Frequency-dependent changes in fractional amplitude of low-frequency oscillations in Alzheimer’s disease: a resting-state fMRI study

Alzheimer’s disease (AD) is the most common neurodegenerative disease in elderly individuals. We conducted this study to examine whether alterations in the fractional amplitudes of low-frequency fluctuations (fALFF) in the AD spectrum were frequency-dependent and symptom-relevant. A total of 43 patients with subjective cognitive decline (SCD), 52 with amnestic mild cognitive impairment (aMCI), 44 with Alzheimer’s dementia (d-AD) and 55 well-matched controls participated in resting-state functional magnetic resonance imaging (rs-fMRI) scans. The amplitudes were measured using fALFF within the slow-4 (0.027–0.073 Hz) and slow-5 (0.01–0.027 Hz) bands. Repeated-measures analysis of variance was performed on fALFF within two bands and correlated with neuropsychological test scores. The significant main effects of frequency and group on fALFF differed widely across brain regions. There were more varied areas in the slow-5 band than the slow-4 band. The fALFF associated with primary disease effects was mainly distributed in the parietal lobe. Obvious frequency band and group interaction effects were observed in the left angular gyrus, left calcarine fissure and surrounding cortex, left superior cerebellum, left cuneus and right lingual gyrus. Neuropsychological tests scores were significantly correlated with the fALFF magnitude of the left cuneus and right lingual in the slow-5 band. Our results suggested that the AD continuum had abnormal amplitudes in intrinsic brain activity, and these abnormalities were frequency-dependent and mainly associated with the slow-5 band rather than the slow-4 band. This may guide the frequency choice of future rs-fMRI studies and provide new insights into the neuropathophysiology of AD.