Carrigan, Maria;
Bocancea, Diana I;
Vogel, Jacob;
van Loenhoud, Anna C;
Tesi, Niccoló;
Barkhof, Frederik;
Lucassen, Paul J;
... Ossenkoppele, Rik; + view all
(2025)
A novel approach to resilience and its links with education and Alzheimer's disease genetics.
Alzheimer's & Dementia
, 21
(7)
, Article e70379. 10.1002/alz.70379.
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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 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.
| Type: | Article |
|---|---|
| Title: | A novel approach to resilience and its links with education and Alzheimer's disease genetics |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1002/alz.70379 |
| Publisher version: | https://doi.org/10.1002/alz.70379 |
| Language: | English |
| Additional information: | © 2025 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
| Keywords: | Alzheimer's disease, canonical correlation analysis, cognitive resilience, genetic risk factors, global cognition, magnetic resonance imaging, Humans, Alzheimer Disease, Male, Female, Aged, Educational Status, Polymorphism, Single Nucleotide, Magnetic Resonance Imaging, Cohort Studies, Resilience, Psychological, Neuropsychological Tests, Apolipoprotein E4, Aged, 80 and over, Genome-Wide Association Study |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10211413 |
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