In this research study we want to learn more about whether taking Niagen, a daily supplement containing a form of Vitamin B3, will improve cognitive function, mood, and daily activity in people with Subjective Cognitive Decline (SCD) or Mild Cognitive Impairment (MCI).

Over a 6 month period, we will ask study participants to take both Niagen or a placebo for 8 weeks each and complete research visits ever 4 or 8 weeks. Most research visits will involve a blood draw, cognitive testing, and mood questionnaires. We will ask you to come to our center 4-5 times to complete some study activities in-person. There will be an option to participate in a lumbar puncture sub-study, in which participants would have up to 3 lumbar punctures. There will also be an option to participate in an MRI sub-study, in which participants would have up to 3 MRIs over the course of the study. In between research visits, we will also ask the participants to wear a Fitbit activity tracker and play computerized brain games a few times a week. This will enable us to get a snapshot of each subject's functioning levels day to day and better determine whether or not the supplement is having an effect on the participant.

Inclusion criteria:

1. Ages 60 and up;

2. Memory and other cognitive complaints consistent with SCD or MCI as defined by the National Institute on Aging:

   a. SCD will be defined as: i. any subjective concern of change in cognitive functioning without objective evidence of cognitive impairment, and ii. complete preservation of functional abilities and independence in instrumental activities of daily living.

   b. MCI will be defined as: i. a preexisting diagnosis of MCI given by a trained physician or behavioral health provider, or ii. evidence of objective impairment in cognitive functioning in one or more domain with preservation of functional abilities and independence in instrumental activities of daily living as defined by the National Institute on Aging;

3. Minimum score of 16 on t-MoCA;

4. Ability to provide direct informed consent as assessed by obtaining a score of 70% on questions 1-10, and answer 'yes' to questions 11-14 of the Informed Consent Worksheet after two attempts;

5. Education level, English language skills and literacy indicates participant able to complete all assessments;

6. Willing and able to complete all assessment and study procedures;

7. Not pregnant, lactating, or of child-bearing potential;

8. If on cholinesterase inhibitor and/or memantine, doses are stable for 3 months prior to baseline.

Exclusion Criteria:

1. Any specific CNS disease history other than suspected ADRD, such as major clinical stroke, brain tumor, normal pressure hydrocephalus, multiple sclerosis, significant head trauma with persistent neurological of cognitive deficits or complaints;

2. Any impairment in instrumental activities of daily living that would indicate a level of cognitive impairment beyond MCI as assessed by a trained rater;

3. Clinically significant unstable medical condition that could affect safety or compliance with the study and would, in the opinion of the investigator, pose a risk to the participant if they were to participate in the study;

4. History of neuroimaging with evidence of major infarction, injury, infection, or other focal lesions that may be related to cognitive dysfunction;

5. If participating in the optional lumbar puncture sub-study, any contraindication to undergo lumbar punctures, such as:

   1. abnormal coagulation PT/INR test result, outside of the normal range of 0.9 to 1.2 platelet counts below 50,000 (determined by a licensed study physician or Nurse Practitioner after reading test results).
   2. Platelet counts below 50,000.
   3. Use of Coumadin, Warfarin, or other blood thinner medications.
   4. Infection near the puncture site, or spinal column deformities (a licensed physician or Nurse Practitioner will examine the site visually for infection or spinal deformities before performing the procedure).
   5. Known allergy to Lidocaine.

6. Major active or chronic unstable psychiatric illness (e.g. depression, bipolar disorder, obsessive compulsive disorder, schizophrenia) within the previous year;

7. Current suicidal ideation or history of suicide attempt;

8. History of alcohol or other substance abuse or dependence within the past two years;

9. Any significant systemic illness or medical condition that could affect safety or compliance with study;

10. Laboratory abnormalities in Vitamin B12, Thyroid Stimulating Hormone (TSH), or other common laboratory parameters that might contribute to cognitive dysfunction or other abnormalities in hematological, hepatic or renal function tests;

11. Current use of medications with psychoactive properties that in the opinion of the principal investigator, may be deleteriously affecting cognition (e.g., anticholinergics, antihistamines, antipsychotics, sedative hypnotics, anxiolytics);

12. Any known hypersensitivity to nicotinamide riboside, or its principal metabolite, nicotinamide mononucleotide;

13. No consumption of dietary supplements containing more than 100mg niacin, nicotinamide riboside (NR), or nicotinamide mononucleotide (NMN) as the primary agents 30 days prior to baseline and for the duration of the trial;

14. Use of other investigational agents or interventions one month prior to entry and for the duration of the trial;

15. If participating in the optional MR sub-study: Any contraindication to undergo MRI studies, such as history of cardiac pacemaker or pacemaker wires, metallic particles in the body, vascular clips in the head, prosthetic heart valves, and/or severe claustrophobia impeding ability to participate in an imaging study.

All data will be DE-Identified

Adverse event data were collected for each participant from the baseline visit to end of study, 20 weeks. In the NR-Placebo group (Sequence 1), there were 22 participants that started Baseline, with 2 withdrawing/Early Termination before crossover. In the Placebo- NR group (Sequence 2), there were 20 participants that started baseline (Placebo) and then 18 who crossed over into the NR group. Data was collected for 22 participants in Sequence 1 and 20 participants in Sequence 2.