The prevalence of impulsive compulsive behaviors in patients treated with apomorphine infusion: a retrospective analysis / Prevalência de comportamentos impulsivo-compulsivos em pacientes tratados com infusão de apomorfina: análise retrospectiva

ABSTRACT Background: Impulsive compulsive behaviors (ICBs) can affect a significant number of Parkinson's disease (PD) patients. Objective: We have studied brain samples from a brain bank of PD patients who received apomorphine via continuous infusion in life to assess the prevalence and outcome of ICBs. Methods: A search on the Queen Square Brain Bank (QSBB) database for cases donated from 2005 to 2016 with a pathological diagnosis of idiopathic PD was conducted. Notes of all donors who used apomorphine via continuous infusion for at least three months were reviewed. Clinical and demographic data were collected, as well as detailed information on treatment, prevalence and outcomes of ICBs. Results: 193 PD cases, 124 males and 69 females, with an average age at disease onset of 60.2 years and average disease duration of 17.2 years were reviewed. Dementia occurred in nearly half of the sample, depression in one quarter, and dyskinesias in a little over 40%. The prevalence of ICBs was 14.5%. Twenty-four individuals used apomorphine infusion for more than three months. Patients on apomorphine had younger age at disease onset, longer disease duration, and higher prevalence of dyskinesias. The prevalence of de novo ICB cases among patients on apomorphine was 8.3%. Apomorphine infusion was used for an average of 63.1 months on an average maximum dose of 79.5 mg per day. Ten patients remained on apomorphine until death. Conclusions: Apomorphine can be used as an alternative treatment for patients with previous ICBs as it has low risk of triggering recurrence of ICBs.

RESUMO Antecedentes: Comportamentos impulsivo-compulsivos (CICs) podem acometer uma parcela significativa de indivíduos com doença de Parkinson (DP). Objetivo: Nós estudamos amostras de tecido cerebral de uma população de pacientes com DP de um banco de cérebros que receberam apomorfina por infusão contínua em vida, com a finalidade de avaliar a prevalência e o desfecho dos CICs. Métodos: Uma pesquisa no banco de dados do Banco de Cérebros de Queen Square foi conduzida à procura de doações recebidas entre 2005 e 2016 com diagnóstico anatomopatológico de DP idiopática. Os prontuários de todos os doadores que usaram apomorfina por infusão contínua por um período mínimo de três meses foram revisados. Dados clínicos e demográficos foram coletados, assim como informações detalhadas sobre o tratamento, prevalência e desfecho dos CICs. Resultados: 193 casos de DP, 124 do sexo masculino e 69 do sexo feminino, com idade média de início da doença de 60,2 anos e tempo médio de duração da doença de 17,2 anos, foram revisados. Aproximadamente metade dos casos apresentaram demência, um quarto depressão, e um pouco mais de 40% discinesias. A prevalência de CICs foi 14,5%. Vinte e quatro indivíduos usaram infusão de apomorfina por mais de três meses. Os pacientes que usaram apomorfina apresentaram DP mais cedo, maior duração da doença, e uma maior prevalência de discinesias. A prevalência de novos casos de CICs entre pacientes usando apomorfina foi de 8,3%. Infusão de apomorfina foi usada em média por 63,1 meses a um dose máxima média de 79,5 mg por dia. Dez pacientes permaneceram usando apomorfina até o óbito. Conclusões: Apomorfina pode ser usada como opção de tratamento alternativo para pacientes que apresentarem CICs no passado considerando seu baixo risco de causar recorrência de CICs.

Parkinson's disease determinants, prediction and gene-environment interactions in the UK Biobank.

OBJECTIVE: To systematically investigate the association of environmental risk factors and prodromal features with incident Parkinson's disease (PD) diagnosis and the interaction of genetic risk with these factors. To evaluate whether existing risk prediction algorithms are improved by the inclusion of genetic risk scores. METHODS: We identified individuals with an incident diagnosis of PD (n=1276) and controls (n=500 406) in UK Biobank. We determined the association of risk factors with incident PD using adjusted logistic regression models. We constructed polygenic risk scores (PRSs) using external weights and selected the best PRS from a subset of the cohort (30%). The PRS was used in a separate testing set (70%) to examine gene-environment interactions and compare predictive models for PD. RESULTS: Strong evidence of association (false discovery rate <0.05) was found between PD and a positive family history of PD, a positive family history of dementia, non-smoking, low alcohol consumption, depression, daytime somnolence, epilepsy and earlier menarche. Individuals with the highest 10% of PRSs had increased risk of PD (OR 3.37, 95% CI 2.41 to 4.70) compared with the lowest risk decile. A higher PRS was associated with earlier age at PD diagnosis and inclusion of the PRS in the PREDICT-PD algorithm led to a modest improvement in model performance. We found evidence of an interaction between the PRS and diabetes. INTERPRETATION: Here, we used UK Biobank data to reproduce several well-known associations with PD, to demonstrate the validity of a PRS and to demonstrate a novel gene-environment interaction, whereby the effect of diabetes on PD risk appears to depend on background genetic risk for PD.

Brain iron deposition is linked with cognitive severity in Parkinson's disease.

BACKGROUND: Dementia is common in Parkinson's disease (PD) but measures that track cognitive change in PD are lacking. Brain tissue iron accumulates with age and co-localises with pathological proteins linked to PD dementia such as amyloid. We used quantitative susceptibility mapping (QSM) to detect changes related to cognitive change in PD. METHODS: We assessed 100 patients with early-stage to mid-stage PD, and 37 age-matched controls using the Montreal Cognitive Assessment (MoCA), a validated clinical algorithm for risk of cognitive decline in PD, measures of visuoperceptual function and the Movement Disorders Society Unified Parkinson's Disease Rating Scale part 3 (UPDRS-III). We investigated the association between these measures and QSM, an MRI technique sensitive to brain tissue iron content. RESULTS: We found QSM increases (consistent with higher brain tissue iron content) in PD compared with controls in prefrontal cortex and putamen (p<0.05 corrected for multiple comparisons). Whole brain regression analyses within the PD group identified QSM increases covarying: (1) with lower MoCA scores in the hippocampus and thalamus, (2) with poorer visual function and with higher dementia risk scores in parietal, frontal and medial occipital cortices, (3) with higher UPDRS-III scores in the putamen (all p<0.05 corrected for multiple comparisons). In contrast, atrophy, measured using voxel-based morphometry, showed no differences between groups, or in association with clinical measures. CONCLUSIONS: Brain tissue iron, measured using QSM, can track cognitive involvement in PD. This may be useful to detect signs of early cognitive change to stratify groups for clinical trials and monitor disease progression.