Cerebral microbleeds: different prevalence, topography, and risk factors depending on dementia diagnosis—the Karolinska Imaging Dementia Study.
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ABSTRACT: 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.
SUBMITTER: Shams S
PROVIDER: S-EPMC7964321 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Background and purposeCerebral microbleeds are thought to have potentially important clinical implications in dementia and stroke. However, the use of both T2* and SWI MR imaging sequences for microbleed detection has complicated the cross-comparison of study results. We aimed to determine the impact of microbleed sequences on microbleed detection and associated clinical parameters.Materials and methodsPatients from our memory clinic (n = 246; 53% female; mean age, 62) prospectively underwent 3T MR imaging, with conventional thick-section T2*, thick-section SWI, and conventional thin-section SWI. Microbleeds were assessed separately on thick-section SWI, thin-section SWI, and T2* by 3 raters, with varying neuroradiologic experience. Clinical and radiologic parameters from the dementia investigation were analyzed in association with the number of microbleeds in negative binomial regression analyses.ResultsPrevalence and number of microbleeds were higher on thick-/thin-section SWI (20/21%) compared with T2*(17%). There was no difference in microbleed prevalence/number between thick- and thin-section SWI. Interrater agreement was excellent for all raters and sequences. Univariate comparisons of clinical parameters between patients with and without microbleeds yielded no difference across sequences. In the regression analysis, only minor differences in clinical associations with the number of microbleeds were noted across sequences.ConclusionsDue to the increased detection of microbleeds, we recommend SWI as the sequence of choice in microbleed detection. Microbleeds and their association with clinical parameters are robust to the effects of varying MR imaging sequences, suggesting that comparison of results across studies is possible, despite differing microbleed sequences.
| S-EPMC8013035 | biostudies-literature
Project description:Cerebral microbleeds, a marker of small vessel disease, are thought to be of importance in cognitive impairment. We aimed to study topographical distribution of cerebral microbleeds, and their involvement in disease pathophysiology, reflected by cerebrospinal fluid biomarkers; 1039 patients undergoing memory investigation underwent lumbar puncture and a brain magnetic resonance imaging scan. Cerebrospinal fluid samples were analyzed for amyloid β(Aβ)42, total tau(T-tau), tau phosphorylated at threonine 18(P-tau) and cerebrospinal fluid/serum albumin ratios. Magnetic resonance imaging sequences were evaluated for small vessel disease markers, including cerebral microbleeds, white matter hyperintensities and lacunes. Low Aβ42 levels were associated with lobar cerebral microbleeds in the whole cohort and Alzheimer's disease ( P < 0.001). High cerebrospinal fluid/serum albumin ratios were seen with increased number of cerebral microbleeds in the brainstem ( P < 0.001). There were tendencies for increased Aβ42 levels and decreased Tau levels with deep and infratentorial cerebral microbleeds ( P < 0.05). Lobar cerebral microbleeds were associated with white matter hyperintensities and lacunes ( P < 0.001). Probable cerebral amyloid angiopathy-related cerebral microbleeds were associated with low Aβ42 levels and lacunes, whereas probable cerebral amyloid angiopathy-unrelated cerebral microbleeds were associated with white matter hyperintensities ( P < 0.001). Our findings show that cerebral microbleed distribution is associated with different patterns of cerebrospinal fluid biomarkers, supporting different pathogenesis of deep/infratentorial and lobar cerebral microbleeds.
| S-EPMC5363477 | biostudies-literature
Project description:ObjectiveTo determine whether microvascular damage, indicated by cerebral microbleeds (CMBs) and retinal microvascular signs, is associated with cognitive function and dementia in older persons.MethodsThis is a cross-sectional study of 3,906 participants (mean age 76 years; 58% women) in the AGES-Reykjavik Study (2002-2006). 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.ResultsPeople with multiple (≥ 2) CMBs had lower Z scores on tests of processing speed (β-coefficient -0.16; 95% confidence interval -0.26 to -0.05) and executive function (-0.14; -0.24 to -0.04); 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 (-0.25; -0.37 to -0.12), poorer executive function (-0.19; -0.31 to -0.07), and an increased odds ratio of vascular dementia (3.10; 1.11 to 8.62).ConclusionHaving 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.
