Cognitive Resilience for the Prevention of Mild Cognitive Impairment in Subjective Cognitive Decline: A Monte Carlo Simulation of a Digital Therapeutic Targeting Dementia Risk Factors

Introduction Subjective cognitive decline (SCD) is an early marker of neurodegenerative disease and a target for preventative interventions. With advances in smartphone-based clinical interventions and understanding of modifiable risk factors for cognitive decline, this simulation study aimed to estimate the potential benefits of a prescription digital therapeutic (PDT) with multi-risk-factor modification on the cognitive trajectory of individuals with SCD. We constructed a Monte Carlo simulation to model progression to mild cognitive impairment (MCI) over a five-year period. Methods A virtual cohort of 10,000 patients with SCD was simulated over five years. Baseline annual risk of progression to MCI was set at 10%. A PDT was assumed to yield a 30% relative risk reduction, modulated by adherence levels (70% full, 20% partial, 10% none). Additionally, 14 modifiable dementia risk factors were modeled based on the 2024 Lancet Commission update, with each risk factor assigned a prevalence, modifiability flag, relative risk reduction, and effectiveness rate. Risk adjustments were applied multiplicatively, and outcomes were tracked annually. Results After five years, 6,487 (65%) of patients remained cognitively stable, 2,496 (25%) progressed to MCI, and 1,017 (10%) dropped out. These results represent a significant improvement over the expected 41% progression rate in untreated SCD populations. Reductions in physical inactivity, hypertension, hearing loss, and social isolation contributed substantially to outcome improvements, particularly when multiple risk factors were addressed concurrently. Conclusion The incorporation of a PDT with systematic modification of multiple modifiable dementia risk factors demonstrates a meaningful reduction in cognitive decline risk among individuals with SCD. These findings highlight the potential of integrated digital-first strategies to meaningfully delay cognitive decline and may inform future PDT trials and dementia prevention programs. Validation in prospective clinical trials is warranted to confirm these simulation-based findings.