帕金森病患者的抑郁与认知功能障碍

目的探讨帕金森病(PD)患者的抑郁与认知功能障碍之间的关系。方法对60名PD患者和38名对照组进行抑郁和认知功能评定。结果PD组HAMD均分(16.8±0.6),对照组(7.2±2.8);PD组的认知功能与对照组相比下降;PD并抑郁患者的认知功能与PD并非抑郁患者的认知功能相比有显著性差异(P<0.05)。结论PD患者存在抑郁与认知功能障碍,抑郁可能是导致认知功能下降的重要因素。     

Influence of chronic bilateral stimulation of the subthalamic nucleus on cognitive function in Parkinson's disease

Background: The clinical efficacy of chronic deep brain stimulation in the treatment of parkinsonian patients with severe levodopa-related motor adverse effects has been repeatedly shown. Bilateral subthalamic nucleus (STN) stimulation has been shown to present an advantage over pallidal stimulation as it induces a higher antiakinetic effect and has positive effects on all parkinsonian symptoms. The morbidity of such surgery is usually considered to be very low. However, few studies have extensively examined the effects of chronic STN stimulation on cognitive function. Objective: The aim of the present study was to assess the effects of chronic bilateral STN stimulation on performance in an extensive battery of neuropsychological tests, three months and one year after surgery. Methods: Nine patients with Parkinson's disease were selected for STN electrodes implantation. They underwent a neuropsychological evaluation at one month before and at three months after surgery. Six of them were examined again at one year after surgery. Results: Before surgery, no patient showed cognitive decline. At three months after surgery, no modification was observed for most tasks. The information processing speed tended to improve. There was a significant reduction of the performance in a delayed free recall test and a trend toward a significant reduction of categorial word fluency. At one year after surgery, most task measures did not change. Slight impairment was observed for tasks evaluating executive function. Examination of individual results showed that some patients (30 % at 3 months after surgery) showed an overall cognitive decline. Behavioural changes were also observed in 4 patients with overall cognitive decline in one of them. Conclusion: In general, STN deep brain stimulation can be considered as a significant contribution to the treatment of severe Parkinson's disease However, in some patients it can induce overall cognitive decline or behavioural changes. Received: 4 May 2000 / Received in revised form: 31 January 2001 / Accepted: 6 February 2001     

Dopamine and cognitive functioning in de novo subjects with Parkinson's disease: Effects of pramipexole and pergolide on working memory

Very few studies have investigated the relationship between dopaminergic therapy and working memory (WM) functioning in Parkinson's disease (PD) patients. The aim of the present study was to explore the effects of pharmacological treatment with pergolide (a D₁ + D₂ receptor agonist) and pramipexole (a D₂ + D₃ receptor agonist) on performance in visual-spatial, visual-object, and verbal WM tasks in PD patients. Participants included 19 “de novo” PD patients and 13 healthy controls (HC). The experimental task consisted of an n-back paradigm with verbal, visual-object, or visual-spatial stimuli. PD patients performed the task twice: after 18-24 h of therapy wash-out and after administration of pergolide (nine patients) or pramipexole (ten patients). HCs performed the task only once, without drug administration. Depending on how they performed in the “Off” and “On” therapy conditions, the nine PD patients each were classified into groups of low performers (i.e., performance on the n-back paradigm was below the median value of the experimental sample) and high performers (i.e., performance was above the median value). One PD patient was excluded from the analysis because his performance pattern clearly revealed that he was an outlier. In the low performer PD patients, administration of both pergolide and pramipexole improved accuracy on all WM tasks. No effect of the drugs was found in the high performer patients. The results of the present study show that stimulation of dopaminergic receptors improves high-level WM processes in PD patients, possibly by modulating activity in frontal-striatal circuits.     

