Women & Alzheimer's disease.

By the time Andee Kaluzna's father died of Alzheimer's disease at age 79, the 48-year-old woman had nearly finished mourning him. By then, she truly understood why Alzheimer's disease, the leading cause of dementia in the elderly, is often called the "Long Goodbye."

"My dad was a friendly, warm and active man with a sense of humor," she recalls. "He enjoyed helping others, singing in a local chorus and taking classes at the junior college and seminars through a local senior center. His greatest joy was his family, particularly his four grandchildren." But by the time he died, he didn't recognize the people around him, could not participate in any activities and rarely even knew where he was. "Not only did I mourn his death, I also mourned what he had lost" to this disease, she says.

An estimated 4.5 million Americans--more than half of them women--have Alzheimer's disease in the United States. Given the aging of the baby boomers and the growing numbers of "oldest old," those 85 and above, that figure is expected to more than triple by 2050, when an estimated 13.1 million Americans will be living with the disease. (1)

Although it affects men and women at nearly the same rates (women are slightly more likely to get Alzheimer's disease than men), Alzheimer's disease has particular relevance for women, notes Laurel Coleman, MD, a member of the Alzheimer's Association's board of directors and a practicing geriatrician in Augusta, ME. That's because the prevalence of the disease in women, or the number of women living with the disease at any one time, is twice as high as for men simply because women live longer. Increasing age is a major risk factor for developing Alzheimer's disease. Thus, Dr. Coleman notes, about half of all women over 85 will eventually be diagnosed with Alzheimer's disease. "That's a huge number of women," she says.

Additionally, in the family women are the primary caregivers for those with Alzheimer's disease. "It just adds to the burden on women overall," Dr. Coleman says, "who often are trying to juggle jobs and caregiving." (For more on caregiving and Alzheimer's disease, see page 5.)

The disease also appears to affect ethnic minorities differently than Caucasians. One study presented at the 9th International Conference on Alzheimer's Disease and Related Disorders in July 2004 found that symptoms begin, on average, almost seven years earlier in U.S. Hispanics than in Caucasians. Another found that African Americans ages 55 to 64 were more than three times more likely to have Alzheimer's disease as their Caucasian counterparts, and more than twice as likely to have the disease between ages 65 and 84. (2)

Overall Knowledge of Alzheimer's Disease is Lacking

Despite the prevalence of the disease--and the recent high-profile death of former President Ronald Reagan from complications associated with it--Americans' overall knowledge about Alzheimer's and the progress being made in preventing, diagnosing and treating it is abysmally lacking, according to a national survey conducted by the Alzheimer's Association in February 2004. (3)

That survey found that fewer than half of all Americans know that treatments are available that can ease the symptoms of the disease and improve the quality of life for those who have it and for their caregivers. Only 19 percent felt well prepared to handle a diagnosis of Alzheimer's disease in a family member. (3)

That doesn't surprise Alzheimer's experts. "I think it's partly related to the way the medical profession, particularly primary care doctors, approaches Alzheimer's disease," says William W. Pendlebury, MD, medical director of the Memory Center and Elder Care Services at the University of Vermont in Burlington. "Alzheimer's disease continues to be extremely under diagnosed and under treated."

Indeed, a study published in 1997 found that just 40 percent of generalist health professionals--primary care physicians, psychologists, social workers and nurses--knew that Alzheimer's disease was the most common cause of severe memory loss in people over 65. (4)

Since then, however, more medical schools have added curriculum about geriatrics, the field of health care focused on the elderly, and Alzheimer's disease. New treatments, potential new diagnostic methods and the hope of a vaccine are all raising the profile of this illness among health care professionals.

"Now we need to find more non-threatening ways of communicating this knowledge to the public," rather than always focusing on the negatives about the disease itself, says George T. Grossberg, MD, the director of geriatric psychiatry at St. Louis University School of Medicine in Missouri. One approach might be to focus more on the personal risk factors for developing Alzheimer's disease and how to reduce them. Another approach could be to more actively promote the benefits of early diagnosis.

