Carmen García-Sánchez

Parkinson's disease-cognitive rating scale: a new cognitive scale specific for Parkinson's disease.

Cognitive defects associated with cortical pathology may be a marker of dementia in Parkinsons disease (PD). There is a need to improve the diagnostic criteria of PD dementia (PDD) and to clarify the cognitive impairment patterns associated with PD. Current neuropsychological batteries designed for PD are focused on fronto‐subcortical deficits but are not sensitive for cortical dysfunction. We developed a new scale, the Parkinsons Disease‐Cognitive Rating Scale (PD‐CRS), that was designed to cover the full spectrum of cognitive defects associated with PD. We prospectively studied 92 PD patients [30 cognitively intact (CogInt), 30 mild cognitive impairment (MCI), 32 PDD] and 61 matched controls who completed the PD‐CRS and neuropsychological tests assessing the cognitive domains included in the PD‐CRS. Acceptability, construct validity, reliability, and the discriminative properties of the PD‐CRS were examined. The PD‐CRS included items assessing fronto‐subcortical defects and items assessing cortical dysfunction. Construct validity, test‐retest and inter‐rater reliability of PD‐CRS total scores showed an intraclass correlation coefficient >0.70. The PD‐CRS showed an excellent test accuracy to diagnose PDD (sensitivity 94%, specificity 94%). The PD‐CRS total scores and confrontation naming item scores‐assessing “cortical” dysfunction—independently differentiated PDD from non‐demented PD. Alternating verbal fluency and delayed verbal memory independently differentiated the MCI group from both controls and CogInt. The PD‐CRS appeared to be a reliable and valid PD‐specific battery that accurately diagnosed PDD and detected subtle fronto‐subcortical deficits. Performance on the PD‐CRS showed that PDD is characterized by the addition of cortical dysfunction upon a predominant and progressive fronto‐subcortical impairment.

Chronic effects of dopaminergic replacement on cognitive function in Parkinson's disease : A two-year follow-up study of previously untreated patients

The cognitive effects of dopaminergic treatment in Parkinsons disease (PD) are still controversial.

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 Parkinsons 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 (≥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 ≥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.

Controlled study of decision‐making and cognitive impairment in Parkinson's disease

Impulse control disorders (ICD) related to reward‐processing dysfunction have been reported in Parkinsons disease (PD). The relationship between clinical markers of limbic dysfunction with demographic variables and cognitive status of PD is incompletely known. Our objective was to further characterize the relationship between limbic and cognitive dysfunction in a representative sample of nondemented PD patients without antecedents of ICD, as assessed by a risk‐taking test of decision‐making and a comprehensive neuropsychological battery. Prospective, controlled study of 35 nondemented PD patients and 31 matched controls who received the Iowa gambling task (IGT), the Mattis Dementia Rating Scale (MDRS) and verbal fluencies for global cognitive function, the Stroop and digit span tests for executive function, and the Rey Auditory Verbal Learning Test for memory. Compared to controls, PD patients performed significantly worse on the IGT. No clear relationship with demographic variables including dopaminergic treatment and motor response to levodopa (stable or fluctuating) emerged. Performance on the IGT was not related to executive function. In contrast, an inverse relationship was found between the IGT and memory and global cognitive performance, with patients with the better MDRS and memory scores performing significantly worse on the IGT. Our results confirm subclinical dysfunction of the limbic system in nondemented PD patients. Although impaired decision‐making appears unrelated to executive dysfunction, patients with the better cognitive status appears more prone to assume risky behaviors.

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

The prevalence of dementia in Parkinsons 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 ≥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 ≤123 on the MDRS total scores to yield high sensitivity (92.65%), specificity (91.4%), positive and negative predictive values (PPV 83.3%, NPV 96.4%). A brief version of the MDRS obtained by the addition of the memory, initiation/perseveration, and conceptualization subscores yielded similar discriminant properties. The MDRS has an excellent discriminant ability to diagnose dementia in PD and provides an objective measure to distinguish PD‐ND from PDD.

