Early seizures and risk of epilepsy and death after intracerebral haemorrhage: The MUCH Italy.

INTRODUCTION: It is unclear which patients with non-traumatic (spontaneous) intracerebral haemorrhage (ICH) are at risk of developing acute symptomatic seizures (provoked seizures occurring within the first week after stroke onset; early seizures, ES) and whether ES predispose to the occurrence of remote symptomatic seizures (unprovoked seizures occurring more than 1 week after stroke; post-stroke epilepsy, PSE) and long-term mortality. PATIENTS AND METHODS: In the setting of the Multicenter Study on Cerebral Haemorrhage in Italy (MUCH-Italy) we examined the risk of ES and whether they predict the occurrence of PSE and all-cause mortality in a cohort of patients with first-ever spontaneous ICH and no previous history of epilepsy, consecutively hospitalized in 12 Italian neurological centers from 2002 to 2014. RESULTS: Among 2570 patients (mean age, 73.4 ± 12.5 years; males, 55.4%) 228 (8.9%) had acute ES (183 (7.1%) short seizures and 45 (1.8%) status epilepticus (SE)). Lobar location of the hematoma (OR, 1.49; 95% CI, 1.06-2.08) was independently associated with the occurrence of ES. Of the 2,037 patients who were followed-up (median follow-up time, 68.0 months (25th-75th percentile, 77.0)), 155 (7.6%) developed PSE. ES (aHR, 2.34; 95% CI, 1.42-3.85), especially when presenting as short seizures (aHR, 2.35; 95% CI, 1.38-4.00) were associated to PSE occurrence. Unlike short seizures, SE was an independent predictor of all-cause mortality (aHR, 1.50; 95% CI, 1.005-2.26). DISCUSSION AND CONCLUSION: The long-term risk of PSE and death after an ICH vary according to ES subtype. This might have implications for the design of future clinical trials targeting post-ICH epileptic seizures.

Frailty and Associated Environmental Factors Only Have Small Effects on Age of Onset in Huntington's Disease.

BACKGROUND: Over one third of age of onset variation in Huntington's disease is unexplained by CAG repeat length. In Alzheimer's disease, frailty partly modulates the relationship between neuropathology and dementia. OBJECTIVE: We investigated whether a multi-domain frailty index, reflecting non-genetic factors in Huntington's disease, similarly modulates the relationship between CAG repeat length and age of onset. METHODS: We created a frailty index assessing comorbidities, substance abuse, polypharmacy, and education. We applied multiple linear regression models to 2,741 subjects with manifest Huntington's disease from the Enroll-HD cohort study, including 729 subjects with late-onset (post-60 years) disease, using frailty index or constituent item scores and CAG repeat length as independent variables. We used actual and "residual" ages of onset (difference between actual and CAG-based predicted onset) as dependent variables, the latter offsetting the increased time available to accumulate comorbidities in older subjects. RESULTS: Higher frailty index scores were associated with significantly lower residual ages of onset in the late-onset subgroup (p = 0.03), though the effect was small (R2 = 0.27 with frailty as a predictor vs. 0.26 without). Number of comorbidities was also associated with significantly lower residual ages of onset in the late-onset subgroup (p = 0.04). Drug abuse and smoking were associated with significantly earlier ages of onset in the whole cohort (p < 0.01, p = 0.02) and late-onset subgroup (p < 0.01, p = 0.03). CONCLUSIONS: The impact of non-genetic factors on age of onset, assessed using a frailty index or separately, in Huntington's disease is limited.

Diet, pace of biological aging, and risk of dementia in the Framingham Heart Study.

