Association Between Telomere Length and Early Midlife Memory Function: Impact of Sex, Reproductive Aging, and Hypertension

Kyoko Konishi, PhD

Massachusetts General Hospital – Faculty
Konishi_Kyoko poster

Scientific Abstract

Background: Shorter telomere length (TL) is an important cellular marker of biological aging that is associated with cognitive decline, hypertension, and hippocampal atrophy, a key region in the memory circuitry. Estradiol, a sex steroid hormone that declines in menopause, regulates TL by decreasing oxidative stress and upregulating enzymes that repairs telomere shortening. Here, we assessed the impact of TL, in relation to sex, reproductive status, and hypertension, on memory circuitry regional brain volumes and memory performance in early midlife.

Methods: Participants (N=212; 106F:106M; ages 45–55) underwent MRI and neuropsychological assessments of memory. Leukocyte TL was determined by extracting genomic DNA.

Results: In women, shorter TL was associated with poor memory performance (β=0.19, pFDR=0.03), and in postmenopause, was further related to smaller right hippocampal volume (β=111.92, pFDR=0.04). In men, longer TL tended to be associated with larger volume in the parahippocampus (β=127.86, pFDR=0.08) and anterior cingulate cortex (β=271.64, pFDR=0.08). We also found that shorter TL was associated with hypertension in midlife (β=-0.41, p=0.007), which in turn was related to poor memory performance in men (β=-1.85, p=0.0006) and women (β=-1.84, p=0.005).

Conclusions: Results demonstrate that longer TL is associated with better memory function and larger volume in memory circuitry regions in early midlife, an effect that differs by sex/reproductive status. Further, findings suggest that TL may partially mediate the relationship between cardiovascular health and cognitive function in later life and may serve as an early biomarker of sex-dependent brain and cardiovascular abnormalities in early midlife.


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Kyoko Konishi, PhD, Emily G. Jacobs, PhD, Brianna Smith, BS, Sarah Aroner, PhD, Hannah Shields, BS, Immaculata De Vivo, PhD, Nikos Makris, MD, PhD, Anne Remington, MA, Harlyn Aizley, EdM, Jill M. Goldstein, PhD

Principal Investigator

Jill M. Goldstein, PhD

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