Article

Relationship of MDS-UPDRS Non-motor Symptoms to Cognitive Functioning in Patients with Parkinson's Disease: MDS-UPDRS Part I and Cognitive Functioning

Authors:
To read the full-text of this research, you can request a copy directly from the authors.

Abstract

Background Few studies assess the relationships between nonmotor aspects of experiences of daily living and cognitive functioning in Parkinson's disease (PD). Objective To evaluate the relationships among the Movement Disorders Society–Unified Parkinson's Disease Rating Scale (MDS‐UPDRS) part I items and neuropsychological tests in PD.Methods: We assessed 151 PD patients with the MDS‐UPDRS part I and a battery of cognitive tests focused on the following 5 cognitive domains: attention/working memory, executive functioning, recent memory, language, visuoperception. Raw scores for individual cognitive tests were transformed to z scores, and cognitive domain scores were calculated by averaging z scores within each domain. Individual items from the MDS‐UPDRS part I were entered in a stepwise linear regression analysis assessing item contribution to cognitive domain scores. Results The MDS‐UPDRS part I item scores for hallucinations and psychosis and light headedness on standing predicted attention/working memory domain scores ( P = 0.004). These same item scores, along with apathy, depressed mood, and dopamine dysregulation syndrome, predicted executive functioning ( P = 0.044). The apathy and dopamine dysregulation syndrome items predicted language ( P = 0.006). In addition, the cognitive impairment and sleep items were predictors of recent memory ( P = 0.031). None of the items were predictors of visuoperception ( P = 0.006). Other part I items were not significantly related to cognitive domain scores. Conclusions Specific nonmotor MDS‐UPDRS part I items, particularly mood, behavior, and autonomic‐related items, exhibited significant relationships with cognitive domains. The highest number of items were predictive of the executive functioning domain, which is the hallmark cognitive dysfunction in PD.

No full-text available

Request Full-text Paper PDF

To read the full-text of this research,
you can request a copy directly from the authors.

... The MDS-UPDRS is correlated with validated rating scales of QOL and functional disability [41]. There is a relationship between the MDS-UPDRS apathy construct and executive functioning, dopamine dysregulation syndrome, and cognitive impairments [42]. In the apathy item derived from the MDS-UPDRS interview section of Part I (question 1.5), the interviewer observes the level of spontaneous activity, motivation, assertiveness, and initiative and then rates the impact of reduced levels of performance in daily life and social interaction. ...
Article
Full-text available
Background: Apathy, often-unrecognized in Parkinson's Disease (PD), adversely impacts quality-of-life (QOL) and may increase with disease severity. Identifying apathy early can aid treatment and enhance prognoses. Whether feelings related to apathy (e.g., loss of pleasure) are present in mild PD and how apathy and related feelings increase with disease severity is unknown. Methods: 120 individuals (M age: 69.0 ± 8.2 y) with mild (stages 1-2, n = 71) and moderate (stages 2.5-4; n = 49) PD were assessed for apathy and apathy-related constructs including loss of pleasure, energy, interest in people or activities, and sex. Correlations were used to determine the association of apathy with apathy-related constructs. Regression models, adjusted for age, cognitive status, and transportation, compared groups for prevalence of apathy and apathy-related feelings. Results: Apathy-related constructs and apathy were significantly correlated. Apathy was present in one in five participants with mild PD and doubled in participants with moderate PD. Except for loss of energy, apathy-related constructs were observed in mild PD at a prevalence of 41% or greater. Strong associations were noted between all apathy-related constructs and greater disease severity. After adjustment for transportation status serving as a proxy for independence, stage of disease remained significant only for loss of pleasure and loss of energy. Conclusion: People with mild PD showed signs of apathy and apathy-related feelings. Loss of pleasure and energy are apathy-related feelings impacted by disease severity. Clinicians should consider evaluating for feelings related to apathy to enhance early diagnosis in individuals who might otherwise not exhibit psychopathology.
Article
Full-text available
Cognitive impairment (CI) is a characteristic non-motor feature of Parkinson disease (PD) that poses a severe burden on the patients and caregivers, yet relatively little is known about its pathobiology. Cognitive deficits are evident throughout the course of PD, with around 25% of subtle cognitive decline and mild CI (MCI) at the time of diagnosis and up to 83% of patients developing dementia after 20 years. The heterogeneity of cognitive phenotypes suggests that a common neuropathological process, characterized by progressive degeneration of the dopaminergic striatonigral system and of many other neuronal systems, results not only in structural deficits but also extensive changes of functional neuronal network activities and neurotransmitter dysfunctions. Modern neuroimaging studies revealed multilocular cortical and subcortical atrophies and alterations in intrinsic neuronal connectivities. The decreased functional connectivity (FC) of the default mode network (DMN) in the bilateral prefrontal cortex is affected already before the development of clinical CI and in the absence of structural changes. Longitudinal cognitive decline is associated with frontostriatal and limbic affections, white matter microlesions and changes between multiple functional neuronal networks, including thalamo-insular, frontoparietal and attention networks, the cholinergic forebrain and the noradrenergic system. Superimposed Alzheimer-related (and other concomitant) pathologies due to interactions between α-synuclein, tau-protein and β-amyloid contribute to dementia pathogenesis in both PD and dementia with Lewy bodies (DLB). To further elucidate the interaction of the pathomechanisms responsible for CI in PD, well-designed longitudinal clinico-pathological studies are warranted that are supported by fluid and sophisticated imaging biomarkers as a basis for better early diagnosis and future disease-modifying therapies.
