Winblad B, Hardy J, Bäckman L, Nilsson L G
Ann N Y Acad Sci. 1985;444:255-68. doi: 10.1111/j.1749-6632.1985.tb37595.x.
One might argue that the decrease in the number of brain cells as a function of age could be the source of the functional age deficits in memory performance. However, this possibility seems less likely since the actual loss of neurons up to advanced age is relatively small. There are no good estimates of the loss of synapses. Golgi staining of cortical neurons would indicate that there is a loss with higher age. So far, however, the most convincing data of marked loss with age appear at the biochemical level. Most human data fail to demonstrate a decrease in cholinergic and serotonergic activity as a function of normal aging, although there is a loss of corresponding receptors. In AD/SDAT, however, there is a marked damage to these systems. Conceivably, acetylcholine may be providing informational rather than tone setting or balancing influence on memory function. This may explain the failure of cholinomimetic drugs to improve memory in AD/SDAT due to their inability to supply the informational properties of normal neuronal transmission. The catecholamines, noradrenaline and dopamine are both lost in normal aging and to a much higher degree in AD/SDAT. Animal data show that noradrenaline deficiency results in scattered attention. Such a pattern might also exist in the intact aged and through guidance by means of instructions, contextual cues, and a richer TBR information, the elderly are being forced to attend. This may promote and supersede the normal functions of the noradrenaline system by directions from external rather than internal influences, conceivably by potentiating the remaining noradrenaline neurons. The cortical motor areas are relatively spared from neuro-degenerative changes in normal aging and in AD/SDAT and this might provide a neuroanatomical basis for the elderly's and mildly to moderately demented patients' success in memory performance when motor action is involved. The role of dopamine in motor function and its stability with age in hippocampus may also provide a neurochemical basis for the preservation of memory when the subjects are allowed to act physically during encoding.
有人可能会认为，作为年龄函数的脑细胞数量减少可能是记忆功能中功能性年龄缺陷的根源。然而，这种可能性似乎较小，因为直至高龄阶段实际的神经元损失相对较少。目前尚无关于突触损失的可靠估计。对皮质神经元进行高尔基染色表明，随着年龄增长会有损失。然而，到目前为止，关于随年龄显著损失的最有说服力的数据出现在生化水平。大多数人体数据未能证明胆碱能和5-羟色胺能活性会随正常衰老而降低，尽管相应的受体存在损失。然而，在阿尔茨海默病/严重失智型老年性痴呆（AD/SDAT）中，这些系统会受到显著损害。可以想象，乙酰胆碱可能是为记忆功能提供信息，而不是调节或平衡影响。这可能解释了拟胆碱药物无法改善AD/SDAT患者记忆的原因，因为它们无法提供正常神经元传递的信息特性。儿茶酚胺、去甲肾上腺素和多巴胺在正常衰老过程中都会减少，而在AD/SDAT中减少程度更高。动物数据表明，去甲肾上腺素缺乏会导致注意力分散。在未受损的老年人中可能也存在这种模式，并且通过指令、情境线索和更丰富的待回忆信息的引导，老年人被迫集中注意力。这可能通过外部而非内部影响的指令来促进和取代去甲肾上腺素系统的正常功能，可以想象是通过增强剩余的去甲肾上腺素神经元来实现的。在正常衰老以及AD/SDAT中，皮质运动区相对免受神经退行性变化的影响，这可能为老年人以及轻度至中度痴呆患者在涉及运动动作时记忆表现良好提供神经解剖学基础。多巴胺在运动功能中的作用及其在海马体中随年龄的稳定性，也可能为受试者在编码过程中进行身体活动时记忆得以保留提供神经化学基础。
