News Roundup: New and Noteworthy Information

Alzheimer's Disease/Dementia
A person whose spouse has dementia is six times more likely to develop incident dementia than are subjects whose spouses are dementia-free, researchers reported in the May Journal of the American Geriatrics Society. The findings are based on 1,221 married couples (ages 65 and older) from Cache County, Utah. Incident dementia was diagnosed in 255 participants, per DSM-III-Revised criteria. In sex-specific analyses, husbands had a higher risk of dementia (hazard rate ratio [HRR], 11.9) than wives (HRR, 3.7). “The finding of a six times greater risk of dementia in persons so exposed than in married men and women whose spouse had not developed dementia remained after adjustment for age, sex, education, socioeconomic status, and apolipoprotein E genotype, all of which were (as expected) associated with dementia risk,” the investigators reported.

Amyloid-beta, which forms plaques in the brains of patients with Alzheimer’s disease, also accumulates in the eyes of persons with Down syndrome, per a study in the May 20 PLoS One. The optical lenses of patients with Down syndrome have a “characteristic pattern of supranuclear opacification accompanied by accelerated supranuclear amyloid-beta accumulation, co-localizing amyloid pathology, and fiber cell cytoplasmic amyloid-beta aggregates identical to the lens pathology identified in Alzheimer’s disease,” researchers reported. “These results establish the genetic etiology of the distinctive lens phenotype in Down syndrome and identify the molecular origin and pathogenic mechanism by which lens pathology is expressed in this common chromosomal disorder,” the researchers concluded. “Moreover, these findings confirm increased amyloid-beta accumulation as a key pathogenic determinant linking lens and brain pathology in both Down syndrome and Alzheimer’s disease.”

Amyotrophic Lateral Sclerosis
Researchers have found a link between sporadic and familial forms of amyotrophic lateral sclerosis (ALS), according to a study in the June Annals of Neurology. The investigators performed immunostaining on the postmortem spinal cords of 78 ALS cases, including 52 with sporadic ALS, 10 with ALS with dementia, and 16 with familial ALS. Postmortem brains or spinal cords from 22 cases with or without frontotemporal lobar degeneration were also analyzed. The researchers observed FUS-immunoreactive inclusions in spinal anterior horn neurons in all sporadic and familial cases, except for those with SOD1 mutations. “Our data suggest that FUS
protein may be a common component of the cellular inclusions in non-SOD1 ALS and some other neurodegenerative conditions, implying a shared pathogenic pathway underlying sporadic ALS, non-SOD1 familial ALS, ALS/dementia, and related disorders,” reported the study authors.

Epilepsy
The pertussis vaccine may trigger an earlier onset of Dravet syndrome—a severe form of epilepsy—in children with a mutation of the sodium channel gene SCN1A, per a study that was published in the June Lancet Neurology. In the vaccination-proximate group (12 subjects with seizure onset the day of or the day after vaccination) of the retrospective study, the average age of seizure onset was 18.4 weeks. In the vaccination-distant group (25 subjects with seizure onset two or more days after vaccination and three subjects with onset before vaccination), the average age of disease onset was 26.2 weeks. Subjects with the SCN1A mutation are “destined to develop the disease,” the investigators noted. “Vaccination should not be withheld from children with SCN1A mutations because we found no evidence that vaccinations before or after disease onset affect outcome,” the authors concluded.

Restless Legs Syndrome
Restless legs syndrome (RLS) aggregates in families with a familial rate of 77%, a sibling relative risk of 3.6, and an offspring relative risk of 1.8, according to research in the May Archives of Neurology. Following 249 RLS probands and their families from Quebec in a sleep center for 15 years, researchers conducted diagnostic interviews via telephone and found that 671 cases matched the diagnostic criteria for familial RLS, comprising 192 probands and 479 affected family members. “RLS significantly aggregated in families with variable phenotypic expressivity, and the siblings of severely affected individuals have an increased risk of developing the disease,” the researchers wrote.

