Cholinergic markers in elderly patients with early signs of Alzheimer disease
Cholinergic markers in elderly patients with early signs of Alzheimer disease
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DOI：
10.1001/jama.281.15.1401
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发表时间：
1999-04-21
影响因子：
120.7
通讯作者：
Haroutunian, V
中科院分区：
文献类型：
--
作者：
Davis, KL;Mohs, RC;Haroutunian, V
阿尔茨海默病（AD）的一个中心原则是死后脑标本中皮质胆碱能功能和胆碱能标记物的丧失。这些在终末期患者中发现的胆碱能标记物的严重缺陷是否也在更早的疾病患者中发现尚不清楚。目的确定AD中胆碱能缺陷是否在认知恶化的最早体征之前、之后或同步发生。临床痴呆评定（CDR）对疗养院居民的尸检研究1986年至1997年间，对66名老年人进行尸检，分别用0.0至2.0和4.0至5.0的量表评分，比较他们大脑皮质中胆碱能标记酶的活性，（CDR评分= 0.0; n = 18），可疑（CDR评分= 0.5; n = 11），轻度（CDR评分= 1.0; n = 22）或中度（CDR评分= 2.0; n = 15）痴呆vs重度痴呆受试者（CDR评分= 4.0-5.0; n = 15）主要指标9个新皮层脑区胆碱能标记酶胆碱乙酰转移酶和乙酰胆碱酯酶的活性。CDR评分为0.0 - 2.0的受试者中，9个新皮层脑区的乙酰转移酶和乙酰胆碱酯酶无显著差异，但重度痴呆受试者中，乙酰转移酶和乙酰胆碱酯酶显著降低（CDR评分= 4.0-5.0），胆碱乙酰转移酶水平与AD的神经病理病变严重程度显著相关，神经炎斑块和神经纤维缠结密度测量。结论虽然新皮质胆碱能缺陷的特点是严重的痴呆症AD患者，在这项研究中，胆碱能缺陷不明显的个人与轻度AD，并不存在，直到相对较晚的过程中的疾病。这些结果表明，更严重的疾病患者应该是胆碱能治疗的目标。
Context A central tenet of Alzheimer disease (AD) is the loss of cortical cholinergic function and cholinergic markers in postmortem brain specimens. Whether these profound deficits in cholinergic markers found in end-stage patients are also found in patients with much earlier disease is not known.Objective To determine whether cholinergic deficits in AD precede, follow, or occur in synchrony with the earliest signs of cognitive deterioration.Design, Setting, and Patients Postmortem study of nursing home residents with Clinical Dementia Rating (CDR) Scale scores of 0.0 to 2.0 and 4.0 to 5.0 who underwent autopsy between 1986 and 1997, comparing the activity of the cholinergic marker enzymes in the cortices of 66 elderly subjects with no (CDR score = 0.0; n = 18), questionable (CDR score = 0.5; n = 11), mild (CDR score = 1.0; n = 22), or moderate (CDR score = 2.0; n = 15) dementia vs subjects with severe dementia (CDR score = 4.0-5.0; n = 15).Main Outcome Measures Activity of the cholinergic marker enzymes choline acetyltransferase and acetylcholinesterase in 9 neocortical brain regions.Results The activity of choline acetyltransferase and acetylcholinesterase in 9 neocortical brain regions did not differ significantly in subjects with CDR scores of 0.0 to 2.0, but was significantly lower in subjects with severe dementia (CDR score = 4.0-5.0), Choline acetyltransferase levels were significantly correlated with severity of neuropathological lesions of AD, as measured by density of neuritic plaques and neurofibrillary tangles.Conclusions Although neocortical cholinergic deficits are characteristic of severely demented AD patients, in this study, cholinergic deficits were not apparent in individuals with mild AD and were not present until relatively late in the course of the disease. These results suggest that patients with more severe disease should be a target for cholinergic treatment.