Ramón Fernández-Bobadilla

Neuropsychiatric symptoms are very common in premanifest and early stage Huntington's Disease.

BACKGROUND Neuropsychiatric symptoms are common features of Huntingtons disease (HD). Whereas most studies have focused on cognitive and neuroimaging markers of disease progression, little is known about the prevalence of neuropsychiatric symptoms in premanifest mutation carriers far-from and close-to disease onset. METHODS We obtained neurological, cognitive and behavioral data from 230 participants classified as premanifest far-from (preHD-A) and close-to (preHD-B) motor-based disease onset, early-symptomatic (early-HD), and healthy controls. Frequency and severity of neuropsychiatric symptoms were assessed with the short Problem Behaviors Assessment for HD (PBA-s). The odds-ratio (OR) to present symptoms in the clinical range was calculated using the control group as reference. Logistic regression analysis was used to explore relationships between neuropsychiatric symptoms and medication use. RESULTS Prevalence of depression was similar in all groups. Apathy was already present in 32% of preHD-A increasing to 62% of early-HD patients. The probability of presenting apathetic symptoms was 15-88 times higher in preHD-A and preHD-B respectively than in healthy controls. Irritability and executive dysfunction were present in both preHD-B and early-HD. CONCLUSION Neuropsychiatric symptoms are highly prevalent in HD, already in the premanifest stage, with increasing prevalence of irritability, apathy and executive dysfunction closer to onset. Compared to controls, HD mutation carriers have the highest probability to develop apathy, with an increasing prevalence along disease stages. Our findings confirm the high prevalence of neuropsychiatric symptoms in HD, already many years before the onset of motor symptoms, with apathy as an early manifestation and core neuropsychiatric feature of the disease.

Normative Data for the Spanish Version of the Addenbrooke's Cognitive Examination III

Background: Addenbrookes Cognitive Examination III (ACE-III) is a cognitive test that has been validated for the diagnosis of cognitive disorders. The aim of this study was to provide normative data for the ACE-III for age, education and gender. Methods: The Spanish version of the ACE-III was administered to a group of 273 healthy subjects in a multicenter study in Spain. Correlation and determination coefficients for age, education and gender were estimated. The overlapping interval strategy and linear regression analyses were used to provide adjusted norms for demographic factors and to explore the potential influence of these factors in the performance of the test. Results: Age and education correlated significantly with the total score and with all the domains. Gender correlated only with the domains of attention and visuospatial skills. Norms for the total score and for cognitive domains (attention, memory, fluency, language, and visuospatial skills) are provided. Conclusion: This study confirms the influence of demographic factors (especially age and education) on the performance in the ACE-III and provides normative data for the Spanish version of the ACE-III.

Non-demented Parkinson’s disease patients with apathy show decreased grey matter volume in key executive and reward-related nodes

Apathy is a common but poorly understood neuropsychiatric disturbance in Parkinson’s disease (PD). In a recent study using event-related brain potentials we demonstrated impaired reward processing and compromised mesocortico-limbic pathways in PD patients with clinical symptoms of apathy. Here we aimed to further investigate the involvement of reward circuits in apathetic PD patients by assessing potential differences in brain structure. Using structural magnetic resonance imaging (MRI) and voxel-based morphometry (VBM) we quantified grey matter volume (GMV) in a sample of 18 non-demented and non-depressed PD patients with apathy, and 18 matched non-apathetic patients. Both groups were equivalent in terms of sociodemographic characteristics, disease stage, cognitive performance and L-Dopa equivalent daily dose. Apathetic patients showed significant GMV loss in cortical and subcortical brain structures. Various clusters of cortical GMV decrease were found in the parietal, lateral prefrontal cortex, and orbitofrontal cortex (OFC). The second largest cluster of GMV loss was located in the left nucleus accumbens (NAcc), a subcortical structure that is a key node of the human reward circuit. Isolated apathy in our sample is explained by the combined GMV loss in regions involved in executive functions, and cortical and subcortical structures of the mesolimbic reward pathway. The correlations observed between apathy and cognition suggests apathy as a marker of more widespread brain degeneration even in a sample of non-demented PD patients.

Neurophysiological evidence of compensatory brain mechanisms in early-stage multiple sclerosis

Multiple sclerosis (MS) is a chronic central nervous system disorder characterized by white matter inflammation, demyelination and neurodegeneration. Although cognitive dysfunction is a common manifestation, it may go unnoticed in recently-diagnosed patients. Prior studies suggest MS patients develop compensatory mechanisms potentially involving enhanced performance monitoring. Here we assessed the performance monitoring system in early-stage MS patients using the error-related negativity (ERN), an event-related brain potential (ERP) observed following behavioral errors. Twenty-seven early-stage MS patients and 31 controls were neuropsychologically assessed. Electroencephalography recordings were obtained while participants performed: a) a stop task and b) an auditory oddball task. Behavior and ERP measures were assessed. No differences in performance were found between groups in most neuropsychological tests or in behavior or ERP components in the auditory oddball task. However, the amplitude of the ERN associated with stop errors in the stop task was significantly higher in patients. ERN amplitude correlated positively with scores on the Expanded Disability Status Scale and the Multiple Sclerosis Severity Score, and negatively with the time since last relapse. Patients showed higher neuronal recruitment in tasks involving performance monitoring. Results suggest the development of compensatory brain mechanisms in early-stage MS and reflect the sensitivity of the ERN to detect these changes.

“String Hallucinations”: Multimodal Tactile and Visual Hallucinations in Parkinson's Disease

The aim of this work was to report on 7 patients presenting a distinctive form of multimodal (tactile and visual) hallucinations for which the term “string hallucinations” is proposed. Having observed a patient interacting with imaginary strips of skin in his hands at our movement disorders unit, we prospectively studied PD patients and caregivers over a 6‐month period using a semistructured interview addressed to this particular phenomenon. Demographic characteristics as well as cognitive and motor function were assessed. A total of 7 of 164 PD patients (4.3%) observed during the study period had string hallucinations. One patient was cognitively intact and the other 6 had some degree of cognitive impairment. Common to the phenomenology of the hallucinations was the unpleasant feeling and vision of threads emerging from the subjects’ hands. Patients interacted with these “threads,” trying to remove them from their hands. Our study identifies a previously undescribed type of hallucinations in PD, characterized by a complex pattern of multimodal tactile and visual hallucinations.

Corrigendum to "Neuropsychiatric symptoms are very common in premanifest and early stage Huntington's disease" [Parkinsonism Relat. Disord. 25C (2016) 58-64].

Corrigendum to “Neuropsychiatric symptoms are very common in premanifest and early stage Huntingtons disease” [Parkinsonism Relat. Disord. 25C (2016) 58e64] Saul Martinez-Horta a, b, c, f, , Jesus Perez-Perez a, b, c, , Erik van Duijn , Ramon Fernandez-Bobadilla a, b, c, , Mar Carceller b, , Javier Pagonabarraga a, b, , Berta Pascual-Sedano a, b, , Antonia Campolongo a, b, , Jesus Ruiz-Idiago , Frederic Sampedro , G. Bernhard Landwehrmeyer , Spanish REGISTRY investigators of the European Huntingtons Disease Network, Jaime Kulisevsky a, b, c, f, *

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

BACKGROUND/AIMS The Parkinsons Disease--Cognitive Functional Rating Scale (PD-CFRS) was designed to avoid motor biases in capturing the functional impact of cognitive impairment in Parkinsons 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 Alzheimers 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.