If getting old were easy, more people would do it. The oldest living human being is a French nun who recently celebrated her 118th birthday. Until a few weeks ago, a Japanese woman beat her in the senescence competition by making it to her 119th birthday before dying. The longest surviving person on record was French and lived to be 122 years old. The French claim it is their wine that keeps their citizens breathing long after the customary expiration date for mere mortals. As a member of that small community of Americans who do not drink alcoholic beverages, I hope the longevity of these women had more to do with their genes than with their choice of Bordeaux.
Of course, our general desire to live long (and prosper) is tied to our overriding desire to remain mentally intact. There is little satisfaction in living if you cannot think. There is no escaping the physical decline associated with ageing, but escaping the intellectual decline that we see in the elderly that surround us may be feasible.
Problems with memory, comprehension, language production, and orientation, as well as with recognizing people we have dealt with for years, are generally referred to as dementia. Dementia is an umbrella term for innumerable intellectual problems caused by dozens, if not hundreds, of diseases and disorders. Vitamin B12 deficiency, syphilis, vascular disease, asphyxia, poisoning, chronic alcoholism, and genetic diseases can all lead to dementia, but the one cause of dementia that America is most obsessed with is Alzheimer’s disease. This progressive brain disease is of unknown cause and has no truly effective treatment. Decades of research and billions of dollars spent on drug trials have led to one dead end after another. We apparently do not have the wisdom to unravel this brain disease.
Alois Alzheimer was a nineteenth century, German physician who described changes in the brains of people with what he called presenile dementia. “Presenile” emphasized the observation that the patient did not need to be old to be affected. The first case he had the opportunity to study was that involving a woman with a several year history of memory problems who died at the age of 56. She started having memory problems in her late 40s, an age that even in the nineteenth century was not considered old. He described changes in the fine structure of this demented woman’s brain, and the changes he described at her autopsy have survived as the hallmarks of this progressive disease. That the disease is currently more prevalent in old people than in young or middle-aged people probably reflects a long disease course, rather than a special vulnerability in the elderly.
Dr. Alzheimer recognized that the memory problems exhibited by the first person with this dementing disease whose brain he was able to examine were distinct from that exhibited by people with late stage syphilis, malnutrition, infections, and other common causes of dementia in nineteenth century Europe. What we now consider a relatively common disease of the elderly was actually first described as an unusual disease of the middle-aged. Of course survival to 80 or 90 years of age was less common in Alzheimer’s era than it is now, but there were many people (including President John Adams) who made it to their ninth or tenth decade of life without exhibiting dementia. Alois Alzheimer, like many of his contemporaries, died at 51 years of age from an infection. In his case, it was his heart, not his brain, that succumbed to a common germ.
Recently developed imaging techniques allow us to diagnose Alzheimer’s Disease without taking a piece of the brain for staining and microscopic study. We now know that some families carry a genetic predisposition to develop this disease, but most people with the disease have no apparent risk factors. Despite numerous claims that drugs are available that slow the progression of the disease, most affected individuals garner no substantial benefit from the drugs approved for the treatment of Alzheimer’s disease. In fact the most recently approved drug, Aduhelm, was not recommended for approval by the scientific committee that reviewed the manufacturer’s data.
The Food and Drug Administration (FDA) is tasked with establishing that drugs approved for sale in the United States are relatively safe and effective. Scientific committees review the manufacturer’s experience with the drug and certify that it is, in fact, relatively safe and effective. The committee reviewing the experience with Aduhelm concluded that effectiveness had not been demonstrated. The FDA approved the drug for sale anyway. The cost of a one year supply of Aduhelm for one patient is $28,200, an extraordinary price for any drug and especially for one that is recommended for multi-year administration to an ever expanding population of Americans. The drug was originally priced at $56,000 for a one year supply, but resistance to adopting what has been widely viewed as an ineffective medicine prompted the price cut.
The willingness of the FDA to approve a drug that failed to show real benefits for Alzheimer’s disease victims and the audacity of the company that developed the drug to initially charge more than $50,000 a year for access to the drug can be explained several ways. The least cynical explanation is that the FDA hoped widespread adoption of the drug would reveal a subpopulation that did benefit from what was viewed as a theoretically useful drug and the company that developed the drug expected it would be required to perform additional clinical tests that would cost it considerably more than its original development costs. A more likely explanation is that the immensely powerful pharmaceutical lobby urged the congressmen and congresswomen that it generously subsidizes to convince FDA employees to approve Aduhelm.
The company promoting the approval of this drug may have expected people desperate for a treatment for their Alzheimer’s disease to pay any price demanded by the manufacturer. In recent decades, the cost of drugs for treating brain conditions has been extraordinary and indefensible and has generally moved higher each year. Rather than regulating the pricing of newly introduced drugs targeting nervous system diseases, our Congress has enacted laws that interfere with competitive pricing. There can be no doubt that eventually, and hopefully soon, there will be drugs that are highly effective in the treatment of Alzheimer’s disease, but without changes to our drug approval system and pricing restrictions, those drugs may be lost in a blizzard of inappropriate approvals and may be too expensive for 99 percent of the affected population.
Dr. Lechtenberg is an Easton resident who graduated from Tufts University and Tufts Medical School in Massachusetts and subsequently trained at The Mount Sinai Hospital and Columbia-Presbyterian Medical Center in Manhattan. He worked as a neurologist at several New York Hospitals, including Kings County and The Long Island College Hospital, while maintaining a private practice, teaching at SUNY Downstate Medical School, and publishing 15 books on a variety of medical topics. He worked in drug development in the USA, as well as in England, Germany, and France.