Structured vs Self-Guided Multidomain Lifestyle Interventions for Global Cognitive Function: The US POINTER Randomized Clinical Trial
Open accessAbstract
Importance: Identifying new interventions to slow and prevent cognitive decline associated with dementia is critical. Nonpharmacological interventions targeting modifiable risk factors are promising, relatively low-cost, accessible, and safe approaches. Objective: To compare the effects of two 2-year lifestyle interventions on cognitive trajectory in older adults at risk of cognitive decline and dementia. Design, Setting, and Participants: Single-blind, multicenter randomized clinical trial enrolling 2111 participants from May 2019 to March 2023 (final follow-up, May 14, 2025) at 5 clinical sites in the US. Participant inclusion criteria enriched risk of cognitive decline and included age 60 to 79 years, sedentary lifestyle, and suboptimal diet plus at least 2 additional criteria related to family history of memory impairment, cardiometabolic risk, race and ethnicity, older age, and sex. Interventions: Participants were randomly assigned with equal probability to structured (n = 1056) or self-guided (n = 1055) interventions. Both interventions encouraged increased physical and cognitive activity, healthy diet, social engagement, and cardiovascular health monitoring, but differed in structure, intensity, and accountability. Main Outcomes and Measures: The primary comparison was difference between intervention groups in annual rate of change in global cognitive function, assessed by a composite measure of executive function, episodic memory, and processing speed, over 2 years. Results: Among the 2111 individuals enrolled (mean age, 68.2 [SD, 5.2] years; 1455 [68.9%] female), 89% completed the year 2 assessment. The mean global cognitive composite z score increased from baseline over time in both groups, with a mean rate of increase per year of 0.243 SD (95% CI, 0.227-0.258) for the structured intervention and 0.213 SD (95% CI, 0.198-0.229) for the self-guided intervention. The mean rate of increase per year was statistically significantly greater for the structured group than the self-guided group by 0.029 SD (95% CI, 0.008-0.050; P = .008). Based on prespecified secondary subgroup comparisons, the structured intervention benefit was consistent for APOE ε4 carriers and noncarriers ( P = .95 for interaction) but appeared greater for adults with lower vs higher baseline cognition ( P = .02 for interaction). Fewer ascertained adverse events were reported in the structured group (serious: 151; nonserious: 1091) vs the self-guided group (serious: 190; nonserious: 1225), with a positive COVID-19 test result being the most common adverse event overall and more frequent in the structured group. Conclusions and Relevance: Among older adults at risk of cognitive decline and dementia, a structured, higher-intensity intervention had a statistically significant greater benefit on global cognition compared with an unstructured, self-guided intervention. Further investigation of functional outcomes, biomarkers, and ongoing extended follow-up will help address clinical relevance and sustainability of the observed cognitive benefits. Trial Registration: ClinicalTrials.gov Identifier: NCT03688126
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
There is much evidence that lifestyle intervention and adoption of healthy lifestyles promotes cognitive health and staves off cognitive decline.