Dopaminergic modulation of cognitive interference after pharmacological washout in Parkinson's disease

The dopaminergic modulation of prefrontal function in Parkinson's disease (PD) has been consistently demonstrated. There is evidence that the effects of pharmacological manipulations on cognitive performances are described by an "Inverted-U" shaped curve. Neuroimaging studies performed before and after an overnight withdrawal from therapy showed significant differences between drug states, but did not control for the relative impact of the long duration response to levodopa. Here we evaluate the brain response after a complete pharmacological washout by correlating dopaminergic-related changes of this response to changes in performance during cognitive interference. Twelve idiopathic PD patients were studied with functional MRI while performing a modified version of the Stroop task. Patients were scanned twice: (1) following a prolonged washout procedure ("OFF" state) and (2) 90-120 min after the administration of levodopa ("ON" state). Task-related changes of PD patients were compared to those of matched healthy controls. Healthy controls displayed prefrontal and parietal responses that were positively correlated with task accuracy. In the "OFF" state, PD patients showed significant responses in anterior cingulate and pre-supplementary motor area, which are hypothesized to operate at a higher level of basal dopaminergic modulation. Levodopa administration attenuated such responses and enhanced the response of prefrontal cortex (PFC), which was correlated with improved accuracy. Results demonstrate that the behavioral effects of pharmacological manipulations of the dopamine system are highly dependent on the baseline status of PFC. When a true hypodopaminergic state is induced in PD patients, cognitive interference might significantly benefit from the administration of levodopa via an enhanced PFC response.     

Effects of cognitive training in Parkinson's disease: A randomized controlled trial

BackgroundIn Parkinson's Disease (PD), cognitive dysfunctions which can reduce patients' quality of life occur frequently. Data on non-pharmacological intervention effects on cognitive functions in patients with PD are rare. The aim of this study was to examine the effects of different cognitive group trainings (structured vs. unstructured) on cognition, depression, and quality of life in non-demented PD patients.MethodsIn this randomized controlled trial, 65 non-demented patients with PD according to UK Brain Bank criteria (Hoehn & Yahr I-III) were allocated to one of two cognitive multi-component treatments (“NEUROvitalis”, a structured training, or the unstructured training “Mentally fit” with randomly assembled cognitive tasks, each including 12 group-sessions à 90 min over 6 weeks) or a waiting list control group (CG). A neuropsychological test battery was performed before and after the training.ResultsCompared to the CG, patients from the “NEUROvitalis” group improved in short-term memory (word list learning “Memo”: p < .01) and working memory (digit span reverse from “DemTect”: p < .05), whereas depression scores where reduced in the “Mentally fit” group (Beck Depression Inventory-II: p < .05). The “NEUROvitalis” group improved significantly more in working memory than the “Mentally fit” group (DemTect: p < .05).DiscussionCognitive and affective functions can be improved by cognitive trainings in PD patients. Specific effects (e.g. on memory and working memory versus depression) seem to be dependent on the type of training. Further research is needed to define long-term effects and the efficacy in PD patients with different extent of cognitive and neuropsychiatric symptoms.     

帕金森病认知障碍研究

目的研究帕金森病痴呆患者的认知障碍特点。方法采用语义流畅性、语音流畅性、动作流畅性测验与物品和动作命名测验,评定30例PD无痴呆患者、30例PDD患者与60名正常老年人。结果与正常对照组比较,PD无痴呆患者存在动作流畅性损害(P0.01),PDD患者3项言语流畅性与物品和动作命名均受损(P0.01)。结论 PDD患者存在执行功能障碍与命名损害,PDD是一种伴有皮质功能损害的、以额叶皮质下功能障碍为主要特点的认知损害性疾病。     

Errors in cognitive performance trigger postural instability in Parkinson's disease