Unraveling Alzheimer's Disease

Although researchers still don't know for sure what causes Alzheimer's disease, most believe it is related to the abnormal processing of normal brain proteins, particularly amyloid precursor protein and tau, another type of protein.

"For some reason, later in life these proteins, which serve a normal function, begin to be abnormally processed and assemble themselves into lesions," says Dr. Pendlebury. These lesions, called neurofibrillary tangles and senile (amyloid) plaques (often referred to simply as plaques), destroy parts of the brain.

Other theories link the disease's development to the death of cells critical for maintaining levels of certain brain chemicals required for awareness and judgement (cognition); chronic inflammation; accumulation of heavy metals in the brain; and vascular factors that affect the health of blood vessels in the brain. (5)

There are two forms of Alzheimer's disease: familial, in which genes directly cause the disease, and sporadic, the most common, in which genes may influence one's risk of developing the disease. (6)

Most cases of familial Alzheimer's disease, also called "early onset Alzheimer's disease," occur before a person turns 60. This form, however, affects less than five percent of those with Alzheimer's disease. The majority of people with the disease are diagnosed after age 65. (1)

The disease itself is progressive, meaning its symptoms inevitably become worse and its victims become more disabled. In the beginning, they may have problems with simple memory-related tasks; writing checks or taking the bus somewhere; but by the end, they "forget" most everything--how to use the toilet, eat, even walk. (5)

Memory loss is just one symptom of the disease, however. People with Alzheimer's disease often exhibit significant personality changes or act in inappropriate ways as the disease progresses. Victims may also have mood changes, including depression, and in the middle stages of the disease become agitated and/or aggressive at times. (5)

Early Diagnosis is Critical

Given that a diagnosis of Alzheimer's disease is inherently fatal, and that existing treatments do little to change the progression of the disease, why would an early diagnosis be important?

Just ask Kathleen Negri, a 45-year-old elder law attorney whose mother died from complications caused by Alzheimer's disease in the summer of 2004. Ms. Negri knew something was terribly wrong when her previously energetic mother stopped cooking and cleaning and just sat and stared out the window. But it took another five years of fear and denial before her mother was finally diagnosed.

Those were five wasted years, says Ms. Negri of Wheat Ridge, CO. Wasted because the lack of a diagnosis meant her mother couldn't begin taking medication that might have slowed the inevitable decline. Wasted because she, her siblings and her father spent too much time being frustrated and angry with the older woman instead of accepting the limitations of the disease.

"If you don't get a diagnosis and talk about it, you miss a huge opportunity for the person with the diagnosis to do some things for themselves and their families" while there's still time, agrees Dr. Coleman. That includes things like advanced care planning, dealing with financial issues and determining how they want to spend their final years.

But getting someone affected with Alzheimer's disease-like symptoms to a health professional for a diagnosis can be difficult, says Dr. Pendlebury, no matter how bad the symptoms get. "The average patient with Alzheimer's disease will deny that they have a problem," he says, "so it's really up to the family to step up to the plate and be proactive in demanding that the primary care physician do a complete workup for Alzheimer's disease."

That's what happened in Ms. Negri's family. Her mother refused to see a doctor for years after her symptoms began. Ms. Negri finally had to threaten her mother with legal action before the older woman agreed to see a doctor. The diagnosis, she said, "changed everything."

"Once we had a word to use, it opened people up to what was going on," she said. Before, her father yelled at her and her siblings for trying to help their mother. After the diagnosis, says Ms. Negri, he accepted the help, allowing her to wash her mother's hair, and hire a home health aide.

"I cannot overestimate the need for early diagnosis both emotionally and cognitively," she says.

