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. 2025 Jun;46(6):2601-2610.
doi: 10.1007/s10072-025-08091-0. Epub 2025 Mar 8.

Impact of amygdala functional connectivity on cognitive impairment in Alzheimer's disease

Ani Kicik  1 , Elif Kurt  2 , Emre Hari  3   4 , Çiğdem Ulasoglu-Yildiz  2 , Hakan Gurvit  5 , Tamer Demiralp  3   6
Affiliations

Impact of amygdala functional connectivity on cognitive impairment in Alzheimer's disease

Ani Kicik et al. Neurol Sci. 2025 Jun.

Abstract

The functional connectivity (FC) of the amygdala in Alzheimer's disease (AD) and its relationship to cognitive impairment is still not well established. Thus, we examined resting-state FC changes in the amygdala among 21 patients with AD dementia (ADD) and 34 individuals with amnestic mild cognitive impairment (aMCI), compared to 33 individuals with subjective cognitive impairment (SCI), to provide insights into the association between amygdala FC and cognitive decline in different clinical stages of Alzheimer's disease. We conducted seed-to-voxel FC analysis, focused on two cognitive functions, episodic memory, and face recognition, and examined the correlations between changes in FC of the amygdala and cognitive test scores. We demonstrated that the left amygdala exhibits progressive disruption in FC, especially with the frontal regions in aMCI and ADD. We further identified that this disrupted FC in the left amygdala showed significant positive correlations with cognitive test scores from the MCI stage onward. Our results indicate that FC changes in the left amygdala may serve as an early marker of AD and this FC pattern of amygdala influence detrimentally affects episodic memory and face recognition functions. These findings highlight that the amygdala may be a critical anatomical region for detecting the early stages of AD.

Keywords: Alzheimer’s disease; Amygdala; Cognitive impairment; Functional connectivity; Magnetic resonance imaging.

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Conflict of interest statement

Declarations. Ethical approval: This study was performed in line with the principles of the Declaration of Helsinki. The study received approval from the Clinical Research Ethics Committee at Istanbul University, Istanbul Faculty of Medicine (Protocol No: 2022/1494). Informed consent: Written informed consent was provided by all participants. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Functional connectivity differences among the ADD, aMCI and SCI groups for the left amygdala. The FC analysis was thresholded with a voxel level threshold set at p < 0.001 (uncorrected) and pFWE < 0.05 at the cluster level
Fig. 2
Fig. 2
Functional connectivity differences for the left amygdala. (A) Regions that showed decreased functional connectivity in the ADD group compared to the SCI group. (B) Regions that showed decreased functional connectivity in the aMCI group compared to the SCI group. The threshold for pairwise comparisons was set to p < 0.001 (uncorrected) at the voxel level and pFWE < 0.05 at the cluster level
See this image and copyright information in PMC

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