Cortical Thickness and Its Association with Clinical Cognitive and Neuroimaging Markers in Cerebral Amyloid Angiopathy

Subotic, Arsenije; McCreary, Cheryl R.; Saad, Feryal; Nguyen, Amanda; Alvarez-Veronesi, Ana; Zwiers, Angela; Charlton, Anna; Beaudin, Andrew E.; Ismail, Zahinoor; Pike, G. Bruce; Smith, Eric E.

doi:10.3233/jad-210138

Cited by 25 publications

(25 citation statements)

References 52 publications

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“…Cerebral amyloid angiopathy (CAA) is a disease where vascular and AD pathologies coexisted. Studies have found that CAA could lead to cognitive decline, which might be achieved by reducing the thickness of the cortex (Subotic et al, 2021 ). A lot of anti-Aβ drugs were proposed but failed in clinical trials, so it is urgent to find new treatments to prevent AD progression in the early stage (Long and Holtzman, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

The Correlation Between White Matter Hyperintensity Burden and Regional Brain Volumetry in Patients With Alzheimer's Disease

Cao

Mai²,

Fang³

et al. 2022

Front. Hum. Neurosci.

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BackgroundWhite matter hyperintensities (WMHs) and regional brain lobe atrophy coexist in the brain of patients with Alzheimer's disease (AD), but the association between them in patients with AD still lacks comprehensive investigation and solid imaging data support.ObjectiveWe explored whether WMHs can promote the pathological process of AD by aggravating atrophy in specific brain regions and tried to explain the regional specificity of these relationships.MethodsA sample of 240 adults including 180 normal controls (NCs) and 80 cases with AD were drawn from the ADNI database. T1-weighted magnetic resonance imaging (MRI) and T2-weighted fluid-attenuated MRI of the participants were downloaded and were analyzed using AccuBrain® to generate the quantitative ratio of WMHs (WMHr, WMH volumes corrected by intracranial volume) and regional brain atrophy. We also divided WMHr into periventricular WMHr (PVWMHr) and deep WMHr (DWMHr) for the purpose of this study. The Cholinergic Pathways Hyperintensities Scale (CHIPS) scores were conducted by two evaluators. Independent t-test, Mann–Whitney U test, or χ2 test were used to compare the demographic characteristics, and Spearman correlation coefficient values were used to determine the association between WMHs and different regions of brain atrophy.ResultsPositive association between WMHr and quantitative medial temporal lobe atrophy (QMTA) (rs = 0.281, p = 0.011), temporal lobe atrophy (rs = 0.285, p = 0.011), and insular atrophy (rs = 0.406, p < 0.001) was found in the AD group before Bonferroni correction. PVWMHr contributed to these correlations. By separately analyzing the relationship between PVWMHr and brain atrophy, we found that there were still positive correlations after correction in QMTA (rs = 0.325, p = 0.003), temporal lobe atrophy (rs = 0.298, p = 0.007), and insular atrophy (rs = 0.429, p < 0.001) in AD group.ConclusionWMH severity tends to be associated with regional brain atrophy in patients with AD, especially with medial temporal lobe, temporal lobe, and insular lobe atrophy. PVWMHs were devoted to these correlations.

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Section: Discussionmentioning

confidence: 99%

The Correlation Between White Matter Hyperintensity Burden and Regional Brain Volumetry in Patients With Alzheimer's Disease

Cao

Mai²,

Fang³

et al. 2022

Front. Hum. Neurosci.

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“…Data were obtained from two referral‐based prospective observational studies: (1) Functional Assessment of Vascular Reactivity (FAVR), 22 and (2) Comprehensive Assessment of Neurodegeneration and Dementia (COMPASS‐ND). 23 …”

