Long-Term Results of Cortical Motor Stimulation for Neuropathic Peripheral and Central Pain: Real-World Evidence From Two Independent Centers.

BACKGROUND AND OBJECTIVES: Cortical motor stimulation (CMS) is used to modulate neuropathic pain. The literature supports its use; however, short follow-up studies might overestimate its real effect. This study brings real-world evidence from two independent centers about CMS methodology and its long-term outcomes. METHODS: Patients with chronic refractory neuropathic pain were implanted with CMS. The International Classification of Headache Disorders 3rd Edition was used to classify craniofacial pain and the Douleur Neuropathique en 4 Questions Scale score to explore its neuropathic nature. Demographics and clinical and surgical data were collected. Pain intensity at 6, 12, and 24 months and last follow-up was registered. Numeric rating scale reduction of ≥50% was considered a good response. The Clinical Global Impression of Change scale was used to report patient satisfaction. RESULTS: Twelve males (38.7%) and 19 females (61.3%) with a mean age of 55.8 years (±11.9) were analyzed. Nineteen (61.5%) were diagnosed from painful trigeminal neuropathy (PTN), and seven (22.5%) from central poststroke pain. The mean follow-up was 51 months (±23). At 6 months, 42% (13/31) of the patients were responders, all of them being PTN (13/19; 68.4%). At last follow-up, only 35% (11/31) remained responders (11/19 PTN; 58%). At last follow-up, the global Numeric rating scale reduction was 34% ( P = .0001). The Clinical Global Impression of Change scale punctuated 2.39 (±0.94) after 3 months from the surgery and 2.95 (±1.32) at last follow-up ( P = .0079). Signs of suspicious placebo effect were appreciated in around 40% of the nonresponders. CONCLUSION: CMS might show long-term efficacy for neuropathic pain syndromes, with the effect on PTN being more robust in the long term. Multicentric clinical trials are needed to confirm the efficacy of this therapy for this and other conditions.

Background Music and Memory in Mild Cognitive Impairment: The Role of Interindividual Differences.

BACKGROUND: Recent research has shown that background music may improve memory consolidation and retrieval. Nevertheless, in the clinical conditions preceding dementia such as mild cognitive impairment (MCI), there is no current evidence speaking to what effect background music during memory tasks has on impaired cognition. OBJECTIVE: Across three experiments, we investigated if background music is able to improve memory performance, the most impacted cognitive domain in amnestic MCI. METHODS: We tested the effect of background music by using a face recognition memory task in patients with amnestic MCI. In Experiment 1, we tested the effect of background music on memory when it was played solely during an encoding phase. In Experiment 2, we explored effects of background music when played during both encoding and recognition phases. In Experiment 3, we explored the role of musically induced arousal on memory. RESULTS: The main finding from these three experiments was that background music played during a memory task did not improve or worsen participant performance. However, when exposed to high-arousal music, memory performance was predicted by individual mood regulation. For low-arousal music conditions, there was a negative relationship between rating scores for music pleasantness and performance on the memory task. CONCLUSION: Our results suggest that the benefits of background music on memory in individuals with MCI are modulated by interindividual preferences towards music.

Functional changes in prefrontal cortex following frequency-specific training.

Numerous studies indicate a significant role of pre-frontal circuits (PFC) connectivity involving attentional and reward neural networks within attention deficit hyperactivity disorder (ADHD) pathophysiology. To date, the neural mechanisms underlying the utility of non-invasive frequency-specific training systems in ADHD remediation remain underexplored. To address this issue, we created a portable electroencephalography (EEG)-based wireless system consisting of a novel headset, electrodes, and neuro program, named frequency specific cognitive training (FSCT). In a double-blind, randomized, controlled study we investigated the training effects in N = 46 school-age children ages 6-18 years with ADHD. 23 children in experimental group who underwent FCST training showed an increase in scholastic performance and meliorated their performance on neuropsychological tests associated with executive functions and memory. Their results were compared to 23 age-matched participants who underwent training with placebo (pFSCT). Electroencephalogram (EEG) data collected from participants trained with FSCT showed a significant increase in 14-18 Hz EEG frequencies in PFC brain regions, activities that indicated brain activation in frontal brain regions, the caudate nucleus, and putamen. These results demonstrate that FSCT targets specific prefrontal and striatal areas in children with ADHD, suggesting a beneficial modality for non-invasive modulation of brain areas implicated in attention and executive functions.

