Caffeine intake interacts with Asian gene variants in Parkinson's disease: a study in 4488 subjects.

Background: Caffeine intake reduces risk of Parkinson's disease (PD), but the interaction with genes is unclear. The interaction of caffeine with genetic variants in those at high PD risk has healthcare importance. We investigate interactions of caffeine intake with risk variants found in Asians, and determine PD risk estimates in caffeine-drinkers carrying these variants. Methods: PD patients and controls without neurological disorders were included. Caffeine intake was assessed using a validated evaluation tool. Leucine rich repeat kinase 2 (LRRK2) risk variants were genotyped. Statistical analysis was conducted with logistic regression models. Gene-caffeine interactions were quantified using attributable proportion (AP) due to interaction (positive interaction defined as AP >0). Findings: 5100 subjects were screened and 4488 subjects (1790 PD, 2698 controls) with genetic data of at least one LRRK2 variant were included. Risk-variant-carriers who were non-caffeine-drinkers had increased PD odds compared to wildtype carriers who were caffeine-drinkers for G2385R [OR 8.6 (2.6-28.1) p < 0.001; AP = 0.71], R1628P [OR 4.6 (1.6-12.8) p = 0.004; AP = 0.50] and S1647T [OR 4.0 (2.0-8.1) p < 0.001; AP = 0.55] variants. Interpretation: Caffeine intake interacts with LRRK2 risk variants across three different groups of gene carriers. Asymptomatic risk-variant-carriers who are non-caffeine-drinkers have four to eight times greater PD risk compared to wildtype-caffeine-drinkers. Lifestyle modifications to mitigate PD risk in asymptomatic healthy risk variant carriers have potential roles in our Asian cohort. Funding: This study was supported by the National Medical Research Council (STaR and PD OF LCG 000207 grants) and Duke-NUS Medical School.

Interictal hemodynamic abnormality during motor activation in sporadic hemiplegic migraine: An explorative study.

INTRODUCTION: The motor weakness in sporadic hemiplegic migraine (SHM) is a poorly understood aura manifestation. Cortical spreading depression affecting motor excitability and alterations of neurovascular coupling may be integral to the development of migraine aura. METHODS: We studied 10 right-handed SHM patients and 17 healthy controls with functional near-infrared spectroscopy (fNIRS) in the interictal period. Subjects performed a finger opposition task and had real time determination of oxyhemoglobin (OxyHb) and deoxyhemoglobin (deOxyHb) changes. Recordings were completed with 10 left and 10 right sided cortical channels. RESULTS: Mean baseline to peak changes were significantly reduced in SHM patients as compared to controls bilaterally only for OxyHb measurements in the anteromedial channels. Mean time to peak changes were significant delayed in SHM patients compared to controls bilaterally largely for OxyHb measurements in the posterolateral channels, with the exception of 2 recording channels. CONCLUSIONS: Our findings suggest presence of abnormal interictal hemodynamic responses to increased metabolic demands during motor activation in SHM. These bilateral cerebrovascular changes involve OxyHb to a much larger degree than deOxyHb. Baseline to peak changes were evident more in the anteromedial channels, whereas time to peak changes were more evident in the posterolateral channels. These findings suggest that oxygen inflow into specific brain regions may be defective in SHM as opposed to oxygen utilization. Our findings suggest that in SHM, enduring hemodynamic deficits in response to an impending motor task are evident, which can be further explored in future studies, and possibly therapeutic trials.

Post-stroke subjective cognitive impairment is associated with acute lacunar infarcts in the basal ganglia.

BACKGROUND AND PURPOSE: While recent studies have examined neuroimaging correlates of post-stroke mild cognitive impairment (MCI), no studies have examined neuroimaging correlates of post-stroke subjective cognitive impairment (SCI). METHODS: Consecutive patients with magnetic resonance imaging-confirmed acute lacunar strokes at a tertiary institute were recruited for this cross-sectional study. All patients underwent cognitive testing, and those with MCI were excluded from these analyses. Two independent neuroradiologists ascertained data on the number and location of any infarcts, as well as the degree of white matter hyperintensities. Multivariate logistic regression analyses were performed to study the association between neuroimaging markers and SCI. Only variables that were significant in the univariate stage and clinically relevant potential confounders were included in multivariable analyses. RESULTS: Of 145 patients evaluated, 48 patients with MCI were excluded from the study. Of the remaining 97 patients, 30 patients had SCI. In multivariable analyses, only mini-mental state examination (OR 0.61; CI 0.38-0.98) and basal ganglia infarcts (OR 8.19; CI 1.18-56.6) were significant predictors of SCI. CONCLUSION: In patients with acute lacunar strokes, we find that basal ganglia infarcts are associated with SCI. As the basal ganglia have been previously shown to be involved with learning of tasks, we hypothesize that infarcts in basal ganglia may affect learning speeds thereby contributing to the development of SCI. Larger studies are needed to confirm these results.

