The fractional amplitude of low-frequency fluctuations (fALFFs) can detect spontaneous brain activity. However, the association between abnormal brain activity and cognitive function, amyloid protein (Aβ), and emotion in Alzheimer's disease (AD) patients remains unclear. This study aimed to survey alterations in fALFF in different frequency bands and the relationship between abnormal brain activity, depressive mood, and cognitive function to determine the potential mechanism of AD. We enrolled 34 AD patients and 32 healthy controls (HC). All the participants underwent resting-state magnetic resonance imaging, and slow-4 and slow-5 fALFF values were measured. Subsequently, the study determined the correlation of abnormal brain activity with mood and cognitive function scores. AD patients revealed altered mfALFF values in the slow-5 and slow-4 bands. In the slow-4 band, the altered mfALFF regions were the right cerebellar crus I, right inferior frontal orbital gyrus (IFOG), right supramarginal gyrus, right precuneus, angular gyrus, and left middle cingulate gyrus. Elevated mfALFF values in the right IFOG were negatively associated with Montreal Cognitive Assessment scores, Boston Naming Test, and Aβ1-42 levels. The mfALFF value of the AD group was lower than the HC group in the slow-5 band, primarily within the right inferior parietal lobule and right precuneus. Altered mfALFF values in AD patients are linked with cognitive dysfunction. Compared with HCs, Aβ1-42 levels in AD patients are related to abnormal IFOG activity. Therefore, mfALFF could be a potential biomarker of AD.
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