Article
Objective: Deep brain stimulation (DBS) is effective for the motor symptoms of Parkinson's disease (PD). Although most patients benefit with minimal cognitive side effects, cognitive decline is a risk, and there is little available evidence to guide preoperative risk assessment. Visual illusions or visual hallucinations (VHs) and impulse-control behaviors (ICBs) are relatively common complications of PD and its treatment and may be a marker of more advanced disease, but their relationship with postoperative cognition has not been established. The authors aimed to determine whether any preoperative history of VHs or ICBs is associated with cognitive change after DBS. Methods: Retrospective chart review identified 54 patients with PD who received DBS of the subthalamic nucleus or globus pallidus internus and who completed both pre- and postoperative neuropsychological testing. Linear regression models were used to assess whether any preoperative history of VHs or ICBs was associated with changes in attention, executive function, language, memory, or visuospatial cognitive domains while controlling for surgical target and duration between evaluations. Results: The investigators found that a history of VHs was associated with declines in attention (b=-4.04, p=0.041) and executive function (b=-4.24, p=0.021). A history of ICBs was not associated with any significant changes. Conclusions: These results suggest that a history of VHs may increase risk of cognitive decline after DBS; thus, specific preoperative counseling and targeted remediation strategies for these patients may be indicated. In contrast, a history of ICBs does not appear to be associated with increased cognitive risk.
Article
Introduction: Dementia with Lewy bodies (DLB) has no approved symptomatic or disease-modifying treatments in the US and Europe, despite being the second most common cause of neurodegenerative dementia. Areas covered: Herein, the authors briefly review the DLB drug development pipeline, providing a summary of the current pharmacological intervention studies. They then focus on the anticonvulsant zonisamide, a benzisoxazole derivative with a sulfonamide group and look at its value for treating parkinsonism in DLB. Expert opinion: Several new compounds are being tested in DLB, the most innovative being those aimed at decreasing brain accumulation of α-synuclein. Unfortunately, new drug testing is challenging in terms of consistent diagnostic criteria and lack of reliable biomarkers. Few randomized controlled trials (RCTs) are well-designed, with enough power to detect significant drug effects. Levodopa monotherapy can treat the parkinsonism in DLB, but it can cause agitation or visual hallucination worsening. Two Phase II/III RCTs of DLB patients recently reported a statistically significant improvement in motor function in those receiving zonisamide as an adjunctive treatment to levodopa. New biomarker strategies and validated outcome measures for DLB or prodromal DLB may enhance clinical trial design for the development of specific disease-modifying treatments.
Article
Full-text available
Background: Impulse control disorders (ICDs) and related behaviors are frequent in Parkinson's disease (PD). Mild cognitive impairment (PD-MCI) and dementia (PDD), both characterized by heterogeneous cognitive phenotypes, are also commonly reported in PD. However, the frequency and severity of ICD within PD cognitive states is unknown. Methods: Three hundred and twenty-six PD patients completed a comprehensive neuropsychological assessment and were classified as PD-MCI, PDD, or without cognitive alterations (PD-NC). The Minnesota impulsive disorders interview was used to ascertain the presence (ICD+) or absence (ICD–) of ICD. The Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale was used to assess ICD severity. A subsample of 286 patients evaluated with the same cognitive tasks was selected in order to investigate the characteristics of ICD in PD cognitive phenotypes. Results: ICDs were present in 55% of PD-NC, in 50% of PD-MCI, and in 42% of PDD patients. Frequencies of ICD+ with attentive (ICD+: 20% vs. ICD–: 4%; p = 0.031) and executive impairments (ICD+: 44% vs. ICD–: 30%; p = 0.027) were higher in the PD-MCI and PDD subgroups, respectively. As expected, no differences were observed in the PD-NC. PD-MCI with attentive impairments presented higher percentage of ICD+ with deficits in the Trail Making Test B-A but not in the Digit Span Sequencing task. In PDD, executive failures concerned Similarities task (ICD+: 67%; ICD–: 29%; p = 0.035), with no differences between ICD+ and ICD– in the Stroop task. Conclusions: Prevalence and severity of ICDs and related behaviors do not differ in PD with different cognitive states. However, ICD+ are more likely to show deficits, respectively in attentive and in executive domains, specifically in the Trail Making Test B-A task for the attention and working memory domain in PD-MCI and in the Similarities task for the executive function domain in PDD. Prospective studies should evaluate if these tests can be used as screening tool for ICDs in PD.
Article
Full-text available
Objective: To investigate the relation between orthostatic hypotension (OH) and posture-mediated cognitive impairment in Parkinson disease (PD) using a cross-sectional and within-group design. Methods: Individuals without dementia with idiopathic PD included 18 with OH (PDOH) and 19 without OH; 18 control participants were also included. Neuropsychological tests were conducted in supine and upright-tilted positions. Blood pressure was assessed in each posture. Results: The PD groups performed similarly while supine, demonstrating executive dysfunction in sustained attention and response inhibition, and reduced semantic fluency and verbal memory (encoding and retention). Upright posture exacerbated and broadened these deficits in the PDOH group to include phonemic fluency, psychomotor speed, and auditory working memory. When group-specific supine scores were used as baseline anchors, both PD groups showed cognitive changes following tilt, with the PDOH group exhibiting a wider range of deficits in executive function and memory as well as significant changes in visuospatial function. Conclusions: Cognitive deficits in PD have been widely reported with assessments performed in the supine position, as seen in both our PD groups. Here we demonstrated that those with PDOH had transient, posture-mediated changes in excess of those found in PD without OH. These observed changes suggest an acute, reversible effect. Understanding the effects of OH due to autonomic failure on cognition is desirable, particularly as neuroimaging and clinical assessments collect data only in the supine or seated positions. Identification of a distinct neuropsychological profile in PD with OH has quality of life implications, and OH presents itself as a possible target for intervention in cognitive disturbance.