Post-COVID-19 fatigue: the contribution of cognitive and neuropsychiatric symptoms.

Fatigue in its many forms of physical, mental, and psychosocial exhaustion is a common symptom of post-COVID-19 condition, also known as "Long COVID." Persistent fatigue in COVID-19 patients is frequently accompanied by cognitive dysfunction and neuropsychiatric symptoms; however, less is known about the relationships between these components of post-COVID-19 condition and fatigue itself. Consequently, the present study sought to (1) distinguish the types of fatigue experienced by participants, and (2) investigate whether cognitive deficits across various domains and neuropsychiatric conditions predicted these different types of fatigue. The study included 136 COVID-19 patients referred for neuropsychological evaluation due to cognitive complaints 8 months on average after SARS-CoV-2 infection. Measures included self-reported fatigue (physical, cognitive, and psychosocial), neuropsychiatric questionnaires (assessing symptoms of depression, anxiety, apathy, and executive functioning), a comprehensive neuropsychological assessment, and self-reported quality of life and everyday functioning. Results showed that reports of clinical significant fatigue were pervasive in our sample (82.3% of participants), with physical fatigue rated highest on average relative to the subscale maximum. Elevated levels of apathy, anxiety, and executive dysfunction in neuropsychiatric measures along with executive and attentional difficulties on cognitive tests were found to be consistently important predictors among different types of fatigue. This implicates both cognitive and neuropsychiatric symptoms as predictors of fatigue in post-COVID-19 condition, and stresses the importance of a holistic approach in assessing and considering potential treatment for COVID-19 patients experiencing fatigue.

Neuropsychological deficits in patients with cognitive complaints after COVID-19.

BACKGROUND: While much of the scientific focus thus far has been on cognitive sequelae in patients with severe COVID-19, subjective cognitive complaints are being reported across the spectrum of disease severity, with recent studies beginning to corroborate patients' perceived deficits. In response to this, the aims of this study were to (1) explore the frequency of impaired performance across cognitive domains in post-COVID patients with subjective complaints and (2) uncover whether impairment existed within a single domain or across multiple. METHODS: Sixty-three patients with subjective cognitive complaints post-COVID were assessed with a comprehensive protocol consisting of various neuropsychological tests and mood measures. Cognitive test performance was transformed into T scores and classified based on recommended guidelines. After performing a principal component analysis to define cognitive domain factors, distributions of test scores within and across domains were analyzed. RESULTS: Results revealed pervasive impact on attention abilities, both as the singularly affected domain (19% of single-domain impairment) as well as coupled with decreased performance in executive functions, learning, and long-term memory. These salient attentional and associated executive deficits were largely unrelated to clinical factors such as hospitalization, disease duration, biomarkers, or affective measures. DISCUSSION: These findings stress the importance of comprehensive evaluation and intervention to address cognitive sequelae in post-COVID patients of varying disease courses, not just those who were hospitalized or experienced severe symptoms. Future studies should investigate to what extent these cognitive abilities are recuperated over time as well as employ neuroimaging techniques to uncover underlying mechanisms of neural damage.

Voluntary Language Switching in the Context of Bilingual Aphasia.

As studies of bilingual language control (BLC) seek to explore the underpinnings of bilinguals' abilities to juggle two languages, different types of language switching tasks have been used to uncover switching and mixing effects and thereby reveal what proactive and reactive control mechanisms are involved in language switching. Voluntary language switching tasks, where a bilingual participant can switch freely between their languages while naming, are being utilized more often due to their greater ecological validity compared to cued switching paradigms. Because this type of task had not yet been applied to language switching in bilingual patients, our study sought to explore voluntary switching in bilinguals with aphasia (BWAs) as well as in healthy bilinguals. In Experiment 1, we replicated previously reported results of switch costs and mixing benefits within our own bilingual population of Catalan-Spanish bilinguals. With Experiment 2, we compared both the performances of BWAs as a group and as individuals against control group performance. Results illustrated a complex picture of language control abilities, indicating varying degrees of association and dissociation between factors of BLC. Given the diversity of impairments in BWAs' language control mechanisms, we highlight the need to examine BLC at the individual level and through the lens of theoretical cognitive control frameworks in order to further parse out how bilinguals regulate their language switching.

