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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.

December 11, 2025pubmed logopapers

Authors

Britton MK,Hoogerwoerd H,Juhasz J,Johnson KJ,Stewart PD,Bharadwaj PK,Merritt SS,Jessup CJ,Wright CB,Hishaw GA,Raichlen DA,Del Bene VA,Wadley VG,Trouard TP,Alperin N,Levin BE,Rundek T,Visscher KM,Alexander GE,Cohen RA,Porges EC,Gullett JM

Affiliations (18)

  • Department of Epidemiology, University of Florida, Gainesville, FL, 32610, USA. [email protected].
  • Center for Cognitive Aging and Memory, Evelyn F. and William L. McKnight Brain Institute, University of Florida, Gainesville, FL, 32610, USA. [email protected].
  • Department of Radiology and Biomedical Imaging, Yale University, New Haven, CT, USA. [email protected].
  • Center for Cognitive Aging and Memory, Evelyn F. and William L. McKnight Brain Institute, University of Florida, Gainesville, FL, 32610, USA.
  • Department of Clinical and Health Psychology, University of Florida, Gainesville, FL, 32610, USA.
  • Department of Neurobiology, University of Alabama at Birmingham, Birmingham, Alabama, 35233, USA.
  • Evelyn F. McKnight Brain Institute, University of Alabama at Birmingham, Birmingham, Alabama, 35233, USA.
  • Department of Psychology, University of Arizona, Tucson, AZ, 85719, USA.
  • Evelyn F. McKnight Brain Institute, University of Arizona, Tucson, AZ, 85719, USA.
  • Department of Neurology, University of Miami, Miami, FL, 33136, USA.
  • Evelyn F. McKnight Brain Institute, University of Miami, Miami, FL, 33136, USA.
  • National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, 20824, USA.
  • Department of Neurology, University of Arizona, Tucson, AZ, 85719, USA.
  • Department of Biological Sciences, University of Southern California, Los Angeles, CA, 90089, USA.
  • Department of Neurology, University of Alabama at Birmingham, Birmingham, Alabama, 35233, USA.
  • Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, 35233, USA.
  • Department of Biomedical Engineering, University of Arizona, Tucson, AZ, 85719, USA.
  • Department of Radiology, University of Miami, Miami, FL, 33136, USA.

Abstract

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.

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