SUMÁRIO

1. Introduction......................................................... 3
2. Fisiopatologia .............................................................. 4
3. Manifestações clínicas............................................. 8
4. Diagnosis .................................................................11
5. Therapeutics.................................................................16
Bibliographic references ........................................21
ALZHEIMER'S DISEASE (NEUROLOGY) 3

1. INTRODUCTION Overall, Alzheimer's disease is

more prevalent among individuals
Alzheimer's disease is the type of over 65 years old, without any relationship
most common dementia, frequent interest with ethnic and racial differences.
mind associated with senile dementia,
They are still not well established.
defined as a process involving
I sell ß-amiloidosis and neurodegeneration
differences in involvement
among the sexes, however, in terms of ab-
limbic and isocortical generation, charac-
there are more women with this
characterized mainly by amnesia
disease, due to life expectancy
anterograde. With the evolution of the do-
the women's being greater than that of the
start, in addition to the loss of memory re-
men. Thus, the risk factors
however, the patient also suffers from
involved with development
other cognitive deficits, such as dis-
The disease of Alzheimer is age.
language functions, reduction of
advanced and family history, in the-
speed of thought, difficult-
tanto, evidências sugerem que o Dia-
given in the spatial-temporal orientation,
diabetes Mellitus and arterial hypertension
in addition to deficit in executive function and
Systemic can have some relation
behavioral changes, mood with the pathogenesis of this disease.
the personality, conditions that turn-
the patient is quite debilitated and
dependent.
ALZHEIMER'S DISEASE (NEUROLOGY) 4

INTRODUCTION TO ALZHEIMER'S DISEASE

ATTACK
BOTH EQUALLY
THE SEXES

ELDERLY > 65 YEARS SENILE DEMENTIA

DISEASE OF
ALZHEIMER
ALTERATIONS OF
AMNESIA BEHAVIOR,
Anterograde HUMOR AND
PERSONALITY

Cognitive deficit

DIFFICULTY REDUCTION OF
DYSFUNCTION OF Dysfunction
OF ORIENTATION SPEED OF
LANGUAGE EXECUTIVE
SPACE-TIME THOUGHT

2. PATHOPHYSIOLOGY a precursor protein of amyloid

(APP) starting from processing es-
The pathophysiology of Alzheimer's disease
improper specific – are proteins
mer involves two main structures
mutants, folded in an unusual way
neurotic plaques and tangles burnout and that cause inflammation
neurofibrillary. As neurotic plaques
in the various bodies that can be
amyloid nuclei, surrounded
deposit. These plates are found
of neurons in degeneration (neuri-
traded mainly in the hippocampus,
dystrophic bodies), which in turn are
amygdala and in the neocortex, usually
fragments of axons and dendrites
saving the motor and sensory cortex
neurons. The main component
(which also happens with the emara-
amyloid of these structures is the peptide-
neurofibrillary tangles.
the beta-amyloid, which is derived from
ALZHEIMER'S DISEASE (NEUROLOGY) 5

Figure 1. Plates with neurites around the amyloid nucleus. Source:[Link]

com/2013/01/[Link]

A PET CT (computed tomography by emission Alzheimer, but it is worth stressing that the
of positron), performed with ligands the amount of this peptide is not
with an affinity for beta-amyloid, mos- related to the severity of the do-
Tram that the amyloid protein begins However, it is believed that these
to accumulate in the neocortex by up to deposits are the main agents
about 20 years before they emerged related to induction or acceleration
the clinical signs of dementia pro- from neuronal injury.
called by Alzheimer's disease.
When this occurs, many deposits
of beta-amyloid peptides are found-
traced in the neurotic plates of the neo-
cortex, thus, these plates represent
it's the final stage of the process of
ALZHEIMER'S DISEASE (NEUROLOGY) 6

