Development of a neuropsychological battery for the Leukoaraiosis and Disability in the Elderly Study (LADIS): experience and baseline data

The relationship between age-related white matter changes and cognitive performance in independent elderly people is still not clear. The Leukoaraiosis and Disability in the Elderly study (LADIS) involves 11 European centers. It aims to assess the role of the age-related white matter changes as an independent factor in the transition to disability, and in cognitive performance of an independent elderly population. A comprehensive neuropsychological battery was constructed in order to harmonize the cognitive assessment across countries. Patients were evaluated at baseline and during the 3-year follow-up with the Mini-Mental State Examination, a modified version of the VADAS-Cog (Alzheimer's Dementia Assessment Scale plus tests of Delayed recall, Symbol digit, Digit span, Maze, Digit cancellation and Verbal fluency), Trail making and Stroop test. Six hundred thirty-eight patients (mean age 74 +/- 5 years; mean educational level 10 +/- 4, F/M: 351/287) were included in this study. Neuropsychological data were analyzed test by test and also grouped in three compound measures (executive, memory and speed/motor control domains). Older subjects (>74 years) performed significantly worse than younger subjects on the ADAS-Mod and on the tests of memory (t(631) = 3.25; p = 0.001), executive functions (t(581) = 4.68; p = 0.001) and speed/motor control (t(587) = 4.01; p = 0.001). Participants with higher educational level (>8 years of school) showed better performances on the compound measures for memory (t(631) = 3.25; p = 0.001), executive functions (t(581) = 4.68; p = 0.001) and speed/motor control (t(587) = 4.01; p = 0.001). Using multiple regression analysis models to study the influence of demographic variables on cognitive performance, age and education remained important variables influencing test performance. In the LADIS population baseline data, older age and lower educational levels negatively influence neuropsychological performance.     

Amino-truncated beta-amyloid42 peptides in cerebrospinal fluid and prediction of progression of mild cognitive impairment

BACKGROUND: Early identification of patients with mild cognitive impairment (MCI) progressing to Alzheimer disease (MCI-AD) by use of biomarkers in cerebrospinal fluid (CSF) is an essential step toward improving clinical diagnosis and drug development. We evaluated whether different beta-amyloid(42) (Abeta42) peptides can add further information to the combined use of tau and Abeta1-42 for predicting risk of progression of MCI to AD. METHODS: We used xMAP technology to simultaneously quantify different Abeta42 peptides modified at the amino terminus, tau, and phosphorylated tau (P-tau181P) in CSF. Abeta42 peptide concentrations were measured by use of immunoreactivity toward Abeta monoclonal antibodies [3D6 (Abeta42-3D6), WO2 (Abeta42-WO2), 6E10 (Abeta42-6E10), and 4G8 (Abeta42-4G8)]. The discriminant ability of the markers was evaluated by ROC curve analysis. RESULTS: The areas under the curves for the separation of MCI-AD from nonprogressing MCI (MCI-N) were significantly higher when we used Abeta42-3D6/Abeta42-WO2, Abeta42-3D6/Abeta42-6E10, or Abeta42-3D6/Abeta42-4G8 compared with Abeta42-3D6. In addition, differentiation of MCI-N from MCI-AD was improved by quantification of full-length Abeta1-42 (Abeta42-3D6) compared with Abeta42-WO2, Abeta42-6E10, or Abeta42-4G8. Several Abeta42 peptides truncated at the amino terminus (Abeta11-42 and Abeta8-42) were identified in CSF by surface-enhanced laser desorption/ionization time-of-flight technology. CONCLUSION: The CSF markers tau, Abeta42 forms, and P-tau181P, when used as adjuncts to clinical diagnosis, have the potential to help identify AD pathology and could be a valuable asset for early AD diagnosis.     

Labour pain treated with cutaneous injections of sterile water: a randomised controlled trial.

OBJECTIVE: To evaluate the relief of pain in labour with subcutaneous and intracutaneous injections of sterile water, compared with placebo. DESIGN: Randomised controlled trial. SETTING: Labour ward with approximately 3000 deliveries annually in a suburban area near Gothenburg, Sweden. PARTICIPANTS: Ninety-nine pregnant women at term, requiring pain relief for severe lower back pain during the first stage of labour. The women were randomised to receive four injections of 0.1 mL sterile water (without salt) intracutaneously (n = 33), four injections of 0.5 mL sterile water subcutaneously (n = 33) or placebo treatment (n = 33). MAIN OUTCOME MEASURES: Reduction of labour pain measured by visual analogue scale. RESULTS: The median visual analogue scale pain score for labour pain was significantly lower compared with initial values in the two study groups and compared with placebo at 10 and 45 minutes after treatment. The median reductions in visual analogue scores after 10 minutes were 5.0 cm and 4.5 cm in the intracutaneous and subcutaneous injection groups, respectively; women in the placebo group scored a median reduction of 1.7 cm. After 45 minutes the median reductions in the visual analogue scores were 4.9 cm and 4.0 cm in the intracutaneous and subcutaneous injection groups, respectively, compared with 1.0 cm for women in the placebo group. No significant differences in analgesic effect or pain experienced during administration were found between the two study groups. CONCLUSION: The new subcutaneous method of administering sterile water, as well as the earlier described intracutaneous injection method, were effective for the relief of pain in labour.     

