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Alzheimer's Disease Clinical and Research Update for Health Care Practitioners

  • International Brain Research Foundation


Of the approximately 6.8 million Americans who have been diagnosed with dementia, over 5 million have been diagnosed with Alzheimer's Disease (AD). Due to the rise in the aging population, these figures are expected to double by 2050. The following paper provides an up-to-date review of clinical issues and relevant research. Research related to the methods of the earliest possible detection of AD is ongoing. Health care professionals should play a critical role in differentially diagnosing AD patients, as well as supporting their families. Novel interventions, including medications, natural supplements, and behavioral techniques, are constantly appearing in the literature. It is necessary for the health practitioner to remain current, regarding AD, as such information will facilitate better care for patients and their families.
Hindawi Publishing Corporation
Journal of Aging Research
Volume , Article ID , pages.//
Review Article
Alzheimer’s Disease Clinical and Research Update for Health
Care Practitioners
Philip A. DeFina,1Rosemarie Scolaro Moser,2Megan Glenn,2
Jonathan D. Lichtenstein,2and Jonathan Fellus1
1International Brain Research Foundation Inc., 227 Route 206 North, Building 2, Suite 101, Flanders, NJ 07836, USA
2RSM Psychology Center, LLC 3131 Princeton Pike, Building 5, Suite 110, Lawrenceville, NJ 08648, USA
Correspondence should be addressed to Rosemarie Scolaro Moser;
Received  June ; Accepted  July 
Academic Editor: Michelle M. Mielke
Copyright ©  Philip A. DeFina et al. is is an open access article distributed under the Creative Commons Attribution
License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly
Of the approximately . million Americans who have been diagnosed with dementia, over  million have been diagnosed with
Alzheimer’s Disease (AD). Due to the rise in the aging population, these gures are expected to double by . e following
paper provides an up-to-date review of clinical issues and relevant research. Research related to the methods of the earliest possible
detection of AD is ongoing. Health care professionals should play a critical role in dierentially diagnosing AD patients, as well
as supporting their families. Novel interventions, including medications, natural supplements, and behavioral techniques, are
constantly appearing in the literature. It is necessary for the health practitioner to remain current, regarding AD, as such information
will facilitate better care for patients and their families.
1. Introduction
Approximately . million individuals in the United States
are aected by dementia [], and approximately . million
have been diagnosed with Alzheimer’s Disease (AD) [].
As the elderly population continues to grow, these numbers
are only expected to increase. AD has emerged as a serious
public health concern, placing an immense burden on the
individual, family, community, and health care resources.
AD most frequently presents with episodic memory
impairment as the earliest and most prominent feature, with
additional decits in language, semantic memory, executive
functioning, visuospatial abilities, and functional impair-
ment that emerge over the disease course []. A common
misconception is that AD is a “normal” or expected occur-
age-related cognitive decline. Rather, healthy aging has been
measures of cognitive functioning when measured longitu-
dinally. However, cross-sectional studies have indicated that
some domains of cognitive functioning do in fact decline with
age []. As individuals live to advanced ages (e.g., over the
age of ), it can become more challenging to dierentiate
between the subtle cognitive declines that accompany aging
and those that signify early dementia [].
e trajectory of AD is characterized along a continuum,
ranging from healthy aging to preclinical AD, mild cogni-
tive impairment (MCI), and dementia. Pathological changes
that underlie AD begin to accumulate for years, or even
decades, before emotional, physical, or cognitive symptoms
emerge, eventually reaching a threshold at which the onset
of a gradual and progressive decline in cognition occurs
[]. Preclinical AD constitutes the presymptomatic phase
during which characteristic neuropathological changes begin
to emerge [].
e transitional period between normal cognitive func-
tioning and dementia is referred to as Mild Cognitive
Impairment (MCI) []; the most common form, the one most
likely to progress to AD, is amnestic MCI (a-MCI). Patients
with a-MCI present with memory decits greater than would
be expected based on age and education; however func-
tional abilities remain relatively preserved and independence
Journal of Aging Research
intact []. Estimates of the annual incidence of individuals
with MCI progressing to dementia range from  to % [].
Regardless of this variation, annual conversion rate of those
with MCI is far greater than the baseline incidence rate [].
AD is oen referred to as a “family disease” because
of the tremendous impact that befalls the patient’s imme-
diate social support system. By identifying AD in its early
stages, recommendations for the most current or ecacious
interventions can be made, with the goal of slowing disease
progression. Early detection may provide patients and their
families with an opportunity to begin the discussion of future
caregiving, nances, and end-of-life issues before the patient’s
autonomous decision-making skills deteriorate. Also, imple-
menting caregiver interventions, such as referral to support
groups, psychoeducation, and counseling or psychotherapy
[], can also assist patients and their families.
2. Epidemiology and Pathogenesis
Over the past  years, researchers have made great strides
in the areas of AD, with respect to etiology, prevention,
diagnosis, and treatment. However, while the exact etiology
still remains a mystery, denitive diagnosis can only be made
postmortem, and current treatments can only slow disease
progression temporarily. Late-onset AD, the most common
While researchers have not found any causal determinants for
this particular type, they have identied several associated
risk factors, including age, female gender, low educational
and occupational attainment, prior head injury, sleep disor-
ders (e.g., sleep apnea), estrogen replacement therapy, and
vascular risk factors, such as diabetes, hypercholesterolemia,
and hypertension [,]. Additionally, the apolipoprotein E
(APOE) gene has been recognized as conferring an increased
likelihood of developing late-onset AD. Depending on the
combination of APOE alleles that an individual possesses,
he or she may have a three to eight times higher risk. e
much rarer, early-onset from of AD, occurring in fewer than
ve percent of individuals with the disease, typically aects
individuals between the ages of approximately thirty and
identied genetic mutations that are passed down in an
autosomal dominant fashion among families: the amyloid
precursor protein (APP), presenilin-, and presenilin- genes
AD is characterized by progressive degenerative neuronal
changes, with associated global deterioration of cognitive
and personality functioning. is pathological sequence
preferentially begins in the medial temporal lobe structures
responsible for memory (the entorhinal cortex and hip-
pocampus) and then progresses to the frontal, temporal,
sensory cortical regions and subcortical regions []. e
most widely held theory accounting for the pathological
changes underlying disease process is the amyloid cascade
hypothesis, positing that the primary, triggering event is
the excessive accumulation and clumping together of beta-
amyloid (A𝛽), leading to the formation and deposition of
amyloid plaques throughout the medial temporal lobe and
cerebral cortex []. A resultant “cascade of events” occurs,
including neuronal damage (and eventually death), disrupted
neuronal communication, inammation, and the initiation
of a second abnormal protein process—the accumulation of
neurobrillary tangles (NFTs) [,].
NFTs are composed of an abnormal form of the intraneu-
ronal protein tau, which normally plays a role in structural
support and cellular communication. Abnormal processes
cause the tau protein to “misfold” and aggregate into NFTs,
and communication and eventually cell death []. e
accumulation of NFTs occurs in a hierarchical pattern,
beginning primarily in the medial temporal lobe (especially,
the entorhinal cortex), gradually progressing into the limbic
system (hippocampus and amygdala), and eventually spread-
ing throughout the neocortex [,,]. ere is evidence that
the presence of both amyloid plaques and NFTs is required for
AD to develop [].
