The latest on drugs for Alzheimer’s Disease

There are currently five drugs approved for the treatment of Alzheimer’s disease: tacrine (not used because of toxicity to the liver), donepezil (Aricept), Rivastigmine (Exelon), galantamine (Razadyne), and memantine (Namenda).  The first three are called cholinesterase inhibitors and have been around since the mid-1990s.  All three medications are effective for mild to severe Alzheimer’s disease.  There does not appear to be a difference in efficacy among the three medications.  All of these treatments produce statistically significant effects but the effects are usually small.  There are many clinical trials attempting to find more effective treatments.  The trials are mostly developed around four strategies: reduce amyloids (reduce plaques), modify tau (reduce tangles), treat with antioxidants, improve ion regulation, reduce inflammation, and improve cholesterol regulation. Treatments to reverse or lessen the amount of amyloids (anti-amyloid aggregation) have been the main stay of clinical trials to date.   The best known of these drugs is Alzmed.  Unfortunately, trials have been a failure so far.  For example, last year, the Lilly drug, semagacestat, terminated clinical trials because: (1) the medication did not slow the disease as expected, (2) the medication made cognition worse, and (3) the medication made treated patients less able to care for their personal needs.   The other anti-amyloid strategy has been to develop vaccinations.  These medications have also failed to live up to their promise and the original vaccine produced unacceptable side effects.  The conclusion from this line of research is that removing plaques is not enough. The other, less researched approach is to halt or stop tangles from forming.  The best known of these medications is methylene blue.  Methylene blue improved cognitive scores but there were problems with the placebo group as the medication turns urine blue making blinding difficult.  If your urine turns blue you know you are not taking a placebo. Attacking tangle formation is a direction for further exploration. Other strategies have also had discouraging results so far.  Attempts to reduce oxidative damage have focused on lowering homocysteine with high doses of folate and B vitamins.  A completed trial showed no benefits on cognition.  The same findings are true for trials with vitamin E, ginkgo balboa and omega 3 fatty acids.  Trials of anti-inflammatory drugs have also failed and these medications produce unacceptable side effects.  Available trials of chelation therapies have not produced lasting benefits.  Finally, a study of the effects of Lipitor (a statin or cholesterol lowering drug) also proved to be ineffective. Despite extensive efforts to develop treatments that modify the assumed pathology or pathologies underlying Alzheimer’s disease, most have proved unsuccessful to date (modifying the development of tangles is the exception).  The clearest conclusion is that removing plaques does not appear to help and may do harm.  This should question the amyloid hypothesis of Alzheimer’s disease.  There are still many ongoing clinical trials but early identification and intervention is still the best way to protect your future.   From an article by Dr. Bill Beckwith Ph.D. Dr. Beckwith is a neuropsychologist, speaker, and author of Managing Your Memory: Practical Solutions for Forgetting.