SlideShare a Scribd company logo
ALZHEIMER'S DEMENTIA
Presenter -Dr.ANUSREE.N
DEFINITION
The word Dementia derives from the Latin worddementatus, meaning out of one’s mind,
and, as such, was potentially applicable to any state of psychopathology.
Dementia refers to a disease process marked by progressive cognitive impairment in clear
consciousness.
The fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5)
describes dementia, now subsumed under the term major neurocognitive disorder, as
significant cognitive impairment in one or more of the domains of
1) complex attention,
2) executive function,
3) learning and memory,
4) language,
5)perceptual motor ability, and
6)social cognition.
• These deficits represent a decline from a previous level
of functioning, so dementia does not refer to low
intellectual functioning or mental retardation that are
developmental and static conditions.
• This decline is often noted by the individual affected, a
family member or other caretaker, or the clinician, and
should be demonstrated on standardized
neuropsychological testing, and if that is not possible,
another measurable clinical assessment.
• These cognitive deficits interfere with independent
functioning in daily activities, and cannot occur
exclusively in the context of a delirium, or be better
explained by another mental disorder.
Dementia of the
Alzheimer's
Type
• In 1907, Alois Alzheimer first described
the condition that later assumed his
name.
• In 1906 , he reported the case of a 51-
year-old woman with a progressive
cognitive disorder marked by memory
loss, confusion, topographical
disorientation, aphasia, and prominent
neuropsychiatric manifestations of
persecutory delusions, misidentifications,
and behavioral disturbances. At her death
4 years later, autopsy revealed profound
atrophy, amyloid plaques, and
neurofibrillary tangles.
EPIDEMIOLOGY
• The incidence of Alzheimer disease increases
with age from about 0.5 percent per year at ages
65 to 69,
• 1 percent per year from age 70 to 74,
• 2 percent per year from age 75 to 79,
• 3 percent per year from age 80 to 84 and
• 8 percent per year after age 85.
• With the aging of the population, projections
estimate that, by the year 2050, 13.8 million
people over the age of 65 are estimated to have
Alzheimer disease.
• While MCI is more common in men, the prevalence of AD dementia is
higher in women.
• The lifetime risk of developing Alzheimer dementia from the age of 45
is approximately 10% for men and 20% for women
• Age is the most important risk factor for AD dementia
Etiology
• The etiology of Alzheimer disease is multifactorial &
is influenced by multiple genes, by environmental
factors, and by their interactions.
• 1) GENETICS: play a major role as evident by twin
studies the concordance rate for monozygotic twins,
which is higher than the rate for dizygotic twins ( 43
percent vs. 8 percent, respectively).
A) Early-Onset Alzheimer Disease.: (<65 years)
Mutations at three genetic loci :
-APP gene located on chromosome 21 (Autosomal
Dominant)
- Presenilin-1 (PS1) on Chromosome 14
(Autosomal Dominant)
- Presenelin-2 (PS2) on Chromosome 2.(These
mutations appear to be rare)
Etiology
1) GENETICS:
B) Late-Onset
Alzheimer
Disease.: (>65
years)
Signifigant
association with
Etiology
2) Neuropathology.
The classic gross neuroanatomical observation
of a brain from a patient with Alzheimer's
disease
is diffuse atrophy with :flattened cortical sulci
and enlarged cerebral ventricles.
• Macroscopically:
• the brains of early Alzheimer disease patients
may appear grossly normal, or with atrophy
confined to the hippocampus, and often most
easily recognized by increased volume of the
inferior horn of the lateral ventricles.
• As the disease progresses, widened sulci
throughout the cortex and increased
ventricular size are seen.
• Atrophy in the posterior temporal, parietal,
and frontal lobes is often most prominent.
Etiology
2) Neuropathology.
The classic and pathognomonic microscopic findings are
- Senile Amyloid plaques,
-neurofibrillary tangles,
-neuronal loss (particularly in the cortex and the hippocampus ),
-synaptic loss (perhaps as much as 50 percent in the cortex),
and granulovascular degeneration of the neurons.
Etiology
• Senile plaques, also referred to as amyloid plaques,
more strongly indicate Alzheimer's disease, although
they are also seen in Down syndrome and, to some
extent, in normal aging.
• are the defining lesion of Alzheimer disease, composed
of insoluble deposits of fibrillar Aβ protein, /31A4.
• Surrounding this central core are dystrophic neurites,
microglial cells, and reactive astrocytes.
• Amyloid plaques are first found throughout the
neocortex, followed by entorhinal cortex and
hippocampus, then subcortical regions.
• The number and the density of senile plaques present in
postmortem brains have been correlated with the
severity of the disease that affected the persons.
Etiology
• Neurofibrillary tangles :
• are intracellular inclusion bodies, composed of cytoskeletal
elements which contain paired helical filaments composed of
aggregates of hyperphosphorylated MAPT .
• Neurofibrillary tangles are first found in the entorhinal cortex
and spread from there to the hippocampus and lateral
temporal lobe, then more widely through the neocortex.
• The presence of neurofibrillary tangles is not pathognomonic
for Alzheimer disease, as they are the principal lesion in
MAPT-related FTDs
• they also occur in Down syndrome, dementia pugilistica
(punch-drunk syndrome), Parkinson-dementia complex of
Guam, Hallervorden Spatz disease, and the brains of normal
people as they age.
Etiology
• Additional pathological features of Alzheimer disease include :
• α-synuclein, which may be detectable in as many as one half of individuals
with Alzheimer disease.
• These Abnormal aggregates most commonly are found as thread-like
deposits or as intraneuronal inclusions (Lewy bodies) in the amygdala and
transentorhinal cortex, though Lewy bodies may also be present in the
neocortex.
• Transactive response DNA-binding protein of 43 kDa (TDP-43) is the most
frequently aggregated disease protein in frontotemporal lobar degeneration.
• Recently it has been found that TDP-43 proteinopathy is also present in many
cases of Alzheimer disease.
• found predominantly in the mesial temporal lobe, and to a lesser degree in
neocortical areas.
• Neuronal loss, most markedly in the entorhinal cortex and hippocampus.
Later in disease, loss of cholinergic neurons in the nucleus basalis, as well as
loss of brain stem noradrenergic and serotonergic neurons, occurs.
• Granulovacuolar degeneration and the presence of Hirano bodies, most
commonly affecting pyramidal neurons in the hippocampus, may be found.
Etiology
2)Neuropathology. Overproduction
& self-aggregation of Aβ into soluble
low-n oligomers is a primary source
of synaptotoxicity in Alzheimer
disease
Etiology
• In addition to the direct effects of Aβ on
synapse loss, Aβ may lead to synapse loss
and neuronal death via other downstream
effectors.
• For example, Aβ contributes to the
hyperphosphorylation of microtubule-
associate protein τ (MAPT), which enhances
its aggregation. Overproduction and
aggregation of MAPT have been shown to
cause synapse loss and neuronal death
independent of the effects of Aβ.
Etiology
• 3) Neurotransmitters:
• The neurotransmitters that are most often implicated in
the pathophysiological condition of Alzheimer's disease are
• 1)Acetylcholine : Level decreased due to specific
degeneration of cholinergic neurons is present in the
nucleus basalis of Meynert .
• Decreased Choline Acetyltransferase concentration in Brain (
Key Enzyme for synthesis of Ach)
• Cholinergic antagonists, such as scopolamine and atropine,
impair cognitive abilities, whereas cholinergic agonists, such
as physostigmine and arecoline, enhance cognitive abilities.
• 2) Norepinephrine, Level decreased due to degeneration of
norepinephrine-containing neurons in the locus ceruleus.
• 3) Two other neurotransmitters implicated in the
pathophysiological condition of Alzheimer's disease are the
neuroactive peptides:
• somatostatin and corticotropin
Etiology
• 3) Other Causes:
• Abnormality in the regulation of membrane phospholipid
metabolism results in membranes that are less fluid-that is,
more rigid-than normal.
• Several investigators are using molecular resonance
spectroscopic imaging to assess this hypothesis directly in
patients with dementia of the Alzheimer's type.
• Aluminum toxicity has also been hypothesized to be a
causative factor because high levels of aluminum have been
found in the brains of some patients with Alzheimer’s disease,
but this is no longer considered a significant etiological factor.
• Excessive stimulation by the transmitter glutamate that may
damage neurons is another theory of causation.
• Aβ appears to destabilize dendritic spines, resulting in
retraction and synapse loss, via modulation of the function of
both α-amino-3-hydroxy-5-methyl-4-isoazole-proprionic acid
(AMPA) and N-methyl-D-aspartate (NMDA) classes of
postsynaptic glutamate receptors. It is therefore not surprising
that memantine (Namenda), a low-affinity NMDA antagonist
that functions to modulate activation of NMDA receptors, has
been shown to be of benefit in Alzheimer disease.
RISK AND
PROTECTIVE
FACTORS.
• 1) Age. Age is the greatest risk factor for developing Alzheimer
disease. Whereas approximately 3 percent of people older than 65
years of age have Alzheimer disease, about one third of people older
than 85 years of age have Alzheimer disease.
• 2)Education. people with less education are at increased risk of
developing Alzheimer disease.
• Functional neuroimaging findings of patients with Alzheimer disease
indicate that people with higher educational attainment or higher
premorbid intellectual functioning but similar levels of dementia
severity have more severe findings on neuroimaging.
• This suggests a protective effect of education, in that greater
neuropathology is needed to produce the same clinical changes.
• Those with higher levels of cognitive reserve may be able to utilize
other alternative neural networks as levels of neuropathology
increase, thus compensating for the disease burden, up to a point.
• Studies have reported that there is a relationship between cognitive
decline and neocortical synaptic density in Alzheimer disease.
• There is also some evidence that education can increase synaptic
density.
• In addition to education, participation in certain leisure activities,
including reading, dancing, playing board games, and playing musical
instruments, is associated with a decreased dementia risk
• Early-life cognitive abilities also may play an important role in
dementia risk. (good linguistic ability and grammatical complexity in
early life>less chance of AD in adult life)
RISK AND
PROTECTIVE
FACTORS.
• 3) Estrogen. A number of observational studies have
suggested that estrogen replacement after menopause
reduced the risk of Alzheimer disease.
1.On a neuronal level, estrogen increases
-density of a synaptic population lost in Alzheimer disease,
-excitatory synapses onto dendritic spines, in both
hippocampus and cortex.
2. It also may interact with APP processing, to increase
brain Aβ concentrations.
3. Estrogen inhibits oxidation of lipids, lipoproteins, and
nucleic acids in vitro and is protective of cells in culture
against a number of insults, including Aβ.
However current recommendation does not approve HRT
in Alzheimers disease.
RISK AND
PROTECTIVE
FACTORS.
4) Head Trauma. can lead to overexpression of APP,
increase inflammatory mediators, and cause
deposition in the brain.
The effects of traumatic injury on Aβ may be
mediated by APOE genotype .
5) Inflammation. increased concentrations of acute
phase reactants, cytokines, and complement protein.
Population studies have demonstrated that
nonsteroidal anti-inflammatory drug (NSAID) or
corticosteroid use is associated with a decreased risk
of developing Alzheimer disease;
But timing of NSAID use & associated risk of bleeding
and peptic ulcer is debatable topic.
RISK AND
PROTECTIVE
FACTORS.
6) Nicotine. The literature is unclear.
Indirect stimulation of nicotinic receptors via use of
acetylcholinesterase inhibitors has benefit in the treatment
of Alzheimer disease..
However Smoking causes signifigant cerebro-
cardiovascular risk and associated oxidative stress ,
neuroinflammation leads to the development of Dementia.
7) Oxidative Stress. Aβ can damage and kill neurons by
inducing oxidative stress, as can the microglial
inflammatory reaction surrounding plaques.
Increased markers of oxidative stress seen in Alzheimers
Disease.
However Antioxidants VIT E & Ginkgo Biloba being tried
