Executive Dysfunction In Parkinson's Disease Research Articles

Executive dysfunction in Parkinson's disease: From neurochemistry to circuits, genetics and neuroimaging.

Cognitive decline is one of the most significant non-motor symptoms of Parkinson's disease (PD), with executive dysfunction (EDF) being the most prominent characteristic of PD-associated cognitive deficits. Currently, lack of uniformity in the conceptualization and assessment scales for executive functions impedes the early and accurate diagnosis of executive dysfunction in PD. The neurobiological mechanisms of executive dysfunction in PD remain poorly understood. Moreover, the treatment of cognitive impairment in PD has progressed slowly and with limited efficacy. Thus, this review explores the characteristics and potential mechanisms of executive dysfunction in PD from multiple perspectives, including the concept of executive function, commonly used neuropsychological tests, neurobiochemistry, genetics, neuroelectrophysiology and neuroimaging. The available evidence indicates that degeneration of the frontal-striatal circuit, along with mutations in the Catechol-O-methyltransferase (COMT) gene and Leucine-rich repeat kinase 2 (LRRK2) gene, may contribute to executive dysfunction in patients with PD. The increase in theta and delta waves, along with the decrease in alpha waves, offers potential biomarkers for the early identification and monitoring of executive dysfunction, as well as the development of dementia in patients with PD. The PD cognition-related pattern (PDCP) pattern may serve as a tool for monitoring and assessing cognitive function progression in these patients and is anticipated to become a biomarker for cognitive disorders associated with PD. The aim is to provide new insights for the early and precise diagnosis and treatment of executive dysfunction in PD.

Resting-state functional connectivity is modulated by cognitive reserve in early Parkinson's disease.

Fronto-striatal disconnection is thought to be at the basis of dysexecutive symptoms in patients with Parkinson's disease (PD). Multiple reserve-related processes may offer resilience against functional decline. Among these, cognitive reserve (CR) refers to the adaptability of cognitive processes. To test the hypothesis that functional connectivity of pathways associated with executive dysfunction in PD is modulated by CR. Twenty-six PD patients and 24 controls underwent resting-state functional magnetic resonance imaging. Functional connectivity was explored with independent component analysis and seed-based approaches. The following networks were selected from the outcome of the independent component analysis: default-mode (DMN), left and right fronto-parietal (l/rFPN), salience (SalN), sensorimotor (SMN), and occipital visual (OVN). Seed regions were selected in the substantia nigra and in the dorsolateral and ventromedial prefrontal cortex for the assessment of seed-based functional connectivity maps. Educational and occupational attainments were used as CR proxies. Compared with their counterparts with high CR, PD individuals with low CR had reduced posterior DMN functional connectivity in the anterior cingulate and basal ganglia, and bilaterally reduced connectivity in fronto-parietal regions within the networks defined by the dorsolateral and ventrolateral prefrontal seeds. Hyper-connectivity was detected within medial prefrontal regions when comparing low-CR PD with low-CR controls. CR may exert a modulatory effect on functional connectivity in basal ganglia and executive-attentional fronto-parietal networks. In PD patients with low CR, attentional control networks seem to be downregulated, whereas higher recruitment of medial frontal regions suggests compensation via an upregulation mechanism. This upregulation might contribute to maintaining efficient cognitive functioning when posterior cortical function is progressively reduced.

Frontal Executive Function Assessment in Patients with Parkinson Disease Using Frontal Assessment Battery (FAB) at a Tertiary Care Center in Western India

Background: Cognitive impairment in Parkinson disease (PD) primarily consists of executive dysfunction. Frontal Assessment Battery (FAB), composed of six subsets to explore different functions related to the frontal lobe is a validated and easily performed tool for executive function assessment. Aims and Objectives: We performed this study to evaluate the clinical utility of the FAB for the assessment of executive dysfunction in PD and to study the correlation of FAB with other tests of executive functions such as fluency tests (lexical and semantic) and trail making tests (TMT A and B) in a group of Indian patients with PD. Material and Methods: We included 60 patients diagnosed with PD per the UK PD Brain Bank criteria. Our study included 40 healthy age, sex, and education-matched controls. We recorded clinical characteristics of patients [age, sex, disease duration, Hoehn and Yahr stage, and Unified Parkinson disease Rating Scale (UPDRS) scores] and Mini-Mental State Examination (MMSE) and FAB scores of both patients and controls in a prescribed pro forma. Results: In the study group, mean age was 52.53 ± 10.42 years, mean disease duration was 5.77 ± 3.27 years, mean MMSE was 28.4 ± 1.53, and mean FAB was 11.53 ± 2.30, and they had significantly decreased mean FAB scores as compared to controls. FAB scores also correlated significantly with age, disease duration, Hoehn and Yahr stage, UPDRS score, MMSE, fluency tests, and TMT. Conclusion: FAB is an easily performed bedside screening test for executive function assessment in PD, and it can be used to detect early and subtle cognitive impairments in PD.

