Alzheimer's Disease

80 Pages·2014·0.72 MB·English

____________________________________________________________________ #9615 Alzheimer’s Disease
COURSE #9615 — 15 CONTACT HOURS/CREDITS Release Date: 09/01/11 expiRation Date: 08/31/14
Alzheimer’s Disease
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• Receive your Certificate(s) of Completion by mail, Period: 3/13/2013 to 3/13/2016. Social workers should con-
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continuing education credits.
This program is approved by the National Association of
Social Workers (Approval #886531582-8272) for Social
Faculty
Work continuing education contact hours.
Joan Needham, MSEd, RNC, was a graduate of Copley
Memorial Hospital School of Nursing. She earned a bacca- CME Resource is an NBCC-Approved Continuing Educa-
laureate degree in nursing from the College of Saint Francis in tion Provider (ACEP™) and may offer NBCC-approved
1977 and a Master’s degree in adult education from Northern clock hours for programs that meet NBCC requirements.
Illinois University in 1981. She was certified in gerontologi- Programs for which NBCC-approved clock hours will be
cal nursing by the American Nurses Association and worked awarded are identified on the course material and website.
in nursing education at various colleges in Illinois for many CME Resource is solely responsible for all aspects of the
years. Regrettably, Ms. Needham passed away in 2010. program. Provider number 6361.
Faculty Disclosure Designation of Credit
Contributing faculty, Joan Needham, MSEd, RNC, has dis- CME Resource designates this enduring material for a maxi-
closed no relevant financial relationship with any product mum of 15 AMA PRA Category 1 Credit(s)™. Physicians
manufacturer or service provider mentioned. should claim only the credit commensurate with the extent
of their participation in the activity.
Division Planners
CME Resource designates this continuing education activity
Ronald Runciman, MD
for 15 ANCC contact hours.
Jane Norman, RN, MSN, CNE, PhD
Alice Yick Flanagan, PhD, MSW CME Resource designates this continuing education activity
for 18 hours for Alabama nurses.
Division Planners Disclosure
AACN Synergy CERP Category A.
The division planners have disclosed no relevant financial
relationship with any product manufacturer or service pro- Social Workers participating in this intermediate to advanced
vider mentioned. course will receive 15 Clinical continuing education clock
hours, in accordance with the Association of Social Work
Audience
Boards.
This course is designed for clinicians who come in contact
This program is approved by the National Association of
with Alzheimer’s patients in hospitals, long-term care facili-
Social Workers for 15 Social Work continuing education
ties, home health care, and the office.
contact hours.
CME Resource designates this continuing education activity
for 10 NBCC clock hours.
This course meets the requirements for 15 Clinical hours as
required by the New Jersey Board of Social Work Examiners.
Copyright © 2011 CME Resource
A complete Works Cited list begins on page 74. Mention of commercial products does not indicate endorsement.
CME Resource • Sacramento, California Phone: 800 / 232-4238 • FAX: 916 / 783-6067 1
#9615 Alzheimer’s Disease ____________________________________________________________________
Individual State Nursing Approvals is to provide clinicians with the skills to care for patients
In addition to states that accept ANCC, CME Resource is with Alzheimer’s disease in any setting as part of the inter-
approved as a provider of continuing education in nursing by: disciplinary team.
Alabama, Provider #ABNP0353 (valid through December
Learning Objectives
12, 2017); California, BRN Provider #CEP9784; California,
Upon completion of this course, you should be able to:
LVN Provider #V10662; California, PT Provider #V10671;
1. Outline the characteristics and impact of Alzheimer’s
Florida, Provider #50-2405; Iowa, Provider #295; Kentucky,
disease.
Provider #7-0054 through 12/31/2017.
2. Summarize the pathophysiological changes in the
Individual State Behavioral Health Approvals
brain related to dementia and Alzheimer’s disease.
In addition to states that accept ASWB, CME Resource is
3. Describe the different types of memory.
approved as a provider of continuing education by the fol-
lowing state boards: Alabama State Board of Social Work 4. List the clinical manifestations of Alzheimer’s
Examiners, Provider #0515; California Board of Behavioral disease in various stages.
Sciences, Provider #PCE 1632; Florida Board of Clinical 5. Identify the goals and components of the diagnostic
Social Work, Marriage and Family Therapy and Mental workup, including assistance in diagnosing non-
Health, Provider #50-2405; Illinois Division of Professional English proficient patients.
