# Short-Term Changes in Depressive Symptoms Among Patients with Alzheimer’s Disease Following a Precision Medicine Intervention

**Authors:** Rammohan V. Rao, Alan Boyd, Sho Okada, William Lipa, Lance Kelly, Christine Coward, Aida L. Bredesen, Julie Gregory, Dale E. Bredesen

PMC · DOI: 10.3390/brainsci16010002 · Brain Sciences · 2025-12-19

## TL;DR

A precision medicine program for Alzheimer’s disease also reduces depressive symptoms, offering benefits for both mood and cognition.

## Contribution

The study demonstrates that the ReCODE program significantly improves depressive symptoms in Alzheimer’s patients alongside cognitive benefits.

## Key findings

- Participants showed statistically and clinically significant reductions in PHQ-9 scores.
- Improvement was observed across all baseline depression categories (mild, moderate, and severe).
- Fewer participants scored above the clinical depression threshold after the intervention.

## Abstract

Background/Objectives: The ReCODE (Reversal of Cognitive Decline) protocol, a precision medicine program for patients with Alzheimer’s disease (AD), has demonstrated promising results in improving cognitive function. However, its impact on mood, specifically depressive symptoms, has been less explored. Depression is highly prevalent in individuals with mild cognitive impairment and AD, shares common risk factors (e.g., systemic inflammation), and negatively affects quality of life and disease trajectory. This study evaluated whether participation in the ReCODE program is associated with measurable improvement in depressive symptoms, as assessed by the Patient Health Questionnaire-9 (PHQ-9). Methods: This retrospective, observational analysis utilized de-identified data from 170 individuals diagnosed with mild to moderate AD enrolled in the ReCODE program. Participants received initial consultations and program orientation. Follow-up visits occurred 31 days post-enrollment, including further guidance on diet, lifestyle, medications, and supplements, along with mood assessment using the PHQ-9. Pre- and post-intervention PHQ-9 scores were analyzed using the non-parametric Wilcoxon signed-rank test. Results: Participants showed a statistically and clinically significant reduction in PHQ-9 scores. Improvement was observed across all baseline depression categories (mild, moderate, and severe). Critically, the proportion of participants scoring above the clinical threshold for depression decreased substantially following the intervention. Conclusions: These findings suggest that the ReCODE precision-medicine framework offers concurrent benefits for both mood and cognition. Extending prior work, our results indicate that the ReCODE program not only benefits cognitive and biological measures but also significantly alleviates depressive symptoms. While the results highlight ReCODE’s potential as a successful multifaceted therapeutic approach addressing both cognitive decline and mental health in Alzheimer’s disease, given the retrospective, uncontrolled design, the findings should be interpreted as associative and hypothesis-generating rather than causal.

## Linked entities

- **Diseases:** Alzheimer’s disease (MONDO:0004975), depression (MONDO:0002050)

## Full-text entities

- **Diseases:** Cognitive Decline (MESH:D003072), Depression (MESH:D003866), AD (MESH:D000544), inflammation (MESH:D007249)
- **Chemicals:** ReCODE (-)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

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## References

59 references — full list in the complete paper: https://tomesphere.com/paper/PMC12838874/full.md

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Source: https://tomesphere.com/paper/PMC12838874