A novel approach to resilience and its links with education and Alzheimer's disease genetics
(2025) In Alzheimer's and Dementia 21(7).- Abstract
INTRODUCTION: Cognitive resilience refers to maintaining cognitive function despite Alzheimer's disease (AD) pathophysiology. METHODS: We analyzed amyloid-positive individuals across clinical stages of AD in two cohorts: the Amsterdam Dementia Cohort (ADC, N = 1036) and Alzheimer's Disease Neuroimaging Initiative (ADNI, N = 685). Cognitive resilience was conceptualized from a canonical correlation analysis of magnetic resonance imaging and neuropsychological data in each cohort separately. Model validation involved education as a resilience proxy and key genetic factors (apolipoprotein E [APOE] ε4 and APOE ε2) of AD. We explored associations between 83 AD risk loci and cognitive resilience. RESULTS: Resilience was correlated with... (More)
INTRODUCTION: Cognitive resilience refers to maintaining cognitive function despite Alzheimer's disease (AD) pathophysiology. METHODS: We analyzed amyloid-positive individuals across clinical stages of AD in two cohorts: the Amsterdam Dementia Cohort (ADC, N = 1036) and Alzheimer's Disease Neuroimaging Initiative (ADNI, N = 685). Cognitive resilience was conceptualized from a canonical correlation analysis of magnetic resonance imaging and neuropsychological data in each cohort separately. Model validation involved education as a resilience proxy and key genetic factors (apolipoprotein E [APOE] ε4 and APOE ε2) of AD. We explored associations between 83 AD risk loci and cognitive resilience. RESULTS: Resilience was correlated with education (ADC: β = 0.144, p < 0.001; ADNI: β = 0.149, p < 0.001) and APOE ε4 (βmeta-analysis= –0.052, p = 0.014). Exploratory single nucleotide polymorphism meta-analysis identified potential involvement of genetic variants around genes UNC5CL, USP6NL, and TPCN1 in lower, and genes COX7C and MINDY2 in higher resilience. DISCUSSION: Our novel resilience approach showed conceptual validity and potential for future discovery of resilience-related genetic variants. Highlights: ·We define a novel approach to resilience using canonical correlation analysis (CCA). ·Apolipoprotein E ε4 is linked to lower resilience, suggesting increased vulnerability. ·Genetic loci around COX7C and MINDY2 are potentially involved in higher resilience. ·This novel approach may be used for multi-cohort studies such as genome-wide association studies in the future.
(Less)
- author
- organization
- publishing date
- 2025-07
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Alzheimer's disease, canonical correlation analysis, cognitive resilience, genetic risk factors, global cognition, magnetic resonance imaging
- in
- Alzheimer's and Dementia
- volume
- 21
- issue
- 7
- article number
- e70379
- publisher
- Wiley
- external identifiers
-
- scopus:105009856783
- pmid:40613482
- ISSN
- 1552-5260
- DOI
- 10.1002/alz.70379
- language
- English
- LU publication?
- yes
- additional info
- Publisher Copyright: © 2025 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.
- id
- 0ffde531-6b11-4521-8d97-410f9f287c06
- date added to LUP
- 2025-12-15 16:50:06
- date last changed
- 2025-12-16 03:00:05
@article{0ffde531-6b11-4521-8d97-410f9f287c06,
abstract = {{<p>INTRODUCTION: Cognitive resilience refers to maintaining cognitive function despite Alzheimer's disease (AD) pathophysiology. METHODS: We analyzed amyloid-positive individuals across clinical stages of AD in two cohorts: the Amsterdam Dementia Cohort (ADC, N = 1036) and Alzheimer's Disease Neuroimaging Initiative (ADNI, N = 685). Cognitive resilience was conceptualized from a canonical correlation analysis of magnetic resonance imaging and neuropsychological data in each cohort separately. Model validation involved education as a resilience proxy and key genetic factors (apolipoprotein E [APOE] ε4 and APOE ε2) of AD. We explored associations between 83 AD risk loci and cognitive resilience. RESULTS: Resilience was correlated with education (ADC: β = 0.144, p < 0.001; ADNI: β = 0.149, p < 0.001) and APOE ε4 (β<sub>meta-analysis</sub>= –0.052, p = 0.014). Exploratory single nucleotide polymorphism meta-analysis identified potential involvement of genetic variants around genes UNC5CL, USP6NL, and TPCN1 in lower, and genes COX7C and MINDY2 in higher resilience. DISCUSSION: Our novel resilience approach showed conceptual validity and potential for future discovery of resilience-related genetic variants. Highlights: ·We define a novel approach to resilience using canonical correlation analysis (CCA). ·Apolipoprotein E ε4 is linked to lower resilience, suggesting increased vulnerability. ·Genetic loci around COX7C and MINDY2 are potentially involved in higher resilience. ·This novel approach may be used for multi-cohort studies such as genome-wide association studies in the future.</p>}},
author = {{Carrigan, Maria and Bocancea, Diana I. and Vogel, Jacob and van Loenhoud, Anna C. and Tesi, Niccoló and Barkhof, Frederik and Lucassen, Paul J. and van der Flier, Wiesje M. and Krugers, Harm J. and Van der Lee, Sven J. and Ossenkoppele, Rik}},
issn = {{1552-5260}},
keywords = {{Alzheimer's disease; canonical correlation analysis; cognitive resilience; genetic risk factors; global cognition; magnetic resonance imaging}},
language = {{eng}},
number = {{7}},
publisher = {{Wiley}},
series = {{Alzheimer's and Dementia}},
title = {{A novel approach to resilience and its links with education and Alzheimer's disease genetics}},
url = {{http://dx.doi.org/10.1002/alz.70379}},
doi = {{10.1002/alz.70379}},
volume = {{21}},
year = {{2025}},
}