Evidence map›Paper›PMID 40874669›Full record

ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2025

Genetically proxied blood pressure, vascular brain injury, and Alzheimer's disease pathology.

Iyas Daghlas, Michelle R Caunca, Lincoln M P Shade, Malik Nassan, Kristine Yaffe, David W Fardo, Dipender Gill

Abstract read
In one paragraph

Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Genetically proxied blood pressure, vascular brain injury, and Alzheimer's disease pathology.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    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

7 authors.

Iyas DaghlasDepartment of Neurology, University of California San Francisco, San Francisco, California, USA.ORCID 0000-0001-6924-0641
Michelle R CauncaDepartment of Neurology, University of California San Francisco, San Francisco, California, USA.
Lincoln M P ShadeDepartment of Biostatistics, College of Public Health, University of Kentucky, Lexington, Kentucky, USA.
Malik NassanMesulam Center for Cognitive Neurology and Alzheimer's Disease, Northwestern University, Chicago, Illinois, USA.
Kristine YaffeDepartment of Psychiatry and Behavioral Sciences, University of California San Francisco, San Francisco, California, USA.
David W FardoDepartment of Biostatistics, College of Public Health, University of Kentucky, Lexington, Kentucky, USA.
Dipender GillDepartment of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.

Funding

Research Education Core FP30AG072977 · NIA · NORTHWESTERN UNIVERSITY AT CHICAGO · PI ROBERT J VASSAR · 2021 to 2026
$26.3M
University of Kentucky Alzheimer's Disease Research CenterP30AG072946 · NIA · UNIVERSITY OF KENTUCKY · PI BRIAN Timothy GOLD · 2021 to 2026
$23.5M
Genetic Architecture of Pure Alzheimer's Disease and Mixed PathologyR01AG082730 · NIA · UNIVERSITY OF WASHINGTON · PI David William Fardo, Shubhabrata Mukherjee · 2023 to 2026
$4.0M
Population Based Research for Alzheimer's Innovation (POP BRAIN)R35AG071916 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI YAFFE, KRISTINE · 2021 to 2024
$3.8M
Lifecourse CVD Risk and Midlife Cognitive Trajectories and Brain Aging: Implications for Alzheimer's and Dementia PreventionR01AG063887 · NIA · NORTHERN CALIFORNIA INSTITUTE/RES/EDU · PI YAFFE, KRISTINE · 2019 to 2022
$3.0M
Lifecourse Predictors and Mechanisms of Early Clinical ADRD among Black and White Adults in their SixtiesR01AG091431 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Kristine Yaffe · 2025 to 2026
$2.6M
Hypertension, Blood Pressure Targets, and Alzheimer’s Disease and Dementia Risk and Disparities among Nationally Representative US VeteransR01AG085481 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Nestor Sebastian Calonico, Kristine Yaffe · 2024 to 2026
$2.4M
Genetic Architecture of Aging-Related TDP-43 and Mixed Pathology DementiaRF1AG082339 · NIA · UNIVERSITY OF KENTUCKY · PI FARDO, DAVID WILLIAM, NELSON, PETER T. · 2023 to 2023
$1.7M
Elucidating Shared Risk of Brain Arteriolosclerosis and Related Pathologies with Multiple 'omics ModalitiesF30NS124136 · NINDS · UNIVERSITY OF KENTUCKY · PI SHADE, LINCOLN · 2022 to 2025
$143k
NIA NIH HHS P30 AG072946NIA NIH HHS P30 AG072977NIA NIH HHS R01 AG063887NIA NIH HHS R01 AG082730NIA NIH HHS R01AG082730NIA NIH HHS R01 AG085481NIA NIH HHS R01 AG091431NIA NIH HHS R35 AG071916NIA NIH HHS R35AG071916NIA NIH HHS RF1 AG082339NINDS NIH HHS F30 NS124136NINDS NIH HHS F30NS124136
6 · The paper itself

Abstract

introductionLower blood pressure (BP) is linked to reduced dementia risk, though it is uncertain whether this benefit stems solely from mitigating vascular brain injury (VBI) or also extends to directly influencing Alzheimer's disease (AD) pathology. We leveraged Mendelian randomization (MR) to assess whether lifelong lower BP is causally associated with neuropathological correlates of VBI and AD.

methodsWe identified genetic proxies for systolic and diastolic BP (n = 1,028,980) and applied them in MR analyses of post mortem neuropathological measures of VBI and AD (n = 6363-7786).

resultsGenetically proxied lower systolic BP associated with reduced risk of all VBI measures, including atherosclerosis, arteriolosclerosis, gross infarcts, and microinfarcts. There was no evidence for associations between systolic BP and AD pathology, including measures of amyloid and tau pathology. Diastolic BP analyses yielded similar results. DISCUSSION: These findings suggest that BP-lowering protects against dementia by mitigating VBI rather than by directly affecting AD pathology. HIGHLIGHTS: It is uncertain whether blood pressure impacts dementia risk solely through its effects on blood vessel health, or whether it also impacts Alzheimer's disease (AD) pathology. We performed a Mendelian randomization study using genetic predictors of blood pressure applied to a unique autopsy study of neuropathological correlates of both vascular brain injury and AD pathology. We found evidence that genetically lowered blood pressure solely impacts vascular brain injury, with no effects on AD pathology.

Indexed as

Alzheimer DiseaseBlood PressureCerebrovascular TraumaAgedBrainFemaleHumansMaleMendelian Randomization AnalysisAlzheimer's dementiaatherosclerosisblood pressureMendelian randomizationsystolic blood pressurevascular dementia

Identifiers

PMID40874669
PMCPMC12276072

What OpenQuestion holds

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Registered trials

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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.