A comparison of sleep profiles in patients with dementia with lewy bodies and Alzheimer's disease

INTRODUCTION: Sleep disturbances are common in healthy old age and in dementia syndromes. Polysomnography has demonstrated typical changes in both Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) with AD being characterised by sundowning and sleep apnoea and DLB patients showing more disturbances of movement control during sleep. The technical difficulties associated with EEG sleep recordings mean that polysomnography is not possible out of specialist centres. OBJECTIVES: To use questionnaires to assess the frequency of sleep disturbances in patients with Alzheimer's disease and dementia with Lewy bodies. METHOD: The sleep profiles of twenty patients with AD and 17 with DLB were assessed using three questionnaires, one designed to assess night time sleep disturbance, one day time sleepiness and the last carer burden. The sleep questionnaires were repeated in a subgroup after treatment with a cholinesterase inhibitor (rivastigmine). RESULTS: Level of sleep disturbance in both groups was high. DLB patients had more overall sleep disturbance, more movement disorders whilst asleep and more abnormal day time sleepiness. Treatment with rivastigmine produced a trend towards normalisation of sleep profile in a small number of subjects. CONCLUSIONS: Both groups have extensive sleep problems. The DLB and AD groups have different sleep profiles that are of diagnostic importance and may suggest different treatment strategies. The results are consistent with those found from polysomnographic assessment and suggest that the questionnaires used are sensitive to detect differences previously documented with polysomnography.     

A multicentre, randomized, double-blind, placebo-controlled study to evaluate the efficacy, tolerability and safety of two doses of metrifonate in patients with mild-to-moderate Alzheimer's disease: the MALT study

BACKGROUND: Metrifonate is a long-lasting acetylcholinesterase inhibitor being developed for the symptomatic treatment of Alzheimer's disease (AD).OBJECTIVES: This study compared the efficacy, tolerability and safety of two doses of metrifonate in patients with mild-to-moderate AD, over a 26-week treatment period. METHODS: Six hundred and five patients were randomized to placebo (n=208), a 40/50 mg dose (40 or 50 mg by weight; n=200) or a 60/80 mg dose (60 or 80 mg by weight; n=197) metrifonate. Patients randomized to receive metrifonate were administered a once-daily loading dose of 80 or 120 mg based on weight for 2 weeks, followed by the relevant maintenance dose for 24 weeks. Four main clinical domains of AD were assessed: cognition (ADAS-cog and MMSE), psychiatric and behavioural symptoms (ADAS-noncog and NPI), instrumental and basic activities of daily living (DAD) and global functioning (CIBIC-plus, CIBIS-plus and GDS).RESULTS: ADAS-cog performance was significantly improved in the 60/80 mg and 40/50 mg dose groups, compared with placebo, in the intention-to-treat (ITT) population. In addition, statistically significant treatment differences were demonstrated between the 60/80 mg dose group and placebo on MMSE, ADAS-noncog, the NPI subitems of hallucinations and apathy, DAD, CIBIC-plus, CIBIS-plus and the GDS. The performance of the 40/50 mg dose group was also significantly superior to placebo on the CIBIS-plus and the NPI subitem aberrant motor behaviour. CONCLUSIONS: Metrifonate significantly improved a wide range of symptoms across all four clinical domains of AD in a dose-dependent manner, and was safe and well tolerated at both doses studied.     

EEG findings in dementia with Lewy bodies and Alzheimer's disease

OBJECTIVES: To evaluate the role of the EEG in the diagnosis of dementia with Lewy bodies (DLB). METHODS: Standard EEG recordings from 14 patients with DLB confirmed at postmortem were examined and were compared with the records from 11 patients with Alzheimer's disease confirmed at postmortem RESULTS: Seventeen of the total of 19 records from the patients with DLB were abnormal. Thirteen showed loss of alpha activity as the dominant rhythm and half had slow wave transient activity in the temporal lobe areas. This slow wave transient activity correlated with a clinical history of loss of consciousness. The patients with Alzheimer's disease were less likely to show transient slow waves and tended to have less marked slowing of dominant rhythm. CONCLUSIONS: The greater slowing of the EEG in DLB than in Alzheimer's disease may be related to a greater loss of choline acetyltransferase found in DLB. Temporal slow wave transients may be a useful diagnostic feature in DLB and may help to explain the transient disturbance of consciousness which is characteristic of the disorder.     

