BACKGROUND AND PURPOSE: Dilated perivascular spaces in the brain are associated with greater arterial pulsatility. We hypothesized that perivascular spaces identify individuals at higher risk for systemic and cerebral vascular events. MATERIALS AND METHODS: Stroke-free participants in the population-based Northern Manhattan Study had brain MR imaging performed and were followed for myocardial infarction, any stroke, and death. Imaging analyses distinguished perivascular spaces from lesions presumably ischemic. Perivascular spaces were further subdivided into lesions with diameters of ≤3 mm (small perivascular spaces) and >3 mm (large perivascular spaces). We calculated relative rates of events with Poisson models and hazard ratios with Cox proportional models. RESULTS: The Northern Manhattan Study participants who had MR imaging data available for review (n = 1228; 59% women, 65% Hispanic; mean age, 71 ± 9 years) were followed for an average of 9 ± 2 years. Participants in the highest tertile of the small perivascular space score had a higher relative rate of all deaths (relative rate, 1.38; 95% CI, 1.01–1.91), vascular death (relative rate, 1.87; 95% CI, 1.12–3.14), myocardial infarction (relative rate, 2.08; 95% CI, 1.01–4.31), any stroke (relative rate, 1.79; 95% CI, 1.03–3.11), and any vascular event (relative rate, 1.74; 95% CI, 1.18–2.56). After we adjusted for confounders, there was a higher risk of vascular death (hazard ratio, 1.06; 95% CI, 1.01–1.11), myocardial infarction (hazard ratio, 2.22; 95% CI, 1.12–4.42), and any vascular event (hazard ratio, 1.04; 95% CI, 1.01–1.08) with higher small perivascular space scores. CONCLUSIONS: In this multiethnic, population-based study, participants with a high burden of small perivascular spaces had increased risk of vascular events. By gaining pathophysiologic insight into the mechanism of perivascular space dilation, we may be able to propose novel therapies to better prevent vascular disorders in the population.

BACKGROUND AND PURPOSE: Perivascular spaces are potential spaces found between brain blood vessels and surrounding leptomeninges that have been associated with cardiovascular risk factors and dementia, but less is known about their relationship to atherosclerosis. We tested the hypothesis that perivascular spaces are associated with atherosclerosis. MATERIALS AND METHODS: Participants from the Northern Manhattan Study who remained stroke-free were invited to participate in an MR imaging substudy. Parenchymal hypointensities of <3 mm identified on brain axial T1-weighted MR imaging were scored as perivascular spaces. A semiquantitative score was created to express the degree of brain involvement. Generalized linear models were used to assess statistical associations with carotid plaque as a surrogate marker of atherosclerosis. RESULTS: The studied sample included 706 participants (mean age, 72.6 ± 8.0 years; 60% women, 61% Hispanic, 68% with hypertension, 19% with diabetes, and 57% with high cholesterol). The perivascular spaces score ranged from 0 to 19 with 52% of the sample having a perivascular spaces score of ≤4. In unadjusted analysis, perivascular spaces were associated with age (β = 0.01 per year, P = < .001), non-Hispanic black race-ethnicity (β = 0.16, P = .02), hypertension (β = 0.24, P = < .001), and carotid plaque (β = 0.22, P < .001). In multivariable analysis, only age (β = 0.01, P = .02), hypertension (β = 0.17, P = .01), and carotid plaque (β = 0.22, P = < .001) remained independently associated with perivascular spaces. CONCLUSIONS: Perivascular spaces were more frequently found in older participants, in those with hypertension, and in the presence of carotid plaque. These results suggest that mechanisms leading to atherosclerosis might also lead to an increased number of perivascular spaces. These results need confirmation in prospective studies.

Objective: To examine the independent association between physical activity and subclinical cerebrovascular disease as measured by silent brain infarcts (SBI) and white matter hyperintensity volume (WMHV). Methods: The Northern Manhattan Study (NOMAS) is a population-based prospective cohort examining risk factors for incident vascular disease, and a subsample underwent brain MRI. Our primary outcomes were SBI and WMHV. Baseline measures of leisure-time physical activity were collected in person. Physical activity was categorized by quartiles of the metabolic equivalent (MET) score. We used logistic regression models to examine the associations between physical activity and SBI, and linear regression to examine the association with WMHV. Results: There were 1,238 clinically stroke-free participants (mean age 70 ± 9 years) of whom 60% were women, 65% were Hispanic, and 43% reported no physical activity. A total of 197 (16%) participants had SBI. In fully adjusted models, compared to those who did not engage in physical activity, those in the upper quartile of MET scores were almost half as likely to have SBI (adjusted odds ratio 0.6, 95% confidence interval 0.4–0.9). Physical activity was not associated with WMHV. Conclusions: Increased levels of physical activity were associated with a lower risk of SBI but not WMHV. Engaging in moderate to heavy physical activities may be an important component of prevention strategies aimed at reducing subclinical brain infarcts.

