Steroid responsive encephalopathy in cerebral amyloid angiopathy: a case report and review of evidence for immunosuppressive treatment

Cerebral amyloid angiopathy (CAA) is a common but often asymptomatic disease, characterized by deposition of amyloid in cerebral blood vessels. We describe the successful treatment of CAA encephalopathy with dexamethasone in a patient with CAA-related inflammation causing subacute progressive encephalopathy and seizures, which is an increasingly recognized subtype of CAA. The two pathological subtypes of CAA-related inflammation are described and a review of the literature is performed concerning immunosuppressive treatment of CAA-related inflammation with special attention to its pathological subtypes. Immunosuppressive therapy appears to be an appropriate treatment for CAA encephalopathy

Homocysteine and cerebral small vessel disease in patients with symptomatic atherosclerotic disease. The SMART-MR study

High homocysteine level is a risk factor for atherosclerosis and has been associated with lacunar infarcts (LIs), white matter lesions (WML) and cognitive dysfunction. It is unclear whether homocysteine is associated with cerebral small vessel disease (cSVD) on top of pre-existent atherosclerosis. We evaluated the association between homocysteine and cSVD in a large cohort of patients with symptomatic atherosclerotic disease. Within the SMART-MR study, a prospective cohort study of patients with symptomatic atherosclerotic disease, we estimated cross-sectional associations of total plasma homocysteine (THCY) and hyperhomocysteinemia (HHCY) with WML volume and presence of LI, using automated brain segmentation in MRIs of 1232 patients and cognitive function in 763 patients. WML were expressed as a logarithmic transformed percentage of total brain volume. Linear regression analyses adjusted for age, sex, vascular risk factors and extent of atherosclerosis showed that THCY and HHCY were significantly associated with larger WML volumes (B=0.01%: 95% CI 0.002-0.02%, and B=0.21%: 95% CI 0.04-0.39%). Increasing THCY was significantly associated with an increased risk of LIs (OR 1.04, 95% CI 1.01-1.07, per 1 μmol). Moreover, HHCY was associated with worse cognitive function (B=-0.12: 95% CI -0.22 to -0.01). In patients with symptomatic atherosclerotic disease, higher homocysteine levels are associated with higher WML volume, presence of LI and slightly worse cognitive functio

Presence and progression of white matter hyperintensities and cognition A meta-analysis

Objective: We aimed to quantify the effects of white matter hyperintensities (WMHs) on specific cognitive functions with particular attention to WMH progression and localization. Methods: PubMed (January 1990-July 2013) and bibliographies from included articles were used. Studies that were included (1) used MRI; (2) had a population-based or case-control design with a healthy control group that could be used for analysis; (3) matched/adjusted for age, sex, and education; and (4) addressed >= 1 predefined cognitive domains with >= 1 validated neuropsychological tests. Data were independently extracted by 2 investigators. Pearson r was extracted/ calculated and used as the common metric for the effect size across studies. Results: Twenty-three cross-sectional and 14 longitudinal studies were included with a total of 8,685 and 7,731 participants. Presence of WMHs was significantly associated with concurrent cognitive deficits in all examined domains: general intelligence (Fisher z - 0.10, 95% confidence interval [CI] -0.19 to -0.04), memory (-0.08, -0.13 to -0.06), processing speed (-0.11, -0.17 to -0.07), attention and executive functions (-0.11, -0.16 to -0.07), and perception/ construction (-0.15, -0.21 to -0.07). Similar effect sizes were observed for cognitive decline over time. WMH progression was associated with greater cognitive decline, particularly for general intelligence (Fisher z - 0.31, 95% CI -0.5 to -0.02) and attention and executive functions (-0.32, -0.34 to -0.28). Conclusions: The small but robust and consistent effects of WMHs on all cognitive domains suggest a more global effect on cognition than previously thought. Progression of WMHs was associated with even worse cognitive functioning, most pronounced in attention and executive functionin

Diabetes and other vascular risk factors for dementia: Which factor matters most? A systematic review

Vascular risk factors, such as type 2 diabetes, hypertension, obesity and dyslipidaemia often co-occur. Each of these factors has been associated with an increased risk of dementia, but it is uncertain which factor imposes the greatest risk. Moreover, the effect of age at time of exposure may differ across factors. This paper systematically reviews the evidence for the association of each of these risk factors with dementia. Longitudinal population-based studies that assessed the incidence of dementia in relation to diabetes (n = 14), hypertension (n = 13), dyslipidaemia (n = 8) or obesity (n = 9) were included. All four risk factors were indeed associated with an increased risk of dementia, but the results of studies on diabetes and obesity were most consistent. The magnitude of the effects was comparable across the risk factors, with odds ratios for 'any dementia' around 1.5. For hypertension, obesity and dyslipidaemia age appeared to modulate the association: the risk of dementia was generally largest in studies that measured the risk factor in midlife (compared to late life) and had a long follow-up time. At midlife, the population attributable risk of dementia was highest for hypertension, up to 30% of cases of late life dementia. Later in life diabetes appears to convey the highest risk of dementia. This review shows that vascular risk factors should be regarded as a major target for preventive measures, but that timing of such measures appears to be critical. (C) 2008 Elsevier B.V. All rights reserved

