BackgroundAlthough curcumin is a blood-brain-barrier permeable molecule with the ability to bind and segregate β-amyloid plaques and neurofibrillary tangles of hyperphosphorylated tau proteins, its poor oral bioavailability, rapid biotransformation to inactive metabolites, fast elimination from the systemic circulation, and hence the poor neuronal uptake has been limiting its clinical efficacy under neurodegenerative conditions.ObjectiveWe hypothesized that the highly bioavailable CurQfen-curcumin (CGM), which has been shown to possess significant blood-brain-barrier permeability and brain bioavailability, would ameliorate dementia in neurodegenerative conditions.MethodsIn the present double-blinded placebo-controlled 3-arm 3-sequence comparative study, 48 subjects characterized with moderate dementia due to the onset of Alzheimer's disease were randomized into three groups (N = 16/group) and supplemented with 400 mg × 2/day of either placebo (MCC), unformulated standard curcumin complex with 95% purity (USC), or CGM as a sachet for six months. The relative changes in cognitive and locomotor functions and biochemical markers were compared.ResultsSupplementation with CGM produced significant (P < 0.05) improvement in the Mini-Mental State Examination (MMSE) and the Geriatric Locomotive Function Scale (GLFS) scores in both intra- and inter-group comparison by 2 × 2 repeated measures (RM) ANOVA. Further, analysis of the serum levels of specific biomarkers (BDNF, Aβ42, tau protein, IL-6, and TNF-α) also revealed a significant (P < 0.05) improvement among CGM subjects as compared to placebo and the USC groups.ConclusionSupplementation with CGM as sachet was found to offer significant delay in the progress of Alzheimer's disease, as evident from the improvements in locomotive and cognitive functions related to dementia.Clinical trial registrationhttp://ctri.nic.in, identifier: CTRI/2018/03/012410.