but no conclusive evidence
• Impaired sleep
• Hypertension (SBP>160)
• High cholesterol levels
• Elevated blood glucose are all risk factors for AD
Dietary factors
• Dietary fat intake has been associated with AD dementia risk
• heavy drinking associated with a higher AD dementia risk
• adherence to the Mediterranean diet, which recommends fish intake,
is associated with decreased risk of AD and decreased risk of
converting from MCI to AD dementia
Diagnosis
and Clinical
Features
• Alzheimer disease dementia has a gradual and
insidious onset, and there must be two
cognitive domains affected, as well as
functional impairment.
• The most common presentation is an amnestic
one, in which the primary deficits are in the
learning and memory domain.
• There are also non-amnestic presentations,
where the prominent impairment could be in
the language, visuospatial or executive
functioning domains.
• Individuals will have increasing difficulty
functioning in their daily activities as the
disease progresses.
Alzheimer Clinical Features
• Early Presentation::
• Typical AD dementia initially presents with an episodic memory
impairment reflecting the selective vulnerability of the medial
temporal lobe to AD pathology
• Recent episodic memory is particularly impaired in early AD.
Pattern of Progression
• While episodic memory is the hallmark of early AD, subsequent
cognitive decline is heterogeneous as the pathology spreads to the
association cortices. While individual presentations vary significantly,
• Feldman and Woodward have described the typical symptom
progression in AD dementia
*Mild AD (recent memory impairment, repetitive questions, loss
of interest in hobbies, anomia, impaired instrumental ADLs),
*moderate AD (aphasia, executive dysfunction, impaired basic
ADLs),
* severe AD (agitation, complete loss of independence, sleep
disturbance)
Common Clinical Features
• Semantic memory dysfunction can be an early feature of AD but
occurs after episodic memory involvement.
• The preservation of semantic memory in a subset of early AD cases
indicates that transentorhinal dysfunction is inadequate to disrupt
semantic memory, which likely requires extension of pathology into
the temporal neocortex
• Executive function (planning, organization, problem solving, set
switching) decline occurs in mild AD
• The executive dysfunction in AD dementia is mild until later in the
disease course compared to bvFTD.
• Language disturbance often occurs in the mild-moderate stage of AD
dementia.
• Initial complaints often include word-finding difficulty.
• In time, other features of aphasia may develop, and in the late stages,
language output can be limited.
• Decline in visuospatial skills is common, often manifesting early
with the complaint of becoming lost or being disorientated in
unfamiliar places.
• Apraxia often occurs later in the course of typical AD, although it may
be an early feature in atypical AD.
• Strikingly, several abilities are preserved until very late in the
development of AD dementia. For example, AD dementia patients
have preserved motor learning (procedural) motor, and sensory skills.
• Patients with AD dementia have episodic memory loss and develop
anomia, executive dysfunction, and visuospatial difficulty in the
setting of preserved ability to walk, see, hear, and feel.
• AD dementia is also characterized by the juxtaposition of “knowing
how” (procedural memory) and “not knowing what” (declarative
memory). The clinical picture of deficits and preserved abilities is
explained by the anatomical distribution of the NFT pathology.
• Tangle burden is greatest in the medial temporal lobe but spares the
primary sensory and motor cortices until very late in the course
• Early AD is characterized by an isolated memory impairment resulting
from significant pathology in the entorhinal cortex and hippocampus,
which serves to disconnect the medial temporal
lobe from other cortices.
The spread of pathology to other association cortices results in
accumulation of other symptoms:
semantic memory involvement from spread to the anterior
temporal lobes,
executive dysfunction from spread to the frontal lobes, and
visual-spatial dysfunction from spread to the occipitotemporal
lobes
• In contrast, the primary motor and sensory cortices are only affected
late in the course.
• The preserved basal ganglia and cerebellum are involved in the
procedural/motor learning (or knowing how).
Neuropsychiatric Features of Alzheimer
Disease Dementia
• apathy (72%) was the most common neuropsychiatric symptom,
followed by agitation (60%) and anxiety (48%)
• Identification of delusions is important because it often precedes
physically aggressive behavior .
• Common delusions in AD include paranoia and infidelity.
• Identification of neuropsychiatric features is important because these
symptoms result in significant caregiver burden and can be targeted
for treatment
DSM 5 &
ICD10 Criteria
DIFFERENTIAL
DIAGNOSIS
Pathology
and
Laboratory
Examination.
• There is no standard specific & sensitive
diagnostic lab test available. However some
battery of test available to differentiate
Alzhiemer’s from others:
NEUROIMAGING
• (CT or MRI), is used largely to identify or exclude
other causes of cognitive impairment.
• Quantification of change in global (whole brain
and ventricles) and regional (entorhinal cortex,
hippocampus, corpus callosum) volumes in
patients with Alzheimer disease frequently
demonstrate group differences in comparison to
cognitively intact elderly patients, with MCI
patients intermediate.
• SPECT or FDG-PET can increase the diagnostic
accuracy.
• PET-amyloid imaging : absence of tracer
retention indicates that dementia is unlikely to be
due to Alzheimer disease
• CSF
• Decreased level of Aβ (Aβ1–42)
• Increased Level of total and phosphorylated tau protein.
• Genetic marker APOE4, is diagnostic predictor of late
onset Alzhiemers
• Current Neuropathological diagnostic criteria for
definite, or a high likelihood of, Alzheimer disease
require
• The presence of a Clinical history of progressive
dementia during life and
• The presence of both Amyloid plaques and
neurofibrillary tangles on postmortem examination.
Biomarkers in Alzheimer Disease
-Cerebrospinal Fluid Biomarkers
• reduction in the CSF Aβ42 and elevation in the CSF tau protein has a
sensitivity of 85% and specificity of 86% for diagnosis of AD dementia
• elevated phosphorylated tau - evidence of pathological tau
accumulation
• the less specific total tau is used as a neurodegenerative biomarker
• novel CSF markers like neurofilament light protein, may be good
index of neurodegeneration
Neuroimaging Biomarkers
• Structural imaging(MRI>CT):
• Medial temporal lobe atrophy of the hippocampus and entorhinal
cortex with concomitant dilatation of the temporal horns is an early
characteristic of AD dementia and can predict conversion from normal
cognition to MCI and MCI to AD dementia
*Reduction in hippocampal volumes correlates with NFT
pathology at autopsy and cognitive decline
* In MCI, atrophy is limited to the medial temporal lobe structures while
with AD onset, atrophy spreads to the lateral temporal and parietal
cortices.
• The presence of white matter hyperintensities observed by FLAIR or
T2 MRI also appears to contribute to cognitive impairment in AD
• *Tau imaging
• *Amyloid imaging
Functional imaging
• Decreased blood flow in a temporal-parietal distribution seen on
SPECT correlates with hypometabolism seen on FDG-PET and is
suggestive of AD.
• In MCI, hypometabolism is primarily in the hippocampus and
posterior cingulate. In AD dementia, the hypometabolism includes
these regions as well as the temporal-parietal regions
Alzheimer Pathophysiology
• The basic hypothesis is that abnormal Aβ metabolism altering the
Aβ42/Aβ40 ratio in the brain causes Aβ oligomer formation and
aggregation to form fibrils, which form the amyloid plaque.
• This oligomer formation and aggregation results in a cascade of
events, including tau protein tangle formation, increased
inflammatory response, and oxidative injury, to cause neurotoxicity
and neurodegeneration
• Aβ is derived from APP through proteolytic processing.
• Aβ is produced normally in the body but under normal circumstances
it is removed efficiently by a number of mechanisms.
• These include breakdown by extracellular proteases, such as insulin-
degrading enzyme, and receptor-mediated endocytosis followed by
lysosomal degradation and drainage through the cerebral vasculature
and into the CSF via the glymphatic system
• In the amyloidogenic pathway, APP is first cleaved by β secretase.
• This cleavage produces a β C-terminal fragment, which stays on the
membrane and soluble APP Aβ.
• This β C-terminal fragment is then cleaved by γ secretase in the
transmembrane region producing APP intracellular domain (AICD)
and Aβ peptide, which is then released into extracellular space.
Alzheimer Pathology
• Alzheimer disease is defined by two pathological findings:
extracellular plaques composed primarily of amyloid and
intraneuronal neurofibrillary tangles composed primarily of
hyperphosphorylated tau.
• Both involve abnormal conformational changes in proteins.
• Proteolytic events are critical in APP processing that leads to Aβ.
• In neurofibrillary pathology, phosphorylation of tau is a critical event.
• Macroscopically, AD is characterized by diffuse brain atrophy
including significantly decreased weight at autopsy.
*Some areas are preferentially affected, including multimodal
association areas, while others, like primary motor, somatosensory,
auditory, and visual cortices, are relatively spared.
• The limbic areas including hippocampi and cingulate gyrus are
severely affected.
• Substantia nigra (unlike in parkinsonian disorders) is relatively spared
while locus coeruleus is severely affected
Amyloid Plaques
• Aβ deposition in the brain occurs in a sequential manner starting in the
cortex, followed sequentially by the hippocampus, basal ganglia, thalamus,
and basal forebrain before in the final stages reaching the brainstem and
cerebellum
• Plaques are complicated heterogeneous lesions composed of extracellular
protein deposits and certain cellular components.
• Aβ derived from APP is the sine qua non of plaques, which are in turn the
defining pathological finding in AD.
• Despite the strong association of Aβ with plaques, in reality plaques
contain many other components.
• Other associated components of the plaque include APOE,
alpha-1 antitrypsin, complement factors, and immunoglobulins
• Plaques can be divided into diffuse (Aβ mainly) and neuritic plaques
(includes damaged tau containing axons and dendrites, i.e., neurites).
• Cell components seen in plaques include neurites, microglia, and
astrocytes.
• The typical neuritic plaque has a dense core of Aβ and less compact rim
consisting of neurites, microglia, and astrogliosis at the periphery.
• Diffuse plaques have less diagnostic specificity and can be seen in a variety
of different disorders.
• They contain Aβ but do not stain with tau-containing neurites
and are not associated with synaptic loss, reactive astrocytes, or microglia.
Neurofibrillary Tangles
• The major component of the NFT is tau within neurons and their
cell processes.
* First, pretangles form in the neuron cytoplasm, often concentrated
around the membrane. Then, tau is organized into
fibrils as NFTs. When the cell dies, the tangle may be situated
extracellularly.
Normal tau is a microtubule-associated protein and is not visible within
the brain
In NFTs, tau has become hyperphosphorylated and abnormally
conformed. This tau can be detected with immunostains that bind
abnormally conformed tau.
Other pathological findings in AD
• CAA, often present in leptomeningeal vessels, capillaries, small arterioles, and
middle-sized arteries, is seen in over 80% of AD cases. In contrast to cerebral
plaques consisting primarily of Aβ42, CAA’s major component is Aβ40.
• Granulovacuolar bodies, typically found in the
hippocampus, are small dense granules within the vacuole and can be
labeled with acid phosphatase, tubulin, ubiquitin, and neurofilament.
• Hirano bodies (eosinophilic rod bodies), also typically found in the
hippocampus, are often in neuronal processes and contain actin and
actin-binding proteins
Treatment
• 1)Acetylcholinesterase Inhibitors:
Donepezil,Rivastigmine,Galantamine
(advanced AD demonstrated depleted cholinergic neurons in the basal
forebrain)
2)NMDA antagonists: Memantine
3) Vitamin E
4) Estrogen replacement therapy
5)Antiinflammatory medications
Course
and
Prognosis.
Course
and
Prognosis.
Course
and
Prognosis.
Course
and
Prognosis.
ALZHEIMER'S DEMENTIA anu_11034nhjjjjjjjjkk5.pptx

