Terry R D, Katzman R
Ann Neurol. 1983 Nov;14(5):497-506. doi: 10.1002/ana.410140502.
The prevalence of severe dementia in the United States is about 1.3 million cases, of which at least 50 to 60% are of the Alzheimer type. Severe dementia of the Alzheimer type is found rarely in a clearly dominant pattern, although often one or more relatives are affected. Down's syndrome in adults is often associated with Alzheimer changes. The diagnosis is a clinicopathological one; there is a considerable error rate in the clinical diagnosis early in the course of the disease, especially in regard to dementia in depression. The differential diagnosis involves a great many disorders, including multi-infarct dementia, tumors, subdural hematomas, and others. Physiological aspects of Alzheimer's disease include a diffusely slow electroencephalogram, reduced cerebral blood flow, and particular patterns noted on positron emission tomographic scanning. The latter technique has also demonstrated that oxygen extraction is normal in Alzheimer's disease, thus excluding ischemia from possible pathogenetic factors. Morphological changes, that is, the presence of plaques and tangles, are widely distributed in neocortex, paleocortex, and many deep gray areas down through the pontine tegmentum, but largely exclude the basal ganglia, thalamus, and substantia nigra. Numerous plaques without neocortical tangles are found in many demented persons older than 75 years. A severe loss of large neocortical neurons is characteristic of the disease. The chemical nature of the paired helical filaments that make up the neurofibrillary tangle has not yet been ascertained. Neurons are markedly deficient in the basal forebrain nuclei, and this deficiency may account for the severe diminution of choline acetyltransferase and acetylcholine in the neocortex and paleocortex. Muscarinic cholinergic receptors are present in normal amounts. Norepinephrine is reduced in some cases, and somatostatin in most. Substance P is low in severe cases. The etiology of the disorder is unknown and the role of aluminum is disputed. Management of patients with Alzheimer's disease is difficult, and neuroleptics are to be used with great caution because of their side effects. Substrate therapy has not been effective; physostigmine improves memory but is not suitable for general use. Trophic factors, gangliosides, and aluminum chelation are being investigated for use in pharmacological intervention.
在美国，重度痴呆症的患病率约为130万例，其中至少50%至60%为阿尔茨海默型。阿尔茨海默型重度痴呆症很少以明显的显性模式出现，尽管通常有一个或多个亲属会受到影响。成人唐氏综合征常与阿尔茨海默病变相关。诊断是临床病理诊断；在疾病早期，临床诊断存在相当高的错误率，尤其是在抑郁症性痴呆方面。鉴别诊断涉及许多疾病，包括多发性梗死性痴呆、肿瘤、硬膜下血肿等。阿尔茨海默病的生理方面包括脑电图弥漫性减慢、脑血流量减少以及正电子发射断层扫描中发现的特定模式。后一种技术还表明，阿尔茨海默病中的氧摄取正常，因此排除了缺血作为可能的致病因素。形态学变化，即斑块和缠结的存在，广泛分布于新皮质、旧皮质以及许多深部灰质区域，一直到脑桥被盖，但基底神经节、丘脑和黑质基本未受影响。在许多75岁以上的痴呆患者中发现了大量没有新皮质缠结的斑块。大脑新皮质大神经元的严重丧失是该疾病的特征。构成神经原纤维缠结的双螺旋丝的化学性质尚未确定。基底前脑核中的神经元明显缺乏，这种缺乏可能是新皮质和旧皮质中胆碱乙酰转移酶和乙酰胆碱严重减少的原因。毒蕈碱胆碱能受体数量正常。在某些情况下去甲肾上腺素减少，在大多数情况下生长抑素减少。在严重病例中P物质含量较低。该疾病的病因尚不清楚，铝的作用也存在争议。阿尔茨海默病患者的管理很困难，由于其副作用，使用抗精神病药物时要非常谨慎。底物疗法尚未有效；毒扁豆碱可改善记忆力，但不适合普遍使用。正在研究营养因子、神经节苷脂和铝螯合在药物干预中的应用。