“There is much evidence that lifestyle intervention and adoption of healthy lifestyles promotes cognitive health and staves off cognitive decline [85–92]”
From Personalized machine learning guided intervention for optimizing lifestyle behaviors in depression: a pilot study (2026) · cites this paper as [92]
The Key Points and Discussion report that a structured multidomain lifestyle intervention produced greater improvement in global cognition than a self-guided intervention over two years in older adults at elevated risk. The Discussion also says that, without a no-intervention control, the trial cannot rule out practice effects or establish that the interventions prevented decline. The claim extends the finding to healthy-lifestyle adoption generally and to staving off cognitive decline. (LLM, conf=0.86)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
General Cardiovascular Risk Profile for Use in Primary Care: The Framingham Heart Study
D’Agostino, R. B., Vasan, R. S., Pencina, M. J., Wolf, P. A., Cobain, M., Massaro, J. M., & Kannel, W. B. (2008) · Circulation · doi:10.1161/circulationaha.107.699579 · Cited by 7,491 · see citing works
Lecanemab in early Alzheimer's disease
van Dyck, C. H., Swanson, C. J., Aisen, P., Bateman, R. J., Chen, C., Gee, M., Kanekiyo, M., Li, D., Reyderman, L., Cohen, S., et al. (2023) · New England Journal of Medicine · doi:10.1056/nejmoa2212948 · Cited by 5,678 · see citing works
Dementia prevention, intervention, and care: 2024 report of the Lancet standing Commission
Livingston, G., Huntley, J., Liu, K. Y., Costafreda, S. G., Selbæk, G., Alladi, S., Ames, D., Banerjee, S., Burns, A., Brayne, C., et al. (2024) · The Lancet · doi:10.1016/s0140-6736(24)01296-0 · Cited by 3,860 · see citing works
Ngandu, T., Lehtisalo, J., Solomon, A., Levälahti, E., Ahtiluoto, S., Antikainen, R., Bäckman, L., Hänninen, T., Jula, A., Laatikainen, T., et al. (2015) · The Lancet · doi:10.1016/s0140-6736(15)60461-5 · Cited by 3,689 · see citing works
Self-citationDonanemab in Early Symptomatic Alzheimer Disease: The TRAILBLAZER-ALZ 2 Randomized Clinical Trial
Sims, J. R., Zimmer, J. A., Evans, C. D., Lu, M., Ardayfio, P., Sparks, J., Wessels, A. M., Shcherbinin, S., Wang, H., Monkul Nery, E. S., et al. (2023) · JAMA · doi:10.1001/jama.2023.13239 · Cited by 2,932 · see citing works
Self-citationUpdate of the Healthy Eating Index: HEI-2015
Krebs‐Smith, S. M., Pannucci, T. E., Subar, A. F., Kirkpatrick, S. I., Lerman, J., Tooze, J. A., Wilson, M. M., & Reedy, J. (2018) · Journal of the Academy of Nutrition and Dietetics · doi:10.1016/j.jand.2018.05.021 · Cited by 2,303 · see citing works
Mixed brain pathologies account for most dementia cases in community-dwelling older persons
Schneider, J. A., Arvanitakis, Z., Bang, W., & Bennett, D. A. (2007) · Neurology · doi:10.1212/01.wnl.0000271090.28148.24 · Cited by 1,992 · see citing works
Boutron, I., Altman, D. G., Moher, D., Schulz, K. F., Ravaud, P., & for the CONSORT NPT Group* (2017) · Annals of Internal Medicine · doi:10.7326/m17-0046 · Cited by 1,538 · see citing works
Prevalence of the metabolic syndrome in the United States, 2003-2012
Aguilar, M., Bhuket, T., Torres, S., Liu, B., & Wong, R. J. (2015) · JAMA · doi:10.1001/jama.2015.4260 · Cited by 1,267 · see citing works
Lecanemab: Appropriate Use Recommendations
Cummings, J., Apostolova, L., Rabinovici, G. D., Atri, A., Aisen, P., Greenberg, S., Hendrix, S., Selkoe, D., Weiner, M., Petersen, R. C., et al. (2023) · The Journal of Prevention of Alzheimer's Disease · doi:10.14283/jpad.2023.30 · Cited by 961 · see citing works
