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

Int J Geriatr Psychiatry. 2020 Sep;35(9):982-988. doi: 10.1002/gps.5319. Epub 2020 Jun 11.

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.

Keywords: cortisol; longitudinal; memory; older adults; serotonin transporter.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aged
  • Alleles
  • Cross-Sectional Studies
  • Genotype
  • Humans
  • Hydrocortisone*
  • Serotonin Plasma Membrane Transport Proteins* / genetics

Substances

  • Serotonin Plasma Membrane Transport Proteins
  • Hydrocortisone