Trait-anxiety and glial-related neuroinflammation of the amygdala and its associated regions in Alzheimer's disease: A significant correlation

Abstract

Background

Positron emission tomography, which assesses the binding of translocator protein radiotracers, ¹¹C-DPA-713, may be a sensitive method for determining glial-mediated neuroinflammation levels. This study investigated the relationship between regional ¹¹C-DPA713 binding potential (BP_ND) and anxiety in patients with Alzheimer's disease (AD) continuum.

Methods

Nineteen patients with AD continuum determined to be amyloid-/p-tau 181-positive via cerebrospinal fluid analysis were included in this cross-sectional study (mild cognitive impairment [MCI, n = 5] and AD [n = 14]). Anxiety was evaluated using the State-Trait Anxiety Inventory (STAI). A whole-brain voxel-based analysis was performed to examine the relationship between ¹¹C-DPA-713-BP_ND values at each voxel and the STAI score. Stepwise multiple regression analysis was performed to determine the predictors of STAI scores using independent variables, including ¹¹C-DPA-713-BP_ND values within significant clusters. ¹¹C-DPA-713-BP_ND values were compared between patients with AD continuum with low-to-moderate and high STAI scores.

Results

Voxel-based analysis revealed a positive correlation between trait anxiety severity and ¹¹C-DPA713-BP_ND values in the centromedial amygdala and the left inferior occipital area [P < 0.001 (uncorrected) at the voxel-level]. ¹¹C-DPA713-BP_ND values in these regions were a strong predictor of the STAI trait anxiety score. Specifically, patients with AD continuum and high trait anxiety had increased ¹¹C-DPA713-BP_ND values in these regions.

Conclusions

The amygdala–occipital lobe circuit influences the control of emotional generation, and disruption of this network by AD pathology-induced inflammation may contribute to the expression of anxiety. Our findings suggest that suppression of inflammation can help effectively treat anxiety by attenuating damage to the amygdala and its associated areas.