BackgroundGlobally, postural stability and cognitive performance are intimately linked in Parkinson's disease (PD). However, a fundamental gap exists in understanding the precise relationship between a disruption in executive function and its impact on postural stability.ObjectiveThis project aimed to determine the precise effects of cognitive errors on postural stability under dual-task conditions in participants with PD and controls.MethodsTwenty-eight individuals with PD and 27 healthy controls completed a series of postural stability tests under single- and dual-tasks. The dual-task required maintenance of balance while performing an audio number discrimination task.ResultsIn general, postural stability in PD and control subjects was similar across single-task conditions. In controls, an error in the cognitive task during dual-task conditions did not impact measures of postural sway. In contrast, in PD, postural sway increased in epochs surrounding cognitive errors relative to epochs without errors.ConclusionsPostural task selection plays a critical role when testing for balance deficits in PD compared to healthy controls. Furthermore, time synchronized analysis of cognitive and balance data revealed the greatest episodes of postural instabilities occurred around cognitive errors. The measurement and evaluation of cognitive-motor linkages, relative to postural stability, could provide a patient-specific fingerprint of balance function and provide more sensitive measures for fall risk in PD.     

Dopamine dependency of cognitive switching and response repetition effects in Parkinson's patients

A group of people with Parkinson's disease and a group of matched controls were tested on a task involving a switch between perceptual dimensions. Patients were tested both ‘on’ and ‘off’ their normal medication cycles. Stimuli appeared in pairs for each trial, with each stimulus consisting of a color and a shape. One dimension of color and one of shape were mapped to each of two response keys. A cue was presented concurrently with each stimulus to indicate whether to respond on the basis of color or shape, following procedures developed by Hayes et al. [Hayes, A.E., Davidson, M.C., Keele, S.W., & Rafal, R.D. (1998). Toward a functional analysis of the basal ganglia.Journal of Cognitive Neuroscience, 10, 178–198]. Replicating previous literature, abnormally large switch costs were observed in patients who were off their normal medication cycles. A novel finding was that patients in the ‘on’ state demonstrated a slight reversal of switch costs. Also novel, reaction time (RT) costs associated with switching between response keys, and interactions between response switching and task switching were influenced predominantly by on–off dopamine manipulations. It is concluded that abnormal task switching costs and response repetition effects likely reflect impairments of activation and inhibition, and both effects are dopamine-dependent.     

Patients with Parkinson's disease learn to control complex systems-an indication for intact implicit cognitive skill learning

Implicit memory and learning mechanisms are composed of multiple processes and systems. Previous studies demonstrated a basal ganglia involvement in purely cognitive tasks that form stimulus response habits by reinforcement learning such as implicit classification learning. We will test the basal ganglia influence on two cognitive implicit tasks previously described by Berry and Broadbent, the sugar production task and the personal interaction task. Furthermore, we will investigate the relationship between certain aspects of an executive dysfunction and implicit learning. To this end, we have tested 22 Parkinsonian patients and 22 age-matched controls on two implicit cognitive tasks, in which participants learned to control a complex system. They interacted with the system by choosing an input value and obtaining an output that was related in a complex manner to the input. The objective was to reach and maintain a specific target value across trials (dynamic system learning). The two tasks followed the same underlying complex rule but had different surface appearances. Subsequently, participants performed an executive test battery including the Stroop test, verbal fluency and the Wisconsin card sorting test (WCST). The results demonstrate intact implicit learning in patients, despite an executive dysfunction in the Parkinsonian group. They lead to the conclusion that the basal ganglia system affected in Parkinson's disease does not contribute to the implicit acquisition of a new cognitive skill. Furthermore, the Parkinsonian patients were able to reach a specific goal in an implicit learning context despite impaired goal directed behaviour in the WCST, a classic test of executive functions. These results demonstrate a functional independence of implicit cognitive skill learning and certain aspects of executive functions.     