More Related Content

Similar to ALZHEIMER'S DEMENTIA anu_11034nhjjjjjjjjkk5.pptx

Alzheimer disease.pptx
Alzheimer disease.pptxAlzheimer disease.pptx
Alzheimer disease.pptx
SafuraIjaz
 
Alzheimer
AlzheimerAlzheimer
Alzheimer
Amira Badr
 
Alzheimers presentation.docx
Alzheimers presentation.docxAlzheimers presentation.docx
Alzheimers presentation.docx
Hena Jawaid
 
Alzheimers presentation.docx
Alzheimers presentation.docxAlzheimers presentation.docx
Alzheimers presentation.docx
teredeloscobos
 
Major neuropathological conditions
Major neuropathological conditionsMajor neuropathological conditions
Major neuropathological conditions
Muhammad Musawar Ali
 
ALZHIMER DISEASE ANKIT.pptx
ALZHIMER DISEASE ANKIT.pptxALZHIMER DISEASE ANKIT.pptx
ALZHIMER DISEASE ANKIT.pptx
AnkitKumar215277
 
Alzheimers disease by Ritika soni
Alzheimers disease by Ritika soniAlzheimers disease by Ritika soni
Alzheimers disease by Ritika soni
Shimla
 
Alzheimer's Disease and its pathophysiology
Alzheimer's Disease and its pathophysiologyAlzheimer's Disease and its pathophysiology
Alzheimer's Disease and its pathophysiology
Achyut Adhikari
 
Biochemistryofalzheimers
BiochemistryofalzheimersBiochemistryofalzheimers
Biochemistryofalzheimers
vince_md
 
Cate buline are buburuza
Cate buline are buburuzaCate buline are buburuza
Cate buline are buburuza
Vizitare StudentVizitare
 
Alzheimers presentation.docx (1)
Alzheimers presentation.docx (1)Alzheimers presentation.docx (1)
Alzheimers presentation.docx (1)
Ashwani Kumar
 
Recent advances in the management of alzheimers disease
Recent advances in the management of alzheimers diseaseRecent advances in the management of alzheimers disease
Recent advances in the management of alzheimers disease
Parthajyoti Neog
 
alzheimersdisease-131223005434-phpapp01.pdf
alzheimersdisease-131223005434-phpapp01.pdfalzheimersdisease-131223005434-phpapp01.pdf
alzheimersdisease-131223005434-phpapp01.pdf
Mohamed Ibrahim
 
ALZHEIMERS DEMENTIA-PATHOLOGY AND PATHOPHYSIOLOGY.pptx
ALZHEIMERS DEMENTIA-PATHOLOGY AND PATHOPHYSIOLOGY.pptxALZHEIMERS DEMENTIA-PATHOLOGY AND PATHOPHYSIOLOGY.pptx
ALZHEIMERS DEMENTIA-PATHOLOGY AND PATHOPHYSIOLOGY.pptx
sarathchandran951352
 