Regulation for Social Workers, License #159.001094; Illinois
6. Discuss the planning issues facing the family
Division of Professional Regulation for Licensed Professional
after the diagnosis is made.
and Clinical Counselors, License #197.000185; Illinois
7. Identify components of a therapeutic
Division of Professional Regulation for Marriage and Fam-
environment for Alzheimer’s disease patients.
ily Therapists, License #168.000190; Texas State Board of
Social Work Examiners, Approval #3011; Texas State Board 8. Describe the appropriate pharmacological and
of Examiners of Professional Counselors, Approval #1121; nonpharmacological management of Alzheimer’s
Texas State Board of Examiners of Marriage and Family disease.
Therapists, Approval #425. 9. Discuss components of care in working with patients
Special Approval with Alzheimer’s disease, including rehabilitation
and management of coexisting illnesses.
This activity is designed to comply with the requirements
of California Assembly Bill 1195, Cultural and Linguistic 10. Describe interventions for impaired communication.
Competency. 11. Describe concerns related to sexuality and intimacy
About the Sponsor that may occur in patients with Alzheimer’s disease.
The purpose of CME Resource is to provide challenging 12. Apply interventions for maintaining and enhancing
curricula to assist healthcare professionals to raise their lev- nutrition.
els of expertise while fulfilling their continuing education
13. Describe several behavioral management skills and
requirements, thereby improving the quality of healthcare.
examples of successful interventions for specific
Our contributing faculty members have taken care to ensure behaviors common to Alzheimer’s disease patients.
that the information and recommendations are accurate and 14. Compare the techniques used for reminiscing,
compatible with the standards generally accepted at the time reality orientation, and validation therapy.
of publication. The publisher disclaims any liability, loss or
15. Describe the care required by those with end-stage
damage incurred as a consequence, directly or indirectly, of
Alzheimer’s disease.
the use and application of any of the contents. Participants
16. Describe interventions for providing support
are cautioned about the potential risk of using limited
to the family.
knowledge when integrating new techniques into practice.
Disclosure Statement
It is the policy of CME Resource not to accept commercial
Sections marked with this symbol include
support. Furthermore, commercial interests are prohibited
evidence-based practice recommend ations.
from distributing or providing access to this activity to
The level of evidence and/or strength
learners.
of recommendation, as provided by the
Course Objective evidence-based source, are also included
In order to increase and maintain a reasonable quality of so you may determine the validity or relevance of the
life for Alzheimer’s disease patients throughout the course information. These sections may be used in conjunc-
of the disease, caregivers must have a thorough knowledge tion with the course material for better application to
and understanding of the disease. The purpose of this course your daily practice.
2 CME Resource • July 21, 2014 www.NetCE.com
____________________________________________________________________ #9615 Alzheimer’s Disease
INTRODUCTION OVERVIEW
The number of adults 65 years of age and older Alzheimer’s disease was first identified and named
in the United States has increased by 26% in the in 1906 by Dr. Alois Alzheimer, a German neuro-
last decade and is anticipated to increase 80% by pathologist [1]. He had been treating a middle-aged
2030 [9]. According to the U.S. Census Bureau, woman who exhibited symptoms of memory loss
of the 40 million adults older than 65 years of age and disorientation. Five years later, the patient
in the United States, almost 40% report at least died after suffering hallucinations and symptoms
one disability [10]. of dementia. The manifestations and course of
the disease were so unusual that Dr. Alzheimer
It is estimated that more than 5.4 million people
was unable to classify the disease into any existing
in the United States have Alzheimer’s disease
category. Postmortem examination of the brain
(AD), the most common form of dementia [4].
revealed microscopic and macroscopic lesions and
Approximately 1 in 8 people 65 years of age or older
distortions, including neuritic plaques and neuro-
age have AD, and the risk increases with age. AD
fibrillary tangles.
is diagnosed in 43% of those 85 years of age and
older. The annual cost of caring for and treating Although it has been more than a century since the
patients with AD and other forms of dementia is disease was identified, it has been only within the
approximately $183 billion [4]. last four decades that it has received recognition. In
the past, symptoms were attributed to the “senility”
Although the disease was identified and named in
of old age and victims were cared for at home. The
the early part of the 20th century, little was known
problems of dementia were gradually recognized as
about AD until more recently. Now, there is much
an issue associated with the older population, but
that can be done to increase and maintain a rea-
the nature of the disease and how to treat it were
sonable quality of life throughout the course of the
still a mystery. In the 1970s, researchers deter-
disease. To accomplish this, caregivers must have
mined that people with AD had a neurochemical
a thorough knowledge and understanding of the
deficiency. This enabled them to study the disease
disease. Successful management involves the “use
in more detail and separate patients with AD from
of self” and application of behavioral interventions.
those with dementia of normal aging.