Progression of motor and cognitive impairment in Parkinson's disease

We performed a longitudinal study (mean follow-up 86.7 months) to evaluate motor and mental deterioration in patients with Parkinson's disease. Of the original 91 patients, only 61 could be re-examined 7 years later and 11 of these had become demented (PD-Dems). PD-Dems were older with worse motor and, obviously, cognitive performance than non-demented parkinsonian patients (PDs). A global cognitive decay index (DI) was calculated for each patient. Based on this, non-demented PDs were further split into 38 stable parkinsonian patients (S-PDs) with DI -30% to +30%, and 10 deteriorated but non-demented parkinsonian patients (D-PDs) with a DI worse than -30% (as had PD-Dems). D-PDs were older and had greater motor impairment than S-PDs but did not differ from PD-Dems on these measures. D-PDs and PD-Dems deteriorated especially in attention, visuospatial and executive ability tests. Ageing seems to be the main predictive factor for mental deterioration.     

帕金森病患者认知功能障碍与抑郁临床分析

目的探讨帕金森病(PD)患者的认知功能障碍及抑郁的特点及关系。方法对50例PD患者和42例对照组进行认知功能及抑郁评定和分析。结果 PD组同对照组相比,简易精神状况检查(MiniMental State Examination,MMSE)及蒙特利尔认知评估(Montreal Cognitive Assessment,MOCA)量表各因子分,除语言因子分外均有显著性差异(P<0.05),汉密尔顿抑郁量表(Hamilton depression scale,HAMD)均分和抑郁自评量表(Self-rating Depression Scale,SDS)均分均有显著性差异(P<0.05),抑郁严重程度与认知功能损害成正相关(r=0.438)。结论 PD患者存在认知功能障碍与抑郁,抑郁可能是导致认知功能下降的重要因素。     

高同型半胱胺酸血症与帕金森病认知功能的相关性研究

目的探究高同型半胱胺酸血症与帕金森病认知功能相关性。方法选取我院收治的130例帕金森病患者作为试验组,同期的健康体检人员110例作为对照组,对影响认知功能的可能危险因素进行Logistic回归分析,并将轻度认知功能障碍患者、痴呆患者及健康人群血清高同型半胱胺酸含量进行对比。结果经Logisitc非条件回归分析可见,年龄、文化程度、吸烟、高血压、糖尿病、高密度脂蛋白、低密度脂蛋白、血清总胆固醇、血浆同型半胱氨酸为认知功能障碍的危险因素。对照组与帕金森非认知障碍组、帕金森认知障碍组的血浆同型半胱氨酸含量相比差异均具有统计学意义(t=3.45,P0.05;t=6.43,P0.05)。帕金森非认知功能障碍组与帕金森认知功能障碍组的血浆同型半胱氨酸含量相比差异具有统计学意义(t=5.23,P0.05)。结论帕金森病认知功能障碍患者同型半胱胺酸含量明显高于无认知功能障碍的帕金森病患者及健康人群,高同型半胱胺酸血症为帕金森病认知功能障碍的危险因素,可作为临床医师可靠的诊断依据。     

A process-model based approach to prospective memory impairment in Parkinson's disease

The present review discusses the current state of research on the clinical neuropsychology of prospective memory in Parkinson's disease. To do so the paper is divided in two sections. In the first section, we briefly outline key features of the (partly implicit) rationale underlying the available literature on the clinical neuropsychology of prospective memory. Here, we present a conceptual model that guides our approach to the clinical neuropsychology of prospective memory in general and to the effects of Parkinson's disease on prospective memory in particular. In the second section, we use this model to guide our review of the available literature and suggest some open issues and future directions motivated by previous findings and the proposed conceptual model. The review suggests that certain phases of the prospective memory process (intention formation und initiation) are particularly impaired by Parkinson's disease. In addition, it is argued that prospective memory may be preserved when tasks involve specific features (e.g., focal cues) that reduce the need for strategic monitoring processes. In terms of suggestions for future directions, it is noted that intervention studies are needed which target the specific phases of the prospective memory process that are impaired in Parkinson's disease, such as planning interventions. Moreover, it is proposed that prospective memory deficits in Parkinson's disease should be explored in the context of a general impairment in the ability to form an intention and plan or coordinate an appropriate series of actions.     