Researchers continue to search for tools that can oer
the same degree of diagnostic certainty during life that
postmortem brain tissue examinations oer. ere are cur-
rently ve biomarkers which show the most promise as
indicators of AD pathology organized into two categories:
biomarkers of beta-amyloid accumulation and biomarkers of
neuronal degeneration or injury []. e accumulation of
beta-amyloid can be detected through the use of radioactive
tracers in conjunction with positron emission tomography
(PET) imaging [], as well as through the analysis of beta-
amyloid levels in the cerebrospinal uid (CSF) []. Analysis
degeneration associated with NFT accumulation [,].
Fluorodeoxyglucose- (FDG-) PET imaging can be employed
to detect hypometabolism in the temporoparietal region,
which has been shown to eectively dierentiate AD from
normal controls []. Finally, structural magnetic resonance
imaging (MRI) can be used to detect the characteristic
pattern of pronounced atrophy in the medial temporal lobes
that oen occurs in mild to moderate AD [].
While biomarker research holds promise for early detec-
tion and diagnosis of AD, standardized guidelines are still
being developed for determining cut-points for diagnosis
[]. us, the use of biomarker data is currently indicated
primarily for research purposes. Newly approved amyloid
imaging techniques (via PET scan) are beginning to be
used in order to supplement the results of other diagnostic
3. Clinical Manifestations
In , the National Institute on Aging and the Alzheimer’s
Association (NIA-AA) joined forces to develop new up-to-
date guidelines for diagnosing AD based on the most current
state of the evidence regarding the clinical and pathological
processes of the disease. e ocial criteria were published in
 and are summarized as follows: () a gradual, progressive
decline in cognition that represents a deterioration from a
previous higher level; () cognitive or behavioral impairment
Journal of Aging Research
evident in at least two of the following domains: episodic
memory, executive functioning, visuospatial abilities, lan-
guage functions, personality and/or behavior; () signicant
functional impairment that aects the individual’s ability
not better accounted for by delirium or another mental
disorder, stroke, another dementing condition (i.e., vascular
dementia, frontotemporal dementia) or other neurological
condition, or the eects of a medication []. e Diagnostic
and Statistical Manual of Mental Disorders is a tool which
is widely employed in clinical settings for diagnosing AD.
e recently released version, the DSM-, contains updated
criteria for diagnosing AD which parallel the NIA-AA diag-
nostic guidelines. It is imperative for clinicians to familiarize
themselves with these revised criteria, listed within the
Neurocognitive Disorders section, as the criteria contained
in the prior DSM-IV-TR are not reective of the current state
of the AD literature [].
e initial presentation of AD typically involves antero-
grade amnesia resulting from progressive declines in episodic
memory. Specic memory tests may reveal decits in the
encoding and consolidating of new information into long
term memory as evidenced by rapid forgetting aer a time
delay and lack of improvement even when recognition cues
are provided. On episodic memory tasks, AD patients com-
monly commit more errors of intrusion and perseveration,
have diculty employing semantic encoding tactics, and
demonstrate less of a primacy eect when compared to
normal elderly individuals [,,]. As memory impairment
begets functional decline, some of the rst overt signs of AD
oen noted by family members include repeating oneself in
conversations, misplacing items,becoming lost while driving
(familiar routes), burning meals while cooking, and diculty
managing nances [,]. With regard to remote memory, a
pattern emerges in the early stages of the disease in which
older memories are relatively spared, while those from the
more recent past are lost [,].
Decits in semantic memory and language may become
evident early in the course of AD, as well. ese diculties
are thought to result from the degenerative disease process
causing a breakdown in the brains interconnected network
of general knowledge for concepts, facts, words, and their
meaning. Impairment may be detected on tests of verbal
uency, with the tendency to perform relatively worse on
tasks requiring generation of words from a given category
versus generation of words that begin with a particular letter
of the alphabet. Patients are unable to employ clustering
strategies to boost their performances and are also unaided by
category retrieval cues [,]. Given that AD leads to a loss
of semantic knowledge, the failure to demonstrate semantic
to be consistent across test methods []. Poor performance
is also typically seen on confrontation naming tests and
semantic categorization (i.e., of pictures) [,]. Language
discourse becomes increasingly lled with circumlocutions
and overlearned phrases, accompanied by diminished mean-
ing and spontaneity []. Decline in executive functioning
memory, mental exibility, and sequencing; decits in these
areas may be detected relatively early on tests such as the
Tower of London puzzle, Porteus Maze task, Trail-Making
Test, and Wisconsin Card Sorting Task and are implicated in
the decline of instrumental activities of daily living (IADLs).
Tests of immediate attention span and focus, such as digit
span and mental control, may remain intact until later in the
disease progression [,,].
Visuospatial functioning tends not to be a prominent
early feature of AD, but instead it regresses over the course
of the disease []. In particular, visuoconstructional decits
copying tasks using drawing or blocks [,]. A hallmark
indicator of AD is the patients’ tendency to perform their
copy of a design extremely close to, touching, or on top of the
stimulus item []. Additionally, visuoperceptual and visual
orientation abilities may become disturbed over time [].
While extrapyramidal motor signs are more prominent
in the latter stages of AD, patients may show decits in ideo-
motor (skilled movement to verbal command or imitation)
and ideational (performing a planned series of motor tasks to
achieve a goal) praxis, even in the early stages of the disease
[]. is has implications for their ability to independently
perform daily living tasks [].
4. Diagnostic Approach
Determining the primary cause of cognitive decline can be
challenging, given the common comorbidity of cerebrovas-
culardisease,Lewybodydisease,andAD[,]. Additionally,
temporal conditions, such as delirium, depression, anxiety,
metabolic disorders, vitamin deciencies, normal pressure
hydrocephalus (NPH), and adverse reactions to medication,
may resemble AD particularly in individuals who are young,
newly symptomatic or whose symptoms are mild [].
Neuropsychological testing can contribute to dierentiating a
true dementia process from a pseudo-dementia, as well as dis-
tinguishing between dierent forms of dementia. However,
there are times when patients meet the diagnostic criteria for
AD, and have a comorbid condition that may be contributing
to cognitive impairment, thus causing a mixed dementia. e
NIA-AA criteria dierentiate between probable and possible
AD and designate patients with mixed dementias to the latter
category [].
Table  oers a schematic for diagnostic guidance when
evaluating a patient for dementia. Generally, when a clin-
ician suspects changes in mental status, a screening test
is performed to assess global cognitive abilities. e Mini-
Mental State Examination (MMSE) is among the most widely
researched instruments for screening cognitive impairment.
is global assessment tool measures orientation to time
and place, word recall, language abilities, attention and
calculation, and visuospatial skills. e MMSE yields a
perfect score of , with cut-o points between  and 
suggesting dementia []. Age and education adjustments
should be utilized for MMSE scoring, as performance may be
aected by demographic factors, particularly education [].