Stroke/Cerebrovascular Disease
Results of the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) were published in the May 26 online New England Journal of Medicine. Initially presented at the 2010 International Stroke Conference (Neurology Reviews, “Carotid Stenting Versus Surgery for Stroke Prevention,” April, page 1), the study of 2,502 patients with symptomatic or asymptomatic carotid-artery stenosis found that the risk of stroke, myocardial infarction, or death among patients with symptomatic or asymptomatic carotid stenosis was statistically similar for patients undergoing carotid-artery stenting or carotid endarterectomy (7.2% and 6.8%, respectively). However, during the periprocedural period, stenting patients had a higher risk of stroke (hazard ratio, 1.50), while endarterectomy patients had a 2.3% rate of myocardial infarction compared to a 1.1% rate for stenting.

The use of transdermal hormone replacement therapy (HRT) containing low doses of estrogen does not seem to increase the risk of stroke, and thus may be safer than oral tablets of HRT, researchers reported in the June 3 online BMJ. The researchers matched 15,710 women (ages 50 to 79) who had a stroke with 59,958 controls. The rate of stroke in the cohort was 2.85 per 1,000 per year, and the adjusted rate ratio (RR) of stroke associated with current use of transdermal HRT was 0.95 relative to no use. “The risk of stroke was not increased with use of low estrogen dose patches (RR, 0.81) compared with no use, whereas the risk was increased with high dose patches (RR, 1.89),” the study authors reported. “Current users of oral HRT had a higher rate of stroke than nonusers (RR, 1.28) with both low dose and high dose.”

The risk of cerebrovasular disease is higher in individuals with elevated blood pressure or fluctuations in blood pressure than those with low blood pressure or fewer fluctuations, a study in the May Archives of Neurology reported. In a community-based epidemiologic study of older adults living in the Washington Heights-Inwood section of Manhattan, researchers measured white matter hyperintensity and the presence of brain infarctions in a group of 686 nondemented older adults whose blood pressure was measured during three visits 24 months apart and who underwent structural MRIs. Participants with the lowest white matter hyperintensity volume had the lowest mean/lowest blood pressure, and those with the highest white matter hyperintensity volume had the highest mean/highest blood pressure. “Given that cerebrovascular disease is associated with disability, these findings suggest that interventions should focus on long-term fluctuating blood pressure and elevated blood pressure,” investigators concluded.

Tourette Syndrome
Histaminergic neurotransmission may play a role in the mechanism and modulation of Tourette syndrome and tics, researchers reported in the May 20 New England Journal of Medicine. “Despite a strong genetic contribution, inheritance is complex and risk alleles have proven difficult to identify,” the investigators noted. “We have characterized a highly unusual two-generation pedigree in which Tourette syndrome is segregated in an autosomal dominant fashion.” The researchers identified “a rare functional mutation in the HDC gene encoding L-histamine decarboxylase, the rate-limiting enzyme in histamine biosynthesis.” They added that “the links between histaminergic neurotransmission and tics, suggested by our genetic findings, are further supported by previous studies of pharmacologic agents that target the presynaptic autoreceptor H3R.”

Traumatic Brain Injury
In patients with traumatic brain injury (TBI), reduced evening melatonin production may indicate disruption to circadian regulation of melatonin synthesis and lead to sleep disturbance, as reported in the May 25 Neurology. In an observational study of 23 patients with TBI and 23 age- and gender-matched healthy volunteers, researchers found two factors contributing to sleep disturbances in patients with TBI—reduced sleep quality due to elevated depression and anxiety and increased slow wave sleep due to mechanical brain damage. “Patients with TBI reported higher anxiety and depressive symptoms and sleep disturbance than controls,” the investigators wrote. “Patients with TBI showed decreased sleep efficiency and increased wake after sleep onset.” In addition, TBI subjects had lower levels of evening melatonin production associated with REM sleep.