Background: Periodontitis is ubiquitous and associated with serological evidence of exposure to periodontal organisms, systemic inflammation and vascular disease. Dementia is a major public health problem likely related to a complex interaction between genetics and diseases associated with systemic inflammation, including diabetes, smoking and stroke.Methods: To assess relationships between systemic exposure to periodontal pathogens and cognitive test outcomes, data were analysed from the Third National Health and Nutrition Examination Survey (NHANES-III), a nationally representative cross sectional observational study among older adults. We included 2355 participants > 60 years who completed measures of cognition and Poryphyromonas gingivalis IgG. Using SUDAAN, logistic regression models examined the association of P gingivalis IgG with cognitive test performance.Results: Poor immediate verbal memory (< 5/9 points) was prevalent in 5.7% of patients, and 6.5% overall had impaired delayed recall (< 4/9); 22.1% had difficulty with serial subtractions (< 5/5 trials correct). Individuals with the highest P gingivalis IgG (> 119 ELISA Units (EU)) were more likely to have poor delayed verbal recall (OR 2.89, 95% CI 1.14 to 7.29) and impaired subtraction (OR 1.95, 95% CI 1.22 to 3.11) than those with the lowest (<= 57 EU), with dose-response relationships for both (p trend, delayed memory = 0.045, subtraction = 0.04). After adjusting for socioeconomic and vascular variables, these relationships remained robust for the highest P gingivalis IgG group (delayed verbal memory OR 3.01 (95% CI 1.06 to 8.53); subtraction OR 2.00 (95% CI 1.19 to 3.36)). In contrast, immediate verbal memory was not significantly associated with P gingivalis.Conclusion: A serological marker of periodontitis is associated with impaired delayed memory and calculation. Further exploration of relationships between oral health and cognition is warranted.

Eosinophilic vasculitis has been described as part of the Churg-Strauss syndrome, but affects the central nervous system (CNS) in <10% of cases. A 39-year-old woman with a history of migraine without aura presented to an institution in an acute confusional state with concurrent headache and left-sided weakness. Laboratory evaluation showed an increased cerebrospinal fluid (CSF) protein level, but otherwise unremarkable serologies. Magnetic resonance imaging showed bifrontal polar gyral-enhancing brain lesions. Her symptoms resolved over two weeks without residual deficits. Eighteen months later the patient presented with similar symptoms and neuroradiological findings showed involvement of territories different from those in her first episode. Brain biopsy showed transmural, predominantly eosinophilic, inflammatory infiltrates and fibrinoid necrosis without granulomas. She improved when treated with corticosteroids. To our knowledge, this is the first case of non-granulomatous eosinophilic vasculitis isolated to the CNS. No aetiology for this patient's primary CNS eosinophilic vasculitis has yet been identified.

Background and Purpose— Moderate alcohol intake has been associated with better cognitive performance, implicating vascular and neurodegenerative processes. Few studies to clarify the importance of vascular disease have included direct measures of atherosclerosis or minority populations at higher risk of vascular disease and dementia. Methods— The Northern Manhattan Study includes stroke-free community based Hispanic (54%), black (25%), and white (22%) participants. We performed a cross-sectional study of alcohol intake and performance on the Mini-Mental State Examination (MMSE) in subjects with sonographic measurement of maximal carotid plaque thickness and adjusted for sociodemographic and vascular risk factors. Results— The median MMSE score was 27 (interquartile range 24 to 29; n=2215). Reported alcohol intake was divided into 5 groups: never (n=509), past (n=494), <1 drink/week (n=300), 1/week to ≤2 drinks/day (n=796), and >2 drinks/day (n=116). Drinking 1 drink weekly up to 2 daily was associated with better performance on the MMSE (odds ratio=1.19; 95% CI, 1.10 to 1.26) compared with nondrinkers in women ( P ≤0.0001) but not in men, adjusting for sociodemographic and vascular risk factors. Maximal carotid plaque thickness (mean 1.1 mm; SD 1.2 mm) was not associated with alcohol intake and did not mediate the relationship between alcohol and cognition. Conclusions— Moderate alcohol consumption was independently associated with better cognitive performance in women from this multiethnic sample. Carotid plaque was not a mediator of this association suggesting alcohol may impact cognition through a separate vascular or degenerative pathway.