A randomized controlled trial of rivastigmine in patients with cognitive impairment no dementia because of cerebrovascular disease.

OBJECTIVES: The safety and efficacy of early acetylcholinesterase inhibitors therapy in patients with cognitive impairment no dementia (CIND) after a cerebrovascular accident have not been examined. In this study, we investigated the safety and efficacy of rivastigmine in cognition, particularly executive function in patients with CIND because of cerebrovascular disease. METHODS: This study was a 24-week, double-blind, randomized, placebo-controlled trial of ischemic stroke patients seen at a tertiary hospital who had cognitive impairment no dementia because of cerebrovascular disease. The intervention was either rivastigmine or placebo up to 9 mg/day. The primary outcome of interest was mean change from baseline in the Ten-Point Clock Drawing and Color Trails 1 and 2. RESULTS: Fifty patients were randomized into rivastigmine (n = 25) and placebo (n = 25) arms. Patients in the rivastigmine group showed statistically significant improvement (1.70 vs 0.13, P = 0.02) on the animal subtask of the verbal fluency measure compared with placebo. There was also a trend (non-significant) towards improvement in Color Trails II. CONCLUSIONS: In this pilot study, we demonstrated that rivastigmine was well tolerated in patients with CIND because of cerebrovascular disease and may potentially improve executive functioning.

Severity of CIND and MCI predict incidence of dementia in an ischemic stroke cohort.

BACKGROUND: The utility of poststroke cognitive status, namely dementia, cognitive impairment no dementia (CIND), mild cognitive impairment (MCI), and no cognitive impairment (NCI), in predicting dementia has been previously examined. However, no studies to date have compared the ability of subtypes of MCI and CIND to predict dementia in a poststroke population. METHODS: A cohort of ischemic stroke patients underwent neuropsychological assessment annually for up to 5 years. Dementia was defined using the DSM-IV criteria. Univariate and multivariable Cox proportional regression was performed to determine the ability of MCI subtypes, CIND severity, and individual domains of impairment to predict dementia. RESULTS: A total of 362 patients without dementia were followed up for a mean of 3.4 years (17% drop out), with 24 developing incident dementia. Older age, previous and recurrent stroke, and CIND and MCI subtypes were significant predictors of dementia. In multivariable analysis controlling for treatment allocation, patients who were older, had previous or recurrent stroke, and had either CIND moderate or multiple domain MCI with amnestic component were at elevated risk for dementia. In multivariable domain analysis, recurrent strokes, age, and previous strokes, verbal memory, and visual memory were significant predictors of dementia. Receiver operating characteristic curve analysis showed that CIND moderate (area under the curve: 0.893) and multiple domain MCI with amnestic component (area under the curve: 0.832) were significant predictors of conversion to dementia. All other classifications of cognitive impairment had areas under the curve less than 0.7. CONCLUSION: Stroke patients with cognitive impairment no dementia (CIND) moderate are at higher risk of developing dementia, while CIND mild patients are not at increased risk of developing dementia.

Differences exist in the cognitive profile of mild Alzheimer's disease and subcortical ischemic vascular dementia.

BACKGROUND/AIMS: Our objective was to characterize the cognitive profile of patients with mild Alzheimer's disease (AD) and subcortical ischemic vascular dementia (SIVD) matched using a functional scale. METHODS: AD and SIVD were diagnosed using the NINCDS-ADRDA and the criteria proposed by Erkinjuntti et al., respectively. The Clinical Dementia Rating (CDR) scale was used to guide the identification of patients with mild dementia from a prospective clinical database. Regression analysis was applied to compare the 2 groups on global and individual cognitive domains. RESULTS: The greatest cognitive differences between the 2 groups were observed in the domains of visuospatial function (p = 0.001), working memory (p = 0.013) and visuomotor speed (p = 0.028). No significant variation was demonstrated in the executive function domain (p = 0.646). Statistically significant differences between AD and SIVD patients were found in episodic memory delayed recall tasks but not in the immediate recall tasks. A trend towards severer depressive symptoms (p = 0.052) was observed among the SIVD patients. CONCLUSIONS: SIVD patients with mild dementia have greater deficits in visuospatial function, working memory and visuomotor speed and may also be more depressed compared to AD patients. Executive function tests in general do not distinguish the 2 groups, although timed executive tasks can separate them.