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Comparison of neuropsychiatric symptoms and diffusion tensor imaging correlates among patients with subcortical ischemic vascular disease and Alzheimer's disease.

ABSTRACT: BACKGROUND:The 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. METHODS:Twenty-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. RESULTS:Overall, 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. CONCLUSION:White 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.

SUBMITTER: Tu MC

PROVIDER: S-EPMC5534111 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Comparison of neuropsychiatric symptoms and diffusion tensor imaging correlates among patients with subcortical ischemic vascular disease and Alzheimer's disease.

Tu Min-Chien MC Huang Wen-Hui WH Hsu Yen-Hsuan YH Lo Chung-Ping CP Deng Jie Fu JF Huang Ching-Feng CF

BMC neurology 20170728 1

<h4>Background</h4>The 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.<h4>Methods</h4>Twenty-four patients with SIVD and 32 with AD we ...[more]

PMID: 28754095

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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:BackgroundAlthough diffusion tensor imaging has been a major research focus for Alzheimer's disease in recent years, it remains unclear whether it has sufficient stability to have biomarker potential. To date, frequently inconsistent results have been reported, though lack of standardisation in acquisition and analysis make such discrepancies difficult to interpret. There is also, at present, little knowledge of how the biometric properties of diffusion tensor imaging might evolve in the course of Alzheimer's disease.MethodsThe biomarker question was addressed in this study by adopting a standardised protocol both for the whole brain (tract-based spatial statistics), and for a region of interest: the midline corpus callosum. In order to study the evolution of tensor changes, cross-sectional data from very mild (N?=?21) and mild (N?=?22) Alzheimer's disease patients were examined as well as a longitudinal cohort (N?=?16) that had been rescanned at 12 months.Findings and significanceThe results revealed that increased axial and mean diffusivity are the first abnormalities to occur and that the first region to develop such significant differences was mesial parietal/splenial white matter; these metrics, however, remained relatively static with advancing disease indicating they are suitable as 'state-specific' markers. In contrast, increased radial diffusivity, and therefore decreased fractional anisotropy-though less detectable early-became increasingly abnormal with disease progression, and, in the splenium of the corpus callosum, correlated significantly with dementia severity; these metrics therefore appear 'stage-specific' and would be ideal for monitoring disease progression. In addition, the cross-sectional and longitudinal analyses showed that the progressive abnormalities in radial diffusivity and fractional anisotropy always occurred in areas that had first shown an increase in axial and mean diffusivity. Given that the former two metrics correlate with dementia severity, but the latter two did not, it would appear that increased axial diffusivity represents an upstream event that precedes neuronal loss.

Project description:Background: Neuropsychiatric symptoms due to Alzheimer's disease (AD) and mild cognitive impairment (MCI) can decrease quality of life for patients and increase caregiver burden. Better characterization of neuropsychiatric symptoms and methods of analysis are needed to identify effective treatment targets. The current investigation leveraged the National Alzheimer's Coordinating Center (NACC) Uniform Data Set (UDS) to examine the network structure of neuropsychiatric symptoms among symptomatic older adults with cognitive impairment. Methods: The network relationships of behavioral symptoms was estimated from Neuropsychiatric Inventory Questionnaire (NPI-Q) data acquired from 12,494 older adults with MCI and AD during their initial visit. Network analysis provides insight into the relationships among sets of symptoms and allows calculation of the strengths of the relationships. Nodes represented individual NPI-Q symptoms and edges represented the pairwise dependency between symptoms. Node centrality was calculated to determine the relative importance of each symptom in the network. Results: The analysis showed patterns of connectivity among the symptoms of the NPI-Q. The network ( M =.28) consisted of mostly positive edges. The strongest edges connected nodes within symptom domain. Disinhibition and agitation/aggression were the most central symptoms in the network. Depression/dysphoria was the most frequently endorsed symptom, but it was not central in the network. Conclusions: Neuropsychiatric symptoms in MCI and AD are highly comorbid and mutually reinforcing. The presence of disinhibition and agitation/aggression yielded a higher probability of additional neuropsychiatric symptoms. Interventions targeting these symptoms may lead to greater neuropsychiatric symptom improvement overall. Future work will compare neuropsychiatric symptom networks across dementia etiologies, informant relationships, and ethnic/racial groups, and will explore the utility of network analysis as a means of interrogating treatment effects.

Dataset Information

Comparison of neuropsychiatric symptoms and diffusion tensor imaging correlates among patients with subcortical ischemic vascular disease and Alzheimer's disease.

Publications

Comparison of neuropsychiatric symptoms and diffusion tensor imaging correlates among patients with subcortical ischemic vascular disease and Alzheimer's disease.

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