Association Between APOE Alleles and Change of Neuropsychological Tests in the Long Life Family Study

Article type: Research Article

Authors: Du, Mengtian^{a; *} | Andersen, Stacy L.^b | Schupf, Nicole^{c; d} | Feitosa, Mary F.^e | Barker, Megan S.^c | Perls, Thomas T.^b | Sebastiani, Paola^f

Affiliations: [a] Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA | [b] Geriatrics Section, Department of Medicine, Boston University School of Medicine, Boston, MA, USA | [c] Department of Neurology, Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, and the Gertrude H. Sergievsky Center, Columbia University Medical Center, New York, NY, USA | [d] Department of Epidemiology, Columbia University Mailman School of Public Health, Sergievsky Center, New York, NY, USA | [e] Division of Statistical Genomics, Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA | [f] Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, Boston, MA, USA

Correspondence: [*] Correspondence to: Mengtian Du, MS, Department of Biostatistics, Boston University, 801 Massachusetts Ave., Boston, MA 02118, USA. Tel.: +1 203 215 7127; E-mail: mandydu@bu.edu.

Abstract: Background:The Long Life Family Study (LLFS) is a family based, prospective study of healthy aging and familial longevity. The study includes two assessments of cognitive function that were administered approximately 8 years apart. Objective:To test whether APOE genotype is associated with change of cognitive function in older adults. Methods:We used Bayesian hierarchical models to test the association between APOE alleles and change of cognitive function. Six longitudinally collected neuropsychological test scores were modelled as a function of age at enrollment, follow-up time, gender, education, field center, birth cohort indicator (≤1935, or >1935), and the number of copies of ɛ2 or ɛ4 alleles. Results:Out of 4,587 eligible participants, 2,064 were male (45.0%), and age at enrollment ranged from 25 to 110 years, with mean of 70.85 years (SD: 15.75). We detected a significant cross-sectional effect of the APOE ɛ4 allele on Logical Memory. Participants carrying at least one copy of the ɛ4 allele had lower scores in both immediate (–0.31 points, 95% CI: –0.57, –0.05) and delayed (–0.37 points, 95% CI: –0.64, –0.10) recall comparing to non-ɛ4 allele carriers. We did not detect any significant longitudinal effect of the ɛ4 allele. There was no cross-sectional or longitudinal effect of the ɛ2 allele. Conclusion:The APOE ɛ4 allele was identified as a risk factor for poorer episodic memory in older adults, while the APOE ɛ2 allele was not significantly associated with any of the cognitive test scores.

Keywords: APOE, cognition, longevity, longitudinal studies

DOI: 10.3233/JAD-201113

Journal: Journal of Alzheimer's Disease, vol. 79, no. 1, pp. 117-125, 2021