Dataset Information

Functional connectivity changes differ in early and late-onset Alzheimer's disease.

ABSTRACT: At a similar stage, patients with early onset Alzheimer's disease (EOAD) have greater neocortical but less medial temporal lobe dysfunction and atrophy than the late-onset form of the disease (LOAD). Whether the organization of neural networks also differs has never been investigated. This study aims at characterizing basal functional connectivity (FC) patterns of EOAD and LOAD in two groups of 14 patients matched for disease duration and severity, relative to age-matched controls. All subjects underwent an extensive neuropsychological assessment. Magnetic resonance imaging was used to quantify atrophy and resting-state FC focusing on : the default mode network (DMN), found impaired in earlier studies on AD, and the anterior temporal network (ATN) and dorso-lateral prefrontal network (DLPFN), respectively involved in declarative memory and executive functions. Patterns of atrophy and cognitive impairment in EOAD and LOAD were in accordance with previous reports. FC within the DMN was similarly decreased in both EOAD and LOAD relative to controls. However, a double-dissociated pattern of FC changes in ATN and DLPFN was found. EOAD exhibited decreased FC in the DLPFN and increased FC in the ATN relative to controls, while the reverse pattern was found in LOAD. In addition, ATN and DLPFN connectivity correlated respectively with memory and executive performances, suggesting that increased FC is here likely to reflect compensatory mechanisms. Thus, large-scale neural network changes in EOAD and LOAD endorse both common features and differences, probably related to a distinct distribution of pathological changes.

SUBMITTER: Gour N

PROVIDER: S-EPMC6869697 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Functional connectivity changes differ in early and late-onset Alzheimer's disease.

Gour Natalina N Felician Olivier O Didic Mira M Koric Lejla L Gueriot Claude C Chanoine Valérie V Confort-Gouny Sylviane S Guye Maxime M Ceccaldi Mathieu M Ranjeva Jean Philippe JP

Human brain mapping 20131005 7

At a similar stage, patients with early onset Alzheimer's disease (EOAD) have greater neocortical but less medial temporal lobe dysfunction and atrophy than the late-onset form of the disease (LOAD). Whether the organization of neural networks also differs has never been investigated. This study aims at characterizing basal functional connectivity (FC) patterns of EOAD and LOAD in two groups of 14 patients matched for disease duration and severity, relative to age-matched controls. All subjects ...[more]

PMID: 24123475

Similar Datasets

Project description:Background: Early-onset Alzheimer's disease (EOAD) presents a different clinical profile than late-onset Alzheimer's disease (LOAD). Neuroimaging studies have demonstrated that patients with EOAD present more atrophy and functional disconnection than LOAD patients. However, it remains unknown whether the interhemispheric functional disconnection or its underlying structural impairment contributes to the different clinical profiles of EOAD and LOAD. Methods: According to the arbitrary cut-off age of 65, we included 22 EOAD patients, 27 LOAD patients and 38 healthy controls (further divided into 21 relatively young and 17 old controls). Participants underwent resting-state functional MRI, diffusion tensor imaging (DTI) and comprehensive neuropsychological assessments. We used voxel-mirrored homotopic connectivity (VMHC) to examine interhemispheric functional connectivity. Then, we calculated the diffusion index based on tract-based spatial statistics (TBSS). Two-sample t-tests were used to assess the interhemispheric connectivity differences between each patient group and its corresponding control group. Results: We found that the EOAD patients had lower VMHC in the hippocampus, parahippocampal gyrus (PHG), superior temporal gyrus (STG) and inferior parietal cortex (IPC) than did controls. Consistently, the EOAD patients exhibited white matter (WM) tract impairment in the posterior regions. On the other hand, the LOAD patients displayed increased VMHC and impaired WM tracts in the frontal region. Correlation analyses showed that VMHC in the IPC was related to executive function in the EOAD patients (r = -0.67, P < 0.05). Conclusion: In contrast to the LOAD patients, patients with EOAD exhibited more widely disrupted interhemispheric functional and structural connectivity, which overlapped well across brain regions. In addition, for the EOAD patients, decreased interhemispheric connectivity related to executive deficits. Our study suggested that different interhemispheric connectivity damage patterns may contribute to the distinct clinical profiles in EOAD and LOAD.

Project description:Co-pathologies play an important role in the expression of the Alzheimer's disease clinical phenotype and may influence treatment efficacy. Early-onset Alzheimer's disease, defined as manifesting before age 65, is viewed as a relatively pure form of Alzheimer's disease with a more homogeneous neuropathological substrate. We sought to compare the frequency of common neuropathological diagnoses in a consecutive autopsy series of 96 patients with early-onset Alzheimer's disease (median age of onset = 55 years, 44 females) and 48 with late-onset Alzheimer's disease (median age of onset = 73 years, 14 females). The UCSF Neurodegenerative Disease Brain Bank database was reviewed to identify patients with a primary pathological diagnosis of Alzheimer's disease. Prevalence and stage of Lewy body disease, limbic age-related TDP-43 encephalopathy (LATE), argyrophilic grain disease, hippocampal sclerosis, cerebral amyloid angiopathy, and vascular brain injury were compared between the two cohorts. We found at least one non-Alzheimer's disease pathological diagnosis in 98% of patients with early-onset Alzheimer's disease (versus 100% of late onset), and the number of comorbid diagnoses per patient was lower in early-onset than in late-onset Alzheimer's disease (median = 2 versus 3, Mann-Whitney Z = 3.00, P = 0.002). Lewy body disease and cerebral amyloid angiopathy were common in both early and late onset Alzheimer's disease (cerebral amyloid angiopathy: 86% versus 79%, Fisher exact P = 0.33; Lewy body disease: 49% versus 42%, P = 0.48, respectively), although amygdala-predominant Lewy body disease was more common in early than late onset Alzheimer's disease (22% versus 6%, P = 0.02). In contrast, LATE (35% versus 8%, P < 0.001), hippocampal sclerosis (15% versus 3%, P = 0.02), argyrophilic grain disease (58% versus 41%, P = 0.052), and vascular brain injury (65% versus 39%, P = 0.004) were more common in late than in early onset Alzheimer's disease, respectively. The number of co-pathologies predicted worse cognitive performance at the time of death on Mini-Mental State Examination [1.4 points/pathology (95% confidence interval, CI -2.5 to -0.2) and Clinical Dementia Rating-Sum of Boxes (1.15 point/pathology, 95% CI 0.45 to 1.84)], across early and late onset cohorts. The effect of sex on the number of co-pathologies was not significant (P = 0.17). Prevalence of at least one APOE ε4 allele was similar across the two cohorts (52% and 54%) and was associated with a greater number of co-pathologies (+0.40, 95% CI 0.01 to 0.79, P = 0.047), independent of age of symptom onset, sex, and disease duration. Females showed higher density of neurofibrillary tangles compared to males, controlling for age of onset, APOE ε4, and disease duration. Our findings suggest that non-Alzheimer's disease pathological diagnoses play an important role in the clinical phenotype of early onset Alzheimer's disease with potentially significant implications for clinical practice and clinical trials design.

Dataset Information

Functional connectivity changes differ in early and late-onset Alzheimer's disease.

Publications

Functional connectivity changes differ in early and late-onset Alzheimer's disease.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets