A Longitudinal Study of Neurocognition in Dementia with Lewy Bodies Compared to Alzheimer's Disease.

INTRODUCTION: There are relatively few longitudinal studies on the differences in cognitive decline between Alzheimer's disease (AD) and dementia with Lewy bodies (DLB), and the majority of existing studies have suboptimal designs. AIM: We investigated the differences in cognitive decline in AD compared to DLB over 4 years and cognitive domain predictors of progression. METHODS: In a longitudinal study, 266 patients with first-time diagnosis of mild dementia were included and followed annually. The patients were tested annually with neuropsychological tests and screening instruments [MMSE (Mini-Mental Status Examination), Clinical Dementia Rating (CDR), the second edition of California Verbal Learning Test (CVLT-II), Trail Making Test A & B (TMT A & B), Stroop test, Controlled Oral Word Associations Test (COWAT) animal naming, Boston Naming Test, Visual Object and Space Perception Battery (VOSP) Cubes and Silhouettes]. Longitudinal analyses were performed with linear mixed effects (LME) models and Cox regression. Both specific neuropsychological tests and cognitive domains were analyzed. RESULTS: This study sample comprised 119 AD and 67 DLB patients. In TMT A, the DLB patients had a faster decline over 4 years than patients with AD (p = 0.013). No other longitudinal differences in specific neuropsychological tests were found. Higher executive domain scores at baseline were associated with a longer time to reach severe dementia (CDR = 3) or death for the total sample (p = 0.032). High or low visuospatial function at baseline was not found to be associated with cognitive decline (MMSE) or progression of dementia severity (CDR) over time. CONCLUSION: Over 4 years, patients with DLB had a faster decline in TMT A than patients with AD, but this should be interpreted cautiously. Beyond this, there was little support for faster decline in DLB patients neuropsychologically than in AD patients.

Stress in School. Some Empirical Hints on the Circadian Cortisol Rhythm of Children in Outdoor and Indoor Classes.

This prospective longitudinal survey compared the stress levels of students taught using an outdoor curriculum in a forest, with children in a normal school setting. We were especially interested in the effect outdoor teaching might have on the children's normal diurnal cortisol rhythm. 48 children (mean age = 11.23; standard deviation (SD) = 0.46) were enrolled, with 37 in the intervention group (IG), and 11 in the control group (CG). The intervention consisted of one full school day per week in the forest over the school year. Stress levels were measured in cortisol with three samples of saliva per day. Furthermore, the data allowed for statistical control of physical activity (PA) values. For data analysis, we used a linear mixed-effects model (LMM) with random intercept and general correlation matrix for the within-unit residuals. The LMM yields that IG have expected greater decline of cortisol compared to CG; rate 0.069 µg/L vs. 0.0102 µg/L (log-units/2 h), p = 0.009. PA does not show a statistically significant interaction with cortisol (p = 0.857), despite being higher in the intervention group (p < 0.001). The main effect in our measures was that the IG had a steady decline of cortisol during the school day. This is in accordance with a healthy child's diurnal rhythm, with a significant decline of cortisol from morning to noon. This effect is constant over the school year. The CG does not show this decline during either measurement day. Further research is needed to fully explain this interesting phenomenon.

A longitudinal study of anxiety and cognitive decline in dementia with Lewy bodies and Alzheimer's disease.

BACKGROUND: Anxiety in dementia is common but not well studied. We studied the associations of anxiety longitudinally in Alzheimer's disease (AD) and dementia with Lewy bodies (DLB). METHODS: In total, 194 patients with a first-time diagnosis of dementia were included (n = 122 patients with AD, n = 72 patients with DLB). Caregivers rated the patients' anxiety using the Neuropsychiatric Inventory, and self-reported anxiety was assessed with the anxiety and tension items on the Montgomery-Åsberg Depression Rating Scale. The Mini Mental State Examination was used to assess cognitive outcome, and the Clinical Dementia Rating (CDR)-Global and CDR boxes were used for dementia severity. Linear mixed effects models were used for longitudinal analysis. RESULTS: Neither in the total sample nor in AD or DLB was caregiver-rated anxiety significantly associated with cognitive decline or dementia severity over a 4-year period. However, in patients with DLB, self-reported anxiety was associated with a slower cognitive decline than in patients with AD. No support was found for patients with DLB with clinical anxiety having a faster decline than patients with DLB without clinical anxiety. Over the course of 4 years, the level of anxiety declined in DLB and increased in AD. CONCLUSIONS: Anxiety does not seem to be an important factor for the rate of cognitive decline or dementia severity over time in patients with a first-time diagnosis of dementia. Further research into anxiety in dementia is needed.

