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Neuroimaging of older adults commonly reveals abnormality (leukoaraiosis) in the cerebral white matter. Studies have established that extensive leukoaraiosis predicts dementia and disability, but the pathogenesis of leukoaraiosis remains unclear. We recruited 5 patients with leukoaraiosis and performed magnetic resonance mapping of the brain for 16 consecutive weeks. We observed tiny lesions arising de novo in the cerebral white matter. These lesions were clinically silent. They had the signature features of acute ischemic stroke. With time, the characteristics of these lesions approached those of pre-existing leukoaraiosis. Together, these findings suggest that tiny silent acute infarcts are a cause of leukoaraiosis., (© 2014 American Neurological Association.)

Objective: A study was undertaken to determine whether diffusion-weighted imaging (DWI) abnormalities in normal-appearing brain tissue (NABT) and in white matter hyperintensities (WMH) predict longitudinal cognitive decline and disability in older individuals independently of the concomitant magnetic resonance imaging (MRI) findings., Methods: A total of 340 LADIS (Leukoaraiosis and Disability Study) participants, aged 65 to 84 years, underwent brain MRI including DWI at baseline. Neuropsychological and functional assessments were carried out at study entry and repeated annually over a 3-year observational period. Linear mixed models and Cox regression survival analysis adjusted for demographics, WMH volume, lacunes, and brain atrophy were used to evaluate the independent effect of the DWI measures on change in cognitive performance and functional abilities., Results: The mean global apparent diffusion coefficient (ADC) and the relative peak height and peak position of the ADC histogram in NABT predicted faster rate of decline in a composite score for speed and motor control. Higher mean ADC and lower peak height were also related to deterioration in executive functions and memory (specifically working memory), with peak height also being related to more rapid transition to disability and higher rate of mortality. Mean ADC in WMH had less pronounced effects on cognitive and functional outcomes., Interpretation: DWI microstructural changes in NABT predict faster decline in psychomotor speed, executive functions, and working memory regardless of conventional MRI findings. Moreover, these changes are related to functional disability and higher mortality., (Copyright © 2013 American Neurological Association.)