Gisela Llebaria

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.

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.

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.

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

The development of visual hallucinations (VH) is a frequent complication of Parkinsons 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 Parkinsons 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.

A prospective study of delusional misidentification syndromes in Parkinson's disease with dementia

Delusional misidentification syndromes (DMS) are a group of neuropsychiatric disorders due to disturbances in familiarity. DMS in organic diseases have been related to deficits in executive, memory, and visuospatial function. DMS are frequently reported in dementia with Lewy bodies (DLB). The presence of DMS in Parkinsons disease with dementia (PDD), which shares similar clinical and neuropsychological features with DLB, has not been studied. We describe the frequency and clinical features of DMS in a cohort of PDD patients, and we compare the neuropsychological profile between PDD patients with and without DMS. Prospective study of 30 PDD patients recruited from an outpatient setting, who received a structured behavioral interview assessing DMS and hallucinations, and a neuropsychological battery assessing executive function, memory, language, and visuospatial abilities. DMS were found in 16.7% of PDD patients. All DMS subjects also exhibited hallucinations that were significantly more severe than in PDD without DMS. DMS were responsive to neuroleptic drugs. PDD subjects with DMS presented a different neuropsychological profile than PDD subjects without DMS, with more severe memory and language deficits, but similar levels of executive and visuospatial impairment. DMS is a neuropsychiatric feature associated with PDD. Greater impairment in language and memory in PDD with DMS suggests a prominent role of the temporal cortex in the genesis of DMS in PDD.

Neural correlates of minor hallucinations in non-demented patients with Parkinson's disease

BACKGROUND Hallucinations are a frequent and severe complication in Parkinsons disease (PD). Minor hallucinations are generally not disturbing, but likely progress to well-structured hallucinations with loss of insight and a great impact on quality of life. Knowledge on the neural bases of minor hallucinations may help to describe those systems associated with the early development of psychotic phenomena in PD. In this study, we aimed to identify the pattern of structural brain alterations associated with minor hallucinations in PD by using voxel-based morphometry (VBM). METHODS We prospectively collected a sample of 46 non-demented PD patients, with (N = 17) and without (n = 29) minor hallucinations (passage and/or presence hallucinations), and 15 healthy controls. Groups were matched for age, education and global cognitive function. Presence and type of minor psychotic phenomena was assessed by the new MDS-UPDRS. Three dimensional T1-weighted MRI images were acquired with a 1.5 T magnet, and analyzed using optimized VBM. RESULTS Compared to controls, PD with minor hallucinations (PD-mH) showed reduced gray matter volume bilaterally in different areas of the dorsal visual stream, and in functionally related midbrain and cerebellar structures. Additionally, bilateral gray matter volume increases were observed in the PD-mH group in limbic and paralimbic regions. CONCLUSIONS Our data support a major role of the dorsal visual stream in the genesis of minor hallucinations in PD, reinforcing the importance of posterior cortical regions for the development of cognitive and psychiatric complications in PD.

Facial Emotion Recognition Impairment in Patients with Parkinson's Disease and Isolated Apathy

Apathy is a frequent feature of Parkinsons 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.

PDD-Short Screen: A Brief Cognitive Test for Screening Dementia in Parkinson's Disease

The diagnosis of Parkinsons 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 ≥1, and PD‐CRS total score ≤64. The PDD‐SS, Mattis Dementia Rating Scale (MDRS), and Mini‐Mental State Examination (MMSE) were administered to all participants. Validity, reliability, and discriminative power of the PDD‐SS were examined. The final version of the scale included the items immediate and delayed verbal memory, clock drawing, alternating verbal fluency, and a questionnaire covering cognitive and psychiatric (hallucinations, apathy) symptoms common in PDD. A cutoff score ≤11 on the PDD‐SS yielded high sensitivity (89.8%) and specificity (88.5%) for diagnosing PDD. The MDRS displayed similar accuracy, but the PDD‐SS administration time was significantly shorter (4.8–6.9 vs. 17.5–25.2 minutes). Diagnosis of dementia using the PDD‐SS was not influenced by age, education, or motor function. The PDD‐SS appears as the first BST for diagnosing PDD, displays an excellent diagnostic accuracy, and takes 5 to 7 minutes to be administered.

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 (1H-MRS). The 1H-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 1H-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.