Mild cognitive impairment in Parkinson disease: heterogenous mechanisms

Cognitive impairment is common in Parkinson disease (PD), with long-term longitudinal studies reporting that most PD patients develop dementia. A high proportion of patients with PD and mild cognitive impairment (MCI) progress to dementia within a short time. Impairments occur in a range of cognitive domains, but single-domain impairment is more common than multiple one, non-amnestic more common than amnestic impairment. Although the term MCI applied to PD (PD-MCI) is not without controversy due to the lack of uniform diagnostic consensus criteria, the biological validity of PD-MCI is supported by many recent studies that show heterogenous mechanisms in the clinical presentation, neuropsychology, neuroimaging, biomarkers, and neuropathology, suggesting abnormal metabolic network activities involving several cortical and subcortical nervous systems. Prospective studies using specific biomarkers, including amyloid imaging, and cerebro-spinal fluid biomarkers are warranted for an exact diagnosis and prognostic assessment of early cognitive deficits in PD patients.     

Mild Cognitive Impairment in Parkinson’s Disease

Prospective studies conducted during the last decade have shown that the majority of patients with Parkinson’s disease (PD) develop dementia. In addition, using a variety of definitions and methods, more recent research suggests that approximately a quarter of PD patients without dementia have mild cognitive impairment (PD-MCI). Furthermore, several studies have shown that approximately 20% have MCI even at time of diagnosis of PD. The typical cognitive deficits include visuospatial, attentional, and executive deficits, but memory deficits have also been shown. The etiology of PD-MCI is not known, but it is likely that mechanisms known to contribute to dementia in PD (ie, limbic and cortical Lewy bodies, amyloid plaques, and cholinergic deficits) play a role, in addition to dysfunction of dopaminergic frontostriatal circuits. PD-MCI predicts a shorter time to dementia, and preliminary evidence suggests that this is particularly true for posterior cognitive deficits. There are currently no systematic clinical trials in PD-MCI.     

Mild cognitive impairment exists in Parkinson’s disease

Cognitive impairment exists in Parkinson’s disease (PD) as a transitional state between cognitively intact and demented PD patients. It seems to be a risk factor for the development of dementia in PD, but the precise criteria and unfavorable cognitive profile of mild cognitive impairment in PD (MCI-PD) have not yet been established. The concept may turn to be different from that in Alzheimer’s disease since we search for those already diagnosed PD patients who are at risk of developing dementia. In addition, clinical variables specific for PD also play role. Importantly, MCI possesses a metabolic basis in PD. Various biomarkers particularly including neuropsychological testing and the brain imaging hold promise in identification of MCI-PD patients with unfavorable prognoses. Well-designed longitudinal studies in MCI-PD cohorts are needed to assess the sensitivity and specificity of the PD-MCI designation as far as dementia development is concerned.     

Cognitive profiling of Parkinson disease patients with mild cognitive impairment and dementia

BackgroundPrevalence of mild cognitive impairment (MCI) and dementia in Parkinson disease (PD) is variable because different classification criteria are applied and there is lack of consensus about neuropsychological tests and cut-off used for cognitive profiling. Given the important therapeutic consequences for patient management, we aimed at identifying suitable diagnostic cognitive tests and respective screening cut-off values for MCI and dementia in PD (PDD).MethodsWe evaluated 105 PD patients using an extensive neuropsychological battery categorized as PD without cognitive impairment (PD-CNT) (35%), PD-MCI (47%) and PDD (18%) based on established criteria and calculated Receiver Operating Characteristic (ROC) curves.ResultsWe found different sensitivity and specificity among neuropsychological tests in detecting PD-MCI and PDD. In particular performance in attention/set shifting, verbal memory and language abilities, discriminated both PD-MCI and PDD from PD-CNT. Abilities involved mainly in semantic retrieval mechanisms discriminated PD-CNT from PD-MCI but also PD-MCI from PDD. Finally deficits in executive and visual-spatial abilities were only affected in PDD.ConclusionOur data point to an independent and different load of each test in defining different PD cognitive statuses. These findings can help selection of appropriate cognitive batteries in longitudinal studies and definition of stage-specific therapeutic targets.     

