Cognitive correlates of visual hallucinations in non-demented Parkinson's disease patients

BackgroundVisual hallucinations (VH) in Parkinson's disease (PD) are associated with PD dementia and have been related to cognitive impairments in non-demented PD patients. Reports on the specific cognitive domains affected are conflicting. The aim of the present study was to investigate the presence of specific cognitive impairments in non-demented PD patients with VH, compared to those without VH.MethodsWe compared the clinical characteristics and neuropsychological test scores of 31 non-demented PD patients with VH with those of 31 PD patients without VH that were carefully matched for sex, age, disease duration and educational level. Several non-motor symptoms, including depression, anxiety and sleep disturbances, were also taken into account, as these may influence cognitive performance.ResultsThe PD with VH group performed significantly worse on the Trail Making Test part A (p = 0.01) and the Rey Auditory Verbal Learning Test, immediate recall (p = 0.01). In addition, PD patients with VH were more anxious, more depressed and reported more sleep disturbances. Verbal learning scores were not associated with levels of anxiety, depression or sleep disruption, whereas worse Trail Making Test A performance was associated with concomitant sleep disturbances.ConclusionsIn non-demented PD patients, the presence of VH is associated with a cognitive profile characterized by impairments in verbal learning and probably attention. Since these cognitive functions are believed to be non-dopaminergic mediated functions, the present results support the hypothesis that multiple neurotransmitter systems, other than dopamine, contribute to the pathophysiology of VH in PD.     

Sensitive measures of executive dysfunction in non-demented Parkinson's disease

BackgroundWe examined the sensitivity of different executive function measures for detecting deficits in Parkinson's disease patients without dementia.MethodsTwenty-one non-demented PD subjects and 21 neurologically healthy controls were administered widely used clinical executive functioning measures as well as the NIH EXAMINER battery, which produces Cognitive Control, Working Memory, and Verbal Fluency scores, along with an overall Executive Composite score, using psychometrically matched scales.ResultsNo significant differences between groups were observed on widely used clinical measures. The PD patients scored lower than controls on the EXAMINER Executive Composite, Cognitive Control, and Working Memory Scores.ConclusionsThe NIH EXAMINER Executive Composite and Cognitive Control Scores are sensitive measures of executive dysfunction in non-demented PD, and may be more sensitive than several widely used measures. Results highlight the importance of careful test selection when evaluating for mild cognitive impairment in PD.     

The impact of executive functions on verb production in patients with Parkinson's disease

A growing number of studies suggest that language problems in Parkinson's disease (PD) are a result of executive dysfunction. To test this hypothesis we compared Dutch verb production in sentence context in a group of 28 PD patients with a control group consisting of 28 healthy participants matched for age, gender and education. All subjects were assessed on both verb production in sentence context as well as on cognitive functions relevant for sentence processing.PD patients scored lower than healthy controls on the verb production ability-scale and showed a response pattern in which performance was worse (1) in base than in derived position; (2) in present than in past tense; (3) for intransitive than in transitive verbs. For the PD group the score on the verb production ability-scale correlated significantly with set-switching and working memory. These results provide support for previous research suggesting that executive dysfunctions underlie the performance of the PD patients on verb production. It is furthermore suggested that because of failing automaticity, PD patients rely more on the cortically represented executive functions. Unfortunately, due to the disturbed intimate relation between the basal ganglia and the frontal cortex, these executive functions are also dysfunctional.     

Cognitive improvement during Tolcapone treatment in Parkinson's disease

Summary The aim of this study was to evaluate the effects of Tolcapone, a reversible, selective inhibitor of catechol-O-methyltransferase, on the cognitive functions of eight patients with advanced Parkinson's disease. They underwent neuropsychological and motor assessment at baseline and were reevaluated after 6 months. During this period, they received Tolcapone three times daily, while the L-dopa dosage was progressively reduced. Significant improvements were observed in the attentional task, auditory verbal short-term memory, visuo-spatial recall, constructional praxia and motor symptoms. These data suggest that treatment with Tolcapone, in combination with L-dopa therapy, may determine a significant improvement in cognitive resources of patients with advanced Parkinson's disease.     