This course contains a significant amount of
Clinicians and researchers began meeting with
information that pertains to necessary care by the
family members of AD patients, leading to the
entire healthcare team. In order to support the
founding of the Alzheimer’s Disease and Related
purpose and unity of the interdisciplinary team,
Disorders Association, now the Alzheimer’s Asso-
the course includes an appendix with specific
ciation [15]. This group has been responsible for
nursing and caregiver interventions (Appendix 1)
advancing research, public awareness, education,
as well as information about special care facilities
family support, and public policy changes [15].
(Appendix 2).
Healthcare professionals now know that while
The term “caregiver” is used throughout the text there is a strong and as yet incompletely understood
and refers to any person interacting with the relationship between aging and AD, they are not
patient with AD, including professional health- the same condition [5]. The disease is recognized
care providers, nursing assistants, other members as a family, social, and economic problem.
of the interdisciplinary team, or family members.
Professional caregivers should accept the family as
contributing members of the healthcare team.
CME Resource • Sacramento, California Phone: 800 / 232-4238 • FAX: 916 / 783-6067 3
#9615 Alzheimer’s Disease ____________________________________________________________________
AD is characterized by insidious, severe, and pro- Economic Impact
gressive cognitive impairment that is irreversible As noted, the economic impact of AD is stagger-
and eventually fatal. AD accounts for roughly 60% ing. As of 2011, it is estimated to cost $183 bil-
to 80% of all dementias in the United States [4]. lion nationwide annually to care for AD patients;
It proceeds relentlessly, gradually destroying all projected costs for 2050 are $1.1 trillion annually
cognitive functions. While the number of adults (in 2010 dollars) [4]. Of the $183 billion annual
with AD doubles for every 5 years of age after 65 direct and indirect costs of AD care, [4]:
years, the disease is also seen less frequently in
• Medicare coverage for hospital and
younger people [18].
physicians’ services accounts for $93 billion.
There are two types of AD: familial and sporadic.
• Medicaid costs associated with long-term
Familial AD follows an autosomal dominant
nursing home care accounts for $37 billion.
inheritance pattern, while sporadic AD has no
• Out-of-pocket costs account for $31 billion.
known inheritance factor. Familial AD can be
further classified as early-onset, when it occurs in • Other related costs account for $36.5 billion.
individuals younger than 60 years of age, or late-
These estimates do not include the costs of care
onset, when it affects individuals older than 60
paid by long-term care or private insurance com-
years of age [18]. Early-onset type occurs in only
panies.
4% to 5% of cases, generally affects people 30 to
With the help of family and friends, individuals
60 years of age, and is considered hereditary [4;
with dementia often live at home. However, as the
18; 65]. There are roughly 200,000 people in the
disease progresses, more care is needed. Depending
United States with early-onset AD [4; 65].
on the severity of the disease progression, home
IMPACT OF ALZHEIMER’S DISEASE care workers may be hired or the individual may
The impact of Alzheimer’s disease has been com- be placed in a nursing home or assisted living
pared to tossing a pebble into a quiet pool—the residence. The only federal program that covers
ripple of the initial toss is just the beginning of the long-term nursing home care is Medicaid; however,
process. In that manner, a diagnosis of AD affects in order to receive these benefits, the individual
the patient first, moving on to touch family mem- must be considered low income [4]. Long-term care
bers and other caregivers. The disease has wide or private insurance may cover long-term nursing
reaching consequences personally, sociologically, home care, but only if the policies are purchased
and economically. before the onset of disease. (Private insurance
funding accounts for only 9% of total care costs.)
