DISCUSSION
Alzheimer’s disease, cognitive decline, dementia, cognitive impairment
As a proof-of-concept trial aimed at implementing a complex, multimodal, individualized medicine care plan in a sample of people with cognitive decline, the intervention demonstrated success in feasibility, thus supporting a larger, controlled, multi-site clinical trial. Additionally, results reported here corroborate the current literature, thus providing rationale for progress in the field of multimodal, individualized medicine in the treatment of cognitive decline. For example, recently published research from Toups et al reported improvements in cognition in 25 participants with cognitive decline who underwent a similar individualized medicine-based intervention for nine months [The improvements in MoCA were reinforced by the use of objective measures of cognition via the CBS Battery, administered online and independent of the study clinicians. The CBS battery of neurocognitive tests demonstrated significant improvements in overall cognition, as well as significant improvements in memory. Overall cognition in our population at baseline was at the 24th percentile compared to age- and gender-matched scores from a large CBS data set of healthy individuals (i.e., We recruited a participant population relatively reflective of those affected by dementia in the normal population. The gender distribution of participants included 74% women, reflective of dementia statistics, which show that 65% of dementia sufferers are female. Four of seventeen women included were women of color, including three African American and one Asian American. Five male participants were Caucasian and one was Hispanic.Despite the overall significance of the clinical findings reported here, we acknowledge there are several limitations. First, our sample size was small, and the research design was uncontrolled, non-randomized, and limited to a single clinical site. Yet the results demonstrate feasibility and proof-of-concept of medium effect sizes, which warrant further research. Future studies will be strengthened by randomization, adding a control group, and including multiple study sites. Secondly, this research did not assess the impact of the intervention on participants with advanced AD. Trial participants with MoCA scores below 12 were excluded from participation. Third, the research was done within a clinical care setting. Although we consider this feature to be pragmatic, and potentially a strength, we recognize this feature does not prove generalizability and therefore needs to be considered a limitation. Finally, the 32% (11/34) withdrawal rate is high; however, it is lower than the 36% withdrawal rate found in the study of Swanson et al, which assessed lecanemab-treated participants [We would like to acknowledge the care model used as the intervention for our study may present significant financial costs for individuals, and the time burden for adherence is high. Additionally, this kind of individualized, integrative care approach requires advanced and specialized training of the clinicians administering the care. Thus, we acknowledge that questions remain as to the accessibility of this intervention on a broad scale. Even so, this study presents a proof-of-concept for a model of care in patients with cognitive impairment. Future research will model whether or not this type of care is effective, scalable, and further generalizable. As further research will inform target-optimizing the approach, including improvements in access, the potential benefits will become more accessible to more of the population affected by cognitive decline.Results reported herein have the potential to advance the field by demonstrating a clinically delivered multimodal, individualized medicine intervention that has the potential to stabilize, if not improve, the cognitive function of patients with cognitive impairment. The trial provides additional data that begins to address gaps in the literature regarding therapeutic options for cognitive decline. Namely, that a multimodal, individualized medicine therapeutic approach is feasible clinically in a cognitively declined population, and that such an approach has the potential to reverse domains of cognitive decline and overall cognition. Given the progressive nature of cognitive decline and dementia, our results also indicate the need for longer intervention and follow-up periods within a randomized trial, in order to determine the possible maximum effects (i.e., how much reversal is possible in cognitive decline with this therapeutic approach?), and how long those effects may be expected to last. This research is part of a broadening body of work that is beginning to reveal the possible positive impact of multimodal, individualized medicine. Given the context of decades of failed efforts to develop effective therapeutics for Alzheimer’s disease and cognitive decline, the findings provide an exciting and hopeful direction for research, medicine, and most importantly, patients.