Alzheimer'S Diseases
Alzheimer'S DiseasesAlzheimer'S Diseases
Alzheimer'S Diseases
AlmasMajeeth
 
Neurodegenerative disorders
Neurodegenerative disordersNeurodegenerative disorders
Neurodegenerative disorders
Dibyajyoti Prusty
 
Alzheimer's disease
Alzheimer's diseaseAlzheimer's disease
Alzheimer's disease
Merin Babu
 
dementia.ppt
dementia.pptdementia.ppt
dementia.ppt
Mostafa Elsapan
 
NEUROBIOLOGY OF SCHIZOPHRENIA FINAL1.pptx
NEUROBIOLOGY OF SCHIZOPHRENIA FINAL1.pptxNEUROBIOLOGY OF SCHIZOPHRENIA FINAL1.pptx
NEUROBIOLOGY OF SCHIZOPHRENIA FINAL1.pptx
vijayraghuwanshi3
 
alzheimersdisease final.pptx
alzheimersdisease final.pptxalzheimersdisease final.pptx
alzheimersdisease final.pptx
Komal Upreti
 

Similar to ALZHEIMER'S DEMENTIA anu_11034nhjjjjjjjjkk5.pptx (20)

Alzheimer disease.pptx
Alzheimer disease.pptxAlzheimer disease.pptx
Alzheimer disease.pptx
 
Alzheimer
AlzheimerAlzheimer
Alzheimer
 
Alzheimers presentation.docx
Alzheimers presentation.docxAlzheimers presentation.docx
Alzheimers presentation.docx
 
Alzheimers presentation.docx
Alzheimers presentation.docxAlzheimers presentation.docx
Alzheimers presentation.docx
 
Major neuropathological conditions
Major neuropathological conditionsMajor neuropathological conditions
Major neuropathological conditions
 
ALZHIMER DISEASE ANKIT.pptx
ALZHIMER DISEASE ANKIT.pptxALZHIMER DISEASE ANKIT.pptx
ALZHIMER DISEASE ANKIT.pptx
 
Alzheimers disease by Ritika soni
Alzheimers disease by Ritika soniAlzheimers disease by Ritika soni
Alzheimers disease by Ritika soni
 
Alzheimer's Disease and its pathophysiology
Alzheimer's Disease and its pathophysiologyAlzheimer's Disease and its pathophysiology
Alzheimer's Disease and its pathophysiology
 
Biochemistryofalzheimers
BiochemistryofalzheimersBiochemistryofalzheimers
Biochemistryofalzheimers
 
Cate buline are buburuza
Cate buline are buburuzaCate buline are buburuza
Cate buline are buburuza
 
Alzheimers presentation.docx (1)
Alzheimers presentation.docx (1)Alzheimers presentation.docx (1)
Alzheimers presentation.docx (1)
 
Recent advances in the management of alzheimers disease
Recent advances in the management of alzheimers diseaseRecent advances in the management of alzheimers disease
Recent advances in the management of alzheimers disease
 
alzheimersdisease-131223005434-phpapp01.pdf
alzheimersdisease-131223005434-phpapp01.pdfalzheimersdisease-131223005434-phpapp01.pdf
alzheimersdisease-131223005434-phpapp01.pdf
 
ALZHEIMERS DEMENTIA-PATHOLOGY AND PATHOPHYSIOLOGY.pptx
ALZHEIMERS DEMENTIA-PATHOLOGY AND PATHOPHYSIOLOGY.pptxALZHEIMERS DEMENTIA-PATHOLOGY AND PATHOPHYSIOLOGY.pptx
ALZHEIMERS DEMENTIA-PATHOLOGY AND PATHOPHYSIOLOGY.pptx
 
Alzheimer'S Diseases
Alzheimer'S DiseasesAlzheimer'S Diseases
Alzheimer'S Diseases
 
Neurodegenerative disorders
Neurodegenerative disordersNeurodegenerative disorders
Neurodegenerative disorders
 
Alzheimer's disease
Alzheimer's diseaseAlzheimer's disease
Alzheimer's disease
 
dementia.ppt
dementia.pptdementia.ppt
dementia.ppt
 
NEUROBIOLOGY OF SCHIZOPHRENIA FINAL1.pptx
NEUROBIOLOGY OF SCHIZOPHRENIA FINAL1.pptxNEUROBIOLOGY OF SCHIZOPHRENIA FINAL1.pptx
NEUROBIOLOGY OF SCHIZOPHRENIA FINAL1.pptx
 
alzheimersdisease final.pptx
alzheimersdisease final.pptxalzheimersdisease final.pptx
alzheimersdisease final.pptx
 

More from ShanuSoni7

KMC Pleural effusion.pptx gggggggggggggg
KMC Pleural effusion.pptx ggggggggggggggKMC Pleural effusion.pptx gggggggggggggg
KMC Pleural effusion.pptx gggggggggggggg
ShanuSoni7
 
jenkuskyP101_MHC_BenzoForPharmacists_011617.ppt
jenkuskyP101_MHC_BenzoForPharmacists_011617.pptjenkuskyP101_MHC_BenzoForPharmacists_011617.ppt
jenkuskyP101_MHC_BenzoForPharmacists_011617.ppt
ShanuSoni7
 
Tic Disorders ppt.pptx bshhsjsjsjsjjss jzjjjz
Tic Disorders ppt.pptx bshhsjsjsjsjjss jzjjjzTic Disorders ppt.pptx bshhsjsjsjsjjss jzjjjz
Tic Disorders ppt.pptx bshhsjsjsjsjjss jzjjjz
ShanuSoni7
 
Dissociative Disorder final pk.pptx
Dissociative Disorder final pk.pptxDissociative Disorder final pk.pptx
Dissociative Disorder final pk.pptx
ShanuSoni7
 
NMS.pptx
NMS.pptxNMS.pptx
NMS.pptx
ShanuSoni7
 
Assessment of Personality Disorders.pptx
Assessment of Personality Disorders.pptxAssessment of Personality Disorders.pptx
Assessment of Personality Disorders.pptx
ShanuSoni7
 
Neurotrophic Factors Presentation.pptx
Neurotrophic Factors Presentation.pptxNeurotrophic Factors Presentation.pptx
Neurotrophic Factors Presentation.pptx
ShanuSoni7
 
OCD seminar Dr. Manish Singh-1.pptx
OCD seminar Dr. Manish Singh-1.pptxOCD seminar Dr. Manish Singh-1.pptx
OCD seminar Dr. Manish Singh-1.pptx
ShanuSoni7
 
GENETICS IN PSYCHIATRY.pdf
GENETICS IN PSYCHIATRY.pdfGENETICS IN PSYCHIATRY.pdf
GENETICS IN PSYCHIATRY.pdf
ShanuSoni7
 
THEORIES OF PERSONALITY(1).pptx
THEORIES OF PERSONALITY(1).pptxTHEORIES OF PERSONALITY(1).pptx
THEORIES OF PERSONALITY(1).pptx
ShanuSoni7
 
Theories of Personality.pptx
Theories of Personality.pptxTheories of Personality.pptx
Theories of Personality.pptx
ShanuSoni7
 

More from ShanuSoni7 (11)

KMC Pleural effusion.pptx gggggggggggggg
KMC Pleural effusion.pptx ggggggggggggggKMC Pleural effusion.pptx gggggggggggggg
KMC Pleural effusion.pptx gggggggggggggg
 
jenkuskyP101_MHC_BenzoForPharmacists_011617.ppt
jenkuskyP101_MHC_BenzoForPharmacists_011617.pptjenkuskyP101_MHC_BenzoForPharmacists_011617.ppt
jenkuskyP101_MHC_BenzoForPharmacists_011617.ppt
 
Tic Disorders ppt.pptx bshhsjsjsjsjjss jzjjjz
Tic Disorders ppt.pptx bshhsjsjsjsjjss jzjjjzTic Disorders ppt.pptx bshhsjsjsjsjjss jzjjjz
Tic Disorders ppt.pptx bshhsjsjsjsjjss jzjjjz
 
Dissociative Disorder final pk.pptx
Dissociative Disorder final pk.pptxDissociative Disorder final pk.pptx
Dissociative Disorder final pk.pptx
 
NMS.pptx
NMS.pptxNMS.pptx
NMS.pptx
 
Assessment of Personality Disorders.pptx
Assessment of Personality Disorders.pptxAssessment of Personality Disorders.pptx
Assessment of Personality Disorders.pptx
 
Neurotrophic Factors Presentation.pptx
Neurotrophic Factors Presentation.pptxNeurotrophic Factors Presentation.pptx
Neurotrophic Factors Presentation.pptx
 
OCD seminar Dr. Manish Singh-1.pptx
OCD seminar Dr. Manish Singh-1.pptxOCD seminar Dr. Manish Singh-1.pptx
OCD seminar Dr. Manish Singh-1.pptx
 
