Alzheimer’s disease (AD) constitutes about two-thirds of all dementia cases. Dementia is defined as cognitive impairment of sufficient severity to interfere with daily functioning. AD currently affects twelve million people worldwide, including over four million in the United States. These numbers could triple by 2050 due to increasing life expectancies. The prevalence of AD is approximately 1 percent among those under 70 years and increases with age to about 40 percent in those 85 years and older. It is the fourth-leading cause of death in the United States among persons older than 65 years. The term senility was used in the past to indicate severe age-related cognitive changes. It is now recognized that subtle cognitive changes do occur with aging, but very marked changes are unexpected unless there is an underlying disease process. The recognition of AD as a disease syndrome has transformed cognitive impairment from an expected stage of life to a medical problem, prompting public concern, new policies, and advocacy.
AD is characterized by a subtle onset and gradual decline. The most prominent early symptom is memory impairment, particularly the ability to remember recent events or names of familiar people or objects. This is accompanied by other, initially subtle, cognitive deficits, such as impaired verbal, spatial, or problem-solving skills. Other symptoms may include disorientation, increased irritability, mood lability, depression, anxiety, and sleep disturbance. Delusions are common, as are behavior problems (e.g., aggression, wandering, disregard for normative social conduct). As the disease progresses, basic activities of daily living, such as eating and dressing, become impaired. Late-stage AD is marked by the loss of recognizable speech and the inability to control bodily functions, leaving patients completely dependent on caregivers. Death occurs approximately eight to ten years after diagnosis (range three to twenty years).
The causes of AD are currently not fully understood. The most evident brain abnormalities are neuritic plaques (clumps of beta amyloid protein) and neurofibrillary tangles (Tau protein strands). Soluble forms of these abnormalities may be toxic to the brain. There is also a deficiency in the neurotransmitter acetylcholine, clogging of the NMDA-glutamate receptor, and considerable brain atrophy (shrinkage).
AD can be familial (inherited) or sporadic. Familial AD is rare and begins earlier in life (age 30 to 60 years). There are at least three genes that can cause familial AD: presenilin 1, presenilin 2, or the amyloid precursor protein gene. Sporadic AD typically occurs after age 65 and accounts for 90 percent of all AD cases. The primary risk factor for sporadic AD is age. Others include a family history of AD, carrying the E4 allele (variant) of the apolipoprotein E (ApoE) gene, being female, Down syndrome, head injury, a prolonged loss of consciousness, diabetes, and cardiovascular disease. Compared to Americans of European descent, African and Hispanic Americans are at greater risk for AD, whereas Asians and Native Americans are at lower risk. It is unclear whether these differences are due to genetic heritage, health, or social or cultural differences between ethnic groups. Protective factors include higher occupational attainment, education, literacy, physical exercise, and engagement in socially and intellectually stimulating leisure activities.
Current drug treatments of AD consist of cholinesterase inhibitors, which increase the neurotrans-mitter acetylcholine, and NMDA receptor antagonists, which block glutamate from activating NMDA receptors. There is some evidence that antioxidants (vitamins E), anti-inflammatory agents (ibuprofen, aspirin), and estrogen may slow the progression of AD. All current treatments are symptomatic and only marginally helpful. There is weak support for the effectiveness of cognitive interventions in improving cognitive and emotional health during early AD.
The burden of AD is enormous, both to society and to individual caregivers, who suffer from financial and emotional distress. Lack of effective treatment, high health care costs, and increasing numbers of patients make AD one of the most challenging medical conditions.