INTRODUCTION: We tested the hypothesis that healthy diet protects against dementia because it slows the pace of biological aging. METHODS: We analyzed Framingham Offspring Cohort data (≥60y). We measured healthy diet using the Dietary Guideline for Americans (DGA, 3 visits 1991-2008), pace of aging using the DunedinPACE epigenetic clock (2005-2008), and incident dementia and mortality using records (compiled 2005-2018). RESULTS: Of n=1,525 included participants (mean age 69.7, 54% female), n=129 developed dementia and n=432 died over follow-up. Greater DGA adherence was associated with slower DunedinPACE and reduced risks for dementia and mortality. Slower DunedinPACE was associated with reduced risks for dementia and mortality. Slower DunedinPACE accounted for 15% of the DGA association with dementia and 39% of the DGA association with mortality. DISCUSSION: Findings suggest that slower pace of aging mediates part of the relationship of healthy diet with reduced dementia risk. Monitoring pace of aging may inform dementia prevention.

Association of a MIND Diet with Brain Structure and Dementia in a French Population.

BACKGROUND: Adherence to the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet, which combines higher consumption of vegetables, berries, nuts, whole grains, olive oil, fish, beans and poultry, with lower consumption of meat, sugars and saturated fats, is a promising strategy to prevent dementia. However, evidence in populations with non-US food culture, especially from Europe, is limited. OBJECTIVES: To evaluate the association of a French-adapted MIND diet score with gray matter volumes, white matter microstructure and incident dementia. DESIGN AND SETTING: This longitudinal study included participants from the population-based Three-City Bordeaux cohort (≥65 years), with a follow-up from June 2001 to February 2018. PARTICIPANTS: Dementia-free participants at dietary assessment, in 2001-2002, who underwent systematic detection of incident dementia (over up to 7 visits). A subset of the cohort was included in an ancillary MRI study in 2010-2011. MEASUREMENTS: A French-adapted MIND diet score (range, 0-15) was computed from a 148-item Food Frequency Questionnaire and a 24-hour recall administered at home. Incident dementia and its subtypes were adjudicated by an expert committee; and gray matter volumes and white matter microstructure were assessed by 3D-T1 MRI and diffusion-MRI. RESULTS: Among 1,412 participants (mean age, 75.8 [SD, 4.8]; 63% women), followed for a median of 9.7 years (maximum 16.3 years), 356 (25.2%) developed incident dementia. In multivariable-adjusted Cox model, a higher French MIND diet score was associated with lower risks of dementia and AD (hazard ratios for 1-point of score = 0.89 [95% confidence interval, 0.83-0.95] and 0.88 [0.81-0.96], respectively). In Tract-Based Spatial Statistics analysis of 175 participants included in the MRI sub-study, a higher MIND diet score was associated with lower diffusivity values in the splenium of the corpus callosum (P < .05 after Family-Wise Error-correction). In contrast, there was no significant association of the adapted MIND diet score with gray matter volumes in Voxel-Based Morphometry analysis. CONCLUSION: In this cohort of French older adults, higher adherence to the French MIND diet was associated with a lower dementia risk and with preserved white matter microstructure. These results provide further evidence for a role of the MIND diet in the prevention of dementia.

Risk Factors for Cerebral Aneurysm Rupture in Mongolia.

PURPOSE: Identification of country-specific demographic, medical, lifestyle, and geoenvironmental risk factors for cerebral aneurysm rupture in the developing Asian country of Mongolia. First-time estimation of the crude national incidence of aneurysmal subarachnoid hemorrhage (aSAH). METHODS: A retrospective analysis of all intracranial digital subtraction angiographies (DSA) acquired in Mongolia during the 2­year period 2016-2017 (1714 examinations) was performed. During this period, DSA was used as primary diagnostic imaging modality for acute severe neurological symptoms in the sole hospital nationwide dedicated to neurological patients. The catchment area of the hospital included the whole country. Patients with incidental and ruptured aneurysms were reviewed with respect to their medical history and living conditions. The data was used to install a Mongolian aneurysm registry. RESULTS: The estimated annual crude incidence of cerebral aneurysm rupture was 6.71 for the country of Mongolia and 14.53 per 100,000 persons for the capital region of Ulaanbaatar. Risk factors common in developed countries also applied for the Mongolian population: A medical history of hypertension, smoking or the presence of multiple aneurysms led to a higher relative risk of rupture. In contrast, female gender was not associated with a higher risk in this national cohort. Males pursuing a traditional nomadic living may exhibit a specifically high risk of rupture. CONCLUSION: Disease management of over 200 individuals/year with aSAH constitutes a socioeconomic burden in Mongolia. Efforts to raise awareness of the risk factors hypertension and smoking among the Mongolian population are desirable. Measures to improve the nationwide availability of modern neurovascular treatment options are currently under consideration.