| S-EPMC3013588 | biostudies-literature
Project description:ImportanceCerebral microbleeds are hypothesized downstream markers of brain damage caused by vascular and amyloid pathologic mechanisms. To date, whether their presence is associated with cognitive deterioration in the general population remains unclear.ObjectiveTo determine whether microbleeds, and more specifically microbleed count and location, are associated with an increased risk for cognitive impairment and dementia in the general population.Design, setting, and participantsThe Rotterdam Study, a prospective population-based study set in the general community, assessed the presence, number, and location of microbleeds at baseline (August 2005 to December 2011) on magnetic resonance imaging studies of the brain in 4841 participants 45 years or older. Participants underwent neuropsychological testing at 2 points a mean (SD) of 5.9 (0.6) years apart and were followed up for incident dementia throughout the study period until January 1, 2013. The association of microbleeds with cognitive decline and dementia was studied using multiple linear regression, linear mixed-effects modeling, and Cox proportional hazards.ExposuresCerebral microbleed presence, location, and number.Main outcomes and measuresCognitive decline measured by a decrease in neuropsychological test battery scores (Mini-Mental State Examination, Letter Digit Substitution Task, Word Fluency Test, Stroop test, 15-word Verbal Learning Test, and Purdue Pegboard Test) and compound scores (eg, G factor, executive function, information processing speed, memory, motor speed) and dementia.ResultsIn total, 3257 participants (1758 women [54.7%]; mean [SD] age, 59.6 [7.8] years) underwent baseline and follow-up cognitive testing. Microbleed prevalence was 15.3% (median [interquartile range] count, 1 [1-88]). The presence of more than 4 microbleeds was associated with cognitive decline. Lobar (with or without cerebellar) microbleeds were associated with a decline in executive functions (mean difference in z score, -0.31; 95% CI, -0.51 to -0.11; P = .003), information processing (mean difference in z score, -0.44; 95% CI, -0.65 to -0.22; P < .001), and memory function (mean difference in z score, -0.34; 95% CI, -0.64 to -0.03; P = .03), whereas microbleeds in other brain regions were associated with a decline in information processing and motor speed (mean difference in z score, -0.61; 95% CI, -1.05 to -0.17; P = .007). After a mean (SD) follow-up of 4.8 (1.4) years, 72 participants developed dementia, of whom 53 had Alzheimer dementia. The presence of microbleeds was associated with an increased risk for dementia after adjustment for age, sex, and educational level (hazard ratio, 2.02; 95% CI, 1.25-3.24), including Alzheimer dementia (hazard ratio, 2.10; 95% CI, 1.21-3.64).Conclusions and relevanceIn the general population, a high microbleed count was associated with an increased risk for cognitive deterioration and dementia. Microbleeds thus mark the presence of diffuse vascular and neurodegenerative brain damage.
| S-EPMC5966721 | biostudies-literature
Project description:Background and purposeThe burden of amyloid β is greater in patients with dementia with Lewy bodies than in those with Parkinson disease dementia, and an increased amyloid β load is closely related to a higher incidence of cerebral microbleeds. Here, we investigated the prevalence and topography of cerebral microbleeds in patients with dementia with Lewy bodies and those with Parkinson disease dementia to examine whether cerebral microbleeds are more prevalent in patients with dementia with Lewy bodies than in those with Parkinson disease dementia.Materials and methodsThe study population consisted of 42 patients with dementia with Lewy bodies, 88 patients with Parkinson disease dementia, and 35 controls who underwent brain MR imaging with gradient recalled-echo. Cerebral microbleeds were classified as deep, lobar, or infratentorial.ResultsThe frequency of cerebral microbleeds was significantly greater in patients with dementia with Lewy bodies (45.2%) than in those with Parkinson disease dementia (26.1%) or in healthy controls (17.1%; P = .017). Lobar cerebral microbleeds were observed more frequently in the dementia with Lewy bodies group (40.5%) than in the Parkinson disease dementia (17%; P = .004) or healthy control (8.6%; P = .001) group, whereas the frequencies of deep and infratentorial cerebral microbleeds did not differ among the 3 groups. Logistic regression analyses revealed that, compared with the healthy control group, the dementia with Lewy bodies group was significantly associated with the presence of lobar cerebral microbleeds after adjusting for age, sex, nonlobar cerebral microbleeds, white matter hyperintensities, and other vascular risk factors (odds ratio, 4.39 [95% CI, 1.27-15.25]). However, compared with the healthy control group, the Parkinson disease dementia group was not significantly associated with lobar cerebral microbleeds.ConclusionsThis study showed that patients with dementia with Lewy bodies had a greater burden of cerebral microbleeds and exhibited a lobar predominance of cerebral microbleeds than did patients with Parkinson disease dementia.
