Sarter Martin, Bruno John P
Departments of Psychology and Neuroscience, Ohio State University, 27 Townshend Hall, 1885 Neil Avenue, Columbus, OH 43210, USA.
Neurobiol Aging. 2004 Oct;25(9):1127-39. doi: 10.1016/j.neurobiolaging.2003.11.011.
Ontogenetic abnormalities in the regulation of the cortical cholinergic input system are hypothesized to mediate early-life cognitive limitations (ECL) that later escalate, based on reciprocal interactions between a dysregulated cholinergic system and age-related neuronal and vascular processes, to mild cognitive impairment (MCI) and, subsequently, for a majority of subjects, senile dementia. This process is speculated to begin with the disruption of trophic factor support of the basal forebrain ascending cholinergic system early in life, leading to dysregulation of cortical cholinergic transmission during the initial decades of life and associated limitations in cognitive capacities. Results from neurochemical and behavioral experiments support the possibility that aging reveals the vulnerability of an abnormally regulated cortical cholinergic input system. The decline of the cholinergic system is further accelerated as a result of interactions with amyloid precursor protein metabolism and processing, and with cerebral microvascular abnormalities. The determination of the developmental variables that render the cortical cholinergic input system vulnerable to age-related processes represents an important step toward the understanding of the role of this neuronal system in the age-related decline in cognitive functions.
基于失调的胆碱能系统与年龄相关的神经元和血管过程之间的相互作用，皮质胆碱能输入系统调节中的个体发育异常被认为介导了早期认知局限（ECL），这种局限随后会升级为轻度认知障碍（MCI），并且对于大多数受试者来说，随后会发展为老年痴呆症。据推测，这个过程始于生命早期基底前脑上行胆碱能系统的营养因子支持被破坏，导致在生命的最初几十年中皮质胆碱能传递失调以及相关的认知能力局限。神经化学和行为实验的结果支持了衰老揭示异常调节的皮质胆碱能输入系统的脆弱性这一可能性。由于与淀粉样前体蛋白代谢和加工以及脑微血管异常的相互作用，胆碱能系统的衰退会进一步加速。确定使皮质胆碱能输入系统易受年龄相关过程影响的发育变量，是朝着理解这个神经元系统在与年龄相关的认知功能衰退中的作用迈出的重要一步。
