The Doctor Weighs In

So let’s be honest, baby boomer, aren’t you worried about turning a geezer boomer soon? After all, the first of you just got on Social Security. And what about those memory lapses? In your heart of hearts, are’nt you scared just a little bit? If you are not—read on.

Here are some sobering statistics.

· More than 5 million Americans are estimated to have Alzheimer’s disease or AD today. It is projected that 14.3 million Americans will have the disease by mid-century: a 350 percent increase from 2000, when there were 4 million people with the disease. Reason for the expected explosive growth: a tidal wave of aging baby boomers turning old geezers.

• In the United States, AD was the 7th leading cause of death in 2004
• , with 65,829 number of deaths (and rising).
• At over $100 billion per year, AD is the third most costly disease in the U.S., after heart disease and cancer.
• There are an estimated 24 million people with dementia worldwide.
• By 2040, it is projected that this figure will have increased to 81 million.

What is AD?

A good description can be found on WebMD.

”Alzheimer's disease is a progressive degeneneration of brain tissue that primarily strikes people over age 65. It is the most common cause of dementia in this age group and is marked by a devastating mental decline. Intellectual functions such as memory, comprehension and speech deteriorate.

Attention tends to stray, simple calculations become impossible and ordinary daily activities grow increasingly difficult, with bewilderment and frustration. These symptoms tend to worsen at night. Dramatic mood swings occur -- outbursts of anger, bouts of fearfulness, and periods of deep apathy. The sufferer, increasingly disoriented, may wander off and become lost. Physical problems, such as an odd gait or a loss of coordination, gradually develop. Eventually, the patient may become physically helpless, incontinent and unable to communicate.

Alzheimer's disease can run its course from insidious onset to death in just a few years, or it may play out over a period of as long as 20 years. More often, however, people suffer with Alzheimer's disease about nine years. By the age of 80, about one person out of three has the disease. Women are more susceptible than men and half of all nursing home residents suffer from Alzheimer's or related disorders.”

What is the cause?

Recent research (after 2000) includes hypotheses centered on the effects of two misfolded and aggregated proteins, amyloid beta and tau. The two warring (and I mean WARRING) schools of thought differ with one stating that the tau protein abnormalities initiate the disease cascade, while the other states that amyloid beta (Aβ) deposits are the causative factor in the disease. The tau hypothesis is supported by the observation that a mutation in this protein correlates with formation of protein aggregates inside the neuron (neurofibrillary tangles) that are characteristic of neurons in AD brains. This camp also points out that deposition of amyloid plaques do not correlate well with neuronal loss;

A universal finding in biopsies of AD brain tissue is the existence of fatty plaques adjacent to the affected neurons. The hypothesis is that these plaques, made up of aggregates of a protein called Amyloid beta or Aβ, or its precursor, which are toxic to the neurons. A majority of researchers support the hypothesis that Aβ is the primary causative agent. Interestingly, ApoE4, the major genetic risk factor for AD, leads to excess amyloid build up in the brain before AD symptoms arise. Thus, Aβ deposition precedes clinical AD.

Is there any treatment?

Early studies discovered that in AD patients there was a marked decrease in the neurotransmitter acetylcholine. So the idea was that by inhibiting the enzyme that breaks down this neurotransmitter (cholinesterase), one could reverse the symptoms of the disease. In hindsight, this was quite a naїve assumption: the devastation in the brain is so extensive that reduction in acetylcholine secretion could be just “collateral damage”. Several drugs based on this principle are on the market:

· tacrine - no longer clinically used (formerly marketed as Cognex)

· donepezil- (marketed as Aricept)

· galantamine- (marketed as Razadyne in the U.S.A. Marketed as Reminyl or Nivalin in the rest of the world)

· rivastigmine- (marketed as Exelon)

The three currently marketed products each comes in an oral form taken once or twice a day. Rivastigmine is also available as a once-daily transdermal patch.

There is a lot of doubt as to the effectiveness of cholinesterase inhibitors. At best, they confer mild and temporary slowdown in the early stage of progression of the disease. Tacrine was the first drug to get approval, but only after intense grassroots lobbying and congressional involvement. The FDA bowed to this pressure with evident reluctance. The three drugs that are currently on the market are based on the same principle as tacrine (inhibition of the enzyme that breaks down acetylcholine, cholinesterase), and have about the same clinical efficacy. A number of recent articles have criticized the design of studies reporting benefit from these drugs, concluding that they have doubtful clinical utility, are costly, and confer many side effects.

A small, but significant step forward

Doctors can diagnose Alzheimer’s only by eliminating other possible causes of mental decline. There is no definitive test for the disease until a person dies, when surgeons can examine his or her brain tissue to look for the protein plaques and tangles that are the hallmark of the disease.

Researchers are trying to change that situation by finding biomarkers — definitive biological signatures of the disease. This week, a team led by neuroscientist Tony Wyss-Coray of Stanford University School of Medicine in California reports in Nature Medicine the discovery of 18 proteins that together seem fairly diagnostic for the condition.

If the biomarkers are confirmed by more rigorous testing, they could result in a simple blood test by which doctors could diagnose the disease.

This is important because...

The test allows the diagnosis of AD 2-5 years earlier than is possible today.

· Sufferers could then take medications to delay the effects of Alzheimer’s, plan to change their finances or living situation, or enroll in clinical trials to test potential new drugs.

· With annual research expenditures by NIH and the pharmaceutical industry approaching 2 billion dollars a year, and a whole raft of drugs in various stages of development, it is just a question of time before effective therapy will be available. At that time, early diagnosis will be crucial to minimize the havoc wreaked upon the the brain by AD.

So take heart, baby boomers reaching geezerhood; this monster is being tamed, and sooner rather than later.

Dov Michaeli MD, Ph.D is in the the biotech industry.