Alzheimer's Update—New Treatments on The Horizon...

There are four drugs currently on the market that can delay the progression of Alzheimer's symptoms for up to a year.

And researchers are investigating dozens of new medications that attack Alzheimer's underlying disease mechanism. Hopefully, at least several will be found effective and approved for use over the next few years.

Here are the drugs currently available for treating Alzheimer's and the experimental drugs that may work better…

Current Medications

Four FDA-approved medications are currently used to treat Alzheimer's disease.

Three drugs—donepezil (Aricept), rivastigmine (Exelon) and galantamine (Razadyne)—are cholinesterase inhibitors, which boost levels of acetylcholine, a chemical in the brain known as a neurotransmitter that is involved in attention and memory. The FDA recently approved an Exelon skin patch. Applied just once a day and worn for 24 hours (as opposed to the pill form, which is taken twice a day), it decreases the likelihood of forgetting a dose, while minimizing the gastrointestinal side effects of nausea and diarrhea sometimes caused by these meclications.

The fourth medication, memantine (Namenda), reduces brain levels of glutamate, a chemical linked to brain cell degeneration. Namenda may be taken alone or with a cholinesterase inhibitor.

All four drugs are equally effective and can be useful in the appropriate circumstances—with mildly affected patients who are otherwise in good health. However, they're basically plugging a leaky dike-improving symptoms temporarily, but doing nothing to prevent the continued destruction of brain cells. They typically delay onset of further Alzheimer's symptoms by six months to a year, after which patients begin to deteriorate. Continuing on these medications will still keep them functioning at a higher level than they would otherwise, delaying the onset of severe symptoms, such as loss of ability to carry out basic daily living activities (bathing, dressing, etc.).

Experimental Medications

What's desperately needed are drugs that intervene in the Alzheimer's disease process to halt, or even reverse, its progression.

About a dozen candidates are now in middle-to-late stages (Phase II or III) of human trials, while many others are in earlier stages (Phase I) of study.

To find out more about clinical trials that you or a loved one may be eligible for, visit the National Institute of Aging's Web site (www.nia, nib.gou Alzheimers) and click on "Search the AD Clinical Trials database."

Many of these new drugs focus on reducing brain levels of beta amyloid, a protein that forms plaque deposits inside the brains of people with Alzheimer's. Many researchers think beta amyloid is the disease's primary cause. These experimental medications either speed removal of beta amyloid particles from the brain, block their production or immunize the brain against them. For Phase II, they include..

Compound LY450139, from Eli Lilly.

Action: Deactivates gamma-secretase, an enzyme involved in beta amyloid production Phase II trials are completed. Phase III trials include...

Tramiprosate (Alzhemed), an amyloid-reducing therapy from Neurochem.

Action: Binds with beta amyloid, preventing it from forming brain deposits. Recently completed its Phase III trials. The results of the trials were inconclusive.

Tarenflurbil (Flurizan), from Myriad Pharmaceuticals.

Action: Modulates gamma-secretase activity to reduce levels of a particularly toxic amyloid sub-type.

Status: Recently completed its Phase III trials.

Bapineuzumab, from Wyeth and Elan.

Action: An Alzheimer's vaccine,"containing antibodies that bind with amyloids and remove them from the brain.

Other experimental medications focus on the fact that the brains of Alzheimer's patients show reduced glucose metabolism, which could be damaging brain cells by depriving them of sustenance. Phase II trials include...

*In Phase 1 of a clinical trial, the drug or treatment is tested for the first time with a small group (20 to 30 people) to evaluate its safety, determine dosage ranges and identify side effects. In Phase II, it is tested with a larger group (100 to 300 people) to evaluate effectiveness, as well as to further evaluate its safety. In Phase III, large groups (1,000 to 3,000 people are given the drug or treatment to confirm effectiveness, monitor side effects, compare it with other commonly used treatments and collect other data that will allow the drug to be used safely.

Compound AC-1202 (Ketasyn), a drug from Accera.

Action: Provides brain cells with an alternative energy source to glucose.

Phase III trials include…

Rosiglitazone (Avandia), from GlaxoSmithKline, a drug already used to treat type 2 diabetes.

Action: Enhances glucose metabolism by increasing insulin sensitivity. Now in Phase III trials for mild to moderate Alzheimer's in a subset of patients with one genetic marker. Questions have been raised about its safety.

A number of other studies are looking at potential benefits of familiar medications for Alzheimer's disease, including…

A variety of statins. Studies have found that people taking statins tend to have lower Alzheimer's rates.

Possible reasons: Statins may modify beta amyloid production processes and/or reduce inflammation. Improved cardiovascular health in general also has been linked to reduced Alzheimer's risk.

Dimebon, a drug used for decades in Russia as an antihistamine, has shown promise in delaying the onset of Alzheimer's symptoms in ongoing Phase II trials.

Alternative Treatments

There is some evidence that several nutritional supplements may have a modest preventive effect against Alzheimer's. Several large studies of these supplements are now under way, including…

A Phase III trial in which subjects are taking 2,000 mg/day of DHA—an omega-3 fatty acid shown to reduce beta amyloid levels and slow the accumulation of tau, a protein linked to the development of neurofibrillary tangles—another signature brain lesion associated with Alzheimer's.
Another study in which 10,000 people are taking daily supplements of the antioxidants vitamin E (400 IU/day) and selenium (200 micrograms/day), which are thought to have neuroprotective properties.
A 10-year study—nearly concluded—of ginkgo biloba, an herb with antioxidant and anti-inflammatory properties, long reputed to improve mental function.

Although these supplements are readily available, they are not yet proven to a reasonable scientific standard to have any effect on Alzheimer's. Use as a preventive or for symptomatic therapy is not recommended.