The neurofibrillary tangles, by

PAY ATTENTION! Most cases of do- your turn, they are intracellular aggregates-
Alzheimer's disease has an idiopathic cause. res in a quite phosphorilated way
yes, however some genes seem to be
from tau protein, associated with mi-
associated with its emergence, all
those involved in the production of the peptide cortubules. The phosphorylated tau protein
beta-amyloid, namely: pro-gene self-aggregates, leading to the formation
Amyloid precursor protein (APP) and the two entangled. These structures
genes of pre-selina 1 and 2 (PS1 and PS2).
The first, APP gene, may present
are frequently found in
to have mutations that cause production entorhinal cortex, basal prosencephalon
excessive of ẞ-amyloid, which leads to raphe nuclei, in addition to the hippocampus
early onset of the disease, and there is evidence
the amygdala.
that these mutations are associated
cities with the emergence of the disease of
Alzheimer in carriers of the Syndrome
Down syndrome (they have a copy of the gene)
of the APP due to trisomy). Regarding
to pre-selina, protein involved in the de-
gradation of the APP molecule, muta-
actions in your genes (PSEN1 and PSEN2)
also lead to excessive production of
Beta-amyloid, being likewise associated
cities with the early onset of the disease
(40 to 60 years old). There is still or-
trouble gene involved in the emergence of
Alzheimer's disease, which is the gene that
codes for the protein apoE, related
with the transport of lipids, whose muta-
actions are associated with the emergence
late stage of Alzheimer's disease.

Figure 2. Neurofibrillary tangles. In D, silver staining showing a tangle in the neuronal cytoplasm. In
And, tangled (upper left) and neurites around a plate (lower right) containing tau. Source: KUMMAR,
Vina, et. Al. Robbins & Cotran. Pathologic Basis of Disease. 8th ed. Rio de Janeiro. Elsevier, 2010
ALZHEIMER'S DISEASE (NEUROLOGY) 7

Meanwhile, as the disease of the disease they are found in the

progress, the neural tangles occipital lobes and motor cortices
brilares have their regional extension primary sensitives.
augmented. These structures appear- The location of the neural tangles
some in the medial temporal lobe and trunk
rofibrillars is directly related
cerebral in people without deficits in nothing to the clinical evolution of the symptoms
cognition around the fourth decade specifics of Alzheimer's, as well as
of life, however in people with pre- the severity of the disease. With that, in
disposition to Alzheimer's disease, initial clinical manifestations, the largest
transsynaptic dissemination occurs the concentration of these structures is in
these entanglements for areas of entorhinal cortex and in the hippocampus, re-
cortical associations. Thus, when- regions related to memory
the symptoms of the disease emerge, the declarative episodic. However, it is worth
neurofibrillary tangles are en- point out that these structures are not
found in the neocortex of associations
specifics of Alzheimer’s disease,
of the frontal, parietal lobes and has- being able to be found in others
temporal, and in the more advanced stages neurological diseases.

