 30% from baseline to epoch 1 to 2 and 48% from baseline to epoch 2 to 3. The decline then stabilized at a 47% decrease from baseline to epoch 3 to 4. The corresponding decreases among men were 4%, 11%, and 36%.

People who developed the disease also did so at a later age as the years progressed. The mean age of onset was 80 years in epoch 1, 82 in epoch 2, 84 in epoch 3, and 85 in epoch 4.

Education also influenced the reduction in incidence. Those with at least high school education had a consistent reduction in dementia incidence across all time periods, while those less educated did not.

"We also observed significant improvements in the use of antihypertensive and statin medication, blood pressure and cholesterol levels, and prevalence of smoking, heart disease, and stroke," Dr. Satizabal added.

However, she said, "our study looks at a small population of white Americans, so we can’t make the same assumptions about other populations."

Gabriele Doblhammer, Ph.D., of the German Center for Neurodegenerative Diseases in Rostock, had some similarly encouraging findings. Her study of short-term dementia trends in Germany – the first ever conducted – concluded that incidence is declining, age at onset is being pushed back, and disease duration has shortened.

"People seem to be enjoying more healthy years of life, and who would not want that?" she said.

Her study examined claims from the country’s largest public health insurer, which covers about 13% of the population overall, and 50% of older citizens.

The analysis comprised 6.5 million people and 600,000 dementia cases in those aged 65 and older, for the years 2007, 2008, and 2009. Over that period, new cases of dementia decreased for both men and women.

The results were better for women, however. For them, prevalence declined significantly: –3.6% from 2007 to 2008, and –1.8% from 2008 to 2009. Prevalence among men also decreased, but the change was not statistically significant. When women developed the disease, they died sooner – 10% more quickly in 2007 than in a sample obtained from 2004, suggesting that the disease was developing later in life, and much sooner to the time of normal expected death.

Neither Dr. Satizabal nor Dr. Doblhammer had any relevant financial disclosures.

[email protected]

On Twitter @alz_gal

COPENHAGEN – The incidence of Alzheimer’s disease appears to be declining in the United States and may be following a similar positive trend in Germany as well.

An analysis of the ongoing Framingham Heart Study suggests that the disease has declined by 44% since 1978 in the United States, Claudia Satizabal, Ph.D., said at the Alzheimer’s Association International Conference 2014. Better management of cardiovascular risk factors and a generally higher education level seem to be driving the change.

"There has been a progressive decrease over that period," Dr. Satizabal of Boston University said during a press briefing. "Our results are in line with other studies from developed countries, and offer cautious hope that some cases might be preventable by managing risk – especially hypertension – and continuing to improve educational status."

She divided the Framingham study period into four epochs, beginning in 1978, 1989, and 1996, and finally, running from 2006 to 2013. She then calculated the 5-year incidence of Alzheimer’s disease in each of those periods, and according to gender and age of onset.

Using epoch 1 as the baseline, Dr. Satizabal found that overall incidence had decreased 22% by epoch 2. From epoch 2 to 3, she found a total decrease of 38% from baseline. From epoch 3 to 4, the total overall decrease was 44% from baseline.

The incidence reduction was somewhat greater in women, dropping 30% from baseline to epoch 1 to 2 and 48% from baseline to epoch 2 to 3. The decline then stabilized at a 47% decrease from baseline to epoch 3 to 4. The corresponding decreases among men were 4%, 11%, and 36%.

People who developed the disease also did so at a later age as the years progressed. The mean age of onset was 80 years in epoch 1, 82 in epoch 2, 84 in epoch 3, and 85 in epoch 4.

Education also influenced the reduction in incidence. Those with at least high school education had a consistent reduction in dementia incidence across all time periods, while those less educated did not.

"We also observed significant improvements in the use of antihypertensive and statin medication, blood pressure and cholesterol levels, and prevalence of smoking, heart disease, and stroke," Dr. Satizabal added.

However, she said, "our study looks at a small population of white Americans, so we can’t make the same assumptions about other populations."

Gabriele Doblhammer, Ph.D., of the German Center for Neurodegenerative Diseases in Rostock, had some similarly encouraging findings. Her study of short-term dementia trends in Germany – the first ever conducted – concluded that incidence is declining, age at onset is being pushed back, and disease duration has shortened.

"People seem to be enjoying more healthy years of life, and who would not want that?" she said.

Her study examined claims from the country’s largest public health insurer, which covers about 13% of the population overall, and 50% of older citizens.

The analysis comprised 6.5 million people and 600,000 dementia cases in those aged 65 and older, for the years 2007, 2008, and 2009. Over that period, new cases of dementia decreased for both men and women.

