Minor hallucinations reflect early gray matter loss and predict subjective cognitive decline in Parkinson's disease.

BACKGROUND AND PURPOSE: Well-structured hallucinations in Parkinson's disease (PD) are associated with poor prognosis and dementia. However, the predictive value of minor psychotic phenomena in cognitive deterioration is not well known. Cross-sectional studies have shown that PD patients with minor hallucinations have more severe cortical atrophy than non-hallucinators, but baseline and longitudinal studies addressing the evolution of these brain differences are lacking. The impact of developing minor hallucinations on cognitive impairment and cortical atrophy progression in early PD was explored. METHODS: One hundred and thirty-one de novo PD patients from the Parkinson's Progression Marker Initiative for whom brain magnetic resonance imaging scans were available were included. Cognitive outcome at 5 years was compared between patients with and without minor hallucinations during follow-up. Additionally, using gray matter volume (GMV) voxel-based morphometry, cross-sectional (at baseline) and longitudinal (1- and 2-year GMV loss) structural brain differences between groups were studied. RESULTS: During follow-up, 35.1% of patients developed minor hallucinations. At 5 years, these patients showed an increased prevalence of subjective cognitive decline compared to non-hallucinators (44.1% vs. 13.9%; p < 0.001), but not formal cognitive impairment. Additionally, compared to non-hallucinators, they exhibited reduced GMV at baseline in visuoperceptive areas and increased GMV loss in left temporal areas (p < 0.05 corrected). CONCLUSIONS: Minor hallucinations seem to be an early clinical marker of increased neurodegeneration and are associated with mid-term subjective cognitive decline. Longer follow-up analyses would be needed to further define if these findings could reflect a higher risk of future cognitive deterioration.

Measuring impulsivity in Parkinson's disease: a correlational and structural neuroimaging study using different tests.

BACKGROUND AND PURPOSE: Impulsivity is an aspect of personality and a major component of multiple neuropsychiatric conditions. In Parkinson's disease, it has been associated with the expression of impulse control disorders, a highly prevalent non-motor complication. Even though multiple tests of impulsivity have been used in this context, the impact of test choice has not been addressed. The aim was to evaluate whether different impulsivity measures in Parkinson's disease share substantial inter-scale and anatomical correlations or rather mirror different underlying phenomena. METHODS: In a consecutive sample of 89 Parkinson's disease patients without impulse control disorders, four common tests were evaluated assessing different aspects of impulsivity: impulsiveness trait, decisions under implicit risk with and without losses, and delay discounting. Correlations among test scores were analysed and each score was used as a regressor in a set of grey matter volume (GMV) voxel-based morphometry analyses to explore their brain structural correlates. RESULTS: No significant correlations were found between the different impulsivity tests. Furthermore, their structural brain correlates were divergent. Impulsiveness trait appeared to be associated with lower GMV in dorsal-lateral prefrontal cortices, implicit risk (with losses) with higher GMV in the left nucleus accumbens and lower left insular GMV, implicit risk (without losses) with higher GMV in the left lingual gyrus and lower GMV in the gyri recti and delay discounting with higher GMV in the left nucleus accumbens. CONCLUSIONS: In Parkinson's disease, different impulsivity measures reflect very dissimilar behavioural and brain structural correlates. Our results suggest that parkinsonian impulsivity is not a unitary phenomenon but rather a heterogeneous entity.

[The essence of essential tremor: neurochemical bases]. / La esencia del temblor esencial: bases neuroquimicas.

INTRODUCTION: Essential tremor is the most frequent movement disorder in adults. It has been considered a benign disease, but can result in significant physical and psychosocial disability. Pharmacological treatment is still not very satisfactory. Its causation, pathophysiology and anatomy remain only partially understood. AIMS: An understanding of its neurochemical basis is essential to be able to develop more efficient therapies. We review what is currently known in this field in order to motivate further research and ideas that allow an enhanced understanding of the disease and which foster the development of new pharmacological therapies. DEVELOPMENT: We review the studies conducted to date in humans and in animal models of neurotransmitters (gamma-aminobutyric acid, glutamate, noradrenalin, serotonin, adenosine), proteins and other neurochemical phenomena, such as T-type calcium channels, in essential tremor. CONCLUSIONS: Four neurochemical dysfunctions have been described that basically occur in the cerebellum and the inferior olivary nucleus: alteration of the GABAergic system, increased post-inhibitory rebound via T-type calcium currents, decreased neuronal inhibition mechanisms and an increase in excitatory neurotransmitter activity. These neurochemical dysfunctions would involve an increase in the activity of the deep neurons of the cerebellum with an oscillatory activity that would shift to the thalamic nucleus and the motor cortex, which in turn would lead to the appearance of tremor. Further research is needed to be able to confirm these hypotheses and to continue to advance towards achieving more efficient pharmacological treatments for patients with essential tremor.

TITLE: La esencia del temblor esencial: bases neuroquimicas.Introduccion. El temblor esencial es el trastorno del movimiento mas frecuente en el adulto. Se ha considerado una enfermedad benigna, pero puede ocasionar una importante discapacidad fisica y psicosocial. El tratamiento farmacologico sigue siendo poco satisfactorio. Su etiologia, fisiopatologia y anatomia siguen sin conocerse del todo. Objetivo. El conocimiento de las bases neuroquimicas es fundamental para el desarrollo de terapias mas eficaces. Se revisan los conocimientos actuales en este campo a fin de incentivar nuevas investigaciones e ideas que permitan mejorar la comprension de la enfermedad y que fomenten el desarrollo de nuevas terapias farmacologicas. Desarrollo. Se revisan los trabajos realizados hasta la fecha en humanos y en modelos animales de neurotransmisores (acido gamma-aminobutirico, glutamato, noradrenalina, serotonina, adenosina), proteinas y otros fenomenos neuroquimicos, como los canales de calcio de tipo T en el temblor esencial. Conclusiones. Se han descrito cuatro disfunciones neuroquimicas que acontecerian basicamente en el cerebelo y el nucleo olivar inferior: alteracion del sistema gabergico, aumento del rebote postinhibitorio mediante corrientes de calcio de tipo T, disminucion de los mecanismos de inhibicion neuronal y aumento de la actividad de los neurotransmisores excitatorios. Estas disfunciones neuroquimicas comportarian un aumento de la actividad de las neuronas profundas cerebelosas con actividad oscilatoria, que se trasladaria al nucleo del talamo y a la corteza motora, y comportarian la aparicion del temblor. Son necesarios nuevos estudios para poder confirmar estas hipotesis y seguir avanzando para conseguir tratamientos farmacologicos mas eficaces para los pacientes con temblor esencial.