| S-EPMC7968772 | biostudies-literature
Project description:Cerebral microbleeds (CMBs) are MRI markers attributed to the most common cerebral angiopathies in the elderly and in patients with dementia: hypertensive and cerebral amyloid angiopathy. CMB detection in asymptomatic persons may help identify those at risk for dementia and may influence preventive strategies and design of clinical trials testing treatments for dementia. We studied the association of CMB with risk of incident dementia in community dwelling individuals. A total of 1296 dementia-free Framingham Heart Study participants (mean age 72 years; 54% women) with available brain MRI and incident dementia data during a mean follow-up period of 6.7 years were included. Using Cox proportional hazards models, we related CMB presence to incident dementia. Multivariable models were adjusted for age, sex, APOE status, and education, with additional models adjusting for vascular risk factors and MRI markers of ischemic brain injury. CMBs were observed in 10.8% and incident dementia in 85 participants (6.6% over study period). Participants with any CMB had 1.74 times higher risk of dementia (hazard ratio [HR] 1.74, 95% confidence interval [CI] 1.00-3.01), whereas those with deep and mixed CMB had a three-fold increased risk (HR 2.99, 95% CI 1.52-5.90). The associations were independent of vascular risk factors, and for deep and mixed CMB also independent of MRI markers of ischemia (HR 2.44, 95% CI 1.22-4.88). Purely lobar CMBs were not associated with incident dementia. Our findings support a role for hypertensive vasculopathy and the interplay of hypertensive and cerebral amyloid angiopathy in risk of dementia and suggest that CMB presence can identify individuals at risk of dementia.
| S-EPMC5401784 | biostudies-literature
Project description:Background:Cerebral microbleeds (CMBs) are associated with cerebrovascular risk factors and cognitive dysfunction among patients with Parkinson's disease (PD). However, whether CMBs themselves are associated with PD is to be elucidated. Methods:We analyzed the presence of CMBs using 3-Tesla brain magnetic resonance imaging in non-demented patients with PD and in age-, sex-, and hypertension-matched control subjects. PD patients were classified according to their motor subtypes: tremor-dominant, intermediate, and postural instability-gait disturbance (PIGD). Other cerebrovascular risk factors and small vessel disease (SVD) burdens were also evaluated. Results:Two-hundred and five patients with PD and 205 control subjects were included. The prevalence of CMBs was higher in PD patients than in controls (16.1% vs. 8.8%; odds ratio [OR], 2.126; P = 0.019); CMBs in the lobar area showed a significant difference between PD patients and controls (11.7% vs. 5.9%; OR, 2.234; P = 0.032). According to the motor subtype, CMBs in those with PIGD type showed significant difference from controls with respect to the overall brain area (21.1% vs. 8.9%; OR, 2.759; P = 0.010) and lobar area (14.6% vs. 4.9%; OR, 3.336; P = 0.016). Among PD patients, those with CMBs had higher age and more evidence of SVDs than those without CMBs. Conclusion:We found that CMBs are more frequent in PD patients than in controls, especially in those with the PIGD subtype and CMBs on the lobar area. Further study investigating the pathogenetic significance of CMBs is required.