Semantic Processing in Bilingual Aphasia: Evidence of Language Dependency.

Individuals with aphasia frequently show lexical retrieval deficits due to increased interference of semantically related competitors, a phenomenon that can be observed in tasks such as naming pictures grouped by semantic category. These deficits are explained in terms of impaired semantic control, a set of abilities that are to some extent dependent upon executive control (EC). However, the extent to which semantic control abilities can be affected in a second and non-dominant language has not been extensively explored. Additionally, findings in healthy individuals are inconclusive regarding the degree to which semantic processing is shared between languages. In this study, we explored the effect of brain damage on semantic processing by comparing the performance of bilingual individuals with aphasia on tasks involving semantic control during word production and comprehension. Furthermore, we explored whether semantic deficits are related to domain-general EC deficits. First, we investigated the naming performance of Catalan-Spanish bilinguals with fluent aphasia and age-matched healthy controls on a semantically blocked cyclic naming task in each of their two languages (Catalan and Spanish). This task measured semantic interference in terms of the difference in naming latencies between pictures grouped by the same semantic category or different categories. Second, we explored whether lexical deficits extend to comprehension by testing participants in a word-picture matching task during a mixed language condition. Third, we used a conflict monitoring task to explore the presence of EC deficits in patients with aphasia. We found two main results. First, in both language tasks, bilingual patients' performances were more affected than those of healthy controls when they performed the task in their non-dominant language. Second, there was a significant correlation between the speed of processing on the EC task and the magnitude of the semantic interference effect exclusively in the non-dominant language. Taken together, these results suggest that lexical retrieval may be selectively impaired in bilinguals within those conditions where semantic competition is higher, i.e.,- in their non-dominant language; this could possibly be explained by an excessive amount of inhibition placed upon this language. Moreover, lexico-semantic impairments seem to be at least somewhat related to conflict monitoring deficits, suggesting a certain degree of overlap between EC and semantic control.

Parkinson's Disease--Cognitive Functional Rating Scale across different conditions and degrees of cognitive impairment.

BACKGROUND/AIMS: The Parkinson's Disease--Cognitive Functional Rating Scale (PD-CFRS) was designed to avoid motor biases in capturing the functional impact of cognitive impairment in Parkinson's disease (PD). Its performance capturing functional impairment in other conditions leading to cognitive dysfunction is unknown. We compare it with non-specific Instrumental Activities of Daily Living scales. METHODS: Two hundred consecutive patients diagnosed in a community hospital with mild cognitive impairment (MCI) [31 MCI-amnestic; 33 MCI-multi-domain; 33 PD-MCI] and dementia [35 Alzheimer's disease; 34 vascular dementia; 34 PD with dementia] were assessed on the PD-CFRS, the Blessed Dementia Scale (BDS), the Clinical Dementia Rating--Sum of Boxes (CDR-SOB), and given a comprehensive cognitive assessment. Diagnostic accuracy and optimal cut-off scores were calculated for the PD-CFRS and compared with each functional measure. RESULTS: The PD-CFRS presented high concurrent validity and significant correlation with both BDS and CDR-SOB, and cognitive scores offering a similar discrimination accuracy to non-specific scales [PD-CFRS ≥ 9 (sensitivity= 0.94; specificity = 0.95)]. No changes appear in cut-off scores when excluding PD patients. Effect size analysis indicated no relevant interference with PD-CFRS scores between the principal cognitive subgroups. DISCUSSION: The findings extend the clinimetric properties of the PD-CFRS and indicate it as an adequate instrument to capture the full spectrum of functional consequences of cognitive decline in the community.

Apathy in Parkinson's disease: neurophysiological evidence of impaired incentive processing.

