Skip to content
DraconiticResearch
Search Sources API
203,948 studies31 sourcesUpdated 22 min ago
Peer-reviewedCC BY-NC-ND 4.0Translational Vision Science & Technology

Longitudinal Multimodal Retinal Imaging in Cognitively Normal Apolipoprotein E4 Carriers and Noncarriers

  • Alex Choi1
  • Alice Haystead1
  • Rachel D'Cunha1
  • John Hsu1
  • Michael Zhu1
  • Kim G. Johnson1,2
  • Heather Whitson1,2,3,4
  • Dilraj S. Grewal1
  • Sharon Fekrat1,2
4 affiliations
  1. 1iMIND Study Group, Duke University School of Medicine, Durham, NC, USA
  2. 2Department of Neurology, Duke University School of Medicine, Durham, NC, USA
  3. 3Department of Medicine, Duke University School of Medicine, Durham, NC, USA
  4. 4Geriatrics Research Education and Clinical Center, Durham VA Medical Center, Durham, NC, USA
Read full textDOICite

Abstract

Purpose: To evaluate longitudinal retinal structural and microvascular changes in cognitively normal apolipoprotein E (APOE) ε4 carriers compared with noncarriers.

Methods: Cognitively normal adults with known APOE genotype underwent multimodal retinal imaging at baseline and follow-up visits. Optical coherence tomography (OCT) metrics included macular central subfield thickness (CST), ganglion cell–inner plexiform layer (GC-IPL) thickness, and retinal nerve fiber layer (RNFL) thickness. OCT angiography (OCTA) parameters included vessel and perfusion density across 3-mm and 6-mm circles and rings, peripapillary capillary perfusion density (CPD), and capillary flux index (CFI). Annual rates of change were estimated using linear mixed-effects models adjusted for age and sex. A subgroup analysis was performed in participants with ≥5-year follow-up.

Results: This study analyzed 871 eyes from 439 participants (230 APOE ε4 noncarriers and 209 carriers). Baseline retinal parameters did not differ significantly between groups. Carriers demonstrated nominally slower annual RNFL decline (β = 0.334; P = 0.023) and attenuated peripapillary CPD decline (β = 0.0010; P = 0.014) versus noncarriers; neither survived false discovery rate (FDR) correction (P = 0.18). In the ≥5-year subgroup (n = 58), carriers demonstrated nominally higher peripapillary CPD than noncarriers (P = 0.011; FDR-adjusted P = 0.17), although rates of change did not differ significantly between groups.

Conclusions: Cognitively normal APOE ε4 carriers demonstrated nominally slower peripapillary CPD and RNFL decline over longitudinal follow-up, with carriers maintaining higher CPD at ≥5 years despite comparable baseline imaging.

Translational Relevance: Longitudinal peripapillary and RNFL changes may reflect early retinal findings associated with APOE ε4 carrier status prior to cognitive decline, supporting further investigation of longitudinal retinal imaging as a potential noninvasive biomarker in preclinical Alzheimer's disease.

Related

  1. Cerebral blood flow as a biomarker of resilience in cognitively unimpaired APOE ɛ4 carriers.
    Melanie Quiring, Arunima Kapoor, John Paul M Alitin +14
    Alzheimer's & dementia : the journal of the Alzheimer's AssociationPeer-reviewedCC BY-NCFull textPsychiatry & mental healthEurope PMC
  2. Beyond retest gains: episodic memory practice effects and longitudinal cognitive trajectories in cognitively healthy adults
    Simon Fankhauser, Gabriele Cattaneo, Gemma Albi-Villuendas +3
    Frontiers in Aging NeurosciencePeer-reviewedCC BY 4.0Full textPsychiatry & mental healthPMCEurope PMC
  3. Clinical and attitudinal outcomes of a personalized, multimodal lifestyle intervention for Alzheimer's disease prevention in high-risk, cognitively normal older adults in north Alabama: A pilot study
    M. Cochran, J. Pugh, T. Coleman +26
    medRxivPreprintCC BY-NC-NDFull textNeurologymedRxiv
  4. Longitudinal associations of hormone therapy and depressive symptoms in cognitively unimpaired older women
    Kelly A. Lopez Garcia, Hannah M. Klinger, Catherine E. Munro +12
    BMC MedicinePeer-reviewedCC BY 4.0Endocrinology & metabolismCrossref
  5. Practice Effects on Repeated Self-Administered Digital Cognitive Assessments in Cognitively Intact Older Adults from the Framingham Heart Study: Longitudinal Observational Study.
    Kieffer Christianson, Chenglin Lyu, Cody Karjadi +10
    JMIR agingPeer-reviewedCC BYFull textPsychiatry & mental healthEurope PMC

