Transcript Alzheimer’s

Dementias
As of 4Feb2015. All items from DSM-IV,
DSM-5, APA Practice Guidelines,
Taman/Mohr Text, or Sadock/Sadock/Ruiz
Text unless otherwise indicated.
Dx criteria
• Q. What is the outline of the DSM dx
criteria of dementia?
Dx criteria - general
•
•
•
•
Ans.
1. Multiple cognitive deficits.
2. Gradual onset and decline
3. Not part of another Disorder
Dx criteria – Specific
Cognitive deficits
• Q. What cognitive deficits are part of the
DSM criteria of dementia?
Dx – specific
cognitive deficits
•
•
•
•
Ans.
1. Memory impairment
AND
2. At least one of the following:
–
–
–
–
Aphasia
Apraxia
Agnosia
Executive functioning deficits
Early onset
• Q. What is the dividing line between early
and late onset dementia?
Early Onset
• Ans.
• < or = 65, early onset
• > 65, late onset
Reasons to hospitalize
• Q. List reasons to hospitalize pts with
dementia.
Reasons to hospitalize
• Ans.
• 1. Symptom severity:
– Dangerousness to self or others, including
inability of caretakers to care for the pt
2. Intensity of care and treatment needed:
-- evaluations or treatments that cannot by
done on outpt basis.
Follow-up
• Q. If you have a “routine” pt with
Alzheimer’s, how often should the pt be
monitored by you?
Follow-up
• Ans. Every 3 to 6 months.
MMSE
• Q. What is the MMSE? And What does it
evaluate?
MMSE
• Ans.
• MMSE = Mini-mental status examination.
• MMSE tests cognitive functioning.
CT or MRI
• Q. When is CT or MRI advised as part of
the initial eval of people with dementia?
CT or MRI
Ans. Some would say in all, but the question
is more likely to focus on when one of
these tests is more indicated than most pts
with dementia:
– Early onset
– Relatively rapid onset
– High vascular risk factors suggested
– Neurological exam suggests local lesions
Neuropsych testing
• Q. When is neuropsych testing indicated?
Neuropsych testing
Ans. When questions arise as to whether
the individual actually has a “dementia.”
• [Keep in mind that only Mental Retardation
and Learning Disorders has psychological
testing as part of a DSM criteria set.]
Gene testing
• Q. Is gene testing recommended?
Gene testing
Ans. Gene testing is not recommended. Dx
is clinically based regardless of genes.
[See exceptions infra]
Apolipoprotein E-4
• Q. What is the significance of
apolipoprotein E-4 (APOE-4)?
Apolipoprotein E-4
Ans. Apolipoprotein E-4 [APOE-4], on
chromosome 19, is more common in
individuals with Alzheimer’s – but not
diagnostic.
Suicidal
• Q. At what stage of a dementia is suicidal
ideation most common?
Suicidal
Ans. Most common when the disease is still
mild.
Suicide and gender
• Q. Which gender is suicide most common
in this illness?
Suicide and gender
Ans. Men
[In answering exam questions as to
“successful” suicides, keep in mind that
men do so far more often than women,
and that is even more true in the elderly.]
Falls
• Q. Give one of major ways a physician can
reduce the chances of falls in pts with
dementia.
Falls
Ans. Review and considered discontinuance
of meds associate with falls.
Driving
• Q. Should a physician report their patient
who has dementia to the state department
of motor vehicles?
Driving
Ans. Varies by state. Required in some,
forbidden in others.
Dosing in the elderly
Q. What are the principles of medicating in
the elderly?
Medicating the elderly
Ans.
-- lower starting doses.
-- longer intervals between dose increases.
-- smaller dose increase
Medicating rules - why
Q. Why the go-slow approach with the
elderly?
Medicating rules - why
Ans.
slower hepatic metabolism
decreased renal clearance
Goal of medicating
Q. What is the goal of medicating a patient
with Alzheimer’s?