White Matter Hyperintensities and Cognition in Mild Cognitive Impairment and Alzheimer's Disease : A Domain-Specific Meta-Analysis

Background: White matter hyperintensities (WMHs) are related to cognitive dysfunction in the general population. The clinical relevance of WMHs in patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI) is, however, unclear. Objective: This meta-analysis aimed to quantify the association of WMHs and specific cognitive domains in patients with MCI or AD. Methods: PubMed (January 1990-January 2017) was searched for studies that used MRI to quantify WMHs, and measured cognitive functioning (≥1 predefined cognitive domain with ≥1 test) in a well-defined population of persons diagnosed with MCI or AD. Fischer's Z was used as the common metric for effect size. Modifying effects of demographics, MMSE, and WMH location were examined. Results: Twelve cross-sectional studies on AD (total n=1,370, median age 75 years) and 10 studies on MCI (9 cross-sectional, 1 longitudinal; total n=2,286, median age 73 years) were included. The association between WMHs and overall cognition was significantly stronger for MCI (-0.25, -0.36 to -0.14) than for AD (-0.11, -0.14 to -0.08; Q M =10.7, p<0.05). For both groups, largest effect sizes were found in attention and executive functions (-0.26, -0.36 to -0.15) and processing speed (-0.21, -0.35 to -0.12). No significant modifying effects of age and gender were found. Conclusion: WMHs have a medium-sized association with different cognitive functions in patients with MCI and a small, but statistically significant, association with cognition in AD. These result underscore the role of co-occurring vascular brain damage in MCI and AD

White Matter Hyperintensities and Cognition in Mild Cognitive Impairment and Alzheimer's Disease: A Domain-Specific Meta-Analysis

Background: White matter hyperintensities (WMHs) are related to cognitive dysfunction in the general population. The clinical relevance of WMHs in patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI) is, however, unclear. Objective: This meta-analysis aimed to quantify the association of WMHs and specific cognitive domains in patients with MCI or AD. Methods: PubMed (January 1990-January 2017) was searched for studies that used MRI to quantify WMHs, and measured cognitive functioning (>= 1 predefined cognitive domain with >= 1 test) in a well-defined population of persons diagnosed with MCI or AD. Fischer's Z was used as the common metric for effect size. Modifying effects of demographics, MMSE, and WMH location were examined. Results: Twelve cross-sectional studies on AD (total n = 1,370, median age 75 years) and 10 studies on MCI (9 cross-sectional, 1 longitudinal; total n = 2,286, median age 73 years) were included. The association between WMHs and overall cognition was significantly stronger for MCI (-0.25, -0.36 to -0.14) than for AD (-0.11, -0.14 to -0.08; Q(M) = 10.7, p < 0.05). For both groups, largest effect sizes were found in attention and executive functions (-0.26, -0.36 to -0.15) and processing speed (-0.21, -0.35 to -0.12). No significant modifying effects of age and gender were found. Conclusion: WMHs have a medium-sized association with different cognitive functions in patients with MCI and a small, but statistically significant, association with cognition in AD. These result underscore the role of co-occurring vascular brain damage in MCI and AD

White Matter Hyperintensities and Cognition in Mild Cognitive Impairment and Alzheimer's Disease: A Domain-Specific Meta-Analysis

Background: White matter hyperintensities (WMHs) are related to cognitive dysfunction in the general population. The clinical relevance of WMHs in patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI) is, however, unclear. Objective: This meta-analysis aimed to quantify the association of WMHs and specific cognitive domains in patients with MCI or AD. Methods: PubMed (January 1990-January 2017) was searched for studies that used MRI to quantify WMHs, and measured cognitive functioning (≥1 predefined cognitive domain with ≥1 test) in a well-defined population of persons diagnosed with MCI or AD. Fischer's Z was used as the common metric for effect size. Modifying effects of demographics, MMSE, and WMH location were examined. Results: Twelve cross-sectional studies on AD (total n=1,370, median age 75 years) and 10 studies on MCI (9 cross-sectional, 1 longitudinal; total n=2,286, median age 73 years) were included. The association between WMHs and overall cognition was significantly stronger for MCI (-0.25, -0.36 to -0.14) than for AD (-0.11, -0.14 to -0.08; Q M =10.7, p<0.05). For both groups, largest effect sizes were found in attention and executive functions (-0.26, -0.36 to -0.15) and processing speed (-0.21, -0.35 to -0.12). No significant modifying effects of age and gender were found. Conclusion: WMHs have a medium-sized association with different cognitive functions in patients with MCI and a small, but statistically significant, association with cognition in AD. These result underscore the role of co-occurring vascular brain damage in MCI and AD

Homocysteine and progression of generalized small-vessel disease The SMART-MR Study

