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Age-, sex-, and pathology-related variability in brain structure and cognition


Bachmann, Dario; Buchmann, Andreas; Studer, Sandro; Saake, Antje; Rauen, Katrin; Zuber, Isabelle; Gruber, Esmeralda; Nitsch, Roger M; Hock, Christoph; Gietl, Anton; Treyer, Valerie (2023). Age-, sex-, and pathology-related variability in brain structure and cognition. Translational Psychiatry, 13(1):278.

Abstract

This work aimed to investigate potential pathways linking age and imaging measures to early age- and pathology-related changes in cognition. We used [18F]-Flutemetamol (amyloid) and [18F]-Flortaucipir (tau) positron emission tomography (PET), structural MRI, and neuropsychological assessment from 232 elderly individuals aged 50-89 years (46.1% women, 23% APOE-ε4 carrier, 23.3% MCI). Tau-PET was available for a subsample of 93 individuals. Structural equation models were used to evaluate cross-sectional pathways between age, amyloid and tau burden, grey matter thickness and volumes, white matter hyperintensity volume, lateral ventricle volume, and cognition. Our results show that age is associated with worse outcomes in most of the measures examined and had similar negative effects on episodic memory and executive functions. While increased lateral ventricle volume was consistently associated with executive function dysfunction, participants with mild cognitive impairment drove associations between structural measures and episodic memory. Both age and amyloid-PET could be associated with medial temporal lobe tau, depending on whether we used a continuous or a dichotomous amyloid variable. Tau burden in entorhinal cortex was related to worse episodic memory in individuals with increased amyloid burden (Centiloid >12) independently of medial temporal lobe atrophy. Testing models for sex differences revealed that amyloid burden was more strongly associated with regional atrophy in women compared with men. These associations were likely mediated by higher tau burden in women. These results indicate that influences of pathological pathways on cognition and sex-specific vulnerabilities are dissociable already in early stages of neuropathology and cognitive impairment.

Abstract

This work aimed to investigate potential pathways linking age and imaging measures to early age- and pathology-related changes in cognition. We used [18F]-Flutemetamol (amyloid) and [18F]-Flortaucipir (tau) positron emission tomography (PET), structural MRI, and neuropsychological assessment from 232 elderly individuals aged 50-89 years (46.1% women, 23% APOE-ε4 carrier, 23.3% MCI). Tau-PET was available for a subsample of 93 individuals. Structural equation models were used to evaluate cross-sectional pathways between age, amyloid and tau burden, grey matter thickness and volumes, white matter hyperintensity volume, lateral ventricle volume, and cognition. Our results show that age is associated with worse outcomes in most of the measures examined and had similar negative effects on episodic memory and executive functions. While increased lateral ventricle volume was consistently associated with executive function dysfunction, participants with mild cognitive impairment drove associations between structural measures and episodic memory. Both age and amyloid-PET could be associated with medial temporal lobe tau, depending on whether we used a continuous or a dichotomous amyloid variable. Tau burden in entorhinal cortex was related to worse episodic memory in individuals with increased amyloid burden (Centiloid >12) independently of medial temporal lobe atrophy. Testing models for sex differences revealed that amyloid burden was more strongly associated with regional atrophy in women compared with men. These associations were likely mediated by higher tau burden in women. These results indicate that influences of pathological pathways on cognition and sex-specific vulnerabilities are dissociable already in early stages of neuropathology and cognitive impairment.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Nuclear Medicine
04 Faculty of Medicine > Institute for Regenerative Medicine (IREM)
Dewey Decimal Classification:610 Medicine & health
Scopus Subject Areas:Health Sciences > Psychiatry and Mental Health
Life Sciences > Cellular and Molecular Neuroscience
Life Sciences > Biological Psychiatry
Language:English
Date:14 August 2023
Deposited On:24 Aug 2023 09:40
Last Modified:29 Jun 2024 01:38
Publisher:Nature Publishing Group
ISSN:2158-3188
OA Status:Gold
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1038/s41398-023-02572-6
PubMed ID:37574523
  • Content: Published Version
  • Language: English
  • Licence: Creative Commons: Attribution 4.0 International (CC BY 4.0)