Cognitive and behavioral disorders in Parkinson’s disease: an update. II: behavioral disorders

Patients with Parkinson’s disease (PD) can experience several behavioral symptoms, such as apathy, agitation, hypersexuality, stereotypic movements, pathological gambling, abuse of antiparkinsonian drugs, and REM sleep behavioral disorders. Psychoses and hallucinations, depression and anxiety disorders, and difficulties in recognizing and experiencing emotions also impair behavior and can cause severe psychosocial problems in patients with PD. Symptoms can be present since early stages of the disease, sometimes even before the appearance of classical motor symptoms, likely in relation to dopamine depletion in basal ganglia and/or to dysfunctions of other neurotrasmitter systems, and others can develop later, in some cases in relation to dopaminergic treatment. In this paper, we review recent literature, with particular attention to the last 5 years, on the main behavioral and emotional disturbances described in PD patients as well as the hypothesized neurofunctional substrate of such impairments. Finally, we provide some suggestions on the most suitable instruments to check and assess PD-associated behavioral defects over time.     

Cognitive and behavioral dysfunction in Parkinson’s disease: neurochemical and clinicopathological contributions

The cognitive and behavioral sequelae (i.e., nonmotor profile) of Parkinson's disease (PD), with executive dysfunction and depression being most prominent, have typically been overshadowed due to an emphasis on motor symptomatology. The apparent categorization of PD as a disorder isolated to the dopaminergic system may be a generalization of the disease pathology. Dopamine therapy, used for the treatment of motor symptoms, has not consistently been shown to resolve nonmotor impairments. Research evidence indicates that nondopaminergic neurotransmitter systems (i.e., serotonergic, noradrenergic, & cholinergic) are disrupted in PD and may contribute to cognitive and behavioral dysfunction. Furthermore, Lewy bodies within cortical and subcortical structures can add to the nonmotor profile in PD. Pharmacological interventions for the treatment of cognitive and behavioral impairments associated with PD are few, especially for nondemented patients. The current review of the literature highlights evidence that associates nonmotor dysfunctions with neurochemical and clinicopathological correlates of PD.     

Parkinson’s disease: an update on pathogenesis and treatment

The Parkinson’s disease research field is a rapidly moving one, as many of the relevant processes underlying PD neurodegeneration are being deciphered, enabling novel approaches to treatment to be assessed both in the laboratory and in the clinic. This review aims to highlight the most relevant updates in the PD field, with emphasis on research that may help lead towards an improvement in the treatment of this condition.     

Exploring recollection and familiarity impairments in Parkinson’s disease

There is conflicting evidence on whether patients diagnosed with Parkinson’s disease (PD) have cognitive deficits associated with episodic memory and particularly with recognition memory. The aim of the present study was to explore whether PD patients exhibit deficits in recollection and familiarity, the two processes involved in recognition. A sample of young healthy participants (22) was tested to verify that the experimental tasks were useful estimators of recognition processes. Two further samples—one of elderly controls (16) and one of PD patients (20)—were the main focus of this research. All participants were exposed to an associative recognition test aimed at estimating recollection followed by a two-alternative forced-choice (2AFC) test designed to estimate familiarity. The analyses showed a deficit in associative recognition in PD patients and no difference between elderly controls and PD patients in the 2AFC test. By contrast, young healthy participants were better than elderly controls and PD patients in both components of recognition. Further analyses of results of the 2AFC test indicated that the measure chosen to estimate conceptual familiarity was adequate.     