Frontal dysfunction contributes to the genesis of hallucinations in non-demented Parkinsonian patients

BACKGROUND: Hallucinations occur in patients with Parkinson's disease (PD) with reported prevalence ranging from 8% to 40%. Hallucinations are significantly associated with dementia in PD, but little is known about possible distinctive cognitive features of non-demented PD patients who develop hallucinations. OBJECTIVE: The aim of the study was to assess selected cognitive abilities in non-demented PD patients with and without hallucinations in order to identify specific neuropsychological correlates of such phenomena. METHODS: Forty-eight consecutive patients with PD and Mini Mental State Examination (MMSE) > or = 23 were examined for the presence of hallucinations and assessed on standardized neuropsychological tasks for semantic and phonological fluency, verbal learning and logical abstract thinking; disease severity was staged according to Hoehn and Yahr scale. RESULTS: Fourteen (29.2%) of 48 patients experienced hallucinations. There was no difference between hallucinators and non-hallucinators on demographic variables, disease severity and dose of any pharmacological treatment. Disease duration was significantly longer in hallucinator vs non-hallucinator patients (p = 0.02). Patients with hallucinations scored significantly lower than patients without hallucinations only on verbal learning-immediate recall task (p = 0.0324), and semantic and phonological fluency tasks (p = 0.0005 and p = 0.0036, respectively). CONCLUSIONS: Our results suggest that PD patients with hallucinations show reduced performance on tasks that explore executive functioning as compared with non-hallucinators. Therefore, executive dysfunction may be considered as a risk factor for the development of hallucinations in non-demented PD patients.     

帕金森病合并快速眼球运动睡眠行为障碍患者的客观睡眠结构及认知功能

目的 评价帕金森病合并快速眼球运动睡眠行为障碍(RBD)患者的睡眠结构及认知功能,并探讨其睡眠结构与认知功能之间的相关性.方法 本研究为横断面研究,以在我院睡眠中心进行睡眠监测的39例帕金森病合并RBD患者作为病例组,并以年龄、性别相匹配的21例原发性快速眼球运动睡眠行为障碍(iRBD)患者及37例不合并RBD的帕金森病患者作为对照组.所有患者均行整夜睡眠监测以定量睡眠相关参数,并且于监测当天使用蒙特利尔(MoCA)评估量表评估其认知功能.采用多重线性回归分析量表得分与睡眠结构之间的相关性.结果 (1)帕金森病合并RBD患者的睡眠效率(60.9％±16.9％)、总睡眠时间[(329.7±96.5)min]、非快速眼动睡眠2期时间[(127.6±67.6) min]及快速眼动睡眠期时间[(45.3 ±33.2) min]较iRBD组的相应值[77.8％±16.9％以及(397.1 ±88.9)、(188.0±94.7)、(70.6 ±25.9) min]比较明显减少(均P＜0.05),较不合并RBD的PD组的相应值[61.3％±21.7％以及(324.9 ±134.6)、(132.6 ±65.6)、(47.1±31.9)min]减少,但差异均无统计学意义.3组的睡眠潜伏期、快速眼球运动睡眠潜伏期、非快速眼球运动睡眠1期,慢波睡眠比例、氧减指数、呼吸暂停低通气指数及周期性肢体运动指数比较差异均无统计学意义.(2)帕金森病合并RBD患者认知功能最差,其中视空间与执行功能得分[(3.8±1.1)分]较iRBD组[(4.4±0.7)分]比较差异有统计学意义(F=3.426,P＜0.05).(3)多重线性回归显示帕金森病合并RBD患者的RBD病程、睡眠效率和非快速眼动睡眠2期与视空间与执行功能得分有相关性.结论 帕金森病合并RBD患者的睡眠效率、总睡眠、非快速眼动睡眠2期及快速眼动睡眠期时间和认知功能均明显下降,认知功能的改变与睡眠结构的变化可能存在相关性.     

Rule-based category learning in patients with Parkinson's disease

Measures of explicit rule-based category learning are commonly used in neuropsychological evaluation of individuals with Parkinson's disease (PD) and the pattern of PD performance on these measures tends to be highly varied. We review the neuropsychological literature to clarify the manner in which PD affects the component processes of rule-based category learning and work to identify and resolve discrepancies within this literature. In particular, we address the manner in which PD and its common treatments affect the processes of rule generation, maintenance, shifting and selection. We then integrate the neuropsychological research with relevant neuroimaging and computational modeling evidence to clarify the neurobiological impact of PD on each process. Current evidence indicates that neurochemical changes associated with PD primarily disrupt rule shifting, and may disturb feedback-mediated learning processes that guide rule selection. Although surgical and pharmacological therapies remediate this deficit, it appears that the same treatments may contribute to impaired rule generation, maintenance and selection processes. These data emphasize the importance of distinguishing between the impact of PD and its common treatments when considering the neuropsychological profile of the disease.     

