First delirium episode in Parkinson's disease and parkinsonism: incidence, predictors, and outcomes.

To define the incidence, predictors and prognosis of the first hospital delirium episode in Parkinson's disease (PD) and atypical parkinsonism (AP), we identified the first hospital episode of delirium after diagnosis in the Parkinsonism Incidence in North-East Scotland (PINE) study, a prospective community-based incidence cohort of parkinsonism, using chart-based criteria to define delirium. Of 296 patients (189=PD, 107=AP [dementia with Lewy bodies, progressive supranuclear palsy, multiple system atrophy, vascular parkinsonism]), 152 developed delirium (PD = 98, AP = 54). Incidence of first hospital delirium episode per 100 person years was 8.1 (95% confidence interval [CI] 6.6-9.9) in PD and 18.5 (95% CI 13.9-24.7) in AP. Independent predictors of delirium were atypical parkinsonism (Hazard ratio [HR] vs PD = 2.83 [95% CI 1.60-5.03], age in PD but not in AP (HR for 10-year increase 2.29 [95% CI 1.74-3.02]), baseline MMSE (HR = 0.94 [95% CI 0.89-0.99]), APOE ε4 in PD (HR 2.16 [95% CI 1.15-4.08]), and MAPT H1/H1 in PD (HR 2.08 [95% CI 1.08-4.00]). Hazards of dementia and death after delirium vs before delirium were increased (dementia: HR = 6.93 [95% CI 4.18-11.48] in parkinsonism; death: HR = 3.76 [95% CI 2.65-5.35] in PD, 1.59 [95% CI 1.04-2.42] in AP). Delirium is a common non-motor feature of PD and AP and is associated with increased hazards of dementia and mortality. Whether interventions for early identification and treatment improve outcomes requires investigation.

Parkinson's disease and patient related outcomes in stroke: A matched cohort study.

OBJECTIVE: To evaluate post-stroke outcomes in patients with Parkinson's disease (PD). METHODS: A matched cohort study was performed. Stroke patients with PD and non-PD controls were extracted from the Thailand Universal Insurance Database. Logistic regressions were used to evaluate the association between PD and in-hospital outcomes (mortality and complications). The PD-associated long-term mortality was evaluated using Royston-Parmar models. RESULTS: A total of 1967 patients with PD were identified between 2003 and 2015 and matched to controls (1:4) by age, sex, admission year, and stroke type. PD patients had decreased odds of in-hospital death: OR (95% CI) 0.66 (0.52 - 0.84) and 0.61 (0.43 - 0.85) after ischaemic and haemorrhagic strokes, respectively. PD was associated with a length-of-stay greater than median (4 days) after both stroke types: 1.37 (1.21 - 1.56) and 1.45 (1.05 - 2.00), respectively. Ischaemic stroke patients with PD also had increased odds of developing pneumonia, sepsis and AKI: 1.52 (1.2 - 1.83), 1.54 (1.16 - 2.05), and 1.33 (1.02 - 1.73). In haemorrhagic stroke patients, PD was associated with pneumonia: 1.89 (1.31 - 2.72). Survival analyses showed that PD was protective against death in the short term (HR=0.66; 95% CI 0.53-0.83 ischaemic, and HR=0.50; 95% CI 0.37 - 0.68 haemorrhagic stroke), but leads to an increased mortality risk approximately 1 and 3 months after ischaemic and haemorrhagic stroke, respectively. CONCLUSION: PD is associated with a reduced mortality risk during the first 2-4 weeks post-admission but an increased risk thereafter, in addition to increased odds of in-hospital complications and prolonged hospitalisation.

Urate and Homocysteine: Predicting Motor and Cognitive Changes in Newly Diagnosed Parkinson's Disease.

BACKGROUND: Urate and homocysteine are potential biomarkers for disease progression in Parkinson's disease (PD). Baseline serum urate concentration has been shown to predict motor but not cognitive decline. The relationship between serum homocysteine concentration and cognitive and motor impairment is unknown. OBJECTIVES: The aim of this study was to examine the association between baseline serum urate and homocysteine, and prospective measures of disease progression and cognition over 54 months in early PD. METHODS: 154 newly diagnosed PD participants and 99 age-matched controls completed a schedule of assessments at baseline, 18, 36 and 54 months. The Movement Disorders Society Unified Parkinson's Disease Scale Part III (MDS-UPDRS III) was used to assess motor severity. The Montreal Cognitive Assessment (MoCA) was used to assess global cognition. Serum samples drawn at baseline were analysed for urate, homocysteine, red cell folate and vitamin B12 concentrations. RESULTS: Baseline urate was 331.4±83.8 and 302.7±78.0µmol/L for control and PD participants, respectively (p = 0.015). Baseline homocysteine was 9.6±3.3 and 11.1±3.8µmol/L for controls and PD participants, respectively (p < 0.01). Linear mixed effects modelling showed that lower baseline urate (ß= 0.02, p < 0.001) and higher homocysteine (ß= 0.29, p < 0.05) predicted decline in motor function. Only higher homocysteine concentrations at baseline, however, predicted declining MoCA scores over 54 months (ß= 0.11, p < 0.01). CONCLUSIONS: Lower serum urate concentration is associated with worsening motor function; while higher homocysteine concentration is associated with change in motor function and cognitive decline. Therefore, urate and homocysteine may be suitable biomarkers for predicting motor and cognitive decline in early PD.