Alzheimer's Disease/Dementia
A person whose spouse has dementia is six times more likely to develop incident dementia than are subjects whose spouses are dementia-free, researchers reported in the May Journal of the American Geriatrics Society. The findings are based on 1,221 married couples (ages 65 and older) from Cache County, Utah. Incident dementia was diagnosed in 255 participants, per DSM-III-Revised criteria. In sex-specific analyses, husbands had a higher risk of dementia (hazard rate ratio [HRR], 11.9) than wives (HRR, 3.7). “The finding of a six times greater risk of dementia in persons so exposed than in married men and women whose spouse had not developed dementia remained after adjustment for age, sex, education, socioeconomic status, and apolipoprotein E genotype, all of which were (as expected) associated with dementia risk,” the investigators reported.

Amyloid-beta, which forms plaques in the brains of patients with Alzheimer’s disease, also accumulates in the eyes of persons with Down syndrome, per a study in the May 20 PLoS One. The optical lenses of patients with Down syndrome have a “characteristic pattern of supranuclear opacification accompanied by accelerated supranuclear amyloid-beta accumulation, co-localizing amyloid pathology, and fiber cell cytoplasmic amyloid-beta aggregates identical to the lens pathology identified in Alzheimer’s disease,” researchers reported. “These results establish the genetic etiology of the distinctive lens phenotype in Down syndrome and identify the molecular origin and pathogenic mechanism by which lens pathology is expressed in this common chromosomal disorder,” the researchers concluded. “Moreover, these findings confirm increased amyloid-beta accumulation as a key pathogenic determinant linking lens and brain pathology in both Down syndrome and Alzheimer’s disease.”

Amyotrophic Lateral Sclerosis
Researchers have found a link between sporadic and familial forms of amyotrophic lateral sclerosis (ALS), according to a study in the June Annals of Neurology. The investigators performed immunostaining on the postmortem spinal cords of 78 ALS cases, including 52 with sporadic ALS, 10 with ALS with dementia, and 16 with familial ALS. Postmortem brains or spinal cords from 22 cases with or without frontotemporal lobar degeneration were also analyzed. The researchers observed FUS-immunoreactive inclusions in spinal anterior horn neurons in all sporadic and familial cases, except for those with SOD1 mutations. “Our data suggest that FUS
protein may be a common component of the cellular inclusions in non-SOD1 ALS and some other neurodegenerative conditions, implying a shared pathogenic pathway underlying sporadic ALS, non-SOD1 familial ALS, ALS/dementia, and related disorders,” reported the study authors.

Epilepsy
The pertussis vaccine may trigger an earlier onset of Dravet syndrome—a severe form of epilepsy—in children with a mutation of the sodium channel gene SCN1A, per a study that was published in the June Lancet Neurology. In the vaccination-proximate group (12 subjects with seizure onset the day of or the day after vaccination) of the retrospective study, the average age of seizure onset was 18.4 weeks. In the vaccination-distant group (25 subjects with seizure onset two or more days after vaccination and three subjects with onset before vaccination), the average age of disease onset was 26.2 weeks. Subjects with the SCN1A mutation are “destined to develop the disease,” the investigators noted. “Vaccination should not be withheld from children with SCN1A mutations because we found no evidence that vaccinations before or after disease onset affect outcome,” the authors concluded.

Restless Legs Syndrome
Restless legs syndrome (RLS) aggregates in families with a familial rate of 77%, a sibling relative risk of 3.6, and an offspring relative risk of 1.8, according to research in the May Archives of Neurology. Following 249 RLS probands and their families from Quebec in a sleep center for 15 years, researchers conducted diagnostic interviews via telephone and found that 671 cases matched the diagnostic criteria for familial RLS, comprising 192 probands and 479 affected family members. “RLS significantly aggregated in families with variable phenotypic expressivity, and the siblings of severely affected individuals have an increased risk of developing the disease,” the researchers wrote.

