Dieter Fabian, Jacobs Karlotta, Quentin Alice, Prvulovic David, Reif Andreas, Pantel Johannes, Pilatus Ulrich, Hattingen Elke, Matura Silke, Eckert Gunter Peter
Institute of Nutritional Science, Justus-Liebig University, Giessen, Germany.
Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, Goethe University Frankfurt, University Hospital, Frankfurt am Main, Germany.
Geroscience. 2025 Aug 6. doi: 10.1007/s11357-025-01813-4.
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).
线粒体功能障碍是衰老和许多与年龄相关的神经退行性疾病的一个标志。轻度认知障碍（MCI）是指一种临床状况，其特征是明显的认知能力下降超过了正常的与年龄相关的变化，但并未严重干扰日常功能。MCI通常被认为是神经退行性疾病的早期阶段，包括阿尔茨海默病。因此，我们研究了遗忘型（aMCI）和非遗忘型轻度认知障碍（naMCI）个体外周血细胞中线粒体功能与认知表现之间的关系。对照组由身心健康的年轻人（YC）和老年人（OC）组成。这是一项横断面观察性研究，涉及90名参与者，包括年轻人、认知健康的老年人以及MCI患者。在冷冻保存的外周血单核细胞（PBMC）中测定线粒体功能。使用德国版的阿尔茨海默病注册协会（CERAD）测试组合评估认知状态。从aMCI患者分离出的冷冻保存PBMC中的ATP水平显著低于OC组和YC组。内源性呼吸在各组之间有显著差异，MCI组的呼吸水平最低。以ATP作为认知表现预测指标的线性回归分析显示，ATP水平与即时回忆和流畅性之间存在显著的正相关关系。回归系数表明ATP水平与两项测试的表现之间存在中度正相关。这表明较高的ATP水平与改善的认知表现相关。我们的数据表明，PBMC中的线粒体功能障碍与MCI相关，并与认知障碍相关。在神经心理学测试中表现较差的受试者也表现出较低的ATP水平。鉴于PBMC易于获取，它们为痴呆风险增加个体的生物能量状态提供了有价值的见解。该研究（PEM-MCI）已在德国临床试验注册中心（DRKS）进行了回顾性注册，注册号为DRKS00036017（于2025年1月30日注册）。
