Association of Butyrylcholinesterase-K Allele and Apolipoprotein E ɛ4 Allele with Cognitive Decline in Dementia with Lewy Bodies and Alzheimer’s Disease

Article type: Research Article

Authors: Vijayaraghavan, Swetha^{a; k; *} | Darreh-Shori, Taher^{a; *} | Rongve, Arvid^b | Berge, Guro^c | Sando, Sigrid B.^{c; d} | White, Linda R.^{c; d} | Auestad, Bjørn H.^{e; f} | Witoelar, Aree^{g; h} | Andreassen, Ole A.^{g; h} | Ulstein, Ingun D.ⁱ | Aarsland, Dag^{j; k; *}

Affiliations: [a] Center for Alzheimer Research,Division of Translational Alzheimer Neurobiology, Department of Neurobiology, Care Sciences and Society, Karolinska Institute, Stockholm, Sweden | [b] Department of Research and Innovation, Helse Fonna, Haugesund Hospital, Haugesund, and Institute of Clinical Medicine, University of Bergen, Bergen, Norway | [c] Department of Neuroscience, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway | [d] Department of Neurology, University Hospital of Trondheim, Trondheim, Norway | [e] Department of Mathematics and Natural Sciences, University of Stavanger, Stavanger, Norway | [f] Research Department, Stavanger University hospital, Stavanger, Norway | [g] K.G. Jebsen Center for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway | [h] Norwegian Centre for Mental Disorders Research (NORMENT), University of Oslo/Oslo University Hospital, Oslo, Norway | [i] Department of Geriatric Medicine, Norwegian Center for Aging and Health, Oslo University Hospital, Oslo, Norway | [j] Center for Alzheimer Research, Division of Neurogeriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institute, Stockholm, Sweden | [k] Center for Age Related Medicine, Stavanger University Hospital, Stavanger, Norway

Correspondence: [*] Correspondence to: Swetha Vijayaraghavan, Center for Alzheimer Research, Division of Translational Alzheimer Neurobiology, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Novum 4th floor, 14157- Stockholm, Sweden. Tel.: +46 858583897; Fax: +46 858585470; E-mail: [email protected].

Correspondence: [*] Correspondence to: Taher Darreh-Shori, Center for Alzheimer Research, Division of Translational Alzheimer Neurobiology, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Novum 4th floor, 14157- Stockholm, Sweden. Tel.: +46 858583612; Fax: +46 858585470; E-mail: [email protected].

Correspondence: [*] Correspondence to: Dag Aarsland, Center for Alzheimer Research, Division of Neurogeriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Novum 5th floor, 14157- Stockholm, Sweden. Tel.: +46 858585379; Fax: +46 858585470; E-mail: [email protected].

Abstract: 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 ɛ4 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 TrønderBrain, were genotyped for BCHE-K and APOE ɛ4. 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 ɛ4 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 ɛ4 allele than in the absence of these polymorphisms. Conclusion:BCHE-K is associated with a reduced risk for AD and DLB whereas APOE ɛ4 is associated with more rapid cognitive decline. The greater cognitive decline in individuals with both APOE ɛ4 and BCHE-K alleles require prospective confirmation in well-controlled trials.

Keywords: Apolipoprotein E genotype, butyrylcholinesterase-K, cognition, dementia, Mini-Mental State Examination

DOI: 10.3233/JAD-150750

Journal: Journal of Alzheimer's Disease, vol. 50, no. 2, pp. 567-576, 2016