Cerebral microbleeds and cognitive impairment

Abstract: Background: With increasingly ageing populations comes an increased prevalence of cognitive impairment and dementia. The pathophysiology behind dementia is still unknown, and there is no cure. Microscopic bleeds in the brain parenchyma, so called cerebral microbleeds, are common in ageing populations, as well as in dementia and stroke, and are primarily a marker of small vessel disease. Due to their high prevalence in memory clinic populations, microbleeds have been hypothesized to be of importance in the cognitive impairment disease process. Purpose: To cross-sectionally study the detection and clinical implications of cerebral microbleeds in cognitive impairment. Study I showed that microbleeds are common in cognitive impairment (22% prevalence), and especially in vascular dementia (59% prevalence). Microbleeds are associated with hypertension, male gender, high age, and increase with increasing risk factors. Topography of microbleeds is predominantly lobar and occipital in Alzheimer disease. The microbleed topography varies depending on underlying diagnosis and risk factors. Study II showed that susceptibility weighted imaging increases the prevalence and number of microbleeds detected on 3.0T magnetic resonance imaging. Inter-rater agreement of microbleeds is excellent on T2' and susceptibility weighted imaging, across raters of different experience. Only minor differences in clinical associations were noted across different sequences. Study III showed that amyloid β42 levels were lower in the cerebrospinal fluid with a high number of microbleeds. This was true in the whole cohort (n=1039), Alzheimer disease and mild cognitive impairment. In the whole cohort cerebrospinal fluid/serum albumin ratios were higher with increasing number of microbleeds. In multivariate regression analysis low amyloid levels in the cerebrospinal fluid with increasing number of microbleeds held true. White matter hyperintensities were likewise associated with low amyloid β42 levels, whereas lacunes were associated with higher amyloid levels in the cerebrospinal fluid. Study IV showed that lobar microbleeds are associated with lower amyloid β42 levels in the cerebrospinal fluid, in the whole cohort and Alzheimer disease. Deep and infratentorial microbleeds showed tendencies to be associated with higher amyloid and lower tau levels in the cerebrospinal fluid. Multivariable logistic regression analysis showed that white matter hyperintensities and lacunes were associated with lobar and deep microbleeds. Conclusions: Cerebral microbleeds are best detected with susceptibility weighted MRI and are common in a memory clinic. Microbleeds show varying associations based on topography. Especially lobar microbleeds are associated with low cerebrospinal fluid amyloid, and specifically in Alzheimer disease, suggesting that primarily lobar microbleeds may be of importance in cognitive impairment.

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