Efficacy and Safety of Pioglitazone in Improving Cognitive Function among Patients with Impaired Cognition as an Add-On Therapy: A Study Protocol.

INTRODUCTION: Management strategy to improve cognition is one of the challenges faced by clinicians. Importantly, pioglitazone, a safe and cost-effective medication, has been shown to improve memory dysfunction in both animal and some clinical studies. Thus, the aim of this study was to assess and compare the effect of pioglitazone as an add-on therapy in treating cognitive decline in patients with Parkinson's disease, stroke, and dementia. METHODS: This is a randomised double blind controlled trial involving individuals with severe to mild cognitive impairment (MoCA score below 26) associated with either Parkinson's disease, stroke, or dementia. All neurological conditions were clinically diagnosed based on the standard criterions. Participants were randomised 1:1 to orally take 15 mg of pioglitazone once daily for 6 months. A total sample size of 252 participants (42 per group across six groups) was calculated to detect a mean difference of 2 points in MoCA score (SD = 3), with 80% power and 5% significance level, accounting for 15% attrition. The primary outcome measure is the change in MoCA score at 6 months. Secondary outcome measures include the assessment of clinical manifestations, cognitive performance, normal neurological markers, adverse drug reactions, and medication adherence over a follow-up period of 6 months and 12 months. CONCLUSION: The findings of our study are hypothesis-generating. If positive, this study will support larger multicentre trials to validate efficacy, clarify subgroup responsiveness, and inform future metabolic-targeted therapeutic strategies rather than immediate clinical guideline changes.