Accelerated Phenotypical Aging in Midlife is Associated With Long-Term Cognitive Decline

TL;DR

This study finds that people whose biological age is higher than their chronological age in midlife experience faster cognitive decline over the next 10 years.

Contribution

The study is the first to link accelerated PhenoAge in midlife with long-term cognitive decline.

Findings

Higher PhenoAge in midlife is associated with worse baseline cognitive performance on the TMT-B.

Accelerated PhenoAge predicts faster cognitive decline over 10 years, especially in men.

PhenoAge may serve as a cost-effective early marker for cognitive impairment and dementia.

Abstract

PhenoAge, a multi-system biomarker uses easily-obtained common clinical blood tests and determines whether a person is younger or older on a biological and physiological level than expected by chronological age. Higher PhenoAge is associated with increased risk of disability, age-related morbidities and all-cause mortality. Its associations with early cognitive changes in midlife are less understood. The aim of this study was to determine whether accelerated PhenoAge in midlife was associated with 10-year cognitive changes in middle-aged to older adults. This longitudinal study is based on N = 2,630 (54% women;mean age 50years) Beaver Dam Offspring Study participants. We measured baseline blood-based clinical markers necessary for calculation of accelerated PhenoAge (PhenoAgeAccel). We tested Trail-making Test B (TMT-B) performance at baseline, 5-year and 10-year follow-up. We used linear mixed-effects model with PhenoAgeAccel as predictor and TMT-B time as outcome, adjusting for random intercepts, education and sex. Models were repeated sex-stratified. With every additional year older in PhenoAge compared to chronological age at baseline, participants performed worse on the TMT-B at baseline [overall:0.60 seconds slower, 95% Confidence Interval (0.29,0.91); women: 0.34(-0.05,0.72); men: 0.91(0.41,1.42)] and had a faster decline in TMT-B over 10-years [overall:0.94 seconds slower (0.58,1.29); women: 0.51(0.08,0.95); men: 1.48(0.90,2.07)]. Accelerated PhenoAge in midlife was associated with 10-year cognitive decline, overall and in men. Longer follow-up will be needed to determine whether PhenoAge might be predictive of cognitive impairment later in life. If confirmed, PhenoAge could become a cost-effective marker of cognitive decline and dementia and help identify at-risk individuals early and inform targeted interventions.