Diagnosis and Evaluation of Dementia / Meds for Cognitive Impairment Flashcards
What is the definition of dementia?
Decline in memory and at least 1 other cognitive function sufficient enough to affect daily life in an alert person
What are the major cognitive domains?
- Complex attention
- Executive function
- Learning and memory
- Language
- Perceptual-motor
- Social cognition
What is dementia now called in the DSM 5, and what are its diagnostic criteria?
Major Neurocognitive Disorder
Significant decline in 1+ cognitive domains, as assessed by clinical assessment. They interfere with daily life and do not occur exclusively in delirium or as a part of another psych disorder.
What is Mild Neurocognitive Disorder?
Decline in 1+ cognitive domains, except that these deficits do not yet have to interfere with capacity for independence in daily activities
What are two formal mental status exams used to evaluate dementia in patients?
- MMSE - mini mental status exam
2. MOCA - montreal cognitive assessment
Why are baseline laboratory assessments done in the dementia workup? Give some example labs taken and how they might be relevant.
Rule out reversible dementias
i.e.
Thyroid studies - hypothyroidism
Syphillis testing - rule out neurosyphillis
B12 (via methylmalonic acid) / folate levels (via homocysteine) - rule out CNS sequelae
What are the biomarkers in the CSF for dementia?
Low CSF A-beta42 (aggregates do not cross BBB into CSF very well)
Elevated CSF tau (hyperphosphorylated tau accumulates)
What are the PET and MRI findings in Alzheimer’s disease?
PET - decreased uptake into the temporoparietal cortex
MRI - Hippocampal atrophy
PET - can also assess amyloid burden in brain
In what conditions will you find decreased Dopamine uptake via DAT on brain scan?
Parkinson’s or Lewy Body Dementia
no hippocampal atrophy
What is a good rapid assessment of dementia and what conditions will it discriminate well?
Clock Drawings Test
Will screen for Alzheimer disease and suspected frontotemporal dementia
-> frontotemporal dementia clocks will be WAYYY off
What is neuropsychological testing and when is it used?
Extensive testing for assessment of specific focal deficits, and determining what the patient’s strengths and weaknesses are to tailor a specific rehab regimen to them. Do repeatedly to measure changes over time.
-> Done when beside assessment fails to differentiate between normal aging vs early dementia often
When would each of the following be consulted: geriatric psychiatrist, neurologist, geriatrician?
Geriatric psychiatrist - severe mood / behavior problems which is not responsive to treatment, having unclear diagnosis
Neurologist - parkinsonian symptoms, early onset, focal neurological signs with rapid progression
Geriatrician - for complex medical problems (i.e. drug interactions)
What three genes are associated with early onset Alzheimer’s disease (AD)?
- Amyloid Precursor Protein - Chromosome 21 (repeated in Down syndrome, high chance of AD)
- PS1 - presenillin1
- PS2 - presenillin2
What gene is a primary risk factor for Late Onset Alzheimer’s Disease and why?
ApoE4 - E4 variant causes ineffective removal of amyloid peptides, leading to amyloid plaque formation
Is genetic testing normally recommended for diagnostics / asymptomatic individuals? In what conditions is it especially warranted?
No
Warranted in:
Huntington’s disease
Frontotemporal dementia - has genetic component
Alzheimer’s disease <35 years (early onset, for genetic counseling)
APOE4 in AD
What is pseudo-dementia / what causes it?
Memory complains which are misdiagnosed as dementia, but are actually due to depression
-> need to be sure to ask about sadness or anhedonia
-BEWARE: depressive symptoms can be a precursor to dementia
What type of dementia is characterized by abrupt onset or stepwise deterioration?
Vascular dementia
What are the characteristics of frontotemporal dementia?
Behavioral changes, apathy, and aphasia
Give two causes of progressive gait disorder.
Vascular dementia, hydrocephalus
Give one type of dementia other than acute delirium which can cause prominent fluctuations in the level of consciousness or cognitive abilities.
Dementia with Lewy bodies
What dementias are associated with hallucinations or delusions?
Lewy body dementias, also delirium
What diagnoses are associated with extrapyramidal signs or gait (acutely)
Vascular dementias -> affecting basal ganglia
Parkinson’s syndromes
Give two conditions causing eye-movement abnormalities.