Sleep alterations are related to cognitive symptoms in Parkinson's disease: A 24-hour ambulatory polygraphic EEG study

BackgroundSleep disorders are frequent and early non-motor symptoms of Parkinson's disease (PD). As a consequence of histopathological changes, the regulation of rapid eye movement (REM) sleep is affected in PD causing REM sleep behaviour disorder in about half of the patients. Considering the well-known role of sleep in memory formation processes, our aim was to investigate the relationship between sleep alterations and cognitive performance to elucidate the possible association between sleep, and especially REM sleep changes and cognitive dysfunction in PD. MethodsWe investigated 25 PD patients and 20 healthy controls. All participants underwent a 24-hour-long 19-channel polygraphic EEG recording, neurological, neuroimaging and neuropsychological examination. The visually analysed sleep-EEG and neuropsychological data were statistically evaluated. ResultsThe intergroup analysis showed significant decrease of REM and N3, but increase of N2 sleep ratio, and significantly lower scores in the verbal fluency in PD compared to healthy controls. While we found significant negative correlation between verbal fluency and REM-sleep in the whole sample, we observed a marginal significant correlation between phonemic fluency and REM sleep in the PD group. ConclusionThe negative correlation between verbal fluency performance and REM sleep duration suggests the role of decreased REM sleep in cognitive dysfunction in PD. The early involvement of REM sleep regulation with parallel executive dysfunction in PD emphasise the important role of REM sleep deterioration in the neurodegenerative process of PD.

Imaging executive functions in Parkinson's disease: An activation likelihood estimation meta-analysis

IntroductionExecutive dysfunction is a common and early cognitive symptom in Parkinson's disease (PD) with a detrimental effect on quality of life of patients and their care givers. Thus, a number of neuroimaging studies investigated the underlying neural correlates of such an impairment. Results of individual studies, however, are not univocal in terms of location and directionality of associated functional brain changes. ObjectiveTo assess convergence of abnormal brain activation in patients with PD during the performance of tasks probing executive functions (EF). MethodsWe screened the functional imaging literature on EF in PD using the PubMed database, extracted reported stereotactic data and tested for convergence of deviant neural activation in patients with PD when compared to healthy controls (HC) using a coordinate-based activation likelihood estimation approach. ResultsWe identified 22 eligible papers from which the main proportion was targeted at the investigation of working memory encompassing 354 patients and 306 HC. Surprisingly, no significant converging aberrant activation between HC and patients (ON, OFF or ON + OFF medication, respectively) could be observed when controlling for multiple comparisons using family-wise error correction on cluster-level. ConclusionWe conclude that there is currently not enough available evidence to pinpoint a specific neural correlate associated with executive dysfunction in PD. This might be due to the small number of studies performed and their methodical inconsistency. Therefore, it is important to conduct more research regarding functional brain changes associated with EF in these patients using more consistent frameworks and bigger samples.

Apolipoprotein Eε4: A Biomarker for Executive Dysfunction among Parkinson's Disease Patients with Mild Cognitive Impairment.

