The Cognitive Effects of Creatine Supplementation in Elderly Patients with Dementia: A Scoping Review Protocol

Cognitive dysfunction in elderly populations represents a significant public health challenge, affecting millions worldwide. Dementia imposes substantial burdens on patients, caregivers, and healthcare systems. Current pharmacological interventions have shown some efficacy, highlighting an urgent need for novel therapeutic approaches. Creatine, in its variety of delivery methods, traditionally recognized for its role in athletic performance, has emerged as a potential neuroprotective agent with promising implications for cognitive health. The brain accounts for approximately 20% of the body's resting metabolic rate, making adequate energy metabolism critical for cognitive function. Creatine serves as a rapid energy buffer through the phosphocreatine system, maintaining ATP homeostasis during periods of high metabolic demand. Bioenergetic support of creatine's cognitive benefits in elderly populations lies in the fact that creatine maintains cerebral ATP levels through the phosphocreatine shuttle system, particularly crucial during physiological stress states. Age-related decline in brain creatine content and mitochondrial function may contribute to dementia, making supplementation a logical intervention. Creatine also plays a neuroprotective role, demonstrating anti-inflammatory properties by modulating the NF-κB pathway and reducing pro-inflammatory cytokines. It also exhibits antioxidant effects, protecting against oxidative stress and free radical production implicated in neurodegenerative processes. Further mechanistic support of creatine's cognitive benefits in elderly populations includes changing brain creatine concentrations with aging, potentially due to reduced endogenous synthesis and altered creatine transporter function. Thus, elderly populations may have greater capacity to benefit from exogenous supplementation. Preliminary evidence from related clinical contexts suggests creatine's neuroprotective potential. Research in sleep deprivation and acute metabolic stress shows cognitive performance preservation with creatine administration. Additionally, emerging evidence in healthy aging populations indicates modest cognitive benefits, though the specific effects in cognitively impaired elderly remain inadequately characterized. Despite mechanistic plausibility and promising preliminary data, the evidence base for creatine supplementation in elderly patients with dementia remains fragmented and has not been systematically synthesized. Key questions remain unanswered regarding optimal dosing regimens, treatment duration, patient selection criteria, and which cognitive outcomes are most responsive to intervention. Furthermore, the safety profile of long-term creatine use in elderly populations with comorbidities requires careful evaluation. A scoping review methodology is appropriate for this topic because the research landscape remains exploratory and given the heterogeneity in cognitive assessment tools, intervention protocols, and study populations, a scoping approach allows comprehensive evidence mapping. This review will establish the foundation for subsequent systematic reviews and guide the design of future randomized controlled trials, including our planned pilot study on creatine supplementation for post-operative delirium prevention. This scoping review will follow the Population-Concept-Context (PCC) framework recommended by JBI. Population: Older adults (aged ≥65 years) with dementia (including Alzheimer's disease, vascular dementia, and all other dementia subtypes). Concept: Creatine monohydrate supplementation as an intervention, encompassing all dosages, durations, and formulations. Outcomes of interest include cognitive function (assessed through validated neuropsychological tests), progression of cognitive decline, functional outcomes, quality of life, biomarkers of brain metabolism, and safety/adverse events. Context: Clinical intervention studies (randomized controlled trials, pilot studies, observational studies) and preclinical models of dementia. Settings may include community-dwelling elderly, memory clinics, long-term care facilities, and other elderly-care settings.