Staying Mentally Active

Finally, there's a very interesting and extensive line of research showing that people who are mentally active have a lower risk of developing Alzheimer's. It's not clear whether this mental activity actually forestalls the disease, or if those who are mentally active have healthier brains to start with-brains that allow them to be more active. That said, it's clear that staying mentally engaged—whether by continuing to work, reading and discussing books, doing challenging crossword puzzles, volunteering or belonging to a group or organization in which you take an active role-is an important factor in maintaining health and vitality as you get older.

Alzheimer’s Warning Signs

Alzheimer's is a degenerative brain disease that starts with occasional memory lapses and eventually progresses to the point where much of one's memory and reasoning power is lost. Ordinary tasks, such as dressing and eating, become difficult or impossible. Early warning signs include…

Decreased ability to recognize common odors.
Forgetting recently learned information or the names of common objects.
Difficulty performing the steps involved in familiar tasks, such as preparing a meal or making a phone call.
Dressing inappropriately.
Inability to perform even simple mental tasks, such as basic arithmetic.
Chronically misplacing objects. Rapid mood swings.
A dramatic personality shift, such as becoming extremely confused, suspicious or fearful, or becoming very dependent on another family member.
Loss of interest in daily activities.

If someone exhibits any of these signs, he/ she should see a neurologist. While there's no single brain scan or lab test that can definitively identify Alzheimer's, an experienced doctor can usually recognize its early stages.

High Blood Pressure May Raise Alzheimer's Risk

High blood pressure may raise Alzheimer's risk, warns researcher Cyrus Raji. High blood pressure reduces blood flow to the part of the brain that controls memory and learning.

Self-defense: Exercise and proper diet are very effective at keeping blood pressure down. Ask your doctor what is best for you.

Drugs That Slow Alzheimer's

Drugs that slow Alzheimer's disease work best when taken early on, says geriatric psychiatrist Richard Powers, MD.

Problem: Many Alzheimer's patients have symptoms years before being diagnosed. Warning signs include short-term memory loss, confusion about time and place, and changes in mood or personality. If you detect symptoms, consult a geriatrician who can do an evaluation.

Drug Boosts Memory for Alzheimer's Patients

A commonly used drug can help patients with A severe Alzheimer's, according to Sandra E. Black, MD. Many patients with mild-to-moderate Alzheimer's disease take donepezil (Aricept to help memory and functioning in everyday life.

New study: Aricept stabilized and sometimes even improved memory, thinking skills and certain other functions in 63% of patients with the advanced stage of Alzheimer's. The comparable figure for patients given a placebo was 39%.

Warning Sign of Alzheimer's

Older people with mild difficulty recognizing scents, such as cinnamon and lemon, are 50% more likely to develop cognitive impairment within five years, compared with people whose odor recognition is intact. This impairment often precedes the development of Alzheimer's.

Overweight Women Are More Likely to Develop Alzheimer's

Overweight women are more likely to develop Alzheimer's than women who are a healthy weight. On average, Alzheimer's risk increases by 36% for every five to eight pounds over your ideal weight (based on your height). If your body mass index (BMD-a ratio relating weight to height-is 25 or above, you are considered overweight. A BMI in the range of 19 to 24.9 is healthy. For an on-line BMI calculator, go to the National Heart, Lung and Blood Institute's Website, www.nblbisupport.com/bmi.

Estrogen Linked to Alzheimer's Disease in Older Men

Men typically have lower levels of the hormone estrogen than women. However, after menopause women have lower estrogen levels than men of the same age.

In a recent study, researchers evaluated hormone levels and cognitive function in 2,974 men ages 71 to 93 over an average of six years.

Result: The risk for Alzheimer's rose with increasing levels of estrogen.

Theory: The production of estrogen involves aromatase, an enzyme that, in some cases, may serve as a marker for Alzheimer's. Previous research found a similar link in women. More studies are needed.

Low Testosterone May Be Hazardous to Your Health

Low testosterone may be hazardous, warns Molly Shores, MD. According to a recent study, which followed men over age 40 for an average of four years, those with low testosterone were up to 88% more likely to die during the study period than men with normal levels.

Self-defense: Men with symptoms of testosterone deficiency-decreased sexual interest, fatigue, irritability, hot flashes and increased abdominal fat—should have their testosterone level checked.

Testosterone Danger

Testosterone levels decline naturally as men age. Despite some advertising claims, supplemental testosterone products—including creams, gels, patches and oral supplements--have no proven age-reversing abilities, and they may increase risk for heart disease and prostate cancer.

Best: Testosterone supplements should be used only by men who have been diagnosed with a significant deficiency and under a doctor's supervision.

Helping the Older HIV Patient

More than 10% of new HIV patients in the M us are 50 or older, reports Barbara Bartlik, MD, Safe-sex messages are not aimed at this age group, but practicing safe sex is as important for older people as it is for younger. Unfortunately, older men, especially those with erectile problems, may be resistant to condom use and women may not insist.

Another issue: As women age, lack of estrogen thins vaginal tissue and genital lesions become common, increasing susceptibility to HIV infection.

Weight Loss? It Could Be an Early Sign of Dementia

Unintended weight loss may occur up to 20 years before dementia is diagnosed.

Recent finding: On average, women with dementia weighed 12 pounds less than women without the condition.

Possible reason: In early dementia, women may develop apathy and lose some sense of smell, so food is less appealing. No correlation was found in men—and the study, unlike others, did not find obesity in middle age to be a risk factor for dementia. Women who have unintentionally lost weight should ask their doctors to check for diseases that might cause weight loss, such as cancer and heart or lung disease. If none are found, consider a dementia connection.