Dementia is a term used to describe

a cluster of symptoms including:

Forgetfulness (progressive)
Difficulty doing familiar tasks
Confusion
Poor judgment
Decline in intellectual functioning
Dementia is not the name of an actual
disease
Dementia is not a part of normal aging

Dementia
Reversible:
D= Drugs, Delirium
E= Emotions (such as depression) and
Endocrine Disorders
M= Metabolic Disturbances
E= Eye and Ear Impairments
N= Nutritional Disorders
T= Tumors, Toxicity, Trauma to Head
I= Infectious Disorders
A= Alcohol, Arteriosclerosis
Dementia
Irreversible:
Alzheimers
Lewy Body Dementia
Picks Disease (Frontotemperal Dementia)
Parkinsons
Heady Injury
Huntingtons Disease
Jacob-Cruzefeldt Disease

Table 8. Diagnostic Criteria for Dementia (DSM-IV)
Memory impairment: impaired ability to learn new information or to
recall old information
One or more of the following: aphasia (language disturbance); apraxia
(impaired ability to carry out motor activities despite intact motor
function); agnosia (failure to recognize or identify objects despite intact
sensory function); disturbance in executive functioning-impaired ability
to plan, organize, sequence, abstract
The cognitive deficits result in functional impairment
(social/occupational)
The cognitive deficits do not occur exclusively solely during a delirium
NOT due to other medical or psychiatric conditions
Alzheimers disease (approximately 70%)
Vascular dementia (Strokes and TIAs)
Parkinsons disease
Frontotemporal dementia (FTD)
Normal-Pressure hydrocephalus (NPH)
Dementia with Lewy Bodies
Delirium/Depression
Other, less common causes
Clinical course
Neuropathorogy and Biochemistry of AD
Neuropathology

Alzheimer's disease is characterised by loss of neurons and
synapses in the cerebral cortex and certain subcortical regions.
This loss results in degeneration in the temporal lobe and
parietal lobe, and parts of the frontal cortex.
Reductions in the size of specific brain regions in patients as
they progressed from mild cognitive impairment to Alzheimer's
disease.



Both amyloid plaques and neurofibrillary tangles are clearly visible by
microscopy in brains of those afflicted by AD.

Plaques are dense, mostly insoluble deposits of amyloid-beta
peptide and cellular material outside and around neurons.
Tangles (neurofibrillary tangles) are aggregates of the microtubule-
associated protein tau which has become hyperphosphorylated and
accumulate inside the cells themselves.


Biochemistry

Enzymes act on the APP (amyloid precursor protein) and cut it
into fragments. The beta-amyloid fragment is crucial in the
formation of senile plaques in AD.

AD has been identified as a protein misfolding disease, caused by
accumulation of abnormally folded A-beta and tau proteins in the
brain.

Plaques are made up of small peptides, 3943 amino acids,
called beta-amyloid (also written as A-beta or A).
fragment from a larger protein called APP, a transmembrane
protein that penetrates through the neuron's membrane.
(APP: neuron growth, survival and post-injury repair)

Neuropathorogy and Biochemistry of AD
Biochemistry

In Alzheimer's disease, an abnormal aggregation of the tau
protein lead to the disintegration of microtubules in brain cells.

Tau protein(microtubule-associated protein) stabilizes the
microtubules when phosphorylated.
In AD, tau becoming hyperphosphorylated; creating
neurofibrillary tangles and disintegrating the neuron's transport
system.
Neuropathorogy and Biochemistry of AD
Genetic: Familial AD and risk factors
The majority of cases of Alzheimer's disease are sporadic
not genetically inherited although some genes may act as risk factors
around 0.1% of the cases are familial forms of autosomal-dominant
inheritance

Autosomal dominant familial AD can be attributed to mutations in one of
three genes: amyloid precursor protein (APP) and presenilins 1 and 2.
Mutations in the APP and presenilin genes increase the production of a
A42.

The best known genetic risk factor is the inheritance of the 4 allele of the
apolipoprotein E (APOE).
Between 40 and 80% of patients with AD possess at least one apoE4 allele.
Therefore the APOE4 allele increases the risk of the disease.
APP and PS families of proteins
Familial Alzheimer disease is caused by mutations in at least 3 genes:

PSEN1 - Presenilin 1 (PSEN1 located on chromosome 14)
Mutations in this gene cause familial Alzheimer's type under 50 years
old.
This protein has been identified as part of the enzymatic complex that
cleaves amyloid beta peptide from APP.