Cite

BibTeXRIS
BibTeX
@article{choi2026longitudinal,
  title = {{Longitudinal Multimodal Retinal Imaging in Cognitively Normal Apolipoprotein E4 Carriers and Noncarriers}},
  author = {Alex Choi and Alice Haystead and Rachel D'Cunha and John Hsu and Michael Zhu and Kim G. Johnson and Heather Whitson and Dilraj S. Grewal and Sharon Fekrat},
  journal = {Translational Vision Science \& Technology},
  year = {2026},
  month = oct,
  doi = {10.1167/tvst.15.10.45},
  url = {https://doi.org/10.1167/tvst.15.10.45},
  note = {CC BY-NC-ND 4.0},
}
RIS
TY  - JOUR
TI  - Longitudinal Multimodal Retinal Imaging in Cognitively Normal Apolipoprotein E4 Carriers and Noncarriers
AU  - Alex Choi
AU  - Alice Haystead
AU  - Rachel D'Cunha
AU  - John Hsu
AU  - Michael Zhu
AU  - Kim G. Johnson
AU  - Heather Whitson
AU  - Dilraj S. Grewal
AU  - Sharon Fekrat
PY  - 2026
DA  - 2026/10/27
JO  - Translational Vision Science & Technology
DO  - 10.1167/tvst.15.10.45
UR  - https://doi.org/10.1167/tvst.15.10.45
AB  - Purpose: To evaluate longitudinal retinal structural and microvascular changes in cognitively normal apolipoprotein E (APOE) ε4 carriers compared with noncarriers.  Methods: Cognitively normal adults with known APOE genotype underwent multimodal retinal imaging at baseline and follow-up visits. Optical coherence tomography (OCT) metrics included macular central subfield thickness (CST), ganglion cell–inner plexiform layer (GC-IPL) thickness, and retinal nerve fiber layer (RNFL) thickness. OCT angiography (OCTA) parameters included vessel and perfusion density across 3-mm and 6-mm circles and rings, peripapillary capillary perfusion density (CPD), and capillary flux index (CFI). Annual rates of change were estimated using linear mixed-effects models adjusted for age and sex. A subgroup analysis was performed in participants with ≥5-year follow-up.  Results: This study analyzed 871 eyes from 439 participants (230 APOE ε4 noncarriers and 209 carriers). Baseline retinal parameters did not differ significantly between groups. Carriers demonstrated nominally slower annual RNFL decline (β = 0.334; P = 0.023) and attenuated peripapillary CPD decline (β = 0.0010; P = 0.014) versus noncarriers; neither survived false discovery rate (FDR) correction (P = 0.18). In the ≥5-year subgroup (n = 58), carriers demonstrated nominally higher peripapillary CPD than noncarriers (P = 0.011; FDR-adjusted P = 0.17), although rates of change did not differ significantly between groups.  Conclusions: Cognitively normal APOE ε4 carriers demonstrated nominally slower peripapillary CPD and RNFL decline over longitudinal follow-up, with carriers maintaining higher CPD at ≥5 years despite comparable baseline imaging.  Translational Relevance: Longitudinal peripapillary and RNFL changes may reflect early retinal findings associated with APOE ε4 carrier status prior to cognitive decline, supporting further investigation of longitudinal retinal imaging as a potential noninvasive biomarker in preclinical Alzheimer's disease.
SN  - 2164-2591
ER  -