Evidence map›Paper›PMID 35005200›Full record

ArticleAlzheimer's & dementia (Amsterdam, Netherlands)2021

Causal association of cognitive reserve on Alzheimer's disease with putative sex difference.

Hao Wang, Brin Sara Rosenthal, Carolina Makowski, Min-Tzu Lo, Ole A Andreassen, Rany M Salem, Linda K McEvoy, Mark Fiecas, Chi-Hua Chen

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Alzheimer's & dementia (Amsterdam, Netherlands), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.5field-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

3 citing papers in PubMed, 3 citations in OpenAlex.

  1. Article
  2. Article
  3. 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

9 authors at 4 institutions in 2 countries.

Hao WangCenter for Multimodal Imaging and Genetics Department of Radiology University of California San Diego La Jolla California USA.ORCID https://orcid.org/0000-0002-1518-9702
Brin Sara RosenthalCenter for Computational Biology and Bioinformatics University of California San Diego La Jolla California USA.
Carolina MakowskiCenter for Multimodal Imaging and Genetics Department of Radiology University of California San Diego La Jolla California USA.
Min-Tzu LoCenter for Multimodal Imaging and Genetics Department of Radiology University of California San Diego La Jolla California USA.
Ole A AndreassenNORMENT Centre Division of Mental Health and Addiction University of Oslo and Oslo University Hospital Oslo Norway.
Rany M SalemDepartment of Family Medicine and Public Health Division of Epidemiology University of California San Diego La Jolla California USA.
Linda K McEvoyCenter for Multimodal Imaging and Genetics Department of Radiology University of California San Diego La Jolla California USA.
Mark FiecasSchool of Public Health Division of Biostatistics University of Minnesota Minneapolis Minnesota USA.
Chi-Hua ChenCenter for Multimodal Imaging and Genetics Department of Radiology University of California San Diego La Jolla California USA.ORCID https://orcid.org/0000-0001-5318-047X
University of California System · USUniversity of California San Diego · USOslo University Hospital · NOUniversity of Minnesota · US

Funding

Alzheimer's Disease Genetics ConsortiumU01AG032984 · NIA · UNIVERSITY OF PENNSYLVANIA · PI SCHELLENBERG, GERARD DAVID · 2009 to 2024
$60.4M
Genetic architecture of the human brain and neuropsychiatric disordersR01MH118281 · NIMH · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CHEN, CHI-HUA · 2019 to 2023
$2.7M
Omic analyses for stratifying Alzheimer's subtypes and identifying novel drug targetsR56AG061163 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CHEN, CHI-HUA · 2018 to 2018
$560k
NIA NIH HHS R56 AG061163NIA NIH HHS U01 AG032984NIMH NIH HHS R01 MH118281
6 · The paper itself

Abstract

introductionSex-dependent risk factors may underlie sex differences in Alzheimer's disease (AD).

methodsUsing sex-stratified genome-wide association studies (GWAS) of AD, we evaluated associations of 12 traits with AD through polygenic risk scores (PRS) and Mendelian randomization (MR), and explored joint genetic architecture among significant traits by genomic structural equation modeling and network analysis.

resultsAD was associated with lower PRS for premorbid cognitive performance, intelligence, and educational attainment. MR showed a causal role for the cognition-related traits in AD, particularly among females. Their joint genetic components encompassed RNA processing, neuron projection development, and cell cycle pathways that overlap with cellular senescence. Cholesterol and C-reactive protein showed pleiotropy but no causality with AD. DISCUSSION: Lower cognitive reserve is causally related to AD. The stronger causal link between cognitive performance and AD in females, despite similar PRS between sexes, suggest these differences may result from gene-environmental interactions accumulated over the lifespan.

Indexed as

Alzheimer's diseasecausalitycognitive performancecognitive reserveeducational attainmentgenomic structural equation modelingintelligenceMendelian randomizationnetwork analysispolygenic risk scoresex differences

Identifiers

PMID35005200
PMCPMC8719428
OpenAlexW4206122670

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

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.