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Dissociable Functional Brain Networks Associated With Apathy in Subcortical Ischemic Vascular Disease and Alzheimer's Disease.

ABSTRACT: Few studies have investigated differences in functional connectivity (FC) between patients with subcortical ischemic vascular disease (SIVD) and Alzheimer's disease (AD), especially in relation to apathy. Therefore, the aim of this study was to compare apathy-related FC changes among patients with SIVD, AD, and cognitively normal subjects. The SIVD group had the highest level of apathy as measured using the Apathy Evaluation Scale-clinician version (AES). Dementia staging, volume of white matter hyperintensities (WMH), and the Beck Depression Inventory were the most significant clinical predictors for apathy. Group-wise comparisons revealed that the SIVD patients had the worst level of "Initiation" by factor analysis of the AES. FCs from four resting state networks (RSNs) were compared, and the connectograms at the level of intra- and inter-RSNs revealed dissociable FC changes, shared FC in the dorsal attention network, and distinct FC in the salient network across SIVD and AD. Neuronal correlates for "Initiation" deficits that underlie apathy were explored through a regional-specific approach, which showed that the right inferior frontal gyrus, left middle frontal gyrus, and left anterior insula were the critical hubs. These findings broaden the disconnection theory by considering the effect of FC interactions across multiple RSNs on apathy formation.

SUBMITTER: Altunkaya S

PROVIDER: S-EPMC8851472 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Dissociable Functional Brain Networks Associated With Apathy in Subcortical Ischemic Vascular Disease and Alzheimer's Disease.

Altunkaya Sabri S Huang Sheng-Min SM Hsu Yen-Hsuan YH Yang Jir-Jei JJ Lin Chien-Yuan CY Kuo Li-Wei LW Tu Min-Chien MC

Frontiers in aging neuroscience 20220203

Few studies have investigated differences in functional connectivity (FC) between patients with subcortical ischemic vascular disease (SIVD) and Alzheimer's disease (AD), especially in relation to apathy. Therefore, the aim of this study was to compare apathy-related FC changes among patients with SIVD, AD, and cognitively normal subjects. The SIVD group had the highest level of apathy as measured using the Apathy Evaluation Scale-clinician version (AES). Dementia staging, volume of white matter ...[more]

PMID: 35185511

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Project description:ObjectiveTo describe and compare diffusion tensor imaging (DTI) parameters between patients with subcortical ischemic vascular disease (SIVD) and Alzheimer's disease (AD) diagnosed using structuralized neuropsychiatric assessments, and investigate potential neuronal substrates related to cognitive performance.MethodsThirty-five patients with SIVD, 40 patients with AD, and 33 cognitively normal control (NC) subjects matched by age and education level were consecutively recruited and underwent cognitive function assessments and DTI examinations. Comparisons among these three subgroups with regards to cognitive performance and DTI parameters including fractional anisotropy (FA) and mean diffusivity (MD) values were performed. Partial correlation analysis after controlling for age and education was used to evaluate associations between cognitive performance and DTI parameters.ResultsWith regards to cognitive performance, the patients with SIVD had lower total scores in frontal assessment battery (FAB) compared to those with AD (p < 0.05) in the context of comparable Mini-Mental Status Examination and Cognitive Abilities Screening Instrument scores. With regards to DTI parameters, there were more regions of significant differences in FA among these three subgroups compared with MD. Compared with NC group, the patients with SIVD had significant global reductions in FA (p < 0.001 ~ 0.05), while significant reductions in FA among the patients with AD were regionally confined within the left superior longitudinal fasciculus, genu and splenium of the corpus callosum, and bilateral forceps major, and the anterior thalamic radiation, uncinate fasciculus, and cingulum of the left side (p < 0.01 ~ 0.05). Analysis of FA values within the left forceps major, left anterior thalamic radiation, and genu of the corpus callosum revealed a 71.8% overall correct classification (p < 0.001) with sensitivity of 69.4%, specificity of 73.8%, positive predictive value of 69.4%, and negative predictive value of 73.8% in discriminating patients with SIVD from those with AD. In combined analysis of the patients with SIVD and AD (n = 75), the total FAB score was positively correlated with FA within the bilateral forceps minor, genu of the corpus callosum, left forceps major, left uncinate fasciculus, and right inferior longitudinal fasciculus (p = 0.001 ~ 0.038), and inversely correlated with MD within the right superior longitudinal fasciculus, genu and body of the corpus callosum, bilateral forceps minor, right uncinate fasciculus, and right inferior longitudinal fasciculus (p = 0.003 ~ 0.040).ConclusionsOur findings suggest the effectiveness of DTI measurements in distinguishing patients with early-stage AD from those with SIVD, with discernible changes in spatial distribution and magnitude of significance of the DTI parameters. Strategic FA assessments provided the most robust discriminative power to differentiate SIVD from AD, and FAB may serve as an additional cognitive marker. We also identified the neuronal substrates responsible for FAB performance.

Project description:BackgroundThe causes of behavioral and psychological symptoms of dementia (BPSD) vary according to the dementia subtype and associated neuropathology. The present study aimed to (i) compare BPSD between patients with subcortical ischemic vascular disease (SIVD) and Alzheimer's disease (AD) across stages, and (ii) explore the associations with diffusion tensor imaging (DTI) in the corpus callosum (CC) and other major fibers.MethodsTwenty-four patients with SIVD and 32 with AD were recruited. Four domains of the Neuropsychiatric Inventory (NPI) (hyperactivity, psychosis, affective, and apathy) and two DTI parameters [fractional anisotropy (FA) and mean diffusivity (MD)] within the genu, body (BCC), and splenium (SCC) of the CC and other major fibers were assessed.ResultsOverall, the patients with clinical dementia rating (CDR) 1 ~ 2 had higher scores in apathy domain than those with CDR0.5. Among those with CDR1 ~ 2, SIVD had higher scores in apathy domain than AD. MD values in the BCC/SCC were positively correlated with total NPI score and psychosis, hyperactivity, and apathy domains. FA values in the SCC were inversely correlated with total NPI score and psychosis domain. The correlations were modified by age, the CASI, and CDR scores. Stepwise linear regression models suggested that FA value within the left superior longitudinal fasciculus predicted the hyperactivity domain. MD value within the SCC/left uncinate fasciculus and FA value within the GCC/left forceps major predicted the psychosis domain. MD value within the right superior longitudinal fasciculus and CDR predicted the apathy domain. Further analysis suggested distinct patterns of regression models between SIVD and AD patients.ConclusionWhite matter integrity within the BCC/SCC had associations with multi-domains of BPSD. Our study also identified important roles of regions other than the CC to individual domain of BPSD, including the left superior longitudinal fasciculus to the hyperactivity domain, the left uncinate fasciculus/forceps major to the psychosis domain, and the right superior longitudinal fasciculus to the apathy domain. The neuronal substrates in predicting BPSD were different between SIVD and AD patients. Of note, apathy, which was more profound in SIVD, was associated with corresponding fiber disconnection in line with dementia severity and global cognition decline.

Dataset Information

Dissociable Functional Brain Networks Associated With Apathy in Subcortical Ischemic Vascular Disease and Alzheimer's Disease.

Publications

Dissociable Functional Brain Networks Associated With Apathy in Subcortical Ischemic Vascular Disease and Alzheimer's Disease.

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