Article
Full-text available
Objective: Dopamine dysregulation syndrome (DDS) refers to a compulsive pattern of dopaminergic drug misuse complicating Parkinson's disease (PD). To date, few data are available on DDS risk factors, cognitive profile and long-term outcome. Methods: In this retrospective case-control study, consecutive PD outpatients fulfilling criteria for DDS were assessed over a 6-year period (2005-2011). They were compared with 70 PD cases matched for age at onset, gender and disease duration, and with 1281 subjects with motor fluctuations and dyskinesias. DDS patients and matched controls underwent extensive neuropsychological assessment. Strategies for DDS patients management and the outcome at the last follow-up visit were recorded. Results: Thirty-five patients with DDS were identified, reporting history of depression, family history of PD and drug abuse, greater difference between 'Off' versus 'On' motor symptoms compared to age-matched controls. They had younger age at onset (but not any gender difference) compared to general PD population. Cognitive profile of DDS did not show major abnormalities, including executive functions. DDS patients have been followed up for 3.2±2.1 years and remission was recorded in 40% of cases. Negative DDS outcome was significantly associated with poor caregiver supervision. Sustained remission occurred more commonly on clozapine and on duodenal levodopa infusion and subthalamic nucleus deep brain stimulation (STN-DBS) than on apomorphine pump treatment. Conclusions: Clinicians should be aware of risk factors predisposing to DDS. Duodenal levodopa infusion and, less consistently, STN-DBS were more commonly associated with DDS remission. Effective caregiving plays a key role in long-term behavioural outcome.
Article
Full-text available
Visual Hallucinations (VH) are a common non-motor symptom of Parkinson’s Disease (PD) and the Lewy body dementias (LBD) of Parkinson's disease with dementia (PDD) and Dementia with Lewy Bodies (DLB). The origin of VH in PD and LBD is debated: earlier studies considered a number of different possible mechanisms underlying VH including visual disorders, Rapid Eye Movement (REM) Sleep Intrusions, dysfunctions of top down or bottom up visual pathways, and neurotransmitter imbalance. More recently newer hypotheses introduce, among the possible mechanisms of VH, the role of attention networks (ventral and dorsal) and of the Default Mode Network (DMN) a network that is inhibited during attentional tasks and becomes active during rest and self referential imagery. Persistent DMN activity during active tasks with dysfunctional imbalance of dorsal and ventral attentional networks represents a new hypothesis on the mechanism of VH. We review the different methods used to classify VH and discuss reports supporting or challenging the different hypothetical mechanisms of VH.
Article
Full-text available
In healthy individuals and those with insomnia, poor sleep quality is associated with decrements in performance on tests of cognition, especially executive function. Sleep disturbances and cognitive deficits are both prevalent in Parkinson's disease (PD). Sleep problems occur in over 75% of patients, with sleep fragmentation and decreased sleep efficiency being the most common sleep complaints, but their relation to cognition is unknown. We examined the association between sleep quality and cognition in PD. In 35 non-demented individuals with PD and 18 normal control adults (NC), sleep was measured using 24-hr wrist actigraphy over 7 days. Cognitive domains tested included attention and executive function, memory and psychomotor function. In both groups, poor sleep was associated with worse performance on tests of attention/executive function but not memory or psychomotor function. In the PD group, attention/executive function was predicted by sleep efficiency, whereas memory and psychomotor function were not predicted by sleep quality. Psychomotor and memory function were predicted by motor symptom severity. This study is the first to demonstrate that sleep quality in PD is significantly correlated with cognition and that it differentially impacts attention and executive function, thereby furthering our understanding of the link between sleep and cognition.
Article
Full-text available
Dopaminergic medication-related impulse control disorders (ICDs) such as pathological gambling and compulsive shopping have been reported in Parkinson's disease (PD). We hypothesized that dopamine agonists (DAs) would be associated with greater impulsive choice or greater discounting of delayed rewards in PD patients with ICDs (PDI). Fourteen PDI patients, 14 PD controls without ICDs, and 16 medication-free matched normal controls were tested on the Experiential Discounting Task (EDT), a feedback-based intertemporal choice task, spatial working memory, and attentional set shifting. The EDT was used to assess choice impulsivity (hyperbolic K value), reaction time (RT), and decision conflict RT (the RT difference between high conflict and low conflict choices). PDI patients and PD controls were tested on and off DA. On the EDT, there was a group by medication interaction effect [F(1,26) = 5.62; p = 0.03] with pairwise analyses demonstrating that DA status was associated with increased impulsive choice in PDI patients (p = 0.02) but not in PD controls (p = 0.37). PDI patients also had faster RT compared to PD controls [F(1,26) = 7.51, p = 0.01]. DA status was associated with shorter RT [F(3,24) = 8.39, p = 0.001] and decision conflict RT [F(1,26) = 6.16, p = 0.02] in PDI patients but not in PD controls. There were no correlations between different measures of impulsivity. PDI patients on DA had greater spatial working memory impairments compared to PD controls on DA (t = 2.13, df = 26, p = 0.04). Greater impulsive choice, faster RT, faster decision conflict RT, and executive dysfunction may contribute to ICDs in PD.
Article
Full-text available
To devise a short bedside cognitive and behavioral battery to assess frontal lobe functions. The designed battery consists of six subtests exploring the following: conceptualization, mental flexibility, motor programming, sensitivity to interference, inhibitory control, and environmental autonomy. It takes approximately 10 minutes to administer. The authors studied 42 normal subjects and 121 patients with various degrees of frontal lobe dysfunction (PD, n = 24; multiple system atrophy, n = 6; corticobasal degeneration, n = 21; progressive supranuclear palsy, n = 47; frontotemporal dementia, n = 23). The Frontal Assessment Battery scores correlated with the Mattis Dementia Rating Scale scores (rho = 0.82, p < 0.01) and with the number of criteria (rho = 0.77, p < 0.01) and perseverative errors (rho = 0.68, p < 0.01) of the Wisconsin Card Sorting Test. These variables accounted for 79% of the variance in a stepwise multiple regression, whereas age or Mini-Mental State Examination scores had no significant influence. There was good interrater reliability (kappa = 0.87, p < 0.001), internal consistency (Cronbach's coefficient alpha = 0.78), and discriminant validity (89.1% of cases correctly identified in a discriminant analysis of patients and controls). The Frontal Assessment Battery is easy to administer at bedside and is sensitive to frontal lobe dysfunction.