Demographic Impact More than 50% of nursing home residents with
Approximately 82,476 AD patients died in 2008, AD and other dementias depend on Medicaid to
making it the fifth leading cause of death in adults pay for their care [4]. Even with Medicare cover-
65 years of age or older. Furthermore, there are age, families incur high out-of-pocket expenses as
about 454,000 new cases of AD diagnosed each a result of premiums, deductibles, co-payments, and
year [4]. As the aging population increases, so will other healthcare costs not covered by Medicare [4].
these numbers. By 2030, it is estimated that about In 2004, annual family expenses were $3,141 per
615,000 new cases will be diagnosed each year, and at-home patient and $21,272 per nursing-home
by 2050, the number will increase to 959,000 [4]. patient.
Barring the development of effective new treat-
ments, there will be an estimated 13.2 million AD
patients in 2050 [4].
4 CME Resource • July 21, 2014 www.NetCE.com
____________________________________________________________________ #9615 Alzheimer’s Disease
AD sufferers often have comorbidities, including
hypertension, congestive heart disease or failure, THE PHYSIOLOGY OF
osteoarthritis, diabetes, peripheral vascular disease, ALZHEIMER’S DISEASE
chronic obstructive pulmonary disease, thyroid
disease, and stroke. The cost of care for Medicare ANATOMY AND PHYSIOLOGY
beneficiaries who suffer from AD and a comorbid ASSOCIATED WITH DEMENTIA
condition is approximately three times higher than With the help of motor and sensory nerves, the
the cost of care for Medicare beneficiaries without brain integrates, regulates, initiates, and controls
AD [4]. the functions of the whole body. These processes
rely on successful chemical and electrical interac-
Impact on Family and Significant Others
tions. Thinking, remembering, and learning do not
The affected individual is not the only victim of
occur in one single place within the brain. These
AD. Nearly 15 million family members, friends,
processes are shared by many structures, especially
and neighbors provide unpaid care for AD patients
the cerebral cortex, which directs the most intri-
[4]. Interventions that assist caregivers to cope
cate and complicated functions of the brain.
and prevent caregiver burnout are as essential as
To review, the longitudinal fissure divides the
interventions for the patient.
cerebrum into two hemispheres. The central and
The AD patient endures a continuing loss of
lateral fissures divide each hemisphere into four
mental acuity while the family witnesses the slow
lobes: the frontal lobe, parietal lobe, temporal lobe,
deterioration of their loved one. There are devas-
and occipital lobe. The frontal lobe is responsible
tating mental, emotional, and physical changes
for voluntary motor activity and higher intellectual
that result in total dependence, and the need for
functions involving conscious thought, such as
care never stops. In the earlier stages, the patient
planning, judgment, decision making, and problem
may wander and get lost or get up frequently during
solving. This lobe is the organizer and classifier of
the night. The sense of self is slipping away, but the
information. Damage to the frontal lobe results
patient is helpless to do anything about it. Familiar
in inhibition of information processing. One sec-
routine tasks become monumental chores, causing
tion controls discrete body movements, while the
frustration and humiliation when they cannot be
centers for speech and smell are found in others.
completed. In the later stages, maximum assistance
Lesions in the frontal region are linked to impul-
with all activities of daily living is required.
siveness and hyperactivity. Broca’s area governs
Family members experience the same roller coaster verbal language skills and is located in the left
ride of emotions as they too become frustrated, frontal lobe.
resentful, and often fatigued as they try to provide
The parietal lobe processes sensory input related
for the needs of their loved one. Marriages suffer
to taste, position sense, touch, shape, and consis-
as adult children with children of their own try
tency of objects. The synthesis of auditory, visual,
to care for aging parents, or as one aging spouse
and somatic input into thought and memory is
feels responsible to meet every need of his or her
accomplished by the temporal lobe. Wernicke’s
increasingly dependent partner. Role reversals are
area, which is responsible for the comprehension
common within a marriage or between parent and
of written and verbal language, is located in the
child. Caregivers have to take on the responsibili-
left temporal lobe.
ties previously assumed by the patients in addition
to providing routine care. Caregivers must be
strong, considerate, and able to anticipate prob-
lems. The support and care of friends may gradually
subside as the situation continues for years.