Cognitive dysfunction and dementia in Parkinson’s disease

Parkinson's disease (PD) is a slowly progressive neurodegenerative disorder mainly characterized by degeneration of dopaminergic neurons in the substantia nigra and the ventral tegmental area, in combination with a varying loss of central noradrenergic (locus coeruleus), cholinergic (nucleus basalis of Meynert) and serotonergic (dorsal raphe nuclei) integrity, leading to a multitude of motor and non-motor behavioral disturbances. Apart from the clinical motor hallmarks, in the early stages of disease, subtle cognitive dysfunction might be seen comprising mainly executive dysfunction, with secondary visuospatial and mnemonic disturbances. In about 20-40% of patients, these problems may eventually proceed to dementia, which constitutes an important risk factor for caregiver distress, decreased quality of life and nursing home placement. Dementia in PD is typically characterized by a progressive dysexecutive syndrome with attentional deficits and fluctuating cognition, often accompanied by psychotic symptoms. It is thought to be the result of a combination of both subcortical and cortical changes. PD-related dopaminergic deficiency in the nucleus caudatus and mesocortical areas (due to degeneration of projections from the substantia nigra and ventral tegmental area) and cholinergic deficiency in the cortex (due to degeneration of ascending projections from the nucleus basalis of Meynert), combined with additional Alzheimer-pathology and cortical Lewy bodies, may greatly contribute to dementia.Current treatment of dementia in PD is based on compensation of the profound cholinergic deficiency. Recent studies with the cholinesterase inhibitors galantamine, donepezil and rivastigmine show promising results in improving cognition and ameliorating psychotic symptoms, which must further be confirmed in randomized controlled trials.     

Cognitive complaints in Parkinson’s disease: its relationship with objective cognitive decline

Cognitive complaint interviews (CCI) have been shown to be useful in the early detection of dementia in elderly people. Surprisingly, CCIs are rarely used in Parkinson’s disease (PD), despite a six-fold higher risk of dementia than in healthy subjects. The present study sought to determine whether a structured CCI could detect cognitive decline in PD. A validated CCI was added to the usual clinical interview for 180 PD patients. Objective cognitive status was assessed by the Mattis dementia rating scale score. The CCIs ability to detect cognitive decline in PD patients was determined using a receiver operating characteristic (ROC) curve. 58 (32.22%) patients had a significant, subjective cognitive complaint (CCI score >3). Of these, 48.27% had objective cognitive decline. Objective cognitive decline was significantly more frequent in the patients with subjective cognitive complaint. However, the ROC curve for discriminating between patients with and without objective cognitive deficits as a function of their subjective cognitive complaint had low sensitivity (0.50, 95% CI: 0.36–0.64) and moderate specificity (0.74, 95% CI: 0.69–0.84). Logistic regression incorporating the main demographical and clinical variables showed that the CCI score’s discriminant power was improved by adding age and the number of years in education to the predictive model. Objective cognitive decline and dementia are more frequent among PD patients reporting a cognitive complaint than among patients not reporting a complaint. However, the CCI does not enable more accurate screening for PD-associated dementia.     

Zonisamide in Parkinson’s disease: a current update

Neurological Sciences - Parkinson’s disease (PD) is a progressive neurodegenerative disease due to the depletion of the neurotransmitter dopamine in basal ganglia. There is a scarcity of...     

Skin function and skin disorders in Parkinson’s disease

Summary. Cutaneous symptoms (seborrhoea and hyperhidrosis) in Parkinson's disease were investigated. In 70 treated patients with Parkinson's disease and 22 control subjects, non-invasive bioengineering methods (sebumetry, corneometry, pH) were carried out on the forehead, sternum and forearm. In addition, concomitant dermatoses and medication were recorded. 18.6% of the patients had seborrhoea on the forehead (>220 μg/cm²), 51.4% showed normal sebum values (100–220 μg/cm²) and 30% a sebostasis (<100 μg/cm²). Males has significantly higher sebum values than females. No relationship between the seborrhoea and the therapy for Morbus Parkinson was found. Patients with hyperhidrosis (n = 36) had significantly lower pH values (p < 0.05) on the forehead than those without hyperhidrosis. 22 patients (31.9%) reported a cold/hot flush and a further 13 (18.8%) had clinical rosacea. Seborrhoea is rare in treated Parkinsonian patients but hyperhidrosis is frequently found. Furthermore, a particular lack of vasostability (flush) appears to be an autonomic dysregulation in the skin related to Morbus Parkinson, which has not been studied to any extent to date. Received April 6, 2000; accepted August 9, 2000     

