A precision medicine protocol designed to treat Alzheimer's disease and mild cognitive impairment has demonstrated significant benefits for depression, according to a new preprint study that evaluated 170 patients with both cognitive decline and depressive symptoms.
The study assessed the Reversal of Cognitive Decline (ReCODE) protocol, a multitherapeutic precision medicine approach developed by Apollo Health. After 31 days of treatment, patients experienced an average reduction of 3.96 points in PHQ-9 depression scores (P<0.0001), with participants moving from moderate depression (score of 10-14) to mild depression (score of 5-9) on average.
Targeting Multiple Biological Pathways
The ReCODE program uses computational algorithms to evaluate and treat a range of contributing factors including metabolic, infectious, immune, vascular, and toxic influences. The protocol addresses specific underlying drivers such as inflammation, insulin resistance, nutrient deficiencies, toxin exposure, and hormonal imbalances through personalized lifestyle and therapeutic interventions.
"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," the authors stated. "This supports the hypothesis that depression is not merely an epiphenomenon of neurodegeneration but a modifiable contributor to the disease course."
Study Design and Patient Outcomes
The research evaluated patients presenting with cognitive decline and depression using the Patient Health Questionnaire (PHQ-9), with scores of 10 or higher serving as the threshold for depression. PHQ-9 scores were measured at baseline and after treatment implementation.
Patients with more severe initial depression demonstrated the greatest improvements, and the data showed a robust and consistent treatment effect across the study population. Participants received detailed guidance from physicians and healthcare teams to address the multiple factors identified by the ReCODE program, with no single causative factor identified but rather several interrelated contributors in all participants.
Clinical Implications for Dual Treatment
"Depression is a common and devastating complication for individuals facing Alzheimer's disease and related conditions," said Dr. Ram Rao, lead author of the study. "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."
The protocol addresses multiple contributors to cognitive decline including sleep apnea, pre-diabetes, chronic infections, toxic exposures such as air pollution, and chronic stress—factors that are also known to influence depression. By treating these underlying drivers, the program may offer dual benefits for both brain function and emotional well-being.
The authors suggest that monitoring depression symptoms using validated tools like the PHQ-9 may offer a low-cost, easily administered, and clinically meaningful approach for tracking treatment response and disease progression in early-stage Alzheimer's disease.
The study represents early but promising evidence of the ReCODE protocol's potential to enhance both cognitive and emotional health, though the results require peer review before publication.