Personalized nutrition for dementia prevention.

The role of nutrition has been investigated for decades under the assumption of one-size-fits-all. Yet there is heterogeneity in metabolic and neurobiological responses to diet. Thus a more personalized approach may better fit biological reality and have increased efficacy to prevent dementia. Personalized nutrition builds on the food exposome, defined as the history of diet-related exposures over the lifetime, and on its interactions with the genome and other biological characteristics (eg, metabolism, the microbiome) to shape health. We review current advances of personalized nutrition in dementia research. We discuss key questions, success milestones, and future roadmap from observational epidemiology to clinical studies through basic science. A personalized nutrition approach based on the best prescription for the most appropriate target population in the most relevant time-window has the potential to strengthen dementia-prevention efforts.

Modifying pathways by age and sex for the association between combined sleep disordered breathing and long sleep duration with neurocognitive decline in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL).

INTRODUCTION: We aimed to determine whether obesity or metabolic syndrome (MetS) modify associations between sleep-disordered breathing (SDB), self-reported sleep duration (SD), and phenotypes of combined SDB/SD with 7-year neurocognitive decline (ND) in a community based-cohort of U.S. Hispanic/Latinos (N = 5500) in different age and sex groups. METHODS: The exposures were baseline SDB (respiratory event index ≥ 15), sleepiness (Epworth Sleepiness Scale ≥ 10), SD (< 6 hours, 6-9 hours, ≥ 9 hours). The outcome was 7-year ND. RESULTS: Mean age was 56.0 years, 54.8% were females. Obesity modified the association between SDB/SD and ND in memory (F = 21.49, P < 0.001) and global cognition (F = 9.14, P < 0.001) in the oldest age group. Women without MetS with combined long sleep/SDB exhibited most pronounced decline in global cognition (F = 3.07, P = 0.010). DISCUSSION: The association between combined SDB/long sleep and declines in memory and global cognition was most pronounced in obese older adults. Among women, MetS status modified the association between long sleep/SDB and decline in global cognition.

Dietary intake is associated with neuropsychological impairment in women with HIV.

BACKGROUND: Diet is a modifiable risk factor that may influence cognition in people with HIV. OBJECTIVES: We examined the association between dietary intake and cognition in women with HIV (WWH) and HIV-seronegative women. METHODS: An 18-item dietary National Cancer Institute screener was completed by 729 WWH and 346 HIV-seronegative Women's Interagency HIV Study participants. Daily intake frequencies of processed meats, sweet beverages, fish, whole milk, and vegetables were calculated. Participants completed biennial neuropsychological (NP) testing. NP domains included attention/working memory, executive function, processing speed, memory, learning, fluency, and motor function. NP impairment was defined as demographically adjusted T-scores (mean = 50; SD = 10) ≤40 at ≥1 visit after completing the dietary screener. Multivariable logistic regression, stratified by HIV serostatus, examined associations between intake frequency tertile (referent = lowest intake) and NP performance. RESULTS: Dietary intake frequencies of individual food line items were similar between WWH and HIV-seronegative women, except for sweet beverages, for which HIV-seronegative women reported higher intake frequencies than WWH (P values < 0.05). In WWH, multivariable-adjusted models indicated higher odds of NP impairment with higher intake frequencies of processed meat [P = 0.006; ORupper tertile = 1.91 (95% CI: 1.23-2.95; P = 0.003); ORmiddle tertile = 1.66 (95% CI: 1.14-2.42; P = 0.01)], sweet beverages [P = 0.02; ORupper tertile = 1.75 (95% CI: 1.17-2.64; P = 0.007)], fish [P = 0.01; ORupper tertile = 1.70 (95% CI: 1.10-2.64; P = 0.02)], and whole milk [P = 0.029; ORupper tertile = 1.66 (95% CI: 1.14-2.42; P = 0.008)]. Lower odds of NP impairment [P = 0.005; ORupper tertile = 0.65 (95% CI: 0.45-0.95; P = 0.02); ORmiddle tertile = 0.42 (95% CI: 0.24-0.73; P = 0.002)] were associated with higher vegetable intakes. In HIV-seronegative women, multivariable-adjusted models did not show associations between food line items/diet quality score and NP outcomes. CONCLUSIONS: Intakes of processed meat, sweet beverages, whole milk, fish, and vegetables may be associated with NP functions among WWH. Associations among WWH are not directly comparable to those among HIV-seronegative women, because models were conducted on each group separately given controls for HIV-specific covariates in WWH. Further studies are needed using more rigorous dietary assessment methods and lengthier longitudinal follow-ups.

