Precision Medicine Approach for Early Dementia & Mild Cognitive Impairment

The precision medicine treatment approach to be evaluated in this clinical trial is a novel, functional, lifestyle intervention for the treatment of mild cognitive impairment or early-stage dementia. The protocol focuses on optimization of a diverse set of metabolic parameters coupled with lifestyle medicine and clinical nutrition strategies that address the mismatch in these contributors. The approach is personalized for each participant and based on more than 150 data points, including lab evaluations, brain scans, genomic evaluation, cognitive testing, and a detailed medical and family history. Importantly, this progressive treatment approach is based on continued optimization through iterative treatment and metabolic characterization. The precision medicine treatment approach includes a core set of interventions (Precision Medicine-Core) and a set of interventions that are based on the clinical subtype of dementia (Precision Medicine-Cognitive Subtypes). All participants randomized to the precision medicine treatment approach group will receive the core treatment program. The elements of the core treatment program include diet, physical exercise, mental exercise, sleep optimization, and stress reduction. In addition, all participants randomized to the precision medicine treatment approach will be evaluated for all putative or potential underlying drivers of dementia including: 1) inflammatory factors (Type 1 Inflammatory), 2) glycotoxic factors (Type 1.5 Glycotoxic), 3) atrophic factors (Type 2 Atrophic), toxic factors (Type 3 Toxic), vascular factors (Type 4 Vascular), and traumatic factors (Type 5 Head Trauma). This study will use a pragmatic, randomized, multicenter, control group design in which participants will be randomized to a 9-month precision medicine treatment approach or a 9-month standard-of-care treatment approach. Participants in the standard-of-care group will receive the standard-of-care mild cognitive impairment and early-stage dementia. Following completion of the 9-month intervention period, participants in the standard-of-care group will be eligible to receive the precision medicine treatment approach. During the course of the 9-month precision medicine treatment approach, participants and study partners will be scheduled for regular visits with members of the study team at each practice. These visits will be scheduled at approximately 4-week intervals following randomization. Cognitive function tests will be performed at baseline (Visit 1), Month 3 (Visit 4), Month 6 (Visit 7), and Month 9 (Visit 10). Cognitive testing includes the MoCA to be performed by a blinded psychometrician prior to randomization and then 1-2 weeks before the 3-, 6-, and 9-month visits. The CNS Vital Signs will be performed by each staff at each of the six participating sites. Participants in the standard-of-care treatment group will complete a similar set of visits at the same intervals during this time. A final follow-up visit will occur within 4 weeks of completion of Visit 10 to complete all effectiveness and safety follow-up assessments. Following completion of the final follow-up visit, all participants in the standard-of-care treatment group will be eligible for initiation of a 6-month precision medicine treatment approach. Safety data will be collected for participants in both groups through completion of the 6-month precision medicine intervention period for participants initially randomized to the standard-of-care treatment group. Periodic unblinded safety reviews are planned at approximately 1-month intervals for the full duration of the trial. These reviews will be conducted by the Study Oversight and Safety Review Committee. Participants will be enrolled from six geographically-diverse clinical practices and randomized to either the precision medicine treatment approach (Group A) or the standard-of-care control group (Group B). The population to be enrolled will be heterogenous in terms of demographic and clinical characteristics of their cognitive dysfunctions. In addition, the precision medicine intervention will be heterogenous because, by definition, precision medicine is personalized to target the specific metabolic abnormalities that are identified in each participant as uniquely associated with mild cognitive impairment or early-stage dementia. Given the real-world settings, heterogeneity in study participants, and heterogeneity of the specific precision medicine components, a pragmatic, randomized, controlled trial will provide the best evaluation of the precision medicine treatment approach while offering maximum external validity and the ability to generalize findings from this study to precision medicine practice settings and patients who are treated in the US.