Background: Cognitive impairment is prevalent in Parkinson's disease (PD), affecting 15–20% of patients at diagnosis. α-synuclein expression and genetic polymorphisms of Apolipoprotein E (ApoE) have been associated with the presence of cognitive impairment in PD although data have been inconsistent.Objectives: To determine the prevalence of cognitive impairment in patients with PD using Montreal Cognitive Assessment (MoCA), Comprehensive Trail Making Test (CTMT) and Parkinson's disease-cognitive rating scale (PDCRS), and its association with plasma α-synuclein and ApoE genetic polymorphisms.Methods: This was across-sectional study involving 46 PD patients. Patients were evaluated using Montreal cognitive assessment test (MoCA), and detailed neuropsychological tests. The Parkinson's disease cognitive rating scale (PDCRS) was used for cognitive function and comprehensive trail making test (CTMT) for executive function. Blood was drawn for plasma α-synuclein measurements and ApoE genetic analysis. ApoE polymorphism was detected using MutaGELAPoE from ImmunDiagnostik. Plasma α-synuclein was detected using the ELISA Technique (USCN Life Science Inc.) according to the standard protocol.Results: Based on MoCA, 26 (56.5%) patients had mild cognitive impairment (PD-MCI) and 20 (43.5%) had normal cognition (PD-NC). Based on the PDCRS, 18 (39.1%) had normal cognition (PDCRS-NC), 17 (37%) had mild cognitive impairment (PDCRS-MCI), and 11 (23.9%) had dementia (PDCRS-PDD). In the PDCRS-MCI group, 5 (25%) patients were from PD-NC group and all PDCRS-PDD patients were from PD-MCI group. CTMT scores were significantly different between patients with MCI and normal cognition on MoCA (p = 0.003). Twenty one patients (72.4%) with executive dysfunction were from the PD-MCI group; 17 (77.3%) with severe executive dysfunction and 4 (57.1%) had mild to moderate executive dysfunction. There were no differences in the plasma α-synuclein concentration between the presence or types of cognitive impairment based on MoCA, PDCRS, and CTMT. TheApoEe4 allele carrier frequency was significantly higher in patients with executive dysfunction (p = 0.014).Conclusion: MCI was prevalent in our PD population. PDCRS appeared to be more discriminatory in detecting MCI and PDD than MoCA. Plasma α-synuclein level was not associated with presence nor type of cognitive impairment, but the ApoEe4 allele carrier status was significantly associated with executive dysfunction in PD.

Contrast Sensitivity and Executive Dysfunction in Parkinson Disease and Healthy Older Adults (P6.012)

Contrast Sensitivity and Executive Dysfunction in Parkinson Disease and Healthy Older Adults (P6.012)

Associative reinstatement memory measures hippocampal function in Parkinson's Disease

In Parkinson's Disease (PD), hippocampal atrophy is associated with rapid cognitive decline. Hippocampal function is typically assessed using memory tests but current clinical tools (e.g., free recall) also rely on executive functions or use material that is not optimally engaging hippocampal memory networks. Because of the ubiquity of executive dysfunction in PD, our ability to detect true memory deficits is suboptimal. Our previous behavioural and neuroimaging work in other populations suggests that an experimental memory task – Associative Reinstatement Memory (ARM) – may prove useful in investigating hippocampal function in PD. In this study, we investigated whether ARM is compromised in PD and we assessed its convergent and divergent validity by comparing it to standardized measures of memory and of attention and executive functioning in PD, respectively. Using fMRI, we also investigated whether performance in PD relates to degree of hippocampal engagement. Fifteen participants with PD and 13 age-matched healthy controls completed neuropsychological testing as well as an ARM fMRI recognition paradigm in which they were instructed to identify word pairs comprised of two studied words (intact or rearranged pairs) and those containing at least one new word (new or half new pairs). ARM is measured by the differences in hit rates between intact and rearranged pairs. Behaviourally, ARM was poorer in PD relative to controls and was correlated with verbal memory measures, but not with attention or executive functioning in the PD group. Hippocampal activation associated with ARM was reduced in PD relative to controls and covaried with ARM scores in both groups. To conclude, ARM is a sensitive measure of hippocampal memory function that is unaffected by attention or executive dysfunction in PD. Our study highlights the benefit of integrating cognitive neuroscience frameworks and novel experimental tasks to improve the practice of clinical neuropsychology in PD.

Functional Connectivity Differences of the Subthalamic Nucleus Related to Parkinson's Disease.