Section: Methodsmentioning

confidence: 99%

Functional connectivity and mild behavioral impairment in dementia‐free elderly

Ghahremani

Nathan

Smith

et al. 2023

A&D Transl Res & Clin Interv

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Background Mild behavioral impairment (MBI) is a syndrome that uses later‐life emergent and persistent neuropsychiatric symptoms (NPS) to identify a group at high risk for incident dementia. MBI is associated with neurodegenerative disease markers in advance of syndromic dementia. Functional connectivity (FC) correlates of MBI are understudied and could provide further insights into mechanisms early in the disease course. We used resting‐state functional magnetic resonance imaging (rs‐fMRI) to test the hypothesis that FC within the default mode network (DMN) and salience network (SN) of persons with MBI (MBI+) is reduced, relative to those without (MBI–). Methods From two harmonized dementia‐free cohort studies, using a score of ≥6 on the MBI Checklist to define MBI status, 32 MBI+ and 63 MBI– individuals were identified (mean age: 71.7 years; 54.7% female). Seed‐based connectivity analysis was implemented in each MBI group using the CONN fMRI toolbox (v20.b), with the posterior cingulate cortex (PCC) as the seed region within the DMN and anterior cingulate cortex (ACC) as the seed within the SN. The average time series from the PCC and ACC were used to determine FC with other regions within the DMN (medial prefrontal cortex, lateral inferior parietal cortex) and SN (anterior insula, supramarginal gyrus, rostral prefrontal cortex), respectively. Age, sex, years of education, and Montreal Cognitive Assessment scores were included as model covariates. The false discovery rate approach was used to correct for multiple comparisons, with a p ‐value of .05 considered significant. Results For the DMN, MBI+ individuals exhibited reduced FC between the PCC and the medial prefrontal cortex, compared to MBI–. For the SN, MBI+ individuals exhibited reduced FC between the ACC and left anterior insula. Conclusion MBI in dementia‐free older adults is associated with reduced FC in networks known to be disrupted in dementia. Our results complement the evidence linking MBI with Alzheimer's disease biomarkers. Highlights Resting‐state functional magnetic resonance imaging was completed in 95 dementia‐free persons from FAVR and COMPASS‐ND studies. Participants were stratified by informant‐rated Mild Behavioral Impairment Checklist (MBI‐C) score, ≥6 for MBI+. MBI+ participants showed reduced functional connectivity (FC) within the default mode network and salience network. These FC changes are consistent with those seen in early‐stage Alzheimer's disease. MBI may help identify persons with early‐stage neurodegenerative disease.

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“…Recently, Subotic et al. demonstrated that CAA was associated with lower cortical thickness than that in controls and that the lower cortical thickness was associated with lower memory scores 31 . In addition, cases of CAA with an amnestic presentation tended to have a smaller hippocampal volume than their non‐amnestic counterparts 32 .…”

Section: Discussionmentioning

confidence: 99%

The vascular risk factors and vascular neuropathology in subjects with autopsy‐confirmed dementia with Lewy bodies

Chen

Gan

Yang

et al. 2022

Int J Geriat Psychiatry

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Background:The frequency of vascular risk factors (VRFs) and the relationship between vascular pathology and cognitive function in neurodegenerative disease remains incompletely understood. Objective:The purpose of this study was to describe the frequency of VRFs and vascular pathology and explore the relationship between vascular pathology and cognitive function in dementia with Lewy bodies (DLB). Methods: This study included 363 autopsy-confirmed DLB and 753 Alzheimer's disease (AD) patients from the National Alzheimer's Coordinating Center (NACC) database. We used chi-squared test and analysis of variance to compare the VRFs and related factors in DLB and AD. Multinomial logistic regression and Spearman's correlation test were used to examine the relationship between vascular pathology and cognitive function.Results: No significant differences of VRFs were identified between DLB and AD.Alzheimer's disease patients had higher rates of microinfarcts (23.5% vs. 16.3%, p = 0.005) and moderate to severe amyloid angiopathy (45.9% vs. 36.1%, p = 0.002).In DLB patients, only cerebral amyloid angiopathy (CAA) pathology was negatively correlated with memory domain (r = −0.263, p < 0.001) and language (r = −0.112, p = 0.034). The rates of APOE ε4 allele carriers (60.0% vs. 44.9%, p = 0.004) and CAA pathology (45.9% vs.23.4%, p < 0.001) were much higher in the group with an intermediate likelihood of DLB than in the group with a high likelihood. There was a negative correlation between CAA pathology and memory (logical memory) in the group with an intermediate likelihood of DLB. Conclusion:No difference of VRFs was identified between autopsy-confirmed DLB and AD. Cerebral amyloid angiopathy was shown to be an important pathology in DLB, which specifically correlated with memory and language. The groups with high and intermediate likelihood of DLB differed in terms of CAA pathology, and CAA pathology may play an important role in the development of DLB.

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Cortical Thickness and Its Association with Clinical Cognitive and Neuroimaging Markers in Cerebral Amyloid Angiopathy

Cited by 25 publications

References 52 publications

The Correlation Between White Matter Hyperintensity Burden and Regional Brain Volumetry in Patients With Alzheimer's Disease

The Correlation Between White Matter Hyperintensity Burden and Regional Brain Volumetry in Patients With Alzheimer's Disease

Functional connectivity and mild behavioral impairment in dementia‐free elderly

The vascular risk factors and vascular neuropathology in subjects with autopsy‐confirmed dementia with Lewy bodies

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