Temporal orientation and factual understanding of current
events may be problematic even in early AD, which may be
revealed by the MMSE.
Journal of Aging Research
T : Diagnostic assessment for dementia.
(i) Initial exam
(signs to look for)
Poor orientation
Increased forgetfulness
Confusion in ADLs and IADLs
Language perseverations and circumlocutions
Change in personality and emotional status
Avoidance of typical activities and hobbies
Social isolation
(ii) Mental status screening-use NIAA criteria
(example of evaluation tools that may be used)
Mini mental state
Clock drawing
Mattis dementia screening
Montreal cognitive assessment
Clinical dementia rating scale
Geriatric depression scale
(iii) Interview for instrumental activities of daily living
(observations by family or caregiver report)
Medication use
Financial management
(iv) Interview for general activities of daily living
(observations by family or caregiver report)
(v) Assessment of visual motor skills
(signs to look for)
Ideomotor apraxia (skilled movement to verbal
command or initiation)
Ideational apraxia (performing a planned series
of tasks to achieve a goal)
Extrapyramidal motor signs
Constructional apraxia
Spatial conceptualization errors
(vi) Neuroimaging
(vii) Neuropsychological testing
(skill areas to assess)
Estimate of premorbid IQ
Processing speed
Executive functioning
Planning, organization, mental exibility
Working memory
Immediate recall
Delayed recall
Long term memory
T : Continu ed.
Semantic uency
Evidence of perseverations
Evidence of circumlocution
e Montreal Cognitive Assessment (MoCA) was more
recently developed to specically detect the more subtle
decits associated with MCI []. Similar to the MMSE,
scores on the MoCA range from  to , with the suggested
cut-o for impairment being less than . However, the
MoCA includes more dicult tasks, making it more sensitive
in dierentiating normal cognition from mild cognitive
impairment. Individuals with MCI oen score in the normal
range on the MMSE and in the impaired range on the MoCA,
highlighting the utility of the MoCA in detecting the earliest
symptoms of AD [].
A thorough patient history should be taken, preferably
involving a knowledgeable spouse or other family member,
in order to determine whether the onset and course of
sudden and/or stepwise, which may occur in the case of
vascular dementia. An appropriate set of medical tests (i.e.,
neuroimaging , laboratory tests) may be conducted to rule out
another neurological condition, medical illness, or another
process which may be present, and patients are oen referred
for a neuropsychological assessment [,].
e neuropsychologist should utilize a battery of assess-
ment measures that are sensitive to the cognitive decits
seen in AD and capable of distinguishing between age-
related cognitive decline, MCI, AD, and other forms of
dementia. An example of such an abbreviated battery, used
by the Alzheimer’s Disease Centers (ADC) program of the
NIA, incorporates measures of global cognition (MMSE),
attention (Digit Span Forward & Backward), processing
speed (Digit Symbol; Trail Making Test—Part A), executive
functions (Trail Making Test—Part B), episodic memory
(Logical Memory Story A—Immediate and Delayed Recall),
and language (Category Fluency; Boston Naming) [].
Additional evidence of episodic memory impairment may
be gathered from word list memory tasks, which can help
identify decits in encoding, storage, and retrieval. Com-
bined visuoconstructional and visual memory tasks may be
used which require the patient to copy shapes and then to
recall those shapes aer a delay, both from memory and with
recognition cues. A diverse range of skills may be assessed
by administering a Clock Drawing task, including planning,
visual attention, spatial orientation, and graphomotor control
[]. Finally, since many patients with dementia have never
undergone previous neuropsychological assessment, an esti-
mate of premorbid IQ may be obtained by administering a
word list reading task, such as the Wechsler Test of Adult
Reading (WTAR).
In addition to evaluating the patients cognitive, the
neuropsychologist will address functional issues related to
Journal of Aging Research
mental activities of daily living (IADLs), such as driving,
medication management, and nancial management. Ability
to perform basic activities of daily living (BADLs) must also
be examined (e.g., toileting, bathing, and dressing), through
observation, informant report, or rehabilitation specialists
such as occupational therapists. e “gold standard” of formal
measures for assessing the level of functional impairment
is the Clinical Dementia Rating Scale (CDR) [], which
is a semistructured interview combining information from
of dementia severity is calculated, along with the CDR
sum of boxes score (CDR-SB), which allows for a detailed,
continuous measure of the subtle dierences between levels
of impairment and has been found to be able to discriminate
MCI from early AD [].
5. Therapeutic Interventions
In the management of AD, a multimodal approach is war-
ranted. Tabl e  provides an outline of eight intervention
areas to address. ese interventions include pharmaceutical,
nutraceutical, medical foods, neurophysiological, physical
health, cognitive, behavioral, and future planning.
At this time, there are no established therapeutic inter-
ventions that have been found which can stop the progression
or reverse the neural deterioration caused by AD. However,
there are four FDA approved pharmaceuticals currently
prescribed which temporarily halt or slow cognitive, func-
tional, and behavioral decline. ree of the medications are
cholinesterase inhibitors, namely, Donepezil, Rivastigmine,
and Galantamine, which work to increase the levels of
acetylcholine, a neurotransmitter in the brain that is involved
in learning and memory. e cholinesterase inhibitors are
indicated for the treatment of individuals in the mild to mod-
erate stages of AD [,]. Memantine works by increasing
the levels of glutamate, another neurotransmitter implicated
in learning and memory. is drug is indicated for the
treatment of moderate to severe AD. ere is also evidence
that Memantine may provide added benets for individuals
with AD who are already taking Donepezil []. Overall, the
approximately one year and in only about half of individuals
Currently, there are no other evidence-supported treat-
ments for AD, however ongoing research aims to nd
disease-modifying treatments. Consensus statements have
pointed to a multifaceted approach for conquering AD,
using a combination of drugs to target a number of factors
associated with the disease process, including A𝛽deposits,
NFTs, inammation, immune dysregulation, and insulin
resistance []. Recent breakthroughs include results from
a phase II clinical trial of IVIG, an immunotherapy agent,
which was found to stabilize cognition and functioning,
in a small sample of AD patients, for three years [].
Another promising nding came from a pilot clinical trial
of an intranasal insulin therapy for AD and a-MCI in which
participants who underwent treatment experienced memory
improvement and/or maintained their current level of overall
cognitive and functional performance [].
