Download JessieMalcolm - University of Colorado Boulder

Despite the mystery of dementia, studies suggest that exercise can prevent the late
onset of Alzheimer’s disease.
Jessie Malcolm
4/29/05
An informative article to be published in US Newsweek
Imagine looking back at a photo album of your life, each picture represents your
past- what you have done, who you have met, and who you are. One day water soaks
your album and you can no longer make out the pictures, you can not recognize the
places or people in the photos. You desperately try to dry off your photos, but it does no
good, only some can vaguely be retrieved, but most are gone. Like water on the photo
album, Alzheimer’s destroys a person’s existence. All of one’s memories are just stories
that his family tells in a hopeless attempt to spark some sort of remembrance. As the
disease begins to deteriorate a person’s brain, his memories slowly dwindle away until
even family is unrecognizable.
The idea of losing one’s memory is terrifying and one that no one wants to
experience, but can anything be done to prevent the late onset of Alzheimer’s disease?
The most frightening part of Alzheimer’s disease, also known as AD is that a
preventative measure is unknown. In the past, scientists believed that old age and
genetics were the main factors that lead to Alzheimer’s, in which case, nothing could be
done to prevent the development of the disease. However recent studies suggest that
stimulation can alter brain function and the development of Alzheimer’s disease. In
addition to the question of whether or not the disease can be prevented, some researchers
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believe that cognitive activity reduces the chance of developing AD while others believe
physical activity is the best preventative mechanism.
Memory loss is the most common and earliest sign of dementia. It is inevitable
that with old age, a person is going to become more forgetful however dementia consists
of a collection of symptoms indicating that thinking processes are deteriorating.
Deterioration in the brain is why someone suffers from memory loss, orientation
problems and changes in behavior. Dementia is the word that is coined for memory loss,
because a patient can not be diagnosed with Alzheimer’s disease until death when an
autopsy is performed. Still, Alzheimer’s disease is the most common form of dementia
and for 60-70% of people that suffer from dementia, Alzheimer’s is the cause.
A healthy brain has about 100 billion nerve cells called neurons (Sherwood,2004).
Neurons generate signals which help people think. For people with Alzheimer’s, neurons
in certain parts of the brain die. At first AD destroys neurons in the hippocampus, the
part of the brain that controls short term memory. Later Alzheimer’s affects the cerebral
cortex specifically areas responsible for reasoning and language. The sequence of brain
death correlates with the development of dementia. At first a person gradually loses short
term memory and mental functions, followed by the inability to plan, execute tasks,
reason, exercise judgment and communicate (Healthy AtoZ, 2005). Eventually many
areas of the brain are affected by the death of neurons and regions in the brain begin to
atrophy, and ultimately the essential qualities that define human existence are lost.
An autopsy of a person with Alzheimer’s disease shows that regions of the brain
affected by the disease are clogged with two abnormal structures, neurofibrillary tangles
and amyloid plaques. It is not clear how these abnormal structures cause problems, but
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researchers believe that their formation is responsible for mental changes and as a result
AD.
Neurofibrillary tangles are made of tau proteins that have become “twisted and
tangled” and can no longer stabilize neurons. It is believed that the amyloid plaques,
which are made up of amyloid precursor protein, are found in the spaces between the
nerve cells of the brain. If plaques interfere with the release of neurotransmitters from
the neurons then signaling communication does not occur and atrophy will result.
Further statistics show that Alzheimer’s disease, also known as AD, affects four million
Americans every year and is the fourth leading cause of death in the United States.
Unlike familial AD which develops between ages thirty to sixty years and is genetic, the
late onset of Alzheimer’s which develops after age sixty-five years is poorly understood.
