Abstract
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.
Highlights
As the most common form of dementia, Alzheimer’s disease (AD) is characterized by memory and other cognitive ability deficits
The early-onset AD (EOAD) and late-onset AD (LOAD) patients matched well with their respective controls for age, gender, education level, GDS and frame-wise displacement (FD) value (P > 0.05, Table 1). Both EOAD and LOAD patients performed worse than their respective controls in MMSE, MoCA, Wechsler Memory Scale Logical Memory (WMS-LM) and AVLT scores (P < 0.05, Table 2)
Our results showed that the superior temporal gyrus (STG) had decreased interhemispheric functional connectivity in the EOAD patients
Summary
As the most common form of dementia, Alzheimer’s disease (AD) is characterized by memory and other cognitive ability deficits. According to the arbitrary age cut-off of 65 years, we can further classify AD into early-onset AD (EOAD) and late-onset AD (LOAD; McKhann et al, 1984; Filley et al, 1986). They share the same neuropathological hallmarks, EOAD features different clinical characteristics from LOAD. Neuroimaging studies have demonstrated that patients with EOAD present more atrophy and functional disconnection than LOAD patients
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