Poster No:
1193
Submission Type:
Abstract Submission
Authors:
James Roe1, Didac Vidal-Piñeiro2, Esten Leonardsen3, Øystein Sørensen2, Håkon Grydeland1, Olena Iakunchykova1, Kristine Beate Walhovd4, Anders Fjell5, Yunpeng Wang1
Institutions:
1University of Oslo, Oslo, Norway, 2Centre for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo, Oslo, Norway, 3NORMENT; University of Oslo, Oslo, Norway, 4Univeristy of Oslo, Oslo, Oslo, 5Department of Psychology, Center for Lifespan Changes in Brain and Cognition, University of Oslo, Oslo, Oslo
First Author:
Co-Author(s):
Didac Vidal-Piñeiro
Centre for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo
Oslo, Norway
Øystein Sørensen
Centre for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo
Oslo, Norway
Anders Fjell
Department of Psychology, Center for Lifespan Changes in Brain and Cognition, University of Oslo
Oslo, Oslo
Introduction:
Across healthy adult life our brain's undergo widespread structural change. Many of these changes occur gradually and are qualitatively similar to atrophy patterns that are accelerated in Alzheimer's disease (AD; 1-2), raising the possibility accelerated brain change across healthy adult life may relate to genetic AD-risk.
Methods:
We modelled subject-specific structural brain change relative to that expected given age, in dense longitudinal adult lifespan data (1430 scans from 420 individuals aged 30 to 89 years; 2-7 timepoints). Using polygenic AD scores (PRS-AD) from four GWAS (3-6), we first tested PRS-AD associations with age-relative change in early Braak stage regions – namely hippocampus, entorhinal cortex, amygdala, and medial temporal cortex. Next, following the hypothesis that brain changes in ageing and AD are largely shared, we performed machine learning classification on brain change trajectories conditional on age in longitudinal AD patient-control data, to obtain a list of AD-accelerated features and model change in these in adult lifespan data, and test PRS-AD-change associations via multivariate methods. Lastly, we tested whether high PRS-AD individuals also high on a multivariate marker of brain change exhibit more longitudinal memory decline over their healthy adult life (30-89 years).
Results:
Healthy individuals losing more brain volume than expected for their age in early Braak stage regions had significantly higher genetic risk for AD, beyond the risk conferred by APOE alone. We found PRS-AD was associated with a multivariate marker of accelerated change in many AD-accelerated features in healthy adults, and that most individuals above ~50 years of age are on an accelerated change trajectory in AD-accelerated brain regions. Directly applying the AD-derived model weights to healthy adult lifespan data also enabled detection of PRS-AD-change associations in healthy adults. Finally, high PRS-AD individuals also high on a multivariate marker of change showed more adult lifespan memory decline, compared to high PRS-AD individuals with less brain change.
Conclusions:
The results support a dimensional account linking gradual lifespan brain changes with AD, suggesting AD risk genes speed up the shared pattern of ageing- and AD-related neurodegeneration that starts early, occurs along a continuum, and tracks memory change in healthy adults.
Disorders of the Nervous System:
Neurodegenerative/ Late Life (eg. Parkinson’s, Alzheimer’s) 2
Genetics:
Genetic Association Studies
Lifespan Development:
Aging 1
Keywords:
Aging
Cognition
Memory
NORMAL HUMAN
STRUCTURAL MRI
1|2Indicates the priority used for review
Provide references using author date format
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