Getting the Diagnosis

Diagnosing Alzheimer's disease can be tricky. In fact, the only way to get a confirmed diagnosis is through a brain autopsy after death. But doctors are getting better at using cognitive memory tests and, if necessary, brain imaging technology like MRIs or PET scans, to evaluate changes in the brain. Most experts also recommend that families seek help at centers devoted to memory problems or, at least, try to find a physician who specializes in age-related disorders. (See Resources, page 4.)

In September 2004, Medicare approved coverage of PET scans in some circumstances to help diagnose dementia, including Alzheimer's disease. "This is important because it's the most sensitive diagnostic method we have for picking up on people at risk for the disease," says Dr. Grossberg. (7)

If you think you or someone else in your family has Alzheimer's disease, make sure you get a complete medical workup, including MRI or CT scans and blood work to rule out other causes of dementia. "More than 150 medical conditions--some temporary--can cause dementia," says Dr. Pendlebury. Those include depression, drug intoxication, thyroid disease, brain tumors and stroke.

To help health care professionals get better at diagnosing the disease, the National Institute on Aging and other organizations launched a $60 million, five-year public-private partnership in October 2004 called the Alzheimer's Disease Neuroimaging Initiative. The study is designed to test whether MRI, PET, other biological markers and clinical and neuropsychological assessment can be combined to measure the progression of mild cognitive impairment and early Alzheimer's disease. (8)

"This study will be a landmark study in our ability to see biological change in Alzheimer's disease," says William H. Thies, PhD, vice president of medical and scientific affairs at the Alzheimer's Association.

Treating Alzheimer's Disease

Today, Alzheimer's disease experts and researchers talk about an air of "optimism" enriching their meetings as studies about new treatments, new diagnostic techniques and new risk factors for the disease are presented.

"It's a very exciting time now," says Dr. Kawas. "I'm not going to say anything like we're going to have a cure in the next 10 years, I'm not sure we're ever going to have one. But I think Alzheimer's disease is going to be quite similar to the cancer story. We're going to chip away at it."

To date, that chipping has resulted in five FDA-approved drugs to treat the disease, none of which do much more than temporarily stabilize or slow the progression.

Four of the drugs--tacrine (Cognex), donepezil (Aricept), rivastigmine (Exelon) and galantamine (Reminyl)--are known as cholinesterase inhibitors. They work by increasing the amount of the neurotransmitter acetyl-choline in the brain, which helps brain cells communicate, and work best when prescribed early in the disease, says Dr. Grossberg.

The newest drug, memantine (Namenda), is the first available for those with moderate to severe Alzheimer's disease. It works on a different neurotransmitter called glutamate, explains Dr. Grossberg. Namenda is now being tested in people with earlier stages of the disease, he noted.

Other drugs in development are directed at the underlying causes of the disease to help prevent the formation of the brain-robbing plaques and tangles in the first place. Additionally, vaccines, which eliminate the plaques after they've formed, are also being developed. (9)

"There is a very rich pipeline of treatments under development right now," says Dr. Thies. "And the more we have in the pipeline, the more likely it is that one or two or three will turn out to be beneficial."

Resources

Alzheimer's Association

225 N. Michigan Avenue 17th Floor

Chicago, IL 60601-7633

1-800-272-3900

http://www.alz.org

Offers a variety of information to heighten public awareness, provide support, and advocate for legislation responsive to Alzheimer's disease.

The Alzheimer's Disease Education and Referral (ADEAR) Center

Building 31, Room 5C27

31 Center Drive, MSC 2292

Bethesda, MD 20892

1-800-438-4380

http://www.alzheimers.org

Provides current information about Alzheimer's disease and related disorders; part of the National Institute on Aging.

Alzheimer's Foundation of America

322 8th Avenue, 6th Floor

New York, NY 10001

1-866-232-8484

http://www.alzfdn.org

Presents a variety of services including counseling by social workers and other professionals, plus referrals to other disease-related resources.