Polygenic risk scores for Alzheimer's disease are related to dementia risk in APOE ɛ4 negatives.

INTRODUCTION: Studies examining the effect of polygenic risk scores (PRS) for Alzheimer's disease (AD) and apolipoprotein E (APOE) genotype on incident dementia in very old individuals are lacking. METHODS: A population-based sample of 2052 individuals ages 70 to 111, from Sweden, was followed in relation to dementia. AD-PRSs including 39, 57, 1333, and 13,942 single nucleotide polymorphisms (SNPs) were used. RESULTS: AD-PRSs (including 39 or 57 SNPs) were associated with dementia (57-SNPs AD-PRS: hazard ratio 1.09, confidence interval 1.01-1.19, P = .03), particularly in APOE ɛ4 non-carriers (57-SNPs AD-PRS: 1.15, 1.05-1.27, P = 4 × 10-3, 39-SNPs AD-PRS: 1.22, 1.10-1.35, P = 2 × 10-4). No association was found with the other AD-PRSs. Further, APOE ɛ4 was associated with increased risk of dementia (1.60, 1.35-1.92, P = 1 × 10-7). In those aged ≥95 years, the results were similar for the AD-PRSs, while APOE ɛ4 only predicted dementia in the low-risk tertile of AD-PRSs. DISCUSSION: These results provide information to identify individuals at increased risk of dementia.

Plasma carotenoids and medial temporal lobe atrophy in older adults.

BACKGROUND & AIMS: Carotenoids are vegetable pigments with neuroprotective properties. Clinical studies found efficacy of specific carotenoids on improving brain perfusion and functioning with aging. However, evidence of an effect on neurodegeneration, which may require longer follow-up period to observe, is more limited. Leveraging biomarkers from a large population-based cohort study of older adults, we investigated whether blood carotenoids were associated with atrophy of the medial temporal lobe (a biomarker of neurodegeneration in aging) over 10 years. METHODS: This study included 461 dementia-free participants from the Three-City Bordeaux study (aged ≥65) who had plasma carotenoids measured at baseline and up to three repeated brain imaging exams in the subsequent 10 years. RESULTS: In adjusted linear mixed models, each increase of 1 SD in plasma level of total carotenoids and of ß-carotene was associated with 0.02 cm3 (95% CI, 0.001-0.04; P = 0.04) and 0.02 cm3 (95% CI, 0.01-0.04; P = 0.008) smaller medial temporal lobe volume loss per year, respectively. CONCLUSIONS: Our results based on a unique long-term prospective evaluation of a neuroimaging biomarker suggest a beneficial role of carotenoids for the prevention of age-related neurodegeneration.

In sickness and in health: when myasthenia gravis is a conjugal matter.