Olfactory performance acts as a cognitive reserve in non-demented patients with Parkinson's disease

ObjectiveTo explore whether olfactory performance acts as a cognitive reserve in non-demented patients with Parkinson's disease (PD).MethodsPatients with non-demented PD (n = 119) underwent T1-weighted MRI and olfactory identification tests. According to their olfactory performance, PD patients were subdivided into three groups of high score (PD-H, n = 38), middle score (PD-M, n = 48), and low score (PD-L, n = 33). We investigated the pattern of gray matter (GM) density according to olfactory performance using voxel-based morphometry (VBM) and analyzed the correlation between GM density and olfactory performance.ResultsNo significant differences in demographic characteristics were observed among the groups. A neuropsychological test showed that cognitive deficits in verbal memory function were more severe in the PD-L group than in the PD-H group. However, a VBM analysis revealed that patients in the PD-H group possessed significantly decreased GM density in the bilateral temporal areas, orbitofrontal areas, mesiofrontal areas extending into the cingulate gyrus, and prefrontal areas, compared with patients in the PD-L group. No areas exhibiting a significant difference in GM density were observed between the PD-H and PD-M groups. Olfactory performance in patients with PD was negatively correlated with both the brain GM volume and intracerebral volume; in particular, GM density in the caudate nucleus and putamen exhibited a negative correlation with olfactory performance.ConclusionsOur data show that a high olfactory performance may compensate GM volume loss in order to minimize the exhibition of cognitive impairment and thus may act as a cognitive reserve in non-demented patients with PD.     

帕金森病患者ApoA-1、ET-1与认知功能的相关性分析

目的 探讨帕金森病(PD)患者载脂蛋白A-1(ApoA-1)、内皮素-1(ET-1)与认知功能的相关性.方法 选择2017年7月至2019年7月西安国际医学中心医院神经内科接诊的90例PD患者为本研究对象,设为观察组,另选择同期在本院体检的70例健康人群作为对照组,分析血清ApoA-1、ET-1水平变化情况,及其与PD...     

帕金森病患者血清EGF和BDNF水平变化与认知障碍的关系

目的探讨帕金森病(PD)患者血清表皮生长因子(EGF)和脑源性神经营养因子(BDNF)的变化及其与认知功能的关系。方法入选PD患者76例和年龄、性别相匹配的40例健康对照组,记录PD患者的性别、年龄、病程、受教育年限、HoehnYahr(H-Y)分级,采用蒙特利尔认知评估量表(Mo CA)对所有研究对象认知功能进行评估,采用酶联免疫吸附法(ELISA)检测血清EGF和BDNF水平,并对结果进行分析。结果 PD组血清EGF、BDNF水平明显低于健康对照组[(745±148)ng·L~(-1)比(952±157)ng·L~(-1),P0.05;(5.1±3.1)μg·L~(-1)比(6.8±3.9)μg·L~(-1),P0.05];早期PD组与中晚期PD组血清EGF和BDNF水平无差异(P0.05);但合并轻度认知功能障碍(MCI)的PD组血清EGF水平低于无MCI的PD组[(713±146)ng·L~(-1)比(865±189)ng·L~(-1),P0.01];PD患者Mo CA评分与受教育年限(β=0.611,P0.01)、血清EGF水平(β=0.513,P0.01)呈正相关,与病程(β=-0.373,P0.05)、H-Y分级(β=-0.264,P0.05)呈负相关。结论 EGF和BDNF水平的改变可能参与了PD患者的发病机制;血清EGF水平的下降可能与PD患者的MCI具有相关性,其可能为PD患者合并认知功能障碍的潜在早期预测指标。     