PATHOPHYSIOLOGY OF ALZHEIMER'S DISEASE

PATHOPHYSIOLOGY
[Link]
ALZHEIMER

Neuritic plaques NEUROFIBRILLARY TANGLES

beta-amyloid TAU PROTEIN

NEOCORTEX Nuclei of the Raphe

PROSENCÉFALO BASAL

ENTORHINAL CORTEX

HIPPOCAMPUS

AMYGDALA
ALZHEIMER'S DISEASE (NEUROLOGY) 8

3. MANIFESTATIONS disease and can be persistent in

CLINICS about 20% of cases.
The initial clinical manifestation more This framework progresses as the
common factor of Alzheimer's disease is the disease advances to the Inter- stages
intermediate and Advanced. In these phases,
anterograde amnesia. This can be
identified from some that the patient encounters difficulties each
such as forgetting events and greater ones to carry out their tasks
recent conversations, incorrect placement daily fasts, becoming dependent
of objects, problems to accompany for basic activities, such as feeding
take a shower, get dressed, and do personal hygiene. In
to lose oneself in neighborhoods
knowns and difficulty to remember terminal stages of the disease, all
to complete usual tasks. the communication capabilities
At the Alzheimer's level, the function of the me-
they are lost, however in many
in cases, mobility is preserved until
declarative episodic memory can be
late.
lost, however the previous knowledge
vio pode permitir que os pacientes Patients with Alzheimer's disease
sigam suas rotinas normais, a menos they usually die by drowning
that something beyond the usual is demanded more diseases that affect the elderly
enabled individuals who do not present this
given to them. However, at this stage
of the disease, errors may occur in the to- dementia, such as sepsis, pneumonia
drug shortage and difficulty and heart failure, main-
to deal with money and finances, mind due to the fact that these
requesting the assistance of family members, individuals lose the ability to
besides changes in behavior express your needs and the fal-
to, personality and humor, manifests- take proper care and well
two like depressed humor, which can trained may let pass if-
occur in parallel with the affliction born of discomfort, which when not
of memory, apathy, loss of initiative noted early, they evolve into
and loss of interest in hobbies, more serious frames. For example,
for example. A smaller portion of patients with Alzheimer's in places
patients can still go through with in- warm or favorable conditions
Sonia or anorexia, a fact that does not exist of suffering from dehydration, whose signs
relationship with more or less pregnant can go unnoticed by the cui-
of the disease. There are also reports of donor, evolving to death by shock
delusions and psychotic behavior, hypovolemic.
that increase with the progression of The duration and clinical evolution of the do-
the onset of Alzheimer ’s is long, however
ALZHEIMER'S DISEASE (NEUROLOGY) 9

variable, taking the patient with de- there are atypical forms of this syndrome,
mild dementia until death during the period of such as posterior cortical atrophy, in the
2 to 3 years or a decade. It's worth it. What are the visuospatial deficits?
it is clear that, despite the main symptom constructive praxia without amnesia
this disease is a memory deficit, anterograde.

Figure 3. Areas of the brain involved with memory. Source://[Link]/wp-content/uploads/2019/05/Captura-

-[Link]
ALZHEIMER'S DISEASE (NEUROLOGY) 10

LEARN MORE!
Memory is the capacity to acquire, store, and recall information, being one of the
main neurological functions that make individuals distinct. Acquisition depends on the
learning mechanisms, while evocation is related to remembrance. Exis-
there are two main types of memory: declarative memory and non-declarative memory (procedural memory)
declarative memory is the one that can be described in words, while
procedural memory is related to the learning of motor sequences. There is
still the classifications of long-term or short-term memory, which differ by time
of information retention, and retrograde and anterograde memory, which are distinguished by
ability to remember previous information or to store new information,
respectively. The cortical areas of the brain responsible for memory include primarily
specifically the hippocampus, the dentate gyrus, the entorhinal cortex, the parahippocampal cortex and the
posterior cingulate cortex, each one more or less involved with certain aspects of
memory. However, other brain regions may be related to this cognitive function,
especially in memory formation, such as the amygdala, important in processing
the emotions, and cerebellum, fundamental in motor functions.

CLINICAL MANIFESTATIONS

REMEMBRANCE
INITIAL EVENTS
PREVIOUS

DEPRECATED HUMOR DELIRIUMS

MANIFESTATIONS
CLINICS

BEHAVIOR
MOTOR DEFICIT
PSYCHOTICS

Cognitive Deficit

DIFFICULTY
REDUCTION OF
OF ORIENTATION DYSFUNCTION OF AMNESIA Dysfunction
SPEED OF
SPACE- LANGUAGE Anterograde EXECUTIVE
THOUGHT
TEMPORAL
ALZHEIMER'S DISEASE (NEUROLOGY) 11