Eldercare Locator

Community Assistance for Seniors

U.S. Administration on Aging 

http://www.eldercare.gov

1-800-677-1116

Mon. to Fri., 9:00 AM to 8:00 PM (ET), or leave message; call will be returned next business day. Connects caregivers and families to trustworthy local support resources. Information available in more than 150 languages.

Family Caregiver Alliance

180 Montgomery Street, Suite 1100

San Francisco, CA 94104

1-800-445-8106

http://www.fca.org

Addresses the needs of providing long-term care at home. FCA offers programs at national, state and local levels to support and sustain caregivers.

References

(1) Kawas CH. Clinical practice. Early Alzheimer's Disease. N Engl J Med. 2003;349(11):1056-63. Review.

(2) Minorities Hardest Hit by Alzheimer's Disease. [press release]. Alzheimer's Association. July 21, 2004.

(3) Alzheimer's Association Survey of Americans' Knowledge and Opinions About Alzheimer's Disease. Alzheimer's Association. February 12, 2004.

(4) Barrett JJ, Haley WE, Harrell LE, et al. Knowledge about Alzheimer disease among primary care physicians, psychologists, nurses, and social workers. Alzheimer Dis Assoc Disord. 1997;11(2):99-106.

(5) Cummings JL. Alzheimer's disease. N Engl J Med. 2004; 1;351(1):56-67. Review.

(6) Fact Sheet: About Genes and Alzheimer's Disease. Alzheimer's Association. October 13, 2004. http://www.alz.org/Resources.

(7) Brain Imaging Techniques Sharpen Focus on Alzheimer's [press release] Alzheimer's Association. July 20, 2004.

(8) National Institute on Aging, Industry Launch Alzheimer's Disease Neuroimaging Initiative. [press release.] National Institute on Aging. October 13, 2004.: http://www.alzheimersupport.com.

(9) Peterson A. A New Approach to Fighting Alzheimer's. The Wall Street Journal. June 29, 2004.

(10) Rapp SR, Espeland MA, Shumaker SA, et al. WHIMS Investigators. Effect of estrogen plus progestin on global cognitive function in postmenopausal women: the Women's Health Initiative Memory Study: a randomized controlled trial. JAMA. 2003;289(20):2663-72.

RELATED ARTICLE: Estrogen and Alzheimer's Disease

For years, researchers thought that estrogen protected women against developing Alzheimer's disease, and that menopausal hormone therapy could delay or even prevent the onset of the disease. Then came the Women's Health Initiative, or WHI, a federally funded study testing the effects of hormone therapy against a variety of conditions.

In 2002, the WHI found that women taking the hormone therapy, Prempro, composed of progestin (a synthetic form of progesterone) and conjugated equine estrogen, had twice the risk of dementia compared to those not using any hormones. (10) Put another way, of the 10,000 women taking hormone therapy in a year, 23 additional women would develop dementia.

Claudia H. Kawas, MD, professor of neurology, neurobiology and behavior at the University of California, Irvine, has been studying the effect of estrogen on Alzheimer's disease for years, publishing one of the first studies suggesting that estrogen use could reduce the risk of developing the disease.

"My message about estrogen management has not changed once in the last 20 years," she says. "I think estrogen is a quality of life issue for the majority of women. If it makes you feel good, take it. If it doesn't make you feel good, you shouldn't take it. But if you're taking it to prevent Alzheimer's disease, there's not enough evidence for that."

RELATED ARTICLE: Facts About Alzheimer's Disease

1. An estimated 4.5 million Americans-over half are women-have Alzheimer's disease, a figure that is expected to more than triple by the year 2050 as the population ages.

2. Women far outnumber men as caregivers for family members with Alzheimer's disease. The chronic stress of caregiving can seriously affect a caregiver's health.

3. Regular exercise, maintaining a healthy weight and eating a balanced, nutritious diet may reduce your risk of developing Alzheimer's disease. Controlling blood cholesterol and diabetes, and lowering blood pressure may also reduce your risk.