Precision Medicine Protocol for Cognitive Decline Also Reduces Depression, New Data Suggest

A precision medicine protocol originally designed to slow or reverse cognitive decline may also offer significant relief from depression in adults with Alzheimer disease and mild cognitive impairment (MCI), according to new data currently in preprint.¹

In a study of 170 adults diagnosed with both cognitive impairment and depression, participation in the ReCODE (Reversal of Cognitive Decline) program was associated with clinically meaningful improvements in mood after just 1 month of treatment. Average Patient Health Questionnaire-9 (PHQ-9) scores fell by 3.96 points (P <.001) over the 31 days between study assessments, a more favorable change compared with the modest PHQ-9 reductions typically observed with selective serotonin reuptake inhibitors of -2 to -3 points on average, often without a change in severity category, according to the study authors. Importantly, many participants moved from moderate (10–14) to mild (5–9) depression categories, an improvement indicating both statistical and clinical significance. The greatest gains were observed in patients with more severe baseline depression.¹

“Depression is a common and devastating complication for individuals facing [Alzheimer] disease and related conditions,” said lead author Ram Rao, PhD, in a statement. “Our findings suggest that by treating root causes of cognitive decline, we may also alleviate depression, significantly improving quality of life for patients and families.”²

Multimodal Approach to Neurodegeneration

ReCODE is a precision medicine protocol developed by Apollo Health and based on the research of Dale Bredesen, MD. Unlike single-target drug therapies, ReCODE uses a multifactorial strategy to identify and address contributors to cognitive decline, including insulin resistance, chronic infections, vascular risk, nutrient deficiencies, toxin exposures, sleep apnea, and chronic stress. Personalized interventions based on individual assessments range from dietary and lifestyle modifications to targeted medical management.^1,2

Participants in the study were provided with detailed guidance from physicians and health care teams to help address the factors identified by the ReCODE program.¹

Rao and colleagues pointed out that these same physiologic drivers are also implicated in depression. By systematically correcting metabolic, inflammatory, infectious, immune, and toxic influences, ReCODE may exert parallel benefits on cognition and mood, they suggested.¹

Early But Promising Evidence

The authors noted that “our results underscore the ReCODE program’s capacity to deliver meaningful improvements in mood, in addition to the cognitive, biomarker, and neuroimaging benefits reported in earlier work. This supports the hypothesis that depression is not merely an epiphenomenon of neurodegeneration but a modifiable contributor to the disease course¹.

They added that monitoring depression symptoms with validated instruments such as the PHQ-9 may offer “a low-cost, easily administered, and clinically meaningful inclusion in tracking treatment response and disease progression in early-stage AD.”¹

While these results are encouraging, the study has not yet undergone peer review. As such, the findings should be considered preliminary, authors cautioned. They also emphasized that no single causative factor was linked to the depression outcomes; rather, participants exhibited a range of overlapping contributors that were addressed through personalized care plans guided by the ReCODE algorithm.

Implications for Clinical Practice

Depression affects up to half of individuals with Alzheimer disease and can accelerate cognitive and functional decline. Current pharmacologic options for depression in this population often have limited efficacy.³ A protocol capable of modifying both cognitive and emotional outcomes would therefore represent an important advance.

Apollo Health continues to validate ReCODE in both clinical trials and real-world cohorts. Previous publications have demonstrated improvements in cognition among patients with early Alzheimer disease and MCI.⁴

"As the prevalence of AD rises globally, approaches that simultaneously improve cognition, mood, and systemic health are likely to become increasingly valuable," Rao et al concluded. "Future randomized controlled trials are warranted to confirm these results and assess the durability of benefits over longer durations."

References

1. Rao RV, Boyd A, Okada S, et al. Significant reduction in depression scores following implementation of the ReCODE program: evidence from PHQ-9 assessments. Preprint posted online September 23, 2025. https://www.preprints.org/frontend/manuscript/b2fd9f23b5008e90a910f9951fdb0cc5/download_pub

2. Precision medicine protocol shows dual benefits: improved cognition and reduced depression. News release. Apollo Health. September 25, 2025. Accessed October 3, 2025. https://www.newswise.com/articles/precision-medicine-protocol-shows-dual-benefits-improved-cognition-and-reduced-depression/

3. Chi S, Wang C, Jiang T, et al. The prevalence of depression in Alzheimer's disease: a systematic review and meta-analysis. Curr Alzheimer Res. 2015;12:189-198. doi:10.2174/1567205012666150204124310

4. Rao RV, Kumar S, Gregory J, et al. ReCODE: A personalized, targeted, multi-factorial therapeutic program for reversal of cognitive decline. Biomedicines. 2021;9(10):1348. doi:10.3390/biomedicines9101348