A typical feature of Parkinson's disease (PD) is pathological activity in the subthalamic nucleus (STN). Here, we tested whether in patients with PD under dopaminergic treatment functional connectivity of the STN differs from healthy controls (HC) and whether some brain regions show (anti-) correlations between functional connectivity with STN and motor symptoms. We used functional magnetic resonance imaging to investigate whole-brain resting-state functional connectivity with STN in 54 patients with PD and 55 HC matched for age, gender, and within-scanner motion. Compared to HC, we found attenuated negative STN-coupling with Crus I of the right cerebellum and with right ventromedial prefrontal regions in patients with PD. Furthermore, we observed enhanced negative STN-coupling with bilateral intraparietal sulcus/superior parietal cortex, right sensorimotor, right premotor, and left visual cortex compared to HC. Finally, we found a decline in positive STN-coupling with the left insula related to severity of motor symptoms and a decline of inter-hemispheric functional connectivity between left and right STN with progression of PD-related motor symptoms. Motor symptom related uncoupling of the insula, a key region in the saliency network and for executive function, from the STN might be associated with well-known executive dysfunction in PD. Moreover, uncoupling between insula and STN might also induce an insufficient setting of thresholds for the discrimination between relevant and irrelevant salient environmental stimuli, explaining observations of disturbed response control in PD. In sum, motor symptoms in PD are associated with a reduced coupling between STN and a key region for executive function.

Cognitive executive impairment and dopaminergic deficits in de novo Parkinson's disease.

Cognitive impairment in Parkinson's disease (PD) is common and does directly impact patients' everyday functioning. However, the underlying mechanisms of early cognitive decline are not known. This study explored the association between striatal dopaminergic deficits and cognitive impairment within a large cohort of early, drug-naïve PD patients and tested the hypothesis that executive dysfunction in PD is associated with striatal dopaminergic depletion. A cross-sectional multicenter cohort of 339 PD patients and 158 healthy controls from the Parkinson's Progression Markers Initiative study was analyzed. Each individual underwent cerebral single-photon emission CT (SPECT) and a standardized neuropsychological assessment with tests of memory as well as visuospatial and executive function. SPECT imaging was performed with [(123) I]FP-CIT, and specific binding ratios in left and right putamen and caudate nucleus were calculated. The association between specific binding ratios, cognitive domain scores, and age was analyzed using Pearson's correlations, partial correlation, and conditional process analysis. A small, but significant, positive association between total striatal dopamine transporter binding and the attention/executive domain was found (r = 0.141; P = 0.009) in PD, but this was not significant after adjusting for age. However, in a moderated mediation model, we found that cognitive executive differences between controls and patients with PD were mediated by an age-moderated striatal dopaminergic deficit. Our findings support the hypothesis that nigrostriatal dopaminergic deficit is associated with executive impairment, but not to memory or visuospatial impairment, in early PD.

Executive dysfunction in Parkinson's disease: A review

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.

Neuroimaging of brain changes associated with cognitive impairment in Parkinson's disease

Cognitive impairment occurs frequently in Parkinson's disease (PD) and the concept of Mild Cognitive Impairment in PD (PD-MCI) has recently emerged. Patients with mild impairment are at risk of developing dementia, and thus it is a topic of growing interest. Many previous studies have investigated the neural correlates of cognitive impairment, in particular executive dysfunction, in PD patients without dementia using neuroimaging techniques including structural MRI, functional MRI and PET imaging. These studies, which have provided a foundation for understanding which brain regions and neurotransmitter systems may be involved in executive dysfunction in PD, will be reviewed. Recent neuroimaging studies that have used specific criteria to classify patients as PD-MCI, in the hopes of gaining further insight into the underlying neural mechanisms will also be discussed. In particular, this review will cover key findings involving structural MRI investigating grey and white matter changes, functional MRI to examine changes in neural activation and PET imaging to investigate metabolic and neurochemical changes that have led to an improved understanding of pathology associated with executive dysfunction in PD without dementia and PD-MCI.

