777 final demantia

Question 1

Epidemiology

Answer 1

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

Question 2

Terminology

Answer 2

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 Fronto-temporal dementia (FTD)
“Late onset” – after the age of 60

Question 3

Diagnosis:DSM-V Criteria for Major Neurocognitive Disorder

Answer 3

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

Question 4

DSM-V Criteria for Major Neurocognitive Disorder cont.

Answer 4

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

Question 5

DSM-V Criteria for Major Neurocognitive Disorder cont.

Answer 5

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.

Question 6

Subtypes

Answer 6

“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

Question 7

Common syndromes encountered in dementia

Answer 7

Aphasia (speech), Apraxia (movement), Agnosia (sensory)
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

Question 8

Aphasia

Answer 8

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

Question 9

Apraxia

Answer 9

Inability to carry out motor activities previously able to do despite intact motor function
Contributes to loss of ADLs

Question 10

Agnosia

Answer 10

The inability to recognize or identify objects despite intact sensory function
Typically occurs later in the course of illness
Can be visual or tactile

Question 11

ADL

Answer 11

Activities of daily living (ADL)
Bathing
Dressing
Grooming
Toileting
Continence
Transferring

Question 12

IADL

Answer 12

Instrumental activities of daily living (IADL)
Using a phone
Travel
Shopping
Preparing meals
Housework
Medication management
Money management

Question 13

Cognitive decline AND associated neuropsychiatric symptoms lead to

Answer 13

increasing dependence on others and often eventual institutionalization

Question 14

The work up

Answer 14

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)

Question 15

Cognitive screening tests

Answer 15

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)

Question 16

Screening test: MMSE

Answer 16

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

Question 17

Screening test: MoCA (Montreal Cognitive Assessment)

Answer 17

Comprehensive, not easy!
Catches those with higher premorbid functioning levels.
Is free unlike MMSE
Mocatest.org

Question 18

Screening test: SLUMS

Answer 18

Better psychometric properties than MMSE, with scoring normed to educational level

Question 19

Screening test: MINI-COG

Answer 19

Instruct the patient to listen carefully to and remember these 3 words: banana-sunrise-chair
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.”
Ask the patient to repeat the 3 previously stated words.

Question 20

Labwork

Answer 20

Chem 10
CBC
LFTs
TSH
B12, Folate
RPR, HIV
Others only if clinical suspicion is high

Question 21

Imaging

Answer 21

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

Question 22

A few words about “reversible” dementias

Answer 22

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

Question 23

Dementia syndromes

Answer 23

Alzheimer’s disease
Vascular dementia
Lewy body dementia (LBD)
Parkinson’s disease dementia (PDD)
Fronto-temporal dementia (FTD)
Mixed pathology
Korsakoff’s

Question 24

Alzheimer’s disease

Answer 24

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

Question 25

Alzheimer’s disease:etiology

Answer 25

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

Question 26

Course of Alzheimer’s Disease

Answer 26

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

Question 27

Vascular dementia

Answer 27

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

Question 28

Vascular dementia: cortical subtype

Answer 28

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.

Question 29

Vascular dementia: subcortical subtype

Answer 29

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

Question 30

Dementia with Lewy Bodies

Answer 30

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!

Question 31

Diagnosis of Lewy Body Dementia

Answer 31

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

Question 32

Parkinson’s disease dementia (PDD)

Answer 32

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

Question 33

Frontotemporal dementia

Answer 33

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

Question 34

Behavioral Variant Frontal-temporal dementia (BvFTD)

Core diagnostic features

Answer 34

Insidious onset and gradual progression
Early decline in social interpersonal conduct
Early impairment in regulation of personal conduct
Early emotional blunting
Early loss of insight

Question 35

Behavioral Variant Frontal-temporal dementia (BvFTD)

Supportive diagnostic features

Answer 35

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

Question 36

Treatment

Answer 36

Address cognitive dysfunction
Address neuropsychiatric symptoms
Address the needs of the caregiver and the dyad of patient/caregiver
Consider the environment/living situation

Question 37

Treatment: Cognitive dysfunction

Answer 37

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

Question 38

Donepezil (Aricept)

Answer 38

Selective inhibitor of AChE, allowing more ACh to accumulate

Once daily dosing
Severe AD
Benefits for all outcomes at 6 months
Some indication of positive changes on ADL and severe impairment battery (SIB) scores

More selective for brain than periphery
GI side-effects usually moderate and transient - nausea, vomiting, diarrhea

No liver toxicity

Hallucinations twice as common than placebo

Question 39

Rivastigmine (Exelon)

Answer 39

Inhibits both AChE and the peripheral buty.

may be more selective for hippocampal

May be more useful for late stage AD, when gliosis increases buty.

Might interfere with plaque formation

Increased incidence of GI side-effects, especially during dose optimization/increase

Question 40

Memantine (artificial magnesium)

Answer 40

Voltage-dependent NMDA antagonist that targets glutamatergic system

Mild side effect profile (dizziness, confusion, headache, constipation)

Administer with or without food

No PK/PD interactions with donepezil or other renally-excreted drugs

Question 41

Neuropsychiatric symptoms

Answer 41

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.

Question 42

Treatment of neuropsychiatric symptoms

Answer 42

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

Question 43

Pharmacologic options

Answer 43

Use medications when nonpharmacological methods failed, or succeeded only partially, or when high risk/violence exist

Question 44

Options for treatment of agitation

Answer 44

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

Question 45

Treatment of depression, psychosis

Answer 45

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

Question 46

Other treatment options for neuropsychiatric sx

Answer 46

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

Question 47

Take home points

Answer 47

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