Deeply affected: as the nation ages, Alzheimer's will strike more people close to us.

It's a simple message, really: Alzheimer's kills and the number of people affected by the disease will grow to epidemic proportions unless something is done.

How bad could it get? About 350 percent worse, according to Dr. Dharma Singh Khalsa, president and medical director of Alzheimer's Prevention Foundation International in Tucson, Ariz.

Alzheimer's-related organizations and government agency nationwide, including APFI, the Chicago-headquartered Alzheimer's Association and the National Institute on Aging in Bethesda, Md., estimate that nearly 4 million Americans currently have the debilitating disorder, which destroys the brain's neurons and progressively affects all of the mind's functions.

These same groups estimate that 14 million will be afflicted by the middle of the century unless a cure or preventative treatment is found.

According to the federal 2002 National Vital Statistics Report, Alzheimer's is the nation's No. 4 cause of death among all persons; among persons age 65 and older, Alzheimer's is the ninth-leading cause of death of men and the fifth-leading cause of death of women nationwide.

Ten percent of all persons currently age 65 or older have been diagnosed with the disease and half of all Americans age 85 are afflicted. Combine those numbers with the fact that the United States as a whole is growing older--34 million Americans are now older than 65, a figure that will double by 2030, according to Census data--and "we are on the brink of an epidemic," Singh Khalsa says.

"The good news," Singh Khalsa adds, "is that if we can slow onset of the disease by five years, we can cut the incidence in half. If we can slow progression by 10 years, we will have eradicated it entirely."

Singh Khalsa and others from APFI have delivered this message many times, including during a recent hearing before the House of Representatives' Subcommittee on Labor, Health and Human Services, when he asked Congress to appropriate $10 million for research into how lifestyle influences the onset of Alzheimer's. The issue is still under consideration by lawmakers.

ARFI's medical director is encouraged by recent changes in thinking toward emphasizing--even considering the possibility of--prevention of Alzheimer's. For more than a decade, he's stressed that the best way to tackle the disease was to prevent it from taking hold of a person's mind.

In the beginning, he was ridiculed. "Many of my conventional medical colleagues did not support the notion that the disease could be prevented," Singh Khalsa says. "I was often met with hostility. Thankfully, modern medical research is finally catching up ... but we are still falling short of our responsibilities to promote prevention over early intervention."

"Early intervention" efforts typically call for diagnosing the disease as soon as possible--typically when a person is in late middle age or older--then treatment with various drugs [see "Doing Drugs," Page 24]. Singh Khalsa believes a renewed emphasis on education about Alzheimer's and how it can be prevented will benefit everyone from afflicted adults to health care professionals, and assisted living and retirement communities.

Conventional treatment for Alzheimer's is only partially effective, Singh Khalsa notes. Currently, there is no definitive test for the disease--outside of an autopsy.

Cognitive tests can assess the degree of memory impairment but are not able to specifically identify Alzheimer's; other efforts, such as MRI and PET brain scans, and attempts to find abnormal proteins in the cerebrospinal fluid and within the lens of the eye, may one day be more reliable tools.

But because the disease takes 20 years or more to develop, most of the damage done to a person's brain is irreversible by the time definite symptoms appear [see "Stages of Loss," below]. This is why we believe prevention is most important," Singh Khalsa says.

Singh Khalsa would like to see the government appropriate $5 million to the U.S. Administration on Aging to jump-start a national education and outreach campaign. "The Administration agrees that many chronic diseases can be prevented through healthy lifestyles, physical activity, and appropriate diet and nutrition," he says. "This is certainly the case with Alzheimer's."

DOING DRUGS

Although there is no "instant cure," there are currently four drugs approved by the U.S. Food and Drug Administration for treating Alzheimer's Disease-related memory problems--and several others are on the way. Here's a rundown of what's available--and what soon could be:

Cholinesterase inhibitors

These drugs block an enzyme that recycles acetylcholine.

Acetylcholine, when allowed to accumulate in the brain, appears to improve memory function in earlier-stage Alzheimer's patients or at least slow disease progress. Side effects include nausea, vomiting, diarrhea and stomach ulcers, as well as possible adverse interactions with other drugs that the patient may be taking:

* Donepezil (Aricept[R]): Approved for mild and moderate stages of Alzheimer's, patients on this drug may demonstrate clearer thinking and maintained physical function. Taken once per day, it's one of the easiest for patients to use. Sold by Pfizer Inc.

