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Mitochondrial dysfunction in peripheral mononuclear blood cells (PBMC) of individuals with mild cognitive impairment
Fabian Dieter1, Karlotta Jacobs2, Alice Quentin1
1Institute of Nutritional Science, Justus-Liebig University, Giessen, Germany.
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).
Insights
Mitochondrial dysfunction, indicated by lower ATP levels in peripheral blood cells, is linked to mild cognitive impairment (MCI). This dysfunction correlates with poorer cognitive performance, suggesting accessible blood cells can reveal dementia risk.
Area of Science:
- Neuroscience
- Gerontology
- Biochemistry
Background:
- Mitochondrial dysfunction is a key factor in aging and neurodegenerative diseases like Alzheimer's.
- Mild cognitive impairment (MCI) signifies a decline beyond normal aging, often preceding dementia.
- Investigating peripheral blood cells offers a accessible window into systemic bioenergetic health.
Purpose of the Study:
- To explore the relationship between mitochondrial function in peripheral blood cells and cognitive performance in individuals with mild cognitive impairment (MCI).
- To compare mitochondrial function in young adults, healthy older adults, and individuals with amnestic (aMCI) and nonamnestic mild cognitive impairment (naMCI).
Main Methods:
- A cross-sectional study of 90 participants, including young controls, older controls, and MCI groups.
- Mitochondrial function assessed via ATP levels and endogenous respiration in cryopreserved peripheral blood mononuclear cells (PBMCs).
- Cognitive status evaluated using the German Consortium to Establish a Registry for Alzheimer's Disease (CERAD) test battery.
Main Results:
- Individuals with aMCI showed significantly lower ATP levels in PBMCs compared to young and older controls.
- The MCI group exhibited the lowest endogenous respiration rates.
- Higher ATP levels positively correlated with immediate recall and fluency, indicating better cognitive performance.
Conclusions:
- Mitochondrial dysfunction in PBMCs is associated with MCI and cognitive impairment.
- Lower ATP levels in blood cells correlate with poorer performance on neuropsychological tests.
- PBMCs serve as a valuable biomarker for assessing bioenergetic status and dementia risk.
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