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Effects of rivastigmine on behavioural symptoms in nursing home patients with Alzheimer's disease
S328
P4. Degenerative and neurological disorders
of disease). Cognitive decline was not associated with seizure control, type of myoclonias, EEG and neuroimaging tindings, antiepileptic treatment or degree of neurological disabilities. All patients showed moderate to severe behavioural disorders. Episodes of irritability, sleep disorders and mental slowness were observed in children. Hyperkinetic and socially inappropriate behaviour, anxiety, emotional instability and occasional panic reactions developed in adolescents. PME with neurodegenerative characteristics, unfavourable neurological and mental outcome, evolution toward dementia and behavioural disorders is one of the greatest therapeutic challenges in developmental epileptology.
-1
Diurnal fluctuations of aldehyde dehydrogenase in the brain regions of rats and-ethanol effects on it
V Satanovskaya, L. Bardina’. Institute of Biochemistry National Academy of Sciences of Belarus, Grodno, Belarus Earlier we demonstrated a characteristic circadian variation in the activity of the liver microsomal ethanol oxidizing system but no changes in aldehyde dehydrogenase (ALDH) in rats. The single ethanol injection (2 gikg SW, i.p.) induced changes in this variation [l]. The aim of the present study was to estimate the acute effects of ethanol on ALDH in rat brain regions during 24-h cycle. Male albino rats (The Rappolovo breeding colony, St. Petersburg, Russia) weighing 140-160 g were housed individually in cages with food and water freely available and regular schedule of 12 hours of light and dark periods. Ethanol at a dose of 2.0 g/kg SW, i.p. was administered at 6.00, 12.00, 18.00, 24.00 h. Thirty mm. after the injection the rats were decapitated. The control animals were injected with saline at the same time points. The brains were dried from the blood, and the brain steam, cerebellum, hypothalamus, basal ganglia and right and left large hemisphere were isolated and stored in liquid nitrogen until required. NADdepending total ALDH activity was measured with 5 mM acetaldehyde as substrate [2]. No diurnal fluctuations were found in comparing ALDH activities in the hypothalamus, basal ganglia and cerebellum. The single ethanol injection activated ALDH only in the left hemisphere and only at 6.00 a.m. and 6.00 p.m. (29.4 f 4.7 pmol NADI-I/h/g protein - control; 51.3 f 3.5 - ethanol, p c 0.001 and 28.7 f 2.4 - control; 48.9 f 9.3 - ethanol, p <: 0.05, respectively). No statistically significant differences were found in ALDH of the right hemisphere and other brain regions. Apparently the results obtained indicate a right-left asymmetry of toxicologic ethanol (acetaldehyde) effects on the rat brain which also affects the circadian rhythm of the enzymes. References 111 Bardina L.R. and Satanovskava VI (1991) Effects of alcohol on ethanol L ’ and acetaldehyde metaboliziig systems o&r 24-hr cycle. Proc. 5-th Int. Congr. Biotechnology, Florence, Italy, 1991, A. 95. [2] Erwin V and Deitrich R.A. (1966). Brain aldehyde dehydrogenase. Localisation, purification and properties. J. Biol. Chem. 241, 35333539.
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Effects of rivastigmine on behavioural symptoms in nursing home patients with Alzheimer’s disease
R. Bullock’, R. Moulias*, K.C. Steinwachs3, A. Cicin-Sain4, R. Spiegel”. ’Victoria Hospital, Swindon, UK; 2Hospital Charles Foix, Zvty sur Seine, Fmnce; ‘Klinikum am Eumpakanal, Erlangen, Germany; 4Novartis Pharma AG, UK Changes in behavioural symptoms were assessed in 184 nursing home residents suffering moderately severe to severe Alzheimer’s disease (AD), treated with rivastigmine (ExelonO) at doses up to 6 mg b.i.d. In this 26 week, open-label, multicenter, European study, the primary outcome measure was change from baseline on the 12-item Neuropsychiatric Inventory-Nursing Home version (NPINHO). Following 26 weeks treatment with rivastigmine, more than 40% of all patients showed at least 30% improvement in total NPINH0 score from baseline. For patients with behavioural symptoms present at baseline, greater than 53% showed improvement in each of the 12 items of the NPI-NHQ. Mean changes from baseline were statistically significant for all NPI-NH0 items except depression. only a minority of patients had no symptoms at baseline, and the majority (greater than 70%) of these did not develop symptoms during treatment with rivastigmine. The study also provided evidence of stabilisation or even slight improvement of cognitive function with rivastigmine treatment. Although gastrointestinal adverse events were relatively frequent, rivastigmine was safe and well tolerated in the vast majority of these mostly multimorbid patients.
