CM- Clinical Diagnosis of Neurodegenerative Disorders Flashcards
What cognitive changes are associated with normal aging?
What 3 things have been shown to decline?
what should remain stable?
- variability in performance on timed tests
- difficulty selectively attending to information while inhibiting irrelevant info
- decline in fluid intellectual ability [new problem solving, spatial manipulation]
- crystallized abilities [general knowledge, vocabulary] should remain stable throughout the lifespan
What is MCI [mild cognitive impairement]?
What will be the patients clinical complaint?
What is MCI one of the earliest clinical features of?
It is a change in the ability to remember things or process information.
MCI is a clinical transition state between cognitive changes of aging that are normal and those that are characteristic of neurodegenerative disorders or Alzheimer’s
Patient will complain of impairment of one or more cognitive domain, but with preservation of function of daily life
What are the major “cognitive domains”?
- IQ and vocab
- attention/executive function
- language
- memory [verbal and visual]
- visuospatial ability
You are evaluating a patient who is complaining about trouble with memory. She has preservation of function in her daily life. On formal cognitive testing, you note a lower performance that is expected for her age and education level [1.5 below SD]. What is here current status?
Mild Cognitive Impairment
What is amnestic MCI?
What tests can be done to note the presence of amnestic MCI?
impaired episodic memory [inability to learn and retain new verbal information]
- List learning
- logical memory immediate and delayed recall
In addition to cognitive testing, what other findings can aid in a diagnosis of Alzheimer’s?
- CSF for concentration of amyloid B and tau
- F-FDG PET scan to see which areas are taking up less glucose [hypometabolism]
- PET with amyloid tracer
- Hippocampal atrophy can be measured over time via MRI
What are the 3 pathological hallmarks of Alzheimer’s disease?
- neurofibrillary tangles [inside cells]
- neuritic plaques
- cortical cell loss/atrophy
What has the strongest epidemiological correlation with Alzheimer’s?
Increased prevalence and incidence is strongly dependent on age. 60 -1% 65- 2% 70- 4% 75- 8% 80- 16% 80-85 = 25-50%
What is the NINCDS-ADRDA Criteria for “Probable” Alzheimer’s disease?
- Dementia est by clinical exam
- Defects in 2 cognitive domains
- Progressive decline in cognition [esp memory]
- NORMAL consciousness [no delerium]
- no other medial/neuro explanations
What is the NINCDS-ADRDA Criteria for “Possible” Alzheimer’s disease?
- dementia with atypical onset or course
- another disease process that COULD cause dementia but is not thought to be the cause [depression]
- progressive deterioration of a SINGLE cognitive domain
What is considered to be “definitive” Alzheimers on the NINCDS-ADRDA criteria?
- Probable Alzheimers criteria
- histopathologic evidence
- tangles, plaques, cortical atrophy on biopsy or autopsy
[now they use APP, presenilin genes too]
What are the six main criteria for DSM-IV for diagnosing Alzheimer’s disease?
- Multiple cognitive defects
- Amnesia [memory] AND one or more of the following:
- apraxia [impaired learned motor acts]
- aphasia [language impairment]
- agnosia [perceptual/constructional difficulty]
- disturbed executive function - significant impairment of social/occupational function
- gradual onset and continuing decline
- not during the course of delerium
- not due to brain, systemic, or substance induced conditions
- not accounted for by another disorder
When evaluating a patient with suspected cognitive decline, what are the 6 steps for evaluation?
[have a caregiver or imformant present]
- earliest clinical sign of dysfunction
- assess language deficits [aphasia]
- assess perceptual deficits [agnosia]
- assess apraxia [perform motor task]
- assess executive function
- assess behavior
When assessing the earliest sign of dysfunction in a patient with suspected dementia, what is the most often cause?
It is almost always short-term memory loss/episodic memory
can’t encode/store new memory [if this is the only cognitive issue = MCI]
What percent of patients with MCI progress to Alzheimer dementia in 10 years?
80%
In Alzheimer’s what is the initial LANGUAGE deficit seen?
How is this assessed in practice?
Anomia- a deficit in trying to recall names and words [difuclity finding words in spontaneous speech]
Assess by:
- low frequency words [parts of pencil, clock]
- MMSE high frequency words [pencil and clock]
SEVERE naming deficits will miss high frequency words
What language deficit is usually present in LATE Alzheimer’s?
Comprehension deficits- it will present like Wernicke’s aphasia- fluent but empty speech
What perceptual deficits are associated with Alzheimer’s?
- environmental disorientation
- constructional apraxia [copying/drawing figures]
- agnosia - difficulty recognizing objects despite intact visual input
What is agnosia and prosopagnosia?
Agnosia- difficulty recognizing an object [not just the name of the object]
Prosopagnosia- difficulty recognizing faces
How does apraxia advance as dementia advances?
- at first, they may have trouble pantomiming and action
- functioning in real situations or with real tools declines
- inability to imitate the gestures of the examiner
What are the 5 main types of apraxia?
- ideomotor apraxia
- transitive gesture
- intransitive gesture
- ideational apraxia
- conceptual apraxia
A patient is unable to pantomine gestures to command. What is this called?
