Abstract
The extent to which white matter changes affect brain function in elderly individuals is a matter for debate. Although there is a consensus that large confluent white matter lesions (WMLs) can be attributed to small-vessel disease and might denote anatomical damage to axons, the clinical effect of WMLs with regard to cognitive impairment is less certain. In this Review, we argue that WMLs are associated with greater detectable progressive cognitive deterioration than is normal aging, but other causes of progressive cognitive deterioration, such as Alzheimer's disease, are associated with greater cognitive decline than are WMLs. This view has important implications for the development of drugs for the treatment and prevention of cognitive impairment and dementia.
Key Points
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Focal white matter lesions (WMLs) can be attributed to small-vessel disease and are associated with variable degrees of demyelination, axonal loss and gliosis
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The effect of WMLs on global cognitive performance in cross-sectional studies is relatively small, even for severe lesions, and amounts at most to 0.7 points out of a maximum of 30 on the Mini-Mental State Examination scale
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In longitudinal studies, the rate of cognitive deterioration attributable to WMLs is, on average, 12 times lower than that attributable to Alzheimer's disease
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Only individuals with the more-severe degrees of WMLs have clinically relevant cognitive decline, and these patients might be candidates for drug therapy targeted to small-vessel cerebrovascular disease
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Frisoni, G., Galluzzi, S., Pantoni, L. et al. The effect of white matter lesions on cognition in the elderly—small but detectable. Nat Rev Neurol 3, 620–627 (2007). https://doi.org/10.1038/ncpneuro0638
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DOI: https://doi.org/10.1038/ncpneuro0638
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