The most difficult consideration about the prevention of Alzheimer’s disease is
the cause is still under investigation and since many studies have not been done regarding
treatment and prevention methods, most researcher’s still accuse genotyping for the
development of the disease. If genes are the root of the disease, then Alzheimer’s is
inevitable and nothing can be done to prevent the onset. In the 1990’s, researcher’s at
Duke University made an important connection between Alzheimer’s disease and a gene
on chromosome 19, called APOE4. The apoE4 genotype which is found in about 40% of
people with AD has been found to increase an individual’s chance of developing the late
onset of the disease, presence of the apoE4 allele can lower the age of onset by seventeen
years (Health AtoZ). Neuropathological data indicates that APOE4 carriers with or
without dementia have increased cerebral amyloid burden. A single copy of the e4 allele
is more adept at binding to amyloid plaques and having two copies of the allele leads to
an even more potent affect (Taddei et al., 1997). Amyloid plaques have been shown to
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induce neuronal degeneration leading to brain atrophy and Alzheimer’s disease. If a
person has the apoE4 allele, he is predisposed to developing AD and nothing can be done
to alter his destiny.
The presence of the allele can not take full responsibility for causing Alzheimer’s,
because only about 15% of the United States population has one apoE4 allele, only 1%
has two alleles present, and 50% of people that develop the disease lack any apoE4
alleles. Since there is a large number of individuals who lack the apoE4 allele but still
develop AD, another factor must be involved in the development of the disease.
Lifestyle factors may have a significant effect on the prevention and reversal of
memory loss. Even though AD has no known cure, findings from research supported by
the National Institute on Aging suggest that there may be a way to delay or even prevent
the late onset of the disease (ADEAR). Dementia is first evaluated by a doctor who
reviews the patient's history and performs a physical examination. Further testing is
chosen according to clues from the history and physical. This testing might include blood
and urine tests, chest x-ray, brain scanning (MRI or CAT scanning),
electroencephalogram (EEG), and spinal fluid analysis by lumbar puncture procedure.
Although it is clear that physical exercise offers health benefits for older people, evidence
supporting a specific effect of exercise for prevention of dementia is still being
investigated. Some researchers believe that physical activity does not have an affect on
the development of plaques and tangles, but cognitive activity can play an influential role
in delaying and even preventing the onset of AD.
Research suggests that higher education levels and leisure activities are more
resistant to the effects of dementia and have increased complexity of neuronal synapses
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and improve cognition (Verghese et. al, 2003). The Bronx Aging Study provided
information about the correlation between leisure activities and the risk of dementia over
a long period of time. The study evaluated 488 non demented subjects every 12 to 18
months for twenty one years examining Blessed Information-Memory-Concentration
tests, verbal IQ, the Fuld Object-Memory Evaluation, and the Zung depression scale.
The study focused on six cognitive activities (reading, writing, crossword puzzles,
playing board games, group discussions, and playing musical instruments) and eleven
physical activities (tennis, golf, swimming, bicycling, dancing, exercising, bowling,
walking for exercise, climbing more than two flights of stairs, doing housework, and
babysitting). Results suggest that subjects whom dementia developed were older, had
lower levels of education, and had significantly lower scores on the cognitively active
scale. Interestingly, scores on the physical activity scale did not differentiate between
subjects whom developed dementia and those whom did not. Physical activity scores
were not significantly associated with dementia. However, the only physical activity that
was at a lower risk for developing dementia was dancing. A limitation to this study is
that the presence of the apoE4 allele was not noted. Also, the time spent in each activity
was not directly measured. The Centers for Disease Control and the American College of
Sports Medicine suggest that the health benefits of physical activity are linked to the
amount of physical activity rather than intensity (Lytle et al, 2004). Duration is
important when assessing the affects of cognitive or physical activity and chance of
developing dementia. The twenty one year study supports that there is a significant
association between leisure activities and decreased risk for dementia, because cognitive
activities slow rate of cognitive decline.
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The value of lifelong learning and mentally stimulating activity is priceless.
Scientists have found that healthy adults have spent more hours engaged in cognitive
activity during early life or middle adulthood than those who ultimately developed AD
(ADEAR). Activities such as going to the museum, reading the newspaper, and listening
to the radio have been found to decrease the risk for developing Alzheimer’s disease.