Self-citationAndrieu, S., Guyonnet, S., Coley, N., Cantet, C., Bonnefoy, M., Bordes, S., Bories, L., Cufi, M.-N., Dantoine, T., Dartigues, J.-F., et al. (2017) · The Lancet Neurology · doi:10.1016/s1474-4422(17)30040-6 · Cited by 838 · see citing works
van Charante, E. P. M., Richard, E., Eurelings, L. S., van Dalen, J.-W., Ligthart, S. A., van Bussel, E. F., Hoevenaar-Blom, M. P., Vermeulen, M., & van Gool, W. A. (2016) · The Lancet · doi:10.1016/s0140-6736(16)30950-3 · Cited by 611 · see citing works
World‐Wide FINGERS Network: A global approach to risk reduction and prevention of dementia
Kivipelto, M., Mangialasche, F., Snyder, H. M., Allegri, R., Andrieu, S., Arai, H., Baker, L., Belleville, S., Brodaty, H., Brucki, S. M., et al. (2020) · Alzheimer's & Dementia · doi:10.1002/alz.12123 · Cited by 553 · see citing works
Self-citationWeinstein, A. M., Voss, M. W., Prakash, R. S., Chaddock, L., Szabo‐Reed, A. N., White, S. M., Wójcicki, T. R., Mailey, E. L., McAuley, E., Kramer, A. F., et al. (2011) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2011.11.008 · Cited by 342 · see citing works
Physical Inactivity Among Adults Aged 50 Years and Older — United States, 2014
Watson, K. B., Carlson, S. A., Gunn, J. P., Galuska, D. A., O’Connor, A. E., Greenlund, K. J., & Fulton, J. E. (2016) · MMWR Morbidity and Mortality Weekly Report · doi:10.15585/mmwr.mm6536a3 · Cited by 328 · see citing works
Fitness Effects on the Cognitive Function of Older Adults: A Meta-Analytic Study—Revisited
Kramer, A. F., & Colcombe, S. J. (2018) · Perspectives on Psychological Science · doi:10.1177/1745691617707316 · Cited by 288 · see citing works
Measuring longitudinal cognition: Individual tests versus composites
Jonaitis, E. M., Koscik, R. L., Clark, L. R., Ma, Y., Betthauser, T. J., Berman, S. E., Allison, S. L., Mueller, K. D., Hermann, B. P., Hulle, C. A. V., et al. (2018) · Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring · doi:10.1016/j.dadm.2018.11.006 · Cited by 144 · see citing works
Alzheimer’s Disease: Novel Targets and Investigational Drugs for Disease Modification
Cummings, J. L., Osse, A. M. L., & Kinney, J. W. (2023) · Drugs · doi:10.1007/s40265-023-01938-w · Cited by 123 · see citing works
Japan‐Multimodal Intervention Trial for the Prevention of Dementia: A randomized controlled trial
Sakurai, T., Sugimoto, T., Akatsu, H., Doi, T., Fujiwara, Y., Hirakawa, A., Kinoshita, F., Kuzuya, M., Lee, S., Matsumoto, N., et al. (2024) · Alzheimer s & Dementia · doi:10.1002/alz.13838 · Cited by 106 · see citing works
Baker, L. D., Snyder, H. M., Espeland, M. A., Whitmer, R. A., Kivipelto, M., Woolard, N., Katula, J. A., Papp, K. V., Ventrelle, J., Graef, S., et al. (2023) · Alzheimer s & Dementia · doi:10.1002/alz.13365 · Cited by 100 · see citing works
Self-citationMarengoni, A., Rizzuto, D., Fratiglioni, L., Antikaínen, R., Laatikainen, T. K., Lehtisalo, J., Peltonen, M., Soininen, H. S., Strandberg, T. E., Tuomilehto, J., et al. (2017) · Journal of the American Medical Directors Association · doi:10.1016/j.jamda.2017.09.020 · Cited by 93 · see citing works
Self-citationZülke, A. E., Pabst, A., Luppa, M., Roehr, S., Seidling, H., Oey, A., Cardona, M. I., Blotenberg, I., Bauer, A., Weise, S., et al. (2024) · Alzheimer's & Dementia · doi:10.1002/alz.13486 · Cited by 90 · see citing works
Brodaty, H., Chau, T., Heffernan, M., Ginige, J. A., Andrews, G., Millard, M., Sachdev, P. S., Anstey, K. J., Lautenschlager, N. T., McNeil, J. J., et al. (2025) · Nature Medicine · doi:10.1038/s41591-024-03351-6 · Cited by 85 · see citing works
Cognitive decline in old age: Separating retest effects from the effects of growing older.