Everyday Executive Function is Associated with Activity Participation in Parkinson Disease without Dementia

Individuals with Parkinson disease (PD) who do not have dementia reliably demonstrate mild executive deficits on laboratory-based tests, but the impact of these deficits on occupational performance is unclear. The purpose of this study was to determine the relevance of executive dysfunction in PD without dementia to instrumental, leisure, and social activity participation. Twenty-four individuals with PD and 30 matched adult volunteers performed an experimental working memory test and rated their everyday executive function and activity participation. Participants with PD had worse working memory performance, tended to report more everyday executive problems, and reported lower activity participation compared to controls. Within PD, lower everyday executive function was associated with reduced activity participation after controlling for motor dysfunction and depressive symptoms. Executive function is an independent predictor of complex activity participation in early PD. These results suggest the need for occupational therapists to consider executive dysfunction during evaluation and treatment of individuals with PD.

Interaction of caudate dopamine depletion and brain metabolic changes with cognitive dysfunction in early Parkinson's disease

Damage to nonmotor dopamine (DA)-mediated frontostriatal circuits has been proposed as the main pathophysiological basis of cognitive dysfunction in Parkinson's disease (PD). In the present study, 18 early nondemented drug naive PD patients were investigated, by dual-tracer N-ω-fluoropropyl-2β-carbomethoxy-3β-4-[123I]iodophenyl-nortropane ([123I]FP-CIT) single-photon emission computed tomography (SPECT)/[18F] fluoro-deoxyglucose (FDG) positron emission tomography (PET) imaging, to test whether an early and not yet treatment-modulated relation exists between cognitive functions, caudate nucleus (CN) DA impairment and brain metabolism (CMRglc) in associative frontostriatal circuits. Verbal fluency performance correlated with DA impairment in CN, and with CMRglc in dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC). Further, CMRglc in orbitofrontal cortex, DLPFC, and ACC was shown to be early modulated by the level of DA impairment in CN. The present study demonstrates in vivo the early functional disruption of nonmotor frontostriatal circuits in PD. The effect of CN DA impairment on DLPFC and ACC metabolism is proposed as a possible early pathophysiological and functional substrate for executive dysfunction in PD.

Quantitative EEG Analysis of Executive Dysfunction in Parkinson Disease

Quantitative EEG evaluation in Parkinson disease (PD) reveals diffuse slowing. This is the first quantitative EEG evaluation of the differences between PD with and without executive dysfunction (ExD). The subjects were 32 PD patients without remarkable dementia. The lack of ischemic lesions was confirmed by magnetic resonance imaging. ExD was defined as <70 points on the age-controlled standardized score of the Behavioral Assessment of the Dysexecutive Syndrome. Absolute power was measured for four frequency bands from delta to beta. Electrodes were placed at frontal pole, frontal, central, parietal, occipital, and temporal locations. Spectral ratio was calculated as the sum of power values for alpha and beta waves divided by the sum of values for the slow waves. In multiple logistic regression analysis of each electrode location, the dependent variable was ExD or not, and the independent variables were spectral ratio, age, and Unified Parkinson Disease Rating Scale. The only significant predictor of ExD was spectral ratio at the frontal pole (P = 0.031) and frontal (P = 0.048) locations. PD with ExD exhibited an increase in slow wave activity and a decrease in alpha and fast wave activities in these locations. These findings indicated that the ExD in PD was caused by frontal dysfunction.

Executive control and deep brain stimulation of the subthalamic nucleus: Inhibition and task switching in the Stroop test

Event Abstract Back to Event Executive control and deep brain stimulation of the subthalamic nucleus: Inhibition and task switching in the Stroop test A. Ahmed1, S. C. Cooper1, M. Deogaonkar1, D. Floden1*, I. Itin1, C. S. Kubu1 and A. Machado1 1 Cleveland Clinic Foundation, Center for Neurological Restoration, United States The subthalamic nucleus (STN) is a common surgical target in deep brain stimulation (DBS) treatment for the motor symptoms of Parkinson disease. Recent work [1] suggests that the right STN is part of a frontal-subcortical network involved in cognitive inhibition. If so, stimulation of the right STN would be expected to impact cognitive control. We examined performance on the Stroop test in 83 non-demented Parkinson patients. The Stroop test requires inhibition of prepotent responses and this version incorporates control and task switching conditions. Patients completed this measure during pre-surgical DBS evaluations (N=62) or six-month postoperative evaluations after left (9 patients) or bilateral (12 patients) STN DBS. Bilateral patients were younger and this was entered as a covariate into the analyses. The groups did not differ on other demographic or disease variables. Patients with bilateral STN electrodes were comparatively slower and/or error prone on inhibition, switching, and colour naming conditions. There was also a trend toward improved switching performance in the left group. The results are discussed in terms of a putative right-STN role in inhibition, and consequences of DBS for treatment of executive dysfunction in Parkinson disease are considered.