More specifically, even in the presence of amyloid plaques, a person with a more formal
education has greater memory and learning skills. However, the problem with the
findings that cognitive activity is enough to prevent Alzheimer’s disease is that the
evidence is not entirely clear. Some researchers believe that mentally stimulating
activities protect the brain by establishing a “cognitive reserve.” While others
hypothesize that these types of activities help the brain become more adaptable and
flexible in some areas of mental function so that it can compensate for declines in other
areas (Scarmeas et al., 2001). Research suggests that engagement in leisure activities
may reduce the risk of incident dementia by creating a reserve that delays the
manifestation of amyloid plaques and tangles that later lead to Alzheimer’s disease.
Since researchers hypothesized cognitive reserve as a result of leisure activities, it
is important to consider if physical activities illustrated the same advantages for reducing
the development of Alzheimer’s disease. Physical activity early in life has been
associated with a higher brain reserve capacity and increasing neuron efficiency. La Rue
and Jarvik found that passive activities were a predictor of later dementia, including
watching movies, television, sports, reading, and listening to the radio (Crawford, 1996).
Exercises can upregulate brain-derived neurotrophic factor gene expression in the
hippocampus. It is important to study characteristics of brain-derived neurotrophic
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factor, because it is a natural aspirant to mediate the benefits of exercise on brain health.
Brain-derived neurotrophic factor, also known as BDNF, enhances neuronal resilience.
Release of BDNF during exercise could be beneficial since most researchers blame
abnormal plaque deposition for neuronal death. Studies have shown that exercise
increases levels of BDNF in the hippocampus, a highly plastic structure. BDNF
promotes neuronal survival and protects the hippocampus and cortex. Mice deficient in
BDNF show decrease synaptic innervations.
Dik et. al examined 1,241 subjects between the ages of 62-85 years to determine
if there was an association between early life physical activity and cognition. The
limitation to a study like this is that the physical activity recall was 40-60 years later and
over a 10 year time span. It is probable that the subjects could have misclassified their
physical activity in their early years. However, the study suggested that there was a
positive correlation for men that were physically active between the ages of 15 and 25
years and the level of information and processing speeds at an older age. Healthy, active
neurons are able to release neurotransmitters for efficient synaptic communication which
could be the reason why physically active men scored 1.24 points higher and moderately
active men scored 1.07 points higher on information processing than inactive men (Dik,
2003). Besides an increase in brain-derived neurotrophic factor, development of new
neurons and increase in neuron survival, animal models suggest that exercise can increase
synaptic development and brain plasticity.
Using animal models, researchers have found that aerobic training increases
cortical capillary supplies, the number of synaptic connections, and the development of
new neurons which results in a brain that is more plastic and adaptive leading to better
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performance. It is important to study animals because recent neuroanatomical evidence
from human populations shows that the same benefits in brain health seen in aging
animals may extend to aging humans (Colcombe et. Al, 2004). A study involving
voluntary wheel running for rats and mice showed that the increase in brain-derived
neurotrophic factor also helped to support and maintain brain plasticity and promote
vascularization, neurogenisis, functional changes in neural structure and neural resistance
to injury. Mice provided with a running wheel were found to have more than twice the
number of cells within the hippocampus undergoing cell division than did the mice
without the running wheel (Ball and Birge, 2002). In a study involving cardiovascular
fitness training, participants that were tested showed significantly greater improvements
over control subjects regardless of cognitive task. Physical activity increases cerebral
circulation by increasing the vascularization of the brain, resulting in enhanced oxygen
transportation. Dr. Kramer, of the Beekman Institute at the University of Illinois says, “it
is fitness as it interacts with age that has a positive effect. Older adults show a real
decline in brain density in white and gray areas; fitness actually slows that decline”
(Warner, 2003). Age-related declines in cortical tissue density (atrophy) are significantly
reduced as a function of cardiovascular fitness (Colcombe et al., 2004).
