Rare before age 60 but increasingly prevalent in each decade thereafter, Alzheimer’s affects 5 percent of Americans age 65 to 74 and nearly half of those age 85 and older. As many as 5.3 million Americans have Alzheimer’s. The disease is predicted to affect approximately 14 million individuals in the United States by the year 2050.
The earliest symptoms of Alzheimer’s include forgetfulness; disorientation as to time or place; and difficulty with concentration, calculation, language, and judgment. As the disease progresses, some patients have severe behavioral disturbances and may even become psychotic. In the final stages, the affected individual is incapable of self-care and becomes bedridden. Patients usually die from pneumonia or some other complication of immobility. Alzheimer’s disease is the seventh leading cause of death in the United States and the fifth leading cause of death for Americans aged 65 and older.
In the earliest stages, the clinical diagnosis of possible or probable Alzheimer’s can be made with greater than 80 percent accuracy. As the course of the disease progresses, the accuracy of diagnosis at Alzheimer’s research centers exceeds 90 percent. The diagnosis depends on medical history, physical and neurological examinations, psychological testing, laboratory tests, and brain imaging studies. New brain imaging strategies promise to enable doctors to visualize Alzheimer’s neuropathology during life. At present, however, final confirmation of the diagnosis requires examination of brain tissue, usually obtained at autopsy.
The causes and mechanisms of the brain abnormalities underlying Alzheimer’s are not yet fully understood, but great progress has been made through the study of genetics, biochemistry, and cell biology, as well as the use of experimental treatments. Neuroscientists do know that reductions occur in markers for many neurotransmitters that allow cells to communicate with one another. These include acetylcholine, somatostatin, monoamines, and glutamate. Damage to these neural systems, which are critical for attention, memory, learning, and higher cognitive abilities, is believed to cause the clinical symptoms.
Microscopic examination of brain tissue from people who died from Alzheimer’s shows abnormal accumulations of a small fibrillar peptide, termed beta amyloid, in the spaces around synapses. These accumulations of tissue are referred to as neuritic plaques. Another abnormal clump of proteins, called neurofibrillary tangles, have been identified as a modified form of the protein tau, which is found in the cell bodies of neurons. In all forms of Alzheimer’s, plaques and tangles mostly develop in brain regions important for memory and intellectual functions. New brain imaging strategies that may one day be used for diagnosis use a mildly radioactive chemical marker that shows amyloid plaques and tau tangles in living people.
Early-onset Alzheimer’s disease is a rare, dominantly inherited form of the disease. Recently, scientists have identified Alzheimer’s disease-associated mutations. The gene encoding the amyloid precursor protein (APP) is on chromosome 21. In some families with early-onset Alzheimer’s, mutations have been identified in the presenilin 1 and 2 genes. Genes that cause dominant Alzheimer’s appear to do so by causing beta amyloid plaques to accumulate. Apolipoprotein E (apoE), which influences susceptibility for Alzheimer’s later in life, exists in three forms. The variant known as APOE epsilon 4 is clearly associated with enhanced risk.