4. DIAGNÓSTICO cerebrovascular (stroke), other diseases

neurodegenerative diseases and even
The diagnosis of Alzheimer's disease secondary neurological manifestations
it is based on the clinical history, doses for the use of medications.
histopathological findings, biomarker-
pains and imaging exams. The histo- Imaging tests assist in
clinical guidance directs the diagnosis to determination of the diagnosis of Al-
in the dementias, it is likely that the Alzheimer, which is a diagnosis of
substitution due to Alzheimer's disease inclusion, that is, if the history and the
when the patient shows onset imaging exams suggest Al-
insidious of the symptoms, that is, has Alzheimer and other exclusions may
gradual onset and evolves into loss of to be verified, it is possible to confirm
memory, in addition to the worsening of the the disease safely. Thus, pa-
cognition through report or observation of patients with suspected Alzheimer's
close people. The cognitive deficits can be submitted to the resonance
magnetic resonance imaging (MRI), computed tomography
Initial infinitives can be divided
in amnesic disorder or disorder positron emission (PET-CT) and to-
not amnesia (uncommon), which in- positron emission tomography
language disorder (aphasia), with fluorodeoxyglucose (FDG-PET).
visuospatial disorder or disorder Brain images can be di-
behavioral/executive. lived in structural, functional or
histological. The structural images
Although there are deficits in capacity
are provided by RM or TC, and are
cognitive daddy, the other aspects
perform neurological examination in the disease of
mainly used to ward off
other causes of dementia, such as
Alzheimer usually presents
tumors, hematomas or accidents
as normal, being relatively
vascular.
frequent extrapyramidal signs,
including rigidity, bradykinesia, gait In RM, patients with Alzheimer's
of dragged feet and postural changes they present exaggerated diffuse atrophy
trials. Motor and sensory functions for the age, involving special-
Riais are saved, thus, abnormal the hippocampal region and others
oculomotor, cerebellar or areas of cortical associations
the identified peripheral nerves and, like the temporal wolves late-
in the neurological exam suggest or- rays, lower parietal lobes, cortex
through neurological diseases and not Al- posterior cingulate and frontal lobes
Alzheimer. It is important to emphasize this, sides. In addition, the RM also
since others must be dismissed reveals the dilation of the ventricles
causes of dementia, such as disease the widening of the grooves
cortical, mainly in the regions
ALZHEIMER'S DISEASE (NEUROLOGY) 12

volumetric MRI has other dementias, being potentially useful

has been used, as Alzheimer's causes early diagnosis of the disease.
reduction of special brain volume In frontotemporal dementia (FTD),
mind in the medial wolf, assisting in for example, atrophy is more marked
differential diagnosis regarding the in the frontal lobe.

Figure 4. Series of coronal images from an MRI of a patient with Alzheimer’s. The image on the left was from a
the exam was conducted when the patient presented clinically normal and the image on the right was taken 11 years later,
when the patient presented with dementia. A drastic hippocampal atrophy is observed with the progression of the disease.
Source: GOLDMAN, Lee, SCHAFER, Andrew L, et al. Goldman-Cecil. Medicine. 25th ed. Rio de Janeiro. Elsevier, 2018.

Positron emission exams provides histological image. Of this

they provide functional images, being The PET-CT is quite useful in the di-
sensitive to brain metabolism, differentiation of Alzheimer and other
being useful for the pre-diagnosis mentions, for this disease presents
Alzheimer's code, as well as for the greater load of amyloid plaques of
follow-up on the evolution of the do- that DFT and other neurodegenerative diseases
The FDG-PET is based on the degree generative. However, how these pla-
of glucose metabolism, displaying cases are also present in pes-
reconstructions of the capture relationship healthy elderly, it is questionable if
regional glucose uptake in the cortex, your identification helps in detection
how PET-CT evaluates specimens early Alzheimer's.
the abnormal deposition of amyloid and
of the tau protein and, therefore, it is also
characterized as an exam that
ALZHEIMER'S DISEASE (NEUROLOGY) 13

Figure 5. Images from PET-CT and MRI in normal individuals, with Alzheimer's disease and with FTD.
The green signal represents low levels of nonspecific binding of white matter. The arrows represent retention.
prominent amyloid imaging agent in the frontal and parietal cortices. Source:[Link]
dementia-role-of-mri/a509797720938b_FDG-[Link]
ALZHEIMER'S DISEASE (NEUROLOGY) 14

Figure 6. Image of the FDG-PET. The warmer colors (yellow and orange) represent areas of normal uptake.
of glucose, while the cool colors (blue and green) represent the regions with hypometabolism, showing that in the
In Alzheimer's disease, there is hypometabolism in the temporal and parietal regions. MCI: mild cognitive impairment (in
Mild cognitive impairment[Link]
[Link]/[Link]