PSEN2 - Presenilin 2 (PSEN2 located on chromosome 1)
The presenilin 2 gene is very similar in structure and function to PSEN1.

APP Amyloid beta (A4) precursor protein

Processing of the amyloid precursor protein
Mutations to the amyloid beta A4 precursor protein (APP) located on the
long arm of chromosome 21 causes familial Alzheimer disease.
Secretase

BACE1
-amyloid cleaving enzyme1
This transmembrane aspartyl protease is directlly involved in
the cleavage of APP at the sites of A in APP.

-secretase
This multiprotein catalytic complex includes PS1 and PS2;
nicastrin (Nct), a type 1 transmembrane glycoprotein; and
Aph-1 and Pen-2, two multipass transmembrane protein.
APP and PS families of proteins
Processing of APP by secretases
Genetic models of A amyloidosis
and AD-linked taupathies
A amyloidosis

Amyloid beta is a peptide of 39-43 amino acids
Main constituent of amyloid plaques in the brains of Alzheimers
disease patients.
A is proteolytically derived from a larger integral membrane
protein, the amyloid precursor protein (APP).


AD-linked taupathies

Taupathies are a class of neurodegenerative diseases resulting
from the pathological aggregation of tau protein in so-called
neurofibrillary tangles (NFT) in the human brain.


Targeting of genes encoding
amyloidogenic secretases
To understand the function of some of the proteins thought to have roles in
AD: targeted a variety of genes including BACE1, PS1, Nct, and Aph-1.

BACE1-/- Mice
BACE1 is a key enzyme in the generation of the A peptide that plays a
central role in the pathogenesis of Alzheimer's disease.

PS1-/- Mice
PS1 knock-in mice exhibited NFT-like tau pathology in the absence of A
deposition.
PS1 mutations contribute to the onset of AD not only by enhancing A
142

production but by also processing that lead to neurodegeneration.


progressive neurologic disorder that results in
memory loss, personality changes, global
cognitive dysfunction, and functional
impairments.
Loss of short-term memory is most prominent
early.
In the late stages of disease, patients are totally
dependent upon others for ADLS
the most common form of dementia in the
elderly, accounting for 60 to 80 % of cases
estimated to affect more than 4 million
Americans

Clinical diagnosis
History, mental status evaluation, physical
examination, limited laboratory testing, and in
many cases, neuroimaging, more extensive
neuropsychological testing and a depression
screen.
An MRI finding of bilateral hippocampal atrophy
suggests AD, but is not specific or sensitive
The laboratory testing includes a CBC,
electrolytes, glucose, BUN and creatinine, serum
B12, TSH and liver function tests.
MMSE score
CDR
CDR (Clinical Dementia Rating) digunakan
untuk menilai gejala klinis dan
menentukan stadium dari demensia
Penilaian CDR :
0 : tidak ada demensia (healthy)
0,5 : demensia dipertanyakan
(questionable)
1 : demensia ringan (mild dementia)
2 : demensia sedang (moderate)
3 : demensia berat (seviere)
Atrophic hippocampus in AD
Compare central sulcus of
Alzheimers patient with
normal 81 year old woman
From Whole Brain Atlas at http://www.med.harvard.edu/AANLIB/home.html

74 year old AD patient: reduced blood
flow on SPECT in temporal areas
Normal vs AD Brain
Normal
brain
Alzheimers
brain
There are 3 consistent
neuropathologicalhallmarks:
Amyloid-rich senile plaques
Neurofibrillarytangles
Neuronal degeneration
These changes eventually lead to
clinical symptoms, but they begin years
before the onset of symptoms
Drugs used to treat Alzheimers
disease act by inhibiting
acetylcholinesterase activity
These drugs block the esterase-
mediated metabolism of acetylcholine to
choline and acetate. This results in:
Increased acetylcholine in the synaptic
cleft
Increased availability of acetylcholine for
postsynaptic and presynaptic nicotinic (and
muscarinic) acetylcholine receptors
VASCULAR DEMENTIA
The onset of cognitive deficits
associated with a stroke
Abrupt onset of symptoms followed
by stepwise deterioration
Findings on neurologic examination
consistent with prior stroke(s)
Infarcts on cerebral imaging
criteria for probable vascular
dementia
Cerebrovascular disease evident on
history, examination or imaging
Two disorders must be related by
onset of dementia within 3 months or
abrupt, fluctuating or stepwise
progression
Features that make vascular
dementia uncertain or unlikely
Early memory loss and progressive
deterioration in the absence of
corresponding focal lesions on imaging
Absence of focal neurological signs
Absence of cerebrovascular lesions on CT
or MRI

