Protocol for a single-arm, pilot trial of creatine monohydrate supplementation in patients with Alzheimer's disease.

BACKGROUND: Impaired brain bioenergetics is a pathological hallmark of Alzheimer's disease (AD) and is a compelling target for AD treatment. Patients with AD exhibit dysfunction in the brain creatine (Cr) system, which is integral in maintaining bioenergetic flux. Recent studies in AD mouse models suggest Cr supplementation improves brain mitochondrial function and may be protective of AD peptide pathology and cognition. AIMS: The Creatine to Augment Bioenergetics in Alzheimer's disease (CABA) study is designed to primarily assess the feasibility of supplementation with 20 g/day of creatine monohydrate (CrM) in patients with cognitive impairment due to AD. Secondary aims are designed to generate preliminary data investigating changes in brain Cr levels, cognition, peripheral and brain mitochondrial function, and muscle strength and size. METHODS: CABA is an 8-week, single-arm pilot study that will recruit 20 patients with cognitive impairment due to AD. Participants attend five in-person study visits: two visits at baseline to conduct screening and baseline assessments, a 4-week visit, and two 8-week visits. Outcomes assessment includes recruitment, retention, and compliance, cognitive testing, magnetic resonance spectroscopy of brain metabolites, platelet and lymphocyte mitochondrial function, and muscle strength and morphology at baseline and 8 weeks. DISCUSSION: CABA is the first study to investigate CrM as a potential treatment in patients with AD. The pilot data generated by this study are pertinent to inform the design of future large-scale efficacy trials. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05383833 , registered on 20 May 2022.

Creatine as a Therapeutic Target in Alzheimer's Disease.

Alzheimer's disease (AD) is the most prevalent neurodegenerative disease, affecting approximately 6.5 million older adults in the United States. Development of AD treatment has primarily centered on developing pharmaceuticals that target amyloid-ß (Aß) plaques in the brain, a hallmark pathological biomarker that precedes symptomatic AD. Though recent clinical trials of novel drugs that target Aß have demonstrated promising preliminary data, these pharmaceuticals have a poor history of developing into AD treatments, leading to hypotheses that other therapeutic targets may be more suitable for AD prevention and treatment. Impaired brain energy metabolism is another pathological hallmark that precedes the onset of AD that may provide a target for intervention. The brain creatine (Cr) system plays a crucial role in maintaining bioenergetic flux and is disrupted in AD. Recent studies using AD mouse models have shown that supplementing with Cr improves brain bioenergetics, as well as AD biomarkers and cognition. Despite these promising findings, no human trials have investigated the potential benefits of Cr supplementation in AD. This narrative review discusses the link between Cr and AD and the potential for Cr supplementation as a treatment for AD.

Correlation of Skin Carotenoid Content with 3-Day Dietary Intake in Community Dwelling Older Adults.

Pressure-mediated reflection spectroscopy (RS) measures skin carotenoid content (SCC). Continued validation of this method is pertinent to validate its use as an objective measure of fruit and vegetable intake. This study aimed to assess relationships between SCC scores and self-reported dietary carotenoid intake from 3-day food records in community dwelling older adults. This was a cross-sectional analysis of baseline data among cognitively normal older adults (n=95) participating in the Nutrition Interventions for Cognitive Enhancement (NICE) study. Food-derived vitamin A (R=0.24, p<0.05) and food plus supplemental vitamin A (R=0.29, p<0.01) were correlated with SCC. All food-derived carotenoids (R: 0.20-0.39, p<0.05) except beta-cryptoxanthin and lycopene were correlated with SCC. Lutein + zeaxanthin from food more strongly correlated with SCC (R=0.38, p<0.001) than combined food plus supplemental intake (R=0.31, p=0.002). Correlations for total fruit and SCC (R=0.23, p=0.02), total vegetable and SCC (R= 0.31, p=0.002), and combined total fruit and vegetable and SCC (R=0.35, p<0.001) were significant; no sub-categories of fruit or vegetables except dark green vegetables (Rho=0.4, p<0.001) had significant correlations with SCC. The current study demonstrates RS-derived SCC scores correlate with 3-day self-reported intakes of F/V and certain carotenoids in community dwelling older adults.