Long-term cognitive outcome of bilateral subthalamic deep brain stimulation in Parkinson’s disease

The effect of subthalamic deep brain stimulation (STN DBS) on cognition in Parkinson’s disease (PD) remains controversial, and it is unclear which factors are related to cognitive decline and dementia after STN DBS, especially over the long term. To this end, we analyzed the cognitive outcome of 103 non-demented patients with PD who were followed-up for at least 12 months after bilateral STN DBS surgery. Preoperatively, the patients were evaluated with the Unified Parkinson's Disease Rating Scale and neuropsychological tests. The rate of global cognitive decline and the incidence of dementia during follow-up for up to 7 years (mean 42.4 ± 24.5 months) were calculated, and preoperative clinical and neuropsychological factors associated with postoperative global cognitive decline or dementia were analyzed. The prevalence of mild cognitive impairment (MCI) and its relation to later cognitive decline or dementia were also evaluated. The annual decline in the mini–mental state examination score was 0.4 ± 1.7 with impaired attention and executive function and a higher levodopa equivalent dose at baseline being the predictors of a faster global cognitive decline after STN DBS. Dementia developed in 13 patients with an incidence rate of 35.7 per 1,000 person-years. Impaired executive function at baseline predicted dementia. At baseline, 63.1 % of the patients had PD-MCI, and these patients were more likely to develop dementia than those without PD-MCI. This study showed that dysfunctions in the frontostriatal circuitry at baseline were associated with a risk of subsequent global cognitive decline and dementia in patients with PD who underwent STN DBS. In addition, preoperative PD-MCI was a risk factor for dementia after STN DBS.     

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.     

Mattis Dementia Rating Scale 2: screening for MCI and dementia

Identifying patients at higher risk of developing dementia is important. The usefulness of the Mattis Dementia Rating scale-Second Edition (MDRS-2) to detect and differentiate between patients with amnestic mild cognitive impairment (A-MCI), Parkinson's disease and MCI (PD-MCI), PD with dementia (PDD), and Alzheimer's disease (AD) was investigated. In all, 22 healthy controls (HC), 22 A-MCI, 22 PD-MCI, 16 PDD, and 22 AD patients were evaluated using an extensive neuropsychological battery, including the MDRS-2. The MDRS-2 total standardized score detected all groups of patients. The dementia groups performed worse than HC on the 5 MDRS-2 subscales. Alzheimer's disease patients scored higher than PDD on MDRS-2 conceptualization and lower on memory. Healthy controls were better than PD-MCI on MDRS-2 initiation/perseveration and memory and better than A-MCI on memory. No difference was found between the MCI groups. The MDRS-2 is a suitable short scale for MCI and dementia screening but is not specific enough to differentiate between A-MCI and PD-MCI.     

Is all cognitive impairment in Parkinson’s disease “mild cognitive impairment”?

Cognitive impairment can be demonstrated in Parkinson’s disease (PD) from the very beginning of the disease. Clinical manifestations range from slight deficits, only demonstrable by means of neuropsychological testing, up to dementia. If a linear involution is supposed for the cognitive worsening in PD, then the relatively subtle cognitive defects should be taken as the earliest signs of dementia implying that PD-MCI concept would be thoroughly equivalent to that used for the early prediction of other dementias among healthy population. Cognitive defects in PD, however, may not follow a normal distribution. While fronto-striatal deficits, such as working memory, set-shifting and free-recall verbal memory appear altered in most patients during long periods of time, certain functions depending on more posterior-cortical regions, such as copying or naming, usually characterize patients with dementia. Fronto-striatal and posterior-cortical cognitive defects may have a different pathophysiological substrates, evolution and prognosis. While fronto-striatal defects appear more related to dopaminergic defects, posterior-cortical defects may obey multiple neurotransmitter failure. Designing criteria to accurately diagnose PD-MCI is highly relevant for clinical treatment, research, care-giving and decision-making. Besides quantitative defects, an operative definition of MCI in PD should clearly distinguish a “risky cognitive profile” among the broad cognitive defects intrinsic to PD. Thus, along with other possible biological markers, from a neuropsychological point of view, posterior-cortical defects probably represent the very syndrome of MCI in PD.     

