Systematic Review on Pathology and Drug Efficacy Clinical Trials (1973-2023) for Cognitive Impairment and Alzheimer’s Dementia
Dasgupta Subhajit, Villa Nina and Bandyopadhyay Mausumi
Rationale: The systematic review evaluates the results of last fifty years (1973-2023) of clinical trials
on pathology and treatment for cognitive impairment including Alzheimer’s dementia (AD dementia).
Objectives: Alzheimer’s dementia is a growing public health concern worldwide. The systematic review
analyzes the disease confirming pathological findings presented by modern imaging techniques MRI/
PET. In addition, we analyze the success of fifty years of therapeutic advancements of the neurological
disabilities and count on the safe drugs to treat clinical conditions of AD dementia.
Findings: We followed the PRISMA guidelines to determine the inclusion and exclusion criteria for
the selection of clinical records collected from the NCBI databases. We analyzed the drug efficacy
results on the three aspects of the AD brain: (a) morphological deformation of the choroid plexus and
hippocampus; (b) senile plaques with amyloid beta42 (Abeta42) including hyperintensities of neurons;
and (c) inhibitory action of acetylcholinesterase enzyme. The pathological findings include detection of
Abeta42 plaques in cerebral cortex and retention ability of trial drugs in cerebrospinal fluid versus blood
plasma of AD patients in the context of disease progression and treatment efficacy. The clinical trial
records demonstrated evidence of genetic susceptibility factor(s) clustered in European populations. The
susceptibility is also found due to mutations in the presenilin-1 gene and expression of the ApoEε-allele
among the population. The clinical records demonstrate moderate efficacy of cholinesterase inhibitors
Donepezil and Rivastigmine in improving cognition. The antibodies aducanumab, donanemab, and
lecanemab show low to moderate success in removing plaques and reducing plasma Abeta burden.
Conclusion: The cholinesterase inhibitors demonstrate moderate success in improving cognition.
However, the overall efficacy of antibody treatment was poor. The findings suggest a need for new
generation drugs which can clear plaques and improve cognition for AD.
