Evidence map›Paper›PMID 27482534›Full record

ArticleeNeuro

An Alzheimer's Disease Genetic Risk Score Predicts Longitudinal Thinning of Hippocampal Complex Subregions in Healthy Older Adults.

Theresa M Harrison, Zanjbeel Mahmood, Edward P Lau, Alexandra M Karacozoff, Alison C Burggren, Gary W Small, Susan Y Bookheimer

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

Article in eNeuro. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
48citing papers in PubMed, 1 pooled it
6.4field-weighted citation impact, top 3% 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

48 citing papers in PubMed, 1 synthesis or guideline pooled it, 73 citations in OpenAlex.

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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

7 authors at 1 institution in 2 countries.

Theresa M HarrisonNeuroscience Interdepartmental Graduate Program, University of California, Los Angeles, Los Angeles, California 90095; Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, California 90095.ORCID 0000-0002-2036-3496
Zanjbeel MahmoodDepartment of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles , Los Angeles, California 90095.
Edward P LauDepartment of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles , Los Angeles, California 90095.
Alexandra M KaracozoffStaglin IMHRO Center for Cognitive Neuroscience, University of California, Los Angeles , Los Angeles, California 90095.
Alison C BurggrenDepartment of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles , Los Angeles, California 90095.ORCID 0000-0002-8322-0118
Gary W SmallDepartment of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, California 90095; Semel Institute for Neuroscience and Human Behaviors, University of California, Los Angeles, Los Angeles, California 90095; UCLA Longevity Center, University of California, Los Angeles, Los Angeles, California 90095.
Susan Y BookheimerDepartment of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, California 90095; Staglin IMHRO Center for Cognitive Neuroscience, University of California, Los Angeles, Los Angeles, California 90095; Semel Institute for Neuroscience and Human Behaviors, University of California, Los Angeles, Los Angeles, California 90095.
University of California, Los Angeles · US

Funding

FUNCTIONAL MRI FOR EARLY DIAGNOSIS OF ALZHEIMER'SR01AG013308 · NIA · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI BOOKHEIMER, SUSAN Y · 1995 to 2011
$4.5M
Effects of heavy adolescent cannabis use on brain morphology in agingK01DA034728 · NIDA · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI BURGGREN, ALISON CLEMENTS · 2013 to 2017
$776k
Beyond APOE: A Polygenic Approach to Risk for Alzheimer's Disease in HumansF31AG047041 · NIA · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI HARRISON, THERESA M. · 2014 to 2016
$96k
NIA NIH HHS F31 AG047041NIA NIH HHS R01 AG013308NIDA NIH HHS K01 DA034728
6 · The paper itself

Abstract

Variants at 21 genetic loci have been associated with an increased risk for Alzheimer's disease (AD). An important unresolved question is whether multiple genetic risk factors can be combined to increase the power to detect changes in neuroimaging biomarkers for AD. We acquired high-resolution structural images of the hippocampus in 66 healthy, older human subjects. For 45 of these subjects, longitudinal 2-year follow-up data were also available. We calculated an additive AD genetic risk score for each participant and contrasted this with a weighted risk score (WRS) approach. Each score included APOE (apolipoprotein E), CLU (clusterin), PICALM (phosphatidylinositol binding clathrin assembly protein), and family history of AD. Both unweighted risk score (URS) and WRS correlated strongly with the percentage change in thickness across the whole hippocampal complex (URS: r = -0.40; p = 0.003; WRS: r = -0.25, p = 0.048), driven by a strong relationship to entorhinal cortex thinning (URS: r = -0.35; p = 0.009; WRS: r = -0.35, p = 0.009). By contrast, at baseline the risk scores showed no relationship to thickness in any hippocampal complex subregion. These results provide compelling evidence that polygenic AD risk scores may be especially sensitive to structural change over time in regions affected early in AD, like the hippocampus and adjacent entorhinal cortex. This work also supports the paradigm of studying genetic risk for disease in healthy volunteers. Together, these findings will inform clinical trial design by supporting the idea that genetic prescreening in healthy control subjects can be useful to maximize the ability to detect an effect on a longitudinal neuroimaging endpoint, like hippocampal complex cortical thickness.

Indexed as

Genetic Predisposition to DiseaseAgingAlzheimer DiseaseApolipoproteins EClinical Trials as TopicClusterinFemaleFollow-Up StudiesHippocampusHumansLongitudinal StudiesMagnetic Resonance ImagingMaleMental Status ScheduleMiddle AgedMonomeric Clathrin Assembly ProteinsApolipoproteins ECLU protein, humanClusterinMonomeric Clathrin Assembly ProteinsPICALM protein, humanclinical trialsnormal agingpolygenic risk scorepreclinical Alzheimer's diseasestructural MRI

Identifiers

PMID27482534
PMCPMC4945997
OpenAlexW2461189143

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.