Article
Full-text available
This study compared the performance of Parkinson's disease (PD) patients with and without depression, patients with depression alone, and normal control subjects on a cognitive screening instrument, the Mattis Dementia Rating Scale (DRS) to evaluate the influences of depression and Parkinson's disease on cognition. PD affects overall level of cognitive functioning and, to a lesser extent, DRS Initiation/Perseveration, Construction, and Attention. Diminished memory was primarily related to depression. Treatment of depression may ameliorate aspects of cognitive dysfunction in the PD patient with depression.
Article
Full-text available
The different distribution of pathologic features in frontotemporal dementia (FTD) and Alzheimer disease (AD) predicts a predominant dysexecutive syndrome in FTD. The Frontal Assessment Battery (FAB) has previously been validated in diseases associated with a frontal lobe dysfunction. To evaluate the sensitivity of the FAB to differentiate FTD and AD. Comparison study. Memory Clinic of the Salpêtrière Hospital, Paris, France. Twenty-six patients with FTD and 64 patients with AD. Comparison of FAB and Mini-Mental State Examination (MMSE) scores between patients with FTD and those with AD. The mean +/- SD FAB scores significantly differed between patients with FTD (7.6 +/- 4.2) and those with AD (12.6 +/- 3.7) (P<.001), but not MMSE scores. The FAB correctly identified 78.9% of the patients. These results were maintained in a subgroup of mildly demented patients (MMSE score, > or =24). In these patients, a cutoff score of 12 on the FAB was optimal to differentiate both disorders (sensitivity, 77%; specificity, 87%). The FAB takes less than 10 minutes to administer and provides an objective measure to distinguish FTD from AD in mildly demented patients.
Article
Full-text available
Little is known about the relative benefits of cognitively stimulating activities at different points in the lifespan. In a cohort of 576 older persons without dementia, we assessed current and past (childhood, young adulthood, middle age) frequency of cognitive activity; availability of cognitively stimulating resources in the home in childhood and middle age; and 5 domains of cognitive function. Past cognitive activity and cognitive resources were positively correlated with both current cognitive activity and current cognitive function. The association with cognitive function was reduced after controlling for current cognitive activity, however. Current cognitive activity was associated with better cognitive function, especially semantic memory and perceptual speed, even after controlling for past activity. The results suggest that past cognitive activity contributes to current cognition principally through its association with cognitive activity in old age.
Article
Orthostatic hypotension and cognitive impairment are common in Parkinson's disease (PD) and significantly impair quality of life. Orthostatic hypotension and cognitive impairment appear to be interrelated. Whether the relationship is causative or associative remains unclear. The vascular hypothesis proposes that recurrent episodic hypotension results in cerebral hypoperfusion, in turn causing anoxic damage to vulnerable areas of the brain and impaired cognitive function. Support for this hypothesis has come from brain MRI studies showing an association between white matter hyperintensities and a postural drop in blood pressure among PD patients. Alternatively, the association between orthostatic hypotension and cognitive decline in PD may reflect shared underlying synuclein-related pathology affecting common neuroanatomical and neurochemical substrates. Cardiac imaging studies demonstrate noradrenergic denervation early in PD, and cardiac denervation has been associated with poorer cognition. Neurogenic orthostatic hypotension occurs as a result of defective norepinephrine release from sympathetic terminals upon standing. Neuropathological studies have also demonstrated Lewy body pathology in the locus coeruleus; the main source of noradrenaline in the brain. Locus coeruleus norepinephrine levels are reduced in PD patients with dementia when compared with PD patients without. In this review, we examine the evidence for an association between orthostatic hypotension and cognitive impairment in PD. We evaluate the literature supporting the hypothesis that progressive noradrenergic denervation underlies both orthostatic hypotension and cognitive impairment, and we examine studies suggesting that recurrent cerebral hypoperfusion results in cognitive decline in PD. Finally, we explore how modulation of blood pressure and the noradrenergic nervous system may improve cognition in PD. © 2016 International Parkinson and Movement Disorder Society.
Article
Mild cognitive impairment (MCI) and sleep disturbances are common features in Parkinson disease (PD). This study sought to investigate whether patients with MCI in PD (PD-MCI) have more pronounced sleep disturbance compared to those without PD-MCI and whether phenotypic presentations differ according to the PD-MCI subtypes. A total of 95 patients with idiopathic PD (53 meeting criteria for PD-MCI and 42 who were not cognitively impaired) and 22 controls underwent neurological and neuropsychological examination. They wore actigraphy watches for 2 weeks, from which measures of nocturnal sleep efficiency were calculated. Patients with PD-MCI has significantly poorer sleep efficiency compared to those without PD-MCI. This effect was particularly apparent in those with multiple-domain PD-MCI, compared to those with single-domain PD-MCI. Furthermore, patients in the PD-MCI group had significantly more nontremor features. These data suggest that PD-MCI is associated with greater sleep disturbance and nontremor features of PD. This is further evidence for the potential role that sleep disturbance plays in the heterogeneity of PD.