Apathy is one of the most common and debilitating nonmotor manifestations of Parkinson's disease (PD) and is characterized by diminished motivation, decreased goal-directed behavior, and flattened affect. Despite its high prevalence, its underlying mechanisms are still poorly understood, having been associated with executive dysfunction, and impaired emotional processing and decision making. Apathy, as a syndrome, has recently been associated with reduced activation in the ventral striatum, suggesting that early- to middle-stage Parkinson's disease patients with this manifestation may have a compromised mesocorticolimbic dopaminergic pathway and impaired incentive processing. To test this hypothesis, we measured the amplitude of the feedback-related negativity, an event-related brain potential associated with performance outcome valence, following monetary gains and losses in human PD patients (12 women) and healthy controls (6 women) performing a gambling task. Early- to middle-stage PD patients presenting clinically meaningful symptoms of apathy were compared with nonapathetic PD patients and healthy controls. Patients with cognitive impairment, depression, and other psychiatric disturbances were excluded. Results showed that the amplitude of the feedback-related negativity, measured as the difference wave in the event-related brain potential between gains and losses, was significantly reduced in PD patients with apathy compared with nonapathetic patients and healthy controls. These findings indicate impaired incentive processing and suggest a compromised mesocorticolimbic pathway in cognitively intact PD patients with apathy.

The Subjective Cognitive Decline Questionnaire (SCD-Q): a validation study.

BACKGROUND: Subjective cognitive decline (SCD) is gaining importance as a focus of investigation, but adequate tools are needed for its quantification. OBJECTIVE: To develop and validate a questionnaire to quantify SCD, termed the Subjective Cognitive Decline Questionnaire (SCD-Q). METHODS: 124 controls (CTR), 144 individuals with SCD, 83 mild cognitive impairment subjects, 46 Alzheimer's disease patients, and 397 informants were included. The SCD-Q contains: part I, named MyCog, which is answered by the subject; and part II, TheirCog, which includes the same questions and is answered by the informant or caregiver. The 24 SCD-Q items assess the perceived subjective decline in memory, language, and executive functions in the last two years. RESULTS: The MyCog scores of controls differed significantly from those of the other groups (p < 0.05) and there were significant differences in TheirCog scores between all groups. The optimal TheirCog cut-off score for discriminating between individuals with and without cognitive impairment was 7/24 (sensitivity 85%, specificity 80%). MyCog scores correlated significantly with anxiety and depression (r = 0.29, r = 0.43, p < 0.005), but no correlations were found with neuropsychological tests. TheirCog scores correlated significantly with most of the neuropsychological tests (p < 0.05). Informants' depression and anxiety influenced TheirCog scores in controls and SCD groups. CONCLUSION: Self-perceived cognitive decline, measured by the SCD-Q part I (MyCog), discriminated SCD from CTR. Part II (TheirCog) was strongly related to subjects' objective cognitive performance, and discriminated between subjects with or without cognitive impairment. The SCD-Q is a useful tool to measure self-perceived cognitive decline incorporating the decliner and the informant perspective.

Measuring functional impact of cognitive impairment: validation of the Parkinson's disease cognitive functional rating scale.

BACKGROUND: Little is known on the impact of cognitive impairment on instrumental activities of daily living (IADL) in pre-dementia stages of Parkinson's disease (PD). OBJECTIVE: To investigate the clinimetric properties, applicability and responsiveness of a brief questionnaire (twelve-item; maximum score = 24) for rating functional abnormalities associated to cognitive impairment in non-demented PD patients (ND-PD). METHODS: Two studies were carried-out: (1) a clinimetric study validated the Parkinson's Disease-Cognitive Functional Rating Scale (PD-CFRS) against the Older Americans Resource Survey (OARS-IADL) in 53 ND-PD patients and 53 matched controls; (2) A prospective multicenter 6-month responsiveness study involving 120 ND-PD patients explored sensitivity to change. RESULTS: In the clinimetric study the PD-CFRS showed intermediate concurrent validity (ICC = 0.50), high test-retest (ICC = 0.82), inter-rater reliability (ICC = 0.80) and internal consistency (Cronbach's α = 0.79), and higher coefficient of variation to detect dysfunction in ND-PD patients (PD-CFRS 86.6% vs. OARS-IADL 8.1%). There was a strong relationship between the PD-CFRS and the global cognitive status determined with the PD-Cognitive Rating Scale (r = -0.72, p < 0.0001). The responsiveness study recruited 63 patients with normal cognition and 57 with mild cognitive impairment (MCI); an increase of 2 points in the PD-CFRS after 6 months was associated with a clinically significant worsening of the cognitive functional status. According to a discriminant analysis a PD-CFRS cut-off score of ≥3 was found to be optimal for detecting functional impairment in PD-MCI patients. CONCLUSIONS: Cognitive impairment exerts measurable impact on IADL in ND-PD patients that can be reliable measured with the PD-CFRS, a PD-validated instrument that can be useful in clinical and research settings.

