Microvascular network alterations in the retina of patients with Alzheimer's disease.
BACKGROUND
Although cerebral small-vessel disease has been implicated in the development of Alzheimer's disease (AD), the cerebral microcirculation is difficult to visualize directly in vivo. Because the retina provides a noninvasive window to assess the microcirculation, we determined whether quantitatively measured retinal microvascular parameters are associated with AD.


METHODS
We conducted a case-control study (case:control matching ≈ 1:2). Retinal photographs were analyzed using a computer program, and a spectrum of quantitative retinal microvascular parameters (caliber, fractal dimension, tortuosity, and bifurcation) were measured. Logistic regression models were used to compute the odds ratio (OR) and 95% confidence interval for AD adjusting for age, gender, ethnicity, smoking, hypertension, diabetes, hypercholesterolemia, and history of myocardial infarction.


RESULTS
We included 136 demented patients with AD and 290 age-gender-race-matched controls. Persons with narrower venular caliber (OR per standard deviation [SD] decrease, 2.01 [1.27-3.19]), decreased arteriolar and venular fractal dimension (OR per SD decrease 1.35 [1.08-1.68], 1.47 [1.17-1.84], respectively) and increased arteriolar and venular tortuosity (OR per SD increase, 1.84 [1.40-2.31], 1.94 [1.48-2.53], respectively) were more likely to have AD. These associations still persisted when only AD cases without a history of cerebrovascular disease were included.


CONCLUSIONS
Patients with AD have altered microvascular network in the retina (narrower retinal venules and a sparser and more tortuous retinal vessels) compared with matched nondemented controls. These changes in retinal microvasculature may reflect similar pathophysiological processes in cerebral microvasculature in the brains of patients with AD.
Singapore Eye Research Institute, Singapore National Eye Centre, Singapore; Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Centre for Quantitative Medicine, Office of Clinical Sciences, Duke-NUS Graduate Medical School, Singapore. Electronic address: carol.cheung.y.l@seri.com.sg.
Carol Yim-Lui
CY
Cheung
Singapore Eye Research Institute, Singapore National Eye Centre, Singapore; Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore.
Yi Ting
YT
Ong
Singapore Eye Research Institute, Singapore National Eye Centre, Singapore; Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Centre for Quantitative Medicine, Office of Clinical Sciences, Duke-NUS Graduate Medical School, Singapore; Memory Aging and Cognition Centre, National University Health System, Singapore; Department of Ophthalmology, Erasmus Medical Center, Rotterdam, The Netherlands.
M Kamran
MK
Ikram
Singapore Eye Research Institute, Singapore National Eye Centre, Singapore; Centre for Quantitative Medicine, Office of Clinical Sciences, Duke-NUS Graduate Medical School, Singapore.
Shin Yeu
SY
Ong
Singapore Eye Research Institute, Singapore National Eye Centre, Singapore; Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Xiang
X
Li
Memory Aging and Cognition Centre, National University Health System, Singapore.
Saima
S
Hilal
Memory Aging and Cognition Centre, National University Health System, Singapore.
Joseree-Ann S
JA
Catindig
Memory Aging and Cognition Centre, National University Health System, Singapore.
Narayanaswamy
N
Venketasubramanian
Department of Geriatric Medicine, Khoo Teck Puat Hospital, Singapore.
Philip
P
Yap
Department of Geriatric Medicine, Singapore General Hospital, Singapore.
Dennis
D
Seow
Memory Aging and Cognition Centre, National University Health System, Singapore; Department of Pharmacology, National University of Singapore, Singapore.
Christopher P
CP
Chen
Singapore Eye Research Institute, Singapore National Eye Centre, Singapore; Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Tien Yin
TY
Wong
D000368:Aged; D000544:Alzheimer Disease / Q000473:pathology*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008297:Male; D055806:Microvessels / Q000473:pathology*; D012160:Retina / Q000473:pathology*; D012171:Retinal Vessels / Q000473:pathology*; D042262:Retinoscopy; D012189:Retrospective Studies
Alzheimer's disease; Microcirculation; Retina; Retinal vasculature; Small-vessel disease