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Transcript
DEMENTIA: EVALUATION
AND TREATMENT
ANNA BORISOVSKAYA, MD
(WITH CONTRIBUTIONS BY
J. FREDERICK, MD AND S. THIELKE, MD)
Epidemiology
2
 US population is “graying”
 By 2030 there may be 70 million elderly in the US
(currently around 35 million)
 Prevalence of dementia in 65+ year olds: 6-8%
 Prevalence of dementia in 80+ year olds: 30%
 Most common type of dementia is Alzheimer’s: 5.2
million Americans have Alzheimer’s as of 2013
Terminology
3
 Deriving from Latin (demens – mad)
 “A mental illness that causes someone to be unable
to think clearly or to understand what is real and
what is not real” – according to Merriam-Webster
dictionary
 In psychiatry, used to be termed dementia, now
called major neurocognitive disorder
 “Early onset” – before the age of 60, often familial,
more common for FTD
 “Late onset” – after the age of 60
DSM-V Criteria for Major Neurocognitive Disorder
4
Evidence of significant cognitive decline from a previous level of
performance in one or more cognitive domains*:
- Learning and memory
-Complex attention
- Language
-Perceptual-motor
- Executive function
-Social cognition
B. The cognitive deficits interfere with independence in everyday
activities. At a minimum, assistance should be required with complex
instrumental activities of daily living, such as paying bills or managing
medications
C. The cognitive deficits don’t occur exclusively in the context of a
delirium
D. The cognitive deficits aren’t better explained by another mental
disorder
A.
* Evidence of decline is based on: concern of
the individual, a knowledgeable informant, or the clinician
that there has been a significant decline in cognitive function and a substantial impairment in cognitive
performance, preferably documented by standardized neuropsychological testing or in its absence another
quantified clinical assessment.
Common syndromes encountered in dementia
5
 Aphasia – problems with language, comprehension
 Apraxia – problems with carrying out motor activities
(that the person was previously able to do)
 Agnosia – inability to recognize objects despite intact
sensory function (visual or tactile)
 Impaired executive function: difficulty with
planning, initiating, sequencing, monitoring, or stopping
complex behaviors
All of the above contribute to loss of IADLs
Cognitive decline AND associated neuropsychiatric
symptoms lead to increasing dependence on others and
often eventual institutionalization
ADL and IADL
6
Activities of daily living
(ADL)
 Bathing
 Dressing
 Grooming
 Toileting
 Continence
 Transferring
Instrumental activities of
daily living (IADL)
 Using a phone
 Travel
 Shopping
 Preparing meals
 Housework
 Medication management
 Money management
Someone presents with cognitive problems…
what do you do?
7
 Thorough history (medical, psychiatric, neurological)
 Speak to the collateral!! Are ADL/IADLs affected?
 Physical and neurological exam
 Cognitive testing (screening, then more detailed if




needed)
Labs and imaging (rule out reversible causes)
Consider neuropsychological testing or referral to
psychiatry or neurology
Determine the etiology/establish the diagnosis
Treat! (or refer)
Labwork/Imaging
8
Labwork
 Chem 10
 CBC
 LFTs
 TSH
 B12, Folate
 RPR, HIV
 Others only if clinical
suspicion is high
Imaging
 CT HEAD
NONCONTRAST is
standard
 MRI if vascular dementia
is suspected
 SPECT or PET – usually
not in the initial workup,
but may be helpful to aid
in difficult diagnosis, r/o
FTD
A few words about “reversible” dementias
9


