Cognitive enhancement therapy for Alzheimer's disease: The way forward
L. Parnetti
Bok Engelsk 1997
| Utgitt | 1997
|
|---|---|
| Omfang | Side 752- 768
|
| Opplysninger | Although at present there is no definitive treatment or cure forAlzheimer's disease, different pharmacological strategies are beingactively investigated, At present, cholinergic therapy and nootropicsand some neuronotrophic agents represent the available approaches tosymptomatic treatment of Alzheimer's disease, The use ofcholinesterase inhibitors (ChEI) constitutes the best cholinergicapproach to increase acetylcholine levels. Available data suggestthat about 15 to 40% of Alzheimer's disease patients show a varyingdegree of cognitive improvement while taking these medications;however, haematological complications (neutropenia oragranulocytosis), together with hepatotoxicity, need to be consideredcarefully, Recent data suggest that long term administration ofnootropics may lead to a significant improvement of cognitivefunctions in Alzheimer's disease patients compared with untreatedindividuals, having excellent tolerabil-ity. Protocols for theintracerebroventricular administration of neuronotrophic substancesare also ongoing.The most promising approaches for the future currently undergoinginvestigation involve attempts to slow the production of beta-amyloidand/or to inhibit beta-amyloid aggregation. Another rationaltherapeutic approach would be to inhibit the formation of pairedhelical filaments (PHF) by increasing and/or modulating theactivities of protein phosphatases and kinases. Antioxidant therapyshould disrupt or prevent the free radical/beta-amyloid recirculatingcascade and the progressive neurodegeneration. Idebenone, a syntheticcompound acting as an 'electron trapper' and free radical scavenger,has shown some efficacy in degenerative and vascular dementia; atpresent, other different molecules having antioxidative propertiesÆlazaroids (21-aminosteroids), pyrrolopyrimidines, nitric oxideblockers, selegiline, some vitaminsÅ are under investigation.Lowering absorption or brain tissue concentrations of aluminium alsooffers possible therapeutic opportunities for slowing the rate ofclinical progression of the disease; in this sense, some evidenceexists using the aluminium chelating agent deferoxamine(desferrioxamine). Inflammation also may play a significantpathogenetic role in Alzheimer's disease. As shown by severalretrospective analyses, there is an inverse association of anti-inflammatory drug use with the frequency of Alzheimer's diseasediagnosis. Consequently, clinical trials using both nonsteroidal andsteroidal molecules have been proposed. These lines ofpharmacological intervention represent an important premise forfuture therapeutic strategies capable of counteracting thepathogenesis of Alzheimer's disease.
|
| Emner |