Association of Butyrylcholinesterase-K Allele and Apolipoprotein E ɛ4 Allele with Cognitive Decline in Dementia with Lewy Bodies and Alzheimer's Disease.

BACKGROUND: A common polymorphism of the butyrylcholinesterase gene, the K-variant (BCHE-K) is associated with reduced butyrylcholinesterase (BuChE) activity. Insufficient studies exist regarding the frequency and role of BCHE-K in dementias. OBJECTIVE: To determine the association of BCHE-K and APOEɛ4 with diagnosis and rate of cognitive decline in dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) patients. METHODS: Genomic DNA from 368 subjects (108 AD, 174 DLB, and 86 controls) from two routine clinical cohort studies in Norway; DemVest and TrønderBrain, were genotyped for BCHE-K and APOEɛ4. The mild dementia DemVest subjects received annual Mini-Mental State Examination assessments for five years. RESULTS: BCHE-K frequency was lower in DLB (33.9% ; p <  0.01) than in control subjects (51.2%), and was numerically lower in AD as well (38.9% ; p = 0.11). More rapid cognitive decline was associated with the APOEɛ4 genotype, but not with the BCHE-K genotype. In an exploratory analysis of patients who completed all five follow-up visits, there was greater cognitive decline in BCHE-K carriers in the presence of the APOEɛ4 allele than in the absence of these polymorphisms. CONCLUSION: BCHE-K is associated with a reduced risk for AD and DLB whereas APOEɛ4 is associated with more rapid cognitive decline. The greater cognitive decline in individuals with both APOEɛ4 and BCHE-K alleles require prospective confirmation in well-controlled trials.

Twelve-month retention of CPR skills with automatic correcting verbal feedback.

AIM: To evaluate the retention of CPR skills 12 months after initial training, using a manikin equipped with a computer-based voice advisory feedback system. METHODS: Thirty-five volunteers had individual 20 min training sessions without an instructor on a manikin with computer-based voice advisory feedback. The feedback depended on the performance as measured by the manikin computer system versus set limits for ventilation and compression variables. Twelve of the volunteers received additional ten 3-min self-training sessions during the following month making a total of 50 min training. All ventilation and compression variables when the volunteers were tested before, immediately after and 6 months after training have previously been reported. The volunteers were now tested 12 months after the initial training session with activated feedback. RESULTS: There were virtually no changes in CPR skills when tested with active feedback 12 months after initial training versus immediately or 6 months post-training. The only exception was a slightly lower number of compressions per minute at 12 months versus immediate post-training in the subgroup with 20 min of initial training, 47+/-4 versus 52+/-4, p = 0.008. There were no differences between the 20 and 50 min training subgroups at 12 months. CONCLUSIONS: Computer-based voice advisory feedback can improve the performance of basic life support skills on a manikin with no deterioration in feedback supported performance after 12 months.

Retention of basic life support skills 6 months after training with an automated voice advisory manikin system without instructor involvement.

AIM: To evaluate the retention of skills 6 months after training in ventilation and chest compressions (CPR) on a manikin with computer based on-line voice advisory feedback and the possible effects of initial overtraining. METHODS: Thirty five volunteers had 20 min provisional CPR training on a manikin with computer based voice advisory feedback but without an instructor. The appropriate feedback was taken from a pre-recorded list depending on performance measured by the manikin--computer system versus set limits for ventilation and compression variables. One group in addition was randomised to receive 10 similar 3 min training sessions during 1 week in the following month (overtrained group). All ventilation and compression variables were measured without feedback before and after the initial training session, with feedback immediately thereafter, and both without and with feedback 6 months after the initial training session. RESULTS: The initial training improved all variables. Compressions with correct depth increased from a mean of 33 to 77%, and correct inflations from a mean of 9 to 58%. After 6 months, the results for the controls were not significantly different from pre-training, except for a higher of correct inflations (18%), while the overtrained group had better retention of skills including the correct compression depth (mean 61%) and inflations (mean 42%). When verbal feedback was added both the compressions and ventilations immediately improved both when tested immediately and 6 months after the initial training session. CONCLUSIONS: The computer-based voice advisory manikin (VAM) feedback system can improve immediate performance of basic life support (BLS) skills, with better long-term retention with overtraining.

White matter hyperintensities and the course of depressive symptoms in elderly people with mild dementia.