* Galantamine (Reminyl[R]): May increase neurons' sensitivity to acetylcholine, thus enhancing the effect of acetylcholine on the brain in early and moderate stages of Alzheimer's. Like donepezil, galantamine has fewer side effects than other drugs. Must be taken twice per day. Sold by Janssen Inc.

* Rivastigmine (Exelon[R]): Believed to block an enzyme that contributes to brain damage during the later stages of Alzheimer's, although no clinical studies support this statement. This is the only drug of the four that does not list diarrhea as a possible side effect. Must be taken twice per day; available in liquid and pill form. Sold by Novartis Pharmaceuticals.

* Tacrine (Cognex[R]): Unlike donepezil, rivastigmine and galantamine, this drug prevents breakdown of acetylcholine in the body as well as the brain, which may help with earlier- and mid-stage Alzheimer cases. Clinical studies show more side effects with tacrine than the others, including possible liver damage. Must be taken four times per day. Sold by First Horizon Pharmaceutical Corp.

Other drugs being tested:

* Memantine: A new drug under clinical trials in the United States but already used in Europe to treat moderate-to-severe cases of Alzheimer's, memantine may block transmission of excessive amounts of glutamate, which is believed to cause neuronal cell dysfunction and cell death. F.D.A. approval is underway; Forest Laboratories Inc. expects to begin selling the product in the United States by mid-2004.

* Dronabinol: A synthetic version of tetrahydrocannabinol (Marinol), currently used as an appetite stimulant in cancer and AIDS patients, dronabinol is being tested to see whether it helps reduce agitation and improve weight gain among Alzheimer's patients.

* Lithium: Originally used to treat bipolar disorder and manic depression, scientists now believe this drug may help block the enzyme that causes Alzheimer-inducing beta amyloid proteins to accumulate in the brain. Ongoing studies also suggest that lithium will be most effective on younger patients or persons who inherited Alzheimer's or Down's syndrome due to its many side effects, such as nausea, increased urine output and trembling hands.

* Additional medications may be prescribed to treat secondary Alzheimer's symptoms, such as agitation, anxiety, depression and insomnia.

Source: Alzheimer's Disease and Related Disorders Association, New England Journal of Medicine, Meridian Institute for Aging

STAGE OF LOSS

Alzheimer's warning signs:

[check] Loss of smell and hearing, typically one to two years before the disease is clinically obvious.

[check] Onset of depression, up to several years before diagnosis.

[check] Gradual loss of short-term memory, beginning as early as 20 years before diagnosis.

[check] Upon diagnosis, Alzheimer's follows four general stages. Transition through these stages can take from 4 to 20 years.

Early stage

[check] Typical duration is two years.

[check] Short-term memory--memory of recent events--is mildly impaired. Person has difficulty remembering new information such as names or location of objects.

[check] Person's personality begins to change, with lack of normal emotional response an early sign.

[check] Long-term memory is still normal.

[check To distinguish Alzheimer's from other forms of memory impairment, diagnosis usually isn't given until memory loss affects daily functioning.

Moderate stage

[check] Typical duration is 18 months to two years.

[check] Person can no longer recall basic memories such as a home phone number or family member names.

[check] Depression and mood swings are common.

[check] Person may become easily lost, agitated or restless.

[check] Dressing and grooming requires assistance.

Moderately Severe stage

[check] Typical duration is two to three years.

[check] Person develops emotional problems such as irrational or compulsive behavior.

[check] Problems with coordination, and urinary and fecal incontinence are common.

[check] Short- and long-term memories are virtually gone.

Advanced stage

[check] Typical duration is up to seven years.

[check] Person becomes aggressive and/or paranoid, suffering from hallucinations and delusions.

[check] Weight loss is common.

[check] Person requires complete care by others; he or she is no longer able to sit or stand.

[check] Vocabulary is reduced to a few words.

[check] Many persons die from other causes before reaching this stage.

Source: Alzheimer's Prevention Foundation International

VITAL STATISTICS

* Alzheimer's disease is named after German physician Lois Alzheimer, who first described the disease in 1907. Alzheimer's stems from the buildup of abnormal amyloid plaques (protein deposits) in the brain.

* The disorder begins with loss of short-term memory and progressively affects all of the brain's functions. Alzheimer's destroys the brain's neurons, starting with the hippocampus, which helps transfer short-term memory to long-term.

* Alzheimer's may begin 10 to 20 years before it is clinically diagnosed; life expectancy is 4 to 20 years after diagnosis.

* Persons with high blood pressure, head trauma or stroke are more susceptible, as are persons with a close relative who develops Alzheimer's.

* Every person with Alzheimer's will die--unless a cure or prevention is found.

Source: Alzheimer's Prevention Foundation International