Cooper J A, Sagar H J, Jordan N, Harvey N S, Sullivan E V
Department of Neurology, Royal Hallamshire Hospital, Sheffield, UK.
Brain. 1991 Oct;114 ( Pt 5):2095-122. doi: 10.1093/brain/114.5.2095.
Current knowledge of cognitive dysfunction in Parkinson's disease (PD) has largely been obtained from studies of chronically treated patients in whom effects of disease chronicity, treatment, depression and dementia are confounding factors. Studies of untreated patients have examined few cognitive domains and relationships between cognition, depression and motor disability have been incompletely explored. Accordingly, we studied 60 consecutive patients with newly diagnosed, untreated, idiopathic PD and 37 matched, healthy control subjects; no subject had clinical dementia or depression. All subjects received tests of specific processes of memory and cognition, including working memory, verbal and non-verbal short- and long-term memory, language, visuospatial capacity, set-formation and shifting and sequencing. Patients also received quantitative global clinical measures of severity of dementia, depression and motor disability. The PD group as a whole showed deficits in immediate recall of verbal material, language production and semantic fluency, set-formation, cognitive sequencing and working memory and visuomotor construction. However, this group was unimpaired in immediate memory span, long-term forgetting, naming, comprehension and visual perception. Language deficits and more severe frontal lobe impairments were confined to those PD patients scoring abnormally on a Mini Mental State examination. Motor disability correlated strongly with severity of depression but weakly with cognitive impairment. Cognitive sequencing, set-formation and set-shifting deficits tended to associate with depression, but otherwise there was no association between cognition and depression. The results indicate dissociation of cognition and motor control in early PD which suggests that cognitive dysfunction is largely independent of frontostriatal dopamine deficiency underlying motor disability. Some, but not all, of the frontal lobe deficits of chronic disease are detectable in early, untreated PD. The pathogenesis of the cognitive deficits shown here appears to involve extrastriatal dopamine systems or non-dopaminergic pathology. Longitudinal study is necessary to determine whether increasing disease duration exacerbates the early cognitive deficits and affects new cognitive domains, in addition to producing increasing motor disability.
帕金森病（PD）认知功能障碍的现有知识很大程度上来自对长期治疗患者的研究，在这些患者中，疾病慢性化、治疗、抑郁和痴呆的影响是混杂因素。对未经治疗患者的研究仅考察了少数认知领域，认知、抑郁和运动障碍之间的关系也未得到充分探索。因此，我们研究了60例连续的新诊断、未经治疗的特发性PD患者以及37例匹配的健康对照者；所有受试者均无临床痴呆或抑郁。所有受试者均接受了记忆和认知特定过程的测试，包括工作记忆、言语和非言语短期及长期记忆、语言、视觉空间能力、定势形成、转换和序列。患者还接受了痴呆、抑郁和运动障碍严重程度的定量整体临床评估。PD组总体上在言语材料的即时回忆、语言表达和语义流畅性、定势形成、认知序列、工作记忆和视运动构建方面存在缺陷。然而，该组在即时记忆广度、长期遗忘、命名、理解和视觉感知方面未受损。语言缺陷和更严重的额叶损伤仅限于在简易精神状态检查中得分异常的PD患者。运动障碍与抑郁严重程度密切相关，但与认知障碍相关性较弱。认知序列、定势形成和转换缺陷往往与抑郁相关，但除此之外，认知与抑郁之间没有关联。结果表明早期PD中认知与运动控制分离，这表明认知功能障碍在很大程度上独立于运动障碍背后的额纹状体多巴胺缺乏。慢性病的一些但并非全部额叶缺陷在早期未经治疗的PD中是可检测到的。此处显示的认知缺陷的发病机制似乎涉及纹状体以外的多巴胺系统或非多巴胺能病理。有必要进行纵向研究，以确定疾病持续时间的增加是否会加剧早期认知缺陷并影响新的认知领域，此外还会导致运动障碍加重。