Additionally, Alpha GPC, phosphatidylserine, Huperzine
A, and choline show promise as nutraceutical agents for
enhancing cognitive performance and slowing cognitive
decline. Alpha GPC, also known as L-Alpha Glycerylphos-
phorylcholine, a naturally occurring form of choline, acts
as a parasympathomimetic acetylcholine precursor and has
shown promise in improving cognitive symptoms related to
AD, vascular dementia, and multi-infarct dementia. Phos-
phatidylserine is a widely abundant anionic phospholipid in
the human body and has been shown to improve age-related
cognitive changes. Huperzine A (a natural cholinesterase
inhibitor) has been linked to improved memory performance
in elderly people with benign forgetfulness, as well as patients
with AD and vascular dementia. Cholinesterase inhibitors
have been shown to have neuroprotective properties in
patients with mild [] as well as moderate-to-advanced AD
Recently, there is the development of medical foods that
Axona, CerefolinNAC, and Souvenaid []. Each works via
a dierent mechanism of action, and all are prescriptive
supplements. However, Souvenaid is not currently available
for use in the USA.
e application of translational models, such as through
animal and cell research, has helped identify certain processes
and elements that may deter the neuropathogenetic progres-
sion of AD []. Research has begun to explore nonpharma-
ceutical interventions through translational models that may
reduce toxins and prevent cell loss including apoptosis. In
other words, once applications of interventions on animals
or cells are deemed successful, they can be translated or
applied to human participants. Laser light therapy is one
such intervention, and animal studies using infrared light
treatment have documented positive results in mice with
traumatic brain injury []. Stimulation of human mitochon-
drial processes and cell proliferation due to laser irradiation
have also been demonstrated []. More recently, researchers
revealed a signicant reduction of Amyloid-B aggregates in
neuroblastoma cells that were irradiated with intense  nm
laser light, leading the authors to suggest that their approach
might inspire a practical therapy for AD [].
Ultimately, the most successful model of treatment for
AD will likely include early detection and control of physical
factors (diabetes, hypertension, hyperlipidemia), followed by
application of multifaceted, disease-modifying interventions
to prevent the early and continued loss of neurons and to
reduce the toxins that result in further cell deterioration[].
Changes in personality and behavioral disturbances aect
most patients with AD and can range from disinterest and
apathy to agitation, aective disinhibition, and restlessness.
Specic behaviors can be dicult to manage, such as aimless
wandering, emotional outbursts, stubbornness, paranoia,
hallucinations, and depression. Behavioral interventions can
complement medication management and include creating a
structured, safe, low stress environment, promoting regular
sleep and eating habits, minimizing unexpected changes, and
employing redirection and distraction [].
Journal of Aging Research
T : Management of dementia: eight intervention areas to be addressed.
(i) Pharmaceutical interventions
(medications that may provide symptom relief for cognitive, emotional, and behavioral issues)
Psychotropic (antidepressants, antianxiety, mood stabilizer, antipsychotic)
(ii) Nutraceutical interventions
(dietary supplements still in research stages)
Omega 
Vitamin D
Alpha GPC
(iii) Medical foods interventions
Souvenaid (not currently available in the USA)
(iv) Neurophysiological interventions
(still in research stages)
Cranioelectric stimulation
Transcranial magnetic stimulation
Laser light therapy
Aerobic exercise
Medical management of disease
(vi) Cognitive inter ventions
Mental exercises/hobbies
Compensatory memory strategies and aids
Cognitive training
(vii) Behavioral interventions
(strategies to manage factors such as wandering, sundowning, agitation, disorientation, aective disinhibition, stubbornness,
paranoia, irritability, apathy, and restlessness)
Occupational therapy safety assessment of home
Low stress calming environment
Regular sleep and meal schedules
Redirection and distraction
Minimization of unexpected changes in environment
Patient counseling and support groups in early stages
Caregiver strategies and resources through support groups and internet
In-home aide/assistant
Journal of Aging Research
T : Continu ed.
Outpatient day program with all inclusive care
assisted living facility
(viii) Future planning interventions
Caregiver counseling to aid in life planning and decision making
Legal services for guardianship and capacity
Financial advisor for estate planning
Since ADLs such as self-care, personal hygiene, and
dressing tend to worsen with the progression of the disease,
patients with advanced AD require a greater level of caretaker
commitment. Caregivers should be alerted to the challenges
they will face as the disease progresses and be provided
with appropriate coping skills, training, and interventions,
through support groups and individual therapy. When at-
home care is no longer an option, families will face the
decision of placing their loved one in an assisted-living
facility. Caregivers should not make this choice in isolation;
mental health practitioners can help provide information
and allow for the processing of the emotional weight of the
decision and any mixed emotions of guilt, hurt, anger, and
Considering that IADLs also decrease in AD, issues such
as management of medical decisions, nancial aairs, and
cessation of driving will also emerge. When the patient is
no longer able to perform basic math calculations, securing
a nancial advisor to oversee assets is oen recommended.
When insight becomes limited and memory is signicantly
compromised, medical decision-making and medication
management may also need to be shied to the hands of a
are not uncommon, especially when estate and legal issues
need to be addressed.
6. Preventative Interventions
AD is believed to emerge as the result of a complicated
interplay of genetic, environmental, and lifestyle factors. Due
to this complex process, it is dicult to pinpoint a denitive
prevention strategy; however, there is mounting evidence
that modifying certain lifestyle factors may lower the risk
of developing AD []. ere is data to suggest that aerobic
exercise may improve cognition []andserveaprotective
role in healthy older adults by inducing neuroplasticity in
areas of the brain associated with episodic memory [].
Additionally, physical activity has been found to improve
scores on cognitive and functional measures in individuals
with MCI and dementia [].
As cardiovascular risk factors, such as diabetes, hyper-
cholesterolemia, and hypertension, have been found to be
associated with AD, it is hypothesized that preventing or
managing these conditions may decrease the likelihood of
developing AD []. Research has shown that healthy eating,
specically adhering to a Mediterranean diet, correlated with
both a lower risk of cardiovascular disease and AD [].
While there is ongoing research investigating the eects of
various vitamins and dietary supplements in preventing AD,
as of yet, clinical trials have not been able to prove their
eectiveness [].
In addition to maintaining physical health, engagement
in cognitively stimulating as well as social activities seems
important for promoting healthy brain functioning. Investi-
gators have found that older adults who frequently participate
in mentally demanding activities (i.e., reading, crossword
puzzles) have decreased odds of developing AD []. Formal
interventions involving cognitive training and time spent
engaging in physical, cognitive, and social activities have been
associated with a lower risk of developing dementia in healthy
older adults, especially for individuals who participated in
7. Summary
Alzheimer’s Disease (AD) is an increasingly common condi-
tion with projected increased incidence rates in the popula-
tion. Fortunately, research geared towards enhancing disease-
modifying and preventative interventions is gaining momen-
tum. Neuropsychological evaluation continues to play a
critical role in early detection and dierential diagnosis of
normal aging versus MCI and the various types of dementia.
Health care practitioners can oer strategies and support
for patients, as well as their families and caregivers, related
to the disruptions that AD has upon daily functioning. As
researchers continue to make strides in our understanding of
the disease, it is imperative for clinicians to remain abreast of
the dementia literature in order to assist patients in obtaining
Dr. Jonathan Fellus has been a consultant on the speakers
is article is dedicated to the memory of Nathan Plafsky and
the Nathan and Bernice Plafsky Center for the Aging Brain
of the International Brain Research Foundation. e authors
have no conict of interests related to this article.
[] NINDS, “Dementia: hope through research,” , http://www dementia.html.
