Healthy versus entorhinal cortical atrophy identification in asymptomatic APOE4 carriers at risk for Alzheimer's disease

Kyoko Konishi, Ridha Joober, Judes Poirier, Kathleen MacDonald, Mallar Chakravarty, Raihaan Patel, John C.S. Breitner, Véronique D. Bohbot

Research output: Contribution to journalArticle

Abstract

Early detection of Alzheimer's disease (AD) has been challenging as current biomarkers are invasive and costly. Strong predictors of future AD diagnosis include lower volume of the hippocampus and entorhinal cortex, as well as the ϵ4 allele of the Apolipoprotein E gene (APOE) gene. Therefore, studying functions that are critically mediated by the hippocampus and entorhinal cortex, such as spatial memory, in APOE ϵ4 allele carriers, may be key to the identification of individuals at risk of AD, prior to the manifestation of cognitive impairments. Using a virtual navigation task developed in-house, specifically designed to assess spatial versus non-spatial strategies, the current study is the first to differentiate functional and structural differences within APOE ϵ4 allele carriers. APOE ϵ4 allele carriers that predominantly use nonspatial strategies have decreased fMRI activity in the hippocampus and increased atrophy in the hippocampus, entorhinal cortex, and fimbria compared to APOE ϵ4 allele carriers who use spatial strategies. In contrast, APOE ϵ4 allele carriers who use spatial strategies have grey matter levels comparable to non-APOE ϵ4 allele carriers. Furthermore, in a leave-one-out analysis, grey matter in the entorhinal cortex could predict navigational strategy with 92% accuracy.

Original languageEnglish (US)
Pages (from-to)1493-1507
Number of pages15
JournalJournal of Alzheimer's Disease
Volume61
Issue number4
DOIs
StatePublished - Jan 1 2018
Externally publishedYes

Fingerprint

Apolipoprotein E4
Atrophy
Alzheimer Disease
Alleles
Entorhinal Cortex
Genes
Hippocampus
Early Diagnosis
Biomarkers
Magnetic Resonance Imaging

Keywords

  • APOE
  • Entorhinal cortex
  • Hippocampus
  • Spatial memory

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health

Cite this

Konishi, K., Joober, R., Poirier, J., MacDonald, K., Chakravarty, M., Patel, R., ... Bohbot, V. D. (2018). Healthy versus entorhinal cortical atrophy identification in asymptomatic APOE4 carriers at risk for Alzheimer's disease. Journal of Alzheimer's Disease, 61(4), 1493-1507. https://doi.org/10.3233/JAD-170540

Healthy versus entorhinal cortical atrophy identification in asymptomatic APOE4 carriers at risk for Alzheimer's disease. / Konishi, Kyoko; Joober, Ridha; Poirier, Judes; MacDonald, Kathleen; Chakravarty, Mallar; Patel, Raihaan; Breitner, John C.S.; Bohbot, Véronique D.

In: Journal of Alzheimer's Disease, Vol. 61, No. 4, 01.01.2018, p. 1493-1507.

Research output: Contribution to journalArticle

Konishi, Kyoko ; Joober, Ridha ; Poirier, Judes ; MacDonald, Kathleen ; Chakravarty, Mallar ; Patel, Raihaan ; Breitner, John C.S. ; Bohbot, Véronique D. / Healthy versus entorhinal cortical atrophy identification in asymptomatic APOE4 carriers at risk for Alzheimer's disease. In: Journal of Alzheimer's Disease. 2018 ; Vol. 61, No. 4. pp. 1493-1507.
@article{04e602b58d864f7ca7c5432dfaea3081,
title = "Healthy versus entorhinal cortical atrophy identification in asymptomatic APOE4 carriers at risk for Alzheimer's disease",
abstract = "Early detection of Alzheimer's disease (AD) has been challenging as current biomarkers are invasive and costly. Strong predictors of future AD diagnosis include lower volume of the hippocampus and entorhinal cortex, as well as the ϵ4 allele of the Apolipoprotein E gene (APOE) gene. Therefore, studying functions that are critically mediated by the hippocampus and entorhinal cortex, such as spatial memory, in APOE ϵ4 allele carriers, may be key to the identification of individuals at risk of AD, prior to the manifestation of cognitive impairments. Using a virtual navigation task developed in-house, specifically designed to assess spatial versus non-spatial strategies, the current study is the first to differentiate functional and structural differences within APOE ϵ4 allele carriers. APOE ϵ4 allele carriers that predominantly use nonspatial strategies have decreased fMRI activity in the hippocampus and increased atrophy in the hippocampus, entorhinal cortex, and fimbria compared to APOE ϵ4 allele carriers who use spatial strategies. In contrast, APOE ϵ4 allele carriers who use spatial strategies have grey matter levels comparable to non-APOE ϵ4 allele carriers. Furthermore, in a leave-one-out analysis, grey matter in the entorhinal cortex could predict navigational strategy with 92{\%} accuracy.",
keywords = "APOE, Entorhinal cortex, Hippocampus, Spatial memory",
author = "Kyoko Konishi and Ridha Joober and Judes Poirier and Kathleen MacDonald and Mallar Chakravarty and Raihaan Patel and Breitner, {John C.S.} and Bohbot, {V{\'e}ronique D.}",
year = "2018",
month = "1",
day = "1",
doi = "10.3233/JAD-170540",
language = "English (US)",
volume = "61",
pages = "1493--1507",
journal = "Journal of Alzheimer's Disease",
issn = "1387-2877",
publisher = "IOS Press",
number = "4",

