Abstract
Neuroimaging studies have demonstrated that patients with Alzheimer’s disease presented disconnection syndrome. However, little is known about the alterations of interhemispheric functional interactions and underlying structural connectivity in the AD patients. In this study, we combined resting-state functional MRI and diffusion tensor imaging (DTI) to investigate interhemispheric functional and structural connectivity in 16 AD, 16 mild cognitive impairment (MCI), as well as 16 cognitive normal healthy subjects (CN). The pattern of the resting state interhemispheric functional connectivity was measured with a voxel-mirrored homotopic connectivity (VMHC) method. Decreased VMHC was observed in AD and MCI subjects in anterior brain regions including the prefrontal cortices and subcortical regions with a pattern of AD<MCI<CN. Increased VMHC was observed in MCI subjects in posterior brain regions with patterns of AD/CN < MCI (sensorimotor cortex) and AD < CN/MCI (occipital gyrus). DTI analysis showed the most significant difference among the three cohorts was the fractional anisotropy in the genu of corpus callosum, which was positively associated with the VMHC of prefrontal and subcortical regions. Across all the three cohorts, the diffusion parameters in the genu of corpus callosum and VMHC in the above brain regions had significant correlation with the cognitive performance. These results demonstrate that there are specific patterns of interhemispheric functional connectivity changes in the AD and MCI, which can be significantly correlated with the integrity changes in the midline white matter structures. These results suggest that VMHC can be used as a biomarker for the degeneration of the interhemispheric connectivity in AD.
Highlights
Alzheimer's disease (AD), the most common form of dementia, presents with memory and cognitive decline
The Mini-Mental State Examination (MMSE), Clinical Dementia Rating (CDR), Montreal Cognitive Assessment (MoCA), Clock Drawing Task (CDT) and Activity of Daily Living scale (ADL) scores were significantly different among the three groups
The voxel-mirrored homotopic connectivity (VMHC) map from cognitive normal healthy subjects (CN) revealed strong interhemispheric connectivities in the brain regions known to be important for cognition, including the anterior and posterior cingulate cortex (ACC and PCC), dorsolateral prefrontal cortex (DLPFC), orbitofrontal cortex (OFC), sensorimotor cortex (SMC), parietal and occipital cortices, hippocampus and various temporal cortices, insula, basal ganglia, and thalamus
Summary
Alzheimer's disease (AD), the most common form of dementia, presents with memory and cognitive decline. Mild cognitive impairment (MCI) is considered a precursor of AD; people with MCI are diagnosed with AD at a rate of 10–15% per year [1] compared to 2–3% per year for the general population of the same age range It is unclear, how the AD pathological lesions initiated in the medial temporal lobes lead to prominent functional deficits in memory and to dementia. It has been shown that AD patients can perform normally for some tasks that relied on intrahemispheric processing but perform poorly for the tasks that required interhemispheric communication [2], which suggests a plausible hypothesis that AD patients may present a deficit in the interhemispheric integration of information This hypothesis is supported by morphologic MRI findings that the corpus callosum, the most important fiber tract for interhemispheric connectivity, has consistently exhibited marked atrophy in AD and MCI [3, 4]. The relationship between these structural changes and the functional deficits remains to be determined [8]
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