The effect of white matter lesions (WMLs) on the brain of elderly individuals is unclear. Most debate has focused on the clinical effect of WMLs on cognitive impairment. Large cross-sectional and longitudinal clinic- and population-based studies suggest that the effect of WMLs on global cognitive performance is relatively small, only individuals with the most severe degrees of WMLs having clinically relevant effects. Here, we review recent data suggesting that WMLs might affect brain function through impairment of brain plasticity and reserve. The clinical effect consists in inability of the brain to respond to interventions such as psychotropic drug medications or rehabilitative interventions.
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