Apathy in Parkinson's disease: more than just executive dysfunction.

Apathy is a frequent syndrome in Parkinson's disease (PD) usually associated with depression, cognitive impairment (CI), and dementia. Whereas executive dysfunction seems to play a major causative role in the development of apathy in PD, recent findings pointed for the possible participation of other underlying mechanisms in the development of clinically meaningful symptoms of apathy. By means of neuropsychological testing focused over global cognitive functioning, set-shifting, decision making, and cognitive effort, we compared to a control group, a carefully selected sample of PD patients presenting apathy as the only neuropsychiatric symptom and without clinically relevant signs of cognitive impairment. In addition to the previously reported executive dysfunction, apathetic patients also exhibited significant difficulties in tasks assessing for cortical functioning, such as naming and clock drawing. Moreover, apathetic patients performed significantly better on a decision-making task, although any of these differences appeared linked to a lack of effort when performing the tasks. On the basis of our findings, we discuss the possible implication of added mechanisms rather than just executive dysfunction in the development of apathy in PD.

Pattern of regional cortical thinning associated with cognitive deterioration in Parkinson's disease.

BACKGROUND: Dementia is a frequent and devastating complication in Parkinson's disease (PD). There is an intensive search for biomarkers that may predict the progression from normal cognition (PD-NC) to dementia (PDD) in PD. Mild cognitive impairment in PD (PD-MCI) seems to represent a transitional state between PD-NC and PDD. Few studies have explored the structural changes that differentiate PD-NC from PD-MCI and PDD patients. OBJECTIVES AND METHODS: We aimed to analyze changes in cortical thickness on 3.0T Magnetic Resonance Imaging (MRI) across stages of cognitive decline in a prospective sample of PD-NC (n = 26), PD-MCI (n = 26) and PDD (n = 20) patients, compared to a group of healthy subjects (HC) (n = 18). Cortical thickness measurements were made using the automatic software Freesurfer. RESULTS: In a sample of 72 PD patients, a pattern of linear and progressive cortical thinning was observed between cognitive groups in cortical areas functionally specialized in declarative memory (entorhinal cortex, anterior temporal pole), semantic knowledge (parahippocampus, fusiform gyrus), and visuoperceptive integration (banks of the superior temporal sulcus, lingual gyrus, cuneus and precuneus). Positive correlation was observed between confrontation naming and thinning in the fusiform gyrus, parahippocampal gyrus and anterior temporal pole; clock copy with thinning of the precuneus, parahippocampal and lingual gyrus; and delayed memory with thinning of the bilateral anteromedial temporal cortex. CONCLUSIONS: The pattern of regional decreased cortical thickness that relates to cognitive deterioration is present in PD-MCI patients, involving areas that play a central role in the storage of prior experiences, integration of external perceptions, and semantic processing.

Spectroscopic changes associated with mild cognitive impairment and dementia in Parkinson's disease.

