Alzheimer's Disease: Clinical Diagnosis and Treatment
Patricio F. Reyes, MD
Lee A. Nowak, MS
S. Gabe Rice, MS
Division of Neurology, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona
Alzheimer's disease is an insidious disease with staggering social, economic, and emotional effects on both loved ones and society. The greatest risk factor of AD is age, and as the population of elderly increases, the burden of AD will also increase. There is no cure and the best medical treatments only manage symptoms. Knowledge gained from basic science and clinical research improves our understanding of AD and associated risk factors. Early diagnosis is key in helping patients to live longer and more productive, independent lives. This article presents the risk factors, signs, and symptoms of AD and reviews diagnostic and histological techniques and the most current treatments.
Key Words: Acetylcholine, acetylcholinesterase, Alzheimer's disease, butyrylcholinesterase, choline acetyltransferase, N-methyl-d-aspartate, neuritic plaque, neurofibrillary tangle
Abbreviations used: ACh, acetylcholine; AChE, acetylcholinesterase; AD, Alzheimer's disease; BChE, butyrylcholinesterase; ChAT, choline acetyltransferase; EEG, electroencephalography; FDA, Food and Drug Administration; NP, neuritic plaque; NFT, neurofibrillary tangle; NMDA, N-methyl-d-aspartate.
Alzheimer's disease, a neurodegenerative disorder, was first described by Dr. Alois Alzheimer in a middle-aged woman with mental illness and a history of seizures. Her postmortem examination revealed abnormal clumps and tangled bundles of fibers in the brain. Today, these abnormal clumps and bundles of fibers, known as NPs and NFTs, respectively, are the pathologic hallmarks of AD.
The social and economic impact of AD on society is tremendous. Since 1980 the number of Americans with AD has doubled to 4.5 million; by 2050, this number could exceed 13 million. Worldwide, the current number of people affected is estimated to be 18 million, which will almost double to 34 million by 2025. Unless medical advances are realized, these projections could lead to a global crisis. Furthermore, these numbers will only continue to increase as the population grows and life expectancy lengthens.
The cost of caring for an AD patient can be astronomical. The average life span after diagnosis is 6 to 9 years although some patients may survive for as many as two decades. As new therapies are discovered, the life expectancy for patients with AD will also increase. In the United States, the estimated cost for direct care of patients with AD is a staggering 110 billion dollars per year.
The financial, emotional, and physical burdens for the caregiver of an AD patient are also considerable. Many productive members of society leave the work force to care for their ailing loved ones, assuming many of the tasks that patients can no longer perform. Ultimately, patients become completely dependent on the caregiver, resulting in economic and emotional difficulties for families and caregivers.
The Family Caregiver Alliance estimates that care-giving spouses between the ages of 66 and 96 years old who are experiencing mental or emotional strain have a 63% higher risk of dying than people the same age who are not caregivers. According to the Alzheimer's Association, the signs and symptoms of caregiver stress frequently include anger, anxiety, denial, exhaustion, health problems, guilt feelings, irritability, lack of concentration, sleeplessness, and social withdrawal. Hence, treating the caregiver becomes as important as treating the patient with AD.
Depression is common among AD caregivers. One study examined 42 couples equally distributed among early phase AD, ischemic stroke, and controls. Evaluation after 6 months showed that depression was significantly higher in AD and stroke caregivers compared to the controls. Furthermore, 21% of caregivers evidenced moderate to severe depression, and the percentage increased to 50% after 1 year. As the mental and physical health of caregivers declines, they may become unable to care for their loved one with AD.
Physicians must be aware of the differences between normal aging and the signs of dementia in middle-aged to elderly patients. There are many similarities between normal aging and dementia such as difficulties with memory and cognition, abnormal behavior, decreased ability to perform activities of daily living, brain atrophy, loss of neurons, and reduction of neurotransmitters. A dementing condition such as AD, however, is a progressive process that impairs social and professional functioning. Because AD is a degenerative brain disorder, it is assumed that the pathologic process begins years before its clinical manifestation.
Assessing risk factors and taking an extensive patient history are vital when interviewing patients with cognitive deficits. Age is the greatest risk factor because most AD patients are late middle-aged and older. About 3% of Americans between the ages of 65 and 74 years and almost half of individuals over the age of 85 years have the disease. In rare genetically linked cases associated with mutation of chromosomes 1, 14, and 21, the onset of symptoms could begin as early as the 30s or 40s. In contrast, the ApoE4 allele is a known risk factor for late onset dementia (onset after age 65). A family history of AD increases the risk to 1.5 times if one parent has the disease and to 5 times if both parents are affected. Most patients with Down's syndrome develop AD-like symptoms and pathology at 40 years and beyond. Mothers who give birth to children with Down's syndrome have a higher than average risk of developing the disease.