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.