Evidence map›Paper›PMID 41936382›Full record

ArticleThe lancet. Healthy longevity2026

Risk factors for early-onset and late-onset dementia: a prospective cohort study.

Katherine Giorgio, John J Stephen, Maxwell Mansolf, Elizabeth A Peterson, Alden L Gross, Emily M Briceño, Deborah A Levine, Catherine Helmer, Stéphanie Debette, Aïcha Soumaré and 30 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The lancet. Healthy longevity, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Review
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

40 authors.

Katherine GiorgioDivision of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis, MN, USA.
John J StephenDepartment of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Maxwell MansolfDepartment of Medical Social Science, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Elizabeth A PetersonDepartment of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Alden L GrossDepartment of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
Emily M BriceñoDepartment of Physical Medicine & Rehabilitation, University of Michigan Medical School, Ann Arbor, MI, USA.
Deborah A LevineDepartment of Internal Medicine, Department of Neurology, University of Michigan Medical School, Ann Arbor, MI, USA.
Catherine HelmerBordeaux Population Health, University of Bordeaux, INSERM U1219, Bordeaux, France.
Stéphanie DebetteBordeaux Population Health, University of Bordeaux, INSERM U1219, Bordeaux, France.
Aïcha SoumaréBordeaux Population Health, University of Bordeaux, INSERM U1219, Bordeaux, France.
M Arfan IkramDepartment of Epidemiology, Erasmus MC University Medical Center, Rotterdam, Netherlands.
Frank J WoltersDepartment of Epidemiology, Erasmus MC University Medical Center, Rotterdam, Netherlands.
Sudha SeshadriGlenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA; The Framingham Heart Study, Framingham, MA, USA.
Claudia L SatizabalGlenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA; The Framingham Heart Study, Framingham, MA, USA.
Jayandra Jung HimaliGlenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA; The Framingham Heart Study, Framingham, MA, USA; Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
Lenore J LaunerNational Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
David LiNational Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
Djass MbangdadjiNational Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
Donald M Lloyd-JonesThe Framingham Heart Study, Framingham, MA, USA; Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.
Farzaneh A SorondDepartment of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Lihui ZhaoDepartment of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Oscar L LopezDepartment of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Suzanne E JuddDepartments of Health Behavior and Biostatistics, School of Public Health, University of Alabama at Birmingham, Birmingham, AL, USA.
Timothy M HughesDepartment of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
Vilmundur GuðnasonIcelandic Heart Association, Kopavoguar, Iceland; Faculty of Medicine, University of Reykjavik, Reykjavik, Iceland.
Allison E AielloRobert N Butler Columbia Aging Center, Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA.
Alison FohnerDepartment of Epidemiology, University of Washington School of Public Health, Seattle, WA, USA.
Archana Singh-ManouxUniversité Paris Cité, Inserm 1153, Paris, France; Faculty of Brain Sciences, University College London, UK.
Behnam SabayanDepartment of Neurology, Hennepin Healthcare Research Institute, Hennepin County Medical Center, Minneapolis, MN, USA; Department of Neurology, University of Minnesota Medical School, Minneapolis, MN, USA.
James S PankowDivision of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis, MN, USA.
Paul S de VriesHuman Genetics Center, Department of Epidemiology, School of Public Health, University of Texas Health Science Center at Houston, Houston, TX, USA.
Kristine YaffeDepartments of Psychiatry, Neurology, and Epidemiology, University of California, San Francisco, San Francisco, CA, USA.
Alexa BeiserThe Framingham Heart Study, Framingham, MA, USA; Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
Abbas DehghanImperial College London School of Public Health, London, UK; UK Dementia Research Institute at Imperial College London, London, UK.
Rachel ZmoraDepartment of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Denise ScholtensDepartment of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Pamela L LutseyDivision of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis, MN, USA.
Norrina B AllenDepartment of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Richard MacLehoseDivision of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis, MN, USA.
Sanaz SedaghatDivision of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis, MN, USA. Electronic address: sedaghat@umn.edu.