Frontal subcortical cognitive defects are predominant in Parkinson's disease (PD). Temporal lobe dysfunction seems more relevant for progression to dementia. We aimed to study the relative importance of temporal lobe defects versus executive impairment in the progression to dementia in PD by using proton magnetic resonance spectroscopy ((1)H-MRS). The (1)H-MRS features of PD patients with intact cognition (PD-CgInt; n = 16), mild cognitive impairment (MCI; n = 15) and dementia (PDD; n = 15) were compared, to delineate the metabolic alterations correlating with cognitive status. Metabolite concentrations were acquired from voxels localized to the hippocampus and dorsolateral prefrontal cortex (DL-PFC). Cognitive status was established following the Movement Disorder Society PDD criteria, administering the Clinical Dementia Rating Scale and Mattis Dementia Rating Scale. The Parkinson's Disease Cognitive Rating Scale (PD-CRS) was used to correlate (1)H-MRS with neuropsychology. N-acetylaspartate (NAA) concentrations in the right DL-PFC were decreased in PD-MCI compared with PD-CgInt patients (p = 0.002), and correlated with frontal subcortical tasks. Decreased NAA concentrations in the left hippocampus in PDD compared to PD-MCI (p = 0.03) correlated with confrontation naming. The present findings support that executive impairment is related to dorsolateral prefrontal dysfunction from the early stages, while progression to dementia is linked to the additional impairment of temporal lobe structures. The PD-CRS was able to capture the differential impairment of prefrontal versus temporal cortical areas.

Facial emotion recognition impairment in patients with Parkinson's disease and isolated apathy.

Apathy is a frequent feature of Parkinson's disease (PD), usually related with executive dysfunction. However, in a subgroup of PD patients apathy may represent the only or predominant neuropsychiatric feature. To understand the mechanisms underlying apathy in PD, we investigated emotional processing in PD patients with and without apathy and in healthy controls (HC), assessed by a facial emotion recognition task (FERT). We excluded PD patients with cognitive impairment, depression, other affective disturbances and previous surgery for PD. PD patients with apathy scored significantly worse in the FERT, performing worse in fear, anger, and sadness recognition. No differences, however, were found between nonapathetic PD patients and HC. These findings suggest the existence of a disruption of emotional-affective processing in cognitive preserved PD patients with apathy. To identify specific dysfunction of limbic structures in PD, patients with isolated apathy may have therapeutic and prognostic implications.

Neuropsychological correlates of mild to severe hallucinations in Parkinson's disease.

The development of visual hallucinations (VH) is a frequent complication of Parkinson's disease (PD). Presence of hallucinations is one of the main risk factors associated with dementia, and severity progression of VH mainly contributes to impaired quality of life in PD. The neuropsychological features associated with severity progression of VH are unknown and might help to detect patients at risk of a more severe outcome. We aimed to explore the neuropsychological deficits associated with the different types of VH observed in PD, from minor hallucinations to well-formed VH with loss of insight. Prospective study of 57 PD patients with (n = 29) and without VH (n = 28) matched for age, education, antiparkinsonian medications, and disease duration. Description of VH was assessed by the Hallucinations and Psychosis item of the MDS-UPDRS. Cognition was assessed with the Parkinson's Disease-Cognitive Rating Scale (PD-CRS) and the Mattis Dementia Rating Scale (MDRS). Patients with minor VH did not differ from patients without VH in any cognitive domain. PD patients with major VH and insight retained performed worse on the action verbal fluency task (P < 0.04), and patients with VH and loss of insight showed a greater impairment on the PD-CRS posterior cortical score (P = 0.021) and the clock copying item (P = 0.01). A double dissociation was found in the neuropsychological profile of patients with VH with and without loss of insight. While the presence of major VH with insight retained appeared related to a predominant frontal-striatal impairment, loss of insight was characterized by further impairment of cognitive functions related to posterior cortical areas. A comprehensible continuum pattern of clinical relationships emerged among VH and cognitive functioning in PD.

PDD-Short Screen: a brief cognitive test for screening dementia in Parkinson's disease.

The diagnosis of Parkinson's disease with dementia (PDD) is currently based on clinical criteria (DSM-IV, MDS-Task Force). In daily practice and research studies, these criteria still depend on the subjective impression of the examiner. Brief screening tests (BST) are helpful in identifying patients with PD with dementia, which can be difficult in patients with advanced PD. We aimed to develop a BST for PD, the PDD-Short Screen (PDD-SS), to accurately and quickly screen for PDD. In this prospective study, 70 patients with nondemented (age 73.8 +/- 4.4) and 32 demented (age 73.8 +/- 4.4) PD regularly attending a Movement Disorders Clinic were included. Diagnosis of dementia was based on DSM-IV criteria, CDR score >or=1, and PD-CRS total score

Levodopa and executive performance in Parkinson's disease: a randomized study.

