Callosal degeneration topographically correlated with cognitive function in amnestic mild cognitive impairment and Alzheimer's disease dementia.
ABSTRACT: Degeneration of the corpus callosum (CC) is evident in the pathogenesis of Alzheimer's disease (AD). However, the correlation of microstructural damage in the CC on the cognitive performance of patients with amnestic mild cognitive impairment (aMCI) and AD dementia is undetermined. We enrolled 26 normal controls, 24 patients with AD dementia, and 40 single-domain aMCI patients with at least grade 1 hippocampal atrophy and isolated memory impairment. Diffusion tensor imaging (DTI) with fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (DA), and radial diffusivity (DR) were measured. The entire CC was parcellated based on fiber trajectories to specific cortical Brodmann areas using a probabilistic tractography method. The relationship between the DTI measures in the subregions of the CC and cognitive performance was examined. Although the callosal degeneration in the patients with aMCI was less extended than in the patients with AD dementia, degeneration was already exhibited in several subregions of the CC at the aMCI stage. Scores of various neuropsychological tests were correlated to the severity of microstructural changes in the subregional CC connecting to functionally corresponding cortical regions. Our results confirm that CC degeneration is noticeable as early as the aMCI stage of AD and the disconnection of the CC subregional fibers to the corresponding Brodmann areas has an apparent impact on the related cognitive performance.
Project description:Background: The cornu ammonis (CA), as part of the hippocampal formation, represents a primary target region of neural degeneration in amnestic mild cognitive impairment (aMCI). Previous studies have revealed subtle structural deficits of the CA subregions (CA1-CA3, bilateral) in aMCI; however, it is not clear how the network function is impacted by aMCI. The present study examined longitudinal changes in resting state functional connectivity (FC) of each CA subregion and how these changes relate to neuropsychological profiles in aMCI. Methods: Twenty aMCI and 20 healthy control (HC) participants underwent longitudinal cognitive assessment and resting state functional MRI scans at baseline and 15 months afterward. Imaging data were processed with published routines in SPM8 and CONN software. Two-way analysis of covariance was performed with covariates of age, gender, education level, follow up interval, gray matter volume, mean FD, as well as global correlation (GCOR). Pearson's correlation was conducted to evaluate the relationship between the longitudinal changes in CA subregional FC and neuropsychological performance in aMCI subjects. Results: Resting state FC between the right CA1 and right middle temporal gyrus (MTG) as well as between the left CA2 and bilateral cuneal cortex (CC) were decreased in aMCI subjects as compared to HC. Longitudinal decrease in FC between the right CA1 and right MTG was correlated with reduced capacity of episodic memory in aMCI subjects. Conclusion: The current findings suggest functional alterations in the CA subregions. CA1 connectivity with the middle temporal cortex may represent an important neural marker of memory dysfunction in aMCI.
Project description:Evidences suggested that both corpus callosum (CC) degeneration and alternations of homotopic inter-hemispheric functional connectivity (FC) are present in Alzheimer's disease (AD). However, the associations between region-specific CC degeneration and homotopic inter-hemispheric FC and their relationships with memory deficits in AD remain uncharacterized. We hypothesized that selective CC degeneration is associated with memory impairment in AD and amnestic mild cognitive impairment (aMCI), which is mediated by homotopic inter-hemispheric functional dysconnectivity. Using structural magnetic resonance imaging (MRI) and task-free functional MRI, we assessed the CC volume and inter-hemispheric FC in 66 healthy controls, 41 aMCI and 41 AD. As expected, AD had CC degeneration and attenuated inter-hemispheric homotopic FC. Nevertheless, aMCI had relatively less severe CC degeneration (mainly in mid-anterior, central, and mid-posterior) and no reduction in inter-hemispheric homotopic FC. The degeneration of each CC sub-region was associated with specific inter-hemispheric homotopic functional disconnections in AD and aMCI. More importantly, impairment of inter-hemispheric homotopic FC partially mediated the association between CC (particularly the central and posterior parts) degeneration and memory deficit. Notably, these results remained after controlling for hippocampal volume. Our findings shed light on how CC degeneration and the related inter-hemispheric FC impact memory impairment in early stage of AD.