Funding

ARIC Neurocognitive Study (ARIC-NCS) Renewal 2023-2028U01HL096812 · NHLBI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI JOSEF CORESH, THOMAS H MOSLEY · 2010 to 2026
$65.7M
Institute for Clinical and Translational ResearchUL1TR001079 · NCATS · JOHNS HOPKINS UNIVERSITY · PI FORD, DANIEL ERNEST · 2013 to 2017
$60.1M
Integrting Information About Aging SurveysR01AG030153 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI Sara Adar, Alden L. Gross · 2007 to 2026
$41.7M
Subclinical Vascular Contributions to Alzheimer's Disease: The Multi-Ethnic Study of Atherosclerosis (MESA) Multisite Study of AD (Renewal)R01AG058969 · NIA · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI Timothy M. Hughes, YONGMEI LIU · 2018 to 2026
$33.4M
Wake Forest Clinical and Translational Science AwardUL1TR001420 · NCATS · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI ARD, JAMY D, FOLEY, KRISTIE L · 2015 to 2023
$32.3M
FRAMINGHAM HEART STUDY - YEAR 5 EXAM75N92019D00031 · NHLBI · BOSTON UNIVERSITY MEDICAL CAMPUS · 2019 to 2024
$29.8M
Clinical and Translational Science AwardUL1TR000040 · NCATS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI GINSBERG, HENRY N · 2012 to 2015
$26.2M
Wake Forest University School of Medicine Alzheimer's Disease Research CenterP30AG072947 · NIA · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI SUZANNE CRAFT · 2021 to 2026
$24.3M
South Texas Alzheimer's Disease Research CenterP30AG066546 · NIA · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI Agustin Ruiz Laza · 2021 to 2026
$24.0M
PRECURSORS OF STROKE INCIDENCE AND PROGNOSISR01NS017950 · NINDS · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI Hugo Javier Aparicio, Jose Rafael Romero · 1985 to 2026
$22.9M
Task Area A Core Study Operations.Task Area A shall encompass annual follow-up of cohort members, clinical endpoints ascertainment, study coordination activities, maintenance of the database and biosp75N92020D00001 · NHLBI · UNIVERSITY OF WASHINGTON · PI MCCLELLAND, ROBYN LEAGH · 2020 to 2025
$17.2M
THE ATHEROSCLEROSIS RISK IN COMMUNITIES (ARIC) STUDY - COORDINATING CENTER - TASK AREA B.2 AND B.375N92022D00001 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI COUPER, DAVID · 2022 to 2025
$13.7M
NCATS NIH HHS UL1 TR000040NCATS NIH HHS UL1 TR001079NCATS NIH HHS UL1 TR001420NHLBI NIH HHS 75N92019D00031NHLBI NIH HHS 75N92020D00001NHLBI NIH HHS 75N92020D00002NHLBI NIH HHS 75N92020D00003NHLBI NIH HHS 75N92020D00004NHLBI NIH HHS 75N92020D00005NHLBI NIH HHS 75N92020D00006NHLBI NIH HHS 75N92020D00007NHLBI NIH HHS 75N92022D00001NHLBI NIH HHS 75N92022D00002NHLBI NIH HHS 75N92022D00003NHLBI NIH HHS 75N92022D00004NHLBI NIH HHS 75N92022D00005NHLBI NIH HHS HHSN268201500001CNHLBI NIH HHS HHSN268201500001INHLBI NIH HHS HHSN268201500003CNHLBI NIH HHS HHSN268201500003INHLBI NIH HHS N01 HC025195NHLBI NIH HHS N01 HC095159NHLBI NIH HHS N01 HC095160NHLBI NIH HHS N01 HC095161NHLBI NIH HHS N01 HC095162NHLBI NIH HHS N01 HC095163NHLBI NIH HHS N01 HC095164NHLBI NIH HHS N01 HC095165NHLBI NIH HHS N01 HC095166NHLBI NIH HHS N01 HC095167NHLBI NIH HHS N01 HC095168NHLBI NIH HHS N01 HC095169NHLBI NIH HHS U01 HL096812NHLBI NIH HHS U01 HL096814NHLBI NIH HHS U01 HL096899NHLBI NIH HHS U01 HL096902NHLBI NIH HHS U01 HL096917NIA NIH HHS K23 AG080035NIA NIH HHS P30 AG066546NIA NIH HHS P30 AG072947NIA NIH HHS R01 AG020098NIA NIH HHS R01 AG030153NIA NIH HHS R01 AG049607NIA NIH HHS R01 AG054069NIA NIH HHS R01 AG054076NIA NIH HHS R01 AG058969NIA NIH HHS R01 AG059421NIA NIH HHS R01 AG059727NIA NIH HHS R01 AG063887NIA NIH HHS R01 AG066524NIA NIH HHS R01 AG068410NIA NIH HHS R01 AG070953NIA NIH HHS R01 AG079108NIA NIH HHS R01 AG082360NIA NIH HHS R01 AG091431NIA NIH HHS R21 AG081689NIA NIH HHS R35 AG071916NIA NIH HHS RF1 AG063507NIA NIH HHS U01 AG052409NIA NIH HHS U01 AG058589NINDS NIH HHS R01 NS017950NINDS NIH HHS R33 NS120245NINDS NIH HHS R61 NS120245NINDS NIH HHS RF1 NS136499NINDS NIH HHS U01 NS125513NINDS NIH HHS UF1 NS125513
6 · The paper itself

