As an unprecedented number of Americans approach old age, there is
growing public concern about the loss of mental acuity that often is
attributed to aging. Progress in health care has dramatically
increased the likelihood of surviving into the period of life that,
since ancient times, has been associated both with wisdom and mental
decline. It has become relatively common to enter into the eighth and
ninth decades of life in generally good physical health, increasing
the probability that the body will outlive the mind.
More than four million Americans have dementia due to Alzheimer's
disease or related disorders, and this number is projected to grow to
14 million in the next 50 years. Currently, there is no cure for
Alzheimer's disease. All people are at risk for dementia, with the
greatest risk factor being increased age. Even if one is fortunate
enough to escape the ravages of Alzheimer's disease, brain function
in old age can be affected by numerous other factors, from stroke to
Given the major implications of cognitive competency for personal
independence and quality of life, together with growing evidence that
how one lives in earlier stages of life affects cognitive aging,
greater attention to memory and the aging brain is likely to have
significant public health benefits. It is now clear that significant
cognitive decline is not an inevitable consequence of advanced age.
Furthermore, Alzheimer's disease and related disorders, which in the
past have been approached with a sense of therapeutic nihilism, are
increasingly being seen as targets for active intervention.
Memory is a complex function, encompassing the encoding, storage,
and retrieval of diverse types of information. There are multiple
memory systems in the brain. For example, there are dissociable
systems underlying such memory functions as new learning of verbal
information, acquisition of a procedural skill, and retrieval of
semantic knowledge from long-term storage. It has been known since
the 1950s that epileptic patients who underwent bilateral temporal
lobectomies developed severe memory impairments (amnesia).
The mesial temporal lobe memory system, including the hippocampus,
parahippocampal gyrus, entorhinal cortex, and perirhinal cortex
(Fig. 1), is essential for the acquisition of new
information (anterograde memory). When this system is damaged, it
becomes difficult or impossible to remember what happened yesterday
or even a few hours or minutes ago. Remote memory for information
acquired in the distant past remains relatively preserved, as does
procedural memory (e.g., memory for skills, such as golfing or
driving a car). The mesial temporal lobe region is vulnerable to
damage from various age-related causes, including anoxia /hypoxia
that may result from cardiac arrest, and head trauma from falls or
motor vehicle accidents. This region also appears to be selectively
affected in the early stages of Alzheimer's disease.
Gross anatomy of the mesial temporal lobe memory system that
is essential for anterograde memory. Left =in Alzheimer 's
disease; right =in a healthy senior individuals
The relationship between normal aging and cognitive decline
depends on many factors, and there is considerable variability in the
extent of cognitive change experienced by different individuals as
they age. A key factor in understanding the relationship between
brain function and aging is how normal aging is defined.
First, there is a correlation between good physical health in old
age and preservation of cognitive abilities. Studies that look at
only the healthiest elderly tend to find minimal cognitive decline
even into the ninth decade. The greater the extent CME to which
studies include patients with diabetes, hypertension, major
surgeries, depression, and other common disorders of the elderly, the
greater the measured change in cognition with increased age.
Second, age does not affect all domains of cognition equally. For
some functions, such as speed of visual-motor processing, slight
decline often can be detected as people enter their 40s and 50s.
However, for most cognitive abilities, no measurable decline is
evident until age 65 or older. For example, the average expected
number of words recalled from a 15-word list after a 30-minute delay
is approximately 10 for people aged 55-65, nine for those aged 66-
70, and eight for those up to age 85. These changes, while
noticeable, are not disabling. Furthermore, some aspects of
cognition, such as one's general fund of information, can actually
continue to improve throughout one's lifetime.
Finally, in addition to maintaining good physical health, other
factors known to facilitate preservation of cognitive abilities in
aging include maintaining a cognitively challenging lifestyle,
regular physical exercise, and generally positive emotions and
relationships, as well as limiting exposure to chronic stress. As far
as their influence on cognitive abilities in old age is concerned,
these factors appear to be operative throughout the lifespan. Genetic
factors also affect the chances of normal aging, leading to a lower
or higher risk of developing Alzheimer's disease and other less
common demential syndromes.
Cognitive decline (dementia) is defined as an acquired
impairment of memory and other cognitive abilities, which is
sufficient to interfere with normal daily activities. Dementia may be
progressive (e.g., inexorably worsening), such as the dementia caused
by Alzheimer's disease; relatively stable, such as that resulting
from a vascular event or anoxia; or partially or completely
reversible, such as that caused by medication toxicity or depression.
Alzheimer's disease accounts for over 50 percent of dementias.
Cerebrovascular disease and Lewy body disease, either alone or
together with Alzheimer's disease, are other common causes.
Alzheimer's disease is characterized by the accumulation of
amyloid plaques and neurofibrillary tangles in characteristic
patterns, involving primarily the mesial temporal lobe and
higher-order association cortices. This distribution of the pathology
results in a profile of cognitive deficits in the context of
preserved basic neurological function. Alzheimer's disease typically
presents as an insidious impairment of recent memory. Over time,
language, personality, and most other aspects of cognition become
progressively impaired. The course is variable, typically running
over eight to 12 years.
Although memory impairment is most often the first sign of
dementia, memory may be relatively preserved in the early stages of
other demential syndromes, with primary involvement of language,
vision, or personality. These more unusual syndromes typically
involve relatively focal degeneration in frontal, temporal, or
occipitoparietal regions and can be caused by variants of Alzheimer's
disease or other frontotemporal lobar degenerative conditions.
Before Alzheimer's disease causes dementia, it passes through a
pre-symptomatic stage. The next stage is one of mild cognitive
impairment (MCI) in which recent memory is impaired but competence in
daily living is not. Many, but not all, patients with MCI go on to
develop Alzheimer's dementia at a rate of about 15 percent per year.
Detection of disease at the stage of MCI is becoming a high priority,
because at this early stage, interventions that slow or reverse
Alzheimer's disease are most likely to be effective and preserve the
most function. At the current time, expert neurologic and
neuropsychologic assessment is the most appropriate way to identify
When impairment of memory is suspected, it is important to pursue
a careful evaluation to determine if dementia or MCI is present and
if any potentially treatable factors are contributing. A
comprehensive dementia evaluation includes a neurological evaluation,
neuropsychological assessment, and neuroimaging, leading to
individually tailored interventions designed to optimize cognitive
and functional abilities.
The current standard of treatment for mild to moderate Alzheimer's
disease is cholinergic augmentation with a centrally acting
cholinesterase inhibitor, but a number of new therapeutic options are
under investigation. In addition, behavioral interventions can be
effective at all stages of the disease to help maintain independence
and minimize caregiver burden.