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Background: <p>Biological age can be quantified by composite proteomic scores, called proteomics-based aging clocks (PACs). We investigated whether a discrepancy between chronological and biological age in midlife and late-life is associated with cognition and dementia risk.</p> Methods: <p>We used two longitudinal population-based studies: the Atherosclerosis Risk in Communities (ARIC) Study and the Multi-Ethnic Study of Atherosclerosis (MESA). PACs were created in ARIC at midlife (mean age: 58 years, 57% female, <i>n</i> = 11,758) and late-life (mean age: 77 years, 56% female, <i>n</i> = 4934) using elastic net regression models in two-thirds of dementia-free participants and validated in the remaining one-third of participants. Proteomics-based age acceleration (PAA) was calculated as residuals after regressing PACs on chronological age. We validated the midlife PAC in the MESA cohort (mean age: 62 years, 52% female, <i>n</i> = 5829). We used multivariable linear and Cox proportional hazards regression to assess the association of PAA with cognitive function and dementia incidence, respectively.</p> Results: <p>In ARIC, every five years, PAA is associated with lower global cognition: difference: −0.11, 95% confidence interval[CI]: −0.16, −0.06) using midlife PAA and difference: −0.17, CI: −0.23, −0.12 using late-life PAA. Midlife PAA is associated with higher dementia risk (hazard ratio[HR]: 1.20 [CI: 1.04, 1.36]) and more prominently when using late-life PAA (HR: 2.14 [CI:1.67, 2.73]). Similar findings are observed in MESA: PAA is associated with lower global cognitive function (difference: −0.08 [CI: −0.14, −0.03]) and higher dementia risk (HR:1.23 [CI: 1.04, 1.46]).</p> Conclusions <p>Accelerated biological age is associated with lower cognition and a higher risk of dementia in midlife and more prominently in late life.</p>

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Proteomics-based aging clocks in midlife or late-life and their associated risk of dementia

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年8月14日

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  • Sanaz Sedaghat,
  • Saeun Park,
  • Rob F. Walker,
  • Shuo Wang,
  • Jialing Liu,
  • Timothy M. Hughes,
  • Behnam Sabayan,
  • Weihong Tang,
  • Josef Coresh,
  • James S. Pankow,
  • Keenan A. Walker,
  • Ramon Casanova,
  • Ruth Dubin,
  • Rajat Deo,
  • Jerome I. Rotter,
  • Alexis C. Wood,
  • Peter Ganz,
  • Pamela L. Lutsey,
  • Weihua Guan,
  • Anna Prizment

摘要

Background:

Biological age can be quantified by composite proteomic scores, called proteomics-based aging clocks (PACs). We investigated whether a discrepancy between chronological and biological age in midlife and late-life is associated with cognition and dementia risk.

Methods:

We used two longitudinal population-based studies: the Atherosclerosis Risk in Communities (ARIC) Study and the Multi-Ethnic Study of Atherosclerosis (MESA). PACs were created in ARIC at midlife (mean age: 58 years, 57% female, n = 11,758) and late-life (mean age: 77 years, 56% female, n = 4934) using elastic net regression models in two-thirds of dementia-free participants and validated in the remaining one-third of participants. Proteomics-based age acceleration (PAA) was calculated as residuals after regressing PACs on chronological age. We validated the midlife PAC in the MESA cohort (mean age: 62 years, 52% female, n = 5829). We used multivariable linear and Cox proportional hazards regression to assess the association of PAA with cognitive function and dementia incidence, respectively.

Results:

In ARIC, every five years, PAA is associated with lower global cognition: difference: −0.11, 95% confidence interval[CI]: −0.16, −0.06) using midlife PAA and difference: −0.17, CI: −0.23, −0.12 using late-life PAA. Midlife PAA is associated with higher dementia risk (hazard ratio[HR]: 1.20 [CI: 1.04, 1.36]) and more prominently when using late-life PAA (HR: 2.14 [CI:1.67, 2.73]). Similar findings are observed in MESA: PAA is associated with lower global cognitive function (difference: −0.08 [CI: −0.14, −0.03]) and higher dementia risk (HR:1.23 [CI: 1.04, 1.46]).

Conclusions

Accelerated biological age is associated with lower cognition and a higher risk of dementia in midlife and more prominently in late life.