Goal of medicating
Ans. Delay progression of the disease. No
med reverses.
FDA for Alzheimer’s
Q. What meds have been approved for
Alzheimer’s?
FDA for Alzheimer’s
Ans.
donepezil
galantamine
memantine
rivastigmine
tacrine
FDA – med action
Q. Which of the five is/are cholinesterase
inhibitors? Which is/are NMDA
antagonist?
Meds - actions
Ans.
donepezil, galantamine, rivastigmine, and
tacrine are cholinesterase inhibitors.
memantine is a noncompetitive N-methylaspartate antagonist, glutamate
antagonist.
Vitamin E
• Q. What about high doses of Vitamin E for
Alzheimer’s?
Vitamin E
Ans. Not proven to be useful and high doses
may be associated with increased risk of
heart failure.
Vitamin E must be avoided in patients with
vitamin K deficiencies.
Q. Selegiline
1] Selegiline’s usefulness in dementia?
2] Especially problematic?
Ans. Selegiline
1] Not proven to be useful.
2] Should not be given to pt on an
antidepressant.
Tacrine
Q. Tacrine status?
Tacrine
Ans. Regarded as less preferred to
donepezil, rivestigmine, and galantamine
because of tacrine’s hepatic toxicity.
ECT
• Q. Indications for ECT in pts with
Alzheimer’s?
ECT
Ans. Indicated for pts with moderate to
severe depression and Alzheimer’s and
who do not respond to or cannot tolerate
antidepressant meds.
Delusions and hallucinations
• Q. Pt is moderately impaired from
Alzheimer’s, has delusions and
hallucinations and is not distressed or
agitated, meds?
Hallucinations and delusions
Ans. No meds, instead reassurance,
redirection and distractions.
Hallucinations and delusions
• Q. Alzheimer’s pt with hallucinations and
delusions and combative, meds?
Hallucinations and delusions
Ans. Low dose antipsychotic.
[This is true of the Guides. Recent FDA
warnings would suggest ordering
antipsychotics at quite low levels to begin - given the increased death rate of the
elderly on antipsychotics.]
Profoundly impaired
• Q. What meds help the cognition of the
severely impaired?
Profoundly impaired
Ans. Memantine is approved for the
profoundly impaired. Cholinesterase
inhibitors are not.
Meds & Delirium
• Q. What classes of meds can cause
delirium in those with Alzheimer’s?
Delirium & meds
Ans. Virtually all psychotropic meds, even
more so, those having anticholinergic
activity.
Anticholinergic
• Q. What are some meds psychiatrists use
that have anticholinergic activity?
Anticholinergic
Ans. Tricyclics, low-potency antipsychotics,
and diphenhydramine.
Dopaminergic meds
• Q. Dopaminergic meds used in
Parkinson’s disease in pt who also has
Alzheimer’s predisposes that pt to?
Dopaminergic meds
Ans. Visual hallucinations
Vascular dementia
• Q. Treatment for vascular dementia?
Vascular dementia
Ans.
• -- control BP
• -- low-dose aspirin
[2 of 3 trials with donepezil found some
positive results, but the 3rd trial lack of
effectiveness probably precludes it being
the correct answer.]
Fronto-temporal dementia
• Q. What med has been shown to decrease
problematic behaviors of fronto-temporal
dementia, e.g., agitation?
Fronto-temporal dementia
Ans. Trazodone.
[If trazodone is not one of the choices,
amantadine has some anecdotal support.]
Caregivers and depression
• Q. To what degree does depression occur
in caregivers?
Caregivers and depression
Ans.
• 30% of spousal care-givers experience a
depressive disorder.
• 22-37% of adult children care-givers, the
higher percentage, > 30%, in those with a
prior hx of a mood disorder.
Federal Regulation
• Q. A major law, passed in 1987, that
regulates the use of physical restraints
and use of meds in nursing home is?
Federal Regulation
Ans. The Omnibus Budget Reconciliation
Act of 1987 [OBRA].
