Effects of Nicotinamide Riboside on Bioenergetics and Oxidative Stress in Mild Cognitive Impairment/Alzheimer's Dementia

Eligibility Criteria

• * Ability of the participant and/or his/her legally authorized representative to understand the purpose and risks of the study, to provide signed and dated informed consent, and to authorize the use of confidential health information.
• * Ability to speak and read fluently in English
• * 55-89 years old (inclusive)
• * Normal or corrected to normal hearing and vision
• * Meet clinical diagnostic criteria for MCI or Mild AD, according to the following criteria:
• 1. CDR Global Score of 0.5 (MCI) or 1.0 (mild AD)
• 2. 2018 NIA-AA guidelines for MCI/mild AD
• * Study partner available for the duration of trial participation
• * At least one copy of the APOE ε4 allele or AD+ including Amyloid positive PET scan, Tau positive PET Scan (MK6240 et al.), or CSF AD biomarkers \[i.e., amyloid-beta beta (Aβ42) total (T)-tau, and phosphorylated (P)-tau\]
• * An aggregate risk score \> 4 according to the risk analysis method developed by Sabbagh et al. (2017)
• * For individuals who are taking niacin (or a vitamin supplement with niacin) of \>200mg, the completion of a two-week wash-out period
• * Current serious or unstable medical or neurological condition that could affect cognitive functioning, as determined by study clinician
• * Clinically unstable mood or anxiety disorder within 6 months prior to screening, as determined by study clinician
• * Lifetime history of psychotic disorder (i.e. Schizophrenia, Schizoaffective Disorder), as determined by study clinician
• * Diagnosis of a mitochondrial disorder
• * Any MRI safety contraindications
• * History of drug hypersensitivity or intolerance to NR
• * Transient ischemic attack or stroke within 1 year prior to screening
• * History of alcohol or substance abuse within prior year, as determined by study clinician and urine toxicology screen
• * History of head injury rated as moderate or worse, per DSM-5 criteria
• * History of seizure within prior 10 years
• * Current use of medication with known adverse effects on cognition (benzodiazepines, barbiturates, opiate analgesics, first generation antipsychotic medication, centrally acting anticholinergics, sedating antihistamines, tricyclic anti-depressants)
• * Change in dose of any psychiatric medications within 4 weeks of screening visit
• * Prior use of L-DOPA, any anti-Parkinsonian medication, or prior treatment with anti-amyloid immunotherapy
• * Current use of putative mitochondrial enhancers and antioxidants (e.g carnitine, creatine Co-Q10, N-acetyl cysteine \[NAC\], pramipexole)
• * Initiation of treatment or change in dosing of acetylcholinesterase inhibitors (AChEIs) and memantine within 4 weeks of baseline visit
• * Prior use of prescription narcotics 4 weeks before baseline visit
• * Female subjects who are pregnant or breastfeeding
• * The use of current use of niacin (or a vitamin supplement with niacin) \>200mg within the last two weeks prior to study visit.
• * Current or lifetime history of cancer.