Association of Butyrylcholinesterase-K Allele and Apolipoprotein E ε4 Allele with Cognitive Decline in Dementia with Lewy Bodies and Alzheimer's Disease

Background: A common polymorphism of the butyrylcholinesterase gene, the K-variant (BCHE-K) is associated with reduced butyrylcholinesterase (BuChE) activity. Insufficient studies exist regarding the frequency and role of BCHE-K in dementias. Objective: To determine the association of BCHE-K and APOE epsilon 4 with diagnosis and rate of cognitive decline in dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) patients. Methods: Genomic DNA from 368 subjects (108 AD, 174 DLB, and 86 controls) from two routine clinical cohort studies in Norway; DemVest and TronderBrain, were genotyped for BCHE-K and APOE epsilon 4. The mild dementia DemVest subjects received annual Mini-Mental State Examination assessments for five years. Results: BCHE-K frequency was lower in DLB (33.9%; p < 0.01) than in control subjects (51.2%), and was numerically lower in AD as well (38.9%; p = 0.11). More rapid cognitive decline was associated with the APOE epsilon 4 genotype, but not with the BCHE-K genotype. In an exploratory analysis of patients who completed all five follow-up visits, there was greater cognitive decline in BCHE-K carriers in the presence of the APOE epsilon 4 allele than in the absence of these polymorphisms. Conclusion: BCHE-K is associated with a reduced risk for AD and DLB whereas APOE epsilon 4 is associated with more rapid cognitive decline. The greater cognitive decline in individuals with both APOE epsilon 4 and BCHE-K alleles require prospective confirmation in well-controlled trials.