Profiling cognitive and neuropsychiatric heterogeneity in Parkinson’s disease

BackgroundParkinson’s disease (PD) is a highly heterogeneous disease, in which motor symptom subtypes are often-described. While it is recognized that motor, cognitive and affective neuropsychiatric symptoms negatively influence the patients’ quality of life, it is currently unknown how these symptoms contribute to phenotypic subtypes. The objective of this study was to assess subtypes of motor, cognitive and affective symptoms in PD.MethodsA hierarchical cluster analysis was conducted on clinical data of 226 PD patients screened at the VU University Medical Center using comprehensive assessment of cognitive, affective and motor symptoms. Subsequent linear discriminant analyses were conducted to investigate discriminating constructs between clusters.ResultsThe cluster analysis yielded four clusters: (1) a young-age (59.9 years), mildly affected cluster (N = 86), (2) an old-age (72.3 years) cluster with severe motor and non-motor symptoms (N = 15), (3) a cluster (age 64.7 years) with mild motor symptoms, below-average executive functioning and affective symptoms (N = 46) and (4) a cluster (age 64.8 years) with severe motor symptoms, affective symptoms and below-average verbal memory (N = 79).ConclusionsCluster 1 and 2 seem to represent opposite ends of the PD disease stages. Patients in clusters 3 and 4 had similar age, educational level and disease duration but different symptom profiles – we therefore suggest that these clusters represent different pathways of disease progression, presumably with distinct underlying pathology localization. Future research on the neuropathophysiological characteristics of these two clusters and monitoring of disease progression is required.     

Undetected ophthalmological disorders in Parkinson’s disease

Journal of Neurology - Ophthalmological disorders are common and frequently disabling for people with Parkinson’s disease (PD). However, details on the prevalence, severity and impact of...     

Mild cognitive impairment in Parkinson’s disease

Parkinson’s disease (PD) has initially been described as a clinical syndrome, although its exact definition has changed over the past centuries. The identification of the pathological changes added another level of complexity, with Lewy bodies, synuclein deposits and neuronal loss in the substantia nigra being used alternatively as criteria. A third level of complexity was added with the recognition of genetic mutations resulting in Parkinsonism, sometimes with and sometimes without Lewy bodies or synuclein deposition. Lastly, frequent additional important pre-motor manifestations, particularly depression, anosmia and sleep-associated phenomena have been described. These different points of view on the definition of PD have important implications on the study of the etiology and even the therapy of PD. Cognitive impairment is also an important feature of PD, while the spectrum of deficits ranges from none to severe dementia. The no-man land in-between normal cognition and dementia has been termed mild cognitive impairment in PD. At present, this term lacks heuristic value or clinical utility, and remains a target for scientific research.     

Unaltered emotional experience in Parkinson’s disease: Pupillometry and behavioral evidence

Introduction: Recognizing emotions in others is a pivotal part of socioemotional functioning and plays a central role in social interactions. It has been shown that individuals suffering from Parkinson’s disease (PD) are less accurate at identifying basic emotions such as fear, sadness, and happiness; however, previous studies have predominantly assessed emotion processing using unimodal stimuli (e.g., pictures) that do not reflect the complexity of real-world processing demands. Dynamic, naturalistic stimuli (e.g., movies) have been shown to elicit stronger subjective emotional experiences than unimodal stimuli and can facilitate emotion recognition.

Method: In this experiment, pupil measurements of PD patients and matched healthy controls (HC) were recorded while they watched short film clips. Participants’ task was to identify the emotion elicited by each clip and rate the intensity of their emotional response. We explored (a) how PD affects subjective emotional experience in response to dynamic, ecologically valid film stimuli, and (b) whether there are PD-related changes in pupillary response, which may contribute to the differences in emotion processing reported in the literature.

Results: Behavioral results showed that identification of the felt emotion as well as perceived intensity varies by emotion, but no significant group effect was found. Pupil measurements revealed differences in dilation depending on the emotion evoked by the film clips (happy, tender, sadness, fear, and neutral) for both groups.

Conclusions: Our results suggest that differences in emotional response may be negligible when PD patients and healthy controls are presented with dynamic, ecologically valid emotional stimuli. Given the limited data available on pupil response in PD, this study provides new evidence to suggest that the PD-related deficits in emotion processing reported in the literature may not translate to real-world differences in physiological or subjective emotion processing in early-stage PD patients.     

