Evidence map›Paper›PMID 40855969›Full record

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

Linkage and association of preserved cognitive function in the midwestern Amish at a higher genetic risk of Alzheimer's disease.

Daniel A Dorfsman, Michael B Prough, Alex V Gulyayev, Laura J Caywood, Jason E Clouse, Sharlene D Herington, Susan H Slifer, Larry D Adams, Renee A Laux, Yeunjoo E Song and 15 more

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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 3 papers.

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0cells of the map it votes in
3citing 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

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3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

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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

25 authors.

Daniel A DorfsmanJohn P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida, USA.
Michael B ProughJohn P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida, USA.
Alex V GulyayevJohn P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida, USA.
Laura J CaywoodJohn P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida, USA.
Jason E ClouseJohn P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida, USA.
Sharlene D HeringtonJohn P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida, USA.
Susan H SliferJohn P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida, USA.
Larry D AdamsJohn P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida, USA.
Renee A LauxDepartment of Population and Quantitative Health Sciences, School of Medicine, Case Western Reserve University, Cleveland, Ohio, USA.
Yeunjoo E SongDepartment of Population and Quantitative Health Sciences, School of Medicine, Case Western Reserve University, Cleveland, Ohio, USA.
Audrey LynnDepartment of Population and Quantitative Health Sciences, School of Medicine, Case Western Reserve University, Cleveland, Ohio, USA.
Sarada L FuzzellDepartment of Population and Quantitative Health Sciences, School of Medicine, Case Western Reserve University, Cleveland, Ohio, USA.
Sherri D HochstetlerDepartment of Population and Quantitative Health Sciences, School of Medicine, Case Western Reserve University, Cleveland, Ohio, USA.
Kristy MiskimenDepartment of Population and Quantitative Health Sciences, School of Medicine, Case Western Reserve University, Cleveland, Ohio, USA.
Leighanne R MainDepartment of Population and Quantitative Health Sciences, School of Medicine, Case Western Reserve University, Cleveland, Ohio, USA.
Ping WangDepartment of Population and Quantitative Health Sciences, School of Medicine, Case Western Reserve University, Cleveland, Ohio, USA.
Yining LiuDepartment of Population and Quantitative Health Sciences, School of Medicine, Case Western Reserve University, Cleveland, Ohio, USA.
Noel MooreDepartment of Population and Quantitative Health Sciences, School of Medicine, Case Western Reserve University, Cleveland, Ohio, USA.
Paula OgrockiDepartment of Neurology, School of Medicine, Case Western Reserve University, Cleveland, Ohio, USA.
Alan J LernerDepartment of Neurology, School of Medicine, Case Western Reserve University, Cleveland, Ohio, USA.
Jeffery M VanceJohn P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida, USA.
Michael L CuccaroJohn P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida, USA.
Jonathan L HainesDepartment of Population and Quantitative Health Sciences, School of Medicine, Case Western Reserve University, Cleveland, Ohio, USA.
Margaret A Pericak-VanceJohn P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida, USA.
William K ScottJohn P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida, USA.

Funding

Protective Genetic Variants for Alzheimer Disease in the AmishRF1AG058066 · NIA · CASE WESTERN RESERVE UNIVERSITY · PI HAINES, JONATHAN L, PERICAK-VANCE, MARGARET A. · 2017 to 2019
$8.2M
Protective Genetic Varients for Alzheimer Disease in the AmishR01AG058066 · NIA · CASE WESTERN RESERVE UNIVERSITY · PI Jonathan L Haines, Margaret A. Pericak-Vance · 2022 to 2026
$8.0M
NIA NIH HHS R01 AG058066NIA NIH HHS RF1 AG058066
6 · The paper itself

Abstract

introductionGenetic factors promoting cognitive preservation in high-risk older adults for Alzheimer's disease (AD) risk remain understudied. Among Midwestern Amish with elevated AD genetic risk, we hypothesized ranking sibships by mean genetic risk scores during linkage analysis would reveal loci influencing preserved cognition.

methodsWe evaluated 1855 Amish adults (≥75 years) using the Modified Mini-Mental Status Exam (3MS), classifying individuals with education-adjusted scores ≥87 as cognitively unimpaired (CU) and lower scores as impaired (CI). Non-parametric linkage analysis (NPL) on 143 sibships with ≥ 2 CU was combined with ordered-subsets analysis (OSA) to incorporate 25 known European AD risk loci.

resultsNPL-OSA and association identified linkage on chromosome 2 (rs6719884) within LINC01122 (logarithm of odds [LOD]* = 3.08) and a significant interaction on chromosome 12 (rs11063479 near KCNA5), suggesting synergy with genetic risk. DISCUSSION: These findings implicate long intergenic non-coding RNAs (lincRNAs) and potassium channel genes in maintaining cognition despite high AD risk, informing future research on protective genetic mechanisms. HIGHLIGHTS: Non-parametric linkage and ordered-subsets analysis in sibships enriched with cognitively unimpaired older adults found significant evidence of linkage on chromosome 2 within the lincRNA LINC01122, along with suggestive evidence at additional loci. Association mapping within significant and suggestively linked regions revealed a significant single nucleoride polymorphism (SNP) x AD genetic risk scores (GRS) interaction effect on chromosome 12, near the potassium channel gene KCNA5. LINC01122 is primarily brain-expressed, while KCNA5 has been linked to multiple cardiovascular phenotypes, supporting their potential role in cognitive function.

Indexed as

Alzheimer DiseaseAmishCognitionGenetic LinkageGenetic Predisposition to DiseaseAgedAged, 80 and overChromosomes, Human, Pair 12Chromosomes, Human, Pair 2FemaleHumansMaleMental Status and Dementia TestsMidwestern United StatesPolymorphism, Single NucleotideRisk FactorsRNA, Long NoncodingAlzheimer's diseaseAmish populationcognitive preservationgenetic risk scorelinkage analysisprotective variants

Identifiers

PMID40855969
PMCPMC12378373

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