Autophagy-Enhancers to Reduce Sleep Disturbances

This clinical trial investigates the effects of spermidine supplementation on sleep quality and memory function in older adults with Mild Cognitive Impairment (MCI), a condition associated with an increased risk of developing dementia, particularly in patients with MCI due to Alzheimer's disease. Impaired sleep has been identified as a modifiable factor contributing to cognitive decline, and interventions targeting sleep architecture could offer therapeutic potential to prevent or slow down this decline. Spermidine is a naturally occurring polyamine found in foods such as wheat germ and soybeans. It induces autophagy, a cellular degradation and recycling process essential for neuronal maintenance and function. In animal studies, spermidine has been shown to improve memory performance, reduce neuroinflammation, and support mitochondrial health. Preliminary findings from human trials in individuals with subjective cognitive decline or MCI suggest potential cognitive benefits of spermidine, but results are not unequivocal, and the impact on sleep has not been systematically evaluated. In this randomized, double-blind, placebo-controlled trial, 76 participants aged 55 to 70 years with MCI will receive either spermidine (6 mg/day) or a placebo for 12 weeks. Sleep will be evaluated using overnight EEG in a controlled laboratory setting, focusing on measures such as slow-wave sleep and sleep spindle activity. Memory performance will be assessed before and after the intervention using standardized neuropsychological testing. Numerical skills will be tested at baseline only to compare MCI patients with healthy controls. Blood samples will be collected to quantify metabolic indicators, neurodegeneration-related biomarkers, and autophagy-associated proteins. A control group of 38 cognitively healthy individuals will undergo comparable sleep and cognitive assessments without receiving any supplementation. The primary objective of the study is to characterize the impact of spermidine on sleep-dependent memory consolidation and to identify associated biological changes relevant to aging and neurodegeneration. The results may inform the development of non-pharmacological strategies aimed at preserving cognitive function in individuals at risk for dementia.