- Progressive supranuclear palsy
2. Wernicke’s encephalopathy - (ataxia, confusion, ophthalmoplegia)
How does Alzheimer’s generally prevent differently than other dementias?
AD: Has a much slower (insidious) onset, with prominent early memory loss. Motor coordination / strength are generally preserved. Atrophy seen on MRI (especially medial temporal lobe = hippocampus).
Other dementias have a rapid or stepwise progression, generally occur younger than 65 years old, and affect focal CNS / motor systems far more than memory.
How do plaques and tangles interfere with the brain in AD as insoluble aggregates?
Interfere with glucose transport -> lead to neuronal cell death
-> these especially deposit along cortical memory pathways
What types of receptors are lost in the hippocampus and cortex in Alzheimer’s disease?
Nicotinic acetylcholine receptors
What is the most significant risk factor for AD for everyone? Do females or males get it more? Other factors?
Age
Females get it more. Other factors include vascular / head trauma, low education, and inactivity
What type of neurological findings will be seen in vascular dementia, and what will neuroimaging show?
Focal neurological findings
Neuroimaging shows infarcts
What are the features of Lewy Body dementia?
Decreased attention / fluctuating cognition
Visual hallucinations
Motor features of parkinsonism
Lewy bodies in cerebral cortex
What describes the drug reactivity of Lewy Body dementia patients?
Neuroleptic sensitivity
-> more likely to develop side effects to antipsychotics since they block dopamine, which is already low
What is the most common cause of Frontotemporal dementia and what are its symptoms?
Pick’s disease
Prominent behavior changes w/ disinhibition (loss of prefrontal cortex)
Language disturbances -> aphasia, from loss of Broca’s and Wernicke’s.
Neuroimaging shows focal atrophy
Why is PET scan useful in diagnosing frontotemporal dementia?
Shows hypo-perfusion prior to structural changes.
What is the best way to assess improvements of cognitive impairment following treatment?
Talking to family members -> rating scales are imprecise
What are the three stages of Alzheimer’s disease?
Stage 1 - presymptomatic, cognition is intact by amyloid is increasing
Stage 2 - Minor cognitive impairment (CI) - impairment is only episodic
Stage 3 - Major cognitive impairment - treatment generally begins
What are the goals of raising acetylcholine in AD thought to do, and are any acetylcholinesterase inhibitors more effective?
Goals - enhance memory, slow decline in function
All are equally effective, tailor based on side effects
What are the common side effects of all acetylcholinesterase inhibitors?
Nausea, vomiting, anorexia (weight loss), urinary incontinence
Abnormal dreams, Bradycardia, and orthostatic hypotension
What are the three primary AChE’s used for treatment of Alzheimer’s? Which one has no CYP interactions?
Alzheimer’s GALA - Galantamine
Reverse the Stigma - Rivastigmine - no CYP interactions
Done the Puzzle - Donepezil
Which cholinesterase inhibitor is approved for the treatment of cognitive impairment in PD? Why else was it developed?
Only Rivastigmine - also developed to have less GI side effects via using transdermal patch
What Alzheimer’s treatment targets glutamate and when is it used? Is it good for other dementias?
Memantine - used for moderate to severe AD
-> uncompetitive NMDA antagonist. Can be used in combination with donepezil
Yes, even AChE’s are also good in other dementias which aren’t alzheimer’s disease
When can you start using AChE’s?
Mild to Moderate AD (but not mild cognitive impairment)
What is BPSD and what are some common reversible precipitants?
Behavioral and Psychological Symptoms in Dementia -> acting out in dementia
- > Environmental changes (being in a nursing home)
- > Medication side effects or withdrawal
- > Pain
What drugs are first line for treatment of BPSD, and some second line options?
First line: SSRIs or SNRIs
Second line options: Anticonvulsants Beta blockers Buspirone Trazodone BENZOS Gabapentin
When would antipsychotics be used to treat BPSD? What are the issues?
When they are at a risk to themselves or others
Issue: Cardiovascular side effects (stroke risk)
How should drug administration with BPSD be done, and when should you taper?
Done lowly and slowly
Taper after 3 months of stability
What are the first-line nonpharmacological approaches for BPSD?
Manage general discomfort, have family visit more, make the patient generally happier with their life, etc
