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Differential associations between retinal signs and CMBs by location: The AGES-Reykjavik Study
Chengxuan Qiu1, Jie Ding2, Sigurdur Sigurdsson2
1From the Intramural Research Program (C.Q., J.D., Q.Z., L.J.L.), Laboratory of Epidemiology and Population Sciences, National Institute on Aging, NIH, Bethesda, MD; Aging Research Center (C.Q.), Department of Neurobiology, Care Sciences and Society, Karolinska Institutet-Stockholm University, Sweden; Icelandic Heart Association (S.S., G.E., V.G.), Kopavogur; Division of Epidemiology and Clinical Research (D.E.F., M.F.C.), National Eye Institute, NIH, Bethesda, MD; Ophthalmology and Visual Sciences (R.K.), University of Wisconsin Madison; Department of Radiology (M.A.v.B.), Leiden University Medical Centre, the Netherlands; and Faculty of Medicine (V.G.), University of Iceland, Reykjavik. LaunerL@nia.nih.gov chengxuan.qiu@ki.se.
Objective:
To test the hypothesis that age-related macular degeneration (AMD) and retinal microvascular signs are differentially associated with lobar and deep cerebral microbleeds (CMBs).
Methods:
CMBs in lobar regions indicate cerebral amyloid angiopathy (CAA). β-Amyloid deposits are implicated in both CAA and AMD. Deep CMBs are associated with hypertension, a major risk factor for retinal microvascular damage. This population-based cohort study included 2,502 participants in the Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study who undertook binocular digital retinal photographs at baseline (2002-2006) to assess retinal microvascular signs and AMD and brain MRI scan at both baseline and follow-up (2007-2011) to assess CMBs. We assessed retinal microvascular lesion burden by counting the 3 retinal microvascular signs (focal arteriolar narrowing, arteriovenous nicking, and retinopathy) concurrently present in the participant. We used multiple logistic models to examine the association of baseline retinal pathology to incident CMBs detected at follow-up.
Results:
During an average 5.2 years of follow-up, 461 people (18.3%) developed new CMBs, including 293 in exclusively lobar regions and 168 in deep regions. Pure geographic atrophy was significantly associated with strictly lobar CMBs (multivariable-adjusted odds ratio 2.59, 95% confidence interval [CI] 1.01-6.65) but not with deep CMBs. Concurrently having ≥2 retinal microvascular signs was associated with a 3-fold (95% CI 1.73-5.20) increased likelihood for deep CMBs but not exclusively lobar CMBs.
Conclusions:
Retinal microvascular signs and pure geographic atrophy may be associated with deep and exclusively lobar CMBs, respectively, in older people. These results have implications for further research to define the role of small vessel disease in cognitive impairment.
Insights
Age-related macular degeneration (AMD) and retinal microvascular signs are linked to different types of cerebral microbleeds (CMBs). Geographic atrophy is associated with lobar CMBs, while retinal microvascular signs predict deep CMBs.
Area of Science:
- Ophthalmology
- Neurology
- Gerontology
Background:
- Cerebral microbleeds (CMBs) in lobar regions are linked to cerebral amyloid angiopathy (CAA), which shares beta-amyloid pathology with age-related macular degeneration (AMD).
- Deep CMBs are associated with hypertension, a risk factor for retinal microvascular damage.
- Understanding the differential associations of retinal and cerebral small vessel disease is crucial for identifying shared pathophysiological mechanisms.
Purpose of the Study:
- To investigate the distinct associations between age-related macular degeneration (AMD) and retinal microvascular signs with lobar versus deep cerebral microbleeds (CMBs).
Main Methods:
- The Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study cohort included 2,502 participants with retinal photographs and brain MRI scans.
- Retinal microvascular signs and AMD were assessed at baseline, and incident CMBs (lobar and deep) were identified via follow-up MRI.
- Multiple logistic regression models were used to analyze the associations between baseline retinal pathology and incident CMBs.
Main Results:
- Over 5.2 years, 18.3% of participants developed new CMBs (293 lobar, 168 deep).
- Pure geographic atrophy (a form of AMD) was significantly associated with lobar CMBs (OR 2.59).
- Having two or more retinal microvascular signs was linked to a threefold increased likelihood of deep CMBs (OR 3.00).
Conclusions:
- Retinal microvascular signs may predict deep CMBs, while pure geographic atrophy is associated with lobar CMBs in older adults.
- These findings suggest distinct links between retinal and cerebral small vessel pathologies.
- Further research is warranted to elucidate the role of small vessel disease in cognitive impairment.
