Evidence map›Paper›PMID 26173052›Full record

ArticlePLoS medicine2015

HHEX_23 AA Genotype Exacerbates Effect of Diabetes on Dementia and Alzheimer Disease: A Population-Based Longitudinal Study.

Wei-Li Xu, Nancy L Pedersen, Lina Keller, Grégoria Kalpouzos, Hui-Xin Wang, Caroline Graff, Bengt Winblad, Lars Bäckman, Laura Fratiglioni

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

Article in PLoS medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed, 3 pooled it
1.1field-weighted citation impact, top 22% 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

11 citing papers in PubMed, 3 syntheses or guidelines pooled it, 17 citations in OpenAlex.

  1. Pooled it
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  8. Targeting Insulin-Degrading Enzyme in Insulin Clearance.International journal of molecular sciences · 2021
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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 2 institutions in 2 countries.

Wei-Li XuAging Research Center, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet and Stockholm University, Stockholm, Sweden; Department of Epidemiology and Biostatistics, School of Public Health, Tianjin Medical University, Tianjin, China.
Nancy L PedersenDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Lina KellerAging Research Center, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet and Stockholm University, Stockholm, Sweden; Alzheimer's Disease Research Center, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.
Grégoria KalpouzosAging Research Center, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet and Stockholm University, Stockholm, Sweden.
Hui-Xin WangAging Research Center, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet and Stockholm University, Stockholm, Sweden.
Caroline GraffAlzheimer's Disease Research Center, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden; Department of Geriatric Medicine, Karolinska University Hospital, Stockholm, Sweden.
Bengt WinbladAging Research Center, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet and Stockholm University, Stockholm, Sweden; Alzheimer's Disease Research Center, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.
Lars BäckmanAging Research Center, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet and Stockholm University, Stockholm, Sweden.
Laura FratiglioniAging Research Center, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet and Stockholm University, Stockholm, Sweden; Stockholm Gerontology Research Center, Stockholm, Sweden.
Karolinska Institutet · SEStockholm University · SE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundResearch has suggested that variations within the IDE/HHEX gene region may underlie the association of type 2 diabetes with Alzheimer disease (AD). We sought to explore whether IDE genes play a role in the association of diabetes with dementia, AD, and structural brain changes using data from two community-based cohorts of older adults and a subsample with structural MRI. METHODS AND

findingsThe first cohort, which included dementia-free adults aged ≥75 y (n = 970) at baseline, was followed for 9 y to detect incident dementia (n = 358) and AD (n = 271) cases. The second cohort (for replication), which included 2,060 dementia-free participants aged ≥60 y at baseline, was followed for 6 y to identify incident dementia (n = 166) and AD (n = 121) cases. A subsample (n = 338) of dementia-free participants from the second cohort underwent MRI. HHEX_23 and IDE_9 were genotyped, and diabetes (here including type 2 diabetes and prediabetes) was assessed. In the first cohort, diabetes led to an adjusted hazard ratio (HR) of 1.73 (95% CI 1.19-2.32) and 1.66 (95% CI 1.06-2.40) for dementia and AD, respectively, among all participants. Compared to people carrying the GG genotype without diabetes, AA genotype carriers with diabetes had an adjusted HR of 5.54 (95% CI 2.40-7.18) and 4.81 (95% CI 1.88-8.50) for dementia and AD, respectively. There was a significant interaction between HHEX_23-AA and diabetes on dementia (HR 4.79, 95% CI 1.63-8.90, p = 0.013) and AD (HR 3.55, 95% CI 1.45-9.91, p = 0.025) compared to the GG genotype without diabetes. In the second cohort, the HRs were 1.68 (95% CI 1.04-2.99) and 1.64 (1.02-2.33) for the diabetes-AD and dementia-AD associations, respectively, and 4.06 (95% CI 1.06-7.58, p = 0.039) and 3.29 (95% CI 1.02-8.33, p = 0.044) for the interactions, respectively. MRI data showed that HHEX_23-AA carriers with diabetes had significant structural brain changes compared to HHEX_23-GG carriers without diabetes. No joint effects of IDE_9 and diabetes on dementia were shown. As a limitation, the sample sizes were small for certain subgroups.

conclusionsA variant in the HHEX_23 gene interacts with diabetes to be associated with a substantially increased risk of dementia and AD, and with structural brain changes among dementia-free elderly people.

Indexed as

AgedAlzheimer DiseaseComorbidityDementiaDiabetes Mellitus, Type 2GenotypeHomeodomain ProteinsHumansInsulysinLongitudinal StudiesPolymorphism, GeneticPrediabetic StateTranscription FactorsHHEX protein, humanHomeodomain ProteinsInsulysinTranscription Factors

Identifiers

PMID26173052
PMCPMC4501827
OpenAlexW1872512487

What OpenQuestion holds

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LicenceCC BY
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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.