Static balance improvement in elderly after dorsiflexors electrostimulation training

The purpose of the present study was to determine the effect of dorsiflexors ElectroStimulation (ES) training, on postural tasks of increasing difficulty in the elderly. Twenty-one elderly adults were randomly assigned into one of two groups: a Training (TG) and a Control Group (CG). The TG (n=10) performed (4 weeks, 4 s/week, 40 min/session) superimposed (electrically evoked and voluntary activation) isometric dorsiflexions (ankle 100°) while seated. Biphasic, rectangular symmetrical pulses (300 ms, 70 Hz, 20–60 mA) were used to provoke maximal muscle activation. Participants performed three static balance tasks (Normal Quiet Stance, Sharpened Romberg, and One-Legged Stance) during which postural sway was quantified using maximum range and standard deviation of Centre of Pressure displacement (Kistler 9281C, 1,000 Hz). Bipolar surface electrodes were used to record the Electromyographic activity (EMG) of Tibialis Anterior, Medial Gastrocnemius, Rectus Femoris and Semi-Tendineous. Two-dimensional kinematic data were collected (60 Hz) and analyzed using the APAS Motion Analysis software. The body was modeled as a five-segment rigid link system. Isometric dorsiflexion moment/angular position relationship was also established using a Cybex dynamometer. ES training resulted in decreased postural sway (P<0.05), greater ankle muscles EMG activity (P<0.001), greater stability of the ankle joint (P<0.05) and significant changes in mean position of all three joints of the lower limb. In addition, dorsiflexion moment significantly (P<0.001) increased as a result of ES training. It is concluded that dorsiflexors ES training, could reduce postural sway and the use of ankle muscles, more characteristic of young adults, might appear in the elderly as well.     

Immunohistochemical evaluation of TGF-β and extracellular matrix proteins expression in rat squamous cell carcinomas

OBJECTIVE: The aim of this study was to establish a possible association between the degree of differentiation of squamous cell carcinomas (SCC) derived from rat oral tissues treated in vivo with the carcinogen 4NQO, and the expression of TGF-β on epithelial cells and the distribution of extracellular matrix proteins (laminin-collagen type IV).
MATERIALS AND METHODS: A parent tumour showing a spectrum of differentiation was used to establish clonal subpopulations that formed differentiated SCC and undifferentiated (spindle cell phenotype) tumours following transplantation to athymic mice.
RESULTS tmmunohistological findings revealed the absence of TGF-β staining on epithelial cells and extracellular matrix proteins in spindle cell tumours. In contrast, staining of SCC revealed a significant number of TGF-β positive cells and the presence of extracellular matrix proteins.
CONCLUSIONS: The findings suggested that there is a positive correlation between histological differentiation, TGF-β expression and the elaboration of extracellular matrix proteins.     

Distribution of T cells and signs of T-cell activation in the rheumatoid joint: implications for semiquantitative comparative histology

A prerequisite for comparative histology of synovial tissue by means of biopsies is insight into the distribution of a marker under study. This investigation focuses on the variation in the presence of T cells and signs of T-cell activation within the rheumatoid joint. For this purpose, multiple slides from several pieces of synovial tissue from different parts of a joint were stained and scored for the expression of CD3, CD25, HLA-DR, Ki67 and interferon-gamma. The variation in scores for the presence of T cells and markers of activation was more pronounced in slides prepared from different pieces of tissue than in slides from one piece of tissue. Based on multiple analysis of variance, methods are suggested to establish a reliable overall score for the expression of a certain marker within a joint. Following validation, such methods may prove to be useful by allowing semiquantitative histology of synovial tissue for studies on arthritis.      

A comparison of computerized and pencil-and-paper tasks in assessing cognitive function in community-dwelling older people in the Newcastle 85+ Pilot Study

OBJECTIVES: To compare the acceptability and feasibility of computerized and pencil-and-paper tests of cognitive function in 85-year-old people. DESIGN: Group comparison of participants randomly allocated to pencil-and-paper (Wechsler Adult Intelligence and Memory Scales) or computerized (Cognitive Drug Research) tests of verbal memory and attention. SETTING: The Newcastle 85+ Pilot Study was the precursor to the Newcastle 85+ Study a United Kingdom Medical Research Council/Biotechnology and Biological Sciences Research Council cohort study of health and aging in the oldest-old age group. PARTICIPANTS: Eighty-one community-dwelling individuals aged 85. MEASUREMENTS: Participant and researcher acceptability, completion rates, time taken, validity as cognitive measures, and psychometric utility. RESULTS: Participants randomized to computerized tests were less likely to rate the cognitive function tests as difficult (odds ratio (OR)=0.16, 95% confidence interval (CI)=0.07-0.39), stressful (OR=0.18, 95% CI=0.07-0.45), or unacceptable (OR=0.18, 95% CI=0.08-0.48) than those randomized to pencil-and-paper tests. Researchers were also less likely to rate participants as being distressed in the computer test group (OR=0.19, 95% CI=0.07-0.46). Pencil-and-paper tasks took participants less time to complete (mean+/-standard deviation 18+/-4 minutes vs 26+/-4 minutes) but had fewer participants who could complete all tasks (91% vs 100%). Both types of task were equally good measures of cognitive function. CONCLUSION: Computerized and pencil-and-paper tests are both feasible and useful means of assessing cognitive function in the oldest-old age group. Computerized tests are more acceptable to participants and administrators.