GENETICS IN PSYCHIATRY.pdf
GENETICS IN PSYCHIATRY.pdfGENETICS IN PSYCHIATRY.pdf
GENETICS IN PSYCHIATRY.pdf
 
THEORIES OF PERSONALITY(1).pptx
THEORIES OF PERSONALITY(1).pptxTHEORIES OF PERSONALITY(1).pptx
THEORIES OF PERSONALITY(1).pptx
 
Theories of Personality.pptx
Theories of Personality.pptxTheories of Personality.pptx
Theories of Personality.pptx
 

Recently uploaded

BÀI TẬP BỔ TRỢ TIẾNG ANH 8 CẢ NĂM - GLOBAL SUCCESS - NĂM HỌC 2023-2024 (CÓ FI...
BÀI TẬP BỔ TRỢ TIẾNG ANH 8 CẢ NĂM - GLOBAL SUCCESS - NĂM HỌC 2023-2024 (CÓ FI...BÀI TẬP BỔ TRỢ TIẾNG ANH 8 CẢ NĂM - GLOBAL SUCCESS - NĂM HỌC 2023-2024 (CÓ FI...
BÀI TẬP BỔ TRỢ TIẾNG ANH 8 CẢ NĂM - GLOBAL SUCCESS - NĂM HỌC 2023-2024 (CÓ FI...
Nguyen Thanh Tu Collection
 
What is Digital Literacy? A guest blog from Andy McLaughlin, University of Ab...
What is Digital Literacy? A guest blog from Andy McLaughlin, University of Ab...What is Digital Literacy? A guest blog from Andy McLaughlin, University of Ab...
What is Digital Literacy? A guest blog from Andy McLaughlin, University of Ab...
GeorgeMilliken2
 
How to Manage Your Lost Opportunities in Odoo 17 CRM
How to Manage Your Lost Opportunities in Odoo 17 CRMHow to Manage Your Lost Opportunities in Odoo 17 CRM
How to Manage Your Lost Opportunities in Odoo 17 CRM
Celine George
 
RHEOLOGY Physical pharmaceutics-II notes for B.pharm 4th sem students
RHEOLOGY Physical pharmaceutics-II notes for B.pharm 4th sem studentsRHEOLOGY Physical pharmaceutics-II notes for B.pharm 4th sem students
RHEOLOGY Physical pharmaceutics-II notes for B.pharm 4th sem students
Himanshu Rai
 
Présentationvvvvvvvvvvvvvvvvvvvvvvvvvvvv2.pptx
Présentationvvvvvvvvvvvvvvvvvvvvvvvvvvvv2.pptxPrésentationvvvvvvvvvvvvvvvvvvvvvvvvvvvv2.pptx
Présentationvvvvvvvvvvvvvvvvvvvvvvvvvvvv2.pptx
siemaillard
 
বাংলাদেশ অর্থনৈতিক সমীক্ষা (Economic Review) ২০২৪ UJS App.pdf
বাংলাদেশ অর্থনৈতিক সমীক্ষা (Economic Review) ২০২৪ UJS App.pdfবাংলাদেশ অর্থনৈতিক সমীক্ষা (Economic Review) ২০২৪ UJS App.pdf
বাংলাদেশ অর্থনৈতিক সমীক্ষা (Economic Review) ২০২৪ UJS App.pdf
eBook.com.bd (প্রয়োজনীয় বাংলা বই)
 
How to deliver Powerpoint Presentations.pptx
How to deliver Powerpoint  Presentations.pptxHow to deliver Powerpoint  Presentations.pptx
How to deliver Powerpoint Presentations.pptx
HajraNaeem15
 
Exploiting Artificial Intelligence for Empowering Researchers and Faculty, In...
Exploiting Artificial Intelligence for Empowering Researchers and Faculty, In...Exploiting Artificial Intelligence for Empowering Researchers and Faculty, In...
Exploiting Artificial Intelligence for Empowering Researchers and Faculty, In...
Dr. Vinod Kumar Kanvaria
 
A Independência da América Espanhola LAPBOOK.pdf
A Independência da América Espanhola LAPBOOK.pdfA Independência da América Espanhola LAPBOOK.pdf
A Independência da América Espanhola LAPBOOK.pdf
Jean Carlos Nunes Paixão
 
Digital Artefact 1 - Tiny Home Environmental Design
Digital Artefact 1 - Tiny Home Environmental DesignDigital Artefact 1 - Tiny Home Environmental Design
Digital Artefact 1 - Tiny Home Environmental Design
amberjdewit93
 
Main Java[All of the Base Concepts}.docx
Main Java[All of the Base Concepts}.docxMain Java[All of the Base Concepts}.docx
Main Java[All of the Base Concepts}.docx
adhitya5119
 
BBR 2024 Summer Sessions Interview Training
BBR  2024 Summer Sessions Interview TrainingBBR  2024 Summer Sessions Interview Training
BBR 2024 Summer Sessions Interview Training
Katrina Pritchard
 
Walmart Business+ and Spark Good for Nonprofits.pdf
Walmart Business+ and Spark Good for Nonprofits.pdfWalmart Business+ and Spark Good for Nonprofits.pdf
Walmart Business+ and Spark Good for Nonprofits.pdf
TechSoup
 
Hindi varnamala | hindi alphabet PPT.pdf
Hindi varnamala | hindi alphabet PPT.pdfHindi varnamala | hindi alphabet PPT.pdf
Hindi varnamala | hindi alphabet PPT.pdf
Dr. Mulla Adam Ali
 
The History of Stoke Newington Street Names
The History of Stoke Newington Street NamesThe History of Stoke Newington Street Names
The History of Stoke Newington Street Names
History of Stoke Newington
 
clinical examination of hip joint (1).pdf
clinical examination of hip joint (1).pdfclinical examination of hip joint (1).pdf
clinical examination of hip joint (1).pdf
Priyankaranawat4
 
ANATOMY AND BIOMECHANICS OF HIP JOINT.pdf
ANATOMY AND BIOMECHANICS OF HIP JOINT.pdfANATOMY AND BIOMECHANICS OF HIP JOINT.pdf
ANATOMY AND BIOMECHANICS OF HIP JOINT.pdf
Priyankaranawat4
 
How to Create a More Engaging and Human Online Learning Experience
How to Create a More Engaging and Human Online Learning Experience How to Create a More Engaging and Human Online Learning Experience
How to Create a More Engaging and Human Online Learning Experience
Wahiba Chair Training & Consulting
 
Life upper-Intermediate B2 Workbook for student
Life upper-Intermediate B2 Workbook for studentLife upper-Intermediate B2 Workbook for student
Life upper-Intermediate B2 Workbook for student
NgcHiNguyn25
 
Film vocab for eal 3 students: Australia the movie
Film vocab for eal 3 students: Australia the movieFilm vocab for eal 3 students: Australia the movie
Film vocab for eal 3 students: Australia the movie
Nicholas Montgomery
 

Recently uploaded (20)

BÀI TẬP BỔ TRỢ TIẾNG ANH 8 CẢ NĂM - GLOBAL SUCCESS - NĂM HỌC 2023-2024 (CÓ FI...
BÀI TẬP BỔ TRỢ TIẾNG ANH 8 CẢ NĂM - GLOBAL SUCCESS - NĂM HỌC 2023-2024 (CÓ FI...BÀI TẬP BỔ TRỢ TIẾNG ANH 8 CẢ NĂM - GLOBAL SUCCESS - NĂM HỌC 2023-2024 (CÓ FI...
BÀI TẬP BỔ TRỢ TIẾNG ANH 8 CẢ NĂM - GLOBAL SUCCESS - NĂM HỌC 2023-2024 (CÓ FI...
 
What is Digital Literacy? A guest blog from Andy McLaughlin, University of Ab...
What is Digital Literacy? A guest blog from Andy McLaughlin, University of Ab...What is Digital Literacy? A guest blog from Andy McLaughlin, University of Ab...
What is Digital Literacy? A guest blog from Andy McLaughlin, University of Ab...
 
How to Manage Your Lost Opportunities in Odoo 17 CRM
How to Manage Your Lost Opportunities in Odoo 17 CRMHow to Manage Your Lost Opportunities in Odoo 17 CRM
How to Manage Your Lost Opportunities in Odoo 17 CRM
 
RHEOLOGY Physical pharmaceutics-II notes for B.pharm 4th sem students
RHEOLOGY Physical pharmaceutics-II notes for B.pharm 4th sem studentsRHEOLOGY Physical pharmaceutics-II notes for B.pharm 4th sem students
RHEOLOGY Physical pharmaceutics-II notes for B.pharm 4th sem students
 
Présentationvvvvvvvvvvvvvvvvvvvvvvvvvvvv2.pptx
Présentationvvvvvvvvvvvvvvvvvvvvvvvvvvvv2.pptxPrésentationvvvvvvvvvvvvvvvvvvvvvvvvvvvv2.pptx
Présentationvvvvvvvvvvvvvvvvvvvvvvvvvvvv2.pptx
 
বাংলাদেশ অর্থনৈতিক সমীক্ষা (Economic Review) ২০২৪ UJS App.pdf
বাংলাদেশ অর্থনৈতিক সমীক্ষা (Economic Review) ২০২৪ UJS App.pdfবাংলাদেশ অর্থনৈতিক সমীক্ষা (Economic Review) ২০২৪ UJS App.pdf
বাংলাদেশ অর্থনৈতিক সমীক্ষা (Economic Review) ২০২৪ UJS App.pdf
 
How to deliver Powerpoint Presentations.pptx
How to deliver Powerpoint  Presentations.pptxHow to deliver Powerpoint  Presentations.pptx
How to deliver Powerpoint Presentations.pptx
 
Exploiting Artificial Intelligence for Empowering Researchers and Faculty, In...
Exploiting Artificial Intelligence for Empowering Researchers and Faculty, In...Exploiting Artificial Intelligence for Empowering Researchers and Faculty, In...
Exploiting Artificial Intelligence for Empowering Researchers and Faculty, In...
 