The Role of Vitamin D in Disease Progression in Early Parkinson's Disease.

BACKGROUND: Previous cross-sectional studies have shown that Parkinson's disease (PD) patients have lower serum 25-hydroxy vitamin D (25(OH)D) concentrations than controls. Vitamin D deficiency was associated with increased disease severity and cognitive impairment in prevalent PD patients. OBJECTIVE: The aim of the study was to determine 25(OH)D in newly diagnosed PD and age-matched controls and to assess if there was an association with clinical outcomes (disease severity, cognition and falls) over the 36-month follow up period. METHODS: A prospective observational study of newly diagnosed PD patients in the North East of England with age-matched controls (PD, n = 145; control, n = 94). Serum 25(OH)D was assessed at baseline and 18 months. Participants underwent clinical assessment at baseline, 18 and 36 months. One hundred and ten participants with PD also took part in a prospective falls study. RESULTS: Mean serum 25(OH)D concentrations were lower in PD than control participants at baseline (44.1±21.7 vs. 52.2±22.1 nmol/L, p < 0.05) and 18 months (44.2±23.6 vs. 55.7±28.8 nmol/L, p < 0.05). Baseline serum 25(OH)D concentration, age, motor score and dosage of dopaminergic medication were significant predictors of variance of motor severity at 36 months ((ΔR2 = 0.039, F = 6.6, p < 0.01). Serum 25(OH)D was not associated with cognition or falls during the follow up period. CONCLUSIONS: Patients with incident PD had significantly lower serum 25(OH)D concentrations than age-matched controls, which may have implications in terms of bone health and fracture risk. There was a small but significant association between vitamin D status at baseline and disease motor severity at 36 months.

Risk of fracture amongst patients with Parkinson's disease and other forms of parkinsonism.

INTRODUCTION: Postural instability, a core feature of parkinsonism, leads to an increased risk of falls and fractures. However, the risk of fracture has not been assessed in an incident cohort of Parkinson's disease and atypical parkinsonism. OBJECTIVES: We determined the absolute and relative fracture risk and predictive variables in a prospective incident cohort of parkinsonian patients and controls. METHODS: Fracture data for 326 incident parkinsonian cases (198 Parkinson's disease, 128 atypical parkinsonism) and 261 controls was recorded annually in the Parkinsonism Incidence in North-East Scotland study. Incidence rates were determined for all fractures and major fractures. Kaplan-Meier curves were used to determine time to first fracture for each group. Stepwise, multivariate Cox regression analysis was used to identify risk factors for fracture in parkinsonian patients. RESULTS: Mean age at recruitment was 74.5 years in all parkinsonian patients (age at diagnosis) and 75 years in controls. The incidence of any fracture was 5.5 (95% CI 4.3-7.0) and 2.0 (1.3-2.9)/100 participant-years for the parkinsonian and control groups respectively, whilst for major fractures due to falls it was 4.2 (3.2-5.5) and 1.4 (0.9-2.2)/100 participant-years respectively. Independent predictors for fractures in parkinsonian patients were osteoporosis, female gender and falling during the follow up period. There was no difference in fracture rates between those with Parkinson's disease and atypical parkinsonism. CONCLUSION: The fracture rate in parkinsonism from the time of diagnosis (about 5% per year) is over three times greater than controls. Fracture risk should be routinely assessed in all parkinsonian patients.

Fibroblast growth factor-20 protects against dopamine neuron loss in vitro and provides functional protection in the 6-hydroxydopamine-lesioned rat model of Parkinson's disease.

Fibroblast growth factor-20 (FGF-20) has been shown to protect dopaminergic neurons against a range of toxic insults in vitro, through activation of fibroblast growth factor receptor 1 (FGFR1). This study set out to examine whether FGF-20 also displayed protective efficacy in the unilateral, 6-hydroxydopamine (6-OHDA) lesion rat model of Parkinson's disease. Initial studies demonstrated that, in embryonic ventral mesencephalic (VM) cultures, FGFR1 was expressed on tyrosine hydroxylase (TH)-positive neurons and that, in line with previous data, FGF-20 (100 and 500 ng/ml) almost completely protected these TH-positive neurons against 6-OHDA-induced toxicity. Co-localisation of FGFR1 and TH staining was also demonstrated in the substantia nigra pars compacta (SNpc) of naïve adult rat brain. In animals subject to 6-OHDA lesion of the nigrostriatal tract, supra-nigral infusion of FGF-20 (2.5 µg/day) for 6 days post-lesion gave significant protection (∼40%) against the loss of TH-positive cells in the SNpc and the loss of striatal TH immunoreactivity. This protection of the nigrostriatal tract was accompanied by a significant preservation of gross locomotion and fine motor movements and reversal of apomorphine-induced contraversive rotations, although forelimb akinesia, assessed using cylinder test reaching, was not improved. These results support a role for FGF-20 in preserving dopamine neuron integrity and some aspects of motor function in a rodent model of Parkinson's disease (PD) and imply a potential neuroprotective role for FGF-20 in this disease.