Modulation of the Cognition–Sleep Nexus in Subjective Cognitive Decline: A 12-Week, Randomized, Double-Blind, Placebo-Controlled Trial of a Standardized Cordyceps militaris Extract

Abstract

Background: Subjective cognitive decline (SCD) and sleep disturbance form a self-reinforcing cycle that accelerates neurodegeneration. Cordyceps militaris (CM), a medicinal fungus rich in nucleosides, has neuroprotective and adenosinergic (sleep-promoting) properties.

Objective: To evaluate the efficacy of a standardized CM extract on the cognition–sleep nexus in adults with SCD.

Methods: In a 12-week, single-center, randomized, double-blind, placebo-controlled, parallel-group trial in Palembang, Indonesia, 120 adults aged 45–65 years with SCD received 300 mg/day of a standardized CM mycelial extract (3% cordycepin) or matching placebo. The primary outcome was change in the Montreal Cognitive Assessment–Indonesian (MoCA-INA) score. Bonferroni-corrected key secondary outcomes were the Pittsburgh Sleep Quality Index (PSQI), Rey Auditory Verbal Learning Test (RAVLT) delayed recall and polysomnography-derived sleep efficiency (SE). Intention-to-treat analyses used a linear mixed-effects model (LMM).

Results: A significant group-by-time interaction favored CM for MoCA-INA (adjusted mean difference [AMD] +1.95; 95% confidence interval [CI] 1.10, 2.80; p < 0.001). All three key secondary outcomes improved: PSQI (AMD −2.90; 95% CI −3.81, −1.99), RAVLT delayed recall (AMD +2.15; 95% CI 1.30, 3.00) and SE (AMD +5.8%; 95% CI 3.1, 8.5); all p < 0.001. After false discovery rate (FDR) correction, benefits were also seen for processing speed, rapid eye movement (REM) sleep percentage, serum brain-derived neurotrophic factor (BDNF) and high-sensitivity C-reactive protein (hs-CRP). The extract was well tolerated.

Conclusion: Twelve weeks of standardized C. militaris extract improved cognitive function, episodic memory and both subjective and objective sleep in adults with SCD, with changes in neuroplasticity and inflammation markers consistent with a multi-target mechanism.