帕金森病相关认知功能障碍

帕金森病认知功能障碍起病隐匿,是帕金森病常见非运动症状,包括帕金森病轻度认知损害和帕金森病痴呆,尤以执行功能障碍突出,亦可见视空间能力、记忆力和言语功能等认知域损害。主要危险因素包括男性、高龄、低受教育程度、严重运动症状、基线认知功能较差和白天过度嗜睡。主要病理改变是脑组织路易小体形成,也可见阿尔茨海默病样病理改变。脑脊液总α-突触核蛋白和β-淀粉样蛋白1~42水平降低作为生物学标志物的价值尚存争议。相关基因研究较少且无法获得肯定结论。PET显像发现多巴胺能通路和乙酰胆碱能通路均参与帕金森病认知功能障碍的发生;MRI研究发现皮质及皮质下结构萎缩与帕金森病认知功能障碍有关。嗅觉障碍可能是帕金森病认知功能障碍的预测因素之一。帕金森病痴呆与路易体痴呆具有共同的生物学特性,二者鉴别诊断困难。胆碱酯酶抑制剂和美金刚有助于改善临床症状,应注意个体化治疗。认知行为疗法具有潜在临床价值,尚待更多研究。     

帕金森病患者视空间障碍及其相关因素的分析

目的 探讨帕金森病(PD)患者视空间障碍情况及其与相关因素的关系. 方法 选择自2007年4月至6月在广州6家医院门诊或住院部连续就诊并且同意参与本次调查的PD患者共107例,用复制立方体评估PD患者的视空间能力,并选用Hoehn-Yahr分级、PD统一评分量表第2部分(UPDRS-Ⅱ)、UPDRS-Ⅲ、UPDRS-Ⅴ、汉密尔顿焦虑量表(HAMA)、汉密尔顿抑郁量表(HRSD)、Fuld物体记忆测验(FOM)、言语流畅性测验(RVR)、韦氏成人智力量表积木测验(WAIS-BD)、韦氏成人量表数字广度测验(WAIS-DS)、简易精神状态量表(MMSE)、神经精神科问卷(NPI)、睡眠量表、Epworth嗜睡量表(ESS)、非运动并发症等量表评估PD患者的运动症状、神经精神症状、认知及日常生活能力.用Spearman相关分析分析视空间能力与各相关因素的双变量相关性,用二分类Logistic回归分析视空间障碍与相关因素的关系. 结果 在107例PD患者中有59例(55.14%)出现视空间损害.Spearman相关分析表明,视空间能力与发病年龄、性别、Hoehn-Yahr分级、病程、UPDRS-Ⅱ、UPDRS-Ⅲ、FOM、RVR、WISC-BD、WAIS-DS、焦虑状态、痴呆等相关(P＜0.05).经二分类Logistic回归分析发现.Hoehn-Yahr分级及病程是视空间障碍的危险因素,而RVR及WISC-BD是视空间障碍的保护因素. 结论 PD患者视空间障碍的发生可能与病情分级、病程、语言流畅性、图像识别及构造能力等有关,临床上可以通过改善患者运动症状及训练患者的语言能力、图像识别及构造能力等综合治疗来改善患者的视空间能力.     

Freezing of gait in Parkinson's disease: The paradoxical interplay between gait and cognition

BackgroundFreezing of gait is a disabling episodic gait disturbance common in patients with Parkinson's disease. Recent evidences suggest a complex interplay between gait impairment and executive functions.Aim of our study was to evaluate whether specific motor conditions (sitting or walking) influence cognitive performance in patients with or without different types of freezing.MethodsEight healthy controls, eight patients without freezing, nine patients with levodopa-responsive and nine patients with levodopa-resistant freezing received a clinical and neuropsychological assessment during two randomly performed conditions: at rest and during walking.ResultsAt rest, patients with levodopa-resistant freezing performed worse than patients without freezing on tests of phonological fluency (p = 0.01). No differences among the four groups were detected during walking. When cognitive performances during walking were compared to the performance at rest, there was a significant decline of verbal episodic memory task (Rey Auditory Verbal Learning Test) in patients without freezing and with levodopa-responsive freezing. Interestingly, walking improved performance on the phonological fluency task in patients with levodopa-resistant freezing (p = 0.04).ConclusionsCompared to patients without freezing, patients with levodopa-resistant freezing perform worse when tested while seated in tasks of phonological verbal fluency. Surprisingly, gait was associated with a paradoxical improvement of phonological verbal fluency in the patients with levodopa-resistant freezing whilst walking determined a worsening of episodic memory in the other patient groups.     

