Evidence map›Paper›PMID 23535033›Full record

ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2014

Genome-wide association study of the rate of cognitive decline in Alzheimer's disease.

Richard Sherva, Yorghos Tripodis, David A Bennett, Lori B Chibnik, Paul K Crane, Philip L de Jager, Lindsay A Farrer, Andrew J Saykin, Joshua M Shulman, Adam Naj and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 110 papers, 9 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
110citing papers in PubMed, 9 pooled it
9.5field-weighted citation impact, top 2% 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

110 citing papers in PubMed, 9 syntheses or guidelines pooled it, 199 citations in OpenAlex.

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  15. Genetic drivers of progression in Alzheimer's disease are distinct from disease risk.medRxiv : the preprint server for health sciences · 2025
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50 more citing papers are in PubMed but not listed here.

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

14 authors at 5 institutions in 1 country.

Richard ShervaDepartment of Medicine (Biomedical Genetics), Boston University School of Medicine, Boston, MA, USA. Electronic address: rcgreen@genetics.med.harvard.edu.
Yorghos TripodisDepartment of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
David A BennettRush Alzheimer's Disease Center, Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA.
Lori B ChibnikProgram in Translational NeuroPsychiatric Genomics, Institute for the Neurosciences, Departments of Neurology & Psychiatry, Brigham and Women's Hospital Boston, MA, USA; Department of Neurology, Harvard Medical School, Cambridge, MA, USA; Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Paul K CraneSchool of Medicine, University of Washington, Seattle, WA, USA.
Philip L de JagerProgram in Translational NeuroPsychiatric Genomics, Institute for the Neurosciences, Departments of Neurology & Psychiatry, Brigham and Women's Hospital Boston, MA, USA; Department of Neurology, Harvard Medical School, Cambridge, MA, USA; Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Lindsay A FarrerDepartment of Medicine (Biomedical Genetics), Boston University School of Medicine, Boston, MA, USA; Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA; Departments Ophthalmology, Neurology, and Epidemiology, Boston University Schools of Medicine and Public Health, Boston, MA, USA.
Andrew J SaykinDepartment of Medical and Molecular Genetics, Center for Neuroimaging, Department of Radiology and Imaging Sciences, Melvin and Bren Simon Cancer Center, Indiana University School of Medicine, Indianapolis, IN, USA.
Joshua M ShulmanDepartments of Neurology and Molecular and Human Genetics Baylor College of Medicine Jan and Dan Duncan Neurological Research Institute, Houston, TX, USA.
Adam NajDepartment of Biostatics and Epidemiology and Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, PA, USA.
Robert C GreenDivision of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
GENAROAD Consortium
Alzheimer's Disease Neuroimaging Initiative
Alzheimer's Disease Genetics Consortium
Harvard University · USRush University Medical Center · USBoston University · USBoston Public Schools · USIndiana University – Purdue University Indianapolis · US