CME Resource • Sacramento, California Phone: 800 / 232-4238 • FAX: 916 / 783-6067 5
#9615 Alzheimer’s Disease ____________________________________________________________________
The temporal lobe contains auditory receptive The amygdala receives input directly and indirectly
areas. Impaired memory for verbal material is from the sensory system. All endocrine, visceral
linked to damage of the left temporal lobe and the motor, and somatic motor effectors are influenced
inability to remember nonverbal material (e.g., by the output of the amygdala. The sexual and
faces) is associated with damage to the right tem- emotional aspects of human behavior are also
poral lobe. The reception and processing of visual controlled by the limbic system.
information passing through the optic nerves is
Parkinson’s disease and Huntington’s disease
controlled by the occipital lobe.
are examples of dementias related to subcortical
All dementias can be categorized as one of two dysfunction. Subcortical structures include the
patterns of brain deterioration: cortical or subcor- basal ganglia, thalamus, and brain stem. Motor
tical. Cortical types of dementia are characterized coordination, vital functions, and central nervous
by marked memory disturbances. AD is a result of system arousal, timing, and sequential activity are
cortical disruption but eventually affects all lobes controlled by the subcortical structures. Move-
to some degree [64]. Magnetic resonance imag- ment disorders (e.g., tremors, rigidity, chorea) are
ing (MRI) has shown that the disease apparently a prominent and early manifestation of subcorti-
occurs in different areas of the brain as it progresses cal dementias. In cortical diseases such as AD,
[73]. Subcortical disorders often have associated impaired motor function occurs late in the course
motor disabilities. of the illness [14].
The entire brain is involved in the process of mem- The neurons form the foundation of a complex
ory. It is believed that the hippocampus (located communication system. They are attached to, and
deep in the brain above the brain stem) and the surrounded by, a myriad of dendrites, which serve
amygdala (situated under the temporal lobe) are to accept incoming information from the adjacent
critical to the formation, storage, and retrieval of nerve cells. The nerve axon terminates in the syn-
memory. These structures are an integral part of aptic knob, which contains a multitude of small
the limbic system. vesicles. These vesicles, or sacs, are the storage
containers for the chemical neurotransmitters that
The hippocampus, connected by afferent pathways
will allow the individual neuron to communicate
to sensory areas of the cortex, is responsible for the
with other nerve cells across the synaptic cleft.
acquisition and temporary storage of declarative
The neurotransmitters combine with the adjacent
memory. Declarative memory enables individuals
dendrite, causing a reaction, such as depolariza-
to organize their world. For example, one learns
tion. They can also be reabsorbed by the emitting
the route to work and after traveling the route a
neuron or be degraded while in the synaptic cleft.
few times is able to get there even though there
may be a detour. The hippocampus maintains the Until recently, it was believed that the human
directory for all of these memories so when they body formed its full complement of neurons before
are needed they can be retrieved. Individuals with and for a short time after birth; it could not create
bilateral loss of the hippocampus can only register new ones after this period. However, researchers,
incoming stimuli until the next stimulus arrives. including those at the Institute of Neurology in
Memories cannot be called up when needed, such Sweden and at the Salk Institute, have found that
as during learning experiences. Some believe the the human brain retains the ability to generate new
hippocampus helps associate affective character- neurons throughout life [8]. These findings may
istics of various sensory signals, thus helping to have an enormous impact on future approaches
control the kinds of information a person will or to the prevention and treatment of neurological
will not remember. disorders, including AD.
6 CME Resource • July 21, 2014 www.NetCE.com
____________________________________________________________________ #9615 Alzheimer’s Disease
There are several chemical neurotransmitters The presence of neurofibrillary tangles and amyloid
active in the brain, including dopamine, sero- plaques are the structural hallmarks of AD. Beta-
tonin, norepinephrine, gamma-amino butyric amyloid and tau are two proteins that participate
acid (GABA), and acetylcholine; each has a fairly in the formation of these abnormal structures.
specific group of actions. Associated neurologic A form of tau, A68, is the major component of
syndromes may be related to a deficit or overabun- these tangles. In healthy neurons, the internal
dance of a particular neurotransmitter. An example structures (called microtubules) are formed like
is dopamine’s effects on movement, learning, and long parallel tracks with crosspieces that carry
emotion and abnormalities in its concentration or nutrients from the body of the cells to the ends of
action leading to pathological conditions such as the axons. In AD, the structure has disintegrated.
