Physical Performance and Amyloid-β in Humans: A Systematic Review and Meta-Analysis of Observational Studies

Article type: Systematic Review

Authors: Solis-Urra, Patricio^{a; b; c; *} | Rodriguez-Ayllon, María^d | Álvarez-Ortega, Miriam^a | Molina-Hidalgo, Cristina^{e; f} | Molina-Garcia, Pablo^{a; g} | Arroyo-Ávila, Cristina^a | García-Hermoso, Antonio^h | Collins, Audrey M.^f | Jain, Shivangi^f | Gispert, Juan Domingo^{i; j; k; l} | Liu-Ambrose, Teresa^{m; n; o} | Ortega, Francisco B.^{a; p; q} | Erickson, Kirk I.^{e; f} | Esteban-Cornejo, Irene^{a; q; r; *}

Affiliations: [a] Department of Physical Education and Sports, Faculty of Sport Sciences, Sport and Health University Research Institute (iMUDS), University of Granada, Granada, Spain | [b] Nuclear Medicine Services, “Virgen de Las Nieves”, University Hospital, Granada, Spain | [c] Faculty of Education and Social Sciences, Universidad Andres Bello, Viña del Mar, Chile | [d] Department of Epidemiology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands | [e] Department of Psychology, University of Pittsburgh, Pittsburgh, PA, USA | [f] AdventHealth Research Institute, Neuroscience, Orlando, FL, USA | [g] Physical Medicine and Rehabilitation Service, Virgen de las Nieves University Hospital, Instituto de Investigacion Biosanitaria ibs.GRANADA, Granada, Spain | [h] Navarrabiomed, Hospital Universitario de Navarra, IdiSNA, Universidad Pública de Navarra (UPNA), Pamplona, Spain | [i] BarcelonaBeta Brain Research Center, Pasqual Maragall Foundation, Barcelona, Spain | [j] Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Spain | [k] Universitat Pompeu Fabra, Barcelona, Spain | [l] IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain | [m] Centre for Aging SMART at Vancouver Coastal Health, Vancouver Coastal Health Research Institute, Vancouver, British Columbia, Canada | [n] Djavad Mowafaghian Centre for Brain Health, Vancouver Coastal Health Research Institute, Vancouver, British Columbia, Canada | [o] Aging, Mobility, and Cognitive Health Laboratory, Department of Physical Therapy, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada | [p] Faculty of Sport and Health Sciences, University of Jyväskylä, Jyväskylä, Finland | [q] Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III, Madrid, Spain | [r] ibs.GRANADA Instituto de Investigación Biosanitaria, Granada, Spain

Correspondence: [*] Correspondence to: Patricio Solis-Urra & Irene-Esteban-Cornejo, Department of Physical Education and Sports, Faculty of Sports Science, University of Granada; Carretera de Alfacar, 21, Granada 18071, Spain. Tel.: +34 958 24 66 51; Fax: +34 958 24 94 28; E-mails: [email protected], [email protected].

Abstract: Background:Accumulation of amyloid-β (Aβ) plaques is one of the main features of Alzheimer’s disease (AD). Physical performance has been related to dementia risk and Aβ, and it has been hypothesized as one of the mechanisms leading to greater accumulation of Aβ. Yet, no evidence synthesis has been performed in humans. Objective:To investigate the association of physical performance with Aβ in humans, including Aβ accumulation on brain, and Aβ abnormalities measured in cerebrospinal fluid (CSF) and blood. Methods:A systematic review with multilevel meta-analysis was performed from inception to June 16th, 2022. Studies were eligible if they examined the association of physical performance with Aβ levels, including the measure of physical performance as a predictor and the measure of Aβ as an outcome in humans. Results:7 articles including 2,619 participants were included in the meta-analysis. The results showed that physical performance was not associated with accumulation of Aβ in the brain (ES = 0.01; 95% CI –0.21 to 0.24; I2 = 69.9%), in the CSF (ES = –0.28; 95% CI –0.98 to 0.41; I2 = 91.0%) or in the blood (ES = –0.19; 95% CI –0.61 to 0.24; I2 = 99.75%). Significant heterogeneity was found across the results , which posed challenges in arriving at consistent conclusions; and the limited number of studies hindered the opportunity to conduct a moderation analysis. Conclusions:The association between physical performance and Aβ is inconclusive. This uncertainly arises from the limited number of studies, study design limitations, and heterogeneity of measurement approaches. More studies are needed to determine whether physical performance is related to Aβ levels in humans.

Keywords: Alzheimer’s disease, amyloid, meta-analysis, physical performance

DOI: 10.3233/JAD-230586

Journal: Journal of Alzheimer's Disease, vol. 96, no. 4, pp. 1427-1439, 2023