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<p>The cognitively-intact oldest-old (85 +) may be the most-resilient members of their birth cohort; due to survivorship effects (e.g., depletion of susceptibles), risk factors associated with brain aging biomarkers in younger samples may not generalize to the cognitively-intact oldest-old. We evaluated associations between established aging-related risk factors and brain-predicted age difference (brainPAD) in a cross-sectional cognitively-intact oldest-old sample. Additionally, we evaluated brainPAD-cognition associations to characterize brain maintenance vs. cognitive reserve in our sample. Oldest-old adults (N = 206; 85–99&#xa0;years; Montreal Cognitive Assessment &gt; 22 or neurologist evaluation) underwent T1-weighted MRI; brainPAD was generated with brainageR, such that more-positive brainPAD reflected more-advanced brain aging. Sex, education, alcohol and smoking history, exercise history, BMI, cardiovascular and metabolic disease history, and anticholinergic medication burden were self-reported. Global cognitive z-score and coefficient of variation were derived from the UDS 3.0 cognitive battery; crystallized-fluid discrepancy was derived from the NIH Toolbox Cognitive Battery. Mean brainPAD was -7.99 (SD: 5.37; range: -24.50, 6.03). Women showed more-delayed brain aging than men (B = -2.9, 95% CI = -4.6, -1.1, p = 0.002). No other exposures were significantly associated with brainPAD. BrainPAD was not associated with any cognitive variable. These findings suggest that cognitively-intact oldest-old adults may be atypically-resistant to risk factors associated with aging in younger samples, consistent with survivorship effects in aging. Furthermore, brainPAD may have limited explanatory value for cognitive performance in cognitively-intact oldest-old adults, potentially due to high cognitive reserve. Overall, our findings highlight the impact of survivorship effects on brain aging research.</p> Graphical Abstract <p></p>

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Your brain doesn’t look a day past 70! Cross-sectional associations with brain-predicted age in the cognitively-intact oldest-old

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月11日

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  • Mark K. Britton,
  • Hannah Hoogerwoerd,
  • Joshua Juhasz,
  • Keyanni Joy Johnson,
  • Paul D. Stewart,
  • Pradyumna K. Bharadwaj,
  • Stacy S. Merritt,
  • Cortney J. Jessup,
  • Clinton B. Wright,
  • G. Alex Hishaw,
  • David A. Raichlen,
  • Victor A. Del Bene,
  • Virginia G. Wadley,
  • Theodore P. Trouard,
  • Noam Alperin,
  • Bonnie E. Levin,
  • Tatjana Rundek,
  • Kristina M. Visscher,
  • Gene E. Alexander,
  • Ronald A. Cohen,
  • Eric C. Porges,
  • Joseph M. Gullett

摘要

The cognitively-intact oldest-old (85 +) may be the most-resilient members of their birth cohort; due to survivorship effects (e.g., depletion of susceptibles), risk factors associated with brain aging biomarkers in younger samples may not generalize to the cognitively-intact oldest-old. We evaluated associations between established aging-related risk factors and brain-predicted age difference (brainPAD) in a cross-sectional cognitively-intact oldest-old sample. Additionally, we evaluated brainPAD-cognition associations to characterize brain maintenance vs. cognitive reserve in our sample. Oldest-old adults (N = 206; 85–99 years; Montreal Cognitive Assessment > 22 or neurologist evaluation) underwent T1-weighted MRI; brainPAD was generated with brainageR, such that more-positive brainPAD reflected more-advanced brain aging. Sex, education, alcohol and smoking history, exercise history, BMI, cardiovascular and metabolic disease history, and anticholinergic medication burden were self-reported. Global cognitive z-score and coefficient of variation were derived from the UDS 3.0 cognitive battery; crystallized-fluid discrepancy was derived from the NIH Toolbox Cognitive Battery. Mean brainPAD was -7.99 (SD: 5.37; range: -24.50, 6.03). Women showed more-delayed brain aging than men (B = -2.9, 95% CI = -4.6, -1.1, p = 0.002). No other exposures were significantly associated with brainPAD. BrainPAD was not associated with any cognitive variable. These findings suggest that cognitively-intact oldest-old adults may be atypically-resistant to risk factors associated with aging in younger samples, consistent with survivorship effects in aging. Furthermore, brainPAD may have limited explanatory value for cognitive performance in cognitively-intact oldest-old adults, potentially due to high cognitive reserve. Overall, our findings highlight the impact of survivorship effects on brain aging research.

Graphical Abstract