A Mitochondrial DNA Haplogroup Defines Patterns of Five-Year Cognitive Change

Article type: Research Article

Authors: Watts, Amber^{a; b} | Chalise, Prabhakar^{a; c} | Hu, Jinxiang^{a; c} | Hui, Dongwei^{a; d} | Pa, Judy^e | Andrews, Shea J.^f | Michaelis, Elias K.^{a; d} | Swerdlow, Russell H.^{a; g; h; i}

Affiliations: [a] University of Kansas Alzheimer’s Disease Research Center, Lawrence, KS, USA | [b] Department of Psychology, University of Kansas, Lawrence, KS, USA | [c] Department of Biostatistics and Data Science, University of Kansas Medical Center, Lawrence, KS, USA | [d] Department of Pharmacology and Toxicology, University of Kansas, Lawrence, KS, USA | [e] Department of Neurosciences, University of California San Diego, La Jolla, CA, USA | [f] Department of Genetics & Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA | [g] Department of Neurology, University of Kansas Medical Center, Lawrence, KS, USA | [h] Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Lawrence, KS, USA | [i] Department of Biochemistry and Molecular Biology, University of Kansas Medical Center, Lawrence, KS, USA

Correspondence: [*] Correspondence to: Amber Watts, PhD, Department of Psychology, University of Kansas, 1415 Jayhawk Blvd., Lawrence, KS 66045, USA. Tel.: +1 785 864 2604; E-mail: [email protected].

Abstract: Background:Mitochondrial DNA (mtDNA) may play a role in Alzheimer’s disease (AD) and cognitive decline. A particular haplogroup of mtDNA, haplogroup J, has been observed more commonly in patients with AD than in cognitively normal controls. Objective:We used two mtDNA haplogroups, H and J, to predict change in cognitive performance over five years. We hypothesized that haplogroup J carriers would show less cognitive resilience. Methods:We analyzed data from 140 cognitively normal older adults who participated in the University of Kansas Alzheimer’s Disease Research Center clinical cohort between 2011 and 2020. We used factor analysis to create three composite scores (verbal memory, attention, and executive function) from 11 individual cognitive tests. We performed latent growth curve modeling to describe trajectories of cognitive performance and change adjusting for age, sex, years of education, and APOE ɛ4 allele carrier status. We compared haplogroup H, the most common group, to haplogroup J, the potential risk group. Results:Haplogroup J carriers had significantly lower baseline performance and slower rates of improvement on tests of verbal memory compared to haplogroup H carriers. We did not observe differences in executive function or attention. Conclusion:Our results reinforce the role of mtDNA in changes to cognitive function in a domain associated with risk for dementia, verbal memory, but not with other cognitive domains. Future research should investigate the distinct mechanisms by which mtDNA might affect performance on verbal memory as compared to other cognitive domains across haplogroups.

Keywords: Alzheimer’s disease, cognition, haplogroup, mitochondrial DNA, mtDNA

DOI: 10.3233/JAD-220298

Journal: Journal of Alzheimer's Disease, vol. 89, no. 3, pp. 913-922, 2022