Functional Magnetic Resonance Imaging in Alzheimer's Disease Drug Trials: A Mini-Review

Area of Science:

• Neuroscience
• Pharmacology
• Medical Imaging

Background:

• Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline and dementia.
• Key pathological hallmarks include neurotoxic amyloid-beta (Aβ) plaques, disrupting brain structure and function.
• Pharmacotherapeutic trials aim to slow AD progression by targeting Aβ and other pathological features.

Purpose of the Study:

• To review the utility of functional magnetic resonance imaging (fMRI) in assessing the efficacy of Alzheimer's disease (AD) pharmacotherapeutic clinical trials.
• Focus on trials conducted within the last seven years.

Main Methods:

• Systematic literature search across two databases.
• Risk of bias assessment for randomized clinical trials (RCTs) using the Revised Cochrane risk-of-bias tool (RoB-2).

Main Results:

• Four studies utilizing fMRI to evaluate AD drug efficacy were included.
• Cholinesterase, glutamatergic, and serotonergic drugs demonstrated positive effects on brain functional activity, particularly in the default mode network.
• Observed changes in functional connectivity (FC) correlated with improved cognition and fMRI task performance, linked to cerebellar and cholinergic decline.

Conclusions:

• Recent RCTs confirm fMRI's capability to track longitudinal FC changes in response to AD drug treatments across various disease stages.
• Positive FC alterations suggest potential drug-induced compensatory mechanisms in the brain.
• Current AD pharmacotherapies exhibit limited efficacy, highlighting the need for advanced pharmacological interventions for clinical use.