OBJECTIVE: Genes and environment contribute to the multifactorial etiology of autoimmune diseases. Familial clusters of autoimmune diseases are often observed among first-degree relatives sharing the same genetic background and environmental exposure. Rarer is the occurrence of the same autoimmune diseases in non-consanguineous spouses. We hereinafter report two non-consanguineous spouses who developed one after the other AChR-positive myasthenia gravis. METHODS: This study has been approved by Catholic University Ethic Committee. The wife, previously affected by Graves-Basedow disease, was the first to be diagnosed with myasthenia gravis, basing on a generalized weakness and an anti-AChR-positive assay. The husband, who suffered from ulcerative colitis, 16 years after his wife diagnosis complained of a mild generalized weakness. Repetitive nerve stimulation test and anti-AChR assay were confirmed myasthenia gravis. In these spouses, myasthenia gravis was not associated with thymoma. Human leukocyte antigen (HLA) class II genotyping showed distinct associations, with the wife carrying the DRB1*03:01 DQB1*02:01 and the husband the DRB1*07 DQB102 alleles. RESULTS: The wife's haplotype is strongly associated with myasthenia gravis and thyroiditis whereas HLA DRB1*07 allele was found to be related both to late-onset myasthenia gravis and ulcerative colitis. CONCLUSIONS: Compared with other autoimmune disorders, myasthenia gravis has a lower prevalence. The surveillance environmental exposure may greatly improve our knowledge of non-genetic drivers of autoimmunity.

Interactions Between Age, Sex, Menopause, and Brain Structure at Midlife: A UK Biobank Study.

OBJECTIVES: Age and female sex are risk factors for dementia, and menopause is associated with cognitive dysfunction. Previous work largely considered the effects of sex and menopause as being independent of age. We studied whether age interacts with sex or menopause in explaining imaging biomarkers of dementia during midlife. METHODS: In this cross-sectional study of UK Biobank participants with brain magnetic resonance imaging (MRI), we explored the interaction of age with sex or menopausal status in explaining total brain volume (TBV), gray matter volume (GMV), white matter volume (WMV), white matter hyperintensity volume (WMHV), regional cortical volume , and subcortical volume. RESULTS: Data were available for 1827 postmenopausal women, 230 pre/perimenopausal women and 2165 men (median age 63.3 years). There was a significant interaction between age and sex (P = .024) for TBV, where the inverse association age with TBV was steeper in women (ß = -5.35 mL/year) than in men (ß = -4.77 mL/year). Similar age-sex interactions were also observed for GMV and WMV. In women, there was a significant interaction between age and menopausal status (P = .007) where the inverse association of age with TBV was steeper in postmenopausal (ß = -5.89 mL/year) than in pre/perimenopausal women (ß = -1.61 mL/year). Similar age-menopause interactions were found in predicting lower GMV and higher WMHV. Differences in the direction of these age-sex and age-menopause interactions were found for regional cortical and subcortical brain volumes. CONCLUSION: Sex and menopause both interact with age during midlife in explaining MRI biomarkers of dementia. Further work is required to understand the mechanisms driving these interactions to develop strategies for delaying dementia.

Pre-diagnostic plasma lipid levels and the risk of amyotrophic lateral sclerosis.

OBJECTIVE: To assess whether pre-diagnostic lipid levels are associated with Amyotrophic lateral sclerosis (ALS) risk. Methods: We conducted a matched case-control study nested in five large prospective US cohorts (the Nurses' Health Study, the Health Professionals Follow-up Study, the Cancer Prevention Study II Nutrition Cohort, the Multiethnic Cohort Study, and the Women's Health Initiative), and identified 275 individuals who developed ALS during follow-up and had provided blood samples before disease diagnosis. For each ALS case, we randomly selected two controls who were alive at the time of the case diagnosis and matched on cohort, birth year (±1 year), sex, race/ethnicity, fasting status, and time of blood draw. We measured total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG) levels in the plasma samples, and used conditional logistic regression to estimate associations between lipid levels and ALS risk. Results: Higher levels of HDL-C were associated with higher ALS risk in an analysis adjusted for the matching factors (risk ratio [RR] Q4 vs. Q1: 1.78, 95% confidence interval [CI]: 1.18-2.69, p trend: 0.007). The estimate remained similar in a multivariable analysis additionally adjusted for body mass index, physical activity, smoking, alcohol intake, plasma urate levels, and use of cholesterol-lowering drugs (RR Q4 vs. Q1: 1.71, 95% CI: 1.07-2.73, p trend: 0.02). Plasma levels of TC, LDL-C, and TG were not associated with ALS risk. Conclusions: Higher pre-diagnostic HDL-C levels, but not levels of other lipids, were associated with a higher risk of ALS.

