Tissue Microstructural Changes Are Independently Associated With Cognitive Impairment in Cerebral Amyloid Angiopathy (original) (raw)
Related papers
Cognitive Impairment Before Intracerebral Hemorrhage Is Associated With Cerebral Amyloid Angiopathy
Stroke, 2018
Although the association between cerebral amyloid angiopathy (CAA) and cognitive impairment is increasingly recognized, it is not clear whether this is because of the impact of recurrent intracerebral hemorrhage (ICH) events, disruptions caused by cerebral small vessel damage, or both. We investigated this by considering whether cognitive impairment before ICH was associated with neuroimaging features of CAA on magnetic resonance imaging. We studied 166 patients with neuroimaging-confirmed ICH recruited to a prospective multicentre observational study. Preexisting cognitive impairment was determined using the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). Magnetic resonance imaging markers of cerebral small vessel disease, including CAA, were rated by trained observers according to consensus guidelines. The prevalence of cognitive impairment before ICH was 24.7% (n=41) and, in adjusted analyses, was associated with fulfilling the modified Boston criteria for p...
Microinfarct disruption of white matter structure: A longitudinal diffusion tensor analysis
Neurology, 2014
Objective: To evaluate the local effect of small asymptomatic infarctions detected by diffusionweighted imaging (DWI) on white matter microstructure using longitudinal structural and diffusion tensor imaging (DTI). Methods: Nine acute to subacute DWI lesions were identified in 6 subjects with probable cerebral amyloid angiopathy who had undergone high-resolution MRI both before and after DWI lesion detection. Regions of interest (ROIs) corresponding to the site of the DWI lesion (lesion ROI) and corresponding site in the nonlesioned contralateral hemisphere (control ROI) were coregistered to the pre-and postlesional scans. DTI tractography was additionally performed to reconstruct the white matter tracts containing the ROIs. DTI parameters (fractional anisotropy [FA], mean diffusivity [MD]) were quantified within each ROI, the 6-mm lesion-containing tract segments, and the entire lesion-containing tract bundle. Lesion/control FA and MD ratios were compared across time points. Results: The postlesional scans (performed a mean 7.1 6 4.7 months after DWI lesion detection) demonstrated a decrease in median FA lesion/control ROI ratio (1.08 to 0.93, p 5 0.038) and increase in median MD lesion/control ROI ratio (0.97 to 1.17, p 5 0.015) relative to the prelesional scans. There were no visible changes on postlesional high-resolution T1-weighted and fluid-attenuated inversion recovery images in 4 of 9 lesion ROIs and small (2-5 mm) T1 hypointensities in the remaining 5. No postlesional changes in FA or MD ratios were detected in the 6mm lesion-containing tract segments or full tract bundles. Conclusions: Asymptomatic DWI lesions produce chronic local microstructural injury. The cumulative effects of these widely distributed lesions may directly contribute to small-vessel-related vascular cognitive impairment. Neurology ® 2014;83:182-188 GLOSSARY CAA 5 cerebral amyloid angiopathy; CMI 5 cerebral microinfarct; DTI 5 diffusion tensor imaging; DWI 5 diffusion-weighted imaging; FA 5 fractional anisotropy; FLAIR 5 fluid-attenuated inversion recovery; MD 5 mean diffusivity; MEMPRAGE 5 multiecho magnetization-prepared rapid-acquisition gradient echo; MNI 5 Montreal Neurological Institute; ROI 5 region of interest.
