Mörgeli Rudolf, Borchers Friedrich, Feinkohl Insa, Piper Sophie K, Pischon Tobias, Slooter Arjen J C, Spies Claudia, Wiebach Janine, Winterer Georg, Zacharias Norman, Lammers-Lietz Florian
Department of Anesthesiology and Intensive Care Medicine| CCM| CVK, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt- Universität zu Berlin, Augustenburger Platz 1, 13353, Berlin, Germany.
Molecular Epidemiology Research Group, Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany.
BMC Geriatr. 2025 Jul 2;25(1):484. doi: 10.1186/s12877-025-05740-z.
The etiology of cognitive impairment in frailty may be related to age or to an independent neurodegenerative process, such as Alzheimer's disease (AD). In this secondary analysis, we examine cognitive frailty in patients aged 65 and older undergoing elective surgery, and explore associations with aging- and AD-related cortical atrophy patterns and amyloid β (Aβ) concentrations.
Cognitive frailty (CF) was defined as the co-occurrence of (pre-)frailty and cognitive impairment (CI). Cognitive performance was assessed using the MMSE and the Cambridge Neuropsychological Teste Automated Battery (CANTAB), while frailty was assessed with a modified version of Fried's frailty phenotype. Aging- and AD-related cortical atrophy patterns were derived from T1-weighted MRI using Freesurfer software. MRI patterns and plasma concentrations of Aβ species 40 and 42 (including Aβ 42/40 ratio) were compared to physically robust, cognitively unimpaired patients using multiple regression analyses and presented as regression coefficient b with 95% confidence intervals.
MRI data of N = 489 patients (N = 251 with frailty, N = 15 with CI, N = 43 with CF) and plasma Aβ concentrations of N = 786 patients (N = 400 with frailty, N = 20 with CI, N = 101 with CF) were analyzed. Cognitive frailty was associated with both aging-related and AD-related MRI signatures (b=-0.070 [-0.113; -0.028], b=-0.069 [-0.118; -0.020]). Amyloid β42 was significantly lower in frail patients (b=-0.14 [-0.29; -0.01]), while β42/β40-ratio was lower in patients with frailty (b=-0.11 [-0.21; -0.01]) and cognitive frailty (b=-0.015 [-0.28; -0.03]).
Our results suggest that atrophy in aging- and AD-related cortical regions is associated with cognitive frailty. Plasma amyloid β42/β40-ratios were significantly lower in patients with frailty and cognitive frailty, suggesting that (pre-)frailty in general, rather than cognitive frailty specifically, is associated with AD-like changes. Hence, AD-related pathology seems to be associated with cognitive frailty, but the available data is not sufficient to indicate shared pathomechanisms between AD and cognitive frailty.
ClinicalTrials.gov. Identifier NCT02265263, Date October 15th, 2014.
衰弱状态下认知障碍的病因可能与年龄有关，也可能与独立的神经退行性过程有关，如阿尔茨海默病（AD）。在这项二次分析中，我们研究了65岁及以上接受择期手术患者的认知衰弱情况，并探讨其与衰老及AD相关的皮质萎缩模式和淀粉样β（Aβ）浓度之间的关联。
认知衰弱（CF）定义为（前期）衰弱和认知障碍（CI）同时存在。使用简易精神状态检查表（MMSE）和剑桥神经心理测试自动成套系统（CANTAB）评估认知表现，同时使用改良版Fried衰弱表型评估衰弱情况。使用Freesurfer软件从T1加权磁共振成像（MRI）中得出衰老及AD相关的皮质萎缩模式。通过多元回归分析，将MRI模式以及Aβ40和Aβ42的血浆浓度（包括Aβ42/40比值）与身体强健、认知未受损的患者进行比较，并以回归系数b及95%置信区间的形式呈现。
分析了N = 489例患者的MRI数据（N = 251例衰弱患者，N = 15例认知障碍患者，N = 43例认知衰弱患者）以及N = 786例患者的血浆Aβ浓度（N = 400例衰弱患者，N = 20例认知障碍患者，N = 101例认知衰弱患者）。认知衰弱与衰老相关及AD相关的MRI特征均有关联（b = -0.070 [-0.113；-0.028]，b = -0.069 [-0.118；-0.020]）。衰弱患者的淀粉样β42显著降低（b = -0.14 [-0.29；-0.01]），而衰弱患者（b = -0.11 [-0.21；-0.01]）和认知衰弱患者（b = -0.015 [-0.28；-0.03]）的β42/β40比值较低。
我们的结果表明，衰老及AD相关皮质区域的萎缩与认知衰弱有关联。衰弱患者和认知衰弱患者的血浆淀粉样β42/β40比值显著较低，这表明一般的（前期）衰弱而非特定的认知衰弱与AD样改变有关。因此，AD相关病理似乎与认知衰弱有关，但现有数据不足以表明AD与认知衰弱之间存在共同的病理机制。
ClinicalTrials.gov。标识符NCT02265263，日期2014年10月15日。
