Longitudinal degeneration of the basal forebrain predicts subsequent dementia in Parkinson's disease.

OBJECTIVES: Cholinergic dysfunction plays a prominent role in cognitive impairment in Parkinson's disease (PD). The aim of this study was to assess the relationship of baseline and longitudinal basal forebrain atrophy with cognitive decline and dementia in PD. METHODS: We included 106 non-demented PD patients, 19 PD dementia (PDD) patients and 42 controls with longitudinal structural MRI and cognitive testing. After 4.2 ± 1.8 years, 20 non-demented PD patients were diagnosed with dementia (PD-dementia converters), whereas the rest of PD patients remained non-demented (stable-PD). We compared MRI volumes of the medial septum/diagonal band (Ch1/Ch2) and nucleus basalis of Meynert (Ch4) between groups. Cox regression analyses were applied to test whether Ch1/Ch2 or Ch4 atrophy could predict future dementia and linear mixed models assessed their association with cognitive decline. RESULTS: Compared to controls, we found reduced Ch4 baseline volumes in PD-dementia converters (p = .003) and those who already had PDD (p < .001) but not in stable-PD. Over time, there was a greater loss in Ch1/Ch2 volumes in PD-dementia converters and PDD compared to the other groups (p = .004). Baseline and longitudinal Ch4 volumes were associated with cognition (p < .002) and longitudinal Ch4 atrophy predicted future dementia (p = .009). CONCLUSIONS: Atrophy of Ch4 precedes and predicts future dementia in PD and is followed by changes in Ch1/Ch2, reflecting a posterior-anterior pattern of basal forebrain atrophy. This pattern could be used to track the spread of cholinergic degeneration and identify patients at risk of developing dementia.

A quick test of cognitive speed can predict development of dementia in Parkinson's disease.

Parkinson's disease (PD) patients frequently develop cognitive impairment. There is a need for brief clinical assessments identifying PD patients at high risk of progressing to dementia. In this study, we look into predicting dementia in PD and underlying structural and functional correlates to cognitive decline in PD. We included 175 patients with PD, 30 with PD dementia, 51 neurologically healthy controls and 121 patients with Alzheimer's disease (AD) from Skane University Hospital, BIOFINDER cohorts. All underwent cognitive tests, including MMSE, 10-word list delayed recall (ADAS-cog), A Quick Test of cognitive speed (AQT), Letter S fluency, Clock Drawing Test (CDT) and pentagon copying. In non-demented patients with PD, abnormal AQT and CDT results predicted an increased risk of subsequent development of dementia (hazard ratio 2.2 for both). When comparing the cognitive profile between PD and AD, decreased performance on AQT, which measures attention and processing speed, was more typical in PD. Lastly, we investigated the underlying structural and functional correlates for the PD-specific test AQT with magnetic resonance imaging. In PD patients, decreased performance on AQT was associated with i) cortical thinning in temporoparietal regions, ii) changes in diffusion MRI, especially in the cingulum tract, and iii) decreased functional connectivity in posterior brain networks.

Early do-not-resuscitate orders in intracerebral haemorrhage; frequency and predictive value for death and functional outcome. A retrospective cohort study.

INTRODUCTION: In former studies from North America early Do-Not-Resuscitate orders (DNR orders) in patients with intracerebral haemorrhage (ICH) had negative prognostic impact on mortality. The influence of DNR orders on functional outcome and whether DNR orders are grounded on relevant patient characteristics is unknown. We aimed to determine the frequency and predictive factors of DNR-orders and its association to prognosis, in ICH patients, in Scandinavia. METHODS: In 197 consecutive ICH patients admitted to Skåne University Hospital, Malmö, Sweden, between January 2007 and June 2009, information of the presence of DNR orders within 48 hours, clinical and radiological characteristics was retrieved by review of patient medical journal and computed tomography scans. Determinants of DNR-orders, one-month case fatality and bad functional outcome (modified Rankin Scale, grade 4-6) were assessed by logistic regression analysis. RESULTS: DNR orders were made in 41% of the cases. After adjustment for confounding factors, age ≥ 75 years (Odds Ratio (95% confidence interval) 4.2(1.8-9.6)), former stroke (5.1(1.9-3.1)), Reaction Level Scale grade 2-3 and 4 (7.0(2.8-17.5) and (4.1(1.2-13.5), respectively) and intraventricular haemorrhage (3.8(1.6-9.4)) were independent determinants of early DNR orders. Independent predictors of one-month case fatality was age ≥ 75 years (3.7(1.4-9.6)) volume ≥ 30 ml (3.5(1.3-9.6)) and DNR orders (3.5(1.5-8.6)). Seizure (6.0(1.04-34.2) and brain stem hemorrhage (8.0(1.1-58.4)) were related to bad functional outcome, whereas early DNR order was not (3.5(0.99-12.7)). CONCLUSIONS: Well known prognostic factors are determinants for DNR orders, however DNR orders are independently related to one-month case fatality. In addition to improvements of the local routines, we welcome a change of attitude with an enhanced awareness of the definition of, and a more careful approach with respect to DNR orders.