The PREVENTION Trial is a 12-month, two-arm randomized clinical trial (RCT) in adults 50-80 years old experiencing cognitive decline. Our study clinicians will refer patients for enrollment based on three categories: 1) a diagnosis of mild AD according to criteria established by the National Institute of Neurological and Communicative Disorders and Stroke (AD and Related Disorders Association [NINCDS-ADRDA]), 2) those with mild cognitive impairment will be diagnosed according to the Petersen method, and 3) subjective memory impairment as assessed by neuropsychological assessments and self-report. Enrollment will require evidence of AD pathophysiological processes (as defined by a positive amyloid positron emission tomography (PET) scan).

The first objective is to evaluate the efficacy of a coached, data-driven, multi-modal lifestyle intervention to treat cognitive decline. Subjects will be randomized into one of two groups: Group 1 (Active Control) or Group 2 (Intervention). Group 1 (Data-driven clinical recommendations (CR)) will serve as the active control group and will receive data-driven clinical recommendations by a study physician based on study assessments and clinical lab values. Group 2 (Data-driven multi-modal intervention with coaching (MMIC)) will receive the same clinical recommendations and also an intensive multi-modal intervention with health coaching, support and resources to carry out these recommendations. This includes health coaching sessions (with an RDN), dietary counseling sessions (with an RDN), and group cognitive and physical exercise classes (CogFit) with a certified personal trainer and a computer-based neurocognitive program at home. Both groups will be measured for treatment related changes in cognitive and functional abilities, quality of life, biological, and biochemical measures.

The second objective is to analyze longitudinal multi-omic data, including metabolomics, proteomics, genetics, microbiome, behavior and cognition into personalized, dense, dynamic data (i.e. PD3) from individuals with cognitive decline and underlying Alzheimer's neuropathology. The goal analysis is to identify models of causation that can further advance knowledge and research in neurodegenerative disorders and healthy living.

Subject identification and recruitment - All participants will be recruited from the Pacific Brain Health Center in Santa Monica, which is a high-volume memory-care and dementia outpatient clinic within a large physician medical group affiliated with Providence Saint John's Health Center. 60 participants will be randomized into the RCT, with 30 in each treatment arm.

Procedures for Obtaining Informed Consent - All participants will receive the Experimental Research Subject's Bill of Rights prior to signing the informed consent form (ICF), authorization of use and disclosure of protected health information (PHI), and authorization of medical record release for the subject's treating physician, will be obtained from each participants prior to enrolling in the study. A copy of all signed ICF's will be given to the participants, and the investigator will retain the original.

A Functional Assessment Staging Test (FAST) will be done before participants are consented to determine whether they or a legally appointed representative (LAR) can consent to participate in the study. In this study, participants with FAST stages 2-4 will be recruited (see Inclusion Criteria).

Considerations for consenting: FAST Stages 2-3 Participants - FAST stages 2-3 participants are usually capable of making medical and legal decisions, and will be consented directly, unless there is a caregiver, legally appointed representative, or other reason to think that an informed consent cannot be given by the participants without approval by a reliable informant acting on their behalf.

Considerations for consenting: FAST Stage 4 (mild dementia) Participants - FAST stage 4 participants will be consented by having them give oral or written assent, indicating their preference with regard to study participation. In addition, the caregiver or legally appointed representative of a demented participants will be consented to assure full understanding of study procedures and willingness on behalf of the participants to participate in the study.

The consenting approach for patients with cognitive impairment has been evaluated by the Department of Psychiatry and Behavioral Sciences at Johns Hopkins, and found to adequately ensure informed consent. They concluded that ADRD participants should not be excluded from study participation if they cannot directly consent themselves, so long as their caregivers can consent, and the participants can assent, either verbally or in writing, their preference to participate in the study.

The caregiver or legally appointed representative will be required to accompany participants to participate in the required procedures. A copy of the appropriate document (e.g., the power of attorney for healthcare) will be obtained and filed with the original ICF.

Inclusion Criteria

• Subjects must be age 50 to 80 at time of informed consent.
• Subjects of any gender, race or ethnicity are eligible to enroll in the study.
• Subjects must have a FAST stage of 2-4.
• Subjects with FAST Stage 4 must have a caregiver or legally appointed representative willing to accompany participants to the required procedures.
• As part of the study screening procedure, subjects must be willing to undergo an amyloid PET scan or have previously undergone an amyloid PET scan and agree to make the results available. Subjects must be amyloid positive to be eligible to enroll in the study.
• Subjects must be proficient in spoken and written English for consenting as well as for study participation since the intervention in this study (e.g., coaching program) is currently only available in English.
• Subjects with medical conditions must be stable for these conditions. Stable control on medication is acceptable. Subjects should not have started any new medications for chronic conditions within the last three months.
• A neurological and physical evaluation will be conducted prior to enrollment of the study by a qualified medical doctor and confirmed through medical records that they do not possess any abnormal physical or neurological sign, and/ whether they are considered to be clinically significant. Also an MMSE >19 will be confirmed by a medical doctor prior to study enrollment.
• Subjects, with or without assistance, must be able to use a computer and web interface. If assistance is needed, it must be readily available to them.
• Subjects must be able to converse with a coach telephonically. Video-based telephone coaching is part of data-driven health coaching.
• Subjects must have regular access to a computer and the Internet along with dedicated email address since certain aspects of the program (e.g. cognitive training) are delivered electronically.
• Subject must have normal visual acuity (or corrected to normal) and normal color vision as indicated by self-report.
• Subject must have adequate hearing acuity as indicated by self-report.
• Subject must have adequate motor capacity to use a mobile phone/iPad/computer as indicated by self-report and confirmed by staff before they are enrolled into a treatment arm.
• Subject must be cleared by a physician to participate in a moderately intensive exercise program.

Exclusion Criteria

• Subjects with an existing diagnosis of a non-AD neurodegenerative disorder (e.g., Lewy Body Dementia, Frontal-Temporal Dementia).
• Subjects with a diagnosis of cerebrovascular disease as the primary cause of cognitive impairment.
• A previously reported AD high-risk mutation (e.g., in the Presenilin Protein (PSEN) or Amyloid Precursor Protein (APP) genes) in the participant or immediate family (children, siblings, or parents). Such patients may accumulate amyloid faster than in late onset AD, and therefore may show less pronounced benefit from intervention.
• Mini Mental State Exam (MMSE) below 20.
• Clinical Dementia Rating (CDR) global score of 2 or above.

Participants will be assigned with a participant identification number (ID), so that data will not be identified by any names or personally identifiable information. This ID will be used throughout this study.