Article
The Movement Disorder Society (MDS) commissioned a revision of the UPDRS with the goals of improving instructions and definitions, more accurately evaluating milder features, and assessing patient-reported outcomes and nonmotor features. To date, no study has evaluated longitudinal changes in components of the MDS-UPDRS over time or correlated these with changes in other scales of various symptoms. We assessed Parts I and II of the MDS-UPDRS (non-Motor and Motor Experiences of Daily Living [nM-EDL, M-EDL]) as well as a number of other scales of motor, cognitive and behavioral function in a large population of patients (n = 383) with early- to mid-stage Parkinson's disease (PD) who had previously participated in a trial of a putative disease-modifying agent. Both parts of a MDS-UPDRS showed significant change over the 3-year follow-up period, with M-EDL scores declining to a greater extent than nM-EDL. Both the scores and their changes over time correlated relatively well with other rating scales of similar disease aspects. Modest correlations with the original version of the UPDRS supported the increased attention to nonmotor symptoms as well as milder levels of severity in the MDS-UPDRS. The M-EDL was much more sensitive to change over time in these early- to mid-stage patients than the original UPDRS Activities of Daily Living (ADL) scale. Finally, we showed no change over time in a small group of individuals with dopamine transporter single-photon emission computed tomography scans without evidence for dopamine deficiency. The nM-EDL and M-EDL components of the MDS-UPDRS provide an effective, relevant measure of change in the broad spectrum of symptoms of PD over the first decade of the disease. © 2013 International Parkinson and Movement Disorder Society.
Article
The recently proposed Movement Disorder Society (MDS) Task Force diagnostic criteria for mild cognitive impairment in Parkinson's disease (PD-MCI) represent a first step toward a uniform definition of PD-MCI across multiple clinical and research settings. However, several questions regarding specific criteria remain unanswered, including optimal cutoff scores by which to define impairment on neuropsychological tests. Seventy-six non-demented PD patients underwent comprehensive neuropsychological assessment and were classified as PD-MCI or PD with normal cognition (PD-NC). The concordance of PD-MCI diagnosis by MDS Task Force Level II criteria (comprehensive assessment), using a range of standard deviation (SD) cutoff scores, was compared with our consensus diagnosis of PD-MCI or PD-NC. Sensitivity, specificity, and positive and negative predictive values were examined for each cutoff score. PD-MCI subtype classification and distribution of cognitive domains impaired were evaluated. Concordance for PD-MCI diagnosis was greatest for defining impairment on neuropsychological tests using a 2 SD cutoff score below appropriate norms. This cutoff also provided the best discriminatory properties for separating PD-MCI from PD-NC compared with other cutoff scores. With the MDS PD-MCI criteria, multiple domain impairment was more frequent than single domain impairment, with predominant executive function, memory, and visuospatial function deficits. Application of the MDS Task Force PD-MCI Level II diagnostic criteria demonstrates good sensitivity and specificity at a 2 SD cutoff score. The predominance of multiple domain impairment in PD-MCI with the Level II criteria suggests not only influences of testing abnormality requirements, but also the widespread nature of cognitive deficits within PD-MCI. © 2013 Movement Disorder Society.
Article
Executive dysfunction can be present from the early stages of Parkinson's disease (PD). It is characterized by deficits in internal control of attention, set shifting, planning, inhibitory control, dual task performance, and on a range of decision-making and social cognition tasks. Treatment with dopaminergic medication has variable effects on executive deficits, improving some, leaving some unchanged, and worsening others. In this review, we start by defining the specific nature of executive dysfunction in PD and describe suitable neuropsychological tests. We then discuss how executive deficits relate to pathology in specific territories of the basal ganglia, consider the impact of dopaminergic treatment on executive function (EF) in this context, and review the changes in EFs with disease progression. In later sections, we summarize correlates of executive dysfunction in PD with motor performance (e.g., postural instability, freezing of gait) and a variety of psychiatric (e.g., depression, apathy) and other clinical symptoms, and finally discuss the implications of these for the patients' daily life.
Article
Clock drawing is described as a novel, easily administered bedside measure of cognitive function. We examined from 77 ambulant elderly persons meeting NINCDS criteria for Alzheimer's disease their drawings of clock faces and overlapping pentagons. Interrater reliability for two previously published scoring scales for clocks and a devised ordinal scale for overlapping pentagons was high. There was moderate correlation with their total scores on the CAMCOG and Mini Mental State Exam (MMSE). However, a considerable number of patients scored within the normal range on all three drawing scales. A third (23/77) on clock drawing demonstrated their only abnormality at setting the time to 10 to 11 instead of the requested 10 past 11. For the clock drawing test to be used as a rapid screening instrument for Alzheimer's disease in the community an accurately drawn clock face must include the correct position of the hands. The pentagon test either alone or in combination did not enhance the accuracy of the clock test.
Article
Mild cognitive impairment is increasingly recognized as a construct in Parkinson's disease (PD) and occurs in about 25% of nondemented PD patients. Although executive dysfunction is the most frequent type of cognitive deficit in PD, the cognitive phenotype of PD mild cognitive impairment (PD-MCI) is broad. PD-MCI subtypes are represented by amnestic and nonamnestic domain impairment as well as single- and multiple-domain impairment. However, it is unclear whether patients with different PD-MCI subtypes also differ in other clinical characteristics in addition to cognitive profile. We studied 128 PD-MCI subjects at our Movement Disorders center, comparing clinical, motor, and behavioral characteristics across the PD-MCI subtypes. We found varying proportions of impairment subtypes: nonamnestic single domain, 47.7%; amnestic multiple domain, 24.2%; amnestic single domain, 18.8%; and nonamnestic multiple domain, 9.5%. Attentional/executive functioning and visuospatial abilities were the most frequently impaired domains. PD-MCI subtypes differed in their motor features, with nonamnestic multiple-domain PD-MCI subjects showing particularly pronounced problems with postural instability and gait. Differences among PD-MCI subtypes in age, PD duration, medication use, mood or behavioral disturbances, and vascular disease were not significant. Thus, in addition to differing cognitive profiles, PD-MCI subtypes differed in motor phenotype and severity but not in mood, behavioral, or vascular comorbidities. Greater postural instability and gait disturbances in the nonamnestic multiple-domain subtype emphasize shared nondopaminergic neural substrates of gait and cognition in PD. Furthermore, increased burden of cognitive dysfunction, rather than type of cognitive deficit, may be associated with greater motor impairment in PD-MCI.
