N-AD: Orally Administered Nicotinamide Riboside Over Two Years as a Potential Disease Modifying Treatment for Alzheimer's Disease

Inclusion criteria

• Diagnosis Early clinical AD, e.g. Stage 3 MCI or Stage 4 (mild AD dementia), as defined by the FDA, 2024.
• Biomarker evidence consistent with AD neuropathologic change, defined by CSF markers, i.e. Aβ42 \< 1030 ng/L and P-tau181/Aβ42 \> 0,023 ng/L and/or T-tau/Aβ42 \> 0,28 ng/L\* or AD amyloid biomarker (as determined either by visual reading of amyloid PET scans using an approved ligand
• Diagnosed with AD within 2 years from baseline.
• Capacity to provide written informed consent for study participation defined as Montreal Cognitive Assessment (MoCA) score ≥ 16 or Mini Mental State Evaluation (MMSE) score ≥ 20. MMSE or MoCA must have been performed within 6 months prior to baseline. If there is any doubt regarding the participants capacity to give informed consent, this will be determined by an evaluation by a consultant clinician who is not associated with the N-AD study.
• Global CDR(33) 0.5-1 (inclusive) at enrollment.
• Age 50 to 85 years (inclusive) at the time of enrollment.
• A study partner with sufficient contact to be able to provide data on ADLs and assist the participant in study drug administration. -
• Cholinesterase inhibitors and memantine can be used if stable for 8 weeks prior to baseline visit.

Exclusion criteria

• Diagnosis of dementia other than probable AD.
• Abundant vascular pathology, i.e. Fazekas \>2. or \>3 lacunar infarcts, stroke involving a major vascular territory, severe small vessel, or white matter disease
• More than 1 core feature of dementia with Lewy bodies, i.e; recurrent visual hallucination, cognitive fluctuations, REM sleep behaviour disorder, one or more spontaneous cardinal features of parkinsonism (tremor, rigidity and bradykinesia).
• Comorbidity that precludes study participation or data interpretation.
• Any psychiatric disorder that would interfere with compliance in the study.
• Use of high dose vitamin B3 supplementation within 30 days of baseline.
• Any active neoplastic malignancy (other than non-metastatic dermatological conditions) within two years of the screening visit or current clinically significant haematological, endocrine, cardiovascular, renal, hepatic, gastrointestinal, or neurological disease. Active neoplastic malignancy is defined as having a known malignant focus and/or receiving anti-cancer treatment. For the non-cancer conditions, if the condition has been stable for at least the one year before the screening visit and/or is judged by the site investigator not to interfere with the subject's participation in the study, the subject may be included.
• Inability to undergo MRI or to comply with study procedures.