}

TY - JOUR

T1 - Healthy versus entorhinal cortical atrophy identification in asymptomatic APOE4 carriers at risk for Alzheimer's disease

AU - Konishi, Kyoko

AU - Joober, Ridha

AU - Poirier, Judes

AU - MacDonald, Kathleen

AU - Chakravarty, Mallar

AU - Patel, Raihaan

AU - Breitner, John C.S.

AU - Bohbot, Véronique D.

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Early detection of Alzheimer's disease (AD) has been challenging as current biomarkers are invasive and costly. Strong predictors of future AD diagnosis include lower volume of the hippocampus and entorhinal cortex, as well as the ϵ4 allele of the Apolipoprotein E gene (APOE) gene. Therefore, studying functions that are critically mediated by the hippocampus and entorhinal cortex, such as spatial memory, in APOE ϵ4 allele carriers, may be key to the identification of individuals at risk of AD, prior to the manifestation of cognitive impairments. Using a virtual navigation task developed in-house, specifically designed to assess spatial versus non-spatial strategies, the current study is the first to differentiate functional and structural differences within APOE ϵ4 allele carriers. APOE ϵ4 allele carriers that predominantly use nonspatial strategies have decreased fMRI activity in the hippocampus and increased atrophy in the hippocampus, entorhinal cortex, and fimbria compared to APOE ϵ4 allele carriers who use spatial strategies. In contrast, APOE ϵ4 allele carriers who use spatial strategies have grey matter levels comparable to non-APOE ϵ4 allele carriers. Furthermore, in a leave-one-out analysis, grey matter in the entorhinal cortex could predict navigational strategy with 92% accuracy.

AB - Early detection of Alzheimer's disease (AD) has been challenging as current biomarkers are invasive and costly. Strong predictors of future AD diagnosis include lower volume of the hippocampus and entorhinal cortex, as well as the ϵ4 allele of the Apolipoprotein E gene (APOE) gene. Therefore, studying functions that are critically mediated by the hippocampus and entorhinal cortex, such as spatial memory, in APOE ϵ4 allele carriers, may be key to the identification of individuals at risk of AD, prior to the manifestation of cognitive impairments. Using a virtual navigation task developed in-house, specifically designed to assess spatial versus non-spatial strategies, the current study is the first to differentiate functional and structural differences within APOE ϵ4 allele carriers. APOE ϵ4 allele carriers that predominantly use nonspatial strategies have decreased fMRI activity in the hippocampus and increased atrophy in the hippocampus, entorhinal cortex, and fimbria compared to APOE ϵ4 allele carriers who use spatial strategies. In contrast, APOE ϵ4 allele carriers who use spatial strategies have grey matter levels comparable to non-APOE ϵ4 allele carriers. Furthermore, in a leave-one-out analysis, grey matter in the entorhinal cortex could predict navigational strategy with 92% accuracy.

KW - APOE

KW - Entorhinal cortex

KW - Hippocampus

KW - Spatial memory

UR - http://www.scopus.com/inward/record.url?scp=85055877855&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85055877855&partnerID=8YFLogxK

U2 - 10.3233/JAD-170540

DO - 10.3233/JAD-170540

M3 - Article

VL - 61

SP - 1493

EP - 1507

JO - Journal of Alzheimer's Disease

JF - Journal of Alzheimer's Disease

SN - 1387-2877

IS - 4

ER -