AKG and Brain Health in Aging

These hypotheses will be tested in a randomized, double-blind, placebo-controlled clinical trial with 24 weeks of AKG supplementation in community dwelling older adults. Our team has the relevant expertise in clinical trials with older adults, NGVC assessments, and EVs analysis, providing a high degree of confidence for the successful completion of this project within the award time frame.

• Calcium AKG (Dietary supplement): Participants will be randomized to receive either oral Calcium AKG at a total daily dose of 1 g or an identically appearing placebo for 24 weeks.
• Oral placebo capsules (Dietary supplement): identically appearing placebo capsule

Primary outcomes

• Change in neurogliovascular coupling using functional near infrared spectroscopy (fNIRS) [24 weeks]: Functional near infrared spectroscopy (fNIRS) will be performed during the cognitive n-back task. fNIRS approach generates data that represent a relative change in oxygenated and deoxygenated hemoglobin measured over the cortical brain tissues. Neurogliovascular coupling will be evaluated as a change in oxy- and deoxy-hemoglobin between before and after treatment. Units of measure - beta. Reported as a %change from baseline, before and after treatment.
• Change in neurovascular coupling using electroencephalography (EEG) [24 weeks]: EEG signal will be collected to generate spectral data. These data will be used for comparison of EEG activity between before and after treatment. Units of measure - power spectral density. Reported as a %change from baseline, before and after treatment.

Secondary outcomes

• Change in Attention [24 weeks]: The allocation of one's limited capacities to deal with an abundance of environmental stimulation will be measured in a combined "Flanker Inhibitory Control and Attention Test".Units of measure - score (from 0 to 10, bigger number is better). Reported as a %change from baseline.
• Change in Working Memory [24 weeks]: The ability to store information until the amount of information to be stored exceeds one's capacity to hold that information will be measured using the "List Sorting Working Memory Test". Unit of measure - overall score (bigger number is better). Reported as a %change from baseline.
• Change in Executive Function [24 weeks]: The capacity to plan, organize and monitor the executive of behaviors that are strategically directed in a goal-oriented manner will be measured using the "Dimensional Change Card Sort Test". Units of measure - score (from 0 to 10, bigger number is better). Reported as a %change from baseline.
• Change in Processing Speed [24 weeks]: Pattern Comparison Processing Speed Test assesses the amount of information that can be processed within a certain unit of time. Items are simple so as to purely measure processing speed. Units of measure - score (from 0 to 130, bigger number is better). Reported as a %change from baseline.
• Change in Episodic Memory [24 weeks]: Cognitive processes involved in the acquisition, storage and retrieval of new information, will be measured using the "Picture Sequence Memory Test". Unit of measure - overall score (bigger number is better). Reported as a %change from baseline.
• Body composition [24 weeks]: Weight and body composition using a bioimpedance scale and/or DXA scan. Reported as a %change from baseline, before and after completion of study
• Change in Language [24 weeks]: Picture Vocabulary Test measures receptive vocabulary administered in a computer-adaptive test (CAT) format. Respondents select the picture that most closely matches the meaning of the word, before and after treatment. Unit of measure - overall score (bigger number is better). Reported as a %change from baseline.
• Self-reported cognitive function [24 weeks]: Self-reported cognitive function will be assessed using the PROMIS Short Form v2.0 Cognitive Function 4a, which measures participants' perceived cognitive abilities and difficulties in daily life.
• Change in blood metabolic panel markers [24 weeks]: Complete metabolic panel (General Chemistry 13 Panel and Lipid Panel from Piccolo Xpress). Reported as a %change from baseline, before and after completion of study
• Physical activity [24 weeks]: We will assess physical activity and classify it as sedentary, lightly active, active, or very active using the self-administered CHAMPS (Community Health Activities Model Program for Seniors) activities questionnaire. Outcome scores will be assessed using the weekly frequency of physical activity and calculated based on the standardized 6-point categorical duration scale, where scores range from a minimum of 0 hours per week (indicating complete inactivity) to an open-ended maximum number of hours. Higher scores indicate a better outcome, representing very active.
• Sleep quality [24 weeks]: Sleep quality will be assessed using the Pittsburgh Sleep Quality Index (PSQI), which evaluates variables including "duration of sleep", "sleep disturbance", "sleep latency", "daytime dysfunction due to sleepiness", "sleep efficiency", "overall sleep quality", and "need meds to sleep". All variables will be scored from a minimum score of 0 (better) to a maximum score of 3 (worse) based on the answers in the questionnaire, to obtain a total score ranging from 0 to 21, with the total score ≤ 5 associated with good sleep quality, and > 5 associated with poor sleep quality.
• Global Rating of Change (GRC) [at final visit]: After 24 weeks of the intervention, participants will complete the Global Rating of Change (GRC) to report whether they perceive any overall change following the study supplement or placebo. The GRC scale quantifies a patient's change in health status over time. We will utilize an 11-point Likert scale from -5 (very much worse) to +5 (very much improved), including 0 (unchanged), as the rating scale. Participants will be asked to rate their change based on one question: (1) "With respect to your cognition (thinking, attention, concentration, memory), how would you describe yourself now compared to the baseline that is starting treatment 24 weeks ago?"

Sex: All, ages: 55 Years to any, accepts healthy volunteers

Inclusion Criteria:

* Age ≥55 years
* Adequate hearing and visual acuity to participate in the examinations (with or without aids)
* Ability to read and write in English
* Competence to provide informed consent
* Montreal Cognitive Assessment score ≥26
* Stable medications for ≥3 months

Exclusion Criteria:

* Vision or hearing impairment that would impair the ability to complete study assessments
* Active CNS disease including multiple sclerosis, uncontrolled seizures, active brain cancer
* Cerebrovascular accident other than TIA within 60 days prior to Visit 0
* Major psychiatric disease, including major depression not currently controlled and alcohol or drug abuse
* Abnormal kidney function (creatinine >2mg/dL or EGFR <30mL/min) by most recent labs within 6 months prior to Visit 0
* Elevated liver enzymes (AST and/or ALT above x2 upper limit of normal) by most recent labs within 6 months prior to Visit 0
* Elevated blood calcium level (above 10.3 mg/dL) by most recent labs within 6 months prior to Visit 0
* History of kidney stones
* Any other medical condition which, in the opinion of investigator, would render the patient inappropriate or too unstable to complete the study protocol
* Current use of AKG or NAD+ supplements

• Andriy Yabluchanskiy, MD, PhD, Principal investigator, University of Oklahoma Harold Hamm Health Campus

NIH grants: R21AG103782