Objective: We compared clinical characteristics of seizures at ischemic stroke presentation (SSP) to seizures during hospitalization post ischemic stroke (SDH), and their impacts on stroke outcome, using the Registry of the Canadian Stroke Network (RCSN) database. Methods: This cohort study included consecutive patients from the RCSN who had an acute ischemic stroke between July 2003 and March 2008. Outcome measures included morbidity, mortality, length of hospital stay, and discharge disposition. Clinical variables for either SSP or SDH were investigated and the stroke outcome was stratified by stroke severity. Results: The study included 10,261 patients with ischemic strokes: 157 patients (1.53%) had SSP and 208 patients (2.03%) had SDH. Compared to stroke patients without seizures, patients with SSP and SDH were younger, had more severe strokes (p <0.001), a higher admission rate to the intensive care unit (p <0.001), higher morbidity, and higher mortality (p <0.05). SSP was associated with female sex and less limb weakness, while SDH was associated with pneumonia and the presence of hemineglect. Importantly, patients with less severe strokes had higher morbidity and mortality (p <0.005) if SDH occurred. Variables predicting overall mortality were SDH, older age, higher Charlson-Deyo index, more severe strokes, and nonalert status on arrival (all p <0.001). Conclusions: SSP and SDH have different characteristics. SDH indicates a poorer prognosis in patients. Increased awareness of SSP and efforts to prevent SDH may be important in improving outcomes following clinical stroke car

Cerebellar Cortical Infarct Cavities : Correlation With Risk Factors and MRI Markers of Cerebrovascular Disease

BACKGROUND AND PURPOSE: Small cerebellar infarct cavities have been recently found on magnetic resonance imaging (MRI) to preferentially involve the cerebellar cortex, but epidemiological studies are lacking. We aimed to determine the prevalence and risk factor profiles of cerebellar cortical infarct cavities (≤1.5 cm) as well as their association with MRI markers of cerebrovascular disease and functioning. METHODS: We analyzed the 1.5 Tesla MRI of 636 patients (mean age, 62±9 years; 81% men) from the Second Manifestations of Arterial Disease-Memory, Depression and Aging (SMART-Medea) study. Logistic regression analyses were performed to estimate the associations of age, sex, vascular risk factors, MRI markers of cerebrovascular disease, and functioning with cerebellar cortical cavities, adjusted for age and sex. RESULTS: Cerebellar cortical infarct cavities occurred on MRI in 10% of patients and were significantly associated with age, intima-media thickness (odds ratio [OR], 2.0; 95% confidence interval [CI], 1.1-3.7), high levels of homocysteinemia (OR, 1.8; 95% CI, 1.0-3.3), cortical infarcts (OR, 2.9; 95% CI, 1.6-5.4), gray matter lacunes of presumed vascular origin (OR, 3.0; 95% CI, 1.6-5.8), brain stem infarcts (OR, 5.1; 95% CI, 1.9-13.6), and decreased brain parenchymal fraction (OR, 0.84; 95% CI, 0.74-0.94), but not with white matter hyperintensities (OR, 1.2; 95% CI, 0.8-1.8) or white matter lacunes of presumed vascular origin (OR, 1.1; 95% CI, 0.5-2.5). They were also associated with worse physical functioning (OR, -2.6; 95% CI, -5.7 to -0.9) but not with mental functioning. CONCLUSIONS: Cerebellar cortical infarct cavities are far more common than previously assumed based on symptomatic case series and are associated with markers of atherothromboembolic cerebrovascular disease

Do Lacunar Infarcts Have Different Aetiologies Risk Factor Profiles of Lacunar Infarcts in Deep White Matter and Basal Ganglia : The Second Manifestations of ARTerial Disease-Magnetic Resonance Study

Background: Evidence suggests that lacunar infarcts have different etiologies, possibly related to their anatomical location and vascular territory. We investigated the risk factor profiles of patients with new lacunar infarcts in the basal ganglia and deep white matter. Methods: Within the Second Manifestations of ARTerial disease-Magnetic Resonance study, a prospective cohort on brain changes on MRI in patients with symptomatic atherosclerotic disease, 679 patients (57 ± 9 years) had vascular screening and MRI at baseline and after a mean follow-up of 3.9 years. We investigated the association between vascular risk factors at baseline and appearance of new lacunar infarcts in the basal ganglia and deep white matter at follow-up. Results: New lacunar infarcts appeared in 44 patients in the basal ganglia and in 37 patients in the deep white matter. In multivariable analysis, older age, history of cerebrovascular disease, and baseline white matter hyperintensity (WMH) volume were associated with increased risk of new lacunar infarcts in both locations. Hyperhomocysteinemia was associated with increased risk of lacunar infarcts in the basal ganglia (relative risk [RR] 2.0; 95% CI 1.0-4.2), whereas carotid stenosis >70% (RR 2.5; 95% CI 1.2-5.0), smoking (per 10 pack-year: RR 1.1; 95% CI 1.0-1.3), hypertension (RR 3.4; 95% CI 1.2-9.7), and progression of WMH volume (RR 2.4; 95% CI 1.1-5.2) were associated with increased risk of lacunar infarcts in the deep white matter. Conclusions: The different risk factor profiles for new lacunar infarcts in basal ganglia and deep white matter indicate different etiologies. The independent association between progression of WMH and new deep white matter lacunar infarcts suggest a common etiology for these radiological abnormalities