Jesus Perez-Perez

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.

Validación de la versión española del test Addenbrooke's Cognitive Examination III para el diagnóstico de demencia

INTRODUCTION Addenbrookes Cognitive Examination is a screening test used to diagnose dementia. The third edition of this test (ACE-III) was recently developed. The aim of this study was to translate and validate the ACE-III in Spanish. METHODS The ACE-III was translated and adapted to Spanish. It was then administered to a group of healthy subjects as well as a group of patients with different types of mild dementia treated in 2 hospitals in Spain. RESULTS Internal reliability (Cronbachs alpha = 0.927), inter-rater reliability (intraclass correlation coefficient = 0.976) and test-retest reliability (kappa 0.995) were excellent. Age (r = -0.512) and education (r = 0.659) showed a significant correlation with total test scores. The diagnostic accuracy of ACE-III was higher than that of the Mini-Mental State Examination, particularly for the group with the highest educational level. Researchers obtained normative data and cut-off points for the diagnosis of dementia. CONCLUSIONS The Spanish version of the ACE-III is a reliable and valid test for diagnosing dementia. Its diagnostic accuracy is high, especially in patients with a higher level of education.

Neurocardiovascular pathology in pre-manifest and early-stage Huntington's disease

Cardiovascular events are a major cause of early death in the Huntingtons disease (HD) population. Dysautonomia as well as deterioration of circadian rhythms can be detected early in the disease progression and can have profound effects on cardiac health. The aim of the present study was to determine if patients with HD and pre‐manifest mutation carriers present a higher risk of cardiovascular disease than non‐mutation‐carrying controls.

“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, *

The impact of bilingualism on brain structure and function in Huntington's disease

INTRODUCTION Bilingualism exerts neuroprotective effects against neurodegeneration. In Huntingtons disease (HD), the systems involved in bilingual control show early compromise, but the effect of bilingualism on the course of HD is unknown. METHODS We addressed the impact of livelong use of bilingualism on the clinical features, brain structure and function in 30 early-mild stage HD patients. Using voxel-wise regression analysis, we explored the effect of levels of use of bilingualism on grey-matter volume (GMV) and 18F-FDG metabolism. RESULTS Higher use of bilingualism was associated with better performance in inhibitory control and set-shifting independently of age and education and with higher GMV in the inferior frontal gyrus. 18F-FDG data revealed a significant effect on multiple fronto-temporal regions, specifically, in the dorsal anterior cingulate cortex, the anterior insula, the ventromedial orbital prefrontal cortex and the inferior frontal gyrus. These changes contributed to better inhibitory control and set-shifting and to more preserved motor and functional capacity. CONCLUSION In HD, lifelong use of bilingualism is associated with structural and metabolic brain changes that have an impact on cognition, movement and functionality. These findings highlight the importance of stimulating cognitive and brain reserve in HD and in other neurodegenerative conditions.

An active cognitive lifestyle as a potential neuroprotective factor in Huntington's disease

ABSTRACT A cognitive stimulating lifestyle has been observed to confer cognitive benefits in multiple neurodegenerative diseases. However, the underlying neurobiological basis of this phenomenon remains unclear. Huntingtons disease can provide a suitable model to study the effects and neural mechanisms of cognitive engagement in neurodegeneration. In this study, we investigate the effect of lifestyle factors such as education, occupation and engagement in cognitive activities in Huntingtons disease gene carriers on cognitive performance and age of onset as well as the underlying neural changes sustaining these effects, measured by magnetic resonance imaging. Specifically, we analyzed both gray matter volume and the strength of connectivity of the executive control resting‐state network. High levels of cognitive engagement were significantly associated with more preserved executive functions, a delay in the appearance of symptoms, reduced volume loss of the left precuneus and the bilateral caudate and a modulation of connectivity strength of anterior cingulate cortex and left angular gyrus with the executive control network. These findings suggest that a cognitively stimulating lifestyle may promote brain maintenance by modulating the executive control resting‐state network and conferring protection against neurodegeneration, which results in a delayed onset of symptoms and improved performance in executive functions. HIGHLIGHTSIn Huntingtons disease, a cognitively active lifestyle is associated with benefits.These include better cognitive performance and delayed onset of symptoms.These effects could be mediated by less grey matter loss in caudate and precuneus.Reduced functional connectivity was related with a cognitively active lifestyle.Engaging in cognitive activities could potentially provide brain resistance.

