Alzheimer's disease: a black cloud on the horizon.

During his first year of retirement, Ronald Reagan was thrown from his horse while vacationing in Mexico.  The 78-year old former president suffered a concussion and was treated at the Mayo Clinic for a subdural hematoma.  Although he made a complete recovery from the horse riding accident, the traumatic brain injury accelerated a process in his brain that had started decades earlier and would ultimately result in his death.

Five years later, the 40th president of the United States of America was diagnosed with Alzheimer's disease (AD).  Doctors told him that the memory problems he was experiencing were early symptoms of this neurological disorder.  They also explained that Alzheimer's is a degenerative and terminal condition in which vulnerable areas of the brain are progressively poisoned by accumulating toxins.    

The history of AD began before Reagan was born.  In 1901, at a Mental Institute in Frankfurt, Germany, Dr. Alois Alzheimer was presented with a 51-year old woman called Auguste Deter.  Her husband, a railway worker, could no longer afford to miss work to care for her and brought her to be admitted.  When the German physician first examined her she was paranoid, confused and suffering memory impairments.  Her symptoms gradually worsened and in 1906, she died. 

The pathological features of disease were first described when Alzheimer conducted post-mortem examination of Auguste Deter's brain.  He immediately noticed a massive amount of tissue loss in the brain regions responsible for memory and cognition.  When he observed these areas of the brain under the microscope he described two distinct abnormalities.  Two toxic substances had accumulated in her brain.  These poisonous deposits were named ‘amyloid plaques' and ‘neurofibrillary tangles'.  Alzheimer concluded that their presence in the brain induced the neuronal loss and memory impairment he had observed in Auguste Deter.

Alzheimer's is an irreversible progressive disease, meaning the longer it lasts, the worse it gets.  The plaques and tangles continue to accumulate and destroy the brain regions in which they reside.  Outward signs of the disease worsen in parallel to the underlying pathology.  Symptoms such as mild memory problems and bouts of confusion provide an overlap between the disease and normal aging.  However, as the condition progresses memory impairment becomes more severe.  Eventually, the patient is left vegetative and incontinent, and completely dependent on professional care.

Following his diagnosis in 1994, and aware of his fate Reagan penned a letter to the American people, famously stating, “I now begin the journey that will lead me into the sunset of my life”.  Ten years later, his mind ravaged and his dignity stolen, he died.  Once the most powerful man in the world, he was powerless to prevent the progression of this cruelest of diseases.   

Unfortunately, this is not a rare story.  AD is the most common form of dementia in the elderly, affecting over 4 million Americans.  Risk factors for AD include family history, heart disease and, as in Reagan's case, acute brain injury.  However, the greatest risk factor for the development of AD is the unavoidable process of aging.  Once you reach retirement age, the probability that you will develop Alzheimer's doubles approximately every five years.  If you are fortunate enough to live until age 85, there is a 50% chance you will suffer from AD.  Perhaps it is even more compelling to apply those statistics to a partner or parent?

After heart disease, cancer and stroke, AD kills more Americans every year than any other ailment.  Of course the cost of AD can be calculated in dollars as well as lives.  It is the third most expensive disease to treat, at an estimated average of $175,000 per patient.  In the US alone, this equates to over $100 billion spent on AD every year. 

More than a medical problem, AD is a growing social and economic issue and it is getting worse.  The cause of AD is unknown and there are currently no effective treatments.  Ominously, the ‘baby boomer' population is now entering the age when vulnerability to AD becomes significant.  This fact, combined with a continually increasing life expectancy predicts that the number of AD cases in the U.S. will triple by the year 2050, providing a potentially crippling fiscal burden.

There is hope though.  For over a century researchers agreed with Alois Alzheimer and focused their energies on understanding plaque and tangle pathology.  Their efforts were rewarded with a surprise.  It turns out, plaques and tangles aren't the bad guys after all.  More likely, they represent a protective attempt by the brain to extinguish their toxic precursors.  The next challenge is to identify the specific disease causing substances that lie upstream of plaques and tangles.

Only when this is achieved will the outlook brighten for a society that expects to reflect on their lives and enjoy their retirement.

Martin Ramsden PhD, Research Fellow, Department of Neurology, University of Minnesota.