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Women and Alzheimer’s
Women and Alzheimer’s
Michael Greicius, MD, MPH, is an associate professor of neurology and, by courtesy, of psychiatry and behavioral sciences at the Stanford School of Medicine. BeWell spoke with Dr. Greicius about Alzheimer’s disease — more commonly diagnosed in women than in men — to learn more about the causes, onset, progression and treatment of this currently incurable neurological disease.
What is Alzheimer’s Disease?
It might make sense to begin with the question, “What is dementia?” Dementia refers to a progressive decline in cognition (or thinking abilities) to the point that a person can no longer care for themselves on their own. They might, for example, no longer be able to handle taking their medications correctly or paying their bills regularly and on time. Numerous different diseases can cause dementia. A person who has had multiple strokes may be demented. Someone with untreated hypothyroidism may be demented. By far the most common cause of dementia, however, is Alzheimer’s disease.
To your first question, then, Alzheimer’s disease is a neurodegenerative disorder that typically, though not always, begins with impairment of short-term memory followed by trouble with language and visuospatial processing, and ultimately progressing to impairing a patient’s personality and ability to walk and even swallow. It is a fatal disease.
What causes it?
In most cases, we are not sure what causes Alzheimer’s disease. We know, when we look at the brains of these patients under a microscope, that the disease is associated with the aggregation of at least two proteins known as beta-amyloid and tau. The beta-amyloid aggregates occur between brain cells, while the tau aggregates occur within brain cells. In rare cases (making up less than about 2% of all Alzheimer’s disease), we know that the disease is caused by a single gene mutation. Rare mutations in three genes, all linked tightly to the beta-amyloid protein, cause familial Alzheimer’s disease at a very young age. People with these gene mutations tend to get sick in their 40s — as opposed to more common, “sporadic” or late-onset Alzheimer’s disease, which tends to affect people in their 60s, 70s, or 80s.
Why is it more common in women?
One reason that we see more women with AD than men is because women still tend to live longer than men and age is a strong risk factor for AD. However, even if we correct for their increased longevity, it seems that women are more prone to AD than men. The reason or (more likely) reasons for this remain unclear, but there are some intriguing possibilities. Estrogen is known to have a wide array of effects (mostly beneficial) on the brain, and when women go through menopause and estrogen levels decline, this may increase their risk for developing AD. In addition, one of the strongest genetic risk factors for late-onset AD, a variant of a gene called APOE4, is influenced by estrogen — as estrogen can directly affect the amount of protein made by the APOE gene. These are just two of many possible explanations for the increased risk of AD in women. This is an important, but still understudied, part of the mystery of AD.
What are the signs and symptoms of the disease? Does it manifest itself differently in men than in women?
In the process of normal aging, there are a number of cognitive domains (memory, language, executive function, etc.) that begin to show some mild changes. It is not particularly worrisome, for example, to head into the garage to complete some task and then to stand in the doorway of the garage scratching your head trying to recall what it was you wanted to do. Almost everyone over the age of 60 (or 45 for that matter) notices more trouble than they used to have attaching a name to a face. This is why everyone loves nametags at holiday parties.
Far more concerning symptoms for AD include things like repeating the same question (or telling the same anecdote) two or three times over the course of just an hour or two; losing your car in the parking lot, to the point that you need to drive around with security to find it; misplacing things more than previously to the point that a person has to buy a new pair of glasses, a new wallet, or new hearing aids; and getting lost while driving in what should be a fairly familiar environment. We have not — yet — seen any clear differences in the way the early signs of AD manifest in men in contrast to women.
What should I do if I suspect that I — or a loved one — might have Alzheimer’s? How is it diagnosed?
If you are concerned that you or a loved one has AD, you should consult a physician. Ideally, this would be a physician with specialty training in AD and dementia, but most primary care doctors are well-trained in the initial steps of working up the patient with cognitive trouble — and that can be a good place to start as well.
Currently, we do not have a definitive test for AD. There is no single blood test or brain scan or spinal fluid study that can tell us a person does or does not have AD. A definitive diagnosis of AD is only made by examining the brain after a patient has died. We diagnose “probable AD” while the patient is still living based on taking a thorough history, doing an extensive neurologic examination including cognitive testing, and running some blood tests and brain imaging studies to rule out other possibilities (like low thyroid or previous strokes).
Recently, we have begun to incorporate some more specific AD-related tests into our diagnosis. We can do a PET scan of the brain that looks for the presence of beta-amyloid. We can also do a lumbar puncture to look for abnormal levels of beta-amyloid and tau in the spinal fluid. These tests are called “biomarkers,” and while they still do not provide 100% accuracy when compared with autopsy results, they tend to move us from about 80-85% accuracy without biomarkers to about 90-99% accuracy with biomarkers.