Here! tau, as well as the genes of PSEN1,

PSEN2 and APP can also sub-
The diagnosis of Alzheimer's disease
manage the diagnosis of Alzheimer.
definitive shit is done through the sheet
two histopathological, characterized Alzheimer's disease can be con-
due to the significant presence of plates merged with other pathologies, that
neuritic and neurofibrillary tangled must be removed at the time of
wolves, being necessary the presence of diagnosis. Dementia by corpus-
at least six neurotic plates and Lewy bodies can be confused
visible neurofibrillary tangles with Alzheimer's due to the characteristics of
in the frontal, temporal, or parietal cortex histological cases, however, it progresses with
together, the diagnosis of Al- Parkinsonism, visual hallucinations
Alzheimer is predominantly made prominent and a specific type of
through the medical history and the examinations sleep disorder. In addition to the dementia-
of image, since the biopsy is a Lewy body disease
invasive procedure and must be avoided Alzheimer presents other diag-
in cases where it can con- differential diagnoses, namely: disease-
to affirm the pathology by other means. Huntington's disease, Wilson's disease,
Thus, the definitive certainty of the disease amyotrophic lateral sclerosis, among
Alzheimer's is only established by others, which differ mainly
necropsy. The biomarkers, for their for presenting a component
can be searched in the liquid motor not characteristic of the disease of
of cerebrospinal fluid (CSF) through Alzheimer. However, Alzheimer is
puncture (less invasive than the biopsy) commonly confused with the disease-
yes, but it is also a method that it is a cerebral vascular, of which it is practice-
should be avoided). The main biomar- mind impossible to distinguish.
What is amyloid beta, but the protein
ALZHEIMER'S DISEASE (NEUROLOGY) 15

MAP – DIAGNOSTIC

PSEN1 GENE
TAU GENE FROM THE APP beta-amyloid
E PSEN2

MARKERS
BIOLOGICALS

FDG-PET
EVENT
insidious
IMAGING EXAMS
CLINICAL HISTORY DIAGNOSIS RM
PRINCIPAIS
SINTOMAS
PET - TC

Apraxia
EXAM
HISTOPATHOLOGICAL

Execution disturbances

NEURITIC PLAQUES ENTANGLED

Difficultiesinorientation NEUROFIBRILLARY
spatio-temporal

Spatial-visual disturbance

Disturbances of
Language

Mainly
Memory disorders
anterograde memory
ALZHEIMER'S DISEASE (NEUROLOGY) 16

5. THERAPEUTICS transmission, since the acetylcholine-

terase is an enzyme that degrades the
Alzheimer's disease is still not
acetylcholine released, regulating its
has an established cure, being bad-
action time. Thus, the inhibitors
just take care of pa-
of acetylcholinesterase are choline
palliatives that reduce the symptoms and
metrics, being in these groups the do-
they seek to ensure higher quality of
nepezil (5 to 10 mg/day), galantamine
life to patients. With that, there are
(16 to 24 mg/day), rivastigmine (6 to 12
two main classes of drugs used in the ICU
mg/day), among others, that can be
used in the treatment of this disease,
administered orally and some
what are acetylcholine inhibitors
the terrace and the mametina.
by transdermal patch. These drugs
delay the progression of symptoms
The main neurotransmitter deficit for 6 to 12 months in patients with
in Alzheimer's disease it is in the trans- Moderate to a level of Alzheimer's
cholinergic mission, that is, significant but clinically marginal
coordinated by acetylcholine. Thus, normal, but they do not do it at 3 years old
acetylcholinesterase inhibitors of the disease (average time it takes to
are used for acting to increase death). However, there is no evidence of
extending the action time of acetylcholine that these medications delay the
at the synaptic cleft, intensifying its biological progression of this dementia.

