Title: The 5-HTTLPR long allele predicts two-year longitudinal increases in cortisol and declines in verbal memory in older adults.

Authors: Hirst, Rayna B; Jordan, Joshua T; Schüssler-Fiorenza Rose, Sophia Miryam; Schneider, Logan; Kawai, Makoto; Gould, Christine E; Anker, Lauren; Chick, Christina F; Beaudreau, Sherry A; Hallmayer, Joachim; O'Hara, Ruth

Published In Int J Geriatr Psychiatry, (2020 09)

Abstract: OBJECTIVES: The short form or s-allele variant of the serotonin transporter polymorphism (5-HTTLPR), as compared with the long-form or l-allele variant, has been associated with the presence of cognitive dysfunction, and particularly memory impairment in older adults. This body of cross-sectional work has culminated in the hypothesis that presence of the s-allele predicts greater memory decline in older adults. Yet, to date, there are no longitudinal studies that have investigated this issue. METHODS/DESIGN: Here, we examine 109 community-dwelling older adults (mean and SD of age = 70.7 ± 8.7 years) who underwent blood draw for genotyping, cognitive, and psychological testing at baseline, 12-, and 24-monthfollow-ups. RESULTS: Multilevel modeling found that s-allele carriers (ss or ls) performed worse than ll homozygotes at baseline on delayed verbal recall. Yet, s-allele carriers' memory performance was stable over the two-yearfollow-up period, while l-allele homozygotes experienced significant memory decline. l-allele homozygote status was associated with both increased cortisol and decreased memory over time, resulting in attenuated verbal memory performance differences compared to s-allele carriers with age. CONCLUSIONS: Overall, our findings do not support the hypothesis that presence of the 5-HTTLPRs-allele is a marker for memory decline in older adults. J Am Geriatr Soc 68:-, 2020.

PubMed ID: 32400901

MeSH Terms: Aged; Alleles; Cross-Sectional Studies; Genotype; Humans; Hydrocortisone*; Serotonin Plasma Membrane Transport Proteins*/genetics