Abstract

backgroundEarly-onset dementia (onset before age 65 years) is an important health concern, but much of our understanding of its risk factors is inferred from studies of late-onset dementia (onset after age 65 years). We investigated associations between several demographic, clinical, and lifestyle factors with early-onset dementia and compared those estimates against their associations with late-onset dementia.

methodsData from five community-based longitudinal cohort studies from the UK and USA were pooled and rigorously harmonised: UK Biobank, Atherosclerosis Risk in Communities Study, Framingham Heart Study, Multi-Ethnic Study of Atherosclerosis, and Whitehall II Study. Dementia was ascertained via hospitalisation and death records with or without clinical assessments according to each cohort's protocol. Risk factors included sex, self-reported race or ethnicity (Hispanic, White, Black, Asian, and Other), low education, hypertension, diabetes, obesity, hypercholesterolaemia, depression, alcohol overconsumption, smoking, and physical inactivity. Cox regression models, with age as the timescale and time-varying coefficients, were fitted to estimate hazard ratios (HRs) for early-onset dementia and late-onset dementia and to test whether the HRs differed by age of onset.

findingsIn 544 442 participants, there were 807 incident early-onset dementia cases and 14 253 incident late-onset dementia cases over a median follow-up of 13·7 years (IQR 12·9-14·4). Female participants had a lower hazard of early-onset dementia compared with males (HR 0·70 [95% CI 0·61-0·80]). Black versus White race (1·61 [1·23-2·11]), grade school education or less (1·99 [1·67-2·38]), diabetes (2·45 [1·99-3·03]), depression (2·73 [2·34-3·20]), smoking (1·86 [1·56-2·22]), obesity (1·24 [1·04-1·48]), physical inactivity (1·33 [1·11-1·59]), and alcohol overconsumption (1·22 [1·01-1·47]) were independently associated with higher hazards of early-onset dementia. Hypertension stage 1 (HR 1·19 [95% CI 0·97-1·47]), hypertension stage 2 (1·16 [0·94-1·43]), and hypercholesterolaemia (1·11 [0·92-1·34]) had positive effect estimates but were not statistically significant. All risk factors had stronger associations with early-onset dementia than with late-onset dementia except race, physical inactivity, and alcohol overconsumption.

interpretationOur findings demonstrate the importance of modifiable risk factors in the development of early-onset dementia and guide future research for identifying high-priority targets for primary prevention.

fundingUS National Institutes of Health, the National Institute for Neurologic Disorders and Stroke, and the National Institute of Aging.

Indexed as

DementiaAgedAge of OnsetFemaleHumansLife StyleLongitudinal StudiesMaleMiddle AgedProspective StudiesRisk FactorsUnited KingdomUnited States

Identifiers

PMID41936382
PMCPMC13560949

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.