Clinical features supportive of
vascular dementia
Early gait disorder
Frequent falls
Urinary incontinence or frequency early in
disorder
Pseudobulbar palsy
Personality and mood changes


characterized by focal atrophy of the frontal and
temporal lobes in the absence of Alzheimer
pathology
Pick's disease was the first recognized subtype
of FTD, one that is characterized pathologically
by the presence of Pick bodies (silver staining
intracytoplasmic inclusions) in the neocortex and
hippocampus.
Clinically, presents with language abnormalities
and behavioral disturbances.
occurs between the ages of 35 and 75
years, and only rarely after age 75; the
mean age of onset is the sixth decade
Both sexes are equally affected.
Familial occurrence occurs in 20 to 40
percent of cases and may be associated
with a variety of identified mutations in the
tau gene on chromosome 17
Frontotemporal Lobe Dementia
Core Features
Insidious onset and gradual progression
Early decline in social/interpersonal conduct
Early impairment in personal conduct
Early loss of insight
Early emotional blunting
Supportive Features
Behavior disorder hygiene, grooming, mental
rigidity, dietary changes, perseverative behavior
Speech and language perseveration, mutism,
economy of speech
Physical signs akinesis, rigidity, tremor, labile
BP

a condition of pathologically enlarged
ventricular size with normal opening
pressures on lumbar puncture
triad of dementia, gait disturbance, and
urinary incontinence
reversible by the placement of a
ventriculoperitoneal shunt
Core And Supportive Features For Clinical Diagnosis Of DLB
1. The central feature required for a diagnosis of DLB is progressive
cognitive decline of sufficient magnitude to interfere with normal
social or occupational function
2. Two of the following core features are essential for a diagnosis of
probable DLB, and one is essential for possible DLB.
Fluctuating cognition with pronounced variations in atten- tion and
alertness
Recurrent visual hallucinations that are typically well formed and
detailed.
Spontaneous motor features of parkinsonism.
3. Features supportive of the diagnosis are
repeated falls
syncope
transient loss of consciousness
neuroleptic sensitivity
systematized delusions
hallucinations in other modalities.
the most common dementia syndrome
associated with parkinsonism
the second most common form of
neurodegenerative dementia after Alzheimer
disease (AD).
characterized by dementia accompanied by
delirium, visual hallucinations, and
parkinsonism. Other common symptoms include
syncope, falls, sleep disorders, and depression.
The presence of both Lewy bodies and amyloid
plaques with deficiencies in both acetylcholine
and dopamine neurotransmitters suggests that
dementia with Lewy bodies represents the
middle of a disease spectrum ranging from
Alzheimers disease to Parkinsons disease
Cardinal motor features
Brady- and akinesia
Rigidity
Resting tremor
Postural instability
Dementia typically occurs in the last
half of the clinical course of PD,
whereas it is often one of the
presenting features of DLB.
Progressive supranuclear palsy
also known as Steele Richardson Olszewski
syndrome
a rare syndrome that can mimic PD in its early
phase
Characteristic features of PSP
vertical supranuclear palsy with downward gaze
abnormalities
postural instability with unexplained falls
Bradykinesia and rigidity are typically symmetrical in
onset
Apathy, disinhibition, dysphoria, and anxiety are
common
classic neuropathologic features
of PSP
globose neurofibrillary tangles (NFT) consisting
of hyperphosphorylated tau proteins.
These lesions and accompanying neuronal loss
are seen primarily in the substantia nigra,
subthalamic nucleus, globus pallidus, superior
colliculus and midbrain, and pontine reticular
formation.
Cortical involvement is more variable but
predominately affects the frontal lobes.
AD Prognosis
Alzheimers has a slowly progressive
decline. These meds can slow the
progression, NOT halt it.

