Brain Deep Medullary Veins on 7T MRI in Dutch-Type Hereditary Cerebral Amyloid Angiopathy

BACKGROUND: Deep medullary vein (DMV) changes occur in cerebral small vessel diseases (SVD) and in Alzheimer's disease. Cerebral amyloid angiopathy (CAA) is a common SVD that has a high co-morbidity with Alzheimer's disease. So far, DMVs have not been evaluated in CAA. OBJECTIVE: To evaluate DMVs in Dutch-type hereditary CAA (D-CAA) mutation carriers and controls, in relation to MRI markers associated with D-CAA. METHODS: Quantitative DMV parameters length, tortuosity, inhomogeneity, and density were quantified on 7 Tesla 3D susceptibility weighted MRI in pre-symptomatic D-CAA mutation carriers (n = 8), symptomatic D-CAA mutation carriers (n = 8), and controls (n = 25). Hemorrhagic MRI markers (cerebral microbleeds, intracerebral hemorrhages, cortical superficial siderosis, convexity subarachnoid hemorrhage), non-hemorrhagic MRI markers (white matter hyperintensities, enlarged perivascular spaces, lacunar infarcts, cortical microinfarcts), cortical grey matter perfusion, and diffusion tensor imaging parameters were assessed in D-CAA mutation carriers. Univariate general linear analysis was used to determine associations between DMV parameters and MRI markers. RESULTS: Quantitative DMV parameters length, tortuosity, inhomogeneity, and density did not differ between pre-symptomatic D-CAA mutation carriers, symptomatic D-CAA mutation carriers, and controls. No associations were found between DMV parameters and MRI markers associated with D-CAA. CONCLUSION: This study indicates that vascular amyloid-β deposition does not affect DMV parameters. In patients with CAA, DMVs do not seem to play a role in the pathogenesis of MRI markers associated with CAA

Harmonizing brain magnetic resonance imaging methods for vascular contributions to neurodegeneration

Introduction Many consequences of cerebrovascular disease are identifiable by magnetic resonance imaging (MRI), but variation in methods limits multicenter studies and pooling of data. The European Union Joint Program on Neurodegenerative Diseases (EU JPND) funded the HARmoNizing Brain Imaging MEthodS for VaScular Contributions to Neurodegeneration (HARNESS) initiative, with a focus on cerebral small vessel disease. Methods Surveys, teleconferences, and an in-person workshop were used to identify gaps in knowledge and to develop tools for harmonizing imaging and analysis. Results A framework for neuroimaging biomarker development was developed based on validating repeatability and reproducibility, biological principles, and feasibility of implementation. The status of current MRI biomarkers was reviewed. A website was created at www.harness-neuroimaging.org with acquisition protocols, a software database, rating scales and case report forms, and a deidentified MRI repository. Conclusions The HARNESS initiative provides resources to reduce variability in measurement in MRI studies of cerebral small vessel disease

Cortical phase changes in Alzheimer's disease at 7T MRI:a novel imaging marker

AbstractBackgroundPostmortem studies have indicated the potential of high-field magnetic resonance imaging (MRI) to visualize amyloid depositions in the cerebral cortex. The aim of this study is to test this hypothesis in patients with Alzheimer's disease (AD).MethodsT2*-weighted MRI was performed in 16 AD patients and 15 control subjects. All magnetic resonance images were scored qualitatively by visual assessment, and quantitatively by measuring phase shifts in the cortical gray matter and hippocampus. Statistical analysis was performed to assess differences between groups.ResultsPatients with AD demonstrated an increased phase shift in the cortex in the temporoparietal, frontal, and parietal regions (P < .005), and this was associated with individual Mini-Mental State Examination scores (r = −0.54, P < .05).ConclusionIncreased cortical phase shift in AD patients demonstrated on 7-tesla T2*-weighted MRI is a potential new biomarker for AD, which may reflect amyloid pathology in the early stages

Distinct functional subnetworks of cognitive domains in older adults with minor cognitive deficits

Abstract: Although past research has established a relationship between functional connectivity and cognitive function, less is known about which cognitive domains are associated with which specific functional networks. This study investigated associations between functional connectivity and global cognitive function and performance in the domains of memory, executive function and psychomotor speed in 166 older adults aged 75-91 years (mean = 80.3 +/- 3.8) with minor cognitive deficits (Mini-Mental State Examination scores between 21 and 27). Functional connectivity was assessed within 10 standard large-scale resting-state networks and on a finer spatial resolution between 300 nodes in a functional connectivity matrix. No domain-specific associations with mean functional connectivity within large-scale resting-state networks were found. Node-level analysis revealed that associations between functional connectivity and cognitive performance differed across cognitive functions in strength, location and direction. Specific subnetworks of functional connections were found for each cognitive domain in which higher connectivity between some nodes but lower connectivity between other nodes were related to better cognitive performance. Our findings add to a growing body of literature showing differential sensitivity of functional connections to specific cognitive functions and may be a valuable resource for hypothesis generation of future studies aiming to investigate specific cognitive dysfunction with resting-state functional connectivity in people with beginning cognitive deficits. Drenth et al. investigated associations between functional connectivity and cognition in 166 non-demented older adults with minor cognitive deficits. The authors show that cognitive performance is differentially associated with functional connectivity per cognitive domain. Distinct subnetworks of functional connections were identified related to memory, executive function and psychomotor speed performance. Graphical Abstrac

Early Magnetic Resonance Imaging and Cognitive Markers of Hereditary Cerebral Amyloid Angiopathy

BACKGROUND AND PURPOSE: Early markers for cerebral amyloid angiopathy (CAA) are largely unknown. We aimed to identify which MRI (performed at 7 tesla and 3 tesla) and cognitive markers are an early sign in (pre-)symptomatic subjects with Hereditary Cerebral Hemorrhage With Amyloidosis-Dutch type (HCHWA-D). METHODS: Twenty-seven DNA-proven Dutch type mutation carriers (15 symptomatic and 12 pre-symptomatic) (mean age of 45.9) and 33 controls (mean age of 45.6) were included. 7T and 3T MRI was performed, CAA and small vessel disease type MRI markers were estimated, and cognitive performance was assessed. Univariate general linear modeling analysis was used to assess the association between MRI markers and cognitive performance on the one hand, and on the other mutation status, adjusted for age, sex and education. RESULTS: In symptomatic patients, all established CAA MRI markers (microbleeds, intracerebral hemorrhages, subarachnoid hemorrhages, superficial siderosis, microinfarcts, volume of white matter hyperintensities (WMHs) and dilated perivascular spaces in centrum semiovale) were increased compared to controls (p<0.05). In pre-symptomatic subjects, the prevalence of microinfarcts and median volume of WMHs were increased in comparison to controls (p<0.05). Symptomatic patients performed worse on all cognitive domains, whereas pre-symptomatic subjects did not show differences in comparison with controls (p<0.05). CONCLUSIONS: WMHs and microinfarcts are more prevalent among pre-symptomatic subjects and precede cognitive and neuropsychiatric symptoms and intracerebral hemorrhages