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


Drug toxicity
Metabolic disturbance
Normal pressure hydrocephalus
Mass lesion (tumor, subdural hematoma)
Infection (meningitis, syphilis)
Collagen-Vascular disease (SLE, Sacroid)
Endocrine disorder (thyroid, parathyroid)
Nutritional disease (B12, thiamine, folate)
Other (COPD, CHF, Liver disease, apnea…)
Only 9% are potentially reversible
Only 0.6% actually reverse with treatment
Cognitive screening
10
 MMSE (beware of false positives and negatives)- useful
to have at baseline, can track changes over time. In
Alzheimer’s, patients lose 3 points/year.
 MOCA – free, comprehensive, not easy! Catches those
with higher premorbid functioning levels. Mocatest.org
 Mini-Cog – combines clock drawing and three item
memory test. See scoring guidelines next slide.
 SLUMS – better psychometric properties than MMSE,
with scoring normed to educational level
http://medschool.slu.edu/agingsuccessfully/pdfsurveys/
slumsexam_05.pdf
MINI-COG
11
Your best bet in a busy clinic setting.
1. Instruct the patient to listen carefully to and remember
these 3 words: banana-sunrise-chair
2. Instruct the patient to draw the face of a clock, after the
numbers are placed, ask them to draw the hands of the
clock to read “one ten.”
3. Ask the patient to repeat the 3 previously stated words.
SCORING: 1 point for each recalled word. Patients recalling
none of the words are cognitively impaired (score 0). Patients
recalling all 3 words are not cognitively impaired (Score 3).
Patients with word recall or 1-2 words are classified based on the
clock drawing test: abnormal clock= cognitively impaired,
normal = not cognitively impaired.
Clock Drawing Test--abnormal
Dementia syndromes
13
 Alzheimer’s disease
 Vascular dementia
 Lewy body dementia (LBD)
 Parkinson’s disease dementia (PDD)
 Fronto-temporal dementia (FTD)
 Mixed pathology
 Korsakoff’s
Alzheimer’s disease
14


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Insidious onset, gradual progression, incidence age-related
Short term memory problems on presentation
Most common dementing illness
Ultimate diagnosis based on pathology of neurofibrillary
tangles and senile plaques
Biochemically characterized by a deficiency of acetylcholine,
with cortex, amygdala, hippocampus all affected
Basal nucleus of Meynert depleted of acetylcholine-containing
neurons
In minority of cases there’s an autosomal dominant
inheritance linked to chromosomes 1, 14, or 21 (early onset)
Apolipoprotein E gene, coded on chromosome 19, when
homozygous for allele E4, increases the risk for late onset
Alzheimer’s
Course of Alzheimer’s Disease
15
Mild (MMSE 20-24) – primarily memory and visuospatial
deficits, mild executive functioning impairment
Moderate (MMSE 11-20) – more pronounced aphasia,
apraxia, loss of IADLs, may need increased assistance with
ADLs, often exhibiting neuropsychiatric symptoms
Severe (MMSE 0-10) – severe language disturbances,
pronounced neuropsych manifestations, neurological
symptoms (rigidity, incontinence, dysphagia, gait
disturbance)
Death 8-12 years after the diagnosis
Institutionalization common with increasing
neuropsychiatric sx, loss of ADLs, caregiver stress
Vascular dementia
16
10-20% of dementia cases in North America (10-15% cases of
AD are actually mixed AD/vascular)
NINDS-AIREN criteria used clinically, defined as presence of
- Dementia
- Cerebrovascular disease (focal signs on neuro exam and
evidence of CVD on imaging)
- Relationship between the two, as in:
a)Onset of dementia within 3 months since a recognized stroke
and/or
b)Abrupt deterioration in cognitive function or stepwise,
fluctuating progression of cognitive deficits
Vascular dementia: cortical subtype
17
Symptoms are related to the areas
affected/strategically placed infarcts:
 Medial frontal: executive dysfunction, abulia, or
apathy. Bilateral medial frontal lobe infarction may
cause akinetic mutism.
 Left parietal: aphasia, apraxia, or agnosia.
 Right parietal: hemineglect (anosognosia,
asomatognosia), confusion, agitation, visuospatial
and constructional difficulty.
 Medial temporal: anterograde amnesia.
Vascular dementia: subcortical subtype
18
Lacunar infarcts and chronic ischemia affect white matter
pathways and deep cerebral nuclei:
 Focal motor signs
 Early presence of gait disturbance
 History of unsteadiness and frequent, unprovoked falls
 Early urinary frequency, urgency, and other urinary
symptoms not explained by urologic disease
 Pseudobulbar palsy
 Personality and mood changes, abulia, apathy, depression,
emotional incontinence
 Cognitive disorder characterized by relatively mild memory
deficit, psychomotor retardation, and abnormal executive
function
Dementia with Lewy Bodies
19
 4-33% of dementia cases are LBD (when autopsy is
performed, greater frequency is found)
 Cortical Lewy bodies are the hallmark
 Tough to diagnose, especially in mixed cases
Diagnosis paramount due to particular treatment
considerations!
Diagnosis of LBD
20
 Dementia
 Presence of fluctuation in cognition/alertness,
Parkinsonism, and visual hallucinations
 Suggestive features are REM sleep disorder, severe
sensitivity to neuroleptics, and low dopamine
transporter uptake in basal ganglia on SPECT or PET
 Falls, syncope, autonomic dysfunction, depression,
delusions are common but not diagnostic in and of
themselves
Parkinson’s disease dementia (PDD)
22
 31-41% of patients with Parkinson’s have dementia
 Cholinergic dysfunction theorized to be involved in
genesis
 Characterized by executive dysfunction, visuospatial
impairments, verbal memory problems, visual
hallucinations
Frontotemporal dementia
23
 Also known as Pick’s disease though that is just a




