Cerebral white matter lesions (CWMLs) have been suggested to be associated with an increased risk of dementia, disability, and death. CWMLs are more common in individuals with Alzheimer’s disease (AD) than in normal elderly individuals of comparable age. Only a few studies have been done to determine whether CWMLs may influence cognitive decline in Parkinson’s disease (PD). Fully developed PD with concurrent AD was reported to likely cause impaired cognition in spite of accumulating evidence suggesting that PD with dementia (PDD) is more closely associated with Lewy body (LB) pathology. Currently, contradictory data on the neuropathology of dementia in PD require further prospective clinicopathological studies in larger cohorts to elucidate the impact of AD and α-synuclein (SCNA) pathologies on the cognitive status in these disorders. Previous reports did not suggest CWMLs to be associated with an increased risk of PDD. After adjusting for age at death, age at onset of PD, and duration of PD, our recent study investigating CWMLs in PDD via autopsy has shown a positive correlation between the burden of CWMLs and PDD. The frequent co-existence of both LB and AD lesions suggests that both pathologies independently or synergistically contribute to both movement disorders and cognitive impairment. The individual and cumulative burden of CWMLs, LB lesions, and AD lesions may synergistically contribute to cognitive decline in LB disorders such as PDD.

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