Stroke/Cerebrovascular Disease
Results of the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) were published in the May 26 online New England Journal of Medicine. Initially presented at the 2010 International Stroke Conference (Neurology Reviews, “Carotid Stenting Versus Surgery for Stroke Prevention,” April, page 1), the study of 2,502 patients with symptomatic or asymptomatic carotid-artery stenosis found that the risk of stroke, myocardial infarction, or death among patients with symptomatic or asymptomatic carotid stenosis was statistically similar for patients undergoing carotid-artery stenting or carotid endarterectomy (7.2% and 6.8%, respectively). However, during the periprocedural period, stenting patients had a higher risk of stroke (hazard ratio, 1.50), while endarterectomy patients had a 2.3% rate of myocardial infarction compared to a 1.1% rate for stenting.

The use of transdermal hormone replacement therapy (HRT) containing low doses of estrogen does not seem to increase the risk of stroke, and thus may be safer than oral tablets of HRT, researchers reported in the June 3 online BMJ. The researchers matched 15,710 women (ages 50 to 79) who had a stroke with 59,958 controls. The rate of stroke in the cohort was 2.85 per 1,000 per year, and the adjusted rate ratio (RR) of stroke associated with current use of transdermal HRT was 0.95 relative to no use. “The risk of stroke was not increased with use of low estrogen dose patches (RR, 0.81) compared with no use, whereas the risk was increased with high dose patches (RR, 1.89),” the study authors reported. “Current users of oral HRT had a higher rate of stroke than nonusers (RR, 1.28) with both low dose and high dose.”

The risk of cerebrovasular disease is higher in individuals with elevated blood pressure or fluctuations in blood pressure than those with low blood pressure or fewer fluctuations, a study in the May Archives of Neurology reported. In a community-based epidemiologic study of older adults living in the Washington Heights-Inwood section of Manhattan, researchers measured white matter hyperintensity and the presence of brain infarctions in a group of 686 nondemented older adults whose blood pressure was measured during three visits 24 months apart and who underwent structural MRIs. Participants with the lowest white matter hyperintensity volume had the lowest mean/lowest blood pressure, and those with the highest white matter hyperintensity volume had the highest mean/highest blood pressure. “Given that cerebrovascular disease is associated with disability, these findings suggest that interventions should focus on long-term fluctuating blood pressure and elevated blood pressure,” investigators concluded.

Tourette Syndrome
Histaminergic neurotransmission may play a role in the mechanism and modulation of Tourette syndrome and tics, researchers reported in the May 20 New England Journal of Medicine. “Despite a strong genetic contribution, inheritance is complex and risk alleles have proven difficult to identify,” the investigators noted. “We have characterized a highly unusual two-generation pedigree in which Tourette syndrome is segregated in an autosomal dominant fashion.” The researchers identified “a rare functional mutation in the HDC gene encoding L-histamine decarboxylase, the rate-limiting enzyme in histamine biosynthesis.” They added that “the links between histaminergic neurotransmission and tics, suggested by our genetic findings, are further supported by previous studies of pharmacologic agents that target the presynaptic autoreceptor H3R.”

Traumatic Brain Injury
In patients with traumatic brain injury (TBI), reduced evening melatonin production may indicate disruption to circadian regulation of melatonin synthesis and lead to sleep disturbance, as reported in the May 25 Neurology. In an observational study of 23 patients with TBI and 23 age- and gender-matched healthy volunteers, researchers found two factors contributing to sleep disturbances in patients with TBI—reduced sleep quality due to elevated depression and anxiety and increased slow wave sleep due to mechanical brain damage. “Patients with TBI reported higher anxiety and depressive symptoms and sleep disturbance than controls,” the investigators wrote. “Patients with TBI showed decreased sleep efficiency and increased wake after sleep onset.” In addition, TBI subjects had lower levels of evening melatonin production associated with REM sleep.