Wilson, R. S., Li, Y., Bienias, L., & Bennett, D. A. (2006) · Psychology and Aging · doi:10.1037/0882-7974.21.4.774 · Cited by 77 · see citing works
Espeland, M. A., Brunner, R. L., Hogan, P. E., Rapp, S. R., Coker, L. H., Legault, C., Granek, I. A., Resnick, S. M., & for the Women's Health Initiative Study of Cognitive Aging Study Group (2010) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.2010.02953.x · Cited by 57 · see citing works
Self-citationLangbaum, J. B. S., Ellison, N., Caputo, A., Thomas, R. G., Langlois, C. M., Riviere, M., Graf, A., López, C. L., Reiman, E. M., Tariot, P. N., et al. (2020) · Alzheimer s Research & Therapy · doi:10.1186/s13195-020-00633-2 · Cited by 40 · see citing works
Systematic Multi-Domain Alzheimer’s Risk Reduction Trial (SMARRT): Study Protocol
Yaffe, K. S., Barnes, D. E., Rosenberg, D. E., Dublin, S., Kaup, A. R., Ludman, E. J., Vittinghoff, E., Peltz, C. B., Renz, A. D., Adams, K. J., et al. (2018) · Journal of Alzheimer s Disease · doi:10.3233/jad-180634 · Cited by 38 · see citing works
Cognitive composite score association with Alzheimer’s disease plaque and tangle pathology
Malek-Ahmadi, M., Chen, K.-W., Perez, S. E., He, A., & Mufson, E. (2018) · Alzheimer's Research & Therapy · doi:10.1186/s13195-018-0401-z · Cited by 34 · see citing works
Rodrigues, B., Coelho, A., Portugal‐Nunes, C., Magalhães, R. J. D. S., Moreira, P. S., Castanho, T. C., Amorim, L., Marques, P., Soares, J. M., Sousa, N., et al. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.00786 · Cited by 32 · see citing works
Zheng, B., Udeh‐Momoh, C. T., Watermeyer, T., Loots, C. A. D. J., Ford, J. K., Robb, C. E., Giannakopoulou, P., Ahmadi‐Abhari, S., Baker, S. A., Novak, G., et al. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.909614 · Cited by 31 · see citing works
An 18‐month multimodal intervention trial for preventing dementia: J‐MINT PRIME Tamba
Oki, Y., Osaki, T., Kumagai, R., Murata, S., Encho, H., Ono, R., Yasuda, H., & Kowa, H. (2024) · Alzheimer's & Dementia · doi:10.1002/alz.14170 · Cited by 31 · see citing works
Moon, S. Y., Park, Y. K., Jeong, J. H., Hong, C. H., Jung, J., Na, H. R., Cho, S. H., Kim, H. S., Song, H., Choi, M., et al. (2025) · Alzheimer s & Dementia · doi:10.1002/alz.14517 · Cited by 30 · see citing works
Soldevila‐Domenech, N., Ayala‐García, A., Barbera, M., Lehtisalo, J., Forcano, L., Diaz-Ponce, A. M., Zwan, M. D., van der Flier, W. M., Ngandu, T., Kivipelto, M., et al. (2025) · Alzheimer s Research & Therapy · doi:10.1186/s13195-025-01691-0 · Cited by 26 · see citing works
Self-citationHarrison, T. M., Ward, T. J., Taggett, J. Z., Maillard, P., Lockhart, S. N., Jung, Y., Lovato, L., Koeppe, R. A., Jagust, W. J., Harvey, D. J., et al. (2024) · Alzheimer s & Dementia · doi:10.1002/alz.14399 · Cited by 16 · see citing works
Self-citationWhitmer, R. A., Baker, L. D., Carrillo, M. C., Snyder, H. M., Cleveland, M. L., Gitelman, D. R., Kivipelto, M., Leng, X., Lovato, L., Papp, K. V., et al. (2025) · Alzheimer s & Dementia · doi:10.1002/alz.70351 · Cited by 14 · see citing works
Self-citationBaseline cognition and demographic, lifestyle, and cardiovascular risk factors in US POINTER
Papp, K. V., Farias, S. T., Howard, M. J., Thro, A. A., Ngandu, T., Caudle, B. A., Sachs, B. C., Chan, M., Krueger, K. R., Hartman, E. R. T., et al. (2025) · Alzheimer s & Dementia · doi:10.1002/alz.70216 · Cited by 4 · see citing works
Self-citationThe U.S. POINTER neurovascular ancillary study: Study design and methods
