Abstract
Objective: We investigated the mediation effects of subcortical volume change in the relationship of amyloid beta (Aβ) and lacune with cognitive function in patients with mild cognitive impairment (MCI).Methods: We prospectively recruited 101 patients with MCI who were followed up with neuropsychological tests, MRI, or Pittsburgh compound B (PiB) PET for 3 years. The mediation effect of subcortical structure on the association of PiB or lacunes with cognitive function was analyzed using mixed effects models.Results: Volume changes in the amygdala and hippocampus partially mediated the effect of PiB changes on memory function (direct effect = −0.168/−0.175, indirect effect = −0.081/−0.077 for amygdala/hippocampus) and completely mediated the effect of PiB changes on clinical dementia rating scale sum of the box (CDR-SOB) (indirect effect = 0.082/0.116 for amygdala/hippocampus). Volume changes in the thalamus completely mediated the effect of lacune on memory, frontal executive functions, and CDR-SOB (indirect effect = −0.037, −0.056, and 0.047, respectively).Conclusions: Our findings provide a better understanding of the distinct role of subcortical structures in the mediation of the relationships of amyloid or vascular changes with a decline in specific cognitive domains.
Highlights
Alzheimer’s disease (AD) and vascular dementia are the most common causes of dementia in the elderly [1]
We investigated whether volume changes in the hippocampus and amygdala mediate the relationships between increased Aβ uptakes and memory decline, whereas volume changes in the basal ganglia and thalamus mediate the relationship between increased SVD burdens and frontal executive dysfunction
Several experienced research neuropsychologists performed the standardized battery of neuropsychological examination, including neuropsychological tests [19], activity of daily living (ADL) scales [20], Neuropsychiatric Inventory (NPI) [21], and Clinical dementia rating (CDR)
Summary
Alzheimer’s disease (AD) and vascular dementia are the most common causes of dementia in the elderly [1]. Amnestic MCI (aMCI) for Alzheimer’s disease dementia and subcortical vascular MCI (svMCI) for subcortical vascular dementia (SVaD) are two examples. The amyloid beta (Aβ) burden is a characteristic pathologic marker of aMCI and AD, and lacune and white matter hyperintensities (WMH) on MRI are characteristic neuroimaging markers of svMCI and SVaD [2, 3]. Previous studies have shown that Aβ burden were associated with memory impairments, whereas SVD, including lacune and WMH, were associated with frontal executive dysfunction [4]. Several studies, including those from our own center, have suggested that Aβ and SVD burdens were correlated with thinning in the temporoparietal and frontal regions, which, in turn, leads to memory and frontal executive dysfunctions, respectively [6,7,8,9]
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