DRD3 Predicts Cognitive Impairment and Anxiety in Parkinson's Disease: Susceptibility and Protective Effects.

Background: A possible genetic contribution of dopamine D3 receptor (DRD3) to cognitive impairment in Parkinson's disease (PD) has yet to be investigated. Objective: To explore the effects of rs6280 (Ser9Gly) genotype on PD patients' cognitive performance and to clarify possible interactions with psychopathology. Methods: Two hundred and fifty-three consecutive PD patients underwent neurological and neuropsychological evaluations, which included: Unified Parkinson's Disease Rating Scale (UPDRS), Hoehn & Yahr scale (H&Y), Dementia Rating Scale-2 (DRS-2), and Hospital Anxiety and Depression Scale (HADS). rs6280 polymorphism was genotyped for all PD patients and for 270 ethnically matched healthy volunteers (HC). Non-parametric group comparisons and logistic regressions were used for data analyses. Results: rs6280 genotype did not differ between PD and HC groups. PD patients with rs6280 CC genotype had more impaired cognitive performance (i.e., <1st percentile of demographically adjusted norms) on DRS-2 subscales Initiation/Perseveration and Construction than those with TT genotype. These associations remained statistically significant when other covariates (e.g., demographic features, disease duration, severity of motor symptoms in OFF and ON states, anti-parkinsonian medication, and psychopathology symptoms) were taken into consideration. PD patients with rs6280 TC had less anxiety (i.e., HADS Anxiety≥11) than those with TT (p = 0.012). This association was also independent of other covariates. Conclusions: Study findings suggest that rs6280 CC genotype predisposes to executive dysfunction and visuoconstructional deficits, whereas the heterozygous genotype protects from anxiety in PD. These effects do not appear to be dependent of one another. rs6280 is not a genotypic susceptibility factor for PD.

Desfechos psicológicos em longo prazo após alta da terapia intensiva / Long-term psychological outcome after discharge from intensive care

RESUMO Objetivo: Investigar o desfecho psicológico em longo prazo em sobreviventes de doenças críticas, após alta da unidade de terapia intensiva. Métodos: Avaliou-se coorte prospectiva de pacientes sobreviventes após admissão a uma unidade de terapia intensiva mista entre janeiro e setembro de 2010, 6 meses e 5 anos após a alta hospitalar. Aplicaram-se em todos os momentos as seguintes escalas: Dementia Rating Scale-2, Hospital Anxiety and Depression Scale, Post-Traumatic Stress Syndrome 14-Questions Inventory, Euro Quality of Life 5 Dimensions (EQ-5-D) e Visual Analogue Scale (EQ VAS). Resultados: Dentre 267 pacientes, 25 foram avaliados após 6 meses (idade: 62 ± 16 anos). Aos 6 meses, 48% apresentavam comprometimento cognitivo; 24% ansiedade, 16% depressão e 16% transtorno de estresse pós-traumático. Foram reavaliados 5 anos após a alta 17 pacientes, com idade: 65 ± 15 anos. Dentre eles, a frequência de comprometimento cognitivo caiu de 47% para 18% (p = 0,063), em razão da melhora destes pacientes ao longo do tempo e do não surgimento desta condição em outros pacientes após a alta. Ainda após 5 anos, apenas 12% da amostra relatou ansiedade, e nenhum tinha depressão ou transtorno de estresse pós-traumático. Não se encontraram diferenças em termos das escalas EQ-5-D e EQ VAS entre as avaliações após 6 meses e 5 anos. Conclusão: Os sobreviventes não apresentaram declínio progressivo da função cognitiva ou da qualidade de vida dentro de 5 anos após a alta da unidade de terapia intensiva. Os sintomas psicopatológicos tenderam a diminuir com o tempo.

ABSTRACT Objective: To investigate the longterm psychological outcome in survivors of critical illness after intensive care unit discharge. Methods: A prospective cohort of survivors admitted to a mixed intensive care unit between January and September 2010 was evaluated six months and five years after hospital discharge. The Dementia Rating Scale-2, the Hospital Anxiety and Depression Scale, the Posttraumatic stress syndrome 14-questions inventory, the Euro Quality of Life 5 Dimensions (EQ-5-D), and the Visual Analogue Scale (EQ VAS) were assessed at both follow-up periods. Results: Of 267 patients, 25 patients were evaluated at 6 months after discharge (62 ± 16 years); 12 (48%) presented cognitive impairment, 6 (24%) anxiety, 4 (16%) depression, and 4 (16%) post-traumatic stress disorder. Among those re-evaluated five years after discharge (n = 17; 65 ± 15 years), the frequency of cognitive impairment dropped from 8 (47%) to 3 (18%) (p = 0.063), due to improvement in these patients over time, and other patients did not acquire any dysfunction after discharge. At five years after discharge, only two patients (12%) reported anxiety, and none had depression or post-traumatic stress disorder. No differences were found between the six-month and five-year follow-ups regarding EQ-5-D and EQ VAS. Conclusion: Survivors do not show a progressive decline in cognitive function or quality of life within five years after intensive care unit discharge. Psychopathological symptoms tend to decrease with time.