Associations of Midlife Lifestyle and Health Factors with Long-Term Changes in Blood-Based Biomarkers of Alzheimer’s Disease and Neurodegeneration

Article type: Research Article

Authors: Merten, Natascha^{a; b; c; *} | Pinto, A. Alex^d | Paulsen, Adam J.^c | Chen, Yanjun^e | Engelman, Corinne D.^c | Hancock, Laura M.^{f; g} | Johnson, Sterling C.^{a; b} | Schubert, Carla R.^c

Affiliations: [a] Division of Geriatrics and Gerontology, Department of Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA | [b] Wisconsin Alzheimer’s Disease Research Center, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA | [c] Department of Population Health Sciences, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA | [d] Department of Biostatistics and Medical Informatics, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA | [e] Department of Ophthalmology and Visual Sciences, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA | [f] Department of Neurology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA | [g] William S Middleton Memorial Veterans Hospital, Madision, WI, USA

Correspondence: [*] Correspondence to: Natascha Merten, PhD, MS, Department of Population Health Sciences and Department of Medicine, Division of Geriatrics and Gerontology, University of Wisconsin, WARF Office Building, 610 Walnut St, Madison, WI 53726, USA. Tel.: +1 608 263 0277; E-mail: [email protected].

Abstract: Background:Pathological biomarkers of Alzheimer’s disease (AD) and other dementias can change decades before clinical symptoms. Lifestyle and health factors might be relevant modifiable risk factors for dementia. Many previous studies have been focusing on associations of lifestyle and health-related factors with clinical outcomes later in life. Objective:We aimed to determine to what extent midlife factors of lifestyle, inflammation, vascular, and metabolic health were associated with long-term changes in blood-based biomarkers of AD (amyloid beta (Aβ)) and neurodegeneration (neurofilament light chain (NfL); total tau(TTau)). Methods:In 1,529 Beaver Dam Offspring Study (BOSS) participants (mean age 49 years, standard deviation (SD) = 9; 54% were women), we applied mixed-effects models with baseline risk factors as determinants and 10-year serum biomarker change as outcomes. Results:We found that education and inflammatory markers were associated with levels and/or change over time across all three markers of AD and neurodegeneration in the blood. There were baseline associations of measures of cardiovascular health with lower Aβ42/Aβ40. TTau changed little over time and was higher in individuals with diabetes. Individuals with lower risk in a number of cardiovascular and metabolic risk factors, including diabetes, hypertension, and atherosclerosis had slower accumulation of neurodegeneration over time, as determined by NfL levels. Conclusion:Various lifestyle and health factors, including education and inflammation, were associated with longitudinal changes of neurodegenerative and AD biomarker levels in midlife. If confirmed, these findings could have important implications for developing early lifestyle and health interventions that could potentially slow processes of neurodegeneration and AD.

Keywords: Alzheimer’s disease, amyloid, biomarker, dementia, education, healthy lifestyle, inflammation, neurofilament light protein, tau protein, vascular diseases

DOI: 10.3233/JAD-221287

Journal: Journal of Alzheimer's Disease, vol. 94, no. 4, pp. 1381-1395, 2023