BuChE-K and APOE epsilon4 allele frequencies in Lewy body dementias, and influence of genotype and hyperhomocysteinemia on cognitive decline.

Apolipoprotein E (APOE) epsilon4 and butyrylcholinesterase-K (BuChE-K) are associated with an increased risk for Alzheimer's disease. The primary objective was to evaluate frequencies of these alleles in dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD). A secondary objective was to evaluate influences on rate of cognitive decline. This analysis used data from participants consenting to pharmacogenetic testing in placebo-controlled rivastigmine studies. Allele frequencies in DLB and PDD were compared using logistic regression. Within the PDD placebo sample, associations with cognitive decline were evaluated (the DLB sample was too small for these evaluations). Fifty-seven DLB and 323 PDD subjects provided APOE and BuChE data. Allelic frequencies were higher in DLB, relative to PDD subjects, for BuChE-K (P = 0.06), APOE epsilon4 (P < 0.001), or both alleles together (P < 0.001). More rapid cognitive decline was seen in PDD patients carrying both alleles, compared with other genotypes. Subjects with hyperhomocysteinemia were associated with more rapid decline in the presence of BuChE-K, with or without APOE epsilon4. These results suggest that genetic and biochemical risk factors for AD and PDD pathology may be important in dementia onset and progression in these Lewy body disorders.