Impaired brain plasticity as a potential therapeutic target for treatment and prevention of dementia

ABSTRACT

Introduction: In 2017, it was estimated that close to 50 million people were living with dementia worldwide and this number is expected to double every 20 years. No effective treatment exists yet probably because by the time Alzheimer’s dementia (AD) has developed it is too late to intervene.

Areas covered: Mild cognitive impairment (MCI) is a clinical state that typically precedes AD. In MCI, the prefrontal cortex supports compensatory mechanisms that depend on robust synaptic plasticity and that delay progression to AD. This review focuses on novel neurostimulation approaches that could enhance prefrontal cortical plasticity in vivo by enhancing prefrontal cortical plasticity and function in patients with MCI or AD. It also describes novel neurophysiological markers that could function as targets for such approaches.

Expert commentary: Targeting synaptic plasticity in patients with early AD or at risk of developing AD could be a promising approach to slow progression or prevent AD.

KEYWORDS:

• Neuroplasticity
• neurostimulation
• TMS
• paired associative stimulation
• prefrontal cortex
• gamma oscillations
• theta–gamma coupling
• tACS
• tDCS

Article highlights

• Focusing on dementia prevention is needed given the limited success of treatments once dementia is clinically manifested.

• Enhancing cognitive compensation could lead to preventing dementia or its progression.

• The prefrontal cortex is a promising target to promote enhanced cognitive compensation.

• Several novel neurostimulation approaches have the potential of enhancing prefrontal cortical function and, in turn, cognitive compensation, via the enhancement of neuroplasticity within the prefrontal cortex.

• Novel neurophysiological markers are also being developed to index prefrontal cortical plasticity and function and, therefore, have the potential to be specific targets for neurostimulation or other interventions.

This box summarizes key points contained in the article.

Declaration of interest

The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

One of the reviewers is an investigator/PI for the Neuronix TMS program for AD. Other peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

T Rajji received during the past five years research support from Brain Canada, Brain and Behavior Research Foundation, CAMH Foundation, Canada Foundation for Innovation, Canada Research Chair, Canadian Institutes of Health Research (CIHR), Ontario Ministry of Health and Long-Term Care, Ontario Ministry of Research and Innovation, the US National Institute of Health (NIH), and the Weston Brain Institute.