Systems Analysis Based Approach for Therapeutic Intervention in Mixed Vascular-Alzheimer Dementia (MVAD) Using Secondary Metabolites

Mixed dementia is a form of dementia where Alzheimer's dementia coexists with vascular dementia (VaD) in the same patient. Currently, the treatment available for mixed dementia is conventional Alzheimer's dementia therapy dispensing symptomatic relief. We aim to delineate the therapeutic possibility of some secondary metabolites, which can provide manageable intervention because of their multitargeting and multiple pathophysiological components of Alzheimer's dementia and VaD. We performed the acquisition of relevant information and data by accessing and analyzing Pubmed, Science Direct, Google Scholar, and Scopus sources, to assess the validity of therapeutic use of secondary metabolites against mixed dementia. For the initial acquisition of data (in vitro, in vivo, and clinical), the keywords that were used were “secondary metabolites,” “plant extract,” “mixed dementia,” “Alzheimer's disease,” and “vascular dementia.” All types of relevant research articles, review articles, and books were included. In our study, clinically, preclinical, in vivo, and in vitro studies of secondary metabolites are encompassed. Furthermore, we undertook the formulation of the mechanism of action of secondary metabolites in terms of systems biology-oriented analysis and signal transduction-based methodology. Firstly, the likely mechanisms through which mixed dementia can take place are identified and analyzed rigorously. Secondly, we demarcate the pharmacological actions of the secondary metabolites in treating mixed dementia by (i) Targeting acetylcholine levels, (ii) Reducing or dissociating amyloid-beta (Aβ) load, (iii) Modulating microglial activation, and (iii) Providing vasodilation concurrently with their various constituents of Alzheimer's dementia and VaD. Thirdly, we formulate how several preclinical and clinical studies furnish evidence that secondary metabolites may have efficacy in Alzheimer's patients with cerebrovascular disorders.

We formulate comprehensive evidence to substantiate the use of secondary metabolites from medicinal plants to enhance therapeutic intervention in mixed dementia.

Keywords: Alzheimer disease, Mixed dementia, Plant extract, Secondary metabolites.