Mitochondrial dysfunction in peripheral mononuclear blood cells (PBMC) of individuals with mild cognitive impairment.

Abstract

Mitochondrial dysfunction is a hallmark of aging and many age-related neurodegenerative diseases. Mild cognitive impairment (MCI) refers to a clinical condition characterized by noticeable cognitive decline that exceeds normal age-related changes but does not significantly interfere with daily functioning. MCI is often considered an early stage of neurodegenerative conditions, including Alzheimer's disease. We therefore investigated the relationship between mitochondrial function in peripheral blood cells and cognitive performance in individuals with amnestic (aMCI) and nonamnestic mild cognitive impairment (naMCI). Control groups consisted of young (YC) and older adults (OC) who were physically and mentally healthy. Cross-sectional observational study involving 90 participants, including young adults, cognitively healthy older adults, and individuals with MCI. Mitochondrial function was determined in cryopreserved PBMCs. Cognitive status was assessed using the German version of the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) test battery. ATP levels in cryopreserved PBMC isolated from individuals with aMCI were significantly lower than those of OC and YC. Endogenous respiration varied significantly between groups, with the MCI group exhibiting the lowest respiration. Linear regression analyses with ATP as a predictor for cognitive performance showed a significant positive relationship between ATP levels and both immediate recall and fluency. The regression coefficients indicated a moderate positive correlation between ATP levels and performance in both tests. This suggests that higher ATP levels are associated with improved cognitive performance. Our data suggest that mitochondrial dysfunction in PBMC is associated with MCI and correlates with cognitive impairment. Subjects who performed poorly on neuropsychological tests also exhibited lower ATP levels. Given that PBMC are easily accessible, they offer valuable insights into the bioenergetic status of individuals at increased risk for dementia. The study (PEM-MCI) has been retrospectively registered at the German Register of Clinical Trials (DRKS) DRKS00036017 (registered on 30.01.2025).