Article
Mild cognitive impairment is common in nondemented Parkinson's disease (PD) patients and may be a harbinger of dementia. In view of its importance, the Movement Disorder Society commissioned a task force to delineate diagnostic criteria for mild cognitive impairment in PD. The proposed diagnostic criteria are based on a literature review and expert consensus. This article provides guidelines to characterize the clinical syndrome and methods for its diagnosis. The criteria will require validation, and possibly refinement, as additional research improves our understanding of the epidemiology, presentation, neurobiology, assessment, and long-term course of this clinical syndrome. These diagnostic criteria will support future research efforts to identify at the earliest stage those PD patients at increased risk of progressive cognitive decline and dementia who may benefit from clinical interventions at a predementia stage.
Article
The UPDRS has been the main outcome measure in studies of PD. Modifications have been made to improve scale properties and represent the breadth of manifestations of PD, particularly nonmotor symptoms (NMS), resulting in the Movement Disorder Society's revision of the UPDRS (MDS-UPDRS). This study was undertaken to determine the validity of MDS-UPDRS Part I (nonmotor experiences of daily living). The MDS-UPDRS and a number of validated scales for the NMS in PD were used in 94 patients with PD from Hoehn and Yahr stage I to V. We assessed reliability, floor and ceiling effects, and correlations with validated scales for the nonmotor symptoms of PD. MDS-UPDRS Part I showed high internal consistency (Cronbach's alpha: 0.85), small floor and ceiling effects (2% floor and 0% ceiling effect), and good concurrent validity (correlation with the original UPDRS Part I: r = 0.81, P < 0.001). The standardized z-score of the MDS-UPDRS Part I score demonstrated high convergent validity with the composite z-score of nonmotor scales (r = 0.89, P < 0.0001), and the two subscores based on the original factor analysis of Part I also had high correlations with the composite z-scores of corresponding nonmotor scales (depression, anxiety, apathy factor score: r = 0.72, P < 0.0001; other nonmotor features factor score: r = 0.87, P < 0.0001). Our data demonstrate that the MDS-UPDRS Part I total score has a strong relationship with a composite score of validated scales for the nonmotor aspects of PD.
Article
Non-motor symptoms are detrimental to health-related quality of life (HRQoL) of Parkinson's disease patients. In this study, the Non-Motor Symptoms Scale (NMSS) was used to assess the impact of the non-motor symptoms on HRQoL of Parkinson's disease patients. In a multicenter, international, cross sectional study on 411 Parkinson's disease patients, the NMSS was applied along with clinical (Hoehn and Yahr staging and SCOPA-Motor) and HRQoL measures (PDQ-39, and EQ-5D). Prevalence of non-motor symptoms was determined also through the NMSS. The association of NMSS and SCOPA-Motor with HRQoL measures and the differences in HRQoL scores between patients with and without non-motor symptoms in each NMSS domain were estimated by non-parametric statistics. Predictors of HRQoL were sought through multiple linear regression analyses. Nocturia (68.4% of the sample), fatigue (65.9%), and dribbling saliva (56.7%), were the most frequent complaints. Total NMSS score: (1) showed a higher correlation coefficient (r(S) = 0.70) with the PDQ-39 Summary Index (SI) than SCOPA-Motor (r(S) = 0.58); (2) showed high-moderate correlation (r(S) = 0.60 - 0.38) with all PDQ-39 domains; and (3) was the best predictor of HRQoL as measured by the PDQ-39 SI. For each NMSS domain, patients with symptoms had significantly worse HRQoL scores than patients without symptoms. To our knowledge, this is the first study to determine in a holistic manner the impact of the non-motor symptoms on HRQoL of Parkinson's disease patients. The results show that non-motor symptoms have, as a whole, a greater impact on HRQoL than motor symptoms and non-motor symptoms progression contributes importantly to HRQoL decline in patients with Parkinson's disease.
Article
To investigate the frequency and subtypes of mild cognitive impairment (MCI) in idiopathic rapid eye movement sleep behavior disorder (RBD) and Parkinson's disease (PD) in association with RBD. One hundred and twelve subjects without dementia or major depression including 32 idiopathic RBD patients, 22 PD patients with polysomnography-confirmed RBD, 18 PD patients without RBD, and 40 healthy control subjects, underwent a comprehensive neuropsychological evaluation. We compared the proportion of patients with MCI between groups using standard diagnostic criteria. MCI was found in 50% of idiopathic RBD patients and 73% of PD patients with RBD. In contrast, only 11% of PD patients without RBD and 8% of control subjects had MCI. The presence of MCI was significantly greater in idiopathic RBD patients and PD patients with RBD than in PD patients without RBD and control subjects. PD patients with RBD also performed worse than idiopathic RBD patients on neuropsychological tests assessing visuoconstructional and visuoperceptual abilities. In both its association with PD and its idiopathic form, RBD is an important risk factor for MCI. Except for visuoconstructional and visuoperceptual problems, RBD may be an important determinant of cognitive impairment in PD. Ann Neurol 2009;66:39-47.
Article
We present a clinimetric assessment of the Movement Disorder Society (MDS)-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS). The MDS-UDPRS Task Force revised and expanded the UPDRS using recommendations from a published critique. The MDS-UPDRS has four parts, namely, I: Non-motor Experiences of Daily Living; II: Motor Experiences of Daily Living; III: Motor Examination; IV: Motor Complications. Twenty questions are completed by the patient/caregiver. Item-specific instructions and an appendix of complementary additional scales are provided. Movement disorder specialists and study coordinators administered the UPDRS (55 items) and MDS-UPDRS (65 items) to 877 English speaking (78% non-Latino Caucasian) patients with Parkinson's disease from 39 sites. We compared the two scales using correlative techniques and factor analysis. The MDS-UPDRS showed high internal consistency (Cronbach's alpha = 0.79-0.93 across parts) and correlated with the original UPDRS (rho = 0.96). MDS-UPDRS across-part correlations ranged from 0.22 to 0.66. Reliable factor structures for each part were obtained (comparative fit index > 0.90 for each part), which support the use of sum scores for each part in preference to a total score of all parts. The combined clinimetric results of this study support the validity of the MDS-UPDRS for rating PD.