OBJECTIVES: To explore the relationship between white matter hyperintensities (WMH) and the prevalence and course of depressive symptoms in mild Alzheimer's disease (AD) and Lewy body dementia. DESIGN: This is a prospective cohort study conducted in secondary care outpatient clinics in western Norway. SUBJECTS: The study population consisted of 77 elderly people with mild dementia diagnosed according to standardised criteria. METHODS: Structured clinical interviews and physical, neurological, psychiatric, and neuropsychological examinations were performed and routine blood tests were taken. Depression was assessed using the depression subitem of the Neuropsychiatric Inventory and the Montgomery-Åsberg Depression Rating Scale (MADRS). A standardised protocol for magnetic resonance imaging scan was used, and the volumes of WMH were quantified using an automated method, followed by manual editing. RESULTS: The volumes of total and frontal deep WMH were significantly and positively correlated with baseline severity of depressive symptoms, and depressed patients had significantly higher volumes of total and frontal deep WMH than non-depressed patients. Higher volumes of WMH were also associated with having a high MADRS score and incident and persistent depression at follow-up. After adjustment for potential confounders, frontal deep WMH, in addition to prior depression and non-AD dementia, were still significantly associated with baseline depressive symptoms (p = 0.015, OR 3.703, 95% CI 1.294-10.593). Similar results emerged for total WMH. CONCLUSION: In elderly people with mild dementia, volumes of WMH, in particular frontal deep WMH, were positively correlated with baseline severity of depressive symptoms, and seemed to be associated with persistent and incident depression at follow-up. Further studies of the mechanisms that determine the course of depression in mild dementia are needed.

Delaying defibrillation to give basic cardiopulmonary resuscitation to patients with out-of-hospital ventricular fibrillation: a randomized trial.

CONTEXT: Defibrillation as soon as possible is standard treatment for patients with ventricular fibrillation. A nonrandomized study indicates that after a few minutes of ventricular fibrillation, delaying defibrillation to give cardiopulmonary resuscitation (CPR) first might improve the outcome. OBJECTIVE: To determine the effects of CPR before defibrillation on outcome in patients with ventricular fibrillation and with response times either up to or longer than 5 minutes. DESIGN, SETTING, AND PATIENTS: Randomized trial of 200 patients with out-of-hospital ventricular fibrillation in Oslo, Norway, between June 1998 and May 2001. Patients received either standard care with immediate defibrillation (n = 96) or CPR first with 3 minutes of basic CPR by ambulance personnel prior to defibrillation (n = 104). If initial defibrillation was unsuccessful, the standard group received 1 minute of CPR before additional defibrillation attempts compared with 3 minutes in the CPR first group. MAIN OUTCOME MEASURE: Primary end point was survival to hospital discharge. Secondary end points were hospital admission with return of spontaneous circulation (ROSC), 1-year survival, and neurological outcome. A prespecified analysis examined subgroups with response times either up to or longer than 5 minutes. RESULTS: In the standard group, 14 (15%) of 96 patients survived to hospital discharge vs 23 (22%) of 104 in the CPR first group (P =.17). There were no differences in ROSC rates between the standard group (56% [58/104]) and the CPR first group (46% [44/96]; P =.16); or in 1-year survival (20% [21/104] and 15% [14/96], respectively; P =.30). In subgroup analysis for patients with ambulance response times of either up to 5 minutes or shorter, there were no differences in any outcome variables between the CPR first group (n = 40) and the standard group (n = 41). For patients with response intervals of longer than 5 minutes, more patients achieved ROSC in the CPR first group (58% [37/64]) compared with the standard group (38% [21/55]; odds ratio [OR], 2.22; 95% confidence interval [CI], 1.06-4.63; P =.04); survival to hospital discharge (22% [14/64] vs 4% [2/55]; OR, 7.42; 95% CI, 1.61-34.3; P =.006); and 1-year survival (20% [13/64] vs 4% [2/55]; OR, 6.76; 95% CI, 1.42-31.4; P =.01). Thirty-three (89%) of 37 patients who survived to hospital discharge had no or minor reductions in neurological status with no difference between the groups. CONCLUSIONS: Compared with standard care for ventricular fibrillation, CPR first prior to defibrillation offered no advantage in improving outcomes for this entire study population or for patients with ambulance response times shorter than 5 minutes. However, the patients with ventricular fibrillation and ambulance response intervals longer than 5 minutes had better outcomes with CPR first before defibrillation was attempted. These results require confirmation in additional randomized trials.