Project description:Altered function of the medial temporal lobe (MTL) is a valuable indicator of conversion from amnestic mild cognitive impairment (aMCI) to Alzheimer's disease. This study is to delineate the functional circuitry of multiple subdivisions of parahippocampal gyrus and hippocampus (HIP) and to examine how this knowledge contributes to a more principled understanding of the contributions of its subregions to memory in aMCI. The functional connectivity (FC) analysis was performed in 85 aMCI and 129 healthy controls. The aMCI demonstrated the distinct disruptive patterns of the MTL subregional connectivity with the whole-brain. The right entorhinal cortex (ERC) and perirhinal cortex (PRC) showed increased connectivity with the left inferior and middle occipital gyrus, respectively, which potentially indicated a compensatory mechanism. Furthermore, the right altered MTL subregional FC was associated with episodic memory performance in aMCI. These results provide novel insights into the heterogeneous nature of its large-scale connectivity in MTL subregions in memory system underlying the memory deficits in aMCI. It further suggests that altered FC of MTL subregions is associated with the impairment of the differential encoding stages of memories and the functional changes in the specific right HIP-ERC-PRC-temporal circuitry may contribute to the impairment of episodic memory in aMCI.
Project description:Impaired structure and function of the hippocampus is a valuable predictor of progression from amnestic mild cognitive impairment (aMCI) to Alzheimer's disease (AD). As a part of the medial temporal lobe memory system, the hippocampus is one of the brain regions affected earliest by AD neuropathology, and shows progressive degeneration as aMCI progresses to AD. Currently, no validated biomarkers can precisely predict the conversion from aMCI to AD. Therefore, there is a great need of sensitive tools for the early detection of AD progression. In this review, we summarize the specific structural and functional changes in the hippocampus from recent aMCI studies using neurophysiological and neuroimaging data. We suggest that a combination of advanced multi-modal neuroimaging measures in discovering biomarkers will provide more precise and sensitive measures of hippocampal changes than using only one of them. These will potentially affect early diagnosis and disease-modifying treatments. We propose a new sequential and progressive framework in which the impairment spreads from the integrity of fibers to volume and then to function in hippocampal subregions. Meanwhile, this is likely to be accompanied by progressive impairment of behavioral and neuropsychological performance in the progression of aMCI to AD.
Project description:The authors assessed whether measures of hippocampal water diffusivity at baseline can predict future progression to Alzheimer disease (AD) in amnestic mild cognitive impairment (aMCI). Higher baseline hippocampal diffusivity was associated with a greater risk of progression to AD in aMCI (p = 0.002). Magnetic resonance diffusion-weighted imaging may help identify patients with aMCI who will progress to AD as well as or better than structural MRI measures of hippocampal atrophy.
Project description:Mild cognitive impairment (MCI) is a heterogeneous cognitive disorder that is often comorbid with Parkinson's diseases (PD). The amnestic subtype of PD-MCI (PD-aMCI) has a higher risk to develop dementia. However, there is a lack of studies on the white matter (WM) structural changes of PD-aMCI. We characterized the WM structural changes of PD-aMCI (n = 17) with cognitively normal PD (PD-CN, n = 19) and normal controls (n = 20), using voxel-based and tract-based spatial statistics (TBSS) analyses on fractional anisotropy (FA) axial diffusivity (AD), and radial diffusivity (RD). By excluding and then including the motor performance as a covariate in the comparison analysis between PD-aMCI and PD-CN, we attempted to discern the influences of two neuropathological mechanisms on the WM structural changes of PD-aMCI. The correlation analyses between memory and voxel-based WM measures in all PD patients were also performed (n = 36). The results showed that PD-aMCI had smaller FA values than PD-CN in the diffuse WM areas, and PD-CN had higher AD and RD values than normal controls in the right caudate. Most FA difference between PD-aMCI and PD-CN could be weakened by the motor adjustment. The FA differences between PD-aMCI and PD-CN were largely spatially overlapped with the memory-correlated FA values. Our findings demonstrated that the WM structural differences between PD-aMCI and PD-CN were mainly memory-related, and the influence of motor adjustment might indicate a common mechanism underlying both motor and memory impairment in PD-aMCI, possibly reflecting a predominant influence of dopaminergic neuropathology.
