# Preclinical amyloid pathology is associated with anxiety but not depression in cognitively normal older adults: Evidence for differential neuropsychiatric pathways

## TL;DR

Early signs of Alzheimer's amyloid buildup are linked to anxiety but not depression in older adults with normal cognition.

## Contribution

This study identifies anxiety as a potential early marker of preclinical Alzheimer's pathology, distinct from depression.

## Key findings

- Amyloid pathology directly correlates with anxiety in cognitively normal older adults.
- Depression is indirectly linked to amyloid through subjective cognitive concerns.
- Anxiety may serve as an early neurobiological marker of Alzheimer's disease.

## Abstract

•Preclinical amyloid pathology directly associates with anxiety in cognitively normal elderly•Depression links to amyloid only indirectly through subjective cognitive concerns•Anxiety may represent an early neurobiological marker of AD pathology•Subjective AD concerns mediate the relationship between amyloid and depression

Preclinical amyloid pathology directly associates with anxiety in cognitively normal elderly

Depression links to amyloid only indirectly through subjective cognitive concerns

Anxiety may represent an early neurobiological marker of AD pathology

Subjective AD concerns mediate the relationship between amyloid and depression

Neuropsychiatric symptoms may represent early Alzheimer's disease (AD) manifestations, but their relationship with amyloid pathology in cognitively unimpaired individuals remains unclear.

We analyzed 4,492 cognitively unimpaired adults (aged 65-85) from the Anti-Amyloid Treatment in Asymptomatic Alzheimer's Study. Participants completed amyloid-PET imaging and assessments of anxiety, depression, memory complaints, and AD concerns.

1,231 participants (27.4%) were amyloid-positive. While anxiety and depression scores remained within normal ranges, amyloid-positive participants reported higher memory complaints (p = 0.008) and AD concerns (p < 0.001) before status disclosure. Regression analyses showed amyloid burden associated with anxiety (β = 0.04, standardized, p = 0.003) but not depression (p = 0.68). Mediation analyses revealed anxiety was directly associated with amyloid, while depression was mediated through subjective cognitive concerns.

Preclinical amyloid pathology directly associates with subclinical anxiety but only indirectly with depression through subjective stress, suggesting distinct neuropsychiatric pathways in early AD that could inform detection strategies.