A Independência da América Espanhola LAPBOOK.pdf
A Independência da América Espanhola LAPBOOK.pdfA Independência da América Espanhola LAPBOOK.pdf
A Independência da América Espanhola LAPBOOK.pdf
 
Digital Artefact 1 - Tiny Home Environmental Design
Digital Artefact 1 - Tiny Home Environmental DesignDigital Artefact 1 - Tiny Home Environmental Design
Digital Artefact 1 - Tiny Home Environmental Design
 
Main Java[All of the Base Concepts}.docx
Main Java[All of the Base Concepts}.docxMain Java[All of the Base Concepts}.docx
Main Java[All of the Base Concepts}.docx
 
BBR 2024 Summer Sessions Interview Training
BBR  2024 Summer Sessions Interview TrainingBBR  2024 Summer Sessions Interview Training
BBR 2024 Summer Sessions Interview Training
 
Walmart Business+ and Spark Good for Nonprofits.pdf
Walmart Business+ and Spark Good for Nonprofits.pdfWalmart Business+ and Spark Good for Nonprofits.pdf
Walmart Business+ and Spark Good for Nonprofits.pdf
 
Hindi varnamala | hindi alphabet PPT.pdf
Hindi varnamala | hindi alphabet PPT.pdfHindi varnamala | hindi alphabet PPT.pdf
Hindi varnamala | hindi alphabet PPT.pdf
 
The History of Stoke Newington Street Names
The History of Stoke Newington Street NamesThe History of Stoke Newington Street Names
The History of Stoke Newington Street Names
 
clinical examination of hip joint (1).pdf
clinical examination of hip joint (1).pdfclinical examination of hip joint (1).pdf
clinical examination of hip joint (1).pdf
 
ANATOMY AND BIOMECHANICS OF HIP JOINT.pdf
ANATOMY AND BIOMECHANICS OF HIP JOINT.pdfANATOMY AND BIOMECHANICS OF HIP JOINT.pdf
ANATOMY AND BIOMECHANICS OF HIP JOINT.pdf
 
How to Create a More Engaging and Human Online Learning Experience
How to Create a More Engaging and Human Online Learning Experience How to Create a More Engaging and Human Online Learning Experience
How to Create a More Engaging and Human Online Learning Experience
 
Life upper-Intermediate B2 Workbook for student
Life upper-Intermediate B2 Workbook for studentLife upper-Intermediate B2 Workbook for student
Life upper-Intermediate B2 Workbook for student
 
Film vocab for eal 3 students: Australia the movie
Film vocab for eal 3 students: Australia the movieFilm vocab for eal 3 students: Australia the movie
Film vocab for eal 3 students: Australia the movie
 