White matter hyperintensity patterns in cerebral amyloid angiopathy and hypertensive arteriopathy
Neurology, 2016
Objective: To identify different white matter hyperintensity (WMH) patterns between 2 hemorrhage-prone cerebral small vessel diseases (SVD): cerebral amyloid angiopathy (CAA) and hypertensive arteriopathy (HA). Methods: Consecutive patients with SVD-related intracerebral hemorrhage (ICH) from a singlecenter prospective cohort were analyzed. Four predefined subcortical WMH patterns were compared between the CAA and HA groups. These WMH patterns were (1) multiple subcortical spots; (2) peri-basal ganglia (BG); (3) large posterior subcortical patches; and (4) anterior subcortical patches. Their associations with other imaging (cerebral microbleeds [CMBs], enlarged perivascular spaces [EPVS]) and clinical markers of SVD were investigated using multivariable logistic regression. Results: The cohort included 319 patients with CAA and 137 patients with HA. Multiple subcortical spots prevalence was higher in the CAA compared to the HA group (29.8% vs 16.8%; p 5 0.004). Peri-BG WMH pattern was more common in the HA-vs the CAA-ICH group (19% vs 7.8%; p 5 0.001). In multivariable logistic regression, presence of multiple subcortical spots was associated with lobar CMBs (odds ratio [OR] 1.23; 95% confidence interval [CI] 1.01-1.50, p 5 0.039) and high degree of centrum semiovale EPVS (OR 2.43; 95% CI 1.56-3.80, p , 0.0001). By contrast, age (OR 1.05; 95% CI 1.02-1.09, p 5 0.002), deep CMBs (OR 2.46; 95% CI 1.44-4.20, p 5 0.001), total WMH volume (OR 1.02; 95% CI 1.01-1.04, p 5 0.002), and high BG EPVS degree (OR 8.81; 95% CI 3.37-23.02, p , 0.0001) were predictors of peri-BG WMH pattern. Conclusion: Different patterns of subcortical leukoaraiosis visually identified on MRI might provide insights into the dominant underlying microangiopathy type as well as mechanisms of tissue injury in patients with ICH. Neurology ® 2016;86:505-511 GLOSSARY BG 5 basal ganglia; CAA 5 cerebral amyloid angiopathy; CI 5 confidence interval; CMB 5 cerebral microbleeds; CSO 5 centrum semiovale; EPVS 5 enlarged perivascular spaces; FLAIR 5 fluid-attenuated inversion recovery; HA 5 hypertensive arteriopathy; ICH 5 intracerebral hemorrhage; MGH 5 Massachusetts General Hospital; OR 5 odds ratio; PV 5 periventricular; SC 5 subcortical; SVD 5 small vessel disease; TE 5 echo time; VBM 5 voxel-based morphometry; WMH 5 white matter hyperintensities. Sporadic cerebral amyloid angiopathy (CAA) and hypertensive arteriopathy (HA) are the 2 most common forms of cerebral small vessel disease (SVD) in older adults. 1 CAA results from b-amyloid deposition within cortical and leptomeningeal arteries whereas HA predominantly affects small perforating end-arteries of the deep gray nuclei and deep white matter. Both CAA and HA are common causes of intracerebral hemorrhage (ICH) 2,3 and cognitive impairment. 4 As they have intrinsically different pathophysiology, clinical significance, and prognosis, 1 specific imaging markers are needed to better understand potential disease mechanisms and facilitate future trials. 5 Both CAA and HA are associated with characteristic neuroimaging markers, including cerebral microbleeds (CMB), 6 white matter hyperintensities (WMH), 7 and enlarged perivascular
Neurobiology of Aging, 2009
C erebral amyloid angiopathy (CAA) has many manifestations, including intracerebral hemorrhage (ICH), microbleeds, superficial siderosis, white matter hyperintensities (WMH) of presumed vascular origin, and microinfarction. 1 Despite the clinical observance of cognitive impairment in CAA, 2 the frequency, severity, and cognitive profile of CAA have not been determined prospectively based on neuropsychological testing. An autopsy-based study found that postmortem evidence of CAA was associated with antemortem declines in global cognition, perceptual speed, episodic memory, and semantic memory. 3 However, in this study, CAA was diagnosed only after death. The cognitive profile of living people diagnosed with CAA is not well understood. To determine the cognitive profile of patients with CAA, we analyzed neuropsychological, neuroimaging, and genetic data from an ongoing prospective cohort study (Functional Assessment of Vascular Reactivity in CAA [FAVR]). 4 We hypothesized that CAA participants would exhibit worse performance on tests of executive function and processing speed than on tests of episodic memory as a result of vascular cognitive impairment. We compared neuropsychological test results in nondemented CAA participants to participants with dementia caused by Alzheimer's disease (AD-dementia), mild cognitive impairment (MCI), and ischemic stroke (IS) (matched for stroke severity to CAA ICH participants). Additionally, we hypothesized that higher WMH volume in CAA participants would be associated with worse executive function and processing speed and that the presence of the apolipoprotein E (APOE) ε4 allele would be associated with worse episodic memory. Background and Purpose-Autopsy studies suggest that cerebral amyloid angiopathy (CAA) is associated with cognitive impairment and risk for dementia. We analyzed neuropsychological test data from a prospective cohort study of patients with CAA to identify the prevalence of cognitive impairment and its associations with brain magnetic resonance imaging features and the apolipoprotein E genotype. Methods-Data were analyzed from 34 CAA, 16 Alzheimer's disease, 69 mild cognitive impairment, and 27 ischemic stroke participants. Neuropsychological test results were expressed as z scores in relation to normative data provided by the test manuals and then grouped into domains of memory, executive function, and processing speed. Results-Mean test scores in CAA participants were significantly lower than norms for memory (−0.44±1.03; P=0.02), executive function (−1.14±1.07; P<0.001), and processing speed (−1.06±1.12; P<0.001). Twenty-seven CAA participants (79%) had mild cognitive impairment based on low cognitive performance accompanied by cognitive concerns. CAA participants had similarly low executive function scores as Alzheimer's disease, but relatively preserved memory. CAA participants' scores were lower than those of ischemic stroke controls for executive function and processing speed. Lower processing speed scores in CAA were associated with higher magnetic resonance imaging white matter hyperintensity volume. There were no associations with the apolipoprotein E ε4 allele. Conclusions-Mild cognitive impairment is very prevalent in CAA. The overall cognitive profile of CAA is more similar to that seen in vascular cognitive impairment rather than Alzheimer's disease. White matter ischemic lesions may underlie some of the impaired processing speed in CAA.