Journal of Aging Research
[] CDC, Alzheimer’s disease,” ,
neuropsychological prole of Alzheimer disease,” Cold Spring
Harbor Perspectives in Medicine,vol.,no.,ArticleIDa,
[] J.M.BurnsandJ.C.Morris,Mild Cognitive Impairment and
Early Alzheimer’s Disease: Detections and Diagnosis,JohnWiley
ropsychology of dementia,” in Neuropsychological Assessment of
Neuropsychiatric and Neuromedical Disorders,I.GrantandK.
Adams, Eds., pp. –, Oxford University Press, New York,
NY, USA, .
[] C.R.JackJr.,M.S.Albert,D.S.Knopmanetal.,“Introduction
to the recommendations from the National Institute on Aging-
Alzheimer’s Association workgroups on diagnostic guidelines
for Alzheimer’s disease,Alzheimer’s and Dementia,vol.,no.,
pp. –, .
[] R. C. Petersen, “Conceptual overview,” in Mild C ognitive Impair-
ment: Aging to Alzheimer’s Disease,R.C.Petersen,Ed.,pp.,
Oxford University Press, New York, NY, USA, .
nosis of mild cognitive impairment due to Alzheimer’s dis-
ease: recommendations from the National Institute on Aging-
Alzheimer’s Association workgroups on diagnostic guidelines
for Alzheimer’s disease,Alzheimer’s and Dementia,vol.,no.,
pp. –, .
[] Association As, “Alzheimer’s disease facts and gures,” , gures .pdf.
[] NIA, 2011-2012 Alzheimer’s Disease Progress Report: Intensifying
the Research Eort,.
[] H. Braak and E. Braak, “Neuropathological stageing of
Alzheimer-related changes,Acta Neuropathologica,vol.,no.
, pp. –, .
[] D. J. Selkoe, “e molecular pathology of Alzheimer’s disease,
Neuron, vol. , no. , pp. –, .
[] J. Hardy and D. J. Selkoe, “e amyloid hypothesis of
Alzheimer’s disease: progress and problems on the road to
[] J. Homan, e Alzheimer’s Project: Momentum in Science,
[] Z. Nagy, D. M. Yilmazer-Hanke, H. Braak, E. Braak, C.
Schultz, and J. Hanke, “Assessment of the pathological stages
of Alzheimer’s disease in thin paran sections: a comparative
study,Dementia and Geriatric Cognitive Disorders,vol.,no.,
pp. –, .
[] G. M. McKhann, D. S. Knopman, H. Chertkow et al., “e diag-
nosis of dementia due to Alzheimer’s dise ase: recommendations
from the National Institute on Aging-Alzheimer’s Association
workgroups on diagnostic guidelines for Alzheimers disease,
Alzheimer’s and Dementia,vol.,no.,pp.,.
[] W. E. Klunk, H. Engler, A. Nordberg et al., “Imaging brain
amyloid in Alzheimer’s disease with pittsburgh compound-B,
Annals of Neurology,vol.,no.,pp.,.
[] J. Q. Trojanowski, H. Vandeerstichele, M. Korecka et al.,
“Update on the biomarker core of the Alzheimer’s disease
neuroimaging initiative subjects, Alzheimer’s and Dementia,
vol. , no. , pp. –, .
[] W. Jagust, “Positron emission tomography and magnetic res-
onance imaging in the diagnosis and prediction of dementia,
Alzheimer’s and Dementia,vol.,no.,pp.,.
[] M. Atiya, B. T. Hyman, M. S. Albert, and R. Killiany, “Structural
magnetic resonance imaging in established and prodromal
Alzheimer disease: a review,Alzheimer Disease and Associated
[] APA, Diagnostic and Statistical Manual of Mental Disorders,
American Psychiatric Association, Washington, DC, USA, th
edition, .
[] J.D.Warren,P.D.Fletcher,andH.L.Golden,“eparadoxof
syndromic diversity in Alzheimer disease,Nature Reviews,vol.
, no. , pp. –, .
[] M. D. Lezak, Neuropsychological Assessment, Oxford University
Press, New York, NY, USA, th edition, .
[] B. L. Malamut and L. M. Ryan, “Dementia: behavioral and
cognitive aspectseds,” in Clinical Neurology of the Older Adult,J.
Health/Lippincott Williams & Wilkins, Philadelphia, Pa, USA,
nd edition, .
[] M. Mitrushina, “Cognitive screening methods,” in Neuropsy-
chological Assessment of Neuropsychiatric and Neuromedical
University Press, New York, NY, USA, .
[] Z. S. Nasreddine, N. A. Phillips, V. B´
edirian et al., “e Mon-
treal Cognitive Assessment, MoCA: a brief screening tool for
mild cognitive impairment,Journal of the American Geriatrics
[] S.Weintraub,D.Salmon,N.Mercaldoetal.,“eAlzheimers
disease denters’ Uniform Data Set (UDS): the neuropsychologic
test battery,AlzheimerDiseaseandAssociatedDisorders,vol.,
[] M. Freedman, Clock Drawing: A Neuropsychological Analysis,
Oxford University Press, .
[] J. C. Morris, “Clinical dementia rating: a reliable and valid
diagnostic and staging measure for dementia of the Alzheimer
type,International Psychogeriatrics, vol. , supplement , pp.
–, .
[] S. E. O’Bryant, L. H. Lacritz, J. Hall et al., “Validation of the new
interpretive guidelines fort heclinical dementia rating scale sum
of boxes score in the national Alzheimer’s coordinating center
database,Archives of Neurolog y,vol.,no.,pp.,.
[] Association As, Current Alzheimer’s Treatments,.
[] N. Herrmann, S. A. Chau, I. Kircanski, and K. L. Lanctˆ
“Current and emerging drug treatment options for Alzheimers
disease: a systematic review,Drugs,vol.,no.,pp.
, .
[] P.N.Tariot,M.R.Farlow,G.T.Grossberg,S.M.Graham,S.
McDonald, and I. Gergel, “Memantine treatment in patients
with moderate to severe Alzheimer disease already receiving
donepezil: a randomized controlled trial,Journal of the Ameri-
can Medical Association,vol.,no.,pp.,.
[] R. Duara, W. Barker, D. Loewenstein, and L. Bain, “e basis for
disease-modifying treatments for Alzheimer’s disease: the sixth
snnual mild cognitive impairment symposium,Alzhe imer’s and
[] N. Relkin, L. Bettger, D. Tsakanikas, and L. Ravdin, “ree
Alzheimer’s & Dementia,vol.,no.,article,.
therapy for Alzheimer disease and amnestic mild cognitive
impairment: a pilot clinical trial,Archives of Neurolog y,vol.,
no. , pp. –, .
Journal of Aging Research
[] A. Venneri, W. J. McGeown, and M. F. Shanks, “Empirical
evidence of neuroprotection by dual cholinesterase inhibition
in Alzheimer’s disease,Neuroreport,vol.,no.,pp.,
memantine for moderate-to-severe Alzheimer’s disease,” e
New England Journal of Medicine,vol.,no.,pp.,
[] P. aipisuttikul and J. E. Galvin, “Use of medical foods and
nutritional approaches in the treatment of Alzheimer’s disease,
Clinical Practice,vol.,no.,pp.,.
