Context: The role of macrostructural white matter changes, such as atrophy and white matter lesions, in cognitive decline is increasingly being recognized. However, in the elderly population, these macrostructural changes do not account for all variability in cognition. Measures reflecting white matter microstructural integrity may provide additional information to investigate the relation between white matter changes and cognition. Objective: To study the relation between white matter integrity and cognition in the general elderly population, using diffusion tensor imaging and taking into account macrostructural white matter changes. Design: Cross-sectional population-based study. Setting: A general community in the Netherlands. Participants: A population-based sample of 860 persons, older than 60 years, free of dementia. We performed multisequence magnetic resonance imaging, which included diffusion tensor imaging, and extensive neuropsychological testing. Fractional anisotropy, mean diffusivity, and directional diffusivities were measured globally in white matter lesions and normal-appearing white matter. Main Outcome Measures: Performance on neuro- psychological tests in the following cognitive domains: memory, executive function, information processing speed, global cognition, and motor speed. Results: Regardless of macrostructural white matter changes, a higher mean diffusivity or higher axial and radial diffusivities within white matter lesions or normal- appearing white matter were related to worse performance on tasks assessing information processing speed and global cognition. In addition, diffusivity within white matter lesions related to memory, while in normal-appearing white matter, it furthermore related to executive function. Lower mean fractional anisotropy in white matter lesions or normal-appearing white matter related to worse information processing speed and motor speed. Conclusions: Microstructural integrity of both white matter lesions and normal-appearing white matter is associated with cognitive function, regardless of white matter atrophy and white matter lesion volume. This suggests that measuring white matter integrity has added value beyond macrostructural assessment of white matter changes to study the relation between white matter and cognition.

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Keywords Netherlands, aged, article, atrophy, brain, cognition, cognitive defect, cohort analysis, controlled study, cross-sectional study, degenerative disease, diffusion tensor imaging, diffusion weighted imaging, female, human, human experiment, image processing, information processing, male, memory, middle aged, myelinated nerve, neuropsychological test, nuclear magnetic resonance imaging, organ size, pathology, physiology, psychometry, reference value, statistics, task performance, temporal lobe, white matter
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Journal Archives of General Psychiatry
Vernooij, M.W, Ikram, M.A, Vrooman, H.A, Wielopolski, P.A, Krestin, G.P, Hofman, A, … Breteler, M.M.B. (2009). White Matter microstructural integrity and cognitive function in a general elderly population. Archives of General Psychiatry, 66(5), 545–553. doi:10.1001/archgenpsychiatry.2009.5