Evidence map›Paper›PMID 37483002›Full record

ArticleJournal of Alzheimer's disease : JAD2023

Incidence of Alzheimer's Disease in Men with Late-Life Hypertension Is Ameliorated by FOXO3 Longevity Genotype.

Randi Chen, Brian J Morris, Timothy A Donlon, G Webster Ross, Kalpana J Kallianpur, Richard C Allsopp, Kazuma Nakagawa, Bradley J Willcox, Kamal H Masaki

Open access · bronzeAbstract read
In one paragraph

Article in Journal of Alzheimer's disease : JAD, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
0.7field-weighted citation impact, top 28% of its field
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

7 citing papers in PubMed, 8 citations in OpenAlex.

  1. Longevity-associatedTranslational lung cancer research · 2026
    Article
  2. Review
  3. Review
  4. Review
  5. Article
  6. Article
  7. The role of Foxo3a in neuron-mediated cognitive impairment.Frontiers in molecular neuroscience · 2024
    Review
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

9 authors at 3 institutions in 2 countries.

Randi ChenNIH Center of Biomedical Reseach Excellence on Aging, Kuakini Medical Center, Honolulu, HI, USA.
Brian J MorrisNIH Center of Biomedical Reseach Excellence on Aging, Kuakini Medical Center, Honolulu, HI, USA.
Timothy A DonlonNIH Center of Biomedical Reseach Excellence on Aging, Kuakini Medical Center, Honolulu, HI, USA.
G Webster RossDepartment of Geriatric Medicine, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI, USA.
Kalpana J KallianpurNIH Center of Biomedical Reseach Excellence on Aging, Kuakini Medical Center, Honolulu, HI, USA.
Richard C AllsoppInstitute for Biogenesis Research, University of Hawaii, Honolulu, HI, USA.
Kazuma NakagawaNIH Center of Biomedical Reseach Excellence on Aging, Kuakini Medical Center, Honolulu, HI, USA.
Bradley J WillcoxNIH Center of Biomedical Reseach Excellence on Aging, Kuakini Medical Center, Honolulu, HI, USA.
Kamal H MasakiNIH Center of Biomedical Reseach Excellence on Aging, Kuakini Medical Center, Honolulu, HI, USA.
University of Hawaiʻi at Mānoa · USBiogen (United States) · USKuakini Medical Center · US

Funding

Epidemiology of Brain Aging in the Very OldU01AG019349 · NIA · KUAKINI MEDICAL CENTER · PI WHITE, LON RAY · 2001 to 2011
$14.0M
Productive and Leisure Activities and Cognition in Later LifeP20GM125526 · NIGMS · KUAKINI MEDICAL CENTER · PI LEE, YEONJUNG · 2019 to 2023
$12.0M
FOXO3 Genotype, InflammAging, Cardiovascular Disease, and Dementia. Kuakini Hawaii Lifespan Study III. Administrative Supplement.R01AG027060 · NIA · KUAKINI MEDICAL CENTER · PI Gregory J. Tranah, BRADLEY JOHN WILLCOX · 2005 to 2026
$8.1M
Energy-sensing Pathways, Healthy Aging and LongevityR01AG038707 · NIA · KUAKINI MEDICAL CENTER · PI WILLCOX, BRADLEY JOHN · 2011 to 2014
$1.4M
HONOLULU ASIA AGING STUDYN01AG042149 · NIA · KUAKINI MEDICAL CENTER · PI FOLEY, DANIEL · 1994 to 2000
$1.1M
HONOLULU HEART PROGRAMN01HC005102 · HC · KUAKINI MEDICAL CENTER · PI CURB, JESS DAVID · 1990 to 1997
–
NHLBI NIH HHS N01 HC005102NIA NIH HHS N01 AG042149NIA NIH HHS R01 AG027060NIA NIH HHS R01 AG038707NIA NIH HHS U01 AG019349NIGMS NIH HHS P20 GM125526
6 · The paper itself

Abstract

backgroundIt is well established that mid-life hypertension increases risk of dementia, whereas the association of late-life hypertension with dementia is unclear.

objectiveTo determine whether FOXO3 longevity-associated genotype influences the association between late-life hypertension and incident dementia.

methodsSubjects were 2,688 American men of Japanese ancestry (baseline age: 77.0±4.1 years, range 71-93 years) from the Kuakini Honolulu Heart Program. Status was known for FOXO3 rs2802292 genotype, hypertension, and diagnosis of incident dementia to 2012. Association of FOXO3 genotype with late-life hypertension and incident dementia, vascular dementia (VaD) and Alzheimer's disease (AD) was assessed using Cox proportional hazards models.

resultsDuring 21 years of follow-up, 725 men were diagnosed with all-cause dementia, 513 with AD, and 104 with VaD. A multivariable Cox model, adjusting for age, education, APOEɛ4, and cardiovascular risk factors, showed late-life hypertension increased VaD risk only (HR = 1.71, 95% CI = 1.08-2.71, p = 0.022). We found no significant protective effect of FOXO3 longevity genotype on any type of dementia at the population level. However, in a full Cox model adjusting for age, education, APOEɛ4, and other cardiovascular risk factors, there was a significant interaction effect of late-life hypertension and FOXO3 longevity genotype on incident AD (β= -0.52, p = 0.0061). In men with FOXO3 rs2802292 longevity genotype (TG/GG), late-life hypertension showed protection against AD (HR = 0.72; 95% CI = 0.55-0.95, p = 0.021). The non-longevity genotype (TT) (HR = 1.16; 95% CI = 0.90-1.51, p = 0.25) had no protective effect.

conclusionThis longitudinal study found late-life hypertension was associated with lower incident AD in subjects with FOXO3 genotype.

Indexed as

Alzheimer DiseaseDementia, VascularHypertensionAgedAged, 80 and overForkhead Box Protein O3GenotypeHumansIncidenceLongitudinal StudiesMaleRisk FactorsForkhead Box Protein O3FOXO3 protein, humanAlzheimer’s diseaseFOXO3geneticshypertensionlongitudinal studyvascular dementia

Identifiers

PMID37483002
PMCPMC10578238
OpenAlexW4384695236

What OpenQuestion holds

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LicenceCC BY-NC
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Registered trials

None linked

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.