Executive dysfunction in non-demented Parkinson's disease patients with hallucinations

Objective –  We investigated executive function in Parkinson's disease (PD) patients, and focused on executive dysfunction in PD with hallucinations, but without dementia.
Methods –  PD patients were classified by cognitive or neuropsychotic status as PD group, PD with vivid dreaming group, PD with hallucinations group and Parkinson's disease dementia (PDD) group. Psychomotor speed tests, the Stroop test, a verbal fluency test and the Self-rating Depression Scale were performed.
Results –  The PDD group showed poorer scores in every test compared with the PD group. The PD with hallucinations group showed results similar to those of the PDD group, while the PD with vivid dreaming group was similar to the PD group.
Conclusions –  The study suggests that PD patients with hallucinations, not extensive enough to qualify as dementia, already have executive dysfunction similar to that seen in PDD patients. Executive dysfunction may be an important substrate for hallucinations even when dementia is not yet apparent.     

抑郁对帕金森病患者执行功能的影响

目的 探讨抑郁对帕金森病(PD)患者执行功能的影响。方法 对41例PD患者及20例对照组进行整体认知功能、执行功能及抑郁状况的评定。整体认知功能评定使用简易智力状态量表(MMSE); 执行功能评定包括言语流畅性测验(VFT),连线测验(TMT),Stroop字色干扰测验(SCWT),画钟测验(CDT),数字符号替换测试(DSST)及数字广度测试(DST)等; 使用贝克抑郁自评量表(BDI)评估抑郁状态。结果 抑郁组SFT, PFT, DST, DSST, CDT, TMA,TMB, Stroop-B, Stroop-C,SIE评分均差于对照组(P<0.05); 非抑郁组PFT, DST, DSST,TMA,TMB, Stroop-C,SIE评分差于对照组(P<0.05); 与非抑郁组比较,抑郁组SFT, PFT, DST, DSST, TMA, TMB, Stroop-B, Stroop-C, SIE评分较差(P<0.05)。结论 PD患者存在明显的执行功能障碍,抑郁可以明显加重PD患者的执行功能障碍。     

蛋白酶体功能下降与散发性帕金森病

帕金森病(Parkinson's disease,PD)是一种中老年常见的进行性神经系统变性疾病,其病理特征为黑质致密部多巴胺能神经元选择性、进行性的丧失和残存神经元内出现Lewy小体.目前认为约10%的患者为遗传性的,约90%的患者为散发性的.到目前为止,散发性PD的病因及发病机制尚不完全清楚.最近的多个研究提示蛋白酶体功能下降导致神经元内异常蛋白聚集,功能紊乱,并进一步造成神经元的凋亡,可能参与了散发性PD的发病.本文就蛋白酶体功能下降与散发性PD发病机制方面的研究进展做一综述.     

Memory and depression in Parkinson's disease

Disorders of learning and memory are a frequent finding in nondemented Parkinson disease (PD) patients. It is not clear to what extent depression, present in at least half the cases of PD, contributes to these disorders. This paper investigates the possible influence of depression on tests of episodic memory in patients with Parkinson's disease (PD). We studied three groups of 11 subjects each (controls, non-depressed PD, mildly to moderately depressed PD). Neuropsychological tests included tests of short and long-term memory in verbal and non-verbal modalities. The two groups of PD patients performed significantly worse than controls on the memory tests, but there were no differences between the depressed and non-depressed PD patients. This lack of influence of depression on neuropsychological performance is compatible with Starkstein's view that cognitive imnpairment is only found beyond a given threshold of depression severity.     

Depressed mood and executive dysfunction in early Parkinson's disease

OBJECTIVES: Studies on neuropsychological functions in early Parkinson's disease (PD) have reported changes with respect to memory and executive control related to dysfunction of fronto-striatal circuitry. The question has been raised, however, whether these findings are at least partly influenced by depression, which as such can also lead to cognitive impairments that depend on the functional integrity of the prefrontal cortex. MATERIAL AND METHODS: In the present investigation early non-depressed PD patients (NPD), early PD patients with mild depressive symptoms (DPD), patients with primary depression (DEP) and healthy controls (HC) completed a range of neuropsychological tests. RESULTS: Group comparisons revealed impairments of DPD patients in comparison with HC with respect to verbal fluency, short-term memory and concept formation. In addition they showed mild working-memory deficits. CONCLUSIONS: In summary the present results indicate that depressed mood in early PD may exacerbate cognitive impairments. Thus careful assessment of affective variables in PD should be an integral part of the treatment of PD.     