subtype (or behavioral variant)
Another type is progressive aphasia
Usually of earlier onset (40-60 years of age)
Memory impairment not that common at the onset
of the disease
Brain imaging characterized either by frank FT
atrophy or by decreased metabolism in FT lobes on
functional imaging
24
“Walnut brain”
Notice the profound loss
of matter in the frontal
lobes, to a slightly lesser
degree in the temporal
lobes, in comparison
with relatively
preserved parietal and
occipital lobes
“Walnut brain”
Behavioral variant FTD (BvFTD)
25
Core diagnostic features
Supportive diagnostic
features
A. Insidious onset and
A.
B.
C.
D.
E.
gradual progression
Early decline in social
interpersonal conduct
Early impairment in
regulation of personal
conduct
Early emotional
blunting
Early loss of insight
B.
C.
D.
Behavioral disorder – decline in
hygiene, mental rigidity,
distractibility, hyperorality,
perseverative behavior, utilization
behavior
Change in speech and language –
altered speech output, stereotypy
of speech, echolalia, perseveration,
mutism
Physical signs – primitive reflexes,
incontinence, akinesia, rigidity,
tremor, low/labile BP
Investigations – impairment of
frontal lobe neuropsych tests,
normal EEG, predominant frontal
and/or anterior temporal
abnormality on brain imaging
Treatment
26
Address cognitive dysfunction
2. Address neuropsychiatric symptoms
3. Address the needs of the caregiver and the dyad of
patient/caregiver
4. Consider the environment/living situation
1.
Treatment: Cognitive dysfunction
27
 Acetylcholinesterase inhibitors (see next slide) – use