Alzheimer's Disease/Dementia
A person whose spouse has dementia is six times more likely to develop incident dementia than are subjects whose spouses are dementia-free, researchers reported in the May Journal of the American Geriatrics Society. The findings are based on 1,221 married couples (ages 65 and older) from Cache County, Utah. Incident dementia was diagnosed in 255 participants, per DSM-III-Revised criteria. In sex-specific analyses, husbands had a higher risk of dementia (hazard rate ratio [HRR], 11.9) than wives (HRR, 3.7). “The finding of a six times greater risk of dementia in persons so exposed than in married men and women whose spouse had not developed dementia remained after adjustment for age, sex, education, socioeconomic status, and apolipoprotein E genotype, all of which were (as expected) associated with dementia risk,” the investigators reported.

Amyloid-beta, which forms plaques in the brains of patients with Alzheimer’s disease, also accumulates in the eyes of persons with Down syndrome, per a study in the May 20 PLoS One. The optical lenses of patients with Down syndrome have a “characteristic pattern of supranuclear opacification accompanied by accelerated supranuclear amyloid-beta accumulation, co-localizing amyloid pathology, and fiber cell cytoplasmic amyloid-beta aggregates identical to the lens pathology identified in Alzheimer’s disease,” researchers reported. “These results establish the genetic etiology of the distinctive lens phenotype in Down syndrome and identify the molecular origin and pathogenic mechanism by which lens pathology is expressed in this common chromosomal disorder,” the researchers concluded. “Moreover, these findings confirm increased amyloid-beta accumulation as a key pathogenic determinant linking lens and brain pathology in both Down syndrome and Alzheimer’s disease.”

Amyotrophic Lateral Sclerosis
Researchers have found a link between sporadic and familial forms of amyotrophic lateral sclerosis (ALS), according to a study in the June Annals of Neurology. The investigators performed immunostaining on the postmortem spinal cords of 78 ALS cases, including 52 with sporadic ALS, 10 with ALS with dementia, and 16 with familial ALS. Postmortem brains or spinal cords from 22 cases with or without frontotemporal lobar degeneration were also analyzed. The researchers observed FUS-immunoreactive inclusions in spinal anterior horn neurons in all sporadic and familial cases, except for those with SOD1 mutations. “Our data suggest that FUS
protein may be a common component of the cellular inclusions in non-SOD1 ALS and some other neurodegenerative conditions, implying a shared pathogenic pathway underlying sporadic ALS, non-SOD1 familial ALS, ALS/dementia, and related disorders,” reported the study authors.

Epilepsy
The pertussis vaccine may trigger an earlier onset of Dravet syndrome—a severe form of epilepsy—in children with a mutation of the sodium channel gene SCN1A, per a study that was published in the June Lancet Neurology. In the vaccination-proximate group (12 subjects with seizure onset the day of or the day after vaccination) of the retrospective study, the average age of seizure onset was 18.4 weeks. In the vaccination-distant group (25 subjects with seizure onset two or more days after vaccination and three subjects with onset before vaccination), the average age of disease onset was 26.2 weeks. Subjects with the SCN1A mutation are “destined to develop the disease,” the investigators noted. “Vaccination should not be withheld from children with SCN1A mutations because we found no evidence that vaccinations before or after disease onset affect outcome,” the authors concluded.

Restless Legs Syndrome
Restless legs syndrome (RLS) aggregates in families with a familial rate of 77%, a sibling relative risk of 3.6, and an offspring relative risk of 1.8, according to research in the May Archives of Neurology. Following 249 RLS probands and their families from Quebec in a sleep center for 15 years, researchers conducted diagnostic interviews via telephone and found that 671 cases matched the diagnostic criteria for familial RLS, comprising 192 probands and 479 affected family members. “RLS significantly aggregated in families with variable phenotypic expressivity, and the siblings of severely affected individuals have an increased risk of developing the disease,” the researchers wrote.

