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

Mitochondrial function is mediated, in part, by nicotinamide adenine dinucleotide (NAD). Unfortunately, decreases in NAD+ levels are associated with normal aging, and also with numerous diseases such as AD. Accumulating evidence suggests that NR can enhance mitochondrial function and help slow or reverse these age-related abnormalities. Numerous preclinical and clinical studies have been performed using NR and related compounds to boost NAD+ level in human subjects with various diseases or animal models. However, no studies to date have investigated in vivo metabolic and bioenergetic changes (target engagement) associated with NR supplementation. In this project, we aim to investigate the neurobiological mechanisms and clinical effects of NR in patients with MCI and mild AD using in vivo novel neuroimaging techniques.

Age

55–89

Sex

ALL

Healthy volunteers

Not accepted

You may be eligible if

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

You may not be if

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.

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

What this study is about

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

What this study is about