The DOI matches its Crossref record; 38 of the 39 references it cites were found in a registry or an index, and 1 are not checked yet.
Physical Activity, Brain Volume, and Dementia Risk: The Framingham Study
Open accessAbstract
BACKGROUND: Several longitudinal studies found an inverse relationship between levels of physical activity and cognitive decline, dementia, and/or Alzheimer's disease (AD), but results have been inconsistent. We followed an older, community-based cohort for over a decade to examine the association of physical activity with the risk of incident dementia and subclinical brain MRI markers of dementia. METHODS: The physical activity index (PAI) was assessed in the Framingham Study Original and Offspring cohorts, aged 60 years or older. We examined the association between PAI and risk of incident all-cause dementia and AD in participants of both cohorts who were cognitively intact and had available PAI (n = 3,714; 54% women; mean age = 70±7 years). We additionally examined the association between PAI and brain MRI in the Offspring cohort (n = 1,987). RESULTS: Over a decade of follow-up, 236 participants developed dementia (188 AD). Participants in the lowest quintile of PAI had an increased risk of incident dementia compared with those in higher quintiles (hazard ratio [HR] = 1.50, 95% confidence interval [CI] = 1.04-1.97, p = .028) in a multivariable-adjusted model. Secondary analysis revealed that this relation was limited to participants who were apolipoprotein (APO)E ε4 allele noncarriers (HR = 1.58, 95% CI = 1.08-2.32; p = .018) and strongest in participants aged 75 years or older. PAI was also linearly related to total brain and hippocampal volumes (β ± SE = 0.24±0.06; p < .01 and 0.004±0.001; p = .003, respectively). CONCLUSION: Low physical activity is associated with a higher risk for dementia in older individuals, suggesting that a reduced risk of dementia and higher brain volumes may be additional health benefits of maintaining physical activity into old age.
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“In contrast, physical activity appears to decrease risk. [119][120]0][121][122][123][124][125][126][127][128]”
From 2023 Alzheimer's disease facts and figures (2023) · cites this paper as [122]
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“Collectively, this suggests that eating a heart-healthy diet [172,173,174,175,176] and increasing physical activity [177,178,179,180] could delay the onset of AD.”
From Mitochondrial Oxidative and Nitrosative Stress and Alzheimer Disease (2020) · cites this paper as [178]
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A Proportional Hazards Model for the Subdistribution of a Competing Risk
Fine, J. P., & Gray, R. J. (1999) · Journal of the American Statistical Association · doi:10.1080/01621459.1999.10474144 · Cited by 14,290 · cited 2×
“The potential competing risk of death in these relations was also assessed, using methods described by Fine and Gray (16).”
MethodResultExercise training increases size of hippocampus and improves memory
Erickson, K. I., Voss, M. W., Prakash, R. S., Basak, C., Szabo, A., Chaddock, L., Kim, J. S., Heo, S., Alves, H., White, S. M., et al. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1015950108 · Cited by 4,855
Aerobic Exercise Training Increases Brain Volume in Aging Humans
Colcombe, S. J., Erickson, K. I., Scalf, P. E., Kim, J. S., Prakash, R., McAuley, E., Elavsky, S., Marquez, D. X., Hu, L., & Kramer, A. F. (2006) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/61.11.1166 · Cited by 2,134
Leisure Activities and the Risk of Dementia in the Elderly
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Larson, E. B., Wang, L., Bowen, J. D., McCormick, W. C., Teri, L., Crane, P., & Kukull, W. (2006) · Annals of Internal Medicine · doi:10.7326/0003-4819-144-2-200601170-00004 · Cited by 1,463
A Proportional Hazards Model for the Subdistribution of a Competing Risk
Fine, J. P., & Gray, R. J. (1999) · Journal of the American Statistical Association · doi:10.2307/2670170 · Cited by 1,375
Participation in Cognitively Stimulating Activities and Risk of Incident Alzheimer Disease
Wilson, R. S. (2002) · JAMA · doi:10.1001/jama.287.6.742 · Cited by 1,352
Physical Activity, Including Walking, and Cognitive Function in Older Women
Weuve, J. (2004) · JAMA · doi:10.1001/jama.292.12.1454 · Cited by 1,175
Leisure-time physical activity at midlife and the risk of dementia and Alzheimer's disease
Rovio, S., Kåreholt, I., Helkala, E.-L., Viitanen, M., Winblad, B., Tuomilehto, J., Soininen, H., Nissinen, A., & Kivipelto, M. (2005) · The Lancet Neurology · doi:10.1016/s1474-4422(05)70198-8 · Cited by 1,054
Research works printed but not linked: 1
- 10.1001/archinte.1979.03630450011006 · DOI
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Ding, H., Brown, S., Paquette, D. R., Orwig, T. A., Spartano, N. L., & Lin, H. (2025) · doi:10.2196/preprints.72946
Self-citationPaulsen, A., Driscoll, I. F., Breidenbach, B. M., Glittenberg, M., Lose, S., Ma, Y., Sager, M. A., Carlsson, C., Gallagher, C., Hermann, B. P., et al. (2025) · medRxiv · doi:10.1101/2025.03.03.25323245
Enette, L. (2019) · theses.fr (ABES) · doi:10.70675/1ad1a02ez8eebz4234z9bdfzf1e991390f85
Développement de formes vectorisables innovantes dans le cadre de maladies liées à l'âge
Iskandar, S. (2019) · theses.fr (ABES) · doi:10.70675/1d771122z75d0z4ba8z8ee6zbd1a858ffc38
DuBois, S. L., & Etnier, J. L. (2026) · Journal of Sport and Exercise Psychology · doi:10.1123/jsep.2025-0287
Relationship between myeloid skewing and colorectal cancer risk in the Framingham Heart Study
Orloff, L. E., & Lisio, M. D. (2026) · Frontiers in Oncology · doi:10.3389/fonc.2026.1773537
“…hours (cid:1) 1 : 5) + ( medium − intensity hours (cid:1) 2 : 4) + ( high − intensity hours (cid:1) 5 : 0) Within each sex, participants were classi fi ed into quintiles (Q1 - Q5) based on their PAI scores, where Q1 represents the lowest physical activity level and Q5 represents the highest (27).”
