The clinical manifestation of Alzheimer disease (AD) is dementia that
typically begins with subtle and poorly recognized
failure of memory
and slowly becomes more severe and, eventually, incapacitating.AD is
the most common cause of dementia in North America and Europe with an
estimate of four million affected
individuals in the US. The prevalence
of the disease increases with age. Approximately 10% of all persons
over the age of 70 years have significant memory loss and more than
half of these individuals have AD No environmental agents (e.g., head
trauma, viruses, toxins) have been proven to be directly involved in
the pathogenesis of AD. About 25% of AD is familial, that is, two or
more persons in a family have AD. Familial cases appear to have the
same clinical and pathologic phenotypes as nonfamilial cases. Genetic
counseling is the process of providing individuals and families with
information on the nature, inheritance, and implications of Genetic
disorders to help them make informed medical and personal decisions.
Genetic counseling for people with nonfamilial AD and their family
members must be empiric and relatively nonspecific.First-degree
relatives of a person with AD have a cumulative lifetime risk of
developing AD of about 15-30%, which is typically reported as a 20-25%
risk.Many individuals diagnosed as having early-onset Alzheimer disease
have another affected family member, although family history is
negative 40% of the time. Individuals with early-onset familial
Alzheimer disease have a 50% chance of transmitting the mutant allele
to each child.The mainstay of treatment for AD is necessarily
supportive and each symptom is managed on an individual basis. In
general, affected individuals eventually require assisted living
arrangements or care in a nursing home.Although the exact biochemical
basis of AD is not well understood, it is known that deficiencies of
the brain cholinergic system and of other neurotransmitters are
present. Drugs that increase cholinergic activity by inhibiting
acetylcholinesterase produce a modest but useful behavioral or
cognitive benefit in a minority of affected individuals. The first such
drug was tacrine; however, this agent is also
hepatotoxic. Newer such
drugs with similar pharmacologic action, such as Aricept (donepezil),
Exelon (rivastigmime), and Galantamine , are not hepatotoxic.Treatment
trials evaluating use of anti-inflammatory agents (NSAIDs), estrogens,
nerve growth factors, and antioxidants are underway.