Medication

Initially, I was excited to see a review article titled, “Efficacy and safety of cognitive enhancers for patients with mild cognitive impairment: a systematic review and meta-analysis” (Canadian Medical Association Journal, 2013, September 16).   However, I was disappointed after carefully reading the paper.  I had hoped to gain insight into whether cognitive enhancing medications (Aricept/donepezil, Exelon/rivastigmine, and Razadyne/galantamine – there were no cognitive data for Namenda) help those with Mild Cognitive Impairment but there are too few studies with too many limitations to get a clear answer to the question of benefits. Mild Cognitive Impairment is usually characterized by mild memory/cognitive deficits in those without functional decline in everyday skills.  These are persons who do not meet the criteria for Alzheimer’s disease but are clearly at greater risk of obtaining the diagnosis in the future.  The question is whether treating […]

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One of the most important yet difficult issues we all face with the proliferation of medications available and in development of new drugs, especially those affecting the central nervous system, is how to determine what is a meaningful drug effect.  How does one know which drugs are effective and which are not?  What is a meaningful treatment effect?  How do professionals decide which drugs to recommend?  Are newly available drugs better than older medications? We rely on large studies called randomized clinical trials (RTCs) to answer these questions.  RTCs are scientifically rigorous studies designed to evaluate the safety and efficacy of medications (often compared to a placebo). The problem comes when we try to interpret the findings from these studies.  What constitutes a meaningful result depends upon whom you ask (Defining a clinically meaningful effect for the design and implementation […]

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I keep hoping for more useful research on treatments and management techniques that may potentially benefit those with memory loss and their caregivers.  There are three recent studies that caught my attention as examples of movement in the right direction. First, “The effect of stimulation therapy and donepezil on cognitive function in Alzheimer’s disease” (BMC Neurology, 2012, 12, 59).  The study compared the effects of stimulation therapy, treatment with donepezil (Aricept), or to combined treatment during the first year after diagnosis with mild to moderate Alzheimer’s disease.  Stimulation therapy consisted of multiple elements including physical activity (e.g., dancing, walking, fitness training), as well as cognitive and social activities (e.g., reading, listening to music, crossword puzzles, reminiscence) for at least 30 minutes each day 5 times per week.  Donepezil (or placebo) was started at 5 mg and increased after four weeks […]

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Type 2 diabetes mellitus is associated with Mild Cognitive Impairment (often presenting as short-term memory loss that is either subjective or confirmed by rigorous memory tests) as well as dementia (moderate to severe short-term memory loss that causes a lack of independence). Furthermore, insulin resistance, the hall mark of adult onset or type 2 diabetes, increases the risk of developing Alzheimer’s disease. Results from the Honolulu aging study provide an example of the association of the balance of glucose and insulin with risk of dementia. Study participants who had either very high or very low levels of serum insulin were more likely than those in between to become demented over the course of 5 years. Other studies, but not all, have shown this link between insulin resistance, impaired glucose metabolism, diabetes and dementia. You have probably read the headlines generated […]

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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 […]

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Alzheimer’s disease is a complicated condition that comes on very slowly over the course of many years.  The first signs may be quite subtle.  The course is irregular with periods of lucid thought interrupted by fluctuations in memory or thinking that are similar to the changes in memory efficiency that happen as a consequence of aging.  This makes early detection of those who develop Alzheimer’s quite difficult and gives rise to a number of beliefs that lead to the attitude that there is nothing you can do. “Aging is a disease.”  Aging is not a disease state that needs treatment.  Many age quite well and have productive fruitful lives into their 90s or even early 100s.  Take for example my wife’s 96 year old aunt who still safely drives, lives alone and is still a whiz at playing cards or […]

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Do we really have a breakthrough in diagnosis and treatment of Alzheimer’s disease?  In our desperation for a cure, we have gotten ahead of biology and cast all of our hopes on the amyloid hypothesis ignoring the complexity of Alzheimer’s disease.  The amyloid hypothesis drives a multitude of clinical trials currently underway by pharmaceutical companies to find the cure for Alzheimer’s disease.  Simply stated, the hypothesis proposes that build up of beta amyloid, an abnormal protein in the brain, is the cause of Alzheimer’s disease.  Hence, treatments are sought that either stop or reverse the production of amyloid proteins in the brain.  One of the medications under investigation was semagacestat, a drug developed by Lilly Pharmaceuticals. The trials had advanced to the point where there were 2600 patients enrolled in the clinical trials comparing semagacestat with a placebo.  This medication […]

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There are four FDA approved medications available for treatment of Alzheimer’s disease: Aricept, Exelon, Razadyne, and Namenda.  The first three are in a class of medications known as cholinesterase inhibitors and the other, Namenda, is an NMDA receptor antagonist.  In simple terms, the cholinesterase inhibitors increase the amount of a neurotransmitter called acetylcholine whereas Namenda decreases the amount of a different neurotransmitter, glutamate.  Often Namenda is used together with one of the cholinesterase inhibitors as the combination appears to be more effective to boost cognition in moderate to severe Alzheimer’s disease than either medication used alone. The news of the week is that the FDA has approved the use of a higher dose of Aricept for those with moderate to severe Alzheimer’s disease as indicated by a score of 20 or fewer of 30 possible points on the Mini-Mental State […]

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Behavioral problems like aggression, agitation, and hallucinations are common among those with memory loss and dementia. They are often treated with medications as a class called “antipsychotics” or “neuroleptics.” The newer medications in this class include Risperdal, Zyprexa, Geodon, Seroquel, and Abilify. Examples of older medications in this class of drugs include Thorazine, Haldol, and Melleril and are not widely used today. The newer medications are used in about 90% of prescriptions written. The belief was that these newer (and more expensive) medications are safer and more effective than older medications. However, these assumptions have been challenged by recent research. The overall risk of death from use of these medications is low – about 3%. However these drugs affect heart rhythm and may cause a higher rate of sudden cardiac deaths in vulnerable individuals. This is true for individuals treated […]

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Type 2 diabetes mellitus is associated with accelerated cognitive decline in the elderly. This includes increased risk for mild cognitive impairment (often seen as short-term memory loss that is either subjective or confirmed by rigorous memory tests) as well as dementia (moderate to severe short-term memory loss that causes a lack of independence). A recent study indicated that type 2 diabetes also accelerated the rate at which those with mild cognitive impairment progress to a diagnosis of dementia. The dementia may be either caused by Alzheimer’s disease, vascular disease or both. Individuals with both mild cognitive impairment and diabetes are at greater risk of becoming more seriously and cognitively impaired over time. As is true of most studies, the studied population consisted of mostly whites of European decent and the design of the study was retrospective or epidemiological. As there […]

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