Sirtuin-NAD Activator in Alzheimer's Disease

Prior treatment

• Neuroimaging: Baseline or prior magnetic resonance imaging (MRI) scans with evidence of cortical stroke or hemorrhage, strategically located lacunar stroke (ex: left thalamus), or severe small vessel ischemic disease.
• Excluded medications: Niacin or dietary supplements containing nicotinamide mononucleotide (NMN) or nicotinamide riboside (NR); antipsychotic medications, antidepressant medications with anticholinergic side effects. Washout from psychoactive medications for at least 8 weeks before screening.

Other illness

• Neurologic diseases: Any significant neurologic disease other than AD that can lead to cognitive impairment, such as Parkinson's disease, vascular dementia, dementia with Lewy bodies, frontotemporal dementia, Huntington's disease, normal pressure hydrocephalus, corticobasal syndrome, brain tumor, seizure disorder, subdural hematoma (within the last 1 year), multiple sclerosis, or history of significant head trauma (e.g. loss of consciousness for 30 minutes or more) followed by persistent neurologic deficits or known structural brain abnormalities.
• History of alcohol or substance use disorder or dependence (DSM V criteria) within the last 2 years.
• Psychiatric disorder: Major depressive disorder (within the last 1 year), bipolar disorder, schizophrenia (DSM V criteria), or current major psychotic symptoms or behavioral problems that could interfere with study procedures.
• Any significant systemic illness or unstable medical condition, which could obfuscate cognitive aging or neurodegenerative trajectories or affect valid cognitive and self-report measurements.
• Current use of anticoagulants; significant back or spine disease that would make a lumbar puncture difficult or unsafe as determined by a clinician.
• Other medical conditions which, in the opinion of the investigator, would jeopardize safety or impact the validity of the study results.

Lab values

• Other laboratory abnormalities: Has AST or ALT \> 3 times the upper limit of normal; serum creatinine \> 2.0 mg/d; HbA1C \> 8.5%

Other

• Subjects may not be enrolled if:
• Participation in an investigational trial to evaluate pharmaceuticals or biologics within the past 3 months or 5 half-lives, whichever is shorter

• A man or a woman between the ages of 55 and 85 years (inclusive)
• Meets National Institute on Aging-Alzheimer's Association (NIA-AA) clinical diagnostic criteria for AD dementia
• Has evidence of AD pathological process by a positive amyloid assessment with cerebrospinal fluid (CSF) Aβ42
• Has a Clinical Dementia Rating (CDR) global score of 0.5 or 1
• Has a Mini-Mental State Exam (MMSE) Score of 18 to 26 (inclusive)
• Has a 15-item Geriatric Depression Scale (GDS) score of \< 6
• Impaired memory performance below education adjusted cut-off score on the Logical Memory II subscale delayed paragraph recall (LM-IIa) of the Wechsler Memory Scale-Revised (WMS-R) (≥16 years: ≤8; 8-15 years: ≤4; 0-7 years: ≤2)
• May take Food and Drug Administration (FDA) approved medications for the treatment of AD dementia (cholinesterase inhibitors and/or memantine), but if taking such medications, they must be stable for at least 8 weeks before screening
• Has adequate visual and auditory acuity to participate in neuropsychological testing and other study assessments
• Has the availability of an informant (study partner) who has regular contact with the participant and knows him/her well
• Is willing and able to participate in all assessments in English
• Is capable of providing written informed consent