Abstract
Objective: To assess the relation between a sum score of imaging markers indicative of cerebral amyloid angiopathy (CAA) and cognitive impairment, stroke, dementia, and mortality in a general population.Methods: One thousand six hundred twenty-two stroke-free and dementia-free participants of the population-based Rotterdam Study (mean age 73.1 years, 54.3% women) underwent brain MRI (1.5 tesla) in 2005–2011 and were followed for stroke, dementia and death until 2016–2017. Four MRI markers (strictly lobar cerebral microbleeds, cortical superficial siderosis, centrum semiovale perivascular spaces, and white matter hyperintensities) were combined to construct the CAA sum score, ranging from 0 to 4. Neuropsychological testing measured during the research visit closest to scan date were used to assess general cognitive function and cognitive domains. The associations of the CAA sum score with cognition cross-sectionally and with stroke, dementia, and mortality longitudinally were determined using linear regression and Cox proportional hazard modeling adjusted for age, sex, hypertension, cholesterol, lipid lowering medication, atrial fibrillation, antithrombotic medication and APOE-ε2/ε4 carriership. Additionally, we accounted for competing risks of death due to other causes for stroke and dementia, and calculated absolute risk estimates.Results: During a mean follow-up of 7.2 years, 62 participants suffered a stroke, 77 developed dementia and 298 died. Participants with a CAA score of 1 showed a lower Mini-Mental-State-Exam (fully-adjusted mean difference −0.21, 95% CI (−0.42–0.00) compared to a score of 0. In general, for increased CAA scores we saw a lower g-factor. The age and sex-adjusted hazard ratios (HRs) per point increase of the CAA score were 1.41 for stroke (95% CI, 0.99–2.00), 1.19 for dementia (95% CI, 0.86–1.65), and 1.26 for mortality (95% CI, 1.07–1.48). The results for dementia and stroke risk did not differ after correcting for the competing risk of death. For all outcomes, higher CAA scores showed higher absolute risk estimates over 10 years.Conclusions: Our results suggest that in this community-dwelling population, a higher CAA score is related to cognitive impairment and a higher risk of stroke, dementia, and death. The composite CAA score can be used to practically quantify the severity of vascular brain injury.
Highlights
Cerebral amyloid angiopathy (CAA) is a frequent form of sporadic cerebral small vessel disease caused by accumulation of amyloid-ß in leptomeningeal and cortical vessels and capillaries [1, 2]
We studied the relation of the CAA score with subgroups of the neurological outcomes and mortality, namely ischemic and hemorrhagic stroke, Alzheimer’s disease, and cardiovascular mortality
62 participants suffered from a stroke, 77 developed dementia and 298 died
Summary
Cerebral amyloid angiopathy (CAA) is a frequent form of sporadic cerebral small vessel disease caused by accumulation of amyloid-ß in leptomeningeal and cortical vessels and capillaries [1, 2]. Brain imaging markers that reflect parenchymal damage caused by small vessel brain injury have shown to be useful in a clinical setting to diagnose CAA [2, 5] These markers visible on magnetic resonance imaging (MRI) include lobar cerebral microbleeds (CMB), cortical superficial siderosis (cSS), centrum semiovale perivascular spaces (CSO-PVS) and white matter hyperintensities of presumed vascular origin ( WMH) [6, 7] Several markers individually are thought to reflect different types of small vessel disease. The authors concluded that this composite score may better reflect the overall CAA-related small vessel disease burden in the brain. Such composite scores reflecting CAA disease burden could be used in clinical practice or research settings [2, 14]
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