Cerebral Microbleeds: Different Prevalence,Topography, and Risk Factors Depending on Dementia Diagnosis—The Karolinska Imaging Dementia Study

BACKGROUND AND PURPOSE:Cerebral microbleeds are thought to represent cerebral amyloid angiopathy when in lobar regions of the brain and hypertensive arteriopathy when in deep and infratentorial locations. By studying cerebral microbleeds, their topography, and risk factors, we aimed to gain an insight into the vascular and amyloid pathology of dementia diagnoses and increase the understanding of cerebral microbleeds in dementia.MATERIALS AND METHODS:We analyzed 1504 patients (53% women; mean age, 63 ± 10 years; 10 different dementia diagnoses) in this study. All patients underwent MR imaging as part of the dementia investigation, and all their clinical parameters were recorded.RESULTS:Among the 1504 patients with dementia, 22% had cerebral microbleeds. Cerebral microbleed topography was predominantly lobar (P = .01) and occipital (P = .007) in Alzheimer disease. Patients with cerebral microbleeds were significantly older (P < .001), were more frequently male (P < .001), had lower cognitive scores (P = .006), and more often had hypertension (P < .001). Risk factors for cerebral microbleeds varied depending on the dementia diagnosis. Odds ratios for having cerebral microbleeds increased with the number of risk factors (hypertension, hyperlipidemia, diabetes, male sex, and age 65 and older) in the whole patient group and increased differently in the separate dementia diagnoses.CONCLUSIONS:Prevalence, topography, and risk factors of cerebral microbleeds vary depending on the dementia diagnosis and reflect the inherent pathology of different dementia diagnoses. Because cerebral microbleeds are seen as possible predictors of intracerebral hemorrhage, their increasing prevalence with an increasing number of risk factors, as shown in our study, may require taking the number of risk factors into account when deciding on anticoagulant therapy in dementia.

Cerebral microbleeds (CMBs) are not usually seen on conventional MR imaging and CT but have been increasingly detected due to the more frequent use of the T2* and SWI MR imaging sequences, sensitive to minute amounts of blood. On MR imaging, CMBs are seen as round hypointense foci, and histologically they are represented by hemosiderin deposits in macrophages, mainly located around small vessels.^1,2 The pathology of CMBs is thought to vary depending on the location: Deep and infratentorial CMBs represent underlying hypertensive arteriopathy, whereas lobar CMBs mainly represent vascular amyloid deposition, so-called cerebral amyloid angiopathy (CAA).³CAA and hypertension are common in patients with dementia. CAA is reported to be present in up to 98% of patients with Alzheimer disease in postmortem studies, and hypertension in middle-aged and elderly populations has been related to the development of dementia.^4,5 Studies have shown a higher prevalence of CMBs in patients with dementia compared with healthy populations. Alzheimer disease, for instance, is reported to have a CMB prevalence of 18%–32% versus 3%–11% in healthy populations imaged with MR field strengths of 1T–1.5T.^6–15 Consequently, CMBs are hypothesized to play an important role in the disease mechanisms of dementia as well as being a marker of the synergistic effects between vascular and amyloid pathology.¹⁶ Of further interest, CAA and hypertension are the most common causes of intracerebral hemorrhage, with CMBs being proposed as a possible predictor of intracerebral hemorrhage.¹⁷Investigating CMBs in dementia is of importance for further understanding the disease mechanisms of different dementia diagnoses and improved clinical and therapeutic treatment. CMBs and their location may give an insight into the vascular and amyloid pathology of dementia diagnoses and thus expose different dementia characteristics. Up-to-date studies on CMBs and dementia have been conducted mainly on small cohorts, without a standardized scale for CMB rating and with a scarcity of included dementia diagnoses. Furthermore, analyses have been made on a whole-cohort basis, rather than separating different dementia diagnoses and their respective CMB characteristics. In this study, we aimed to examine the prevalence, topography, and risk factors associated with CMBs in a large and diverse dementia population with subgroup analysis. By doing so, we hoped to gain insight in the pathophysiologic mechanisms in different dementia diagnoses. We hypothesized that CMB prevalence would be dependent on risk factors, depending on the dementia diagnosis, and that vascular risk factors would be important in the development of CMBs in dementia.