ReCODE: A Personalized, Targeted, Multi-Factorial Therapeutic Program for Reversal of Cognitive Decline

Abstract

Background: Alzheimer's disease (AD) is the major cause of age-associated cognitive decline, and in the absence of effective therapeutics is progressive and ultimately fatal, creating a dire need for successful prevention and treatment strategies. We recently reported results of a successful proof-of-concept trial, using a personalized, precision medicine protocol, but whether such an approach is readily scalable is unknown.

Objective: In the case of AD, there is not a single therapeutic that exerts anything beyond a marginal, unsustained, symptomatic effect. This suggests that the monotherapeutic approach of drug development for AD may not be an optimal one, at least when used alone. Using a novel, comprehensive, and personalized therapeutic system called ReCODE (reversal of cognitive decline), which proved successful in a small, proof-of-concept trial, we sought to determine whether the program could be scaled to improve cognitive and metabolic function in individuals diagnosed with subjective cognitive impairment, mild cognitive impairment, and early-stage AD.

Methods: 255 individuals submitted blood samples, took the Montreal Cognitive Assessment (MoCA) test, and answered intake questions. Individuals who enrolled in the ReCODE program had consultations with clinical practitioners, and explanations of the program were provided. Participants had follow-up visits that included education regarding diet, lifestyle choices, medications, supplements, repeat blood sample analysis, and MoCA testing between 2 and 12 months after participating in the ReCODE program. Pre- and post-treatment measures were compared using the non-parametric Wilcoxon signed rank test.

Results and conclusions: By comparing baseline to follow-up testing, we observed that MoCA scores either significantly improved or stabilized in the entire participant pool-results that were not as successful as those in the proof-of-concept trial, but more successful than anti-amyloid therapies-and other risk factors including blood glucose, high-sensitivity C-reactive protein, HOMA-IR, and vitamin D significantly improved in the participant pool. Our findings provide evidence that a multi-factorial, comprehensive, and personalized therapeutic program designed to mitigate AD risk factors can improve risk factor scores and stabilize or reverse the decline in cognitive function. Since superior results were obtained in the proof-of-concept trial, which was conducted by a small group of highly trained and experienced physicians, it is possible that results from the use of this personalized approach would be enhanced by further training and experience of the practicing physicians. Nonetheless, the current results provide further support indicating the potential of such an approach for the prevention and reversal of cognitive decline.

Keywords: AD risk factors; Alzheimer’s disease; blood analysis; cognitive decline; diet; lifestyle; supplements; therapeutics.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1

Changes in risk factor levels among participants enrolled in the ReCODE program. (a) A significant decline in hs-CRP (p < 0.001) was observed in the treatment group (n = 177) compared to the high levels at baseline. While baseline hs-CRP ranged from 0.09 to 3.1 with a mean of 0.8, post-treatment levels ranged from 0.03 to 2 with a mean of 0.64. The baseline median score was 0.6, post-treatment median score was 0.5 (b) Baseline Vit D levels among participants (n = 207) ranged from 3.6 to 91 with a mean of 45 and median score of 42, post-treatment levels ranged from 18 to 82 with a mean of 50 and median score of 52. This increase in the post-treatment group was statistically significant (p < 0.001).

Figure 2

Changes in HOMA-IR and Fasting Glucose levels among participants enrolled in the ReCODE program. (a) A significant decline in HOMA-IR (p < 0.002) was observed in the treatment group (n = 176) compared to the high levels at baseline. While baseline HOMA-IR ranged from 0 to 2.7 with a mean of 1.2, post-treatment levels ranged from 0 to 2.5 with a mean of 1.07. The baseline median score was 1.1, post-treatment median score was 1.0. (b) A significant reduction in fasting glucose (p < 0.01) is observed among participants (n = 208) following the treatment protocol. While baseline fasting glucose levels ranged from 67 to 119 with a mean of 93, post-treatment scores ranged from 73 to 111 with a mean of 91. The baseline median score was 92, post-treatment median score was 91.

Figure 3

MoCA test scores from participants prior to and after the inception of the program. While there is a trend toward increased scores (a) among the entire participant pool (n = 251), statistical significance was not achieved (p = 0.484). (b). MoCA test scores were evaluated among participants with baseline score ≥ 10 (n = 212). Improvement in the post-treatment scores was statistically significant (p < 0.05). (c). MoCA test scores of participants (n = 151) with a baseline score of ≥ 19 showed statistically significant improvement in the post-treatment scores (p < 0.005).