{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T14:24:27Z","timestamp":1782311067259,"version":"3.54.5"},"reference-count":52,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2024,10,8]],"date-time":"2024-10-08T00:00:00Z","timestamp":1728345600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAD"],"published-print":{"date-parts":[[2024,10,8]]},"abstract":"<jats:p>Background: Modifiable (physical activity) and non-modifiable (sex and genotype) risk factors interact to affect Alzheimer\u2019s disease (AD) risk. Further investigation is necessary to understand if these factors influence brain volume and cognition. Objective: The study aimed to assess the effect of physical activity, APOE genotype, and sex on AD risk, brain volume, and cognition. Methods: UK Biobank data from 2006 to 2023 was accessed. Physical activity was measured by accelerometers, and International Physical Activity Questionnaire. Outcomes were AD incidence; brain volume (ventricular cerebrospinal fluid and total brain); and cognition (executive function, memory, visuospatial ability, processing speed, and reaction time). Logistic and linear regression models were conducted. Results: 69,060 participants met inclusion criteria (mean age: 62.28 years, SD: 7.84; 54.64% female). Higher self-reported (OR\u200a=\u200a0.63, 95% CI [0.40, 1.00], p\u200a=\u200a0.047) and accelerometer-assessed (OR\u200a=\u200a0.96 [0.93, 0.98], p\u200a=\u200a0.002) physical activity was associated with lower disease incidence. Smaller ventricular cerebrospinal fluid volume (\u03b2=\u200a\u2013 65.43 [\u2013 109.68, \u2013 17.40], p\u200a=\u200a0.007), and larger total brain volume (\u03b2=\u200a4398.46 [165.11, 8631.82], p\u200a&lt;\u200a0.001) was associated with increased accelerometer-assessed and self-reported physical activity respectively. Both brain volume analyses were moderated by sex. Increased accelerometer-assessed physical activity levels were associated with faster reaction time (\u03b2=\u200a\u2013 0.43 [\u2013 0.68, \u2013 0.18], p\u200a=\u200a0.001); though poorer visuospatial ability (\u03b2=\u200a\u2013 0.06 [\u2013 0.09, \u2013 0.03], p\u200a&lt;\u200a0.001), and executive function (\u03b2=\u200a0.49 [0.31, 0.66], p\u200a&lt;\u200a0.001; \u03b2=\u200a0.27 [0.10, 0.45], p\u200a=\u200a0.002) was related to self-reported physical activity levels. Conclusions: Higher levels of physical activity reduce AD risk independently of non-modifiable risk factors. Moderation of sex on brain volume highlighted the importance of incorporating non-modifiable risk factors in analysis.<\/jats:p>","DOI":"10.3233\/jad-240269","type":"journal-article","created":{"date-parts":[[2024,9,13]],"date-time":"2024-09-13T11:34:20Z","timestamp":1726227260000},"page":"1029-1042","source":"Crossref","is-referenced-by-count":7,"title":["The Relationship Between Physical Activity and Non-Modifiable Risk Factors on Alzheimer\u2019s Disease and Brain Health Markers: A UK Biobank Study"],"prefix":"10.1177","volume":"101","author":[{"given":"Felicity S.E.","family":"Spencer","sequence":"first","affiliation":[{"name":"School of Sport, Exercise and Rehabilitation Sciences, University of Birmingham, Birmingham, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard J.","family":"Elsworthy","sequence":"additional","affiliation":[{"name":"School of Sport, Exercise and Rehabilitation Sciences, University of Birmingham, Birmingham, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leigh","family":"Breen","sequence":"additional","affiliation":[{"name":"School of Sport, Exercise and Rehabilitation Sciences, University of Birmingham, Birmingham, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Bishop","sequence":"additional","affiliation":[{"name":"Birmingham Clinical Trials Unit, Institute of Applied Health Research, Public Health Building, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sol","family":"Morrissey","sequence":"additional","affiliation":[{"name":"Norwich Medical School, Faculty of Medicine and Health Sciences, University of East Anglia, Norwich, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Aldred","sequence":"additional","affiliation":[{"name":"School of Sport, Exercise and Rehabilitation Sciences, University 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