Hypothalamic volume is associated with age, sex and cognitive function across lifespan: a comparative analysis of two large population-based cohort studies

Peng Xu; Santiago Estrada; Rika Etteldorf; Dan Liu; Mohammad Shahid; Weiyi Zeng; Deborah Früh; Martin Reuter; Monique M B Breteler; N Ahmad Aziz

doi:10.1016/j.ebiom.2024.105513

Hypothalamic volume is associated with age, sex and cognitive function across lifespan: a comparative analysis of two large population-based cohort studies

EBioMedicine. 2024 Dec 20:111:105513. doi: 10.1016/j.ebiom.2024.105513. Online ahead of print.

Authors

Affiliations

¹ Population Health Sciences, German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
² Population Health Sciences, German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany; Artificial Intelligence in Medical Imaging, German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
³ Artificial Intelligence in Medical Imaging, German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany; A.A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Boston, MA, USA; Department of Radiology, Harvard Medical School, Boston, MA, USA.
⁴ Population Health Sciences, German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany; Institute for Medical Biometry, Informatics and Epidemiology (IMBIE), Faculty of Medicine, University of Bonn, Germany.
⁵ Population Health Sciences, German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany; Department of Neurology, Faculty of Medicine, University of Bonn, Germany. Electronic address: Ahmad.Aziz@dzne.de.

PMID: 39708426
DOI: 10.1016/j.ebiom.2024.105513

Abstract

Background: Emerging findings indicate that the hypothalamus, the body's principal homeostatic centre, plays a crucial role in modulating cognition, but comprehensive population-based studies are lacking.

Methods: We used cross-sectional data from the Rhineland Study (N = 5812, 55.2 ± 13.6 years, 58% women) and the UK Biobank Imaging Study (UKB) (N = 45,076, 64.2 ± 7.7 years, 53% women), two large-scale population-based cohort studies. Volumes of hypothalamic structures were obtained from 3T structural magnetic resonance images through an automatic parcellation procedure (FastSurfer-HypVINN). The standardised cognitive domain scores were derived from extensive neuropsychological test batteries. We employed multivariable linear regression to assess associations of hypothalamic volumes with age, sex and cognitive performance.

Findings: In older individuals, volumes of total, anterior and posterior hypothalamus, and mammillary bodies were smaller, while those of medial hypothalamus and tuberal region were larger. Larger medial hypothalamus volume was related to higher cortisol levels in older individuals, providing functional validation. Volumes of all hypothalamic structures were larger in men compared to women. In both sexes, larger volumes of total, anterior and posterior hypothalamus, and mammillary bodies were associated with better domain-specific cognitive performance, whereas larger volumes of medial hypothalamus and tuberal region were associated with worse domain-specific cognitive performance.

Interpretation: We found strong age and sex effects on hypothalamic structures, as well as robust associations between these structures and domain-specific cognitive functions. Overall, these findings thus implicate specific hypothalamic subregions as potential therapeutic targets against age-associated cognitive decline.

Funding: Institutional funds, Federal Ministry of Education and Research of Germany, Alzheimer's Association.

Keywords: Age-associated cognitive decline; Brain imaging; Cognitive function; Cortisol; Hypothalamus; Sexual dimorphism.