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.
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