Ideomotor apraxia
A patient can make gestures involving the use of a tool or utensil [scissors, knife, screwdiver]. What does this demonstrate?
They are able to make transitive gestures
What is the difference between a transitive and intransitive gesture?
Which is more sensitive?
Transitive- gesture involving the use of a tool or utensil
{More sensitive}
Intransitive- communicative gestures like waving, saluting, hitchhiking. they are NOT acting on something so it is intransitive
What is ideational apraxia?
Inability to properly sequence the actions of a multistep process [writing and sending a letter]
What is conceptual apraxia?
Loss of semantic knowledge involving tool use.
- Inability to select the correct tool for a task
- misunderstanding the mechanical properties of a tool
A patient complains that she is having difficulty balancing her checkbook and paying bills on time. She has resorted to “one dish meals” because she cannot seem to “keep up” with larger meals. What is this showing a decline in?
Executive function
When evaluating someone for Alzheimer’s, you want to assess behavior. What 4 major aspects of their behavior are you looking for?
- apathy [indifference] - frontal lobe/cingulate gyrus
- irritability/agitation
- delusions
- hallucinations
What are the 3 types of delusions someone with Alzheimer’s may present with?
- paranoia/suspiciousness [usually stealing]
- phantom border [someone is living in their house, but they can’t see them]
- Capgras syndrome [spouse is an imposter]
Hallucinations appear early in the course of cognitive disease. What are you suspicious of?
Lewy body Dementia
[if it was Alzheimer’s it would occur very late in the course]
When doing an examination on someone suspected of Alzheimer’s disease or dementia, what 3 things should you assess?
- physical exam- look for systemic diseases that may cause cognitive decline
- General neuro exam
- look for asymmetry because this may be a red flag for a focal lesion [tumor, vascular disease] and not alzheimer’s
- Parkinsonism
- gait - Mental status exam
What is included on the screening test for dementia in a person without complaints?
What if the person has complaints?
Screening:
- clock drawing test
- mini-cog [3 words, repeat, more interview, repeat again]
Complaints:
- MMSE
- 10 orientation questions [5 time, 5 location]
- 3 memory test
- 5 attention/concentration [World backwards]
- Language - low frequency items to name
- clock drawing [visuospatial/executive]
- category fluency [name as many animals as you can]
What CSF findings would have a positive predictive value of alzheimer’s of 90%?
- increased tau
2. decreased amyloid B- 42
What medications are used for Alzheimers?
- AchE inhibitors- prevent breakdown of Ach
2. NMDA receptor antagonists- prevent excess glutamate from causing excitotoxicity
How does the presentation of Frontotemporal Lobar Degeneration [FTD, Pick’s, Primary Progressive Aphasia, Semantic Dementia] differ from Alzheimer’s?
How does the histology differ?
- Presents at a younger age [ before 65]
- something other than memory is presenting symptoms [personality change, language prob]
Histology = Tauopathy
What are the genetic markers for FTD?
- GRN [progranulin]
- tau [MAPT]
- chromosome 9 ORF 72
How is Dementia with Lewy bodies differentiated from Alzheimer’s?
- early hallucinations
- parkinsonism
- fluctuating cognition
- REM behavioral disorder [person acts out dreams]
- a-synuclein inclusions
A person has a history of clinical strokes. Dementia started 3 months after the stroke and there has been a stepwise progression of dementia.
The neurological findings are lateralized.
What will CT/MRI likely show?
What is the problem?
CT/MRI should show vascular lesions in the cortex and/or thalamus.
This is vascular dementia from multiple strokes.
A patient presents with rapid onset and progression dementia.
The patient has ataxia, myoclonus, an abnormal EEG and visuoperceptual derangements.
What is the problem?
What will CSF show?
What will MRI show?
Creuzfeldt-Jacob disease - a prion disease
CSF = 14-3-3 protein MRI = increased signal on DWI sequence in thalamus in ribbon pattern
What are 5 infectious causes of dementia?
- HIV- MRI has white matter lesions
- Syphilis
- Cryptococcus meningitis
- Whipple’s disease
- HSV - temporal lobes
What are the 2 main inflammatory/autoimmune conditions that can cause dementia?
- Hashimoto’s encephalopathy- TPO-Ab TgAb affect neuro function [rapid progressive dementia], seizures
- Granulomatous Angiitis - leptomeningeal biopsy
What are the 5 general reversible causes of dementia?
- Structural defects
- subacute encephalitis
- depressive “pseudodementia”
- metabolic disorder
- Non-convulsive status epilepticus
What are 3 structural causes of reversible dementia?
- normal pressure hydrocephalus
- tumor
- subdural hematoma
What metabolic disorders are associated with dementia?
- B12 deficiency
- Thyroid disease
- Folate, thiamine, niacin deficiency
What disease is associated with each of the following “key features”?
- amyloid and tau
- tauopathy
- a-synuclein
- stroke
- prion
- autoimmune
- Alzheimer’s
- Frontotemporal Lobar Degeneration
- Dementia of Lewy Bodies, Parkinsonism
- vascular dementia
- CJD
- Hashimoto’s, Granulomatous Angiitis
