Foster Thomas C
Department of Neuroscience, McKnight Brain Institute, University of Florida, Gainesville, Florida 32610-0244, USA.
CNS Drugs. 2006;20(2):153-66. doi: 10.2165/00023210-200620020-00006.
In humans, age-related memory impairments begin in mid-life and cognitive weakening continues with advancing age. An important aspect of defining memory decline is the distinction between dementia as a result of neurological diseases, such as Alzheimer's disease, and memory loss not specifically associated with disease. Within the population of elderly without dementia, there is considerable variability in memory. This variability is likely to be a result of the interaction of genetic make-up and environment, which influences several processes for cell maintenance and repair including oxidative damage and cholesterol metabolism, leading to disruption of Ca(2+) homeostasis, and ultimately Ca(2+)-dependent processes that underlie memory. In humans, several methods have been employed to distinguish biological markers of aging that may predict cognitive decline. Memory deficits associated with normal aging and Alzheimer's disease have been linked to a decrease in the volume of brain structures, such as the hippocampus and to genetic markers, such as apolipoprotein E. In this regard, examination of CSF for biomarkers of disease can help in differentiating normal aging from Alzheimer's disease. Measures of oxidative stress and cholesterol in plasma correlate with memory deficits; research suggests that treatments that reduce oxidative stress or cholesterol through exercise, diet or the use of antioxidant vitamins may delay cognitive decline.Nevertheless, to date, very little treatment is available to reverse memory deficits in later life. In this regard it is important to identify individuals at risk for memory deficits in order to discriminate different mechanisms of brain aging and develop treatments. Considerable effort is driving research to develop accurate biological markers of brain aging. In turn, these markers will provide information on mechanisms of aging and cognitive decline and point to potential treatments. Accordingly, the effectiveness of treatment needs to be verified for both cognitive changes and biological markers that are specific for age-related memory deficits.
在人类中，与年龄相关的记忆障碍始于中年，且随着年龄的增长认知能力持续减弱。定义记忆衰退的一个重要方面是区分由神经疾病（如阿尔茨海默病）导致的痴呆与并非特定与疾病相关的记忆丧失。在无痴呆的老年人群中，记忆存在相当大的变异性。这种变异性可能是基因构成与环境相互作用的结果，这会影响包括氧化损伤和胆固醇代谢在内的细胞维持和修复的多个过程，导致钙（Ca²⁺）稳态被破坏，最终影响记忆所依赖的钙依赖过程。在人类中，已经采用了多种方法来区分可能预测认知衰退的衰老生物标志物。与正常衰老和阿尔茨海默病相关的记忆缺陷与脑结构（如海马体）体积的减少以及基因标志物（如载脂蛋白E）有关。在这方面，检测脑脊液中的疾病生物标志物有助于区分正常衰老和阿尔茨海默病。血浆中氧化应激和胆固醇的测量与记忆缺陷相关；研究表明，通过运动、饮食或使用抗氧化维生素来降低氧化应激或胆固醇的治疗方法可能会延缓认知衰退。然而，迄今为止，几乎没有治疗方法可用于逆转晚年的记忆缺陷。在这方面，识别有记忆缺陷风险的个体以区分脑衰老的不同机制并开发治疗方法很重要。大量努力推动着研发准确的脑衰老生物标志物的研究。反过来，这些标志物将提供有关衰老和认知衰退机制的信息，并指出潜在的治疗方法。因此，需要针对与年龄相关的记忆缺陷所特有的认知变化和生物标志物来验证治疗的有效性。