ALZHEIMER'S DEMENTIA anu_11034nhjjjjjjjjkk5.pptx

  • 2. DEFINITION The word Dementia derives from the Latin worddementatus, meaning out of one’s mind, and, as such, was potentially applicable to any state of psychopathology. Dementia refers to a disease process marked by progressive cognitive impairment in clear consciousness. The fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) describes dementia, now subsumed under the term major neurocognitive disorder, as significant cognitive impairment in one or more of the domains of 1) complex attention, 2) executive function, 3) learning and memory, 4) language, 5)perceptual motor ability, and 6)social cognition.
  • 3. • These deficits represent a decline from a previous level of functioning, so dementia does not refer to low intellectual functioning or mental retardation that are developmental and static conditions. • This decline is often noted by the individual affected, a family member or other caretaker, or the clinician, and should be demonstrated on standardized neuropsychological testing, and if that is not possible, another measurable clinical assessment. • These cognitive deficits interfere with independent functioning in daily activities, and cannot occur exclusively in the context of a delirium, or be better explained by another mental disorder.
  • 4. Dementia of the Alzheimer's Type • In 1907, Alois Alzheimer first described the condition that later assumed his name. • In 1906 , he reported the case of a 51- year-old woman with a progressive cognitive disorder marked by memory loss, confusion, topographical disorientation, aphasia, and prominent neuropsychiatric manifestations of persecutory delusions, misidentifications, and behavioral disturbances. At her death 4 years later, autopsy revealed profound atrophy, amyloid plaques, and neurofibrillary tangles.
  • 5. EPIDEMIOLOGY • The incidence of Alzheimer disease increases with age from about 0.5 percent per year at ages 65 to 69, • 1 percent per year from age 70 to 74, • 2 percent per year from age 75 to 79, • 3 percent per year from age 80 to 84 and • 8 percent per year after age 85. • With the aging of the population, projections estimate that, by the year 2050, 13.8 million people over the age of 65 are estimated to have Alzheimer disease.
  • 6. • While MCI is more common in men, the prevalence of AD dementia is higher in women. • The lifetime risk of developing Alzheimer dementia from the age of 45 is approximately 10% for men and 20% for women • Age is the most important risk factor for AD dementia
  • 7. Etiology • The etiology of Alzheimer disease is multifactorial & is influenced by multiple genes, by environmental factors, and by their interactions. • 1) GENETICS: play a major role as evident by twin studies the concordance rate for monozygotic twins, which is higher than the rate for dizygotic twins ( 43 percent vs. 8 percent, respectively). A) Early-Onset Alzheimer Disease.: (<65 years) Mutations at three genetic loci : -APP gene located on chromosome 21 (Autosomal Dominant) - Presenilin-1 (PS1) on Chromosome 14 (Autosomal Dominant) - Presenelin-2 (PS2) on Chromosome 2.(These mutations appear to be rare)
  • 8. Etiology 1) GENETICS: B) Late-Onset Alzheimer Disease.: (>65 years) Signifigant association with
  • 9. Etiology 2) Neuropathology. The classic gross neuroanatomical observation of a brain from a patient with Alzheimer's disease is diffuse atrophy with :flattened cortical sulci and enlarged cerebral ventricles. • Macroscopically: • the brains of early Alzheimer disease patients may appear grossly normal, or with atrophy confined to the hippocampus, and often most easily recognized by increased volume of the inferior horn of the lateral ventricles. • As the disease progresses, widened sulci throughout the cortex and increased ventricular size are seen. • Atrophy in the posterior temporal, parietal, and frontal lobes is often most prominent.
  • 10. Etiology 2) Neuropathology. The classic and pathognomonic microscopic findings are - Senile Amyloid plaques, -neurofibrillary tangles, -neuronal loss (particularly in the cortex and the hippocampus ), -synaptic loss (perhaps as much as 50 percent in the cortex), and granulovascular degeneration of the neurons.
  • 11. Etiology • Senile plaques, also referred to as amyloid plaques, more strongly indicate Alzheimer's disease, although they are also seen in Down syndrome and, to some extent, in normal aging. • are the defining lesion of Alzheimer disease, composed of insoluble deposits of fibrillar Aβ protein, /31A4. • Surrounding this central core are dystrophic neurites, microglial cells, and reactive astrocytes. • Amyloid plaques are first found throughout the neocortex, followed by entorhinal cortex and hippocampus, then subcortical regions. • The number and the density of senile plaques present in postmortem brains have been correlated with the severity of the disease that affected the persons.
  • 12. Etiology • Neurofibrillary tangles : • are intracellular inclusion bodies, composed of cytoskeletal elements which contain paired helical filaments composed of aggregates of hyperphosphorylated MAPT . • Neurofibrillary tangles are first found in the entorhinal cortex and spread from there to the hippocampus and lateral temporal lobe, then more widely through the neocortex. • The presence of neurofibrillary tangles is not pathognomonic for Alzheimer disease, as they are the principal lesion in MAPT-related FTDs • they also occur in Down syndrome, dementia pugilistica (punch-drunk syndrome), Parkinson-dementia complex of Guam, Hallervorden Spatz disease, and the brains of normal people as they age.
  • 13.
  • 14. Etiology • Additional pathological features of Alzheimer disease include : • α-synuclein, which may be detectable in as many as one half of individuals with Alzheimer disease. • These Abnormal aggregates most commonly are found as thread-like deposits or as intraneuronal inclusions (Lewy bodies) in the amygdala and transentorhinal cortex, though Lewy bodies may also be present in the neocortex. • Transactive response DNA-binding protein of 43 kDa (TDP-43) is the most frequently aggregated disease protein in frontotemporal lobar degeneration. • Recently it has been found that TDP-43 proteinopathy is also present in many cases of Alzheimer disease. • found predominantly in the mesial temporal lobe, and to a lesser degree in neocortical areas. • Neuronal loss, most markedly in the entorhinal cortex and hippocampus. Later in disease, loss of cholinergic neurons in the nucleus basalis, as well as loss of brain stem noradrenergic and serotonergic neurons, occurs. • Granulovacuolar degeneration and the presence of Hirano bodies, most commonly affecting pyramidal neurons in the hippocampus, may be found.
  • 15.
  • 16. Etiology 2)Neuropathology. Overproduction & self-aggregation of Aβ into soluble low-n oligomers is a primary source of synaptotoxicity in Alzheimer disease
  • 17. Etiology • In addition to the direct effects of Aβ on synapse loss, Aβ may lead to synapse loss and neuronal death via other downstream effectors. • For example, Aβ contributes to the hyperphosphorylation of microtubule- associate protein τ (MAPT), which enhances its aggregation. Overproduction and aggregation of MAPT have been shown to cause synapse loss and neuronal death independent of the effects of Aβ.
  • 18.
  • 19. Etiology • 3) Neurotransmitters: • The neurotransmitters that are most often implicated in the pathophysiological condition of Alzheimer's disease are • 1)Acetylcholine : Level decreased due to specific degeneration of cholinergic neurons is present in the nucleus basalis of Meynert . • Decreased Choline Acetyltransferase concentration in Brain ( Key Enzyme for synthesis of Ach) • Cholinergic antagonists, such as scopolamine and atropine, impair cognitive abilities, whereas cholinergic agonists, such as physostigmine and arecoline, enhance cognitive abilities. • 2) Norepinephrine, Level decreased due to degeneration of norepinephrine-containing neurons in the locus ceruleus. • 3) Two other neurotransmitters implicated in the pathophysiological condition of Alzheimer's disease are the neuroactive peptides: • somatostatin and corticotropin
  • 20. Etiology • 3) Other Causes: • Abnormality in the regulation of membrane phospholipid metabolism results in membranes that are less fluid-that is, more rigid-than normal. • Several investigators are using molecular resonance spectroscopic imaging to assess this hypothesis directly in patients with dementia of the Alzheimer's type. • Aluminum toxicity has also been hypothesized to be a causative factor because high levels of aluminum have been found in the brains of some patients with Alzheimer’s disease, but this is no longer considered a significant etiological factor. • Excessive stimulation by the transmitter glutamate that may damage neurons is another theory of causation. • Aβ appears to destabilize dendritic spines, resulting in retraction and synapse loss, via modulation of the function of both α-amino-3-hydroxy-5-methyl-4-isoazole-proprionic acid (AMPA) and N-methyl-D-aspartate (NMDA) classes of postsynaptic glutamate receptors. It is therefore not surprising that memantine (Namenda), a low-affinity NMDA antagonist that functions to modulate activation of NMDA receptors, has been shown to be of benefit in Alzheimer disease.
  • 21. RISK AND PROTECTIVE FACTORS. • 1) Age. Age is the greatest risk factor for developing Alzheimer disease. Whereas approximately 3 percent of people older than 65 years of age have Alzheimer disease, about one third of people older than 85 years of age have Alzheimer disease. • 2)Education. people with less education are at increased risk of developing Alzheimer disease. • Functional neuroimaging findings of patients with Alzheimer disease indicate that people with higher educational attainment or higher premorbid intellectual functioning but similar levels of dementia severity have more severe findings on neuroimaging. • This suggests a protective effect of education, in that greater neuropathology is needed to produce the same clinical changes. • Those with higher levels of cognitive reserve may be able to utilize other alternative neural networks as levels of neuropathology increase, thus compensating for the disease burden, up to a point. • Studies have reported that there is a relationship between cognitive decline and neocortical synaptic density in Alzheimer disease. • There is also some evidence that education can increase synaptic density.
  • 22. • In addition to education, participation in certain leisure activities, including reading, dancing, playing board games, and playing musical instruments, is associated with a decreased dementia risk • Early-life cognitive abilities also may play an important role in dementia risk. (good linguistic ability and grammatical complexity in early life>less chance of AD in adult life)
  • 23. RISK AND PROTECTIVE FACTORS. • 3) Estrogen. A number of observational studies have suggested that estrogen replacement after menopause reduced the risk of Alzheimer disease. 1.On a neuronal level, estrogen increases -density of a synaptic population lost in Alzheimer disease, -excitatory synapses onto dendritic spines, in both hippocampus and cortex. 2. It also may interact with APP processing, to increase brain Aβ concentrations. 3. Estrogen inhibits oxidation of lipids, lipoproteins, and nucleic acids in vitro and is protective of cells in culture against a number of insults, including Aβ. However current recommendation does not approve HRT in Alzheimers disease.
  • 24. RISK AND PROTECTIVE FACTORS. 4) Head Trauma. can lead to overexpression of APP, increase inflammatory mediators, and cause deposition in the brain. The effects of traumatic injury on Aβ may be mediated by APOE genotype . 5) Inflammation. increased concentrations of acute phase reactants, cytokines, and complement protein. Population studies have demonstrated that nonsteroidal anti-inflammatory drug (NSAID) or corticosteroid use is associated with a decreased risk of developing Alzheimer disease; But timing of NSAID use & associated risk of bleeding and peptic ulcer is debatable topic.
  • 25. RISK AND PROTECTIVE FACTORS. 6) Nicotine. The literature is unclear. Indirect stimulation of nicotinic receptors via use of acetylcholinesterase inhibitors has benefit in the treatment of Alzheimer disease.. However Smoking causes signifigant cerebro- cardiovascular risk and associated oxidative stress , neuroinflammation leads to the development of Dementia. 7) Oxidative Stress. Aβ can damage and kill neurons by inducing oxidative stress, as can the microglial inflammatory reaction surrounding plaques. Increased markers of oxidative stress seen in Alzheimers Disease. However Antioxidants VIT E & Ginkgo Biloba being tried but no conclusive evidence
