Associations between sex and lifestyle activities with cognitive reserve in mid-life adults with genetic risk for Alzheimer's disease

Qing Qi, Feng Deng, Rebecca Sammon, Karen Ritchie, Graciela Muniz-Terrera, Ivan Koychev, Paresh Malhotra, Siobhan Hutchinson, David Robinson, John T O'Brien, Craig W Ritchie, Brian Lawlor, Lorina Naci*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

BACKGROUND: Females have a higher age-adjusted incidence of Alzheimer's Disease (AD) than males, even when accounting for longer lifespan and, therefore, stand to benefit the most from dementia prevention efforts. As exposure to many modifiable risk factors for dementia begins in mid-life, interventions must be implemented from middle-age. Building cognitive reserve, particularly through stimulating avocational activities and occupational attainment presents a crucial, underexplored, dementia prevention approach for mid-life. It is currently unknown, however, whether modifiable lifestyle factors can protect against AD processes, from mid-life, differentially for females and males who carry inherited risk for late-life dementia. To address this gap, this study investigated the impact of biological sex and APOE4 carrier status on the relationship between stimulating activities, occupational attainment, and cognition in mid-life.

METHODS: We leveraged the PREVENT-Dementia program, the world's largest study investigating the origins and early diagnosis of dementia in mid-life at-risk individuals (N = 700; 40-59 years). Cognitive performance was measured using the Cognito Battery and the Visual Short Term Memory Binding task. Mid-life specific reserve contributors were assessed via the Lifetime of Experiences Questionnaire.

RESULTS: Females had significantly better episodic and relational memory (p < 0.001), and lower occupational attainment than males (p < 0.001). Engagement in stimulating activities was positively associated with episodic and relational memory, regardless of sex and APOE4 status (β = 0.05, CI 0.03-0.07, p < 0.001). APOE4 carriers showed significant sex differences in the association between occupational attainment and episodic and relational memory (β = 0.38, CI 0.12-0.63, p = 0.003). APOE4 carrier females with higher occupational attainment showed better cognition (β = 0.16, CI -0.002-0.32, p = 0.053), whereas APOE4 carrier males showed the opposite effect (β = -0.20, CI -0.40 - -0.001, p = 0.049).

CONCLUSION: Our findings suggest that occupational attainment in mid-life contributes to cognitive reserve against inherited risk of dementia in females, but not males. They highlight the need for high precision approaches that consider biological sex and APOE4 carrier status to inform Alzheimer's disease prevention strategies and clinical trials.

Original languageEnglish
Pages (from-to)246
JournalAlzheimer's research & therapy
Volume16
Issue number1
Early online date13 Nov 2024
DOIs
Publication statusE-pub ahead of print - 13 Nov 2024

Keywords / Materials (for Non-textual outputs)

  • Humans
  • Male
  • Female
  • Alzheimer Disease/genetics
  • Cognitive Reserve/physiology
  • Middle Aged
  • Life Style
  • Apolipoprotein E4/genetics
  • Adult
  • Sex Factors
  • Genetic Predisposition to Disease
  • Risk Factors
  • Neuropsychological Tests

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