Gender
• Q. In Alzheimer’s, which gender is more
frequent?
Gender
Ans. More common in women.
African Americans
• Q. Relative to Caucasians, Which
dementias do African Americans have
more and which do they have less?
African Americans
Ans. More vascular dementia [could guess
from their higher hypertension rate] and
less Parkinsonian dementias.
Family Hx
• Q. If Mrs. X has Alzheimer’s, what the
chances of her siblings or children getting
Alzheimer’s?
Family hx
Ans. Two to four times that of the general
population.
Genes – early onset
• Q. What are the three genes that have an
increased association with early on-set
Alzheimer’s?
Genes – early onset
Ans.
• 1. Amyloid precursor protein [APP] on
chromosome 21
• 2. Presenilin 1 [PSEN1] on chromosome
14
• 3. Presenilin 2 [PSEN2] on chromosome 1
Vascular dementia
• Q. Onset and course of vascular
dementia?
Vascular dementia
Ans. Acute onset and step-wise decline.
Alzheimer’s onset - age
• Q. Give the approximate onset of Alzheimer’s
per the age of the individual, such as % per year
of:
• < 65
• 65-70
• 70-75
• 75-80
• 80-85
• >85
Alzheimer’s onset - age
• < 65 – rare
• 65-70 – 0.5%/ year [i.e., one in 200 will develop
Alzheimer’s within a year]
• 70-75 – 1%
• 75-80 – 2%
• 80-85 – 3%
• >85 – 8% [Means that the odds of someone who does
not have Alzheimer’s at 85 has an 8% chance of having
the onset over the next 12 months. The jump from 3% to
8% doesn’t seem correct for 85 y/o compared to 84 y/o,
so the “8” percent must be based on the average of all
over 85. I’m not sure.]
Mild cognitive impairment
• Q. Criteria for “mild cognitive impairment”?
Mild cognitive impairment
• 1. Subjective memory complaints
• 2. Objective cognitive deficits on testing
• 3. Functioning OK
Vascular dementia - onset
• Q. Relative to age, what is the incidence of
the onset of vascular dementia?
Vascular dementia - onset
Ans. Gradually increases with age, so forms
an increased percentage of those with
neurocognitive disorders with age, such as
those >85. More common in men.
Lewy body disease
• Q. Lewy body disease differs in clinical
presentation from Alzheimer’s in what
ways?
Lewy body disease
Ans. Differs:
• -- early and more prominent visual
hallucinations
• -- early and more prominent Parkinsonian
features [leading to falls]
• -- more rapid decline
Lewy body disease - meds
• Q. When you decide to prescribe
antipsychotic medications to someone with
Lewy body disease has, what prominent
signs are your concern?
Lewy body disease - meds
Ans. Very sensitive to extrapyramidal signs.
Frontotemporal dementia
• Q. Characteristics of frontotemporal
dementia in comparison to Alzheimer’s?
Frontotemporal dementia
Ans.
• -- personality change early
• -- apathy early
• -- emotional blunting early
• -- disinhibition early
• -- language abnormalities early
• -- memory problems late
• -- apraxia late
• [the examiner may use “Pick’s disease” for this entity]
• [Hard to remember all 7 items, but recalling that memory
is relatively late may get you the correct answer.]
Frontotemporal dementia - onset
• Q. Common age of onset?
Frontotemporal dementia - onset
Ans. Onset tends to be between 50 and 60.
Huntington’s disease - gene
• Q. Genetic aspect of Huntington’s?
Huntington’s - genes
Ans. Autosomal dominate.
Huntington’s - pathology
• Q. Pathology of Huntington’s?
Huntington’s - pathology
Ans. While there is damage to many
subcortical structures, the answer they are
probably looking for is “basal ganglia.”
Creutzfeldt-Jakob disease etiology
• Q. What two etiologies are seen in this
disease?
Creutzfeldt-Jakob disease etiology
Ans.
