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White matter hyperintensities (WMH) are a frequent finding on brain MRI of elderly subjects, and have been associated with various risk factors, as well as with development of cognitive and functional impairment. While an overall association between WMH load and risk factors is well described, possible spatially restricted vulnerability remains to be established. The aim of this study was to investigate the spatial distribution of WMH in normally functioning elderly subjects. We introduce a voxel-based approach in which lesion probability is mapped as a function of clinical risk factors using logistic regression, and validate the method using simulated datasets. The method was then applied in a total of 605 participants of the LADIS study (age 74 ± 5 years, all with WMH), and the location of manually delineated WMH was investigated after spatial normalisation. Particularly strong and widespread associations were found for age, gender and hypertension. Different distribution patterns were found for men and women. Further, increased probability was found in association with self-reported alcohol and tobacco consumption, as well as in those with a history of migraine. It is concluded that the location of WMH is dependent on the risk factors involved pointing towards a regionally different pathogenesis and/or vulnerability of the white matter., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Vascular dementia is a major cause of mental and physical disability in Western countries. Treatment of vascular dementia is currently based on the recognition and control of vascular risk factors, while specific drugs have not been approved yet. The aim of the present multinational, double-blind, placebo-controlled study was to evaluate the safety and efficacy of nimodipine administered for as long as 26 weeks in improving cognition or slowing cognitive deterioration in patients defined as having multi-infarct dementia (DSM-III-R criteria). Two hundred and fifty-nine patients were included (128 nimodipine, 131 placebo), and 251 were available for the intention-to-treat analysis. No significant difference between drug-treated and placebo patients was noted on the Gottfries-Brâne-Steen scale score (primary efficacy criterion), the remaining neuropsychological tests (Zahlen-Verbindungs-Test, Fuld-Object-Memory Evaluation, Word Fluency Test, Digit Span, Mini-Mental State Examination), and the functional scales (index of Activity of Daily Living, Instrumental Activity of Daily Living, Rapid Disability Scale, Clinical Dementia Rating), although the majority of changes were in favor of the active drug group. A lower incidence of cerebrovascular and cardiac events was observed in the nimodipine-treated patients in comparison with the placebo group. This study failed to show a significant effect of nimodipine on cognitive, social or global assessments in patients defined as affected by multi-infarct dementia according to the DSM-III-R criteria. A post-hoc analysis (presented in an accompanying paper) suggests that nimodipine may have a favorable effect in the subgroup of patients defined as affected by subcortical (small vessel) vascular dementia.