Effects of pallidotomy and bilateral subthalamic stimulation on cognitive function in Parkinson disease

Abstract. Unilateral pallidotomy and bilateral subthalamic deep brain stimulation (STN-DBS) for Parkinson’s disease (PD) have demonstrated a positive effect on motor functions. However, further studies are needed of the unintended cognitive effects accompanying these new surgical procedures. We studied the consequences of unilateral pallidotomy and STN-DBS on cognitive function in a controlled comparative design. Sixteen consecutive PD patients were assessed before and 6 months after unilateral pallidotomy (n = 8) and bilateral STN-DBS (n = 8). The same assessments were performed in a control group of eight non-operated matched PD patients recruited from surgery candidates who refused operation. The neuropsychological battery consisted of test measuring memory, attention, arithmetic, problem solving and language, as well as visuospatial, executive and premotor functions. An analysis of variance (factors time and treatment) was applied. No statistically significant differences were found in the presurgical evaluation of clinical and demographic data for the three treatment groups. The controlled comparison between presurgical and postsurgical performance revealed no significant changes in the cognitive domains tested in the pallidotomy group. The STN-DBS group showed a selective significant worsening of semantic verbal fluency (p = 0.005). This controlled comparative study suggests that neither unilateral pallidotomy nor bilateral STN-DBS have global adverse cognitive consequences, but bilateral STN-DBS may cause a selective decrease in verbal fluency.

Semantic Knowledge of Famous People in Mild Cognitive Impairment and Progression to Alzheimer’s Disease

Patients with dementia of Alzheimer’s type (DAT) show severe impairment in recognizing famous people. The aim of the current study was to investigate if this well-known memory impairment of famous faces is already present in the preclinical phase of DAT and if the famous faces test can help to differentiate patients with mild cognitive impairment (MCI) who progress to dementia and those who do not. We compared baseline performance in a task of famous face identification in a sample of 116 patients with subjective memory complaints classified in three groups: 17 participants with no evidence of cognitive impairment; 26 patients with MCI who had not developed dementia, and 27 patients with MCI who had developed probable DAT 2 years later. The remaining patients were excluded because they abandoned or did not meet the applied restrictive criteria for DAT, MCI or control. MCI patients who were diagnosed 2 years later with DAT performed significantly worse in the preclinical phase than MCI and control participants (p < 0.004). Patients with MCI but not DAT obtained intermediate results between control subjects and MCI patients who develop Alzheimer’s disease. A neuropsychological task of semantic knowledge of famous people may be useful in the early diagnosis of Alzheimer’s disease.

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.

Right Hemisphere Dysfunction in Subjects With Attention-Deficit Disorder With and Without Hyperactivity

The attention-deficit disorder, with and without hyperactivity, is associated with defective attention, response inhibition and, in attention-deficit disorder with hyperactivity, with motor restlessness. In adults, inattention, defective response inhibition, and impersistence are more commonly seen in right hemisphere lesions. In the present study, we investigate possible right hemisphere dysfunctions in attention-deficit disorder with hyperactivity and attention-deficit disorder without hyperactivity. The right hemisphere performance of 60 teenagers, 16 having attention-deficit disorder with hyperactivity, 9 having attention-deficit disorder without hyperactivity, and 35 controls, selected clinically (DSM-III) and experimentally (through Continuous Performance Test and Paced Auditory Addition Task), with normal IQ was assessed using a wide-ranging battery of visuospatial, visuoperceptive, and visuoconstructive functions (Bentons Line Orientation, Bentons Visual Retention, Ravens Progressive Matrices, Wechsler Adult Intelligence Scale [WAIS] Block-Design, Reys Complex Figure). Teenagers with attention-deficit disorder with and without hyperactivity performed significantly worse than controls. Greater differences were found between subjects with attention-deficit disorder without hyperactivity and control than between subjects with attention-deficit disorder with hyperactivity and control subjects. Our results seem to be consistent with right-hemisphere dysfunction, especially in subjects with attention-deficit disorder without hyperactivity. Additionally, WAIS Block-Design and Bentons Line Orientation are the visuospatial tests with the highest discriminant power to differentiate between controls, subjects with attention-deficit disorder without hyperactivity, and subjects with attention-deficit disorder with hyperactivity. (J Child Neurol 1997;12:107-115).

Acute effects of immediate and controlled‐release levodopa on mood in Parkinson's disease: A double‐blind study

Mood fluctuations related to levodopa (LD) dosing are well‐known psychiatric complications of Parkinsons disease (PD). No formal studies explored how affective response to LD relates to the type of motor response to oral LD (stable or wearing‐off) and to different pharmacokinetic profiles of oral LD. We used an intrasubject randomized double‐blind crossover design to study 14 patients (7 stable, 7 wearing‐off) who were monitored for motor status, mood, anxiety, and plasma LD levels 1 hour before and 6 hours after an oral dose of immediate‐release (IR) and controlled‐release LD formulations. Analysis of the dose–response curves showed a significant interaction between the type of motor response and the type of LD. Only the wearing‐off patients had a significant mood elevation, and this effect was only significant following challenge with IR LD. Motor status strongly correlated with LD plasma levels and anxiety but not with mood ratings. Mood changes in PD patients are related to the patients type of motor response to oral LD and also to the kinetic profile of the LD formulation used for dopaminergic replacement.