DEMENTIA: EVALUATION AND TREATMENT
Anna Borisovskaya, MD
(with contributions by
J. Frederick, MD and S. Thielke, MD)
Objectives: At the end of this talk you will be able to
Describe the epidemiology of dementia
Be able to define and diagnose dementia, as
well as its different types
Understand the options for treatment of
cognitive and neuropsychiatric symptoms of
dementia
2
Epidemiology
• 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
3
Terminology
• Deriving from Latin (demens – mad)
• In psychiatry, used to be termed dementia,
now called major neurocognitive disorder
• “Early onset” – before the age of 60, often
familial, more common for Frontotemporal
dementia (FTD)
• “Late onset” – after the age of 60
4
Diagnosis:DSM-V Criteria for Major Neurocognitive
Disorder
A. 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
5
DSM-V Criteria for Major Neurocognitive Disorder cont.
• 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
6
DSM-V Criteria for Major Neurocognitive
Disorder cont.
• * 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.
7
Subtypes
• “Early onset” – before the age of 60, often
familial, more common for Frontotemporal
dementia (FTD)
– Strong genetic link
– Tends to progress more rapidly
• “Late onset” – after the age of 60
– Represents majority of cases
8
Common syndromes encountered in
dementia
• Aphasia, Apraxia, Agnosia
• Impaired executive function: difficulty with
planning, initiating, sequencing, monitoring, or
stopping complex behaviors
• All of the above contribute to loss of
instrumental activities of daily living
9
Aphasia
•
•
•
•
Problems with language, comprehension
Initially characterized by fluent aphasia
Able to initiate and maintain conversations
Syntax and grammar intact but speech is
vague with nonspecific phrases like “the
thing”
• Later language can be severely impaired with
mutism, echolalia
10
Apraxia
• Inability to carry out motor activities
previously able to do despite intact motor
function
• Contributes to loss of ADLs
11
Agnosia
• The inability to recognize or identify objects
despite intact sensory function
– Typically occurs later in the course of illness
– Can be visual or tactile
12
ADL and IADL
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
13
• Cognitive decline AND associated
neuropsychiatric symptoms lead to increasing
dependence on others and often eventual
institutionalization
14
Someone presents with cognitive
problems…what do you do?
15
The work up
•
•
•
•
•
•
•
•
Thorough history (medical, psychiatric, neurological)
Get 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)
16
Cognitive screening tests
• Mini-Mental Status Exam (MMSE)
• Montreal Cognitive Assessment (MoCA)
• Mini-Cog – combines clock drawing and three
item memory test.
• Saint Louis University Mental Status (SLUMS)
17
Screening test: MMSE
•
•
•
•
Useful to have at baseline
Can track changes over time
In Alzheimer’s, patients lose 3 points/year
Careful of false positives in those with little
education
• Careful of false negatives in those with high
premorbid intellectual functioning
18
Screening test: MoCA
• Comprehensive, not easy!
• Catches those with higher premorbid
functioning levels.
• Is free unlike MMSE
• Mocatest.org
19
Screening test: SLUMS
• Better psychometric properties than MMSE,
with scoring normed to educational level
• http://medschool.slu.edu/agingsuccessfully/p
dfsurveys/slumsexam_05.pdf
20
Screening test: MINI-COG
1. Instruct the patient to listen carefully to and
remember these 3 words: banana-sunrisechair
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.
21
Clock Drawing Test--abnormal
Mini-Cog scoring
3 word recall
1-2 = potential
cognitive deficitlook at clock
Normal clock=
no cognitive
deficit
0 of 3= cognitive
deficit
3 of 3= no
cognitive deficit
Abnormal
clock= cognitive
deficit
23
Labwork
•
•
•
•
•
•
•
Chem 10
CBC
LFTs
TSH
B12, Folate
RPR, HIV
Others only if clinical
suspicion is high
24
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
25
A few words about “reversible”
dementias
•
•
•
•
•
•
•
•
•
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
26
Dementia syndromes
•
•
•
•
•
•
•
Alzheimer’s disease
Vascular dementia
Lewy body dementia (LBD)
Parkinson’s disease dementia (PDD)
Fronto-temporal dementia (FTD)
Mixed pathology
Korsakoff’s
27
Alzheimer’s disease
• 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
28
Alzheimer’s disease:etiology
• 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
29
Course of Alzheimer’s Disease
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
30
Vascular dementia
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
31
Vascular dementia: cortical subtype
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.
32
Vascular dementia: subcortical
subtype
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
33
Dementia with Lewy Bodies
• 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!
34
Diagnosis of LBD
• 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
35
Parkinson’s disease dementia (PDD)
• 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
37
Frontotemporal dementia
• 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
38
“Walnut brain”
“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
39
Behavioral variant FTD (BvFTD)
Core diagnostic features
A. Insidious onset and
gradual progression
B. Early decline in social
interpersonal conduct
C. Early impairment in
regulation of personal
conduct
D. Early emotional blunting
E. Early loss of insight
Supportive diagnostic features
A.
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
40
Treatment
1. 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
41
Treatment: Cognitive dysfunction
• Acetylcholinesterase inhibitors (see next slide) – use in
all stages of AD, earlier is better (but not in mild
cognitive impairment)
• 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
42
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.
43
Neuropsychiatric symptoms
•
•
•
•
•
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.
44
Treatment of neuropsychiatric
symptoms
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
45
Pharmacologic options
• Use medications when
nonpharmacological
methods failed, or
succeeded only
partially, or when high
risk/violence exist
46
Options for treatment of agitation
• Acetylcholinesterase inhibitors and memantine – not
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
47
Treatment of depression, psychosis
• Antidepressants for depression in dementia are
somewhat controversial. There is little evidence
for their use in anxiety in dementia.
• For severe depression/suicidality, consider
hospitalization, consider ECT
• 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
48
Other treatment options for
neuropsychiatric sx
• 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
49
Take home points
• It is paramount to diagnose dementia!
• Always obtain collateral from caregivers, and provide them
with education and support
• Evaluation of cognitive function is key
• Earlier treatment preserves functioning
• Correct diagnosis prevents poor outcomes – as in giving
haloperidol to patients with DLB
• 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
50