Parkinson’s disease. The crosspieces formed from tau are twisted like
two threads wound around each other. Amyloid
The neurotransmitter that features most promi-
plaques, made up of beta-amyloid mixed with
nently in AD is acetylcholine. Dysfunction and
dendritic debris from surrounding cells, are found
reduction of nicotinic acetylcholine receptors is
in areas of the brain associated with memory. It is
linked to adverse cognitive and neurodegenerative
not known why beta-amyloid causes neuron death,
effects [143]. As will be discussed later, the drugs
but it is known that the normally soluble amyloid
that increase the cerebral levels of acetylcholine,
becomes insoluble when the apolipoprotein E4
such as the cholinesterase inhibitors, have been
susceptibility gene (ApoE4) protein latches onto
shown to provide some improvement in the cogni-
the beta-amyloid. The deposition of beta-amyloid
tion and function of people with AD [74].
plaques and tau tangles are the primary pathologi-
PATHOPHYSIOLOGY OF cal features of the AD brain, but it is now known
ALZHEIMER’S DISEASE that plaques and tangles are late-stage lesions and
are considered “tombstones” of the disease, not the
Symptoms seen in individuals with AD are par-
causes of it [169].
tially the result of damage to the hippocampus
and the cerebral cortex, reflected in memory loss, Individuals with more advanced AD show decreased
impaired cognition, and atypical behaviors. The activity of the enzyme choline acetyltransferase in
damage seen in AD is caused by changes in three their brains. This enzyme is involved in the pro-
major processes. The first process is based on the duction of acetylcholine, and a significant drop
communication between neurons. Successful in acetylcholine is linked to memory impairment
communication depends on reliable neuronal [128]. Dysfunction and reduction in nicotinic ace-
functions and the production of neurotransmitters. tylcholine receptors are linked to adverse cognitive
Any disruption of this process interferes with the and neurodegenerative effects [143].
normal function of cell-to-cell communication.
The second process is cellular metabolism. Suf-
ficient blood circulation is required to supply the
cells with oxygen and nutrients such as glucose.
The third process is the repair of injured neurons.
Neurons have the capacity to live more than 100
years, and as such, they must continuously main-
tain and adapt themselves in order to survive. If
this process slows or stops for any reason, the cell
cannot function properly.
CME Resource • Sacramento, California Phone: 800 / 232-4238 • FAX: 916 / 783-6067 7
#9615 Alzheimer’s Disease ____________________________________________________________________
Genetic Factors One area of exploration is a theory of aging. This
There are genetic factors that predispose certain theory pertains to certain types of molecules, spe-
individuals to AD. Genes are comprised of four cifically free radicals, that are a product of normal
nucleotides in a wide variety of combinations, metabolism. These substances may assist healthy
each of which directs the manufacture of a differ- cells in some functions, but an overabundance
ent protein. Even slight changes in a gene’s DNA of free radicals can injure cells. The oxidative
sequence can produce a faulty protein, which can damage due to free radicals may contribute to the
lead to cell breakdown and eventually disease. development of AD. Because brain cells have a
Research indicates there are at least four genes high rate of metabolism and a long life span, they
involved in the development of AD, including the are vulnerable to oxidative stress.
amyloid precursor protein (APP) gene, ApoE4, and
Another area of investigation involves the role
the presenilin 1 and 2 genes [12]. APP is a protein
of inflammation of the brain. Certain genes pro-
from which beta-amyloid, the chief component
duce an inflammation-promoting protein via the
of plaques seen in the brains of AD patients, is
immune system. One study has shown indirect evi-
formed, while ApoE helps transport cholesterol
dence that use of nonsteroidal anti-inflammatory
in the blood [8]. Mutations of the presenilin 1,
drugs (NSAIDs), particularly ibuprofen, may have
presenilin 2, and APP genes cause early-onset,
a protective effect against AD [69]. Direct evidence
autosomal dominantly inherited AD; mutations
reveals that various compounds involved in the
on chromosomes 1, 14, and 21 account for the
inflammatory process can be found in the plaques
majority of all of these cases [127; 155].
of AD [8].
Every person inherits an ApoE gene with one of
The relationship between brain infarction and AD,
four alleles (1–4) from each parent. ApoE3 is the
related to the effects of neurons being deprived of
most common allele found in the general popula-
oxygen and glucose, is another area of interest. It
tion, but ApoE4 is found in about two-thirds of the
has been suggested that some brain infarcts may not
cases of late-onset AD. A person with two copies
be sufficient to cause dementia but may play a role
of the allele has a 98% risk of developing AD. One
in increasing the severity of AD’s clinical signs [8].
copy of the allele drops the risk to 60%, and persons
Researchers have also studied the role of circulat-
without the allele have a 25% risk of developing
ing sex hormone levels in the development of AD.
