Crossover Trial for Nicotinamide Riboside in Subjective Cognitive Decline and Mild Cognitive Impairment

Inclusion criteria: 1. Ages 60 and up; 2. Memory and other cognitive complaints consistent with SCD or MCI as defined by the National Institute on Aging: a. SCD will be defined as: i. any subjective concern of change in cognitive functioning without objective evidence of cognitive impairment, and ii. complete preservation of functional abilities and independence in instrumental activities of daily living. b. MCI will be defined as: i. a preexisting diagnosis of MCI given by a trained physician or behavioral health provider, or ii. evidence of objective impairment in cognitive functioning in one or more domain with preservation of functional abilities and independence in instrumental activities of daily living as defined by the National Institute on Aging; 3. Minimum score of 16 on t-MoCA; 4. Ability to provide direct informed consent as assessed by obtaining a score of 70% on questions 1-10, and answer 'yes' to questions 11-14 of the Informed Consent Worksheet after two attempts; 5. Education level, English language skills and literacy indicates participant able to complete all assessments; 6. Willing and able to complete all assessment and study procedures; 7. Not pregnant, lactating, or of child-bearing potential; 8. If on cholinesterase inhibitor and/or memantine, doses are stable for 3 months prior to baseline. Exclusion Criteria: 1. Any specific CNS disease history other than suspected ADRD, such as major clinical stroke, brain tumor, normal pressure hydrocephalus, multiple sclerosis, significant head trauma with persistent neurological of cognitive deficits or complaints; 2. Any impairment in instrumental activities of daily living that would indicate a level of cognitive impairment beyond MCI as assessed by a trained rater; 3. Clinically significant unstable medical condition that could affect safety or compliance with the study and would, in the opinion of the investigator, pose a risk to the participant if they were to participate in the study; 4. History of neuroimaging with evidence of major infarction, injury, infection, or other focal lesions that may be related to cognitive dysfunction; 5. If participating in the optional lumbar puncture sub-study, any contraindication to undergo lumbar punctures, such as: 1. abnormal coagulation PT/INR test result, outside of the normal range of 0.9 to 1.2 platelet counts below 50,000 (determined by a licensed study physician or Nurse Practitioner after reading test results). 2. Platelet counts below 50,000. 3. Use of Coumadin, Warfarin, or other blood thinner medications. 4. Infection near the puncture site, or spinal column deformities (a licensed physician or Nurse Practitioner will examine the site visually for infection or spinal deformities before performing the procedure). 5. Known allergy to Lidocaine. 6. Major active or chronic unstable psychiatric illness (e.g. depression, bipolar disorder, obsessive compulsive disorder, schizophrenia) within the previous year; 7. Current suicidal ideation or history of suicide attempt; 8. History of alcohol or other substance abuse or dependence within the past two years; 9. Any significant systemic illness or medical condition that could affect safety or compliance with study; 10. Laboratory abnormalities in Vitamin B12, Thyroid Stimulating Hormone (TSH), or other common laboratory parameters that might contribute to cognitive dysfunction or other abnormalities in hematological, hepatic or renal function tests; 11. Current use of medications with psychoactive properties that in the opinion of the principal investigator, may be deleteriously affecting cognition (e.g., anticholinergics, antihistamines, antipsychotics, sedative hypnotics, anxiolytics); 12. Any known hypersensitivity to nicotinamide riboside, or its principal metabolite, nicotinamide mononucleotide; 13. No consumption of dietary supplements containing more than 100mg niacin, nicotinamide riboside (NR), or nicotinamide mononucleotide (NMN) as the primary agents 30 days prior to baseline and for the duration of the trial; 14. Use of other investigational agents or interventions one month prior to entry and for the duration of the trial; 15. If participating in the optional MR sub-study: Any contraindication to undergo MRI studies, such as history of cardiac pacemaker or pacemaker wires, metallic particles in the body, vascular clips in the head, prosthetic heart valves, and/or severe claustrophobia impeding ability to participate in an imaging study.