Effects of donepezil on the amplitude of low-frequency fluctuations in the brain of patients with Alzheimer's disease: evidence from resting-state functional magnetic resonance imaging

Neuroreport. 2021 Aug 4;32(11):907-912. doi: 10.1097/WNR.0000000000001659.

Abstract

Objectives: To monitor the effects of donepezil on spontaneous neuronal activity (SNA), and the mechanisms underlying these effects in patients with mild-to-moderate Alzheimer's disease, using the amplitude of low-frequency fluctuations (ALFFs), a metric of resting-state functional MRI (rs-fMRI).

Methods: Eleven patients with Alzheimer's disease were treated with donepezil for 6 months. Before and after treatment, the Mini-Mental State Examination (MMSE), Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog), Clinical Dementia Rating (CDR), Neuropsychiatric Inventory and Activities of Daily Living scores, along with rs-fMRI of patients were assessed. Eleven age-, sex-, and education-matched controls underwent MMSE and CDR assessments and rs-fMRI at enrollment. The ALFFs of the whole brain were obtained and compared between the groups.

Results: Following donepezil treatment, MMSE scores increased (P = 0.043) and ADAS-cog scores decreased (P = 0.010). Regarding SNA post-treatment, ALFF increased significantly in the right triangular part of the inferior frontal gyrus (IFGtriang; P = 0.030; d = -0.595) and the right orbital part of the inferior frontal gyrus (P = 0.044; d = -0.628) and decreased significantly in the left medial orbital part of the superior frontal gyrus (P = 0.039; d = 0.606) and the right gyrus rectus (P = 0.010; d = 0.609). Furthermore, the changes in ADAS-cog scores from before to after treatment were positively correlated with the changes in ALFF in the right IFGtriang (r = 0.645; P = 0.032).

Conclusions: Donepezil improved SNA in the frontal lobe of patients with Alzheimer's disease. Therefore, ALFF was demonstrated to be a potential tool for assessing the effectiveness of Alzheimer's disease treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activities of Daily Living / psychology
  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / diagnostic imaging*
  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / psychology
  • Brain / diagnostic imaging*
  • Brain / drug effects
  • Cholinesterase Inhibitors / pharmacology
  • Cholinesterase Inhibitors / therapeutic use*
  • Donepezil / pharmacology
  • Donepezil / therapeutic use*
  • Female
  • Humans
  • Magnetic Resonance Imaging / methods*
  • Male
  • Mental Status and Dementia Tests
  • Rest*
  • Treatment Outcome

Substances

  • Cholinesterase Inhibitors
  • Donepezil