777 final demantia Flashcards
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
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 Fronto-temporal dementia (FTD)
“Late onset” – after the age of 60
Diagnosis:DSM-V Criteria for Major Neurocognitive Disorder
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
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
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.
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
Common syndromes encountered in dementia
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
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
Apraxia
Inability to carry out motor activities previously able to do despite intact motor function
Contributes to loss of ADLs
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
ADL
Activities of daily living (ADL) Bathing Dressing Grooming Toileting Continence Transferring
IADL
Instrumental activities of daily living (IADL) Using a phone Travel Shopping Preparing meals Housework Medication management Money management
Cognitive decline AND associated neuropsychiatric symptoms lead to
increasing dependence on others and often eventual institutionalization
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)
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)
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
Screening test: MoCA (Montreal Cognitive Assessment)
Comprehensive, not easy!
Catches those with higher premorbid functioning levels.
Is free unlike MMSE
Mocatest.org
Screening test: SLUMS
Better psychometric properties than MMSE, with scoring normed to educational level
Screening test: MINI-COG
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.
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
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
Dementia syndromes
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
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
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
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
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
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.
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
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!
Diagnosis of Lewy Body Dementia
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)
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
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
Behavioral Variant Frontal-temporal dementia (BvFTD)
Core diagnostic features
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
Behavioral Variant Frontal-temporal dementia (BvFTD)
Supportive diagnostic features
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
Address cognitive dysfunction
Address neuropsychiatric symptoms
Address the needs of the caregiver and the dyad of patient/caregiver
Consider the environment/living situation
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
Donepezil (Aricept)
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
Rivastigmine (Exelon)
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
Memantine (artificial magnesium)
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
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.
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
Pharmacologic options
Use medications when nonpharmacological methods failed, or succeeded only partially, or when high risk/violence exist
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
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
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
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