Another Look at Obesity Paradox in Acute Ischemic Stroke: Association Rule Mining.

Though obesity is generally associated with the development of cardiovascular disease (CVD) risk factors, previous reports have also reported that obesity has a beneficial effect on CVD outcomes. We aimed to verify the existing obesity paradox through binary logistic regression (BLR) and clarify the paradox via association rule mining (ARM). Patients with acute ischemic stroke (AIS) were assessed for their 3-month functional outcome using the modified Rankin Scale (mRS) score. Predictors for poor outcome (mRS 3-6) were analyzed through BLR, and ARM was performed to find out which combination of risk factors was concurrently associated with good outcomes using maximal support, confidence, and lift values. Among 2580 patients with AIS, being obese (OR [odds ratio], 0.78; 95% CI, 0.62-0.99) had beneficial effects on the outcome at 3 months in BLR analysis. In addition, the ARM algorithm showed obese patients with good outcomes were also associated with an age less than 55 years and mild stroke severity. While BLR analysis showed a beneficial effect of obesity on stroke outcome, in ARM analysis, obese patients had a relatively good combination of risk factor profiles compared to normal BMI patients. These results may partially explain the obesity paradox phenomenon in AIS patients.

Actigraphic sleep patterns and cognitive decline in the Hispanic Community Health Study/Study of Latinos.

INTRODUCTION: We determined if actigraphy-derived sleep patterns led to 7-year cognitive decline in middle-aged to older Hispanic/Latino adults. METHODS: We examined 1035 adults, 45 to 64 years of age, from the Hispanic Community Health Study/Study of Latinos. Participants had repeated measures of cognitive function 7 years apart, home sleep apnea studies, and 1 week of actigraphy. Survey linear regression evaluated prospective associations between sleep and cognitive change, adjusting for main covariates. RESULTS: Longer sleep-onset latency was associated with declines in global cognitive function, verbal learning, and verbal memory. Longer sleep-onset latency was also cross-sectionally associated with verbal learning, verbal memory, and word fluency. Sleep fragmentation was not associated with cognitive change. CONCLUSION: In a cohort of mostly middle-aged Hispanic/Latinos, actigraphy-derived sleep-onset latency predicted 7-year cognitive change. These findings may serve as targets for sleep interventions of cognitive decline.

Blood polyunsaturated omega-3 fatty acids, brain atrophy, cognitive decline, and dementia risk.

INTRODUCTION: We searched for consistent associations of an omega-3 index in plasma (sum of eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]) with several dementia-related outcomes in a large cohort of older adults. METHODS: We included 1279 participants from the Three-City study, non-demented at the time of blood measurements at baseline, with face-to-face neuropsychological assessment and systematic detection of incident dementia over a 17-year follow-up. An ancillary study included 467 participants with up to three repeated brain imaging exams over 10 years. RESULTS: In multivariable models, higher levels of plasma EPA+DHA were consistently associated with a lower risk of dementia (hazard ratio for 1 standard deviation = 0.87 [95% confidence interval, 0.76-0.98]), and a lower decline in global cognition (P = .04 for change over time), memory (P = .06), and medial temporal lobe volume (P = .02). DISCUSSION: This prospective study provides compelling evidence for a relationship between long-chain omega-3 fatty acids levels and lower risks for dementia and related outcomes.

Endovascular aneurysm closure during out of office hours is not related to complications or outcome.