帕金森病患者轻度认知损害的临床调查

目的 研究帕金森病(Parkinson's disease,PD)伴有轻度认知功能缺损(mild cognitiveimpairment,MCI,即PD-MCI)患者患病率及其神经心理学特征.方法 设立PD患者组(n=103)及健康对照组(n=32)进行比较.心理学测验工具由MMSE、痴呆评定量表及其他神经心理学测试组成,汉密尔顿抑郁量表用以评定患者的抑郁程度.结果 (1)21例(20.4%)PD患者被诊断为痴呆,37例(35.9%)患者认知功能完整,45例(43.7%)患者有MCI;(2)与认知正常的PD患者相比,PD-MCI患者年龄更大,PD起病更晚,且运动损害更为严重;(3)PD-MCI的患病率和神经心理学特征与PD症状主要累及何侧及分型有一定关系:左侧组比右侧组患者出现MCI的概率要高(74.2%和42.2%,χ2=7.589,P<0.05);震颤为主型患者与混合型患者相比,Stroop测词试验(SWT)的耗时(s)显著减少(80.8±39.9和94.4±30.0,t=3.332,P<0.01).结论在PD患者中,筛查出PD-MCI患者有着重要的临床意义,有助于临床医生针对性地处理不同PD患者,并易化对其预后的判断.     

帕金森病患者的轻度认知功能障碍

目的评估帕金森病(Parkinson’s disease,PD)患者的认知功能状态,分析帕金森病合并轻度认知功能障碍(Parkinson’s Disease with Mild Cognitive Impairment,PD-MCI)的特点。方法纳入PD患者64例,采用神经心理测试组评估其注意、视空间、执行和记忆等认知域的功能。结果本组PD患者中,认知功能正常24例(37.5%),PD-MCI 30例(46.9%),帕金森病痴呆10例(15.6%)。在PD-MCI患者中,单个认知领域轻度损害(60.0%)较多个认知域型轻度认知损害(40.0%)更常见,累及较多的认知域依次为记忆(20例,66.7%),执行(13例,43.3%),视空间(12例,36.7%)。早期PD患者PD-MCI发生率为36.4%,痴呆发生率为3.0%;中晚期PD患者PD-MCI发生率为58.1%,痴呆发生率达29.0%,两组差异有显著性(χ2=18.222,P<0.001)。PD患者的病情程度与认知功能状态呈负相关(Spearman相关系数=-0.553,P<0.001)。结论轻度认知功能障碍(mild cogni-tive impairment,MCI)在PD患者中常见,即使在疾病早期,其发生率也较高,其中单个认知领域轻度损害较多个认知域型轻度认知损害更常见。PD患者的病情越严重,认知功能状态越差。     

Exploring the relationship between motor impairment,vascular burden and cognition in Parkinson’s disease

Objective

To determine frequency and type of cognitive disorders in cross-sectional analysis of a Parkinson’s disease (PD) cohort, and explore its relations to motor symptoms, modifiable vascular risk factors and white matter lesions (WML) volume.

Methods

In a group of 133 PD patients, mild cognitive impairment (PD-MCI) and dementia (PDD) were diagnosed according to Movement Disorders Society Task Force criteria (level 2 for PD-MCI). Detailed motor measurements were applied, including rigidity, axial, bradykinesia, tremor and postural instability gait disorders (PIGD) scores. Vascular risk was estimated by the Framingham General Cardiovascular Disease risk scoring algorithm and WML volume was measured for whole brain and frontal lobe.

Results

Sixty-one (46.9%) patients fulfilled criteria for PD-MCI, and 23 (17.7%) for PDD. Non-amnestic multiple domain MCI was most frequent (52% of PD-MCI patients). Motor scores were significantly higher in cognitively impaired patients, but only axial score discriminated between MCI and dementia. High vascular risk was related to impaired cognition, bradykinesia, axial, PIGD and freezing of gait (FOG) score, while whole brain WML volume was associated with PDD, FOG and attention deficits. Furthermore, high vascular risk was identified as a potential predictor of both MCI and dementia in PD. Additionally, age and bradykinesia score were independently associated with PD-MCI and age, axial score and whole brain WML volume with PDD.