AD [13]. It is possible to test family members with
Some data have suggested a correlation between
no symptoms of the disease to determine whether
decreased levels of circulating testosterone and AD
they carry the mutated gene, thus ascertaining
in men [91]. Depletion of testosterone levels in
their risk for developing AD. There appears to be
the brain is a normal consequence of male aging.
evidence that the ApoE2 allele may be protective
Because levels of the hormone decrease prior to
against AD, or at least the maintenance of cogni-
the development of AD, it is not believed to be
tion with age [12; 172].
a consequence of the disease but rather a possible
Non-Genetic Factors contributor to its development [92]. The mecha-
Although it is generally known what occurs in the nism by which the depletion may effect or cause
brain of people with AD, it is still not clear why AD has not been established. However, it has
these events occur in certain individuals. There are been hypothesized that low testosterone levels may
nongenetic factors related to AD, and research is increase brain levels of beta-amyloid [92]. There
being conducted to investigate these factors and to are also some preliminary studies examining the
develop new theories about the processes involved ability of estrogen to prevent the hyperphosphory-
in triggering the onset of the disease. lation of tau and, by extension, AD [96]. More
research regarding the role of sex hormones in the
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____________________________________________________________________ #9615 Alzheimer’s Disease
development of AD is necessary before definitive hypothesized that antihypertensive medications
recommendations may be made. may reduce the risk of dementia or AD. A study
of more than 5000 men and women older than 65
Comorbid Factors
years of age found that those taking blood pressure
A possible connection between herpes simplex lowering medications had a significantly lower
virus-1 (HSV1) and AD has been explored. risk of AD [95]. Cellular changes associated with
Researchers have found that the virus is able to vascular disease are also implicated in AD patho-
enter the brain in later life as the immune system physiology [170].
weakens, causing inflammation, oxidative dam-
age, and increases in beta-amyloid and tau, espe- Possible Environmental Risk Factors
cially in individuals with the ApoE4 allele [147]. Aluminum, a metal associated with chronic toxic-
HSV1 is found in a high proportion of the brains ity, has been linked with Alzheimer’s disease. High
of elderly individuals with and without AD, but concentrations of aluminum have been found in
certain individuals, such as those with the ApoE4 the brains of some individuals with AD, although
allele, will suffer greater viral damage [147; 152]. the exact nature of the correlation is not known
Interestingly, the ApoE4 allele is also a risk factor [96]. The accumulation of aluminum may be
for symptomatic, HSV1 reactivation (i.e., “cold responsible for the changes within the brain, or it
sores”). It should be noted that while the presence might be secondary to the cause(s) of AD. Some
and activation of HSV1 in the brain is apparently research suggests that exposure to aluminum in
common in the elderly, herpes simplex encepha- municipal drinking water (used as a clearing agent
litis, a serious brain disease, is an exceedingly rare, during treatment) possesses greater potential for
separate condition. chronic toxicity than exposure from other sources,
such as aluminum cookware, and that high intake
Researchers at Brown University and Rhode
of aluminum from tap water may be a risk factor
Island Hospital have proposed that AD is a neuro-
for AD [144; 145]. Other researchers speculate that
endocrine disorder “associated with brain-specific
fluoride ingestion (at exposure levels experienced
perturbations in insulin and insulin growth factor
by regular fluoridated drinking water consumption
(IGF) signaling mechanisms;” essentially, they
and toothpaste use) greatly enhances aluminum’s
hypothesize that AD is a distinct type of diabetes,
neurodegenerative effects [146]. A higher level of
termed “type 3 diabetes” [148]. Animal experi-
silicon intake is thought to protect against alumi-
ments have demonstrated that many of the hall-
num toxicity. Research into the possible role of
mark signs of AD can be reproduced by artificially
aluminum in the development of AD is ongoing.
