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

Prior treatment

• Clinically unstable mood or anxiety disorder within 6 months prior to screening, as determined by study clinician
• 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 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)
• Prior use of L-DOPA, any anti-Parkinsonian medication, or prior treatment with anti-amyloid immunotherapy
• 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
• The use of current use of niacin (or a vitamin supplement with niacin) \>200mg within the last two weeks prior to study visit.

Other illness

• Current serious or unstable medical or neurological condition that could affect cognitive functioning, 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
• History of drug hypersensitivity or intolerance to NR
• History of head injury rated as moderate or worse, per DSM-5 criteria
• Change in dose of any psychiatric medications within 4 weeks of screening visit
• Current or lifetime history of cancer.

Other

• Any MRI safety contraindications
• Current use of putative mitochondrial enhancers and antioxidants (e.g carnitine, creatine Co-Q10, N-acetyl cysteine \[NAC\], pramipexole)
• Female subjects who are pregnant or breastfeeding

• 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:
  • CDR Global Score of 0.5 (MCI) or 1.0 (mild AD)
  • 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