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.

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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

Friedreich's ataxia.
Idebenone  and reduced cardiac hypertrophy in Friedreich's ataxia.
Ideb
enone  causes improvement in mitochondrial cardiomyopathy
Idebenone  cerebellar improvement in Friedreich's ataxia after 3 months
Idebenone   effect of idebenone on cardiomyopathy in Friedreich's ataxia
Idebenone  Friedreich's ataxia and frataxin
Idebenone   Frataxin: Its role in iron metabolism and Friedreich's Ataxia
Idebenone   mitochondrial dysfunction in Friedreich's ataxia
Idebenone   helps heart function in Friedreich's ataxia

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

Idebenone 
effects 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

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