Efficacy of preclinical pharmacological interventions against alterations of neuronal network oscillations in Alzheimer's disease: A systematic review

Exp Neurol. 2021 Sep:343:113743. doi: 10.1016/j.expneurol.2021.113743. Epub 2021 May 14.

Abstract

Despite the development of multiple pharmacological approaches over the years aimed at treating Alzheimer's Disease (AD) only very few have been approved for clinical use in patients. To date there still exists no disease-modifying treatment that could prevent or rescue the cognitive impairment, particularly of memory aquisition, that is characteristic of AD. One of the possibilities for this state of affairs might be that the majority of drug discovery efforts focuses on outcome measures of decreased neuropathological biomarkers characteristic of AD, without taking into acount neuronal processes essential to the generation and maintenance of memory processes. Particularly, the capacity of the brain to generate theta (θ) and gamma (γ) oscillatory activity has been strongly correlated to memory performance. Using a systematic review approach, we synthesize the existing evidence in the literature on pharmacological interventions that enhance neuronal theta (θ) and/or gamma (γ) oscillations in non-pathological animal models and in AD animal models. Additionally, we synthesize the main outcomes and neurochemical systems targeted. We propose that functional biomarkers such as cognition-relevant neuronal network oscillations should be used as outcome measures during the process of research and development of novel drugs against cognitive impairment in AD.

Keywords: Alzheimer's disease; Gamma oscillations; Memory impairment; Systematic review; Theta oscillations.

Publication types

  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / physiopathology
  • Animals
  • Brain / drug effects*
  • Brain / physiology
  • Cholinergic Agents / administration & dosage
  • Dopamine Agents / administration & dosage
  • Drug Evaluation, Preclinical / methods
  • Electroencephalography / drug effects
  • Electroencephalography / methods
  • Gamma Rhythm / drug effects*
  • Gamma Rhythm / physiology
  • Humans
  • Memory Disorders / drug therapy
  • Memory Disorders / physiopathology
  • Nerve Net / drug effects*
  • Nerve Net / physiology
  • Nootropic Agents / administration & dosage*
  • Theta Rhythm / drug effects*
  • Theta Rhythm / physiology
  • Treatment Outcome

Substances

  • Cholinergic Agents
  • Dopamine Agents
  • Nootropic Agents