Retinal microvascular alterations and glymphatic dysfunction mediate the association between APOE ε4 and cognitive decline in Alzheimer's disease.
WR, K., C, W., Y, W., S, H., Y, H., S, W., C, Z., IYM, B., M, W., & Z, W. (2026). Retinal microvascular alterations and glymphatic dysfunction mediate the association between APOE ε4 and cognitive decline in Alzheimer's disease.. Alzheimer's & dementia : the journal of the Alzheimer's Association. https://doi.org/10.1002/alz.71785
WR K, C W, Y W, S H, Y H, S W, et al. Retinal microvascular alterations and glymphatic dysfunction mediate the association between APOE ε4 and cognitive decline in Alzheimer's disease.. Alzheimer's & dementia : the journal of the Alzheimer's Association. 2026; doi: 10.1002/alz.71785
WR K, C W, Y W, et al. Retinal microvascular alterations and glymphatic dysfunction mediate the association between APOE ε4 and cognitive decline in Alzheimer's disease.[J]. Alzheimer's & dementia : the journal of the Alzheimer's Association. 2026. DOI: 10.1002/alz.71785.
@article{wr2026,
author = {Kwapong WR and Wen C and Wang Y and Hu S and Hu Y and Wu S and Zheng C and Bonaventure IYM and Wang M and Wang Z},
title = {Retinal microvascular alterations and glymphatic dysfunction mediate the association between APOE ε4 and cognitive decline in Alzheimer's disease.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
year = {2026},
doi = {10.1002/alz.71785},
note = {PMID: 42639646},
}
TY - JOUR AU - Kwapong WR AU - Wen C AU - Wang Y AU - Hu S AU - Hu Y AU - Wu S AU - Zheng C AU - Bonaventure IYM AU - Wang M AU - Wang Z TI - Retinal microvascular alterations and glymphatic dysfunction mediate the association between APOE ε4 and cognitive decline in Alzheimer's disease. T2 - Alzheimer's & dementia : the journal of the Alzheimer's Association PY - 2026 DO - 10.1002/alz.71785 AN - PMID:42639646 ER -
BACKGROUND: Vascular and glymphatic dysfunction are increasingly implicated in Alzheimer's disease (AD), particularly among apolipoprotein E (APOE) ε4 carriers. We investigated relationships among retinal microvasculature, glymphatic markers, and AD pathology. METHODS: Seventy-six AD participants underwent retinal imaging, magnetic resonance imaging, and plasma biomarker assessment. Retinal fractal dimension (FD) and tortuosity (T), diffusion tensor imaging along the perivascular space (DTI-ALPS), periventricular diffusivity (PVeD), and small vessel disease (SVD) markers were analyzed. RESULTS: APOE ε4 carriers showed reduced FD, increased T, and lower PVeD. Sparser microvasculature was associated with impaired glymphatic markers, greater vascular burden, abnormal plasma biomarkers, and worse cognition. Mediation analyses indicated that retinal FD and PVeD partially mediated the relationship between APOE ε4 and cognitive performance. DISCUSSION: Retinal microvascular alterations reflect vascular-glymphatic dysfunction and may serve as non-invasive biomarkers linking genetic risk to cognitive decline in AD.