Most of the caregivers of people with Alzheimer’s Disease are women. Do you have any advice for them in terms of how they can take care of themselves while taking care of a loved one with the disease?
This gets to the damned-if-you-do, damned-if-you-don’t aspect of AD and women. On the one hand, women are more likely to develop AD; on the other hand, they are also more likely to find themselves as the primary caregiver for someone with AD. It is now well known that caring for someone with AD has a powerful, negative impact on physical and emotional well-being. Particularly as the disease progresses and patients require more care, there is a large physical toll taken when, for example, having to lift patients out of a chair or off the toilet or out of bed. Sleep becomes fractured for the patient. which means it becomes fractured for the caregiver. Delusions (false fixed beliefs) are common in AD patients (“you are stealing my things,” “you are trying to poison me,” etc.) and are often directed at the caregiver, which is hard not to take personally, especially after all the work the caregiver is doing for the patient.
As such, it is important for caregivers to try and share the burden. This can mean explicitly asking other people for help, which can come from other family members (siblings or adult children of the patient), close friends, or paid caregivers. In any case, the help is always better if it is regular and dependable and frequent. Most patients, although quite attached to their primary caregiver, will adapt to having someone else in the house for four hours a day, three times per week. These large chunks of time are critical for enabling the primary caregiver to get out and about and away in order to decompress and do things they enjoy doing. It is hard, however, to catch up on hours of disrupted sleep with relatively short breaks during the week, which is why we encourage caregivers to set up longer blocks of time (such as an entire weekend) when the patient is with another caregiver.
Ultimately, most spouses have trouble caring safely for the patient at home as the disease progresses. The physical labor, coupled with sleep deprivation and emotional toil, becomes too much — particularly as a patient develops incontinence and becomes bed-bound. This is important to recognize because no matter how well and how long someone has cared for their spouse at home, moving them to a care facility is invariably associated with profound feelings of guilt. When the time comes, it is critical for other family members and for the physician to help the caregiver come to terms with this transition and recognize the remarkable work they have done to keep the patient in their home as long as possible.
What can we do to reduce our risk for developing the disease?
We do not know of anything that definitely reduces a person’s risk of developing Alzheimer’s, although there is strong data to suggest that regular aerobic exercise and a heart-smart diet will reduce risk. Head trauma is an important risk factor for AD and another type of dementia, so minimizing exposure to head trauma can also reduce risk of AD. Numerous companies make explicit or implicit claims about their “nutraceutical” or vitamin or “brain-training” software being able to stave off AD. None of these claims are true and most, if not all, of these purveyors are modern-day snake-oil salesmen and saleswomen.
What can we do to slow the progression of the disease?
As with prevention, we encourage aerobic exercise and a heart-smart diet, but nothing thus far has been proven to slow the progression of AD.
What does a diagnosis of Alzheimer’s Disease mean for our quality of life?
I don’t think we can get around the fact that quality of life is reduced following a diagnosis of AD. There may be some mild, transient benefits in terms of getting a firm, early diagnosis for symptoms that have perplexed the patient and their family. In the early stages, this can also preserve a patient’s independence by allowing them to take control of their future; for example, taking the opportunity to state explicitly what sorts of care and intervention they would or would not like as the disease progresses. In many cases, an early, accurate diagnosis also allows a patient and their family to focus on the next few years of relatively intact cognition. The disease progresses slowly, over years; therefore, understanding at age 70 that you have a disease that will progress over the next 10 years tends to make patients and families focus on getting the most out of the next couple of years for activities such as family travel.
… any final thoughts?
Alzheimer’s disease is a tough and long haul for most patients and families. At Stanford, we feel it is critical for our caregiving team (physicians, nurses, and social workers) to be a continuous source of support to the patient and their family from the first visit all the way through to the patient’s death. We do not like to soft-pedal the fact that this is, for now, a fatal and incurable disease. I say “for now” because, while working with families on day-to-day care issues, we are striving, in parallel, to cure this fatal disease. Stanford has a long history of ground-breaking AD research and we have recently been named an NIH-sponsored Alzheimer’s Disease Research Center (ADRC).1 Staff at the Stanford ADRC will work closely with our patients to better understand the causes of the disease and, critically, to develop novel treatments to prevent, slow, or cure AD. To do so, we need the support of patients and their families lending their time, energy, optimism and effort to fighting this battle with us.
1 A new Stanford-based Alzheimer’s Disease Research Center will receive nearly $7.3 million in funding over a five-year period to conduct interdisciplinary research on Alzheimer’s disease and related disorders. See the recent announcement.