Brinkley, T. E., Garcia, K. R., Mitchell, G. F., Tegeler, C. H., Sarwal, A., Bennett, J., Kitzman, D. W., Leng, I., Baker, L. D., Espeland, M. A., et al. (2025) · Alzheimer s & Dementia · doi:10.1002/alz.14574 · Cited by 3 · see citing works
Self-citationMolina‐Henry, D. P., Baker, L. D., Woolard, N., et al. (2020) · Alzheimer s & Dementia · doi:10.1002/alz.041440 · Cited by 1 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Nan, J., Purpura, S., Jaiswal, S., Afshar, H., Maric, V., Manchanda, J. K., Taylor, C. T., Ramanathan, D., & Mishra, J. (2026) · NPP—Digital Psychiatry and Neuroscience · doi:10.1038/s44277-026-00062-3 · Cited by 1 · see citing works
“There is much evidence that lifestyle intervention and adoption of healthy lifestyles promotes cognitive health and staves off cognitive decline [85 – 92], but again effects of personalized lifestyle optimization for cognition in depression have not been studied.”
- Authors
- Baker, L. D., Espeland, M. A., Whitmer, R. A., Snyder, H. M., Leng, X., Lovato, L., Papp, K. V., Yu, M., Kivipelto, M., Alexander, A. S., Antkowiak, S., Cleveland, M., Day, C., Elbein, R., Tomaszewski Farias, S., Felton, D., Garcia, K. R., Gitelman, D. R., Graef, S., Howard, M., Katula, J., Lambert, K., Matongo, O., McDonald, A. M., Pavlik, V., Raman, R., Salloway, S., Tangney, C., Ventrelle, J., Wilmoth, S., Willliams, B. J., Wing, R., Woolard, N., & Carrillo, M. C.
- Affiliations
- Wake Forest University Health Sciences (US)
- University of California, Davis (US)
- Alzheimer's Association (US)
- Brigham and Women's Hospital (US)
- Baylor College of Medicine (US)
- University of Eastern Finland (FI)
- Kelsey Research Foundation (US)
- Department of Neurology, University of California, Davis, Sacramento
- Advocate Health Care (US)
- Rush University Medical Center (US)
- Wake Forest University (US)
- University of Southern California (US)
- Brown University (US)
- Division of Medical and Scientific Relations, Alzheimer’s Association, Chicago, Illinois
- Corresponding author
- Baker, Laura D.
- Espeland, Mark A.
- ORCID
- Venue
- JAMA
- Publisher
- American Medical Association (AMA)
- Published
- 2025-08-26
- Volume
- 334
- Issue
- 8
- Pages
- 681
- ISSN
- 0002-9955 (ISSN-L)
- 0098-7484
- PMC
- PMC12305445
- OpenAlex
- W4412703754
- Cited by
- 270
- References
- 38
- Citations by year
- 2026: 216 · 2025: 54
- FWCI
- 180.78
- Type
- journal article
- Language
- en
- Open access
- green
- pmc.ncbi.nlm.nih.gov
- Locations
- JAMA (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (submittedVersion)
- Funders
- National Institute on Aging (P30AG072947)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Nutritional Studies and Diet
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Cognitive Abilities and Testing
- Keywords
- lifestyle intervention, cognitive decline, dementia prevention, older adults, global cognitive function, executive function, episodic memory, processing speed, APOE ε4, physical activity, cognitive activity, healthy eating, social engagement, cardiovascular monitoring, sedentary lifestyle, cardiometabolic risk, modifiable risk factors, non-pharmacological treatment
- MeSH terms
- Diet, Healthy, Healthy Aging, Aged, Cognition, Dementia, Female, Follow-Up Studies, Humans, Male, Middle Aged, Exercise, Single-Blind Method, Treatment Outcome, Sedentary Behavior, Social Participation, Cognitive Dysfunction
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