The results were better for women, however. For them, prevalence declined significantly: –3.6% from 2007 to 2008, and –1.8% from 2008 to 2009. Prevalence among men also decreased, but the change was not statistically significant. When women developed the disease, they died sooner – 10% more quickly in 2007 than in a sample obtained from 2004, suggesting that the disease was developing later in life, and much sooner to the time of normal expected death.

Neither Dr. Satizabal nor Dr. Doblhammer had any relevant financial disclosures.

[email protected]

On Twitter @alz_gal

COPENHAGEN – The incidence of Alzheimer’s disease appears to be declining in the United States and may be following a similar positive trend in Germany as well.

An analysis of the ongoing Framingham Heart Study suggests that the disease has declined by 44% since 1978 in the United States, Claudia Satizabal, Ph.D., said at the Alzheimer’s Association International Conference 2014. Better management of cardiovascular risk factors and a generally higher education level seem to be driving the change.

"There has been a progressive decrease over that period," Dr. Satizabal of Boston University said during a press briefing. "Our results are in line with other studies from developed countries, and offer cautious hope that some cases might be preventable by managing risk – especially hypertension – and continuing to improve educational status."

She divided the Framingham study period into four epochs, beginning in 1978, 1989, and 1996, and finally, running from 2006 to 2013. She then calculated the 5-year incidence of Alzheimer’s disease in each of those periods, and according to gender and age of onset.

Using epoch 1 as the baseline, Dr. Satizabal found that overall incidence had decreased 22% by epoch 2. From epoch 2 to 3, she found a total decrease of 38% from baseline. From epoch 3 to 4, the total overall decrease was 44% from baseline.

The incidence reduction was somewhat greater in women, dropping 30% from baseline to epoch 1 to 2 and 48% from baseline to epoch 2 to 3. The decline then stabilized at a 47% decrease from baseline to epoch 3 to 4. The corresponding decreases among men were 4%, 11%, and 36%.

People who developed the disease also did so at a later age as the years progressed. The mean age of onset was 80 years in epoch 1, 82 in epoch 2, 84 in epoch 3, and 85 in epoch 4.

Education also influenced the reduction in incidence. Those with at least high school education had a consistent reduction in dementia incidence across all time periods, while those less educated did not.

"We also observed significant improvements in the use of antihypertensive and statin medication, blood pressure and cholesterol levels, and prevalence of smoking, heart disease, and stroke," Dr. Satizabal added.

However, she said, "our study looks at a small population of white Americans, so we can’t make the same assumptions about other populations."

Gabriele Doblhammer, Ph.D., of the German Center for Neurodegenerative Diseases in Rostock, had some similarly encouraging findings. Her study of short-term dementia trends in Germany – the first ever conducted – concluded that incidence is declining, age at onset is being pushed back, and disease duration has shortened.

"People seem to be enjoying more healthy years of life, and who would not want that?" she said.

Her study examined claims from the country’s largest public health insurer, which covers about 13% of the population overall, and 50% of older citizens.

The analysis comprised 6.5 million people and 600,000 dementia cases in those aged 65 and older, for the years 2007, 2008, and 2009. Over that period, new cases of dementia decreased for both men and women.

The results were better for women, however. For them, prevalence declined significantly: –3.6% from 2007 to 2008, and –1.8% from 2008 to 2009. Prevalence among men also decreased, but the change was not statistically significant. When women developed the disease, they died sooner – 10% more quickly in 2007 than in a sample obtained from 2004, suggesting that the disease was developing later in life, and much sooner to the time of normal expected death.

Neither Dr. Satizabal nor Dr. Doblhammer had any relevant financial disclosures.

[email protected]

On Twitter @alz_gal

COPENHAGEN – Researchers appear to be tracking contradictory trends in the global incidence and prevalence of Alzheimer’s disease.

There’s no doubt that both are declining in the United States and other high-income countries. But the disease appears to be claiming more people in less-developed countries, particularly in Asia and sub-Saharan Africa, and that disparity will become much worse by 2050.

Half of the 7.7 million new cases diagnosed per year are occurring in China alone, Dr. Martin Prince said at the Alzheimer’s Association International Conference 2014. And while African and Latin American countries contribute a lower portion of the total (7% and 5%, respectively), they are projected to proportionally outstrip even China’s expected tripling of cases, with each poised for a fourfold increase by 2050.

Taken together with the doubling of cases expected in the United States and European countries, the global incidence could exceed previous projections by more than 30 million cases worldwide by 2050, said Dr. Prince, a primary author of the G8 report "The Global Impact of Dementia, 2013-2050." The report contains updated numbers based on data supplied by the United Nations.