Article
The authors examined a consecutive series of 50 patients for the presence of apathy, depression, anxiety, and neuropsychological deficits using a neuropsychological battery that included a recently designed apathy scale. This scale was found to be reliable and valid in the diagnosis of apathy in patients with PD. Of patients in the study, 12% showed apathy as their primary psychiatric problem, and 30% were both apathetic and depressed. Patients with apathy (with or without depression), showed significantly more deficits in both tasks of verbal memory and time-dependent tasks. Results suggest that apathy is a frequent finding in PD, is significantly associated with specific cognitive impairments, and may have a different mechanism than depression.
Article
The clinical details of 100 cases of histologically confirmed Parkinson's disease were examined and correlated with pathologic findings. Age at disease onset (mean, 62.4 years), disease duration (mean, 13.1 years), and age at death (mean, 75.5 years) were similar to those in previous smaller series. Asymmetric, tremulous onset was most common, although 23% of patients had no rest tremor. Motor fluctuations and dyskinesias occurred in 60% of levodopa-treated patients. All patients had clinical parkinsonism; however, 12 had atypical clinical features of Parkinson's disease, including severe early dementia, fluctuating confusional states, no response to levodopa, and early marked autonomic disturbance. Neuropathologic examination found coexistent Alzheimer-type change in 17 cases and striatal abnormality--mainly vascular--in 34 cases. Cortical Lewy bodies were present in all cases, but only four satisfied proposed criteria for diffuse Lewy body disease. Dementia occurred in 44% of cases; 29% had Alzheimer's disease, 10% had numerous cortical Lewy bodies, and 6% had a possible vascular cause; in 55% no definite pathologic cause was found. Nigral cell loss correlated with disease duration and severity. Although the general pattern of disease conformed to traditional descriptions, the findings broaden the present clinical and pathologic spectrum of Parkinson's disease.
Article
To assess apathy in patients with Parkinson's disease and its relation to disability, mood, personality, and cognition. Levels of apathy in 45 patients with Parkinson's disease were compared with a group of 17 similarly disabled patients with osteoarthritis. Additional neuropsychiatric data were collected concerning levels of depression, anxiety, and hedonic tone. Personality was assessed with the tridimensional personality questionnaire. Cognitive testing included the mini-mental state examination, the Cambridge examination of cognition in the elderly, and specific tests of executive functioning. Patients with Parkinson's disease had significantly higher levels of apathy than equally disabled osteoarthritic patients. Furthermore, within the Parkinson sample, levels of apathy appear to be unrelated to disease progression. The patients with Parkinson's disease with the highest levels of apathy where not more likely to be depressed or anxious than those with the lowest levels of apathy, though they did show reduced hedonic tone. No differences in personality traits were detected in comparisons between patients with Parkinson's disease and osteoarthritis, or between patients in the Parkinson group with high or low levels of apathy. As a group, the patients with Parkinson's disease tended not to differ significantly from the osteoarthritic group in terms of cognitive skills. However, within the Parkinson's disease sample, the high apathy patients performed significantly below the level of the low apathy patients. This was particularly evident on tests of executive functioning. Apathy in Parkinson's disease is more likely to be a direct consequence of disease related physiological changes than a psychological reaction or adaptation to disability. Apathy in Parkinson's disease can be distinguished from other psychiatric symptoms and personality features that are associated with the disease, and it is closely associated with cognitive impairment. These findings point to a possible role of cognitive mechanisms in the expression of apathy.
Article
Visual hallucinations (VH) in Parkinson's disease (PD) are a chronic complication in 30 to 60% of treated patients and have a multifaceted phenomenology. Flickering, faultive impressions, and illusionary misperceptions precede the core syndrome of stereotyped, colorful images. The patient variably recognizes these images as hallucinations, being rarely irritated or frightened and more often amused as a bystander. Although studies on VH in PD focus on several research domains, no comprehensive, unified theory has been developed to study their pathophysiology. We have adapted Hobson's work on the states of consciousness and propose a model integrating seemingly disparate data on VH. We suggest that VH should be considered as a dysregulation of the gating and filtering of external perception and internal image production. Contributive elements and anatomical links for the model include poor primary vision, reduced activation of primary visual cortex, aberrant activation of associative visual and frontal cortex, lack of suppression or spontaneous emergence of internally generated imagery through the ponto-geniculo-occipital system, intrusion of rapid eye movement dreaming imagery into wakefulness, errative changes of the brainstem filtering capacities through fluctuating vigilance, and medication-related overactivation of mesolimbic systems. Different etiologies likely produce different phenomenologies and the prognosis may not be uniform. This new conceptual framework permits an anatomical view of VH and suggests new, testable hypotheses regarding their pathophysiology and therapy.
Article
The long-term objective of the Rush Memory and Aging Project is to identify the postmortem indices linking genetic and environmental risk factors to the development of Alzheimer's disease (AD). The overall study design involves a detailed assessment of risk factors for AD in older persons without known dementia who agree to annual clinical evaluation and organ donation at the time of death. In contrast to other clinical-pathologic studies which are conducted on special populations, the Rush Memory and Aging Project enrolled a cohort with much greater diversity in terms of educational attainment, in addition to gender, race, and ethnicity. From September of 1997 through April of 2005, more than 1,000 older persons without known dementia from more than 30 residential facilities across the Chicago metropolitan area agreed to participate. Their mean age was 81 years, about a third had 12 or fewer years of education, a third were men, and about 10% were members of a racial or ethnic minority group. More than 950 already have completed their baseline clinical evaluation.