Perinatal services and outcomes in Quang Ninh province,Vietnam

Aim: We report baseline results of a community‐based randomized trial for improved neonatal survival in Quang Ninh province, Vietnam (NeoKIP; ISRCTN44599712). The NeoKIP trial seeks to evaluate a method of knowledge implementation called facilitation through group meetings at local health centres with health staff and community key persons. Facilitation is a participatory enabling approach that, if successful, is well suited for scaling up within health systems. The aim of this baseline report is to describe perinatal services provided and neonatal outcomes. Methods: Survey of all health facility registers of service utilization, maternal deaths, stillbirths and neonatal deaths during 2005 in the province. Systematic group interviews of village health workers from all communes. A Geographic Information System database was also established. Results: Three quarters of pregnant women had ≥3 visits to antenatal care. Two hundred and five health facilities, including 18 hospitals, provided delivery care, ranging from 1 to 3258 deliveries/year. Totally there were 17 519 births and 284 neonatal deaths in the province. Neonatal mortality rate was 16/1000 live births, ranging from 10 to 44/1000 in the different districts, with highest rates in the mountainous parts of the province. Only 8% had home deliveries without skilled attendance, but those deliveries resulted in one‐fifth of the neonatal deaths. Conclusion: A relatively good coverage of perinatal care was found in a Vietnamese province, but neonatal mortality varied markedly with geography and level of care. A remaining small proportion of home deliveries generated a substantial part of mortality.     

Neurological abnormalities predict disability: the LADIS (Leukoaraiosis And DISability) study

To investigate the role of neurological abnormalities and magnetic resonance imaging (MRI) lesions in predicting global functional decline in a cohort of initially independent-living elderly subjects. The Leukoaraiosis And DISability (LADIS) Study, involving 11 European centres, was primarily aimed at evaluating age-related white matter changes (ARWMC) as an independent predictor of the transition to disability (according to Instrumental Activities of Daily Living scale) or death in independent elderly subjects that were followed up for 3 years. At baseline, a standardized neurological examination was performed. MRI assessment included age-related white matter changes (ARWMC) grading (mild, moderate, severe according to the Fazekas’ scale), count of lacunar and non-lacunar infarcts, and global atrophy rating. Of the 633 (out of the 639 enrolled) patients with follow-up information (mean age 74.1 ± 5.0 years, 45 % males), 327 (51.7 %) presented at the initial visit with ≥1 neurological abnormality and 242 (38 %) reached the main study outcome. Cox regression analyses, adjusting for MRI features and other determinants of functional decline, showed that the baseline presence of any neurological abnormality independently predicted transition to disability or death [HR (95 % CI) 1.53 (1.01–2.34)]. The hazard increased with increasing number of abnormalities. Among MRI lesions, only ARWMC of severe grade independently predicted disability or death [HR (95 % CI) 2.18 (1.37–3.48)]. In our cohort, presence and number of neurological examination abnormalities predicted global functional decline independent of MRI lesions typical of the aging brain and other determinants of disability in the elderly. Systematically checking for neurological examination abnormalities in older patients may be cost-effective in identifying those at risk of functional decline.     

Disease progression and costs of care in Alzheimer’s disease patients treated with donepezil: a longitudinal naturalistic cohort

Background/Aims

Improved data and methods are needed for modeling disease progression in Alzheimer’s disease (AD) for economic evaluation of treatments. The aim is to estimate prediction models for long-term AD progression and subsequently economic outcomes.

Methods

Three-year follow-up data on 435 patients treated with the cholinesterase inhibitor donepezil in clinical practise were analyzed. Regression models were estimated for long-term prediction of decline in cognitive function (ADAS-cog) and activities in daily living (ADL) ability, risk of institutionalization and costs of care.

Results

The cognitive deterioration was estimated at between 1.6 and 4 ADAS-cog points per every 6?months, increasing with disease severity. Cognitive function was an important predictor of ADL-ability, which itself was the most important predictor of the risk of institutionalization and costs of care. Combining all models in a cross-validation process generated accurate predictions of costs of care at each 6?months follow-up.

Conclusion

The proposed methods for representing AD progression and economic outcomes can be used in micro-simulation models for the economic evaluation of new treatments.