帕金森病与阿尔茨海默病

普遍认为帕金森病和阿尔茨海默病是两个独立的、有着显著判别的疾病。但是,相当数量为证据表明,二者具有相互重叠的临床和神经病理特征、相似的病因和病变发生机制。因此,现在有人认为这两种疾病的部分病例可能是同一种神经元退行性变疾病的不同表现形式。本文拟对此作一介绍。     

Education and cognitive decline in Parkinson's disease: a study of 102 patients

OBJECTIVE: To understand the correlation between low education level (EL) and the cognitive impairment in Parkinson's disease (PD). PATIENTS AND METHODS: This is a cross-sectional study of cognitive function in 102 non-demented PD patients, from a special clinic (behavioral neurology) in a referral medical center. PD patients were divided into low, middle and high EL groups. We used the Chinese version of the Cognitive Ability Screening Instrument as a neuropsychological test, which covers nine domains of cognitive function. A full score is 100. When determining the abnormality rate of each item of CASI, we used age/education stratified normal control groups as reference to obliterate the influence of education and age on cognitive decline. RESULTS: Recent memory, language and attention are the three items in which there were differences between the groups, in terms of abnormal performance rates. The high EL group is at less risk of recent memory impairment, but at more risk of impairment in language and attention. The other six items and total score showed no differences among the groups. Thirty-eight percent of the patients had a total score below 1.5 SD of the means of the general population. CONCLUSION: This study shows that high EL exerts no protective effect on the cognitive decline in PD patients in general, except in recent memory. The rate of cognitive dysfunction in PD patients is high. This deserves more attention.     

Mild cognitive impairment and cognitive reserve in Parkinson's disease

Patients with Parkinson’s disease (PD) typically present with motor symptoms, but non-motor symptoms, including cognitive impairment, autonomic dysfunction and neuropsychiatric symptoms, are usually also present, when looked for carefully. The objective of this paper is to provide an up-to-date, comprehensive review of two undecided issues about cognitive impairment in PD patients without dementia: the concept of Mild Cognitive Impairment (MCI) and the concept of Cognitive Reserve (CR). Empirical findings support the value of the concept of MCI in this population, from the early untreated stages onwards. Further studies are needed to establish 1) the clinical-neuroimaging characteristics of MCI subtypes in PD, in comparison to those MCI subtypes in patients without PD; 2) whether different types of MCI in PD are associated with different rates of cognitive decline during the progression of the disease. Preliminary empirical evidence also shows that education might exert a protective effect on cognitive decline in PD and that less educated subjects are at increased risk for developing dementia, lending support to the CR hypothesis, in this population as well. Further studies are necessary to investigate how CR modulates cognitive decline in PD and other frontal-subcortical disorders, e.g. by identifying possible differential effects of CR on different cognitive domains.     

Correlating rates of cerebral atrophy in Parkinson's disease with measures of cognitive decline

Summary. We studied eight clinically non-demented PD patients and ten age-matched controls with serial volumetric T₁-weighted MRI. All PD patients underwent full neuropsychological testing at baseline and follow up scans. Sub-voxel coregistration of the serial MRI scans with quantification of changes in total brain substance and ventricular size per year was performed. The PD patients had significant reductions in both percentage and absolute annual brain volume loss when compared to age-matched controls (p < 0.001). There were significant correlations between reductions in percentage brain volume loss and estimated reductions in performance IQ (r = 0.841, p = 0.004) and full scale IQ (r = 0.63, p = 0.049), measured by subtracting IQ measures at time of follow up scan from premorbid estimates. In conclusion, PD patients have a significant rate of median brain volume loss [10.35 (range) 6.69–16.90 ml/year] with no significant loss seen in age-matched controls, and these changes correlate with global measures of cognitive decline. Further longitudinal studies could evaluate whether serial volumetric MRI is a useful technique in predicting the preclinical onset of dementia in Parkinson's disease patients, and its role in the assessment of putative treatments for slowing disease progression. Received October 9, 2000; accepted December 21, 2000