Neural Correlates of Anxiety in Alzheimer's Disease: An Analysis of the Amplitude of Low-Frequency Fluctuations in Resting-State fMRI.

OBJECTIVE: To characterise the neural correlates of anxiety in Alzheimer's disease (AD) using the amplitude of low-frequency fluctuations (ALFF) derived from resting-state fMRI. STUDY DESIGN: A cross-sectional study. Place and Duration of the Study: Department of Psychiatry, Tongde Hospital of Zhejiang Province, Affiliated to Zhejiang Chinese Medical University (College of Integrated Traditional Chinese and Western Medicine Clinical Medicine), Zhejiang, China, from May to November 2025. METHODOLOGY: Fifty-four participants were categorised into three groups: 20 AD patients with anxiety (AD-A), 14 without anxiety (AD-nA), and 20 healthy controls (HCs). Probable AD was diagnosed according to the NIA-AA criteria. Cognitive and anxiety symptoms were assessed using the Mini-Mental State Examination (MMSE) and Hamilton Anxiety Scale (HAMA). Based on normality testing, group comparisons were performed using Kruskal-Wallis tests, except for HAMA scores, which were normally distributed. All participants underwent fMRI scanning, and ALFF values were calculated. RESULTS: Groups did not differ in age or gender. HCs showed significantly higher MMSE scores compared to both AD groups. HAMA scores were significantly higher in the AD-A group than in the AD-nA group. In the AD-A group, there was a positive but non-significant correlation between MMSE and HAMA scores (r = 0.267, p = 0.255). Neuroimaging results revealed that compared to the AD-nA group, the AD-A group exhibited decreased ALFF in the left insula and left anterior cingulate cortex. Relative to HCs, the AD-A group showed decreased ALFF in the right fusiform gyrus. In contrast, the AD-nA group displayed decreased ALFF in the right lingual gyrus and left precuneus, alongside increased ALFF in the right dorsolateral superior frontal gyrus. CONCLUSION: The AD-A group shows a distinct pattern of intrinsic brain activity. In the AD-A group, ALFF is lower in the salience network than in the AD-nA group, and lower in the visual cortex compared to HCs; the AD-nA group shows complex ALFF changes. This suggests ALFF as a potential neuroimaging biomarker for neuropsychiatric symptoms in AD. KEY WORDS: Alzheimer's disease, Anxiety, Resting-state fMRI, Amplitude of low-frequency fluctuation.