Role of an Ayurvedic formulation 'Kalyanaka Ghrita' in mild cognitive impairment: A single-patient, quasi-randomized, controlled, open-label N-of-1 trial.

ETHNOPHARMACOLOGICAL RELEVANCE: Kalyanaka Ghrita (KG) is a classical Ayurvedic polyherbal formulation traditionally indicated for disorders of memory, intellect, and mental well-being. Ayurveda emphasizes individualized therapeutic decision-making, which the N-of-1 trial design aligns with conceptually and methodologically, enabling systematic evaluation of traditional formulations at the single-patient level, where inter-individual variability is central.

AIM OF THE STUDY: To assess the efficacy and safety of Kalyanaka Ghrita in a patient diagnosed with Mild Cognitive Impairment (MCI) using an N-of-1 trial design.

MATERIALS AND METHODS: A quasi-randomized N-of-1 trial was conducted to evaluate the effects of KG in a patient with MCI. The study comprised six alternating treatment and no-treatment periods of two months each, spanning a total of 14 months. Cognitive outcomes were assessed using the Hindi Mental State Examination (HMSE) and the Clinical Dementia Rating (CDR) scales. Functional abilities were measured with the Instrumental Activities of Daily Living (IADL) scale, and affective status was evaluated using the Geriatric Depression Scale (GDS)- short form. Bayesian modeling estimated posterior probabilities and 95% highest posterior density intervals (HPDIs) for treatment effects.

RESULTS: KG administration improved overall cognitive abilities, as indicated by global HMSE scores (posterior probability >97%, 95% HPDI excluding zero), with the most substantial gains in orientation (posterior probability >98%) and recall (posterior probability >93%) domains. Reduction in CDR-Sum of Boxes scores indicated strong improvement (posterior probability >98%; 95% HPDI excluded zero). Benefits were consistent in orientation and community affairs, with moderate effects on memory and judgment/problem-solving. Functional outcomes assessed using IADLs showed a probable benefit (posterior probability >80%, HPDI overlapping zero). Depressive symptoms, as measured by the GDS, decreased markedly (posterior probability = 100%; 95% HPDI -2.23 to -0.80). All safety lab parameters remained within physiological limits, confirming good tolerability of KG.

CONCLUSION: KG produced measurable improvements across cognitive, functional, and affective domains in a patient with MCI, suggesting a potential role in the management of early cognitive decline. The formulation was well tolerated. The study also demonstrates the feasibility of applying an N-of-1 trial within Ayurveda. Despite limitations such as the single-patient, quasi-randomized, open-label design and absence of biomarker testing, the findings offer preliminary support for both the therapeutic potential of KG in MCI and the methodological value of N-of-1 trials in Ayurvedic research.