Total Magnetic Resonance Imaging Burden of Small Vessel Disease in Cerebral Amyloid Angiopathy
JAMA Neurology, 2016
IMPORTANCE Cerebral amyloid angiopathy (CAA) is characteristically associated with magnetic resonance imaging (MRI) biomarkers of small vessel brain injury, including strictly lobar cerebral microbleeds, cortical superficial siderosis, centrum semiovale perivascular spaces, and white matter hyperintensities. Although these neuroimaging markers reflect distinct pathophysiologic aspects in CAA, no studies to date have combined these structural imaging features to gauge total brain small vessel disease burden in CAA. OBJECTIVES To investigate whether a composite score can be developed to capture the total brain MRI burden of small vessel disease in CAA and to explore whether this score contributes independent and complementary information about CAA severity, defined as intracerebral hemorrhage during life or bleeding-related neuropathologic changes. DESIGN, SETTING, AND PARTICIPANTS This retrospective, cross-sectional study examined a single-center neuropathologic CAA cohort of eligible patients from the Massachusetts
Distinctive Clinical Effects of Haemorrhagic Markers in Cerebral Amyloid Angiopathy
Scientific reports, 2017
Restricted lobar cerebral microbleeds (CMBs) and cortical superficial siderosis (CSS) are the characteristic markers of cerebral amyloid angiopathy (CAA). However, their effects on clinical features has not been evaluated well. The purpose of this study is to investigate the clinical implication of these markers in clinical-radiologically diagnosed CAA. A total of 372 patients with possible or probable CAA who met the modified Boston criteria were recruited in a memory clinic setting. Cortical thickness was measured using surface based methods. Presence of restricted multiple lobar CMBs were independently associated with cortical thinning across the entire cortical regions while presence of CSS was independently associated with cortical thinning primarily in the bilateral frontal region. Presence of restricted multiple lobar CMBs was associated with impairment in all cognitive domains such as attention, language, visuospatial, memory and frontal executive functions while presence of...
Alzheimer's & Dementia, 2020
INTRODUCTION: Microstructural alterations as assessed by diffusion tensor imaging (DTI) are key findings in both Alzheimer's disease (AD) and small vessel disease (SVD). We determined the contribution of each of these conditions to diffusion alterations. METHODS: We studied six samples (N=365 participants) covering the spectrum of AD and SVD, including genetically-defined samples. We calculated diffusion measures from DTI and free water imaging. Simple linear, multivariable random forest, and voxel-based regressions were used to evaluate associations between AD biomarkers (amyloid-beta, tau), SVD imaging markers, and diffusion measures. RESULTS: SVD markers were strongly associated with diffusion measures and showed a higher contribution than AD biomarkers in multivariable analysis across all memory clinic samples. Voxel-wise analyses between tau and diffusion measures were not significant. DISCUSSION: In memory clinic patients, the effect of SVD on diffusion alterations largely exceeds the effect of AD, supporting the value of diffusion measures as markers of SVD.
Cerebral amyloid angiopathy in the elderly: vessel walls changes and relationship with dementia
Acta Neuropathologica, 2003
Aβ peptide deposits are observed in brain cortical and leptomeningeal microvessels in a few families, in patients with Alzheimer's disease and in cognitively normal elderly subjects. These deposits, which cause Aβ amyloid angiopathy, are usually associated with other lesions induced by Aβ peptide and tau pathologies. To investigate the consequences of cerebral amyloid angiopathy on arterial morphology and search for correlations with the degree of cognitive impairment, we carried out a prospective clinicopathological and morphometric study in 29 institutionalized elderly patients cognitively normal or affected with sporadic dementia associated with Alzheimer-type lesions, cerebral infarcts or both. We measured the external and internal diameters of arteries 40-120 µm wide, containing moderate or severe Aβ deposits, and of unaffected arteries in the temporal and frontal lobes. We found no differences in the mean external diameters. In contrast, the mean internal diameters of vessels with moderate Aβ deposits were smaller than those of unaffected vessels. Conversely, the internal diameters of severely affected vessels were larger than those of unaffected vessels. This suggests that arterial walls become thicker during the early stages of amyloid angiopathy, and the diameter of the lumen decreases, whereas during advanced stages, the walls become thinner and the lumen becomes larger. In addition, we assessed the overall severity of amyloid angiopathy. This showed that thinner arterial walls and the severity of amyloid angiopathy were correlated to dementia. In a multivariate model that integrates the other macroscopic and microscopic lesions that may be implied in the mechanism of cognitive impairment, the severity of amyloid angiopathy per se explained 10% of the variability in the cognitive impairment.