Time
F
u
n
c
t
i
o
n

End-stage Dementia
Prognosis < 6 mos:
Severe dementia with need for total assistance
in ADLs (dressing, bathing, continence), unable
to walk, only able to speak a few words
Comorbid conditions aspiration pneumonia,
urosepsis, decubiti, sepsis
*Unable to maintain caloric intake with weight
loss of 10% or more in 6 months (and no feeding
tubes)

Complications from dementia
Delusions in up to 50%, most with paranoia
Hallucinations in up to 25%
Depression, social isolation may also occur
Aggressive behavior in 20-40% (may be related
to above problems, misinterpretation)
Dangerous behavior driving, creating fires,
getting lost, unsafe use of firearms, neglect
Sundowning nocturnal episodes of confusion
with agitation, restlessness

Treatment of complications
Hallucinations, delusions, agitation, sun-downing may be
improved with anti-psychotics like haloperidol, risperdal,
mellaril
If any signs of depression, may be beneficial to treat
Anxiety may respond to benzodiazepines
Behavioral mod reinforce good behavior, DONT fight
aggressive behavior
Familiarity (change in environments make things worse)
Safety key locks, knobs off stoves, take away car
keys/cigarettes/firearms, lights, watch stairs
Avoid restraints, use human contact/music/pets/
distraction

Artificial Nutrition in Dementia
Many excellent reviews demonstrate no
improvement in quality of life and quantity
of life with G-tubes.
5% morbidity and mortality with the
procedure itself
No decrease in aspiration with them
Risk of infection
Can keep patient comfortable without it
Complications from dementia
Delusions in up to 50%, most with paranoia
Hallucinations in up to 25%
Depression, social isolation may also occur
Aggressive behavior in 20-40% (may be related
to above problems, misinterpretation)
Dangerous behavior driving, creating fires,
getting lost, unsafe use of firearms, neglect
Sundowning nocturnal episodes of confusion
with agitation, restlessness

Drug treatment in Alzheimers
disease
Many drugs aim to stimulate the
cholinergic system
These drugs have limited positive effects
and do not reverse the causes of AD
Dementia patients are very
sensitive to additional
disabilities
Illness
Pain
Medications
Poor hearing
Poor vision
Management of depression at
end of life
Psychotherapy behavioral, cognitive, and
other supportive approaches by psychologists,
licensed social workers, chaplains, even
bereavement counselors may help
New coping strategies like meditation,
relaxation, guided imagery, hypnosis may help
Medications

Suicide
Women attempt it twice as much, but men are 4x
more likely to succeed
White men over 85 are at highest risk to do it
All patients with depressive symptoms should be
assessed for it
Talking about it can decrease risks
High risk of attempt if thoughts are recurring or if
have thought out the plan
ONE OTHER POTENTIAL EMERGENCY:
If risk high DONT leave client alone, immediately
consult a psychiatrist may need in-patient care or
involvement of authorities
Anxiety
May be a normal response to the situation
fears, uncertainty, reaction to physical condition,
social or spiritual needs
Usually with 1 or more of the following signs
agitation, restless, sweating, tachycardia,
hyperventilation, insomnia, excessive worry,
tension
Look for signs of depression, delirium,
alcohol/drug abuse, caffeine abuse
About 5% are affected by agoraphobia
Related anxiety conditions
Panic attacks acute onset of palpitations,
sweating, hot, shaking, chest pain, nausea,
dizzy, derealization, fear, numbness; usually
short lived
Phobias fears with avoidance, feelings of
being trapped, exposed
Post-traumatic Stress Syndrome in response
to severe trauma, get more intense fear, terror,
dreams, feelings of helplessness, detachment
that can occur later on
Alzheimers Association: http://www.alz.org/
National Institute of Neurological Disorders
and Strokes page on dementia:
http://www.ninds.nih.gov/disorders/dementias/de
mentia.htm
How to manage difficult behaviors from the
Association for Frontotemporal Disorders:
http://www.ftd-picks.org/?p=caregiver.managing