Although neuronal plasticity declines with age, it is preserved to some extent
throughout life. Middle aged rats exposed to an enriched environment develop greater
brain volumes than animals deprived of stimulation (Ball, 2002). Researcher Sangram
Sisodia from the University of Chicago focused on genetically engineered mice to mimic
Alzheimer’s disease in humans by clumping amyloid proteins around brain cells. Two
different environments were established for the mice. Some of the mice were placed in
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an “enriched environment” while others lived in a less engaging, less active surrounding.
Compared to the less active mice, amyloid tangles and plaques, associated with AD, were
lower in mice within the challenging environment. Animals with higher levels of
physical activity show the most significant reduction in amyloid burden (Karsten and
Geschwind). Sisodia suggests that the enriched, active environment acts like a
“protective factor” for the mice by keeping amyloid levels low enough to prevent
clumping.
Beyond physiological functioning improvements in the brain, studies show that
exercise benefits can be observed through written examinations. The Mini Mental State
Examination, MMSE is a well known general mental status test that briefly and broadly
screens global functioning. The scores range between 0-30 and 30 is considered a perfect
score. The MoVIES was a study that examined the outcome of dementia and cognitive
impairment in a community of elders. The sample consisted of 1,422 subjects aged 65
years and older who were recruited in 1987 to 1989 and reassessed every two years. The
exercise assessment was self-reported and evaluated frequency and duration, because
intensity could not be measured. “High,” “low,” and “no” levels of exercise were the
groups for this study. High exercise was considered 30 minutes or more of aerobic
exercise, 3 days a week, and low exercise involved all other exercise groups. This study
found that higher levels of exercise were associated with the absence of cognitive decline
approximately two years after the first MMSE. Figure. Several studies support this
finding, DiPietro et al. found that adults who regularly engaged in physical activities light
to strenuous intensity performed better on cognitive tasks including abstraction, naming,
and copying (Ball and Birge, 2002).
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In regards to the 50% of people who posses the apoE4 allele and develop
Alzheimer’s disease, exercise may still play a preventative role. Jarvik et al. reported a
relationship between the APOE genotype and blood cholesterol in Alzheimer’s subjects
indicating a correlation between high cholesterol and AD. Scientists have found that high
blood cholesterol levels in special breeds of genetically engineered mice may increased
the rate of plaque deposition. Exercise can reduce a person’s cholesterol levels, and
evidence obtained from a hampster study shows that stabilizing cholesterol levels in the
blood shows some protection against sporadic AD.
There is no magic bullet that can absolutely prevent the disease from happening.
The brain is subject to many factors that could result in damage to the cellular make up of
neurons and supporting cells. Alzheimer’s disease develops over many years and appears
to be influenced by a number of risk factors.
However recent studies suggest that
stimulation can be a preventative mechanism for the development of AD.
If Alzheimer’s disease is the result of aging or genetic predisposition then there is no
preventative measure. Until the cause of neurofibrillary tangles and amyloid plaques is
known, the prevention mechanisms of Alzheimer’s disease will remain a mystery.
However, studies show that lifestyle choices, especially physical activity throughout life
could modify the factors that lead to neuronal damage and brain atrophy. Similar to other
chronic disease, some of the risks for Alzheimer’s disease may be due to our own actions.
Even though the benefits of exercise for reducing the chance of developing amyloid
plaques and neurofibrillary tangles have not been proven, studies involving brain scans
and written examinations support a higher level of brain functioning throughout life with
physical activity. Mens sana in corpore sano in Latin means “a sound mind in a sound
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body” and exercise seems to be the best mechanism for achieving this state. Because
prevention of AD appears to be a life long process, exercise needs to be adapted early and
maintained throughout life (Pope, 2003). Memory is a complicated phenomenon; it is
essential to incorporate exercise into our life so we can enjoy this precious treasure.
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