Medication

The cholinesterase inhibitors like Aricept (i.e., donepezil) have been available for treatment of dementias such as Alzheimer’s disease since the mid 1990s. It is clear that long term use of these medications slows the progression of Alzheimer’s disease (in those who tolerate them) and that discontinuing the medication after extended use produces a more rapid decline even in those so impaired that they are in skilled nursing facilities. Despite these findings, the cholinesterase inhibitors are often maligned, not used, or discontinued too soon because they do not produce dramatic effects and do not stop or reverse decline. One way to determine the efficacy of these medications is to determine if treatment reduces the burden that caregivers express (“Effects on caregiver burden of donepezil hydrochloride dosage increase to 10 mg in patients with Alzheimer’s disease,” Nakamura et al. Patient Preference and […]

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Benzodiazepines are widely used to treat anxiety and/or insomnia. They include medications like Valium (diazepam), Xanax (alprazolam), Ativan (lorazepam), and Klonopin (clonazepam) that are used for anxiety and Restoril (temazepam) and Halcion (triazolam) that are used to help induce sleep. Benzodiazepines may also be separated into those that are long acting (e.g., Valium and Klonopin) and those that are short acting (e.g., Xanax and Halcion). Long acting medications tend to remain in the body for extended periods of time (e.g., days) whereas short acting medications remain in the body for hours – hence you need to take the medication more than once a day to maintain effects. Benzodiazepines are probably most effectively used as short-term management of anxiety and insomnia. As with any medication, there are trade offs that must be considered by both prescribers and consumers. First, there are […]

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Caffeine appears to enhance memory consolidation according to a study published in Nature Neuroscience (“Post-study caffeine administration enhances memory consolidation in humans,” 2014, 17, 201-203).  But before you down an extra cup of coffee or an extra diet Coke, consider the details of the study.  The subjects were 160 young adults who reported they consume little caffeine each week – < 500 mg, which is less than the equivalent 2-3 cups of coffee per week.  Furthermore, they consumed caffeine pills not coffee.  Participants studied 200 pictures, swallowed the caffeine pill, and returned the next day for a surprise memory test.  Those who had the caffeine were better able to discriminate items similar to those actually seen from different items – familiarity not memory as most of us think of it. Let’s break down this result.  First, there were three doses […]

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Does taking a multivitamin/mineral supplement help prevent or delay cognitive decline?  In 2012, Mayo Clinic Health Letter (March 2012) reviewed well-conducted research concluding that many vitamins and minerals that we used to think prevented diseases may not help after all.  Furthermore, there are consistent findings that under some circumstances vitamins and supplements may cause harm – even use of a multivitamin in those who are well nourished may slightly increase the risk of premature death. A recent editorial, “Enough is enough: stop wasting money on vitamin and mineral supplements,”  in the Annals of Internal Medicine (2013, 59: 851) pushed the issue even further.  The journal published three articles presenting data that indicate no benefits from a multivitamin/mineral supplement in well-nourished adults. A review of primary prevention studies focused on community dwelling adults with no nutritional deficiencies.  There was no clear […]

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In 2004 the best available research indicated that supplementation with vitamin E slowed Alzheimer’s disease.  A major clinical trial at the time indicated that taking 2000 IU of vitamin E per day delayed placement in care facilities by several months compared to placebo.  By the way, treatment with selegiline (a type of antidepressant) produced the same effect.  Another study at the time demonstrated that eating a diet high in vitamin E was correlated with higher mental function in men and women aged 65 – 100.  Hence, many were taking high doses of vitamin E and supplementation was the standard of care for Alzheimer’s disease. However, there were concerns regarding such a high dose of vitamin E as it produced side effects such as potentiating the effects of anticoagulants such as aspirin and Coumadin and increasing bruising and risk of bleeding.  […]

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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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