[] L. Hong, “Translational research in neurology: dementia,
Archives of Neurology,vol.,no.,pp.,.
[] Q. Wu, W. Xuan, T. Ando et al., “Low-level laser therapy for
closed-head traumatic brain injury in mice: eect of dierent
wavelengths,Lasers in Surgery and Medicine,vol.,no.,pp.
–, .
[] W.-P. Hu, J.-J. Wang, C.-L. Yu, C.-C. E. Lan, G.-S. Chen, and H.-
S. Yu, “Helium-neon laser irradiation stimulates cell prolifera-
tion through photostimulatory eects in mitochondria,Journal
of Investigative Dermatology,vol.,no.,pp.,.
[] A. P. Sommer, J. Bieschke, R. P. Friedrich et al., “ nm laser
light and EGCG complementarily reduce amyloid-𝛽aggre-
gates in human neuroblastoma cells: basis for treatment of
alzheimer’s disease?” Photomedicine and Laser Surgery,vol.,
no. , pp. –, .
[] C. H. Sadowsky and J. E. Galvin, “Guidelines for the man-
agement of cognitive and behavioral problems in dementia,
Journal of the American Board of Family Medicine,vol.,no.
, pp. –, .
[] National Institute on Aging NIoH, Department of Health and
Human Services, Preventing Alzheimer’s Disease: What Do We
[] M. W. Voss, K. I. Erickson, R. S. Prakash et al., “Neurobiological
markers of exercise-related brain plasticity in older adults,
Brain, Behavior, and Immunity,vol.,pp.,.
exercise training on elderly persons with cognitive impairment
and dementia: a meta-analysis,Archives of Physical Medicine
and Rehabilitation,vol.,no.,pp.,.
Luchsinger, “Mediterranean diet and risk for Alzheimer’s dis-
ease,Annals of Neurology,vol.,no.,pp.,.
activity and incident AD in a population-based sample of older
[] A. Karp, S. Paillard-Borg, H.-X. Wang, M. Silverstein, B.
Winblad, and L. Fratiglioni, “Mental, physical and social com-
ponents in leisure activities equally contribute to decrease
dementia risk,Dementia and Geriatric Cognitive Disorders,vol.
, no. , pp. –, .
... The other form of disease, which is much rarer, known as early-onset Alzheimer's disease, occurs in individuals between the age of thirty to sixty five years [22]. This is caused by the genetic mutations in Amyloid Precursor Protein (APP) and Presenilin-1 (PS1) and Presenilin-2 (PS2) proteins (sub components of γ-secretase) [23]. ...
... Deposition of Aβ plaques initiates hyperphosphorylation of tau protein, which is a structural protein associated with the cytoskeleton of neurons, resulting in misfolding of tau protein and the formation of aggregates named neurofibrillary tangles (NFTs). These lead to impaired communication between neurons and finally, death of the neuron [23,38]. ...
... Also, it restores the Aβ induced Ca 2+ imbalance in cells [55]. Therefore, this drug plays a neuroprotective role while providing symptomatic treatment for AD [23]. ...
Alzheimer's disease (AD) is a neurodegenerative disorder and is identified as the most common cause for dementia. Despite huge global economic burden and the impact on the close family of the patients, there is no definitive cure and thus, improved treatment methods are of need. While memory and cognition are severely affected in AD, exact etiology is yet unknown. The β-Amyloid plaque formation and aggregation hypothesis is among the well-known hypotheses used to explain disease pathogenesis. Currently there are five Food and Drug Administration (FDA) approved drugs as treatment options. All these drugs are used for symptomatic treatment of AD. Thus, disease modifying therapies which can directly address the pathological changes in AD, are needed. Such therapies could be designed based on inhibiting key steps of pathogenesis. Currently there are novel AD drug candidates with various therapeutic mechanisms, undergoing different stages of drug development. Extensive research is being done globally to broaden understanding of the exact mechanisms involved in AD and to develop therapeutic agents that can successfully hinder the occurrence and progression of the disease. In this review, we present a comprehensive approach to understanding AD and suggestions to be considered in the development of therapeutics for it.
... The most neurotoxic form, A , accumulates and binds to the AMPA ( -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptor, as well as Ca 2 + channels, because of this influx of Ca 2 + increases thus increases the level of intracellular Ca 2 + [ 29 , 30 ]. This causes neuronal cells to undergo apoptosis, which results in cell death [31] . These accumulates also trigger a local inflammatory response, resulting in the death of the neuronal cells [32] . ...
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Alzheimer's disease is an insidious, slowly progressive neurodegenerative disease in aged people and the most prevalent form of dementia, characterized by loss of memory, behavioral changes, cognitive deterioration, and loss of functional abilities that affect the capability of a person to carry out daily tasks. The pathogenesis of AD is attributed to the accumulation of amyloid-beta (Aβ) plaques and neurofibrillary tangles (NFTs) in the brain. Thus there is an urgent need for disease-modifying medication for its treatment. Conventional therapies like Acetylcholinesterase inhibitor and NMDAR antagonist are only used for symptomatic relief. Aducanumab is a human IgG1 monoclonal antibody that decreases plaque deposition by targeting accumulated insoluble and soluble forms of Aβ. Aducanumab was approved in June 07, 2021, by USFDA with the brand name ADUHELM as the first and only therapy to deal with a significant pathology of AD by lowering Aβ plaques in the brain. In this review, various aspects related to aducanumab have been summarized, including the pathophysiology of AD, pharmacological and non-pharmacological treatment of AD, mechanism as well as pharmacokinetics and pharmacodynamics of aducanumab, adverse reaction and various reported clinical trials. Aducanumab is a human IgG1 (immunoglobulin gamma1) monoclonal antibody that targets the aggregated, insoluble and soluble forms of Aβ and lowers the deposition of Aβ plaques in the brain. Aducanumab emerged as a potential drug to slow down the development of AD.
... This impairment advances with age and is expected to increase in the future with an increasing older population worldwide. Patients with mild cognitive impairment frequently progress to dementia and Alzheimer's disease (AD), placing a heavy burden on the public health system (1)(2)(3). Hence, it is necessary to delay this progression for which there are many strategies including the use of cognitive enhancers (also referred as nootropics). ...
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Patients with mild cognitive impairment eventually progress to Alzheimer's disease (AD) causing a strong impact on public health. Rosmarinus officinalis has long been known as the herb of remembrance and can be a potential cognition enhancer for AD. The aim of this review was to summarize the qualitative and quantitative aspects of R. officinalis and its active constituents in enhancing cognition. A structured search was conducted on Google Scholar and PubMed to find relevant studies that assessed the effect of R. officinalis extract or any of its active constituents on cognitive performance in animals. The following information was extracted from each study: 1) article information; 2) characteristics of study animals; 3) type of intervention: type, dose, duration, and frequency of administration of R. officinalis; and 4) type of outcome measure. Data were analyzed using Review Manager and meta-analysis was performed by computing the standardized mean difference. Twenty-three studies were selected for qualitative analysis and fifteen for meta-analysis. From the fifteen included papers, 22 with 35 comparisons were meta-analyzed. Effect sizes for intact and cognitively impaired animals were 1.19 (0.74, 1.64) and 0.57 (0.19, 0.96), indicating a positive effect on both groups. The subgroup analyses showed substantial unexplained heterogeneity among studies. Overall, R. officinalis improved cognitive outcomes in normal and impaired animals, and results were robust across species, type of extract, treatment duration, and type of memory. However, studies had a considerable amount of heterogeneity, and subgroup analyses failed to find any heterogeneity moderator.