PURPOSE: A possible disadvantage of endovascular occlusion outside work hours is that complex procedures might expose patients to additional risk when performed in a suboptimal setting. In this prospective cohort study, we evaluated whether treatment during out of office hours is a risk factor for per-procedural complications and clinical outcome. METHODS: We included 471 endovascular-treated, consecutive aneurysmal subarachnoid hemorrhage patients (56.6 ± 13.1, 69% female), from two prospective observational databases which were retrospectively analyzed. Primary outcome was the occurrence of per-procedural complications. Secondary outcomes were good clinical outcome (modified ranking scale ≤ 2) and death at 6-month follow-up. We determined odds ratios (OR) with 95% confidence intervals (CI) by ordered polytomous logistic regression analysis and adjusted odds ratios (aOR) for age, World Federation of Neurosurgical Societies grade, and time to treatment. RESULTS: Most patients were treated during office hours (363/471; 77.1%). Treatment during out of office hours did not result in an increased risk of per-procedural complications (OR 0.85 (95% CI 0.53-1.37; p = 0.51). Patients treated during out of office hours displayed similar odds of good clinical outcome and death after 6 months (OR 1.14, 95% CI 0.68-1.97 and 1.16 95% CI 0.56-2.29, respectively) compared to patients treated during office hours. CONCLUSION: In our study, endovascular coil embolization during out of office hours did not expose patients to an increased risk of procedural complications or affect functional outcome after 6 months.

Is Midlife Metabolic Syndrome Associated With Cognitive Function Change? The Study of Women's Health Across the Nation.

CONTEXT: Metabolic syndrome (MetS) affects cognitive function in late life, particularly in women. But longitudinal research is scarce on associations of MetS with cognitive function during midlife. OBJECTIVE: To determine associations between MetS exposure and cognitive function trajectories in midlife women. DESIGN AND SETTING: This is a 17-year prospective, longitudinal study of multiracial/ethnic women in 7 US communities, with annual/biennial assessments. PARTICIPANTS: Participants were 2149 US women traversing menopause. EXPOSURE: Exposure consisted of MetS assessments (median 4 assessments over 4 years). MAIN OUTCOME MEASURES: Main outcome measures were assessments of cognitive function in 3 domains: perceptual speed (symbol digit modalities test, SDMT), episodic memory (East Boston Memory Test, EBMT), and working memory (Digit Span Backward Test, DSB). RESULTS: By their first cognitive assessment (age 50.7 ± 2.9 years), 29.5% met the criteria for MetS. Women completed a median (interquartile range [IQR]) of 6 (IQR 4-7) follow-up cognitive assessments over 11.2 (IQR 9.2-11.5) years. Women with MetS, compared with those without, had a larger 10-year decline in SDMT z-score (estimate -0.087, 95% confidence interval, -0.150 to -0.024; P = 0.007), after adjustment for cognitive testing practice effects, sociodemographics, lifestyle, mood, and menopause factors. As such, MetS accelerated the 10-year loss of perceptual speed by 24%. MetS did not differentially affect the rate of decline in either immediate (P = 0.534) or delayed (P = 0.740) episodic memory or in working memory (P = 0.584). CONCLUSIONS: In midlife women MetS exposure was associated with accelerated decline in perceptual speed, but not episodic or working memory.

Subjects at risk of Parkinson's disease in health checkup examinees: cross-sectional analysis of baseline data of the NaT-PROBE study.