Progress of visual dysfunction in Parkinson's disease

Studies on progression of Parkinson's disease (PD) mainly focus on the nigrostriatal dopaminergic decline, but not on the visual system. We determined progression of (i) disturbed color vision, assessed with the Farnsworth-Munsell 100 Hue test (FMT) and (ii) intensity of PD in 18 patients. Significant differences occurred between (i) initial FMT error scores and follow-up results 3 years later (P=0.002) and analogously (ii) scored intensity of PD (P=0.002). A relation between computed differences of FMT error scores and rated activities of daily living appeared. Deterioration of color vision progresses in PD.     

Impaired intentional content learning but spared incidental retention of contextual information in non-demented patients with Parkinson's disease

We investigated the incidental and intentional learning performance of 29 patients with idiopathic Parkinson's disease (PD) and 20 healthy volunteers. Measures of incidental and intentional memory were assessed with a spoken verbal recall task followed by a temporal word order task, a picture recall task followed by a spatial picture location task, and a written word recall task followed by a judgement of word frequency task. A multivariate analysis of variance and appropriate post hoc tests revealed significant differences for all intentional learning variables. In all cases, PD patients performed worse than normal controls. No group differences were found for the incidental retention of contextual information. The results indicate that PD patients have a selective problem of intentional learning, whereas incidental learning of contextual information remains intact. Elaborate processing, attentional and organizing strategies in the systematic encoding, and recollection of information have been attributed to dorsolateral prefrontal activation. Preferential dysfunction of dorsolateral prefrontal cortex-associated memory processes is consistent with the previously reported uneven patterns of dopamine loss in the striatum of patients with idiopathic PD showing most severe dopamine depletion in the portion of the caudate nucleus that is anatomically connected to the dorsolateral frontal cortex.     

Neural correlates of minor hallucinations in non-demented patients with Parkinson's disease

BackgroundHallucinations are a frequent and severe complication in Parkinson's disease (PD). Minor hallucinations are generally not disturbing, but likely progress to well-structured hallucinations with loss of insight and a great impact on quality of life. Knowledge on the neural bases of minor hallucinations may help to describe those systems associated with the early development of psychotic phenomena in PD.In this study, we aimed to identify the pattern of structural brain alterations associated with minor hallucinations in PD by using voxel-based morphometry (VBM).MethodsWe prospectively collected a sample of 46 non-demented PD patients, with (N = 17) and without (n = 29) minor hallucinations (passage and/or presence hallucinations), and 15 healthy controls. Groups were matched for age, education and global cognitive function. Presence and type of minor psychotic phenomena was assessed by the new MDS-UPDRS. Three dimensional T1-weighted MRI images were acquired with a 1.5 T magnet, and analyzed using optimized VBM.ResultsCompared to controls, PD with minor hallucinations (PD-mH) showed reduced gray matter volume bilaterally in different areas of the dorsal visual stream, and in functionally related midbrain and cerebellar structures. Additionally, bilateral gray matter volume increases were observed in the PD-mH group in limbic and paralimbic regions.ConclusionsOur data support a major role of the dorsal visual stream in the genesis of minor hallucinations in PD, reinforcing the importance of posterior cortical regions for the development of cognitive and psychiatric complications in PD.     

The effects of visual, auditory, and mixed cues on choice reaction in Parkinson's disease

We investigated the effects of visual, auditory, and mixed cues on complex choice reaction in people with Parkinson's disease (PD). The paradigm using a computerized task was based on a game, “paper–rock–scissors.” Four types of sensory cues were employed: simple visual cues, auditory cues, visual cues with auditory distracters, and auditory cues with visual distracters. Subjects were instructed to win, draw, or even lose the games and were required to respond as soon as possible after the sensory cues. When bradykinesia was taken into account, the PD patients had slower motor reactions. Further, when asked to lose in response to auditory cues, they displayed a significant delay in cognitive processing as compared to the healthy controls (HC), with a greater delay in the presence of a visual distracter. The error rates in the PD group were significantly higher than those in the HC group. These results suggest that PD patients are more influenced in choice reaction than the HC and by visual rather than auditory cues, especially under conditions with stimulus–response incompatibility that requires overriding habitual behavior. These data may be helpful in designing effective rehabilitation programs for PD to avoid inhibition of overlearned and contextually compatible reactions with visual distracters.