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Meike W. Vernooij, MD; M. Arfan Ikram, MD; Henri A. Vrooman, PhD; Piotr A. Wielopolski, PhD; Gabriel P. Krestin, MD, PhD; Albert Hofman, MD, PhD; Wiro J. Niessen, PhD; Aad Van der Lugt, MD, PhD; Monique M. B. Breteler, MD, PhD

Arch Gen Psychiatry. 2009;66(5):545-553.

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 neuropsychological 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.

Author Affiliations: Departments of Epidemiology (Drs Vernooij, Ikram, Hofman, and Breteler), Radiology (Drs Vernooij, Vrooman, Wielopolski, Krestin, Niessen, and Van der Lugt), and Medical Informatics (Drs Vrooman and Niessen), Erasmus MC University Medical Center, Rotterdam, the Netherlands.

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