INTRODUCTION: The present study aimed to survey the prevalence of prodromal symptoms of Parkinson's disease (PD) in Japanese health checkup examinees, for identifying at-risk subjects. METHODS: We conducted a questionnaire survey of annual health checkup examinees without neurological symptoms using the following self-reported questionnaires: Japanese version of the Scale for Outcomes in Parkinson's disease for Autonomic Symptoms (SCOPA-AUT); Self-administered Odor Question (SAOQ); REM Sleep Behavior Disorder Screening Scale (RBDSQ); Beck Depression Inventory-Second Edition (BDI-II); Epworth Sleepiness Scale (ESS); and Physical Activity Scale for the Elderly (PASE). The presence of prodromal symptoms was determined using the 90th percentile threshold of each questionnaire. Subjects ≥ 50 years of age with ≥ 2 core prodromal symptoms (dysautonomia, hyposmia, and RBD), were classified as at risk. RESULTS: Between March 2017 and March 2018, 4,953 participants sufficiently answered the questionnaires. Among 2,726 subjects ≥ 50 years of age, 155 were classified as at risk. These subjects had worse values of BDI-II (12.0 ± 8.3 vs. 4.4 ± 3.8, p < 0.001) and ESS (9.6 ± 5.0 vs. 6.3 ± 3.2, p < 0.001), in addition to SCOPA-AUT, SAOQ, and RBDSQ. Male at-risk subjects showed lower values of hemoglobin (14.8 ± 1.3 vs. 15.0 ± 1.1, p = 0.032) and low density lipoprotein cholesterol (114.5 ± 30.3 vs. 123.0 ± 28.9, p = 0.004) than the examinees reporting no prodromal symptoms. CONCLUSION: Approximately 6% of the population aged 50 years or older was at risk for PD. Male at-risk subjects had mild hematological and metabolic changes relevant to PD.

The Profile and Prognosis of Youth With Status Migrainosus: Results From an Observational Study.

OBJECTIVE: To characterize the clinical features of a large sample of children, adolescents, and young adults with a history of status migrainosus (SM) and to describe their short-term prognosis. BACKGROUND: Data on the clinical characteristics of children and adolescents with SM are sparse and little is known about the prognosis of this population. METHODS: This was a retrospective clinical cohort study that included patients from the Cincinnati Children's Headache Center if they had a diagnosis of migraine and data available for a 1-3 months follow-up interval. Data extracted from the initial interval visit (visit A) included: age, sex, race, migraine diagnosis, SM history, chronic migraine, medication overuse headache (MOH), body mass index (BMI), headache frequency, headache severity, disability, allodynia and lifestyle habits: caffeine intake, meal skipping, sleep duration, exercise frequency, and fluid intake. Data extracted from the initial consultation visit included: months with headache at initial consultation visit, patient endorsing "feeling depressed" and anxiety symptoms. Headache frequency and visit type were also measured at the second visit (visit B) in the follow-up interval. A multivariate logistic regression model with a backward elimination procedure was created to model the odds of having a diagnosis of SM using the cross-sectional predictor variables above. Second, chi-square tests were used to compare the proportion of patients with SM to the proportion of patients without SM who had each of the following outcomes in the short-term follow-up window: treatment response (50% or greater reduction in headache frequency), overall reduction in headache frequency (reduction of 1 or more headache days/month), minimal change in headache frequency (increase in 0-3 headache days/month), and clinical worsening (increase in 4 or more headache days/month). RESULTS: A total of 5316 youth with migraine were included and 559 (10.5%) had a history of SM. In the multivariate logistic regression model, predictors significantly associated with SM were: older age (OR = 1.13, 95% CI = 1.09-1.17, P < .0001), migraine with aura (MWA) (OR = 1.30, 95% CI = 1.03-1.65, P = .03), MOH (OR = 1.72, 95% CI = 1.30-2.28, P = .0001), headache frequency (OR = 0.99, 95% CI = 0.97-0.99, P = .030), higher headache severity (OR = 1.08, 95% CI = 1.02-1.15, P = .009), months with headache at initial consultation (OR = 1.00, 95% CI = 1.00-1.01, P = .042), and admission to infusion center at visit B (OR = 2.27, 95% CI = 1.38-3.72, P = .001). Patients with a history of SM were more likely to experience an increase in 4 or more headache days per month at follow-up: 15.2% as compared to 11.1% of those without SM, χ2 (1, n = 5316) = 8.172, P = .0043. CONCLUSIONS: Youth with SM represent a distinct subgroup of the migraine population and have an unfavorable short-term prognosis.