-- slow virus
OR
-- a prion [proteinaceous infectious particle]
Tardive Diskinesia risks
Q. Relatively to age, gender, and dementia,
what are TD risks when using
antipsychotics?
TD risks
Ans. Relative to use of antipsychotics,
increased risk:
1. in women,
2. increased risk in the elderly and
3. increased in those with dementia
delirium
Q. What meds used in psychiatry are
associated with delirium when used with
people with Alzheimer’s?
delirium
Ans. “Virtually all” [Practice Guideline]
Exercise
Q. Role of exercise in pts with Alzheimer’s?
Exercise
Ans. Reduces depression in addition to
other health benefits.
MMSE & “moderate level”
Q. Moderate level of dementia is associated
with what MMSE score?
MMSE & “moderate level”
Ans. 9 -18.
Alzheimer’s Neuropathology?
Ans. Alzheimer’s Neuropathology
1] Flattened cortical sulci
2] Enlarged cerebral ventricles
3] Senile plaques
4] Neurofibrillary tangles
5] Neuronal loss, especially in the cortex
and hippocampus
6] Granulovascular degeneration in the
neurons
Also seen in?
Neuropathology of Alzheimer’s also seen in?
Ans. Also seen in.
1] Down’s
2] Dementia pugilistica
3] Parkinson-dementia complex of Guam
4] Hallervoren-Spatz Disease
5] Familial Multiple System Taupathy
6] Normals as they age
Senile Plaques
Composed of?
Senile Plaques
Composed of
Beta/A4
Neurotransmitters Often
Implicated in Alzheimer’s?
Neurotransmitters Often
Implicated in Alheimer’s
1] Acetylcholine, hypoactive
2] Norepinephrine, hypoactive
Cholinergic Antagonists?
Two cholinergic antagonists that impair
cognitive ability?
Cholinergic Antagonists
1] Scopolamine
2] Atropine
[Not complete, but likely to reach questions.]
Cholinergic Agonists?
Name of cholinergic agonists that would
enhance cognition?
Cholinergic Agonist
Physostigmine
Vascular Dementia
Seen In?
Gender?
Medical History?
Vascular Dementia
Is Seen In
Men with hypertension
Binswanger’s Disease?
Pathology of Binswanger’s Disease?
Binswanger’s Disease
Many small infarcts of the white matter that
spares the cortical region.
Pick’s Disease
Pathology?
Pick’s Disease
Pathology
Also called Frontotemporal Dementia.
Atrophy in the frontotemporal region where
neuronal loss, gliosis, and masses of
cytoskeletal elements are most present.
What is
Kluver-Bucy Syndrome?
Kluver-Bucy Syndrome
1] Hypersexuality
2] Placidity
3] Hyperorality
Kluver-Bucy
Syndrome Caused By?
Kluver-Bucy
Syndrome Caused By
Damage to both medial temporal lobes.
Bradyphrenia?
Means?
And seen in?
Bradyphrenia
• Bradyphrenia is a neurological term
referring to the slowness of thought
common to many disorders of the brain.
• Disorders characterized by bradyphrenia
include Parkinson's disease and forms of
schizophrenia. Bradyphrenia can also be a
side effect of psychiatric medications
Sundowner Syndrome?
1] Clinical picture?
2] Causes?
Sundowner Syndrome
Clinical picture: confusion and ataxia.
Causes: in demented patients when external
stimuli, light or interpersonal cues are
diminished.
Step-wise Cognitive
Deterioration?
Seen in?
Step-wise Deterioration
Seen in vascular dementia
Alcohol withdrawal?
Manifestations?
Treatment?
Alcohol withdrawal
Manifestations
Irritability, nausea, vomiting, insomnia,
malaise, autonomic hyperactivity,
shakiness
Alcohol withdrawal
treatment
Fluids, sedate with benzodiazepines, 100
mg thiamine IM
Idiosyncratic Alcohol
Intoxication?
1] manifestation?
