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

Inclusion Criteria:

• Ability of the participant and/or his/her legally authorized representative tounderstand the purpose and risks of the study, to provide signed and dated informedconsent, 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 followingcriteria:

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 bySabbagh 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

Exclusion Criteria:

• Current serious or unstable medical or neurological condition that could affectcognitive functioning, as determined by study clinician

• Clinically unstable mood or anxiety disorder within 6 months prior to screening, asdetermined by study clinician

• Lifetime history of psychotic disorder (i.e. Schizophrenia, SchizoaffectiveDisorder), 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 studyclinician 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, tricyclicanti-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 withanti-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 withinthe last two weeks prior to study visit.

• Current or lifetime history of cancer.