Alzheimer's polygenic hazard score in SuperAgers: SuperGenes or SuperResilience?

Barbara E. Spencer, Sarah J. Banks, Anders M. Dale, James B. Brewer, Beth Makowski-Woidan, Sandra Weintraub, M. Marsel Mesulam, Changiz Geula, Emily Rogalski*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Introduction: SuperAgers are individuals over age 80 with superior episodic memory, at a level consistent with individuals 20 to 30 years their junior and who seem to show resistance to age-related neurofibrillary degeneration. Here we examine whether low genetic risk for Alzheimer's disease (AD) contributes to SuperAgers’ unusually high episodic memory performance in advanced age. Methods: The AD polygenic hazard score (PHS) was calculated for each SuperAger and cognitively normal participant and compared between groups. Results: A total of 37 SuperAgers (73% female, mean [standard deviation] 82.7 [2.8] years old) and 35 controls (54% female, 83.7 [4.3] years old) were included. There was no significant difference in the AD PHS between SuperAgers and cognitively normal controls. Discussion: Unusually successful cognitive aging cannot be simply explained by low polygenic risk for AD as assessed by common genetic variants. However, rare variants and common protective genetic factors may contribute to resistance or resilience. Highlights: SuperAging cannot be simply explained by low polygenic risk for Alzheimer's disease. Rare variants and common protective genetic factors may contribute to SuperAging. A protective factors polygenic score may uncover mechanisms for SuperAging.

Original languageEnglish (US)
Article numbere12321
JournalAlzheimer's and Dementia: Translational Research and Clinical Interventions
Volume8
Issue number1
DOIs
StatePublished - 2022

Keywords

  • Alzheimer's disease
  • aging
  • dementia
  • episodic memory
  • polygenic risk
  • resilience
  • resistance
  • successful aging

ASJC Scopus subject areas

  • Clinical Neurology
  • Psychiatry and Mental health

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