2] treatment?
Idiosyncratic Alcohol
Intoxication, Manifestation
Marked aggressive and assaultiveness.
Idiosyncratic Alcohol
Intoxication - treatment
Protective environment.
Q. Alzheimer’s
Diagnostic Markers
Ans. Alzheimer’s
Diagnositc Markers
1] cortical atrophy
2] amyloid-predominant neuritic plaques
3] tau-predominant neurofibrillary tangles
Q. Markedly Diminished
in Alzheimer’s
Ans. Markedly Diminished
in Alzheimer’s
Choline acetyltransferase
Acetylcholine
Q. If need a benzodiazepine
in treating Alzheimer’s
Ans. If needing a benzodiazepine
in treating Alzheimer’s
Go with short acting, lorazepam or
oxazepam
Q. If Needing to
use an antipsychotic?
In pts with Alzheimer’s
Q. If needing to
use an antipsychotic
Ans. Select with low anticholinergic activity
Q. Pathology of
Parkinsonian’s Disease?
Ans. Pathology of
Parkinsonian’s Disease
Pathology is especially seen in substantia
nigra
Q. Parkinson’s
Halluncinations?
Ans. Parkinson’s
Hallucinations
Visual
Q. Head Trauma
Physical Findings
Ans. Head Trauma
Physical Findings
Ans.
1. Blood behind tympanic membrane
2. Subconjunctival ecchymosis [raccoon
eye sign]
3. Pupillary abnormalities
Q. Wilson’s genetic finding?
Which chromosome?
Ans. Wilson’s
Genetic Finding
Ans. On chromosome 13
Q. Chronic Traumatic
Encephalopathy – signs?
Ans. Chronic Traumatic
Encephalopathy - signs
1] Dysarthric speech
2] Emotional liability
3] Slow thinking
4] Impulsivity
Q. Compare
as to cognitive severity
Amyloid-predominant neuritic plaques?
Tau-predominant neurofibrillary tangles?
Ans. Compare as to
Severity
The plaques are more a sign of severity than
the tangles
Q. Apolipoprotein?
Ans. Apolipoprotein
Risk factor for Alzheimer’s but neither
necessary or sufficient factor.
Q. Frontotemporal
Neurocognitive Disorder
Pathology?
Name two types and associated pathology.
Ans. Frontotemporal
Neurocognitive Disorder
Behavioral-variant has both frontal lobes
and anterior temporal lobes are atrophied
Semantic language-variant has temporal
lobe atrophy at the middle, inferior, and
anterior parts of that lobe
Q. Wing-beating tremor?
Seen in?
Ans. Wing-beating tremor,
Seen In
Wilson’s
Q. Lewy Body
Pathology?
Ans. Lewy
Body
The underlying neurodegenerative disease
is synucleinopathy due to alpha-synuclein
misfolding and aggregation.
Q. Tramantic Brain
Injury
Neurological/Mental Signs?
Ans. TBI
loss of consciousness
posttraumatic amnesia
Disorientation and confusion
Neurological signs, e.g., seizures
Q. Creutzfeldt-Jakob
A form of?
Ans. Creutzfeldt-Jakob
One of the prion diseases
Q. Huntington’s Disease
Diagnostic marker?
Ans. Huntington’s Disease
Genetic testing for trinucleotide CAG on
chromosome #4.
Q. Hirano’s bodies?
Ans. Hirano’s bodies
Seen in Alzheimer’s.
• Hirano bodies are intracellular aggregates of actin and
actin-associated proteins first observed in neurons
(nerve cells) by Asao Hirano in 1965.[1]
• Hirano bodies are found in the nerve cells of individuals
afflicted with certain neurodegenerative disorders, such
as Alzheimer's disease and Creutzfeldt-Jakob
disease.[2]
• Hirano bodies are often described as rod-shaped,
crystal-like, and eosinophilic.
• Hirano bodies have been noted as a function of age
without obvious underlying neurodegeration