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.

Anomalies of asymmetry of clinical signs in parkinsonism.

Parkinson's disease (PD) is characterized by a minimum of two of three features: tremor, rigidity, and bradykinesia. Asymmetry of these features is often considered to support a diagnosis of PD in contrast to other parkinsonian syndromes. All major manifestations of PD are often more pronounced on the side first manifesting features of PD. Significant dissociation of features on the contralateral side, along with other variants of presentation involving the contralateral side, are rarely observed. To determine the frequency and significance of unusual asymmetry in parkinsonism, we retrospectively examined 613 patients clinically diagnosed as idiopathic PD for presence of unusual asymmetries of clinical features. Three groups of patients with unusual asymmetrical clinical findings were identified. Group 1 comprised 10 patients followed for an average of 6 years presenting with rest tremor most prominent in one lower limb and contralateral upper limb. Group 2 comprised 24 patients followed for an average of 5.5 years with action tremor most prominent on the side contralateral to the side of most prominent rest tremor. Group 3 comprised 33 patients followed for an average of 10 years who had parkinsonian signs of greatest severity on one side but subsequently, over an average of 5.4 years, became gradually more prominent on the opposite side. In Group 3, 15 of 33 patients (45%) demonstrated evolution to a rigid form of parkinsonism with disappearance of rest tremor over an average of 7.1 years after presentation. A small percentage (11%) of Parkinson's patients in our clinic demonstrated anomalous asymmetrical clinical findings, which indicates that (1) the disease process may begin in different topographic sites on each side; (2) rest tremor and action tremor may have different anatomical bases; (3) the disease process may progress at different rates on different sides; and (4) tremor becomes less pronounced with progression of disease in some patients with Parkinsonism.