Does any of the research on Alzheimer’s disease also apply to primary progressive aphasia (PPA)? Would the new oral slow-release medication that has been shown to have a positive effect on mice engineered to show features of Alzheimer’s and Huntington's diseases also help with PPA? I never see specific research on PPA, so I'm always hoping that Alzheimer’s research might also apply to this neurological condition. [ 06/22/11 ]
Primary progressive aphasia is a neurodegenerative disorder characterized by increasing difficulty with finding words. Ultimately there can be a profound disturbance of language function, often accompanied by other cognitive difficulties. There is no cure and there continues to be controversy about PPA's appropriate classification. It is most commonly considered a form of frontotemporal dementia; however, autopsy studies identify a significant number of individuals diagnosed during their lives with PPA who actually had Alzheimer's disease. Typically, PPA is treated with supportive medications to manage anxiety, depression, or insomnia, if these occur, and the central language deficit is addressed with speech therapy. The treatments for Alzheimer's disease might be worth trying in some cases, on the assumption that a subset of people diagnosed with PPA might actually have Alzheimer's disease that has presented in an atypical way. Most cases of PPA, however, are believed to represent a different disease process and therefore might not be responsive to current or experimental Alzheimer's treatments.
Can you please comment on what peer-reviewed studies indicate concerning homocysteine, Alzheimer’s disease, and general brain health? [ 06/01/11 ]
For several decades, there has been interest in whether homocysteine plays a role in various medical disorders, and evidence has been identified to connect elevated homocysteine levels with conditions including coronary artery disease, stroke, silent white matter infarcts, Alzheimer's disease, and possibly Parkinson's disease. A genetic disorder associated with elevated homocysteine levels includes, among other damaging symptoms, a heightened risk for mental retardation. Peer-reviewed, influential findings from the Framingham Study linked elevated homocysteine levels with an increased risk for development of Alzheimer's disease, and subsequent research suggested that homocysteine makes hippocampal neurons more vulnerable to the toxic effects of beta amyloid, which is produced in this neurological disease. Efforts to reduce the symptoms of Alzheimer's disease through dietary supplementation with B12 and folic acid, however, have produced inconsistent results and have not supported initial hopes that dementia symptoms could be reduced by lowering elevated homocysteine levels. Although the information above provides evidence of a connection between homocysteine and a number of medical conditions, there is no conclusive evidence in humans linking diet to incidence of Alzheimer's disease.
I have read that there is a new 23 milligram Aricept tablet. Does that mean two tablets of 10 milligrams can be taken twice each day? My mother has been on 10 milligrams for about four years, and I am wondering if we should double the dosage as she is showing signs of deterioration. [ 05/20/11 ]
Aricept (brand name for donepezil), is one of several “cholinesterase inhibitors” approved for the treatment of Alzheimer's disease, and is thought to work by increasing the availability of the important neurotransmitter acetylcholine. Previously available in 5 and 10 milligram tablets, the FDA has also recently approved (in July 2010) a 23 milligram pill that allows a higher once-daily dosage. A randomized, controlled study of donepezil, using 23 milligrams per day, showed a small improvement in cognitive functioning, versus the 10 milligram per day dose, in moderate to severe Alzheimer's disease subjects, but there was no statistically significant difference in the global functioning assessment test. It is likely that some patients who take the higher dose of donepezil will show a clinical benefit, but the benefit may be limited, and is accompanied by an increased risk for side effects.
It is inevitable that clinicians, caregivers, and patients will consider using two 10 milligram tablets daily instead of the single 23 milligram tablet. On the plus side, this might provide a similarly increased dose at a lower cost, if generic donepezil is used. Other considerations, however, are the following:
- The 10 milligram tablets are not FDA indicated for use above 10 milligrams per day.
- The 23 milligram tablet is formulated for single dosage and may produce a slower release of medication, which would lead to a more tolerable blood level peak than would occur with administration of two 10 milligram tablets
- Giving the donepezil on a twice daily basis might increase side effects such as daytime gastrointestinal problems or nighttime disruption of sleep.
- A twice-daily schedule is more prone to forgetful omission of a dose than is a once-daily schedule.
If your mother's disease has progressed, an increase in donepezil is only one of several possible treatment choices. Your prescribing clinician can work with you and your mother to determine the most appropriate choice regarding donepezil dosage, and whether an increase by either means is the right intervention at this time.
One year ago, at the age of 52, I was struck by a truck when crossing a street, and I suffered severe and multiple traumatic brain injuries. My only residual effects include anosmia (olfactory nerve damage) and benign paroxysmal positional vertigo. A neurological rehabilitation doctor stated that I am at higher risk now for developing Alzheimer’s disease. My maternal grandfather died with during the early stages of Alzheimer’s disease from a heart problem, but there is no other familial history. Now, I become deeply distressed when I have difficulty recalling a specific word or confuse an appointment time because such things rarely happening to me prior to the accident. Given my situation, what are my odds of developing Alzheimer’s now or in the future? Are my symptoms early signs of the Alzheimer’s disease process, residual effects of the traumatic brain injuries, or simply the result of normal aging? [ 05/19/11 ]
Traumatic brain injuries, particularly severe and/or repetitive ones, have been linked with an increase in the risk of developing Alzheimer's disease. Anosmia is known to accompany early Alzheimer's disease, but your anosmia is almost certainly post-traumatic rather than associated with dementia, if there was a sudden onset of this symptom after your injury. Your family history is positive, but not alarming, if your grandfather was elderly at the time of his death because Alzheimer's disease is so very common among the elderly. It is not unusual for someone who is 54 years old to occasionally experience minor difficulties such as you describe, and thank goodness (since they are so very common!) these may be signs of normal aging rather than approaching dementia. Anxiety, such as you experience when you consider the worst case scenarios that might be causing momentary lapses, will only make them worse and more distressing.