reducing insulin and IGF levels, but additional
research with human subjects is necessary before In addition to aluminum, other transition metals
a link can be definitively proven [149; 173]. (e.g., copper, zinc, iron) are implicated as causative
factors for AD [144; 150; 151]. Oxidative stress,
RISK FACTORS ASSOCIATED
induced from either excesses or deficiencies of
WITH ALZHEIMER’S DISEASE
these metals, is theorized as being pathogenic. Iron
As noted, the risk of AD rises with age, doubling overload, copper depletion, and zinc overload/
every 5 years after age 65. Other well-established depletion have been found in AD brains by vari-
risk factors include family history of dementia ous research groups. However, these findings were
and Down syndrome [129; 130]. There is also called into question by a 2011 meta-analysis that
some evidence that people suffering head trauma discovered citation bias towards irreproducible
involving loss of consciousness have a higher risk research, especially regarding iron overload [151].
of developing AD [16]. Additionally, some studies Concrete evidence for transition metal pathogen-
have linked hypertension to a heightened risk for esis is currently lacking.
AD [93; 94]. As a result of these findings, it was
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#9615 Alzheimer’s Disease ____________________________________________________________________
While scholars agree that there may be several been suggested that supplementation levels used in
environmental factors for AD, no exposures, studies were too low [153]. Low vitamin B12 and
including pesticides, general air pollutants, lead, folate levels have been suspected for increasing AD
and other toxins, have been positively linked risk; however, folate deficiency is rare in the U.S.
to this form of dementia. Taking proactive steps due to widespread use of enriched grain products
to prevent oxidative damage, improve vascular [153]. Therefore, it is suggested that high folate
health, and create a healthier lifestyle overall, intake combined with low B12 levels may instead
seems to be the best defense against many envi- be a risk factor for AD.
ronmental risks.
Fat composition is also suspect. High saturated
or trans fat intake and low polyunsaturated and
Possible Cognitive Risk Factors
monounsaturated fat intake can cause hypercholes-
There is increasing evidence that individuals
terolemia, a risk factor for AD [153]. Omega-3 fatty
who do not engage in regular mental, social, and
acids (especially docosahexaenoic acid or DHA)
physical activities (and possibly a combination
are protective against inflammation, oxidative
of all three) are at heightened risk for AD [153].
damage, and synaptic loss. Individuals consuming
Activities and interactions provide opportunities
one fish meal per week are better protected against
for exercise, which maintains vascular health,
dementia than those eating fish less often [153].
and intellectual stimulation and problem solv-
ing, which maintain cognition. Individuals with
THE ROLE OF MEMORY
large social networks perform better in cognitive
Alzheimer’s disease is characterized by cognitive
testing despite having similar amounts of brain
impairment. Cognition includes all of the mental
lesions as individuals with few social contacts. It
processes that are acquired over a lifetime. These
is not known which specific component of leisure,
processes provide humans with the ability to learn,
work, and/or mental activities in late life prevent
think, make judgments, use logic and reason, and
or delay AD; however, researchers have noted a
have insight. Memory is a major antecedent for
protective effect when greater mental complexity
developing mastery in these intellectual functions.
is required throughout life at work and if cognitive/
Memory deficits are an early and progressive sign of
social/physical activities are maintained during
AD. In order to understand the behaviors of indi-
mid-life [153].
viduals with AD, it is necessary to understand the
significance of memory, the process of remembering
Possible Dietary Risk Factors
and recall, and the various types of memory.
In addition to the lack of conclusive evidence for
an environmental cause of AD, nutritional factors Memory is dynamic, developing in stages and
are also thus far unsubstantiated [171]. However, a constantly changing. Memory and learning are not
relationship between AD and certain deficiencies separate functions. Both depend on the storage of
has been suggested. Low vitamin E intake from data that can be retrieved at a later date. The abil-
food sources is associated with an increased risk of ity to remember simplifies life, allowing minimum
AD [153]. Oxidative damage, a major component energy to be expended on routine activities. For
of AD progression, is greatly reduced in individu- example, arising in the morning and completing
als with adequate dietary vitamin E intake, and the activities of daily living requires little con-
although other antioxidants and antioxidant scious thought. The tasks are performed by rote.
cofactors are thought to have a protective effect, However, the person with memory deficits may
consistent data regarding the efficacy of vitamin be unable to recognize the bedroom, unable to
C, flavonoids, and carotenoids, for example, is find the bathroom, and unaware that teeth must
lacking. Research so far has shown that vitamin E be brushed or where the items are that are used to
supplementation does not offer protection equiva- complete these tasks.
lent to dietary intake of vitamin E, although it has
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