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

  • Liu Yang
  • Yan Yan
  • Yuxia Li
  • Xiaochen Hu
  • Jie Lu
  • Piu Chan
  • Tianyi YanEmail author
  • Ying HanEmail author
Original Research


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.


Alzheimer’s disease Subjective cognitive decline Resting-state functional MRI fALFF Frequency dependence 



This article was supported by the National Key Research and Development Program of China (2016YFC1306300, 2016YFC0103000, 2017YFB1002504); the National Natural Science Foundation of China (Grants 61633018, 81430037,81471731, 31371007, 81671776, 61727807, 81522021, 81801052); Beijing Municipal Nature Science Foundation (7161009, 7132147); the Beijing Municipal Commission of Health and Family Planning (PXM2019_026283_000002); the Beijing Nova Program (Grant No. Z171100001117057, Z191100010618004); the Beijing Municipal Science & Technology Commission; and China Postdoctoral Science Foundation (2018 M641414).

Compliance with ethical standards

Ethics approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The research was authorized by the Medical Research Ethics Committee and the Institutional Review Board of Xuanwu Hospital, Beijing, China.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

11682_2019_169_MOESM1_ESM.docx (6.4 mb)
ESM 1 (DOCX 6582 kb)


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Authors and Affiliations

  1. 1.Department of NeurologyXuanwu Hospital of Capital Medical UniversityBeijingChina
  2. 2.School of Life ScienceBeijing Institute of TechnologyBeijingChina
  3. 3.Department of Psychiatry and Psychotherapy, Medical FacultyUniversity of CologneCologneGermany
  4. 4.Department of RadiologyXuanwu Hospital of Capital Medical UniversityBeijingChina
  5. 5.Beijing Institute of GeriatricsBeijingChina
  6. 6.National Clinical Research Center for Geriatric DisordersBeijingChina
  7. 7.Center of Alzheimer’s DiseaseBeijing Institute for Brain DisordersBeijingChina

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