# Mood Symptoms are Associated With Cognitive Status, Brain Amyloid-Beta Deposition, and Plasma Biomarkers

## TL;DR

Mood symptoms like depression and anxiety are linked to cognitive decline and Alzheimer's disease biomarkers in the brain and blood, suggesting potential for early diagnosis.

## Contribution

This study identifies associations between mood symptoms and plasma biomarkers in Alzheimer's disease, even after adjusting for brain amyloid-beta deposition.

## Key findings

- Patients with Alzheimer's disease showed higher depression scores compared to normal cognition individuals.
- Plasma neurofilament light chain levels were associated with depression scores after adjusting for brain amyloid-beta.
- Plasma p-tau181 levels were linked to anxiety scores in individuals with brain amyloid-beta deposition.

## Abstract

Previous studies have indicated an association between mood symptoms and cognitive decline in the Alzheimer's disease (AD) spectrum. Amyloid-beta (Aβ) deposition in the brain, which is a core pathological characteristic of AD, along with the presence of plasma biomarkers, such as phosphorylated tau protein (p-tau), constitutes an early predictive indicator for AD. We attempted to explore the relationship between mood symptoms and the presence of AD-related plasma biomarkers in patients with brain Aβ deposition.

We included 2612 participants aged ≥50 years (707 males; average age 66.98 ± 7.75 years) in this study. We used the Hamilton depression rating scale (HAMD) and Hamilton anxiety rating scale (HAMA) to assess mood symptoms. Cognitive status was categorized into AD, mild cognitive impairment (MCI), subjective cognitive decline (SCD), and normal cognition (NC). We used analysis of covariance (ANCOVA) to compare mood symptoms assessment scores in different cognitive groups after making adjustments for age, gender, and education. Linear regression analysis was used to investigate the association between mood scores and plasma biomarker levels, adjusting for positivity in Aβ PET imaging.

Compared to NC patients, patients with AD exhibited higher levels of depression (mean of 4.72 versus 3.39, p < 0.05), whereas patients with SCD exhibited higher levels of anxiety (mean of 6.28 versus 4.26, p < 0.05). After accounting for brain Aβ deposition and presence of plasma biomarkers, the plasma neurofilament light chain (NFL) levels (B = 0.211, SE = 0.059, p=0.001) were associated with HAMD scores. The plasma p-tau181 levels (B = 1.328, SE = 0.576, p=0.025) were associated with HAMA scores.

Plasma biomarkers have significant potential in predicting anxiety and depressive symptoms in individuals with brain Aβ deposition. This can aid the early clinical diagnosis and intervention of AD.