Apolipoprotein E epsilon4 and catechol-O-methyltransferase alleles in autopsy-proven Parkinson's disease: relationship to dementia and hallucinations.

We determined whether apolipoprotein E epsilon4 (ApoE4) or catechol-O-methyltransferase (COMT) genotypes were associated with dementia, hallucinations, Alzheimer's disease pathological findings (AP), or cortical Lewy bodies (CLBs) in autopsy-confirmed cases of Parkinson's disease (PD). Outcomes were obtained from medical records. Pathology reports identified AP and CLBs. Brain tissue was genotyped. A total of 47 subjects (33 men, 14 women) had PD onset at 62.4 +/- 8.7 years of age and died at 77.8 +/- 5.6 years of age. Demented and hallucinating patients did not differ in age at onset (AO) of PD or age at death, or the proportion ApoE4+, AP+, or CLB+ compared to nondemented patients or non-hallucinating patients. ApoE4 and COMT (low metabolizer [LH], intermediate metabolizer [HL], or high metabolizer [HH]) did not influence AO, death, or dementia- or hallucination-free survival, based on age or duration of treatment. All seven subjects with AP were demented and had hallucinations. CLBs were associated with dementia but not hallucinations. In Cox regression models adjusting for AO and duration of treatment, increased risk of dementia was associated with male sex but not significantly with ApoE4; inclusion of AP in the model did not affect the results; COMT was not a risk factor for dementia. Psychosis risk was not associated with ApoE4, COMT, or sex. The observation that males have increased dementia risk and the trend for ApoE4 requires confirmation in larger prospective autopsy studies.