Conclusion

Cognitive disorders in PD are associated with more severe, predominantly axial motor deficits and increased, but partly modifiable vascular burden, thus opening a possibility for development of preventive strategies in PD.

     

Diagnostic and screening power of neuropsychological testing in detecting mild cognitive impairment in Parkinson’s disease

Prevalence of mild cognitive impairment (MCI) in Parkinson’s disease (PD) is variable likely due to methodological differences in classification criteria and lack of consensus about neuropsychological tests used for cognitive profiling. The main objective of our study was to identify the most suitable neuropsychological tests and determine their screening and diagnostic cutoff scores for PD-MCI. A series of 104 consecutive PD patients performed an extensive neuropsychological evaluation. Individual test values were converted into Z-scores using relative published normative data. According to published criteria, PD patients were categorized as PD-CNT (PD without cognitive impairment), PD-MCI (patients performing ?1.5 SDs below the mean score in at least one cognitive domain), and PDD. We used receiver operating characteristic (ROC) curves and K-means clustering analyses to calculate the best discriminating power of each neuropsychological tests in detecting PD-MCI. PD patients were categorized as follows: 55 PD-CNT (53 %), 34 PD-MCI (33 %), and 15 PDD (14 %). PD-MCI had lower education, longer disease duration and greater frequency of hallucinations than PD-CNT. We found that only the Trail Making test, Rey-Osterrieth Complex Figure Test (ROCF) copy, Frontal Assessment Battery (FAB), Digit Span Backward, and Rey’s word auditory verbal learning test (RVLT) immediate recall reached significant screening and diagnostic validity in predicting PD-MCI (AUC 0.705–0.795) with cutoff scores calculated by ROC analyses lying within normal range for normative data. Specific neuropsychological tests covering verbal memory, attention/set-shifting, and visual-spatial deficits are the best predictors of MCI in PD if valid cutoff scores are used. These results have consequences for cognitive diagnosis and potentially in establishing the rate of PD cognitive decline.     

帕金森病患者轻度认知功能损害

目的 探讨帕金森病(PD)患者伴轻度认知功能损害(MCI)即PD-MCI的特征及其相关因素.方法 采用多种量表[MMSE、Hoehn-Yahr分期、Webster评分、PD统一评分量表-运动(UPDRS-motor)及剑桥老年认知检查量表中文版(CAMCOG-C)]评估PD患者的病情严重程度、运动和认知功能;应用Petersen改良标准诊断PD-MCI.结果 89例PD患者中,认知正常(PDCOGNL)56例(63%),PD-MCI 20例(22%),PD痴呆(PDD)13例(15%).PD-MCI组较PDCOGNL组在定向、语言、记忆、注意、执行、思维、知觉等方面均存在明显损害,两组年龄和起病年龄差异无统计学意义,受教育程度差异有统计学意义(PD-MCI:4.4±4.3,PDCOGNL:7.1±4.9;q=3.270,P<0.05);PD-MCI组的年龄、起病年龄及受教育程度较PDD组差异均无统计学意义;而PDD组较PDCOGNL组在年龄、起病年龄、受教育程度等方面差异均有统计学意义(q=-4.913、-4.997、4.740,均P<0.01);3组间病程差异无统计学意义.Hoehn-Yahr分期、Webster评分及UPDRS-motor评分与PD认知功能均存在负相关.结论 PD-MCI是PD认知正常与PDD之间的过渡状态,存在多个区域的认知损害;高龄、起病年龄迟、受教育程度低可能是PD认知损害的危险因素;疾病严重程度及运动功能与PD认知功能存在着负相关.     

