A 2025 review in the Journal of Psychiatry and Brain Science and pilot trial in Alzheimer’s and Dementia: Translational Research and Clinical Interventions report creatine supplementation elevates neuronal phosphocreatine and slows cognitive decline by 30% in early Alzheimer's patients. The brain consumes 20% of body energy despite 2% mass; creatine kinase converts phosphocreatine to ATP during high-demand firing when oxidative phosphorylation lags. Alzheimer's tissue shows reduced phosphocreatine and creatine kinase activity, creating a bioenergetic deficit partially offset by exogenous creatine. Mitochondrial impairment documented in Alzheimer's neurons reduces ATP output; the phosphocreatine buffer provides millisecond-scale regeneration independent of mitochondria. Age-related creatine system decline compounds this deficit, with lower brain creatine levels measured in patients versus controls. Controlled data link supplementation to improved working memory and resilience under sleep deprivation, metrics absent from fitness-focused creatine labeling.