Stroke/Cerebrovascular Disease
Results of the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) were published in the May 26 online New England Journal of Medicine. Initially presented at the 2010 International Stroke Conference (Neurology Reviews, “Carotid Stenting Versus Surgery for Stroke Prevention,” April, page 1), the study of 2,502 patients with symptomatic or asymptomatic carotid-artery stenosis found that the risk of stroke, myocardial infarction, or death among patients with symptomatic or asymptomatic carotid stenosis was statistically similar for patients undergoing carotid-artery stenting or carotid endarterectomy (7.2% and 6.8%, respectively). However, during the periprocedural period, stenting patients had a higher risk of stroke (hazard ratio, 1.50), while endarterectomy patients had a 2.3% rate of myocardial infarction compared to a 1.1% rate for stenting.

The use of transdermal hormone replacement therapy (HRT) containing low doses of estrogen does not seem to increase the risk of stroke, and thus may be safer than oral tablets of HRT, researchers reported in the June 3 online BMJ. The researchers matched 15,710 women (ages 50 to 79) who had a stroke with 59,958 controls. The rate of stroke in the cohort was 2.85 per 1,000 per year, and the adjusted rate ratio (RR) of stroke associated with current use of transdermal HRT was 0.95 relative to no use. “The risk of stroke was not increased with use of low estrogen dose patches (RR, 0.81) compared with no use, whereas the risk was increased with high dose patches (RR, 1.89),” the study authors reported. “Current users of oral HRT had a higher rate of stroke than nonusers (RR, 1.28) with both low dose and high dose.”

The risk of cerebrovasular disease is higher in individuals with elevated blood pressure or fluctuations in blood pressure than those with low blood pressure or fewer fluctuations, a study in the May Archives of Neurology reported. In a community-based epidemiologic study of older adults living in the Washington Heights-Inwood section of Manhattan, researchers measured white matter hyperintensity and the presence of brain infarctions in a group of 686 nondemented older adults whose blood pressure was measured during three visits 24 months apart and who underwent structural MRIs. Participants with the lowest white matter hyperintensity volume had the lowest mean/lowest blood pressure, and those with the highest white matter hyperintensity volume had the highest mean/highest blood pressure. “Given that cerebrovascular disease is associated with disability, these findings suggest that interventions should focus on long-term fluctuating blood pressure and elevated blood pressure,” investigators concluded.

Tourette Syndrome
Histaminergic neurotransmission may play a role in the mechanism and modulation of Tourette syndrome and tics, researchers reported in the May 20 New England Journal of Medicine. “Despite a strong genetic contribution, inheritance is complex and risk alleles have proven difficult to identify,” the investigators noted. “We have characterized a highly unusual two-generation pedigree in which Tourette syndrome is segregated in an autosomal dominant fashion.” The researchers identified “a rare functional mutation in the HDC gene encoding L-histamine decarboxylase, the rate-limiting enzyme in histamine biosynthesis.” They added that “the links between histaminergic neurotransmission and tics, suggested by our genetic findings, are further supported by previous studies of pharmacologic agents that target the presynaptic autoreceptor H3R.”

Traumatic Brain Injury
In patients with traumatic brain injury (TBI), reduced evening melatonin production may indicate disruption to circadian regulation of melatonin synthesis and lead to sleep disturbance, as reported in the May 25 Neurology. In an observational study of 23 patients with TBI and 23 age- and gender-matched healthy volunteers, researchers found two factors contributing to sleep disturbances in patients with TBI—reduced sleep quality due to elevated depression and anxiety and increased slow wave sleep due to mechanical brain damage. “Patients with TBI reported higher anxiety and depressive symptoms and sleep disturbance than controls,” the investigators wrote. “Patients with TBI showed decreased sleep efficiency and increased wake after sleep onset.” In addition, TBI subjects had lower levels of evening melatonin production associated with REM sleep.