Both early and late cognitive dysfunction affects the electroencephalogram in Parkinson's disease

We sought to define quantitative electroencephalographic (EEG) measures as biomarkers of both early and late cognitive decline in Parkinson's disease (PD). PD subjects classified as cognitively normal (PD-CogNL), mild cognitive impairment (PD-MCI), and dementia (PD-D) were studied. Cognitive status and neuropsychological testing was correlated with background rhythm and frequency band EEG power across five frequency bands. We conclude that global EEG measures have potential use as biomarkers in the study of both early and late cognitive deterioration in PD, including for evaluating its treatment. PD-MCI has mean quantitative EEG characteristics that represent an intermediate electrophysiological state between PD-CogNL and PD-D.     

Early neuropsychological detection and the characteristics of Parkinson's disease associated with mild dementia

Parkinson's disease (PD) may exhibit patterns of cognitive deficits, yet physicians are currently lacking operational criteria to define the clinical boundaries between PD and PD dementia (PDD). Therefore, we investigated the characteristics of the cognitive impairments in mild PDD. We recruited 30 PDD, 20 PD-MCI (PD with mild cognitive impairment without dementia) and 33 controls. All subjects were evaluated with detailed neuropsychological tests. Our results showed that visual memory, visuospatial functions, naming and calculation displayed more marked impairment than that of the other domains. Thus we suggest that adding cognitive dysfunctions of cortical type to the early cognitive deficits of PD-MCI can help predict the development of dementia.     

Cerebral white matter hyperintensity in Parkinson's disease: A major risk factor for mild cognitive impairment

BackgroundMild cognitive impairment (MCI) and dementia contribute to a poor quality of life among patients with PD. The influence of cerebral ischemia as a risk factor for MCI in PD has not been adequately investigated. To address this issue, we examined the influence of the volume and distribution of white matter hyperintensity (WMH) as a risk factor for MCI in early PD.MethodsProspective study of patients with early idiopathic PD. All patients had baseline MRI-FLAIR, clinical assessment and detailed neuropsychological evaluation. Data on demographics, vascular risk factors, cognitive performance and WMH volumes were analyzed.Results91 patients; mean age 64.9 years, mean education of 10.5 years. 24 patients fulfilled the Movement Disorder Society criteria for MCI and were classified as PD-MCI while the rest were classified as PD with no cognitive impairment (PD-NCI). Patients with PD-MCI and PD-NCI did not differ in Hoehn & Yahr staging. PD-MCI patients had a higher prevalence of diabetes mellitus, hypertension and hyperlipidemia. PD-MCI patients had significantly greater volume of periventricular (6.04 ml vs. 2.66 ml, p = 0.001) and deep subcortical WMH (2.16 vs.1.44, p = 0.002). Regional WMH was significantly greater among PD-MCI in the frontal, parietal and occipital regions. Logistic regression analyses demonstrated WMH to be associated with PD-MCI independent of age, education, and vascular risk factors. Increasing WMH volume was associated with lower performance on executive function, memory and language.ConclusionsWMH is an important risk factor for PD-MCI independent of vascular risk factors. PD patients with WMH should be regularly screened for MCI.     

Heterogenous mechanisms of mild cognitive impairment in Parkinson’s disease

Mild cognitive impairment in Parkinson disease (PD-MCI) shows heterogeneity in the clinical presentation, neuropsychology, neuroimaging, and neuropathology, suggesting abnormal metabolic network activities involving several cortical and subcortical systems. Prospective studies using specific biomarkers, including amyloid imaging and CSF biomarkers are important for the diagnosis and prognostic assessment of early cognitive deficits in PD patients.     

Diagnosing mild cognitive impairment in Parkinson’s disease: which tests perform best in the Italian population?

