Plant sterols and cholesterol metabolism are associated with five-year cognitive decline in the elderly population

Christopher Clark; Mehdi Gholam; Leonardo Zullo; Anja Kerksiek; Enrique Castelao; Armin von Gunten; Martin Preisig; Dieter Lütjohann; Julius Popp

doi:10.1016/j.isci.2023.106740

Plant sterols and cholesterol metabolism are associated with five-year cognitive decline in the elderly population

iScience. 2023 Apr 24;26(6):106740. doi: 10.1016/j.isci.2023.106740. eCollection 2023 Jun 16.

Authors

Christopher Clark^{1

2}, Mehdi Gholam², Leonardo Zullo³, Anja Kerksiek⁴, Enrique Castelao⁵, Armin von Gunten³, Martin Preisig⁵, Dieter Lütjohann⁴, Julius Popp^{1

3}

Affiliations

¹ Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zürich, Lenggstrasse 31, PO Box 363, 8032 Zürich, Switzerland.
² Department of Mathematics, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
³ Old Age Psychiatry, Department of Psychiatry, Lausanne University Hospital, Route de Cery 60, 1008 Prilly, Switzerland.
⁴ Institute of Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn, Bonn, Germany.
⁵ Department of Psychiatry, Center for Research in Psychiatric Epidemiology and Psychopathology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.

Abstract

Dysregulations in cholesterol metabolism are associated with neurodegenerative and vascular pathologies, and dementia. Diet-derived plant sterols (phytosterols) have cholesterol-lowering, anti-inflammatory, and antioxidant properties and may interfere with neurodegeneration and cognitive decline. Here we performed multivariate analysis in 720 individuals enrolled in a population-based prospective study to determine whether circulating cholesterol precursors and metabolites, triglycerides, and phytosterols, are associated with cognitive impairment and decline in the older population. We report specific dysregulations of endogenous cholesterol synthesis and metabolism, and diet-derived phytosterols, and their changes over time associated with cognitive impairment, and decline in the general population. These findings suggest circulating sterols levels could be considered in risk evaluation and are relevant for the development of strategies to prevent cognitive decline in older people.

Keywords: Age; Behavioral neuroscience; Human metabolism.