-1
Statins in the treatment of Alzheimers Disease
B. Winblad’, L.A. Carlsson*, M. Crisby’. ‘Neumtec, Division of Geriatric Medicine, Karolinska Institute, Huddinge University Hospital, 141 86 Huddinge; ‘Gustaf Vth Research Institute, Karolinska Institute, I71 76 Stockholm, Sweden Alzheimers Disease (AD) and cardiovascular disease (CAD) have multi-factorial causes, some of which are related to genetic disorders and chronic intlammation. There is ample evidence suggesting that risk factors for CAD and stroke are also associated with cognitive impairment and AD. The challenge of early detection of dementia is to accurately distinguish the symptoms of brain failure. As patients move from cognitively normal state to dementia, they pass through the transitional phase of mild cognitive impairment (MCI). Deposition of P-amyloid (A@) in the amyloid plaques and cerebrovascular wall and neurofibrillatory tangles are neuropathological hallmarks of AD. Activated microglia, astrocyte proliferation and increased expression of cytokines in the vicinity of amyloid plaques are prominent markers of inflammation seen in AD. The brain capillary endothelium is of major importance for the delivery of oxygen, glucose and other vital nutrients that are essential in maintaining a stable internal milieu in the CNS. Imbalance in these processes, due to chronic impaired capillary flow caused by changes in the vasculature and blood brain barrier (BBB) may contribute to progression of AD. Prevoius neuropathological studies illustrate the close anatomic relationship between capillaries and plaques in AD brains. Furthermore, brain endothelial cells are structurally and biochemically altered in AD. It has been hypothesized that AP deposition results in damage
P4. Degenerative and neurological disorders
of disease). Cognitive decline was not associated with seizure control, type of myoclonias, EEG and neuroimaging tindings, antiepileptic treatment or degree of neurological disabilities. All patients showed moderate to severe behavioural disorders. Episodes of irritability, sleep disorders and mental slowness were observed in children. Hyperkinetic and socially inappropriate behaviour, anxiety, emotional instability and occasional panic reactions developed in adolescents. PME with neurodegenerative characteristics, unfavourable neurological and mental outcome, evolution toward dementia and behavioural disorders is one of the greatest therapeutic challenges in developmental epileptology.
-1
Diurnal fluctuations of aldehyde dehydrogenase in the brain regions of rats and-ethanol effects on it
V Satanovskaya, L. Bardina’. Institute of Biochemistry National Academy of Sciences of Belarus, Grodno, Belarus Earlier we demonstrated a characteristic circadian variation in the activity of the liver microsomal ethanol oxidizing system but no changes in aldehyde dehydrogenase (ALDH) in rats. The single ethanol injection (2 gikg SW, i.p.) induced changes in this variation [l]. The aim of the present study was to estimate the acute effects of ethanol on ALDH in rat brain regions during 24-h cycle. Male albino rats (The Rappolovo breeding colony, St. Petersburg, Russia) weighing 140-160 g were housed individually in cages with food and water freely available and regular schedule of 12 hours of light and dark periods. Ethanol at a dose of 2.0 g/kg SW, i.p. was administered at 6.00, 12.00, 18.00, 24.00 h. Thirty mm. after the injection the rats were decapitated. The control animals were injected with saline at the same time points. The brains were dried from the blood, and the brain steam, cerebellum, hypothalamus, basal ganglia and right and left large hemisphere were isolated and stored in liquid nitrogen until required. NADdepending total ALDH activity was measured with 5 mM acetaldehyde as substrate [2]. No diurnal fluctuations were found in comparing ALDH activities in the hypothalamus, basal ganglia and cerebellum. The single ethanol injection activated ALDH only in the left hemisphere and only at 6.00 a.m. and 6.00 p.m. (29.4 f 4.7 pmol NADI-I/h/g protein - control; 51.3 f 3.5 - ethanol, p c 0.001 and 28.7 f 2.4 - control; 48.9 f 9.3 - ethanol, p <: 0.05, respectively). No statistically significant differences were found in ALDH of the right hemisphere and other brain regions. Apparently the results obtained indicate a right-left asymmetry of toxicologic ethanol (acetaldehyde) effects on the rat brain which also affects the circadian rhythm of the enzymes. References 111 Bardina L.R. and Satanovskava VI (1991) Effects of alcohol on ethanol L ’ and acetaldehyde metaboliziig systems o&r 24-hr cycle. Proc. 5-th Int. Congr. Biotechnology, Florence, Italy, 1991, A. 95. [2] Erwin V and Deitrich R.A. (1966). Brain aldehyde dehydrogenase. Localisation, purification and properties. J. Biol. Chem. 241, 35333539.
