Imhof Anouk, Kövari Enikö, von Gunten Armin, Gold Gabriel, Rivara Claire-Bénédicte, Herrmann François R, Hof Patrick R, Bouras Constantin, Giannakopoulos Panteleimon
Department of Psychiatry, HUG, Belle-Idée, University of Geneva School of Medicine, Geneva, Switzerland.
J Neurol Sci. 2007 Jun 15;257(1-2):72-9. doi: 10.1016/j.jns.2007.01.025. Epub 2007 Feb 15.
Brain aging is characterized by the formation of neurofibrillary tangles (NFT) and senile plaques (SP) in both cognitively intact individuals and patients with Alzheimer's disease (AD). The ubiquitous presence of these lesions and the steady increase of the prevalence of dementia up to 85 years have strongly supported a continuum between normal brain aging and AD. In this context, the study of nonagenarians and centenarians could provide key informations about the characteristics of extreme aging. We provide here a detailed review of currently available neuropathological data in very old individuals and critically discuss the patterns of NFT, SP and neuronal loss distribution as a function of age. In younger cohorts, NFTs are usually restricted to hippocampal formation, whereas clinical signs of dementia appear when temporal neocortex is involved. SPs would not be a specific marker of cognitive impairment as no correlation was found between their quantitative distribution and AD severity. The low rate of AD lesions even in severe AD as well as the weakness of clinicopathological correlations reported in the oldest-old indicate that AD pathology is not a mandatory phenomenon of increasing chronological age. Our recent stereological observations of hippocampal microvasculature in oldest-old cases challenge the traditional lesional model by revealing that mean capillary diameters is an important structural determinant of cognition in this age group.
脑老化的特征是在认知功能正常的个体以及阿尔茨海默病（AD）患者中均出现神经原纤维缠结（NFT）和老年斑（SP）。这些病变的普遍存在以及痴呆患病率在85岁之前的稳步上升，有力地支持了正常脑老化与AD之间存在连续性。在此背景下，对九旬老人和百岁老人的研究可以提供有关极端衰老特征的关键信息。我们在此详细综述了目前可得的关于极老年人的神经病理学数据，并批判性地讨论了NFT、SP和神经元丢失分布模式随年龄的变化情况。在较年轻的队列中，NFT通常局限于海马结构，而当颞叶新皮质受累时会出现痴呆的临床症状。SP并非认知障碍的特异性标志物，因为未发现其定量分布与AD严重程度之间存在相关性。即使在重度AD中AD病变的发生率也较低，而且在最年长者中报告的临床病理相关性较弱，这表明AD病理学并非随着实际年龄增长而必然出现的现象。我们最近对最年长者海马微血管的体视学观察揭示，平均毛细血管直径是该年龄组认知的重要结构决定因素，这对传统的病变模型提出了挑战。
