Ask an Expert about Alzheimer's Disease

Although your mother is only 57, she may be experiencing an age-related decline in memory that is considered “normal.” On the other hand, she may genuinely have some mild memory impairments, which she may already be aware of, and perhaps this is why she becomes defensive when you question her. However, it may be premature to think that she has Alzheimer's disease even though at least two relatives were diagnosed with it. Memory problems can result from a wide variety of causes, such as sleep disturbances (insomnia, sleep apnea), depression, hormonal imbalances, vitamin deficiencies, drug interactions, head or brain injury, stroke, and even viral or bacterial infections that affect the brain (encephalitis). Many of these conditions are treatable, and upon treatment any memory deficiencies associated with the conditions will also often be resolved. Therefore, the best way you can help your mother at this point is to have her schedule an appointment with a physician for a checkup and memory screening test. If your mother's memory is impaired (more than normal aging can account for), a proper diagnosis can mean that she can receive the appropriate therapy for whatever might be the cause of her condition.

Of course, this will require actually getting your mother to the doctor, which may be a challenge, if she is as stubborn as you say she is. Any way you can get her there is fine, even if you have to bribe her to go. Another approach is to tell her that you are concerned about her overall well-being (perhaps do not mention the memory problems because she is already sensitive about this) and would feel better if she had a check-up from her doctor. Volunteer to take your mother to her visit. If she does not want you to accompany her, you can always call the physician's office ahead of time to inform her doctor of your concerns and that they should be on the lookout for memory problems. If this method fails, you could try making an appointment for “yourself” and ask that your mother accompany you, because you are anxious and do not want to go alone. Really, the appointment is for her, but she won't know that hopefully until you're already in the exam room. You can ask the doctor to “mock” examine you and, having finished, turn to her and say “since you're here, let's look at you too.” You'd have to have a pretty agreeable doctor to play along with the act in order to pull this trick off, but it could work.

Vertigo caused by inner ear disturbances is very common in older adults, and can cause dizziness and an inability to walk steadily. However, vertigo is unlikely to cause shaking on its own. Also, because vertigo can be so disturbing to a person (probably even more so to a person with dementia), it could be causing anxiety attacks, which could lead to the shaking that your mother experiences.

Sometimes the medications that are commonly prescribed to treat Alzheimer's disease, such as memantine (Namenda®) or rivastigmine (Exelon®), can cause side effects such as dizziness (which would cause unsteadiness) and shaking or trembling of the hands or fingers. If your mother recently started taking one or both of these medications, you may want to revisit the dosages with her doctor.

It is also possible that your mother may have another neurological issue on top of Alzheimer's disease (AD). It is not uncommon, for example, to see AD patients with mild Parkinson's disease (PD)-like symptoms, and vice versa (PD patients with mild dementia). It really just depends on which area(s) of the brain are affected by the disease. Seizures can also cause shaking and loss of muscle control, and can occur as a result of AD. Because of the length of your mother's episodes (20 – 40 minutes), however, the shaking is probably not due to seizures, which typically will resolve themselves within 5-15 minutes or less. And it is also possible that you mother may be experiencing mini-strokes that are causing her to feel dizzy and unsteady. Therefore, it is important that your mother be properly diagnosed by her doctor to determine the cause of her dizziness and shaking so that, if necessary, she can receive the appropriate treatment.

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.

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.

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.

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.

Because of the nature of Alzheimer's disease, it is certainly possible for a patient to have brief moments of clarity interspersed amongst long periods of confusion and forgetfulness. Depending on the areas of the brain damaged by the disease, it is also possible for a patient to retain certain memories (recognition of specific people and events, for example) up through the final disease stages. While the disease in general follows a progressively degenerative course, the specific symptoms and their severity are typically unique for each patient.

Temporary periods of lucidity can therefore sometimes occur in Alzheimer's disease; however, it is unknown what these “remissions” might mean (if anything) as no formal studies have been undertaken to investigate this phenomena. One informal survey of the literature noted that a return of mental clarity can occur shortly before death, which they termed “terminal lucidity.” Of course, this was based on only a very small number of case reports, so it is not possible to draw any solid conclusions from this survey.

Alzheimer's disease patients often confuse the past and the present, and may think that someone from their distant past is still among the living. Your mother's continued asking to see her mother might stem from an underlying fear of being alone, or being left behind by those that she loves. The next time she asks about her mother, take it as an opportunity to talk to her about these underlying emotions. Say to her "You miss your mother, don't you? Why don't you tell me about your mother and her favorite song, recipe, or holiday,” for example. Sometimes when you engage Alzheimer's patients in such topics, they become interested in telling you a story rather than repeatedly asking about their loved ones whereabouts. So if you keep her distracted by asking open-ended questions about her mother, then it may become unnecessary for you to directly answer about where her mother is.

However, like you suggested, it may also reasonable to tell your mother that your grandmother has passed away. Be gentle when you deliver such news because it may come as a shock to her—she truly does not remember or understand that her mother is gone. Make sure you provide your mother with plenty of reassurance that she is loved, valued, and will be well cared for. Also, don't be surprised if you have to repeat the whole conversation the next day (or even later the same day). Never yell at her because your mother likely has forgotten what you told her previously.