in all stages of AD, earlier is better (but not in MCI)
Memantine – for moderate to severe stages of the
disease
Do not use AchE inhibitors in FTD, do try them in
other types of dementia
Consider cognitive interventions (stimulation,
rehabilitation, training)
Physical exercise
Mediterranean diet has the best evidence
28
Treatment:
Cognitive
Enhancers
Caution: side effects
ahead. AchE inhibitors
cause bradycardia,
diarrhea, nausea.
Gradual dose
adjustments
recommended.
Memantine is relatively
free of these side
effects.
Adjust doses in
renal/hepatic
impairment.
Medication
Donepezil
Dosing Guidelines
Initial dose 5 mg at bedtime
Titrate to 10 mg once daily at 4-6 weeks
For moderate to severe dementia, may titrate
to 23 mg at 3 months
Notes
The only AchE inhibitor FDA approved for
treatment of moderate to severe dementia
Galantamine
Initial dose 4 mg twice a day
Titrate to 8 mg twice a day at 4 weeks
Titrate to 12 mg twice a day at 4 weeks
Extended release capsules to provide once a day
dosing are also available.
Dosing adjustment recommended in renal and
hepatic impairment.
Rivastigmine
Initial dose 1.5 mg twice daily for 2 weeks
Increase in increments of 1.5 mg twice daily
every 2 weeks if well tolerated
Maximum dose 12 mg a day
Dosing adjustment recommended in renal and
hepatic impairment.
Use caution when treating low body weight
patients.
The only AchE inhibitor FDA approved for
treatment of cognitive impairment in Parkinson’s
disease
Rivastigmine
patch
Initial dose 4.6 mg/24 hrs topical once daily
for 4 weeks
Titrate to 9.5 mg/24 hrs topical once daily
For severe dementia, may titrate to 13.3
mg/24 hrs topical once daily after 4 weeks at
prior dose
Dosing adjustment recommended in hepatic but
not in renal impairment.
Use caution when treating low body weight
patients.
Dose adjustment may be needed in high body
weight patients.
Memantine
Initial dose 5 mg daily, at one week increase
to 5 mg twice a day, in another week increase
to 5 mg in the morning and 10 mg in the
evening, and in another week increase to
target dose of 10 mg twice a day
FDA approved for use in moderate to severe AD
Dose adjustment recommended in severe renal
and hepatic impairment.
Neuropsychiatric symptoms
29
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Agitation
Aggression
Depression
Anxiety
Psychosis
These symptoms are distressing and disruptive for the patients and
their caregivers.
Agitation and aggression are the reasons why patients end up
hospitalized/institutionalized.
Caregiver support and psychoeducation may prevent such outcomes.
There’s evidence to support this finding, and physician
reimbursements reflect their attention to this great need!
Treatment of neuropsychiatric symptoms
30
Nonpharmacological approaches should be tried first!
 And even before that, psychiatric/medical causes of
agitation must be ruled out
 Identify precipitating/contributing factors to
agitation/anxiety
 Teach caregivers how to do the same and provide them
with support
 Address the unmet needs of the patient
 Allow the patient to remain as independent as possible
when helping them with ADLs
Use medications when nonpharmacological methods
failed, or succeeded only partially, or when high
risk/violence exist
Options for treatment of agitation
31
 Acetylcholinesterase inhibitors and memantine – not

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great when effect needed urgently
Atypical antipsychotics (not FDA approved, increase risk
of mortality – black box warning, modest efficacy)
Antidepressants – citalopram (consider QTc
prolongation)
Carbamazepine – evidence not great (consider numerous
side effects and drug interactions)
Propranolol, prazosin – very limited evidence base,
though promising for prazosin (consider falls)
Benzodiazepines – emergent use only
Treatment of other neuropsychiatric sx
32
 Antidepressants for depression in dementia are somewhat

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controversial. There is little evidence for their use in anxiety in
dementia.
For severe depression/suicidality, consider hospitalization,
consider ECT
Recommend psychotherapy, exercise, pleasurable activities,
support groups, memory aids
Minimize changes in caregivers/environment
Music therapy is gaining strength as evidence based
intervention for treatment of anxiety
Treatment of hallucinations/delusions is not always needed –
but when it is, start antipsychotics (atypical) slowly and titrate
gradually
Use quetiapine preferentially in LBD and PDD
Conclusions
33
 It is paramount to diagnose dementia!
 Earlier treatment preserves functioning
 Correct diagnosis prevents poor outcomes – as in giving

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haloperidol to patients with DLB
Always obtain collateral from caregivers, and provide
them with education and support
Neuropsych sx are common and are best addressed with
nonpharmacological strategies
Use cognitive enhancing medications whenever possible
Use medications for agitation/neuropsych sx when
unavoidable