Recognition and diagnosis of sleep disorders in Parkinson’s disease

Sleep disturbances are among the most frequent and incapacitating non-motor symptoms of Parkinson’s disease (PD), and are increasingly recognized as an important determinant of impaired quality of life. Here we review several recent developments regarding the recognition and diagnosis of sleep disorders in PD. In addition, we provide a practical and easily applicable approach to the diagnostic process as a basis for tailored therapeutic interventions. This includes a stepwise scheme that guides the clinical interview and subsequent ancillary investigations. In this scheme, the various possible sleep disorders are arranged not in order of prevalence, but in a ‘differential diagnostic’ order. We also provide recommendations for the use of sleep registrations such as polysomnography. Furthermore, we point out when a sleep specialist could be consulted to provide additional diagnostic and therapeutic input. This structured approach facilitates early detection of sleep disturbances in PD, so treatment can be initiated promptly.     

Comorbid disorders and hospitalisation in Parkinson’s disease: a prospective study

Abstract. Parkinsons disease (PD) is often associated with other disorders, typical of the disease or of the age of PD patients, that can lead to hospitalisation, sometimes as emergencies. In this one-year prospective, longitudinal study, we investigated the comorbid events prompting the hospitalisation, or occurring during the planned hospitalisation, of an unselected group of 180 PD patients, admitted to 9 general hospitals in the course of the study. The most frequent acute comorbid events were trauma (30.5%), mostly due to falls, and vascular disorders (29.3%). Comorbidities were closely related to PD in 50% of cases. More than 50% of patients did not require (in addition to PD therapy) specific treatment for the acute comorbid event. Older age was associated with increased risk of complications. The setting up of multidisciplinary networks covering entire territories could help to improve the way in which we tackle the clinical and social problems generated by PD and its comorbidities. *Members of the Parkinsons Disease Comorbidity Study Group D. Porazzi, F. Reverberi, Department of Neurology, Hospital of Busto Arsizio; G. Chiodelli, G. Guarneri, Department of Neurology, Hospital of Cremona; M. B. Zappacosta, Department of Neurology, Hospital of Gallarate; G. Mariani, R. Freschi, Department of Neurology, Hospital of Legnano; F. Sasanelli, G. Molini, Department of Neurology, Hospital of Melegnano; F. Schieroni, M. Di Costanzo, Department of Neurology, Hospital of Merate; G. Bargnani, E. Donati, Department of Neurology, Hospital of Rovato; G. Bono, Department of Neurology, Hospital of Varese; E. Magrotti, Department of Neurology, Hospital of Voghera.     

Association between sleep disorders and cognitive dysfunctions in non-demented patients with advanced Parkinson’s disease

Journal of Neurology - Parkinson’s disease (PD) is increasingly recognized as a multidimensional disorder, characterized by several non-motor symptoms, including disturbances of sleep and...     

Impulse control disorders in Parkinson’ disease: the role of personality and cognitive status

This study reviews empirical findings on two debated issues related to the phenomenon of impulse control disorders (ICD) in patients with Parkinson’s disease (PD) treated with dopamine agonists: the role of “premorbid” or “baseline” personality traits and the role of cognitive status. A review of both these issues may help clinicians to understand why only some PD patients, when treated with dopamine agonists, develop an ICD: besides the treatment, which other neuropsychiatric characteristics represent a risk factor to develop an ICD? A literature review was performed on studies of ICD in PD patients, in electronic databases ISI Web of Knowledge, Medline and PsychInfo, conducted in January 2011. In the general population, impulsivity, depression and difficulties with executive functions, especially of inhibitory control, are factors associated with ICD development. As regards cognitive functions, PD patients present executive difficulties, and patients with ICD present more difficulties in comparison to patients without ICD. As regards personality characteristics, PD patients present a trait of negative affect, which could predispose them to affective disorders and could represent an affective risk factor for the development of ICD; as regards impulsivity, preliminary findings support the hypothesis that premorbid “baseline” levels may moderate the decrease of impulsivity because of the progressive dopaminergic deficit in PD patients and therefore also moderate the development of ICD. Longitudinal psychometric and cognitive studies, following PD patients since the clinical diagnosis and during dopaminergic treatment, are needed to confirm the role of personality traits and cognitive status on ICD development in this clinical population.     

Drug-induced impulse control disorders in Parkinson’s disease

Journal of Neurology -     

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.