Mild cognitive impairment (MCI) is common in patients with Parkinson’s disease (PD) and should be recognized early because it represents a predictor of PD-related dementia and worse disease course. Diagnostic criteria for PD-related MCI (PD-MCI) have recently been defined by a Movement Disorders Society (MDS) task force. The present study explored which neuropsychological tests perform best for a level II (i.e., comprehensive neuropsychological assessment) diagnosis of PD-MCI according to the MDS task force criteria in Italian-speaking PD patients. To this aim, we assessed a comprehensive 23-item neuropsychological battery, derived the best-performing 10-test battery (i.e., two tests per domain for each of the five cognitive domains), and explored its accuracy for diagnosing PD-MCI in comparison to the full battery in a group of PD patients. A secondary aim was to explore the role of this battery for subtyping PD-MCI according to single-domain vs. multiple-domain involvement. The 10-test battery showed 73% sensitivity and 100% specificity for diagnosing PD-MCI, and 69% sensitivity and 100% specificity for PD-MCI subtyping. In patients older than 70 years, we derived a slightly different 10-test battery with 84% sensitivity and 100% specificity for PD-MCI diagnosis, and 86% sensitivity and 100% specificity for PD-MCI subtyping. These 10-item neuropsychological batteries might represent a good trade-off between diagnostic accuracy and time of application, and their role in PD-MCI diagnosis and subtyping should be further explored in future prospective studies.     

Dissociations among daytime sleepiness,nighttime sleep,and cognitive status in Parkinson's disease

BackgroundDaytime and nighttime sleep disturbances and cognitive impairment occur frequently in Parkinson's disease (PD), but little is known about the interdependence of these non-motor complications. Thus, we examined the relationships among excessive daytime sleepiness, nighttime sleep quality and cognitive impairment in PD, including severity and specific cognitive deficits.MethodsNinety-three PD patients underwent clinical and neuropsychological evaluations including the Epworth Sleepiness Scale (ESS) and Pittsburgh Sleep Quality Index (PSQI). Patients were classified as having normal cognition (PD-NC), mild cognitive impairment (PD-MCI), or dementia (PDD) using recently proposed Movement Disorder Society PD-MCI and PDD criteria. Relationships between the sleep and cognitive measures and PD cognitive groups were examined.ResultsThe PD cohort included PD-NC (n = 28), PD-MCI (n = 40), and PDD (n = 25) patients. ESS scores, as a measure of daytime sleepiness, were significantly worse (p = 0.005) in cognitively impaired PD patients, particularly PDD patients. ESS scores correlated significantly with Mini-Mental State Examination scores and also with cognitive domain scores for attention/working memory, executive function, memory, and visuospatial function. In contrast, PSQI scores, as a measure of nighttime sleep quality, neither differed among cognitive groups nor correlated with any cognitive measures.ConclusionsDaytime sleepiness in PD, but not nighttime sleep problems, is associated with cognitive impairment in PD, especially in the setting of dementia, and attention/working memory, executive function, memory, and visuospatial deficits. The presence of nighttime sleep problems is pervasive across the PD cognitive spectrum, from normal cognition to dementia, and is not independently associated with cognitive impairment or deficits in cognitive domains.     

Cognitive decline and quality of life in incident Parkinson's disease: The role of attention

IntroductionParkinson's disease dementia (PDD) is associated with poorer quality of life (QoL). Prior to the onset of PDD, many patients experience progressive cognitive impairment. There is a paucity of longitudinal studies investigating the effects of cognitive decline on QoL. This study aimed to determine the longitudinal impact of cognitive change on QoL in an incident PD cohort.MethodsRecently diagnosed patients with PD (n = 212) completed a schedule of neuropsychological assessments and QoL measures; these were repeated after 18 (n = 190) and 36 months (n = 158). Mild cognitive impairment (PD-MCI) was classified with reference to the Movement Disorder Society criteria. Principal component analysis was used to reduce 10 neuropsychological tests to three cognitive factors: attention, memory/executive function, and global cognition.ResultsBaseline PD-MCI was a significant contributor to QoL (β = 0.2, p < 0.01). For those subjects (9%) who developed dementia, cognitive function had a much greater impact on QoL (β = 10.3, p < 0.05). Multivariate modelling showed attentional deficits had the strongest predictive power (β = −2.3, p < 0.01); brief global tests only modestly predicted decline in QoL (β = −0.4, p < 0.01).ConclusionsPD-MCI was associated with poorer QoL over three years follow up. Cognitive impairment had a greater impact on QoL in individuals who developed dementia over follow-up. Impaired attention was a significant determinant of QoL in PD. Interventions which improve concentration and attention in those with PD could potentially improve QoL.