Figure 7. Mechanism of action of acetylcholinesterase inhibitors. The first image shows the normal action of
enzyme, converting choline into acetic acid, while the second image shows the inhibition of this enzyme by car-
Organophosphates, which can be reversible or irreversible. The drugs used in the treatment of the disease
Alzheimer's inhibitors can be reversible or irreversible. Source:[Link]
blank-8
ALZHEIMER'S DISEASE (NEUROLOGY) 17

Memantine is a non-antagonist neural and neurotoxicity. The activation

competitive NDMA receptor of These receptors promote the opening
low to moderate affinity, which of calcium and sodium channels, favors-
acts on the transmission of glutamate. I give my influx, as well as the exit
Non-competitive antagonists of potassium. Memantine prevents the
we act on a different receiver than calcium and sodium intake, as well as the
agonist, causing attenuation of the potassium output, regulating the levels
effect generated by the agonist. The recep- elevated levels of glutamate that can
the NMDA receptor of glutamate is one of generate neuronal dysfunction. This dro-
main receptors of the glu system it seems to slow the progression of
taminergic, developing impose- functional decline of patients with
such a role in the mediation of functions Moderate to severe Alzheimer's when
of cognition, memory, plasticity used in a dose of 20mg/day.

Figure 8. Mechanism of action of memantine. Source:[Link]

ALZHEIMER'S DISEASE (NEUROLOGY) 18

Other treatments! dementia, however there is no evidence

In addition to the drugs already mentioned, al- what are protective against the disease
that of Alzheimer. When it begins
guns estudos revelaram que a vita-
the manifestations of this disease are
mine E is efficient in the control of pro-
I need to properly guide the fami-
Alzheimer's progression in patients
lia and caregivers, especially in
in moderate to severe stages. The
regarding security issues
Vitamin E acts as an antioxidant.
regarding the supervision of medications,
Dante, 'fighting' the free radicals
finance and in the direction of vehicles.
of organisms, reducing the injury of It is still advisable to avoid and/or supervise
neurological tissue. However, other vi-
the use of potentially useful tools
tamins did not show equal efficacy
dangerous, like focus weapons. Besides
in the treatment of Alzheimer.
therefore, like patients with Alzheimer's
It is important to point out that there does not exist
they commonly roam and get lost
there are preventive treatments for them, distancing themselves from their homes,
Alzheimer. A healthy diet and it is important for the family to pay attention to
balanced, associated with physical exercises identify them in some way, such as
psychological and cognitive leisure activities with necklaces or even tattoos
stimulating minds are advised visible that have information of
you see, especially for protecting family contacts.
against arterial hypertension and diabetes
yes, what are the risk factors for this
ALZHEIMER'S DISEASE (NEUROLOGY) 19

Management Map

MANAGEMENT

Pharmacological Non-pharmacological

Contact and Social Interaction

INHIBITORS OF
MEMANTINE
COLINESTERASES

Supervised physical activity

ANTAGONIST
POTENTIALIZES
OF RECEPTOR OF
ACETYLCHOLINE Productive activities (e.g., handicrafts)
GLUTAMATE

DONEPEZILA

Galantamine

RIVASTIGMINE
ALZHEIMER'S DISEASE (NEUROLOGY) 20

MENTAL MAP - ALZHEIMER'S DISEASE

AMNESIA
DEPRESSED HUMOR Cognitive deficit
Anterograde

MANIFESTATIONS
CLINICS

MEMANTINE

Neuritic plaques
DISEASE OF INHIBITORS OF
PATHOPHYSIOLOGY THERAPEUTICS
ALZHEIMER COLINESTERASES
ENTANGLED
Neurofibrillary
NON- CONDUCTS
PHARMACOLOGICAL

DIAGNOSIS

EXAM MARKERS
CLINICAL HISTORY IMAGING EXAMS
HISTOPATHOLOGICAL BIOLOGICALS
ALZHEIMER'S DISEASE (NEUROLOGY) 21

REFERENCES
BIBLIOGRAPHICAL
GOLDMAN, Lee, SCHAFER, Andrew L, et al. Goldman-Cecil. Medicine. 25th ed. Rio de Ja-
Neuro. Elsevier, 2018.
KUMMAR, Vina, et al. Robbins & Cotran. Pathological Basis of Disease. 8th ed. Rio de
January. Elsevier, 2010.
Rowland LP, Pedley TA. Merritt: Treatise on Neurology. 12th ed. Rio de Janeiro. Publisher
Guanabara Koogan, 2011.
MACHADA, Angelo, HAERTEL, Lucia M. Functional Neuroanatomy. 3rd ed. São Paulo.
Atheneu, 2013.
ALZHEIMER'S DISEASE (NEUROLOGY) 22