Prohovnik I, Dwork A J, Kaufman M A, Willson N
New York Psychiatric Institute, NY 10032.
Schizophr Bull. 1993;19(4):805-16. doi: 10.1093/schbul/19.4.805.
Traditionally, schizophrenia has been studied in early adulthood. Its course and outcome during senescence are largely unknown and subject to controversy. We reviewed the consecutive neuropathologic records of 1,046 patients who were chronically hospitalized in New York State mental institutions, and we selected for analysis all 802 patients who died after age 50 with a clinical antemortem diagnosis, as recorded in the autopsy notes, of schizophrenia (n = 544) or dementia (n = 258). The prevalence of neuropathologic diagnoses consistent with Alzheimer's disease (AD) was 51 percent in the dementia group and 28 percent in the schizophrenia sample. This prevalence rate in the schizophrenia sample (mean age = 77) was considerably higher than that estimated for the general population. When evaluated against age of death, AD findings in demented patients were age invariant, whereas the rate of such findings in schizophrenia patients rose monotonously from under 5 percent below age 60 to 50 percent at age 90 and over. The age-relative rate of AD diagnosis in schizophrenia patients was similar to a curve postulated for first-degree relatives of familial AD patients and was markedly higher than population estimates. These findings as a basis for comparison with other retrospective studies of pathological records are presented. Our own study, as well as others, suffers from three intrinsic limitations. The clinical diagnoses are taken from death notes and have no formal verification. Likewise, neuropathologic diagnoses were based upon informal criteria in use at the time; since that time, formal diagnostic criteria have been evolving, and new staining methods have become available. Finally, it is not possible to determine from this material whether these patients are representative of all elderly schizophrenia patients or even of those who are institutionalized. Therefore, despite the large sample size on which our current findings are based, a new study has begun to address these weaknesses by complete review and rediagnosis of medical records and neuropathological material, using current methods, standardized criteria, and quantitative measures of degenerative changes. Specifically, the new ongoing study examines whether autopsied patients are representative by performing detailed diagnostic reviews of a control sample of nonautopsied patients from the same institutions. These results, if confirmed in the new study, demonstrate substantially greater vulnerability of chronic schizophrenia patients to the development of AD (or, at least, to histological changes typical of this disease). Possible association with chronic neuroleptic treatment and pathophysiological mechanisms remains to be elucidated.
传统上，精神分裂症的研究主要集中在成年早期。其在衰老过程中的病程和转归在很大程度上尚不清楚且存在争议。我们回顾了纽约州精神病院1046例长期住院患者的连续神经病理学记录，并选择了所有802例50岁以后死亡且尸检记录中有临床生前诊断为精神分裂症（n = 544）或痴呆症（n = 258）的患者进行分析。痴呆症组中符合阿尔茨海默病（AD）的神经病理学诊断患病率为51%，精神分裂症样本中为28%。精神分裂症样本（平均年龄 = 77岁）中的这一患病率显著高于一般人群的估计值。与死亡年龄进行评估时，痴呆患者的AD发现与年龄无关，而精神分裂症患者的此类发现率从60岁以下的不到5%单调上升至90岁及以上的50%。精神分裂症患者中AD诊断的年龄相对率与家族性AD患者一级亲属假设的曲线相似，且明显高于人群估计值。本文展示了这些作为与其他病理记录回顾性研究比较基础的发现。我们自己的研究以及其他研究都存在三个内在局限性。临床诊断取自死亡记录，且没有正式验证。同样，神经病理学诊断是基于当时使用的非正式标准；自那时以来，正式诊断标准一直在演变，新的染色方法也已出现。最后，从这些资料中无法确定这些患者是否代表所有老年精神分裂症患者，甚至是否代表那些住院患者。因此，尽管我们目前的发现基于大量样本，但一项新的研究已开始通过使用当前方法、标准化标准和退行性变化的定量测量对病历和神经病理学材料进行全面回顾和重新诊断来解决这些弱点。具体而言，正在进行的新研究通过对来自同一机构的非尸检患者对照样本进行详细诊断回顾，来检验尸检患者是否具有代表性。如果这些结果在新研究中得到证实，将表明慢性精神分裂症患者患AD（或至少患这种疾病典型组织学变化）的易感性显著更高。与慢性抗精神病药物治疗的可能关联及病理生理机制仍有待阐明。