"Because of this new U.N. data, and new data coming out of China, we realized that our 2009 global estimates were about 10% too low," said Dr. Prince, who is also a professor of epidemiological psychiatry in the Institute of Psychiatry at King’s College London. "We are talking about not 36 million right now, but 44 million. Not 66 million by 2030, but 76 million. And by 2050, not 115 million as we previously thought, but 135 million."

The upward trend doesn’t reflect so much an increase in disease incidence as an increase in disease reporting, he noted. While China has published papers on incidence and prevalence, they were almost exclusively in Chinese journals and unavailable outside the country. The biggest change came from a groundbreaking paper in 2013 (Lancet 2013;381:2016-23) – the first widely accessible English language paper on the topic. It concluded that the burden of dementia in China is increasing faster than previously assumed.

According to the G8 report, about 67 million are living with Alzheimer’s in China now, and that number could increase to nearly 200 million by 2050.

But that paper probably doesn’t tell the whole story, Dr. Prince added. China is suffering from the same epidemics of obesity and diabetes that plague other countries, and in contrast to many, cigarette smoking is on a huge rise in China. All of these factors contribute to the development of Alzheimer’s and other dementias, so the numbers will most likely continue to change.

Perhaps not surprisingly, national prosperity is directly tied to Alzheimer’s incidence. By 2050, the incidence is projected to increase by 106% in the G8 countries and by 185% in the G20 countries. This is mainly due to higher educational levels and better risk management, Dr. Prince said. Reducing the prevalence of diabetes, physical inactivity, smoking, depression, low education, and midlife hypertension and obesity could reduce the Alzheimer’s population-attributable risk fraction by more than 50%.

"Even a 10% reduction in risk exposure would result in 250,000 fewer new cases [3.3%]. A 25% reduction in risk exposure would result in 680,000 fewer new cases," an incidence reduction of almost 9% worldwide, he said.

No one has yet modeled the global economic impact of the rising Alzheimer’s tide, Dr. Prince said. Current worldwide spending on Alzheimer’s disease exceeds $600 billion per year. In developed countries, most of this is associated with care in long-term facilities and the cost of professional caregivers. "In less-developed countries, the largest proportion is the informal costs of family care, especially lost employment opportunities. This needs to be calculated, and I’m not aware that’s being done. But it will be a lot of money."

Dr. Prince had no financial disclosures.

[email protected]

On Twitter @alz_gal

COPENHAGEN – Researchers appear to be tracking contradictory trends in the global incidence and prevalence of Alzheimer’s disease.

There’s no doubt that both are declining in the United States and other high-income countries. But the disease appears to be claiming more people in less-developed countries, particularly in Asia and sub-Saharan Africa, and that disparity will become much worse by 2050.

Half of the 7.7 million new cases diagnosed per year are occurring in China alone, Dr. Martin Prince said at the Alzheimer’s Association International Conference 2014. And while African and Latin American countries contribute a lower portion of the total (7% and 5%, respectively), they are projected to proportionally outstrip even China’s expected tripling of cases, with each poised for a fourfold increase by 2050.

Taken together with the doubling of cases expected in the United States and European countries, the global incidence could exceed previous projections by more than 30 million cases worldwide by 2050, said Dr. Prince, a primary author of the G8 report "The Global Impact of Dementia, 2013-2050." The report contains updated numbers based on data supplied by the United Nations.

"Because of this new U.N. data, and new data coming out of China, we realized that our 2009 global estimates were about 10% too low," said Dr. Prince, who is also a professor of epidemiological psychiatry in the Institute of Psychiatry at King’s College London. "We are talking about not 36 million right now, but 44 million. Not 66 million by 2030, but 76 million. And by 2050, not 115 million as we previously thought, but 135 million."

The upward trend doesn’t reflect so much an increase in disease incidence as an increase in disease reporting, he noted. While China has published papers on incidence and prevalence, they were almost exclusively in Chinese journals and unavailable outside the country. The biggest change came from a groundbreaking paper in 2013 (Lancet 2013;381:2016-23) – the first widely accessible English language paper on the topic. It concluded that the burden of dementia in China is increasing faster than previously assumed.

According to the G8 report, about 67 million are living with Alzheimer’s in China now, and that number could increase to nearly 200 million by 2050.

But that paper probably doesn’t tell the whole story, Dr. Prince added. China is suffering from the same epidemics of obesity and diabetes that plague other countries, and in contrast to many, cigarette smoking is on a huge rise in China. All of these factors contribute to the development of Alzheimer’s and other dementias, so the numbers will most likely continue to change.