Article
The clinical diagnosis of Parkinson's disease rests on the identification of the characteristics related to dopamine deficiency that are a consequence of degeneration of the substantia nigra pars compacta. However, non-dopaminergic and non-motor symptoms are sometimes present before diagnosis and almost inevitably emerge with disease progression. Indeed, non-motor symptoms dominate the clinical picture of advanced Parkinson's disease and contribute to severe disability, impaired quality of life, and shortened life expectancy. By contrast with the dopaminergic symptoms of the disease, for which treatment is available, non-motor symptoms are often poorly recognised and inadequately treated. However, attention is now being focused on the recognition and quantitation of non-motor symptoms, which will form the basis of improved treatments. Some non-motor symptoms, including depression, constipation, pain, genitourinary problems, and sleep disorders, can be improved with available treatments. Other non-motor symptoms can be more refractory and need the introduction of novel non-dopaminergic drugs. Inevitably, the development of treatments that can slow or prevent the progression of Parkinson's disease and its multicentric neurodegeneration provides the best hope of curing non-motor symptoms.
Article
The Addenbrooke's Cognitive Examination (ACE) is reported to be a highly sensitive and specific "bedside" test for the diagnosis of dementia, but large pragmatic studies of its use in day-to-day clinical practice are lacking. This study measured diagnostic accuracy of ACE in a large cohort of consecutive patients referred to a dedicated Cognitive Function Clinic. Consecutive new referrals over a 3.5-year period were administered the ACE (n=285). ACE scores and subscores (VLOM ratio) were compared to clinical diagnoses of dementia and dementia subtype, established on the basis of widely accepted diagnostic criteria and at least 12-month follow-up. ACE had good sensitivity, specificity, and positive predictive value for the diagnosis of dementia, with excellent diagnostic accuracy as measured by area under the receiver operating characteristic curve. However, a lower cutoff than that used in the index paper was required for optimum test sensitivity and specificity. ACE VLOM ratio subscore for the differential diagnosis of Alzheimer's disease and frontotemporal dementia proved less accurate. This study suggests that ACE is useful for the diagnosis of dementia in routine clinical practice but that other instruments may be required for the differential diagnosis of the dementia syndrome.
Article
Although cognitive impairment has been identified as a risk factor for visual hallucinations (VHs), more specific neuropsychological deficits underlying such phenomena have not been established. Here, we investigate the link between executive dysfunction and the occurrence of VHs. We evaluated three groups--17 patients with Parkinson's disease (PD) with VHs, 20 patients with PD without VHs and 20 age-matched controls--on a battery of tests previously reported to evaluate executive functions, namely tests of inhibitory ability, short-term memory and working memory. Differences were found on tests of inhibitory ability, for which the patient group with VHs showed impairment when compared with the non-hallucinating group. Patients with PD with VHs have substantially greater impairment of inhibitory ability than patients without VHs. These findings support interactive models of the genesis of visual hallucinations in PD.
Article
To develop a short, practical instrument that is sensitive to the specific cognitive deficits in Parkinson's disease (PD) for comparing groups in research situations and for assessing change in cognitive functioning over time. A literature search was conducted to identify the most frequently affected cognitive domains in PD and to select candidate items for the initial scale. This scale was tested in 85 patients and 75 age-, education-, and sex-matched control subjects. Items that met predefined criteria for data quality, reproducibility, and discriminative properties were included in the final scale. The final scale, the SCOPA-COG (SCales for Outcomes of PArkinson's disease-cognition), consists of 10 items with a maximum score of 43, with higher scores reflecting better performance. The test-retest reliability of the total score was 0.78 (intraclass correlation coefficient) and ranged from 0.40 to 0.75 for individual items (weighted kappa). Cronbach's alpha was 0.83. Construct validity of the scale was supported by the expected correlations with the CAMCOG (Cambridge Cognitive Examination) and the Mini-Mental State Examination (MMSE) and by differences found between groups of participants classified by dementia status and between patients grouped by disease severity. The scale showed a clear trend toward lower cognition scores for patients with more advanced PD. The coefficient of variation of the SCOPA-COG was higher than that of the CAMCOG or the MMSE, indicating a better ability to detect differences between individuals. The SCOPA-COG is a short, reliable, and valid instrument that is sensitive to the specific cognitive deficits in PD.
Psychological Assessment Resources
  • F L Lutz
Lutz, FL: Psychological Assessment Resources; 2001.
Multilingual Aphasia Examination
  • A L Benton
  • K Hamsher
  • G L Rey
  • A B Sivan
Benton AL, Hamsher K, Rey GL, Sivan AB. Multilingual Aphasia Examination (3rd ed. Iowa City, IA: AJA Associates; 1994.
Weschler Adult Intelligence Scale-IV
  • D Weschler
Weschler D. Weschler Adult Intelligence Scale-IV. New York: The Psychological Corporation;
Diagnostic criteria for mild cognitive impairment in
  • I Litvan
  • J G Goldman
  • A I Troster
Litvan I, Goldman JG, Troster AI, et al. Diagnostic criteria for mild cognitive impairment in
Parkinson's disease: Movement Disorder Society Task Force guidelines
Parkinson's disease: Movement Disorder Society Task Force guidelines. Mov Disord 2012; 27: 349-356.
Weschler Adult Intelligence Scale‐IV
  • D. Wecshler
Hopkins Verbal Learning Test–Revised. Administration Manual
  • J Brandt
  • RHB Benedict
Weschler Adult Intelligence Scale-IV. New York: The Psychological Corporation
  • D Wecshler
Wecshler D. Weschler Adult Intelligence Scale-IV. New York: The Psychological Corporation; 2008.