Project description:Changes in white matter (WM) microstructure may relate to the pathophysiology of cognitive impairment. Whether WM microstructure differs in two common pre-dementia subtypes, vascular mild cognitive impairment (VaMCI) and amnestic mild cognitive impairment (aMCI), is largely unknown. This study included 28 VaMCI (12 men, age: 46 ~ 77 years) and 34 aMCI patients (14 men, age: 51 ~ 79 years). All patients underwent a battery of neuropsychological tests and structural and diffusion magnetic resonance imaging (MRI) scanning. WM microstructure was quantified using diffusion MRI parameters: fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AxD) and radial diffusivity (RD). These parameters were compared between the two patient groups using tract-based spatial statistics (TBSS) after controlling for age, gender, and education. No significant differences in FA/MD/AxD/RD were observed between the VaMCI and aMCI groups, which suggests a similar pattern of WM microstructure in the early stage of cognitive impairment for different dementia types. However, the two groups exhibited significant differences in the relationship between FA and the Auditory Verbal Learning Test (AVLT), which were primarily located around the corona radiate and corpus callosum. Specifically, there were significant positive correlations (R = 0.64, P < 0.001) between the FA and AVLT in the VaMCI group, but the opposite trend was observed in the aMCI group (R = -0.34, P = 0.047). The differential relationship between WM and memory between VaMCI and aMCI indicates an independent neuropathology for specific memory deficits in different types of dementia.
Project description:We evaluate a fully automatic technique for labeling hippocampal subfields and cortical subregions in the medial temporal lobe in in vivo 3 Tesla MRI. The method performs segmentation on a T2-weighted MRI scan with 0.4 × 0.4 × 2.0 mm(3) resolution, partial brain coverage, and oblique orientation. Hippocampal subfields, entorhinal cortex, and perirhinal cortex are labeled using a pipeline that combines multi-atlas label fusion and learning-based error correction. In contrast to earlier work on automatic subfield segmentation in T2-weighted MRI [Yushkevich et al., 2010], our approach requires no manual initialization, labels hippocampal subfields over a greater anterior-posterior extent, and labels the perirhinal cortex, which is further subdivided into Brodmann areas 35 and 36. The accuracy of the automatic segmentation relative to manual segmentation is measured using cross-validation in 29 subjects from a study of amnestic mild cognitive impairment (aMCI) and is highest for the dentate gyrus (Dice coefficient is 0.823), CA1 (0.803), perirhinal cortex (0.797), and entorhinal cortex (0.786) labels. A larger cohort of 83 subjects is used to examine the effects of aMCI in the hippocampal region using both subfield volume and regional subfield thickness maps. Most significant differences between aMCI and healthy aging are observed bilaterally in the CA1 subfield and in the left Brodmann area 35. Thickness analysis results are consistent with volumetry, but provide additional regional specificity and suggest nonuniformity in the effects of aMCI on hippocampal subfields and MTL cortical subregions.
Project description:Subjective cognitive decline (SCD) may be an at-risk stage of Alzheimer's disease (AD) occurring prior to amnestic mild cognitive impairment (aMCI). To examine white matter (WM) defects in SCD, diffusion images from 27 SCD (age=65.3±8.0), 35 aMCI (age=69.2±8.6) and 25 AD patients (age=68.3±9.4) and 37 normal controls (NC) (age=65.1±6.8) were compared using Tract-Based Spatial Statistics (TBSS). WM impairments common to the three patient groups were extracted, and fractional anisotropy (FA) values were averaged in each group. As compared to NC subjects, SCD patients displayed widespread WM alterations represented by decreased FA (p<0.05), increased mean diffusivity (MD; p<0.05), and increased radial diffusivity (RD; p<0.05). In addition, localized WM alterations showed increased axial diffusivity (AxD; p<0.05) similar to what was observed in aMCI and AD patients (p<0.05). In the shared WM impairment tracts, SCD patients had FA values between the NC group and the other two patient groups. In the NC and SCD groups, the AVLT-delayed recall score correlated with higher AxD (r=-0.333, p=0.045), MD (r=-0.351, p=0.03) and RD (r=-0.353, p=0.025). In both the aMCI and AD groups the diffusion parameters were highly correlated with cognitive scores. Our study suggests that SCD patients present with widespread WM changes, which may contribute to the early memory decline they experience.
Project description:The notion that procedural learning and memory is spared in Alzheimer's disease (AD) has important implications for interventions aiming to build on intact cognitive functions. However, despite these clinical implications, there are mixed findings in the literature about whether or not procedural learning remains intact. This meta-analysis examines the standard mean difference of all published studies regarding procedural learning in AD dementia or amnestic Mild Cognitive Impairment (aMCI) compared to cognitively healthy older adults. Additionally, we conducted statistical equivalence analyses. Our systematic review showed that only a limited number of studies (k?=?17) have compared procedural learning between individuals with aMCI or AD dementia and healthy controls. Our meta-analysis, which synthesized these studies, demonstrated that while procedural learning performance was not statistically equivalent between individuals with aMCI or AD dementia, and healthy older adults, the difference was clinically and statistically trivial. Although larger studies are needed, the present findings suggest that procedural learning does appear to remain spared in aMCI and AD dementia.