Parkinson's disease (PD) patients may experience fluctuations in executive performance after oral levodopa (LD). Their relationship with the pharmacokinetic profile of LD and with distinct cognitive processes associated with frontal-basal ganglia circuits is not well understood. In this randomized, double-blind, crossover study we plotted acute cognitive changes in 14 PD patients challenged with faster (immediate-release, IR) versus slower (controlled-release, CR) increases in LD plasma concentrations. We monitored motor status, LD plasma levels, and performance on four tasks of executive function (Wisconsin Card Sorting Test-WCST, Sternberg test, Stroop and Tower of Hanoi), 1 hr before and over +6 hr after IR and CR-LD dose. Analysis of variance demonstrated significant but divergent changes in the Sternberg (6-digit but not 2- and 4-digit) test: improvement after CR-LD and worsening after IR-LD. Marginal improvement (p = .085) was observed with CR-LD in the WCST, while no significant differences were seen for the Stroop or Tower of Hanoi tests. Executive-related performance after LD challenge may differ depending on the LD time-to-peak plasma concentration and specific task demands. A slower rise in LD levels appears to have a more favorable impact on more difficult working memory tests. These results require replication to determine their generalization.

Prevalence and correlates of neuropsychiatric symptoms in Parkinson's disease without dementia.

A cross-sectional study of the profile of psychiatric symptoms and their relationships to medications, executive performance, and excessive daytime somnolence (EDS) was conducted on 1351 consecutive Parkinson's disease patients without dementia (PD-ND). Ratings were: neuropsychiatric inventory (NPI); hospital anxiety and depression scale (HADS); executive performance (semantic, phonemic, and alternating verbal fluencies); and the Epworth sleepiness scale (ESS). Eighty-seven percent of the subjects reported at least one psychiatric symptom. The most common were depression (70%), anxiety (69%), apathy (48%), and irritability (47%). Fifty percent of the patients had HADS-depression scores ranging from possible (8-10; 22%) to probable (>or=11; 28%) depression. Executive impairment was found in 41% and EDS in 26% of subjects. All considered variables were significantly more common with longer duration and more severe disease. Only depression appeared to be influenced by type of medication, being less prevalent among patients treated with DAs. Five NPI clusters were identified among patients scoring >or=1 on the NPI (87.3%): patients exhibiting predominantly apathy (12.7%), psychosis (3%), depression (13%), anxiety (15.6%), and "low-total NPI" (43.2%). Neuropsychiatric symptoms are common in nondemented PD patients suggesting that they are an integral part of PD from the beginning of the disease and appears more related to disease progression than to the type of antiparkinsonian medication. Apathy emerged as an independent construct in PD-ND, indicating the need to address specific therapeutical approaches targeted toward this particular symptom.

Cut-off score of the Mattis Dementia Rating Scale for screening dementia in Parkinson's disease.

The prevalence of dementia in Parkinson's disease (PD) is close to 30%, and its incidence is 4 to 6 times higher than in age-matched general population. PD with dementia (PDD) is mainly characterized by a predominant and progressive frontal-subcortical impairment. The Mattis Dementia Rating Scale (MDRS) is a commonly used screening test that sensitively measures the degree of frontal-subcortical defects. Although the MDRS has been validated as a screening test of cognitive dysfunction in nondemented PD patients (PD-ND), its utility for screening dementia in PD is unknown. In order to validate the MDRS for diagnosis of PDD it was prospectively administered to 92 PD patients (57 PD-ND, 35 PDD) fulfilling UK-PDSBB criteria. Dementia was diagnosed according to DSM-IV-TR and a Clinical Dementia Rating (CDR) scale score >or=1. Univariate, logistic regression, and ROC curve analysis were carried out to measure the discriminative power of MDRS in PDD. Regression analysis showed MDRS total scores to independently differentiate PD-ND from PDD (P < 0.001). Age and education did not predict the presence of dementia. ROC curve analysis showed a cut-off score of