| S-EPMC6221857 | biostudies-other
Project description:To assess the association of the number and anatomic location of cerebral microbleeds (CMBs), visible indicators of microvascular damage on MRI, with incident cognitive disease in the general population of older people.In the longitudinal population-based Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study, 2,602 participants 66 to 93 years of age and free of prevalent dementia underwent brain MRI and cognitive testing of verbal memory, processing speed, and executive function at baseline and a mean of 5.2 years later. Adjudicated incident dementia cases were diagnosed according to international guidelines.In the multiple linear regression models adjusted for demographic, genetic, cardiovascular risk, and other cerebrovascular MRI markers, the presence of CMBs located in deep or mixed (deep and lobar) areas was associated with a greater decline in all 3 cognitive domains. Mixed CMBs were the strongest correlate for decline in memory and speed. Compared to those with no CMBs, participants with ?3 CMBs had a steeper decline in a composite measure of global cognitive function, memory, and speed. Among those with ?3 deep or mixed CMBs, associations were strongest for memory; the association with speed was strongest in those having ?3 strictly lobar CMBs. People with ?3 CMBs, regardless of their locations, had a higher incidence of all-cause dementia and vascular dementia.Mixed or a higher load of CMBs, with some specificity for location, is associated with accelerated cognitive decline in older people. These findings suggest a role for hypertensive vasculopathy and the combined effect of hypertensive and cerebral amyloid angiopathy in the pathogenesis of cognitive deterioration.
| S-EPMC5447401 | biostudies-other
Project description:BackgroundThe prevalence of cerebral microbleeds (CMBs) in gradient echo T2*-weighted brain MRI has a positive correlation with hemorrhagic stroke incidence. However, the prevalence of CMBs in patients with left ventricular assist devices (LVADs) has not been evaluated. We evaluated the prevalence of CMBs and the relationship with hemorrhagic stroke incidence in patients with LVADs.Method and resultsWe analyzed results from brain MRI in prospective examinations of 35 consecutive patients who had undergone LVAD explantation for heart transplantation or recovery since 2011. The number and distribution of CMBs were counted, then the relationship between baseline characteristics and adverse events during LVAD support were analyzed. The mean age was 37.7±12.4 years and the mean LVAD duration was 2.43±1.08 years. Thirty-four (97%) patients had at least one CMB. Nine (26%) developed hemorrhagic stroke during LVAD support, and patients with hemorrhagic stroke had a significantly greater number of CMBs compared with patients without hemorrhagic stroke (5 [interquartile range (IQR), 4-7] versus 9 [IQR, 5-23]; odds ratio 1.14 [95% Confidence Interval (CI), 1.02-1.32], P=0.05). There was no significant relationship between age, LVAD support duration, or systolic blood pressure during LVAD. However, patients who had at least one episode of bacteremia (9 [IQR, 4-16] versus 5 [IQR, 3-7], P=0.06) and pump pocket infection (14 [IQR, 4-27] versus 5 [IQR, 3-7], P=0.08) showed a trend toward a greater number of CMBs than patients without bacteremia.ConclusionsThirty-four (97%) patients with continuous-flow LVAD had at least one CMB, and the number of CMBs were more prevalent in patients with hemorrhagic stroke and in patients with LVAD-related infection.
| S-EPMC5634264 | biostudies-literature
Project description:Background:We investigated the prevalence of and risk factors for cerebral microbleeds (CMBs) in a cross-sectional study of a general population of Japanese elderly. Methods:In 2012, brain MRI scanning at 1.5T and comprehensive health examination were conducted for 1281 residents aged 65 years or older. CMBs were defined as ovoid hypointensity lesions less than 10 mm in diameter on T2*-weighted images and classified into deep/infratentorial or lobar CMBs. Age- and sex-specific and overall prevalence of CMBs were estimated, and the associations of traditional cardiovascular risk factors and APOE polymorphism with the presence of CMBs were examined using a logistic regression analysis. Results:The crude prevalences of total, deep/infratentorial, and lobar CMBs were 18.7% (n = 240), 13.5% (n = 173), and 9.6% (n = 123), respectively. The prevalence of total CMBs was 23.0% in men and 15.5% in women and increased with aging in both sexes (both p for trend <0.01). Hypertension was significantly associated with the presence of both deep/infratentorial and lobar CMBs. Lower serum total cholesterol was a significant risk factor for deep/infratentorial CMBs, but not for lobar CMBs, while APOE ?4 carriers had a significantly higher likelihood only of lobar CMBs compared with noncarriers. Conclusions:Our study suggests that approximately 1 of 5 Japanese elderly people have CMBs, and that risk factors for deep/infratentorial and lobar CMBs are different, indicating the distinct pathologic backgrounds of these lesions.
| S-EPMC6075994 | biostudies-literature