  • 26. • Impaired sleep • Hypertension (SBP>160) • High cholesterol levels • Elevated blood glucose are all risk factors for AD
  • 27. Dietary factors • Dietary fat intake has been associated with AD dementia risk • heavy drinking associated with a higher AD dementia risk • adherence to the Mediterranean diet, which recommends fish intake, is associated with decreased risk of AD and decreased risk of converting from MCI to AD dementia
  • 28. Diagnosis and Clinical Features • Alzheimer disease dementia has a gradual and insidious onset, and there must be two cognitive domains affected, as well as functional impairment. • The most common presentation is an amnestic one, in which the primary deficits are in the learning and memory domain. • There are also non-amnestic presentations, where the prominent impairment could be in the language, visuospatial or executive functioning domains. • Individuals will have increasing difficulty functioning in their daily activities as the disease progresses.
  • 29. Alzheimer Clinical Features • Early Presentation:: • Typical AD dementia initially presents with an episodic memory impairment reflecting the selective vulnerability of the medial temporal lobe to AD pathology • Recent episodic memory is particularly impaired in early AD.
  • 30. Pattern of Progression • While episodic memory is the hallmark of early AD, subsequent cognitive decline is heterogeneous as the pathology spreads to the association cortices. While individual presentations vary significantly, • Feldman and Woodward have described the typical symptom progression in AD dementia
  • 31. *Mild AD (recent memory impairment, repetitive questions, loss of interest in hobbies, anomia, impaired instrumental ADLs), *moderate AD (aphasia, executive dysfunction, impaired basic ADLs), * severe AD (agitation, complete loss of independence, sleep disturbance)
  • 32. Common Clinical Features • Semantic memory dysfunction can be an early feature of AD but occurs after episodic memory involvement. • The preservation of semantic memory in a subset of early AD cases indicates that transentorhinal dysfunction is inadequate to disrupt semantic memory, which likely requires extension of pathology into the temporal neocortex
  • 33. • Executive function (planning, organization, problem solving, set switching) decline occurs in mild AD • The executive dysfunction in AD dementia is mild until later in the disease course compared to bvFTD.
  • 34. • Language disturbance often occurs in the mild-moderate stage of AD dementia. • Initial complaints often include word-finding difficulty. • In time, other features of aphasia may develop, and in the late stages, language output can be limited. • Decline in visuospatial skills is common, often manifesting early with the complaint of becoming lost or being disorientated in unfamiliar places.
  • 35. • Apraxia often occurs later in the course of typical AD, although it may be an early feature in atypical AD. • Strikingly, several abilities are preserved until very late in the development of AD dementia. For example, AD dementia patients have preserved motor learning (procedural) motor, and sensory skills.
  • 36. • Patients with AD dementia have episodic memory loss and develop anomia, executive dysfunction, and visuospatial difficulty in the setting of preserved ability to walk, see, hear, and feel. • AD dementia is also characterized by the juxtaposition of “knowing how” (procedural memory) and “not knowing what” (declarative memory). The clinical picture of deficits and preserved abilities is explained by the anatomical distribution of the NFT pathology.
  • 37. • Tangle burden is greatest in the medial temporal lobe but spares the primary sensory and motor cortices until very late in the course • Early AD is characterized by an isolated memory impairment resulting from significant pathology in the entorhinal cortex and hippocampus, which serves to disconnect the medial temporal lobe from other cortices.
  • 38. The spread of pathology to other association cortices results in accumulation of other symptoms: semantic memory involvement from spread to the anterior temporal lobes, executive dysfunction from spread to the frontal lobes, and visual-spatial dysfunction from spread to the occipitotemporal lobes
  • 39. • In contrast, the primary motor and sensory cortices are only affected late in the course. • The preserved basal ganglia and cerebellum are involved in the procedural/motor learning (or knowing how).
  • 40. Neuropsychiatric Features of Alzheimer Disease Dementia • apathy (72%) was the most common neuropsychiatric symptom, followed by agitation (60%) and anxiety (48%) • Identification of delusions is important because it often precedes physically aggressive behavior . • Common delusions in AD include paranoia and infidelity. • Identification of neuropsychiatric features is important because these symptoms result in significant caregiver burden and can be targeted for treatment
  • 41. DSM 5 & ICD10 Criteria
  • 43.
  • 44. Pathology and Laboratory Examination. • There is no standard specific & sensitive diagnostic lab test available. However some battery of test available to differentiate Alzhiemer’s from others:
  • 45. NEUROIMAGING • (CT or MRI), is used largely to identify or exclude other causes of cognitive impairment. • Quantification of change in global (whole brain and ventricles) and regional (entorhinal cortex, hippocampus, corpus callosum) volumes in patients with Alzheimer disease frequently demonstrate group differences in comparison to cognitively intact elderly patients, with MCI patients intermediate. • SPECT or FDG-PET can increase the diagnostic accuracy. • PET-amyloid imaging : absence of tracer retention indicates that dementia is unlikely to be due to Alzheimer disease
  • 46.
  • 47. • CSF • Decreased level of Aβ (Aβ1–42) • Increased Level of total and phosphorylated tau protein. • Genetic marker APOE4, is diagnostic predictor of late onset Alzhiemers • Current Neuropathological diagnostic criteria for definite, or a high likelihood of, Alzheimer disease require • The presence of a Clinical history of progressive dementia during life and • The presence of both Amyloid plaques and neurofibrillary tangles on postmortem examination.
  • 48. Biomarkers in Alzheimer Disease -Cerebrospinal Fluid Biomarkers • reduction in the CSF Aβ42 and elevation in the CSF tau protein has a sensitivity of 85% and specificity of 86% for diagnosis of AD dementia • elevated phosphorylated tau - evidence of pathological tau accumulation • the less specific total tau is used as a neurodegenerative biomarker • novel CSF markers like neurofilament light protein, may be good index of neurodegeneration
  • 49. Neuroimaging Biomarkers • Structural imaging(MRI>CT): • Medial temporal lobe atrophy of the hippocampus and entorhinal cortex with concomitant dilatation of the temporal horns is an early characteristic of AD dementia and can predict conversion from normal cognition to MCI and MCI to AD dementia *Reduction in hippocampal volumes correlates with NFT pathology at autopsy and cognitive decline * In MCI, atrophy is limited to the medial temporal lobe structures while with AD onset, atrophy spreads to the lateral temporal and parietal cortices.
  • 50.
  • 51. • The presence of white matter hyperintensities observed by FLAIR or T2 MRI also appears to contribute to cognitive impairment in AD • *Tau imaging • *Amyloid imaging
  • 52. Functional imaging • Decreased blood flow in a temporal-parietal distribution seen on SPECT correlates with hypometabolism seen on FDG-PET and is suggestive of AD. • In MCI, hypometabolism is primarily in the hippocampus and posterior cingulate. In AD dementia, the hypometabolism includes these regions as well as the temporal-parietal regions
  • 53. Alzheimer Pathophysiology • The basic hypothesis is that abnormal Aβ metabolism altering the Aβ42/Aβ40 ratio in the brain causes Aβ oligomer formation and aggregation to form fibrils, which form the amyloid plaque. • This oligomer formation and aggregation results in a cascade of events, including tau protein tangle formation, increased inflammatory response, and oxidative injury, to cause neurotoxicity and neurodegeneration
  • 54. • Aβ is derived from APP through proteolytic processing. • Aβ is produced normally in the body but under normal circumstances it is removed efficiently by a number of mechanisms. • These include breakdown by extracellular proteases, such as insulin- degrading enzyme, and receptor-mediated endocytosis followed by lysosomal degradation and drainage through the cerebral vasculature and into the CSF via the glymphatic system
  • 55.
  • 56. • In the amyloidogenic pathway, APP is first cleaved by β secretase. • This cleavage produces a β C-terminal fragment, which stays on the membrane and soluble APP Aβ. • This β C-terminal fragment is then cleaved by γ secretase in the transmembrane region producing APP intracellular domain (AICD) and Aβ peptide, which is then released into extracellular space.
  • 57. Alzheimer Pathology • Alzheimer disease is defined by two pathological findings: extracellular plaques composed primarily of amyloid and intraneuronal neurofibrillary tangles composed primarily of hyperphosphorylated tau. • Both involve abnormal conformational changes in proteins. • Proteolytic events are critical in APP processing that leads to Aβ. • In neurofibrillary pathology, phosphorylation of tau is a critical event.
  • 58. • Macroscopically, AD is characterized by diffuse brain atrophy including significantly decreased weight at autopsy. *Some areas are preferentially affected, including multimodal association areas, while others, like primary motor, somatosensory, auditory, and visual cortices, are relatively spared. • The limbic areas including hippocampi and cingulate gyrus are severely affected. • Substantia nigra (unlike in parkinsonian disorders) is relatively spared while locus coeruleus is severely affected
  • 59.
  • 60. Amyloid Plaques • Aβ deposition in the brain occurs in a sequential manner starting in the cortex, followed sequentially by the hippocampus, basal ganglia, thalamus, and basal forebrain before in the final stages reaching the brainstem and cerebellum • Plaques are complicated heterogeneous lesions composed of extracellular protein deposits and certain cellular components. • Aβ derived from APP is the sine qua non of plaques, which are in turn the defining pathological finding in AD. • Despite the strong association of Aβ with plaques, in reality plaques contain many other components. • Other associated components of the plaque include APOE, alpha-1 antitrypsin, complement factors, and immunoglobulins
  • 61. • Plaques can be divided into diffuse (Aβ mainly) and neuritic plaques (includes damaged tau containing axons and dendrites, i.e., neurites). • Cell components seen in plaques include neurites, microglia, and astrocytes. • The typical neuritic plaque has a dense core of Aβ and less compact rim consisting of neurites, microglia, and astrogliosis at the periphery. • Diffuse plaques have less diagnostic specificity and can be seen in a variety of different disorders. • They contain Aβ but do not stain with tau-containing neurites and are not associated with synaptic loss, reactive astrocytes, or microglia.
  • 62. Neurofibrillary Tangles • The major component of the NFT is tau within neurons and their cell processes. * First, pretangles form in the neuron cytoplasm, often concentrated around the membrane. Then, tau is organized into fibrils as NFTs. When the cell dies, the tangle may be situated extracellularly. Normal tau is a microtubule-associated protein and is not visible within the brain In NFTs, tau has become hyperphosphorylated and abnormally conformed. This tau can be detected with immunostains that bind abnormally conformed tau.
  • 63. Other pathological findings in AD • CAA, often present in leptomeningeal vessels, capillaries, small arterioles, and middle-sized arteries, is seen in over 80% of AD cases. In contrast to cerebral plaques consisting primarily of Aβ42, CAA’s major component is Aβ40. • Granulovacuolar bodies, typically found in the hippocampus, are small dense granules within the vacuole and can be labeled with acid phosphatase, tubulin, ubiquitin, and neurofilament. • Hirano bodies (eosinophilic rod bodies), also typically found in the hippocampus, are often in neuronal processes and contain actin and actin-binding proteins
  • 64. Treatment • 1)Acetylcholinesterase Inhibitors: Donepezil,Rivastigmine,Galantamine (advanced AD demonstrated depleted cholinergic neurons in the basal forebrain) 2)NMDA antagonists: Memantine 3) Vitamin E 4) Estrogen replacement therapy 5)Antiinflammatory medications