Plasma Brain-Derived Neurotropic Factor Levels are Associated with Aging and Smoking But Not with Future Dementia in the Rotterdam Study

Article type: Research Article

Authors: Galle, Sara A.^{a; b; *} | Licher, Silvan^b | Milders, Maarten M.^a | Deijen, Jan Berend^{a; c} | Scherder, Erik J.A.^a | Drent, Madeleine L.^{a; d} | Arfan Ikram, M.^b | van Duijn, Cornelia M.^{b; e; f}

Affiliations: [a] Department of Clinical, Neuro- and Developmental Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands | [b] Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands | [c] Hersencentrum Mental Health Institute, Amsterdam, The Netherlands | [d] Department of Internal Medicine, Endocrinology Section, Amsterdam University Medical Center, Amsterdam, The Netherlands | [e] Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom | [f] Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, Oxford, United Kingdom

Correspondence: [*] Correspondence to: Sara A. Galle, Vrije Universiteit Amsterdam –Faculteit der Gedrags- en Bewegingswetenschappen, t.a.v. Sara A. Galle MF-B535, Van der Boechorststraat 7-9, 1081 BT Amsterdam, The Netherlands. Tel.: +31 205 988 769; E-mail: [email protected].

Abstract: Background:Brain-derived neurotropic factor (BDNF) plays a vital role in neuronal survival and plasticity and facilitates long-term potentiation, essential for memory. Alterations in BDNF signaling have been associated with cognitive impairment, dementia, and Alzheimer’s disease. Although peripheral BDNF levels are reduced in dementia patients, it is unclear whether changes in BDNF levels precede or follow dementia onset. Objective:In the present study, we examined the association between BDNF plasma levels and dementia risk over a follow-up period of up to 16 years. Methods:Plasma BDNF levels were assessed in 758 participants of the Rotterdam Study. Dementia was assessed from baseline (1997–1999) to follow-up until January 2016. Associations of plasma BDNF and incident dementia were assessed with Cox proportional hazards models, adjusted for age and sex. Associations between plasma BDNF and lifestyle and metabolic factors are investigated using linear regression. Results:During a follow up of 3,286 person-years, 131 participants developed dementia, of whom 104 had Alzheimer’s disease. We did not find an association between plasma BDNF and risk of dementia (adjusted hazard ratio 0.99; 95%CI 0.84–1.16). BDNF levels were positively associated with age (B = 0.003, SD = 0.001, p = 0.002), smoking (B = 0.08, SE = 0.01, p = <  0.001), and female sex (B = 0.03, SE = 0.01, p = 0.03), but not with physical activity level (B = –0.01, SE = 0.01, p = 0.06). Conclusion:The findings suggest that peripheral BDNF levels are not associated with an increased risk of dementia.

Keywords: Aging, Alzheimer’s disease, brain-derived neurotropic factor, dementia, genetic epidemiology

DOI: 10.3233/JAD-200371

Journal: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-11, 2021