-1
Effects of rivastigmine on behavioural symptoms in nursing home patients with Alzheimer’s disease
R. Bullock’, R. Moulias*, K.C. Steinwachs3, A. Cicin-Sain4, R. Spiegel”. ’Victoria Hospital, Swindon, UK; 2Hospital Charles Foix, Zvty sur Seine, Fmnce; ‘Klinikum am Eumpakanal, Erlangen, Germany; 4Novartis Pharma AG, UK Changes in behavioural symptoms were assessed in 184 nursing home residents suffering moderately severe to severe Alzheimer’s disease (AD), treated with rivastigmine (ExelonO) at doses up to 6 mg b.i.d. In this 26 week, open-label, multicenter, European study, the primary outcome measure was change from baseline on the 12-item Neuropsychiatric Inventory-Nursing Home version (NPINHO). Following 26 weeks treatment with rivastigmine, more than 40% of all patients showed at least 30% improvement in total NPINH0 score from baseline. For patients with behavioural symptoms present at baseline, greater than 53% showed improvement in each of the 12 items of the NPI-NHQ. Mean changes from baseline were statistically significant for all NPI-NH0 items except depression. only a minority of patients had no symptoms at baseline, and the majority (greater than 70%) of these did not develop symptoms during treatment with rivastigmine. The study also provided evidence of stabilisation or even slight improvement of cognitive function with rivastigmine treatment. Although gastrointestinal adverse events were relatively frequent, rivastigmine was safe and well tolerated in the vast majority of these mostly multimorbid patients.
-1
Statins in the treatment of Alzheimers Disease
B. Winblad’, L.A. Carlsson*, M. Crisby’. ‘Neumtec, Division of Geriatric Medicine, Karolinska Institute, Huddinge University Hospital, 141 86 Huddinge; ‘Gustaf Vth Research Institute, Karolinska Institute, I71 76 Stockholm, Sweden Alzheimers Disease (AD) and cardiovascular disease (CAD) have multi-factorial causes, some of which are related to genetic disorders and chronic intlammation. There is ample evidence suggesting that risk factors for CAD and stroke are also associated with cognitive impairment and AD. The challenge of early detection of dementia is to accurately distinguish the symptoms of brain failure. As patients move from cognitively normal state to dementia, they pass through the transitional phase of mild cognitive impairment (MCI). Deposition of P-amyloid (A@) in the amyloid plaques and cerebrovascular wall and neurofibrillatory tangles are neuropathological hallmarks of AD. Activated microglia, astrocyte proliferation and increased expression of cytokines in the vicinity of amyloid plaques are prominent markers of inflammation seen in AD. The brain capillary endothelium is of major importance for the delivery of oxygen, glucose and other vital nutrients that are essential in maintaining a stable internal milieu in the CNS. Imbalance in these processes, due to chronic impaired capillary flow caused by changes in the vasculature and blood brain barrier (BBB) may contribute to progression of AD. Prevoius neuropathological studies illustrate the close anatomic relationship between capillaries and plaques in AD brains. Furthermore, brain endothelial cells are structurally and biochemically altered in AD. It has been hypothesized that AP deposition results in damage