The Frontal Assessment Battery (FAB) in Parkinson’s disease and correlations with formal measures of executive functioning

The Frontal Assessment Battery (FAB) is a short tool for the assessment of executive functions consisting of six subtests that explore different abilities related to the frontal lobes. Several studies have indicated that executive dysfunction is the main neuropsychological feature in Parkinson's disease (PD). To evaluate the clinical usefulness of the FAB in identifying executive dysfunction in PD; to determine if FAB scores in PD are correlated with formal measures of executive functions; and to provide normative data for the Portuguese version of the FAB. The study involved 122 healthy participants and 50 idiopathic PD patients. We compared FAB scores in normal controls and in PD patients matched for age, education and Mini-Mental State Examination (MMSE) score. In PD patients, FAB results were compared to the performance on tests of executive functioning. In the healthy subjects, FAB scores varied as a function of age, education and MMSE. In PD, FAB scores were significantly decreased compared to normal controls, and correlated with measures of executive functions such as phonemic and semantic verbal fluency tests, Wisconsin Card Sorting Test and Trail Making Test Part A and Part B. The FAB is a useful tool for the screening of executive dysfunction in PD, showing good discriminant and concurrent validities. Normative data provided for the Portuguese version of this test improve the accuracy and confidence in the clinical use of the FAB.

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

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

An Examination of Executive Dysfunction Associated with Frontostriatal Circuitry in Parkinson's Disease

Parkinson's disease (PD) is a neurodegenerative movement disorder presenting with subcortical pathology and characterized by motor deficits. However, as is frequently reported in the literature, patients with PD can also exhibit cognitive and behavioral (i.e., nonmotor) impairments, cognitive executive deficits and depression being the most prominent. Considerable attention has addressed the role that disruption to frontostriatal circuitry can play in mediating nonmotor dysfunction in PD. The three nonmotor frontostriatal circuits, which connect frontal cortical regions to the basal ganglia, originate from the dorsolateral prefrontal cortex (DLPFC), anterior cingulate cortex (ACC), and orbitofrontal cortex (OFC). The objective of the current study was to use our understanding of frontostriatal circuit function (via literature review) to categorize neuropsychological measures of cognitive and behavioral executive functions by circuit. To our knowledge, such an approach has not been previously attempted in the study of executive dysfunction in PD. Neuropsychological measures of executive functions and self-report behavioral inventories, categorized by circuit function, were administered to 32 nondemented patients with Parkinson's disease (NDPD) and to 29 demographically matched, healthy normal control participants (NC). Our findings revealed significant group differences for each circuit, with the PD group performing worse than the NC group. Among the patients with PD, indices of impairment were greater for tasks associated with DLPFC function than with OFC function. Further, only an index of DLPFC test performance was demonstrated to significantly discriminate individuals with and without PD. In conclusion, our findings suggest that nondemented patients with PD exhibit greater impairment on neuropsychological measures associated with DLPFC than with ACC or OFC circuit function.

Efficacy and Safety of Donepezil in the Treatment of Executive Dysfunction in Parkinson Disease

Cognitive disturbances in Parkinson's disease (PD) are dominated by troubles in executive functions which affects to a vast majority of parkinsonian patients since the onset of the disease. A common clinical observation is that parkinsonian patients, who eventually develop dementia, exhibit subtle cognitive disturbances quite earlier. The main biochemical substrate of cognitive dysfunction in PD, even of the early dysexecutive syndrome, might be a cholinergic deficiency. The aim of this pilot study was to determine the efficacy and safety of donepezil in the treatment of 10 patients with PD and dysexecutive alterations without dementia. All the items of the Clinical Global Impression were significantly improved. An improvement on both the modified Wisconsin Card Sorting Test and DIGIT Span was found. Parkinsonism remained unchanged during the study. Only 1 out of 10 patients experienced transient and mild gastrointestinal side effects. This study suggests that donepezil may be useful in the treatment of the dysexecutive syndrome associated with PD.