Background— Total homocysteine (tHcy) has been implicated as a risk factor for stroke and dementia, but the mechanism is unclear. White matter hyperintensities may be a risk factor for both, but studies of the relationship between tHcy and quantitative measures of white matter hyperintensity volume (WMHV) are lacking, especially in minority populations. Methods— A community-based sample of 259 subjects with baseline tHcy levels underwent pixel-based quantitative measurement of WMHV. We examined the relationship between tHcy and WMHV adjusting for age, sociodemographics, vascular risk factors, and B12 deficiency. Results— Higher levels of tHcy were associated with WMHV adjusting for sociodemographics and vascular risk factors. Conclusions— These cross-sectional data provide evidence that tHcy is a risk factor for white matter damage.

Objective: Several studies implicate elevated homocysteine as a risk factor for dementia and cognitive decline, but most studies have involved subjects older than 55 years from homogeneous populations. The authors examined homocysteine and cognition in a tri-ethnic community sample 40 years and older. Method: The Northern Manhattan Study includes 3,298 stroke-free subjects. Of these 2,871 had baseline fasting total homocysteine (tHcy) levels and Mini-Mental State Examination (MMSE) scores available. The authors used multiple linear regression to examine the cross-sectional association between baseline tHcy levels and mean MMSE scores adjusting for sociodemographic and vascular risk factors. Results: Homocysteine levels were related to age, renal function, and B12 deficiency. Those with B12 deficiency had tHcy levels five points higher (9.4 vs 14.4 nmol/L). Mean MMSE scores differed by age, sex, and race-ethnic group. Those with hypertension, diabetes, cardiac disease, and B12 deficiency had lower MMSE scores. In multivariate analyses, elevated tHcy was associated with lower mean MMSE scores for those older than 65 but not for those 40 to 64. Adjusting for B12 deficiency and sociodemographic factors the mean MMSE was 2.2 points lower for each unit increase in the log tHcy level (95% CI - 3.6, - 0.9). Adding vascular risk factors to the model did not attenuate this effect ( mean MMSE - 2.2 points; 95% CI - 3.5, - 0.9). Conclusions: Elevated homocysteine was independently associated with decreased cognition in subjects older than 65 in this tri-ethnic cohort, adjusting for sociodemographic and vascular risk factors.

True drop attacks are characterized by a sudden fall without loss of consciousness. Cardiac disease and epilepsy are widely accepted causes, but other etiologies have been described, including vestibulopathy, hypothyroidism, third ventricle or posterior fossa cysts, cervical spine disease, and brainstem ischemia.1-3 We present a case of drop attacks caused by an anomalous circle of Willis in the setting of a critical stenosis of the ipsilateral internal carotid artery (ICA). A 73-year-old right-handed man with a history of hypertension and past smoking, on oral anticoagulation for atrial fibrillation, presented to an outside institution with several months of drop attacks. The episodes occurred one to four times per week and he described his legs giving out, seeing the floor “coming up,” and then being on the ground. There were no prodromal symptoms such as lightheadedness, palpitations, or residual weakness after an attack. Witnesses confirmed no alteration …

BACKGROUND:Stroke incidence is greater in blacks than in whites; data on Hispanics are limited. Comparing subtype-specific ischemic stroke incidence rates may help to explain race-ethnic differences in stroke risk. The aim of this population-based study was to determine ischemic stroke subtype incidence rates for whites, blacks, and Hispanics living in one community.METHODS AND RESULTS:A comprehensive stroke surveillance system incorporating multiple overlapping strategies was used to identify all cases of first ischemic stroke occurring between July 1, 1993, and June 30, 1997, in northern Manhattan. Ischemic stroke subtypes were determined according to a modified NINDS scheme, and age-adjusted, race-specific incidence rates calculated. The annual age-adjusted incidence of first ischemic stroke per 100,000 was 88 (95% CI, 75 to 101) in whites, 149 (95% CI, 132 to 165) in Hispanics, and 191 (95% CI, 160 to 221) in blacks. Among blacks compared with whites, the relative rate of intracranial atherosclerotic stroke was 5.85 (95% CI, 1.82 to 18.73); extracranial atherosclerotic stroke, 3.18 (95% CI, 1.42 to 7.13); lacunar stroke, 3.09 (95% CI, 1.86 to 5.11); and cardioembolic stroke, 1.58 (95% CI, 0.99 to 2.52). Among Hispanics compared with whites, the relative rate of intracranial atherosclerotic stroke was 5.00 (95% CI, 1.69 to 14.76); extracranial atherosclerotic stroke, 1.71 (95% CI, 0.80 to 3.63); lacunar stroke, 2.32 (95% CI, 1.48 to 3.63); and cardioembolic stroke, 1.42 (95% CI, 0.97 to 2.09).CONCLUSIONS:The high ischemic stroke incidence among blacks and Hispanics compared with whites is due to higher rates of all ischemic stroke subtypes.