... Phosphoryl choline reaches the cholinergic nerve terminals and stimulates Ach synthesis [35]. α-GPC has shown improved cognitive health by increasing the hippocampal Ach levels; its efficacy in ameliorating dementia and AD is proved [133]. It is also reported to show cognitive improvement by increasing neuroblast formation, reducing neuronal death and BBB disruption in animals suffering from seizures, suggesting its significance in improving cognition in epileptic patients [134]. ...
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The incidences of traumatic brain injuries (TBIs) are increasing globally because of expanding population and increased dependencies on motorized vehicles and machines. This has resulted in increased socio-economic burden on the healthcare system, as TBIs are often associated with mental and physical morbidities with lifelong dependencies, and have severely limited therapeutic options. There is an emerging need to identify the molecular mechanisms orchestrating these injuries to life-long neurodegenerative disease and a therapeutic strategy to counter them. This review highlights the dynamics and role of choline-containing phospholipids during TBIs and how they can be used to evaluate the severity of injuries and later targeted to mitigate neuro-degradation, based on clinical and preclinical studies. Choline-based phospholipids are involved in maintaining the structural integrity of the neuronal/glial cell membranes and are simultaneously the essential component of various biochemical pathways, such as cholinergic neuronal transmission in the brain. Choline or its metabolite levels increase during acute and chronic phases of TBI because of excitotoxicity, ischemia and oxidative stress; this can serve as useful biomarker to predict the severity and prognosis of TBIs. Moreover, the effect of choline-replenishing agents as a post-TBI management strategy has been reviewed in clinical and preclinical studies. Overall, this review determines the theranostic potential of choline phospholipids and provides new insights in the management of TBI.
... The genetic inheritance is also a significant risk factor for AD after age. The risk of AD increases three to eight times in people with apolipoprotein E (ApoE) depending on their specific genetics (DeFina et al., 2013). Individuals having cardiovascular disease (CVD) including hypertension, high levels of low-density lipoprotein, atrial fibrillation, and thrombosis are more likely to develop AD and dementia (Breteler, 2000). ...
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Berberine is one of the most important quinoline alkaloids, which has shown numerous pharmacological activities. There are pieces of evidence that berberine serves as a promising substance for treating Alzheimer’s disease (AD). Recently, numerous studies on animal models have shown the neuroprotective role of berberine. AD is a complex disease having multiple pathological factors. Berberine restrains the deposition of amyloid plaques and neurofibrillary tangles. Substantial studies have demonstrated that berberine may also exhibit the protective effect against the risk factors associated with AD. This review illustrates the role of berberine in neuroinflammation, oxidative stress and its activity against acetylcholinesterase enzyme. It also focuses on the bioavailability and safety of berberine in AD. However, more investigations are required to explore the bioavailability and safety assessment of berberine and its new perspectives in limiting the AD-related pathogenesis and risk factors. Practical applications Current therapeutic measures only provide symptomatic relief against AD by slowing memory loss, resolving thinking problems and behavioral issues. In recent past years, many biological actions and potential therapeutic applications have been observed by berberine particularly in neurological diseases. Berberine has been investigated by various researchers for its activity against AD. This review demonstrates a variety of mechanisms by which berberine imparts its neuroprotective roles and provides the possible mechanism of action of berberine by which it prevents the formation of neurofibrillary tangles and disaggregation of amyloid beta plaques in AD. It also focuses that berberine limits the neuroinflammation and oxidative stress in AD. Pre-clinical aspects of berberine against AD are also discussed. Eventually, a prospect is formulated that berberine might be a therapeutically significant agent for treating and preventing AD.
... This compound can improve cognitive abilities [31] and isometric strength [32], and appears to have benefits for various other physical and mental performance tasks [33]. More importantly, α-GPC is marketed as a nootropic nutraceutical and pharmaceutical for the treatment of Alzheimer's disease [34]. It is estimated that by 2050, more than 130 million people will be diagnosed with Alzheimers [35]. ...
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As barley and oat production have recently increased in Canada, it has become prudent to investigate these cereal crops as potential feedstocks for alcoholic fermentation. Ethanol and other coproduct yields can vary substantially among fermented feedstocks, which currently consist primarily of wheat and corn. In this study, the liquified mash of milled grains from 28 barley (hulled and hull-less) and 12 oat cultivars were fermented with Saccharomyces cerevisiae to determine concentrations of fermentation products (ethanol, isopropanol, acetic acid, lactic acid, succinic acid, α-glycerylphosphorylcholine (α-GPC), and glycerol). On average, the fermentation of barley produced significantly higher amounts of ethanol, isopropanol, acetic acid, succinic acid, α-GPC, and glycerol than that of oats. The best performing barley cultivars were able to produce up to 78.48 g/L (CDC Clear) ethanol and 1.81 g/L α-GPC (CDC Cowboy). Furthermore, the presence of milled hulls did not impact ethanol yield amongst barley cultivars. Due to its superior ethanol yield compared to oats, barley is a suitable feedstock for ethanol production. In addition, the accumulation of α-GPC could add considerable value to the fermentation of these cereal crops.
Conference Paper
Alzheimer’s disease (AD) is a type of neuron disease; its nature causes the brain cells to degenerate and die. It’s a progressive disorder. It’s an incurable disease and develops memory impairment as it progresses. The precise diagnosis of AD plays a vital role in the patient’s health care, especially at its initial stage. The early detection of the disorder can help the patient get proper treatment and prevent further irreversible damage to the brain. This paper focuses on a comprehensive study of computer-aided diagnosis of AD by Convolution Neural Network (CNN). Many researchers have performed various ways through CNN for predicting AD at its dawn stage. The comprehensive study of paper shows various algorithms in CNN for early diagnosis of the disease through neuroimaging biomarkers
Alzheimer's disease is a fatal illness associated with two persistent problems in treatment i. ineffective drug transportation across the bio-membranes and ii. on-site targeting. Such problems originate from the combinational factors for non-specific targets, physicochemical limitations in the delivery of the active agents and insignificant permeability across blood-brain-barrier. In this context, block copolymers such as PLGA-PEG, PEG-PLA, Poloxamers, PLGA-PEG-PLGA triblock copolymers, etc. present interesting potential in the development of nano-sized carrier systems like polymerosomes, polymeric micelles, etc. for the management and treatment of Alzheimer's disease. Modifications of block copolymers display improvement in solubility and reduction in toxicity due to the process of complexation, functionalization, dose reduction and modification of kinetics for the rate of release. This review article focuses on new insights into different copolymers and their superiority over conventional polymers in Alzheimer's disease for long-term therapy in the body. Association of block copolymers to therapy of Alzheimer's disease overcome the limitations of drug delivery by offering attributes such as smaller molecular size (less than 150 nm), higher solubility owing to hydrophilic interactions between polymeric components and systemic environment, better entrapment efficiency (above 80%) due to large effective surface area and long-term stability for sensitive actives such as peptides, monoclonal antibodies, curcumin, resveratrol, catechins, etc. With such multifunctional features, block copolymers actively permeate the bio-membrane as polymeric nanoparticles, nanomicelles and polymerosomes using different mechanisms such as transcellular- and receptor-mediated transportation to reach target neural network as well as extra-neuronal amyloid-β plaques for anti-Alzheimer's disease activity with neuroprotective action. These polymers emerge as important components for personalized therapy with potential applications in biosensing, drug delivery, theranostics, etc. for qualitative and quantitative predictions in the detection and treatment of Alzheimer's disease.