It will eventually be possible, I believe, to refine our estimate of risk for individuals, like yourself, through the use of such tests as MRI, CSF biomarkers, and genotyping—but presently, perhaps the most important advice is to make appropriate lifestyle decisions that can help you stay as healthy as possible. For example, it would be prudent to properly manage medical illnesses, and make time in your life for exercise, stress reduction, diet, cognitive stimulation, and meaningful social connections. If forgetfulness or other cognitive changes are of more than limited concern, please consider seeking evaluation with a neurologist or psychiatrist experienced in the evaluation of cognitive symptoms. Neuropsychological testing at a memory clinic, in addition, may contribute to an overall assessment of your current condition and prognosis.
What methods are biologists using to try and solve the problem of Alzheimer's disease? Specifically, can you talk about some of the new treatment modalities, such as the drug called bapineuzumab? [ 05/18/11 ]
We are fortunate that this is an era of important advances in the understanding the causes of Alzheimer's disease (AD). Furthermore, progress is likely to be accelerated as a result of recommendations from a recent task force that redefines clinical Alzheimer's disease as the final stage of a disorder that begins with a long pres-symptomatic phase (demonstrable through the use of cerebrospinal fluid and PET scan measurements, among other biomarkers), followed by a symptomatic pre-dementia phase (mild cognitive impairment), during which individuals may be more amenable to therapeutic interventions. Studies of individuals in these earlier disease phases are likely to increase our understanding of the risk factors for development of AD, the mechanisms by which it develops, and the therapeutic approaches most helpful in delaying or preventing AD's damaging effects.
Currently, much interest in the treatment of AD focuses on reducing the amount of beta amyloid that is produced and accumulated in the brain. Researchers have been enthusiastic about “immunotherapeutic” approaches that attempt to lower beta amyloid levels through immunologic mechanisms. Initial testing of a vaccine (which is an “active immunotherapy” because it induces the formation of amyloid-reducing antibodies in the vaccine recipient) was aborted due to unacceptable adverse effects, ushering in an era of testing “passive immunotherapies.” These medications are called “passive” because they provide pre-made antibodies rather than inducing production of antibodies in the patient. These antibodies attach to the damaging beta amyloid molecules and help the body remove them. Bapineuzumab is one of several “passive immunotherapy” interventions currently in testing and has been in the news, in part, because a large phase III clinical trial is nearing completion, the results of which are eagerly awaited.
Is there a connection between gum disease and Alzheimer’s disease? [ 04/28/11 ]
At first glance, it might be difficult to imagine how inflamed gums might be associated with Alzheimer's disease (AD), but the possible links are many, and the interactions between periodontitis and AD have been the subject of a significant amount of research. Periodontal disease is known to be associated with systemic inflammatory diseases such as rheumatoid arthritis and atherosclerosis. AD, too, has an important inflammatory component. A link between periodontal disease and AD could conceivably represent the consequence of increased systemic inflammation associated with higher levels of circulating pro-inflammatory cytokines that may contribute to the ongoing inflammatory neurodegenerative component of AD. Other hypotheses include the possibility that periodontal bacteria influence the neurodegenerative process, that anaerobic oral flora interact with dental amalgam to produce neurotoxic mercuric compounds that in turn affect the brain, or that severe tooth disease with tooth loss and dentures that are removed at night might result in a compromised airway and obstructive sleep apnea with nocturnal hypoxemia (low levels of oxygen in the blood).
These proposed relationships suggest ways in which the occurrence of periodontal disease might increase the risk for AD, but the link may be more complex: some authorities have suggested that a genetic predisposition to produce increased proinflammatory factors might underlie a concurrent greater risk for periodontal disease and AD. In that case, there would be relationship of association rather than causality. A further possibility is that dementia is associated with reduced self-care and oral hygiene neglect. The possibility that the stress of living with AD, as either patient or caregiver, might also help us understand the observation of increased gingivitis observed in caregivers of AD patients. In any case, it seems clear that oral hygiene's importance reaches far beyond the mouth.
My mother has Alzheimer's disease, and has been taking Aricept and Namenda for years. Recently, her primary care physician stopped the Aricept symptoms because of severe side effects (very loose bowels and stomach pain). I am concerned that her symptoms will become worse more quickly now. Could you give me your opinion? [ 04/13/11 ]
It is true that studies have demonstrated a rapid loss of the cholinesterase inhibitor benefits following cessation of treatment. Your mother, if she has benefited from the donepezil, may show an increase in symptoms. On the other hand, it would be a shame to expose her to a medication that has probably created gastrointestinal discomfort. A transdermal delivery system, such as the patches used to administer rivastigmine, may provide your mother with the therapeutic benefits of a cholinesterase inhibitor while avoiding the gastrointestinal side effects so common with these medications.
Is there any increase in likelihood of developing Alzheimer's disease if you have had electroconvulsive therapy (ECT) to treat depression? [ 04/12/11 ]
ECT is not generally thought to increase the likelihood for developing Alzheimer's disease or other causes of dementia. In fact, ECT has been used to treat depression or agitation, common “noncognitive behavioral symptoms,” seen in dementia patients. The limited evidence available does not find ECT producing lasting cognitive impairment in patients with dementia.