Perhaps not surprisingly, national prosperity is directly tied to Alzheimer’s incidence. By 2050, the incidence is projected to increase by 106% in the G8 countries and by 185% in the G20 countries. This is mainly due to higher educational levels and better risk management, Dr. Prince said. Reducing the prevalence of diabetes, physical inactivity, smoking, depression, low education, and midlife hypertension and obesity could reduce the Alzheimer’s population-attributable risk fraction by more than 50%.

"Even a 10% reduction in risk exposure would result in 250,000 fewer new cases [3.3%]. A 25% reduction in risk exposure would result in 680,000 fewer new cases," an incidence reduction of almost 9% worldwide, he said.

No one has yet modeled the global economic impact of the rising Alzheimer’s tide, Dr. Prince said. Current worldwide spending on Alzheimer’s disease exceeds $600 billion per year. In developed countries, most of this is associated with care in long-term facilities and the cost of professional caregivers. "In less-developed countries, the largest proportion is the informal costs of family care, especially lost employment opportunities. This needs to be calculated, and I’m not aware that’s being done. But it will be a lot of money."

Dr. Prince had no financial disclosures.

[email protected]

On Twitter @alz_gal

COPENHAGEN – Researchers appear to be tracking contradictory trends in the global incidence and prevalence of Alzheimer’s disease.

There’s no doubt that both are declining in the United States and other high-income countries. But the disease appears to be claiming more people in less-developed countries, particularly in Asia and sub-Saharan Africa, and that disparity will become much worse by 2050.

Half of the 7.7 million new cases diagnosed per year are occurring in China alone, Dr. Martin Prince said at the Alzheimer’s Association International Conference 2014. And while African and Latin American countries contribute a lower portion of the total (7% and 5%, respectively), they are projected to proportionally outstrip even China’s expected tripling of cases, with each poised for a fourfold increase by 2050.

Taken together with the doubling of cases expected in the United States and European countries, the global incidence could exceed previous projections by more than 30 million cases worldwide by 2050, said Dr. Prince, a primary author of the G8 report "The Global Impact of Dementia, 2013-2050." The report contains updated numbers based on data supplied by the United Nations.

"Because of this new U.N. data, and new data coming out of China, we realized that our 2009 global estimates were about 10% too low," said Dr. Prince, who is also a professor of epidemiological psychiatry in the Institute of Psychiatry at King’s College London. "We are talking about not 36 million right now, but 44 million. Not 66 million by 2030, but 76 million. And by 2050, not 115 million as we previously thought, but 135 million."

The upward trend doesn’t reflect so much an increase in disease incidence as an increase in disease reporting, he noted. While China has published papers on incidence and prevalence, they were almost exclusively in Chinese journals and unavailable outside the country. The biggest change came from a groundbreaking paper in 2013 (Lancet 2013;381:2016-23) – the first widely accessible English language paper on the topic. It concluded that the burden of dementia in China is increasing faster than previously assumed.

According to the G8 report, about 67 million are living with Alzheimer’s in China now, and that number could increase to nearly 200 million by 2050.

But that paper probably doesn’t tell the whole story, Dr. Prince added. China is suffering from the same epidemics of obesity and diabetes that plague other countries, and in contrast to many, cigarette smoking is on a huge rise in China. All of these factors contribute to the development of Alzheimer’s and other dementias, so the numbers will most likely continue to change.

Perhaps not surprisingly, national prosperity is directly tied to Alzheimer’s incidence. By 2050, the incidence is projected to increase by 106% in the G8 countries and by 185% in the G20 countries. This is mainly due to higher educational levels and better risk management, Dr. Prince said. Reducing the prevalence of diabetes, physical inactivity, smoking, depression, low education, and midlife hypertension and obesity could reduce the Alzheimer’s population-attributable risk fraction by more than 50%.

"Even a 10% reduction in risk exposure would result in 250,000 fewer new cases [3.3%]. A 25% reduction in risk exposure would result in 680,000 fewer new cases," an incidence reduction of almost 9% worldwide, he said.

No one has yet modeled the global economic impact of the rising Alzheimer’s tide, Dr. Prince said. Current worldwide spending on Alzheimer’s disease exceeds $600 billion per year. In developed countries, most of this is associated with care in long-term facilities and the cost of professional caregivers. "In less-developed countries, the largest proportion is the informal costs of family care, especially lost employment opportunities. This needs to be calculated, and I’m not aware that’s being done. But it will be a lot of money."

Dr. Prince had no financial disclosures.

[email protected]

On Twitter @alz_gal