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There is currently no cure for Alzheimer's disease. Currently available medications offer relatively small symptomatic benefit for some patients but do not slow disease progression. The American Association for Geriatric Psychiatry published a consensus statement on Alzheimer's treatment in 2006.
Acetylcholinesterase inhibitors
Acetylcholinesterase (AChE) inhibition was thought to be important because there is a reduction in activity of the cholinergic neurons. AChE-inhibitors reduce the rate at which acetylcholine (ACh) is broken down and hence increase the concentration of ACh in the brain (combatting the loss of ACh caused by the death of the cholinergin neurons). Acetylcholinesterase-inhibitors seemed to modestly moderate symptoms but do not alter the course of the underlying dementing process.
Examples include:
* tacrine - no longer clinically used
* donepezil - (marketed as Aricept)
* galantamine - (marketed as Razadyne in the U.S.A. Marketed as Reminyl or Nivalin in the rest of the world)
* rivastigmine - (marketed as Exelon)
There is significant doubt as to the effectiveness of cholinesterase inhibitors. A number of recent articles have criticized the design of studies reporting benefit from these drugs, concluding that they have doubtful clinical utility, are costly, and confer many side effects. The pharmaceutical companies, but also some independent clinicians, dispute the conclusions of these articles. A transdermal patch is under development that may ease administration of rivastigmine.
Ginkgo biloba
One of the natural extracts that has been examined in Alzheimer's is Ginkgo (Ginkgo biloba), also known as the Maidenhair Tree. The extract of the Ginkgo leaves contains flavonoid glycosides and terpenoids, and both seeds and leaves have been used pharmaceutically in China and the West. Examining over 50 studies conducted on Ginkgo for the treatment of "cognitive impairment and dementia," a Cochrane Review concludes that "there is promising evidence of improvement in cognition and function associated with Ginkgo." According to this review the two randomized controlled studies that focused on Alzheimer's patients both showed significant improvement in these areas. The review calls for a large study which can "provide robust estimates of the size and mechanism of any treatment effects." The AAGP review did not recommend Ginkgo neither did it warn against its use. A large, randomized clinical study in the US called the GEM study is underway (fully enrolled) and examining the effect of Ginkgo to prevent dementia.
NMDA antagonists
Recent evidence of the involvement of glutamatergic neuronal excitotoxicity causes Alzheimer's disease led to the development and introduction of memantine. Memantine is a novel NMDA receptor antagonist, and has been shown to be moderately clinically efficacious. Memantine is marketed as Akatinol, Axura, Ebixa and Namenda.
Psychosocial interventions
Cognitive and behavioral interventions and rehabilitation strategies may be used as an adjunct to pharmacologic treatment, especially in the early to moderately advanced stages of disease. Treatment modalities include counseling, psychotherapy (if cognitive functioning is adequate), reminiscent therapy, reality orientation therapy, and behavioral reinforcements as well as cognitive rehabilitation training.
Treatments in clinical development
A large number of potential treatments for Alzheimer's disease are currently under investigation, including four compounds being studied in phase 3 clinical trials. Xaliproden had been shown to reduce neurodegeneration in animal studies. Tramiprosate (3APS or Alzhemed) is a GAG-mimetic molecule that is believed to act by binding to soluble amyloid beta to prevent the accumulation of the toxic plaques. R-flurbiprofen (MPC-7869) is a gamma secretase modulator sometimes called a selective amyloid beta 42 lowering agent. It is believed to reduce the production of the toxic amyloid beta in favor of shorter forms of the peptide. Leuprolide has also been studied for Alzheimer’s. It is hypothesized to work by reducing leutenizing hormone levels which may be causing damage in the brain as one ages.
* Vaccines or immunotherapy for Alzheimer's, unlike typical vaccines, would be used to treat diagnosed patients rather than for disease prevention. Ongoing efforts are based on the idea that, by training the immune system to recognize and attack beta-amyloid, the immune system might reverse deposition of amyloid and thus stop the disease. Initial results using this approach in animals were promising, and clinical trials of the drug candidate AN-1792 showed results in 20% of patients. However, in 2002 it was reported that 6% of multi-dosed participants (18 of 300) developed symptoms resembling meningoencephalitis, and the trials were stopped. Participants in the halted trials continued to be followed, and 20% "developed high levels of antibodies to beta-amyloid" and some showed slower progression of the disease, maintaining memory-test levels while placebo-patients worsened. Microcerebral haemorrhages with passive immunisation and meningoencephalitis with active immunisation still remains to be potent threats to this strategy. Work is continuing on less toxic A? vaccines, such as a DNA-based therapy that recently showed promise in mice. Researchers from University of South Florida announced a patch version of the drug was shown to be safe and effective when tested on mice.
* Proposed alternative treatments for Alzheimer's include a range of herbal compounds and dietary supplements. In the AAGP review from 2006, Vitamin E in doses below 400 IU was mentioned as having conflicting evidence in efficacy to prevent AD. Higher doses were discouraged as these may be linked with higher mortality related to cardiac events.
Laboratory studies with cells and animals continually fuel the pipeline of potential treatments. Some currently approved drugs such as statins and thiazolidinediones have also been under investigation for the treatment and prevention of Alzheimer’s. Recent clinical trials for Phase 2 and Phase 3 in this category have taken 12 to 18 months under study drug, plus additional months for patient enrollment and analysis. Compounds that are just entering into human trials or are in pre-clinical trials would be at least 4 years from being available to the public and would be available only if they can demonstrate safety and efficacy in human trials.
Occupational and lifestyle therapies
Modifications to the living environment and lifestyle of the Alzheimer's patient can improve functional performance and ease caretaker burden. Assessment by an occupational therapist is often indicated. Adherence to simplified routines and labeling of household items to cue the patient can aid with activities of daily living, while placing safety locks on cabinets, doors, and gates and securing hazardous chemicals and guns can prevent accidents and wandering. Changes in routine or environment can trigger or exacerbate agitation, whereas well-lit rooms, adequate rest, and avoidance of excess stimulation all help prevent such episodes. Appropriate social and visual stimulation, however, can improve function by increasing awareness and orientation. For instance, boldly colored tableware aids those with severe AD, helping people overcome a diminished sensitivity to visual contrast to increase food and beverage intake.
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Important notice:
The content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other
qualified health provider with any questions you may have regarding a medical condition.
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