Structural and metabolic brain correlates of apathy in Huntington's disease: Apathy in Huntington's Disease

Apathy is the most prevalent and characteristic neuropsychiatric feature of Huntingtons disease. Congruent with the main early pathological changes, apathy is primarily associated with subcortical damage in frontal‐striatal circuits. However, little is known about its precise subserving mechanisms and the contribution of regions other than the basal ganglia.

A11 Skin fibroblasts from huntington´s disease patients show distinct signature of MIRNAS expression along disease progression

Background Most cellular dysfunctions in HD are associated with alterations in gene expression, with transcriptional dysregulation being a prominent feature of the disease. One of the mechanisms involved in this deregulation is the aberrant expression of microRNAs (miRNAs). Aberrant expression profiles of miRNAs have been identified as biomarkers in many different diseases. So far, several studies in the context of neurodegenerative disorders have focused on the identification and clinical application of miRNAs as biomarkers. However, the study of miRNAs in HD need to be further explored in particular related to the progression of the disease. Aims In this study we aim to explore and validate miRNA expression profiles in fibroblasts of HD patients at pre-symptomatic and symptomatic stages. Methods/techniques In a discovery phase we have assessed comprehensive genome-wide miRNA expression analysis of fibroblasts from pre-symptomatic, early symptomatic, middle/advanced symptomatic patients and controls. We have used the GeneChip miRNA 4.0 array from Affymetrix including probes for 2578 mature human miRNAs. In a validation phase we validated candidate miRNAs differentially expressed using the Taman Advance qPCR. Results/outcome Our investigations have revealed specific signatures of miRNAs expression in HD patients along the disease progression with a downregulation of miRNAs at pre-symptomatic stages and an upregulation of miRNAs at symptomatic stages. Furthermore, we identified some mRNAs as biomarkers of disease progression that might identify when a patient become symptomatic such as, miR6124, miR210 and miR493, or when patients progress to a middle or advance stage of the disease, such as miR127. Conclusions Our results indicate that miRNA alterations precede the onset of motor symptoms and highlight the potential of miRNA panels from fibroblasts as biomarkers for Huntington´s disease progression.

Parkinson’s disease: Impulsivity does not cause impulse control disorders but boosts their severity

Introduction: Impulse control disorders (ICDs) are a common complication of Parkinsons disease (PD) receiving dopamine agonist (DAA) Impulsivity is considered an underlying mechanism but evidence of this relationship is scarce. To explore the relationship between impulsivity and the presence and severity of ICD in PD. Methods: Prospective cross-sectional study of consecutive PD outpatients. Patients with dementia or previously known ICDs were excluded. Two measures of impulsivity were assessed: Barratt Impulsiveness Scale (BIS-11) for impulsiveness trait (main exposure) and commission errors in the Continuous Performance Test (CE) for motor inhibition. Main outcomes were diagnosis of ICD based on a comprehensive clinical interview and severity of ICD based on the Questionnaire for Impulsive-Compulsive Disorders. Results: Of 100 patients (mean [SD] age, 67.2 [8.8], 54 male), 31 had ICD. Patients with ICDs were 5.3 years younger (p = 0.01), used more frequently dopamine agonist (p = 0.02), alcohol (p = 0.009) and tobacco (p = 0.02). They were not more impulsive on BIS-11 (56 vs. 58, p = 0.23, adjusted p = 0.46) and CE (p = 0.96). No relationship was found between dopaminergic medications and impulsivity or ICD severity. Among patients with ICD, impulsivity was correlated with ICD severity (BIS-11 r = 0.33, p = 0.001, adjusted p = 0.002, CE r = 0.53, p = 0.006). Multivariate regression analysis confirmed the independent predictive role of both measures. Conclusions: Impulsivity is not associated with increased prevalence of ICD in PD but it is strongly linked to ICD severity. When considering dopamine replacement therapy, assessment of impulsivity may be a useful approach to detect those patients at risk of severe forms of ICD.