This chapter focuses on common neurologic diseases, especially those with greater impact on the orofacial region and/or dental treatment. With optimal medical monitoring and poststroke care, patients can safely undergo invasive dental treatment, with appropriate consideration for stress reduction, medication interactions, adverse effects, neurologic deficit management, and control of underlying cardio/cerebrovascular risk factors. Patients with multiple sclerosis often experience exacerbation of neurologic symptoms in response to an elevation of the body's core temperature. Therapy for MS can be divided into three categories: treatment of acute attacks; disease‐modifying therapies; and symptomatic therapy. The genetic basis of Alzheimer's disease has been studied extensively, and specific genetic mutations have been implicated in both the familial and sporadic forms of the disease. Genetic implies the existence of known or presumed genetic mutation(s) where seizures are a known complication of the genetic disorder that is the result of the mutation(s).
Alzheimer's disease (AD) is considered as the most common cause of dementia in elderly population. While the exact mechanism of AD has not been discovered, hyperbolic oxygen therapy (HBOT) has been proven to be effective in the treatment of this degenerative disease. The objectives of this article are to review the literature available on molecular and physiological mechanisms underlying HBOT and its efficacy in treating AD and to review the effectiveness of HBOT as an alternate treatment intervention in both human and animal models. 391 full text articles were included in the review after literature search between 1980-2021 from two online data base (ScienceDirect and PubMed). The following key words were used: 'hyperbaric oxygen therapy' and 'Alzheimer disease.' Based on the outcomes of clinical and experimental studies, this review advocates the use of HBOT for the treatment of AD. This review explores future directions and recommends further research into a treatment protocol that will maintain long-term cognitive health of AD patients.
OBJECTIVE: Most investigations of pharmacotherapy for treating Alzheimer’s disease focus on patients with mild-to-moderate symptoms, with little evidence to guide clinical decisions when symptoms become severe. We examined whether continuing donepezil, or commencing memantine, is cost-effective for community-dwelling, moderate-to-severe Alzheimer’s disease patients. METHODS: Cost-effectiveness analysis was based on a 52-week, multicentre, double-blind, placebo-controlled, factorial clinical trial. A total of 295 community-dwelling patients with moderate/severe Alzheimer’s disease, already treated with donepezil, were randomised to: (i) continue donepezil; (ii) discontinue donepezil; (iii) discontinue donepezil and start memantine; or (iv) continue donepezil and start memantine. RESULTS: Continuing donepezil for 52 weeks was more cost-effective than discontinuation, considering cognition, activities of daily living and health-related quality of life. Starting memantine was more cost-effective than donepezil discontinuation. Donepezil–memantine combined is not more cost-effective than donepezil alone. CONCLUSIONS: Robust evidence is now available to inform clinical decisions and commissioning strategies so as to improve patients’ lives whilst making efficient use of available resources. Clinical guidelines for treating moderate/severe Alzheimer’s disease, such as those issued by NICE in England and Wales, should be revisited.
This report discusses the public health impact of Alzheimer’s disease (AD), including incidence and prevalence, mortality rates, costs of care and the overall effect on caregivers and society. It also examines the challenges encountered by health care providers when disclosing an AD diagnosis to patients and caregivers. An estimated 5.3 million Americans have AD; 5.1 million are age 65 years, and approximately 200,000 are age <65 years and have younger onset AD. By mid-century, the number of people living with AD in the United States is projected to grow by nearly 10 million, fueled in large part by the aging baby boom generation. Today, someone in the country develops AD every 67 seconds. By 2050, one new case of AD is expected to develop every 33 seconds, resulting in nearly 1 million new cases per year, and the estimated prevalence is expected to range from 11 million to 16 million. In 2013, official death certificates recorded 84,767 deaths from AD, making AD the sixth leading cause of death in the United States and the fifth leading cause of death in Americans age 65 years. Between 2000 and 2013, deaths resulting from heart disease, stroke and prostate cancer decreased 14%, 23% and 11%, respectively, whereas deaths from AD increased 71%. The actual number of deaths to which AD contributes (or deaths with AD) is likely much larger than the number of deaths from AD recorded on death certificates. In 2015, an estimated 700,000 Americans age 65 years will die with AD, and many of them will die from complications caused by AD. In 2014, more than 15 million family members and other unpaid caregivers provided an estimated 17.9 billion hours of care to people with AD and other dementias, a contribution valued at more than $217 billion. Average per-person Medicare payments for services to beneficiaries age 65 years with AD and other dementias are more than two and a half times as great as payments for all beneficiaries without these conditions, and Medicaid payments are 19 times as great. Total payments in 2015 for health care, long-term care and hospice services for people age 65 years with dementia are expected to be $226 billion. Among people with a diagnosis of AD or another dementia, fewer than half report having been told of the diagnosis by their health care provider. Though the benefits of a prompt, clear and accurate disclosure of an AD diagnosis are recognized by the medical profession, improvements to the disclosure process are needed. These improvements may require stronger support systems for health care providers and their patients.
Eighty-three brains obtained at autopsy from nondemented and demented individuals were examined for extracellular amyloid deposits and intraneuronal neurofibrillary changes. The distribution pattern and packing density of amyloid deposits turned out to be of limited significance for differentiation of neuropathological stages. Neurofibrillary changes occurred in the form of neuritic plaques, neurofibrillary tangles and neuropil threads. The distribution of neuritic plaques varied widely not only within architectonic units but also from one individual to another. Neurofibrillary tangles and neuropil threads, in contrast, exhibited a characteristic distribution pattern permitting the differentiation of six stages. The first two stages were characterized by an either mild or severe alteration of the transentorhinal layer Pre-alpha (transentorhinal stages I-II). The two forms of limbic stages (stages III-IV) were marked by a conspicuous affection of layer Pre-alpha in both transentorhinal region and proper entorhinal cortex. In addition, there was mild involvement of the first Ammon's horn sector. The hallmark of the two isocortical stages (stages V-VI) was the destruction of virtually all isocortical association areas. The investigation showed that recognition of the six stages required qualitative evaluation of only a few key preparations.