Passive Sensor Identification of Digital Biomarkers to Assess Effects of Orally Administered Nicotinamide Riboside

Inclusion 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
• 18-89 years old (inclusive)
• Normal or corrected to normal hearing and vision
• Meet clinical diagnostic criteria for MCI or Mild AD, according to the criteria outlined above
• Study partner available for duration of trial participation
• At least one copy of the APOE ε4 allele
• 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

Exclusion criteria

• 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, 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 or antioxidants (e.g. carnitine, creatine, Co-Q10, N-acetyl cysteine, pramipexole)
• Initiation of treatment or change in dosing of acetylcholinesterase inhibitors (AChEIs) and memantine within 4 weeks of screening
• Prior use of prescription narcotics 4 weeks before screening
• Female subjects who are pregnant or breastfeeding
• The current use of niacin (or a vitamin supplement with niacin) \>200mg within the last two weeks prior to study visit