Funding

Alzheimer's Disease Neuroimaging Initiative - SupplementU01AG024904 · NIA · NORTHERN CALIFORNIA INSTITUTE RES &EDUC · PI WEINER, MICHAEL W · 2004 to 2015
$121.0M
National Centralized Repository for Alzheimer's Disease and Related Dementias (NCRAD)U24AG021886 · NIA · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI TATIANA M. FOROUD · 2002 to 2026
$119.8M
RECRUITMENT COREU19AG010483 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI FELDMAN, HOWARD · 2013 to 2020
$80.6M
NATIONAL ALZHEIMERS COORDINATING CENTER (NACC)U01AG016976 · NIA · UNIVERSITY OF WASHINGTON · PI KUKULL, WALTER ANTHONY · 1999 to 2020
$72.8M
Alzheimer's Disease Genetics ConsortiumU01AG032984 · NIA · UNIVERSITY OF PENNSYLVANIA · PI SCHELLENBERG, GERARD DAVID · 2009 to 2024
$60.4M
Research Education ComponentP30AG010133 · NIA · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI SAYKIN, ANDREW J · 1991 to 2020
$37.3M
Neuropathology CoreP30AG013846 · NIA · BOSTON UNIVERSITY MEDICAL CAMPUS · PI KOWALL, NEIL W. · 1996 to 2020
$29.1M
UC Davis Alzheimer's Disease Core CenterP30AG010129 · NIA · UNIVERSITY OF CALIFORNIA DAVIS · PI JOHNSON, DAVID K · 1991 to 2020
$28.3M
Quality Assurance and Quality Control Project Management: Improving Submissions and Study Conduct in the Human Subjects Research Prior Approval ProcessUL1TR002529 · NCATS · INDIANA UNIVERSITY INDIANAPOLIS · PI MOE, SHARON M, WIEHE, SARAH ELIZABETH · 2018 to 2022
$27.2M
Indiana Clinical and Translational Sciences InstituteUL1TR001108 · NCATS · INDIANA UNIVERSITY INDIANAPOLIS · PI DENNE, SCOTT C., SHEKHAR, ANANTHA · 2013 to 2017
$23.3M
RISK FACTORS, PATHOLOGY, AND CLINICAL EXPRESSIONS OF ADR01AG015819 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 1998 to 2024
$21.4M
Risk Evaluation and Education for Alzheimer's Disease (REVEAL IV)R01HG002213 · NHGRI · BRIGHAM AND WOMEN'S HOSPITAL · PI GREEN, ROBERT C. · 1999 to 2012
$7.6M
NCATS NIH HHS UL1 TR001108NHGRI NIH HHS HG02213NHGRI NIH HHS R01 HG002213NHGRI NIH HHS U01 HG006375NIA NIH HHS AG027841NIA NIH HHS K01 AG030514NIA NIH HHS K08 AG034290NIA NIH HHS K24 AG027841NIA NIH HHS K25 AG041906NIA NIH HHS P30 AG010129NIA NIH HHS P30AG010129NIA NIH HHS P30 AG010133NIA NIH HHS P30 AG013846NIA NIH HHS R01 AG015819NIA NIH HHS R01 AG019771NIA NIH HHS U01 AG016976NIA NIH HHS U01 AG024904NIA NIH HHS U01AG024904NIA NIH HHS U01 AG032984NIA NIH HHS U19 AG010483NIA NIH HHS U24 AG021886NIA NIH HHS UO1 AG032984
6 · The paper itself

Abstract

backgroundSubstantial interindividual variability exists in the disease trajectories of Alzheimer's disease (AD) patients. Some decline rapidly whereas others decline slowly, and there are no known explanations for this variability. We describe the first genome-wide association study to examine rate of cognitive decline in a sample of AD patients with longitudinal measures of cognition.

methodsThe discovery sample was 303 AD cases recruited in the Alzheimer's Disease Neuroimaging Initiative and the replication sample was 323 AD cases from the Religious Orders Study and Rush Memory and Aging Project. In the discovery sample, Alzheimer's Disease Assessment Scale-cognitive subscale responses were tested for association with genome-wide single-nucleotide polymorphism (SNP) data using linear regression. We tested the 65 most significant SNPs from the discovery sample for association in the replication sample.

resultsWe identified SNPs in the spondin 1 gene (SPON1), the minor alleles of which were significantly associated with a slower rate of decline (rs11023139, P = 7.0 × 10(-11)) in the discovery sample. A SPON1 SNP 5.5 kb upstream was associated with decline in the replication sample (rs11606345, P = .002).

conclusionSPON1 has not been previously associated with AD risk, but is plausibly related because the gene product binds to the amyloid precursor protein and inhibits its cleavage by β-secretase. These data suggest that SPON1 may be associated with the differential rate of cognitive decline in AD.

Indexed as

AgedAged, 80 and overAlzheimer DiseaseApolipoprotein E4Cognition DisordersExtracellular Matrix ProteinsFemaleFollow-Up StudiesGenome-Wide Association StudyGenotypeHumansMaleNeuropsychological TestsPhenotypePolymorphism, Single NucleotideApolipoprotein E4Extracellular Matrix ProteinsSPON1 protein, humanAlzheimer's diseaseCognitive declineGWAS

Identifiers

PMID23535033
PMCPMC3760995
OpenAlexW2034937783

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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.