|
Cognitive enhancement
therapy for Alzheimer's disease. The way forward.
Parnetti L, Senin U, Mecocci P.
Perugia University, Italy. parnetti@unipg.it
Drugs 1997 May;53(5):752-68
Abstract
Although at present there is no
definitive treatment or cure for Alzheimer's disease, different
pharmacological strategies are being actively investigated. At present,
cholinergic therapy and nootropics and some neuronotrophic agents represent
the available approaches to symptomatic treatment of Alzheimer's disease.
The
use of cholinesterase inhibitors (ChEI) constitutes the best cholinergic
approach to increase acetylcholine levels. Available data suggest that about
15 to 40% of Alzheimer's disease patients show a varying degree of cognitive
improvement while taking these medications; however, haematological
complications (neutropenia or agranulocytosis), together with hepatotoxicity,
need to be considered carefully. Recent data suggest that long term
administration of nootropics may lead to a significant improvement of
cognitive functions in Alzheimer's disease patients compared with untreated
individuals, having excellent tolerability. Protocols for the
intracerebroventricular administration of neuronotrophic substances are also
ongoing. The most promising approaches for the future currently undergoing
investigation involve attempts to slow the production of beta-amyloid and/or
to inhibit beta-amyloid aggregation. Another rational therapeutic approach
would be to inhibit the formation of paired helical filaments (PHF) by
increasing and/or modulating the activities of protein phosphatases and
kinases. Antioxidant therapy should disrupt or prevent the free radical/beta-amyloid
recirculating cascade and the progressive neurodegeneration. Idebenone, a
synthetic compound acting as an 'electron trapper' and free radical scavenger,
has shown some efficacy in degenerative and vascular dementia; at present,
other different molecules having antioxidative properties [lazaroids
(21-aminosteroids), pyrrolopyrimidines, nitric oxide blockers, selegiline,
some vitamins] are under investigation. Lowering absorption or brain tissue
concentrations of aluminium also offers possible therapeutic opportunities for
slowing the rate of clinical progression of the disease; in this sense, some
evidence exists using the aluminium chelating agent deferoxamine (desferrioxamine).
Inflammation also may play a significant pathogenetic role in Alzheimer's
disease. As shown by several retrospective analyses, there is an inverse
association of anti-inflammatory drug use with the frequency of Alzheimer's
disease diagnosis. Consequently, clinical trials using both nonsteroidal and
steroidal molecules have been proposed. These lines of pharmacological
intervention represent an important premise for future therapeutic strategies
capable of counteracting the pathogenesis of Alzheimer's disease.
Idebenone
- the ultimate anti-aging drug. (article)
Alzheimer's disease
Idebenone in
the treatment of Alzheimer's disease
Idebenone
efficacy of idebenone in the treatment of Alzheimer's
disease
Idebenone
Nerve Growth Factor synthesis stimulators in Alzheimer's
disease
Idebenone
in the treatment of dementia of the Alzheimer type
Idebenone
cognitive enhancement therapy for Alzheimer's
disease
MELAS
Idebenone
improves cerebral mitochondrial oxidative metabolism in MELAS
Idebenone
in young patients with mitochondrial encephalomyopathy (MELAS)
Idebenone
therapy in Mitochondrial encephalomyopathy (MELAS)
Idebenone
and Mitochondrial encephalomyopathy (MELAS)
Idebenone
successful therapy with idebenone in Mitochondrial
encephalomyopathy (MELAS)
.
Cardiomyopathy
Idebenone
improvement in mitochondrial cardiomyopathy following
treatment with idebenone
Idebenone
effect of idebenone on
cardiomyopathy in Friedreich's ataxia
.
Leber hereditary optic neuropathy (LHON)
Idebenone
does it shorten the time to visual recovery in Leber hereditary optic
neuropathy?
Idebenone
improvement in a patient with Leber's hereditary optic neuropathy (LHON)
Misc.
Idebenone
use in age-related cognitive disorders
Idebenone
protects hippocampal neurons against beta amyloid neurotoxicity
Idebenone
functions as a potent protective
hepatocyte antioxidant
Idebenone
neuroprotective effects of
idebenone can be attributed to its antioxidant ability
Idebenone
inhibition of brain mitochondrial
swelling
Idebenone
suppression of cold ischemia/reperfusion
injury of liver endothelium
Idebenone
ability to eliminate a nitroxide
radical in the rat
Idebenone
interaction with respiratory complexes of heart
mitochondria
Idebenone
effect on serotonin release and seroton receptors in rats
Idebenone
protects hepatic microsomes against damage in organ preservation solutions
Idebenone
protects against toxicity
induced by low density lipoprotein
Idebenone
protects against disorders due to cerebral hypoxia or
ischemia
Idebenone
protects against toxicity induced by low density
lipoprotein
Idebenone
attenuates neuronal degeneration induced by excitotoxins
Idebenone
augments long-term potentiation in
hippocampal slices in the guinea pig
Idebenoneeffects
on lipid peroxidation
in erythrocytes of stroke-prone, hypertensive rats
Idebenone
brain distribution and its effect on local cerebral
glucose utilization in rats
Idebenone
effects
on acetylcholine levels
in the brains of rats with cerebral ischemia
Idebenone
protective effect of idebenone against hypoxia in mice
Idebenone
improves learning and memory impairment induced in rats
Idebenone
effects
of idebenone on
neurological deficits in stroke-prone rats
Idebenone
effects
on memory induced impairment in rats
Idebenone
effects of idebenone on cerebral blood flow in rats with cerebral ischemia
Idebenone
inhibition
of brain mitochondrial swelling by idebenone
Idebenone
inhibition of platelet aggregation by
idebenone
Idebenone
effects of idebenone on monoamine metabolites of patients
with dementia
Idebenone
effects of idebenone on
metabolism of monoamines and cyclic AMP formation
Idebenone effects
on impairment of radial maze learning in cerebral embolized rats
Idebenone
effect of idebenone on lipid peroxidation in rat
brain homogenate
Idebenone
effects on muricidal behavior in rats with raphe
lesions
Idebenone
inhibitory effect of idebenone on vascular lesions in
hypertensive rats
|