LUCENA, S. O. D. D., Rossi, F. E., Barbosa, F. P. L., Barbosa, M. P. D. C. D. R., Bachi, A. L. L., Filho, J. C. J., & Neves, L. M. (2026) · Journal of Aging and Physical Activity · doi:10.1123/japa.2025-0053
APOE ε4, physical activity, and the brain: a review of systematic reviews
Ali, N., Chakbazof, N., Pour, S. G., Contreras, L., Estrada, J., Alexander, G. E., Raichlen, D. A., & Yassine, H. N. (2026) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2026.1798639 · Cited by 1
Dog ownership and healthy brain aging: a pilot study
Potter, K., Martini, D. N., Sands, C. J., Falck, R. S., & Nagarajan, R. (2026) · PeerJ · doi:10.7717/peerj.21560 · Cited by 1
“…2021 ) and the physically active or fit brain has greater total volume, regional gray matter volumes ( e.g. , hippocampal volume ( Erickson et al., 2009 ; Gu et al., 2020 ; Hamer, Sharma & Batty, 2018 ; Tan et al., 2017 ; Varma et al., 2015 )) and white matter volume ( Sexton et al., 2016 ).”
Association between physical activity and incident dementia among individuals with hypertension
Yang, C., Zhao, Y., Li, J., Lei, L., Li, Y., Wang, W., Meng, X., Xia, C., Zhang, L., Wang, X., et al. (2026) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2026.1833102
“Previous cohort studies have extensively examined the inverse association between self-reported PA and dementia (Sabia et al., 2017; Tan et al., 2017; Soni et al., 2019; Dupré et al., 2020), which is consistent with our findings.”
Zheng, W., Wu, M., Chen, Y., Li, S., & Huang, L. (2026) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2026.1949679
Metadata
- Authors
- Tan, Z. S., Spartano, N. L., Beiser, A. S., DeCarli, C., Auerbach, S. H., Vasan, R. S., & Seshadri, S.
- Affiliations
- University of California, Los Angeles (US)
- Framingham Heart Study (US)
- Boston University (US)
- University of California, Davis (US)
- ORCID
- Venue
- The Journals of Gerontology Series A: Biological Sciences and Medical Sciences
- Publisher
- Oxford University Press (OUP)
- Published
- 2016-07-15
- Volume
- 72
- Issue
- 6
- Pages
- glw130
- ISSN
- 1079-5006 (ISSN-L)
- 1758-535X
- PMC
- PMC6075525
- OpenAlex
- W2468595961
- Cited by
- 212
- References
- 38
- Citations by year
- 2026: 10 · 2025: 24 · 2024: 20 · 2023: 20 · 2022: 35 · 2021: 25 · 2020: 21 · 2019: 25 · 2018: 18 · 2017: 13 · 2016: 1
- FWCI
- 16.88
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journals of Gerontology Series A (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institutes of Health
- National Heart, Lung, and Blood Institute (NIH/NHLBI, HHSN268201500001I, N01-HC-25195, N01HV28178, R01HL093029, R01 HL131029, U01 HL096917, 2K24HL04334)
- National Institute on Aging (R01 AG016495, AG008122, AG031287, AG047645)
- National Institute of Neurological Disorders and Stroke (NINDS, R01 NS017950)
- American Heart Association (AHA Award 11CRP4930020, 16MCPRP30310001)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Physical Activity and Health
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Keywords
- physical activity, dementia risk, Alzheimer's disease, brain volume, hippocampal volume, APOE ε4, older adults, cognitive decline, physical activity index, brain MRI markers, Framingham Heart Study
- MeSH terms
- Age Factors, Aged, Alleles, Alzheimer Disease, Brain, Dementia, Female, Humans, Longitudinal Studies, Magnetic Resonance Imaging, Male, Risk, United States, Cohort Studies, Exercise, Apolipoprotein E4
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