Atrophy of specific amygdala subregion precedes the conversion from mild cognitive impairment with neuropsychiatric symptoms to dementia.

Abstract

Background: The amygdala is known to exhibit early signs of Alzheimer's disease (AD) pathology. However, it remains unclear whether atrophy in its specific subregions contributes to the transition from mild cognitive impairment (MCI) with neuropsychiatric symptoms (NPS) to dementia.

Methods: We recruited 376 participants at baseline: 130 MCI with NPS (MCI+NPS), 154 MCI without NPS (MCI-NPS), and 92 cognitively unimpaired (CU) individuals. Upon clinical follow-up, the MCI cohort was classified into 17 converters who progressed to dementia (MCI-c) and 96 non-converters who remained stable (MCI-nc). All participants underwent baseline and follow-up neuropsychological evaluations and multimodal magnetic resonance imaging (MRI). From the MRI data, we extracted volumes of amygdala subregions and used partial Spearman's correlations to assess their associations with NPS and cognitive alterations.

Results: Compared to the CU group, the MCI + NPS group exhibited more extensive bilateral amygdala atrophy, involving all subregions, whereas the MCI-NPS group showed atrophy confined to the bilateral centromedial (CeM) amygdala. Furthermore, relative to the MCI-nc group, the MCI-c group exhibited greater annual volume loss in the bilateral amygdalae and their subregions, except for the right CeM. The annual atrophy rate of the right basolateral (BLA) amygdala correlated with more severe affective (r = -0.274, p = 0.005) and hyperactivity symptoms (r = -0.343, p < 0.001). The annual atrophy rate of the left superficial (SUP) amygdala correlated with more severe affective symptoms (r = -0.273, p = 0.011).

Conclusions: Progressive atrophy of the BLA and SUP is associated with NPS-related cognitive decline in MCI, suggesting a potential mechanistic role for these subregions and highlighting them as candidates for future targeted intervention.