Dataset Information

Increased Hippocampal-Inferior Temporal Gyrus White Matter Connectivity following Donepezil Treatment in Patients with Early Alzheimer's Disease: A Diffusion Tensor Probabilistic Tractography Study.

ABSTRACT: The incidence of Alzheimer's disease (AD) has been increasing each year, and a defective hippocampus has been primarily associated with an early stage of AD. However, the effect of donepezil treatment on hippocampus-related networks is unknown. Thus, in the current study, we evaluated the hippocampal white matter (WM) connectivity in patients with early-stage AD before and after donepezil treatment using probabilistic tractography, and we further determined the WM integrity and changes in brain volume. Ten patients with early-stage AD (mean age = 72.4 ± 7.9 years; seven females and three males) and nine healthy controls (HC; mean age = 70.7 ± 3.5 years; six females and three males) underwent a magnetic resonance (MR) examination. After performing the first MR examination, the patients received donepezil treatment for 6 months. The brain volumes and diffusion tensor imaging scalars of 11 regions of interest (the superior/middle/inferior frontal gyrus, the superior/middle/inferior temporal gyrus, the amygdala, the caudate nucleus, the hippocampus, the putamen, and the thalamus) were measured using MR imaging and DTI, respectively. Seed-based structural connectivity analyses were focused on the hippocampus. The patients with early AD had a lower hippocampal volume and WM connectivity with the superior frontal gyrus and higher mean diffusivity (MD) and radial diffusivity (RD) in the amygdala than HC (p < 0.05, Bonferroni-corrected). However, brain areas with a higher (or lower) brain volume and WM connectivity were not observed in the HC compared with the patients with early AD. After six months of donepezil treatment, the patients with early AD showed increased hippocampal-inferior temporal gyrus (ITG) WM connectivity (p < 0.05, Bonferroni-corrected).

SUBMITTER: Kim GW

PROVIDER: S-EPMC9917574 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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Increased Hippocampal-Inferior Temporal Gyrus White Matter Connectivity following Donepezil Treatment in Patients with Early Alzheimer's Disease: A Diffusion Tensor Probabilistic Tractography Study.

Kim Gwang-Won GW Park Kwangsung K Kim Yun-Hyeon YH Jeong Gwang-Woo GW

Journal of clinical medicine 20230127 3

The incidence of Alzheimer's disease (AD) has been increasing each year, and a defective hippocampus has been primarily associated with an early stage of AD. However, the effect of donepezil treatment on hippocampus-related networks is unknown. Thus, in the current study, we evaluated the hippocampal white matter (WM) connectivity in patients with early-stage AD before and after donepezil treatment using probabilistic tractography, and we further determined the WM integrity and changes in brain ...[more]

PMID: 36769615

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Project description:Primary progressive aphasia is a clinical syndrome that encompasses three major phenotypes: non-fluent/agrammatic, semantic and logopenic. These clinical entities have been associated with characteristic patterns of focal grey matter atrophy in left posterior frontoinsular, anterior temporal and left temporoparietal regions, respectively. Recently, network-level dysfunction has been hypothesized but research to date has focused largely on studying grey matter damage. The aim of this study was to assess the integrity of white matter tracts in the different primary progressive aphasia subtypes. We used diffusion tensor imaging in 48 individuals: nine non-fluent, nine semantic, nine logopenic and 21 age-matched controls. Probabilistic tractography was used to identify bilateral inferior longitudinal (anterior, middle, posterior) and uncinate fasciculi (referred to as the ventral pathway); and the superior longitudinal fasciculus segmented into its frontosupramarginal, frontoangular, frontotemporal and temporoparietal components, (referred to as the dorsal pathway). We compared the tracts' mean fractional anisotropy, axial, radial and mean diffusivities for each tract in the different diagnostic categories. The most prominent white matter changes were found in the dorsal pathways in non-fluent patients, in the two ventral pathways and the temporal components of the dorsal pathways in semantic variant, and in the temporoparietal component of the dorsal bundles in logopenic patients. Each of the primary progressive aphasia variants showed different patterns of diffusion tensor metrics alterations: non-fluent patients showed the greatest changes in fractional anisotropy and radial and mean diffusivities; semantic variant patients had severe changes in all metrics; and logopenic patients had the least white matter damage, mainly involving diffusivity, with fractional anisotropy altered only in the temporoparietal component of the dorsal pathway. This study demonstrates that both careful dissection of the main language tracts and consideration of all diffusion tensor metrics are necessary to characterize the white matter changes that occur in the variants of primary progressive aphasia. These results highlight the potential value of diffusion tensor imaging as a new tool in the multimodal diagnostic evaluation of primary progressive aphasia.

Project description:Background: Neurovascular coupling is associated with white matter (WM) structural integrity, and it is regulated by specific subtypes of dopaminergic receptors. An altered activity of such receptors, highly expressed in reward-related regions, has been reported in carriers of obesity-risk alleles of the fat mass and obesity associated (FTO) gene. Among the reward-related regions, the thalamus and the nucleus accumbens are particularly vulnerable to blood pressure dysregulation due to their peculiar anatomo-vascular characteristics, and have been consistently reported to be altered in early-stage obesity. We have thus hypothesized that a disruption in thalamus and nucleus accumbens WM microstructure, possibly on neurovascular basis, could potentially be a predisposing factor underlying the enhanced risk for obesity in the risk-allele carriers. Methods: We have tested WM integrity in 21 male participants genotyped on the FTO risk single nucleotide polymorphisms (SNP) rs9939609, through a deterministic tractography analysis. Only homozygous participants (9 AA, 12 TT) were included. 11 tracts were selected and categorized as following according to our hypothesis: "risk tracts", "obesity-associated tracts", and a control tract (forcpes major). We investigated whether an association existed between genotype, body mass index (BMI) and WM microstructural integrity in the "risk-tracts" (anterior thalamic radiation and accumbofrontal fasciculus) compared to other tracts. Moreover, we explored whether WM diffusivity could be related to specific personality traits in terms of punishment and reward sensitivity, as measure by the BIS/BAS questionnaire. Results: An effect of the genotype and an interaction effect of genotype and BMI were detected on the fractional anisotropy (FA) of the "risk tracts". Correlations between WM diffusivity parameters and measures of punishment and reward sensitivity were also detected in many WM tracts of both networks. Conclusions: A disruption of the structural connectivity from the nucleus accumbens and the thalamus might occur early in carriers of the FTO AA risk-allele, and possibly act as a predisposing factor to the development of obesity.

Dataset Information

Increased Hippocampal-Inferior Temporal Gyrus White Matter Connectivity following Donepezil Treatment in Patients with Early Alzheimer's Disease: A Diffusion Tensor Probabilistic Tractography Study.

Publications

Increased Hippocampal-Inferior Temporal Gyrus White Matter Connectivity following Donepezil Treatment in Patients with Early Alzheimer's Disease: A Diffusion Tensor Probabilistic Tractography Study.

Similar Datasets

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