Cerebral microbleeds, retinopathy, and dementia

Abstract

Objective: To determine whether microvascular damage, indicated by cerebral microbleeds (CMBs) and retinal microvascular signs, is associated with cognitive function and dementia in older persons.Methods: This is a cross-sectional study of 3,906 participants (mean age 76 years; 58% women) in the AGES-Reykjavik Study (2002)(2003)(2004)(2005)(2006). We assessed CMBs on MRI and retinal microvascular signs on digital retinal images. Composite Z scores of memory, processing speed, and executive function were derived from a battery of neurocognitive tests. Dementia and subtypes were diagnosed following international criteria. Regression models were used to relate cognitive Z scores and dementia to CMBs and retinal microvascular signs, adjusting for demographics, cardiovascular factors, and brain ischemic lesions. Results:People with multiple (Ն2) CMBs had lower Z scores on tests of processing speed (␤-coefficient Ϫ0.16; 95% confidence interval Ϫ0.26 to Ϫ0.05) and executive function (Ϫ0.14; Ϫ0.24 to Ϫ0.04); results were strongest for having multiple CMBs located in the deep hemispheric or infratentorial areas. The odds ratio of vascular dementia was 2.32 (95% confidence interval 1.02 to 5.25) for multiple CMBs and 1.95 (1.04 to 3.62) for retinopathy. Having both CMBs and retinopathy, compared to having neither, was significantly associated with markedly slower processing speed (Ϫ0.25; Ϫ0.37 to Ϫ0.12), poorer executive function (Ϫ0.19; Ϫ0.31 to Ϫ0.07), and an increased odds ratio of vascular dementia (3.10; 1.11 to 8.62). Conclusion:Having multiple CMBs or concomitant CMBs and retinopathy is associated with a profile of vascular cognitive impairment. These findings suggest that microvascular damage, as indicated by CMBs and retinopathy lesions, has functional consequences in older men and women living in the community. Neurology ® 2010;75:2221-2228 GLOSSARY AD ϭ Alzheimer disease; AGES ϭ Age, Gene/Environment Susceptibility; CAA ϭ cerebral amyloid angiopathy; CI ϭ confidence interval; CMB ϭ cerebral microbleed; DSM-IV ϭ Diagnostic and Statistical Manual of Mental Disorders, 4th edition; DSST ϭ Digit Symbol Substitution Test; FA ϭ flip angle; FLAIR ϭ fluid-attenuated inversion recovery; FOV ϭ field of view; FSE ϭ fast spin-echo; MR ϭ magnetic resonance; OR ϭ odds ratio; PD ϭ proton density; TE ϭ echo time; TR ϭ repetition time; VaD ϭ vascular dementia; VCI ϭ vascular cognitive impairment; WMH ϭ white matter hyperintensity.

Susceptibility-Weighted Imaging is More Reliable Than T2*-Weighted Gradient-Recalled Echo MRI for Detecting Microbleeds

“…Previous studies of CMBs on GRE report ICCs of 0.91 to 0.97 for total CMB counts, 14,15,17 and κ values generally between 0.40 to 0.75 for CMB presence or absence. 14,15,[17][18][19][20][21] By contrast, the ICC on GRE in our study was lower than for these other studies, probably reflecting differences in the populations studied. Our 9 CAA patients had a very large number of CMBs ( Table 1) that exceeded the numbers of CMBs per patient reported in other studies; therefore, interpretation of the images was time-consuming and difficult, which might have affected the reliability.…”

Clinicoradiologic Correlations of Cerebral Microbleeds in Advanced Age

“…It has been shown that SWI sequences detect more CMBs than 2D gradient-recalled echo sequences, [30][31][32] with an increase in detected lesions of 67% according to Nandigam et al 30 As in our study, the prevalence of CMBs was relatively similar in patients with MCI and controls (14% and 11%, respectively) in the cohort of Ayaz et al, 33 including 28 healthy controls and 75 subjects with MCI examined at 1.5T with a SWI sequence. Other studies found an association between CMBs and low cognitive performance 12 or cognitive decline. 13 This variability may be due to differences in study design with varying cohort sizes and composition (eg, absence of a control group, varying exclusion criteria) and variable definitions of cognitive impairment.…”

“…In previous studies, greater or increasing numbers of CMBs with time were related to impaired cognitive functioning, in both cross-sectional 12,24 and longitudinal analyses 13,[33][34][35][36] in different types of cohorts (eg, population-based or in a memory clinic setting). The nature of the associations between CMBs and cognitive performance was, however, variable and not necessarily independent.…”

“…[8][9][10][11] Their impact on cognition is still a matter of debate. Several studies supported a deleterious effect of CMBs, including increased prevalence in vascular dementia but also in Alzheimer disease, 3,[12][13][14] associations with poorer cognitive function in cross-sectional studies of patients with dementia, 15 lower A␤42 levels in the CSF in Alzheimer disease and vascular dementia, 16 and decreased frontal-executive performances at 5-year follow-up in patients with stroke. 17 However, negative data were also reported with no or marginal impact of CMBs in early Alzheimer disease (for a review see van der Flier 18 and Heringa et al 19 ) and in subjects with subcortical vascular cognitive impairment 20 and symptomatic small-vessel disease.…”

Relationship Between Radiation Dose and Microbleed Formation in Patients With Malignant Glioma

“…CMBs have also been observed in elderly patients without known underlying pathology [13,14], as well as in other degenerative central nervous system conditions, including cerebral amyloid angiopathy (CAA) associated with Alzheimer's disease and vascular cognitive impairment [11], where they have been linked to cognitive dysfunction [15][16][17][18]. Thus, quantification of CMB characteristics may serve as a valuable metric for radiation-induced vasculopathy and resultant cognitive decline.…”