Term
| How do delirium and dementia differ from aphasia or amnesia? |
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Definition
| They have cognitive symptoms in multiple domains instead of a single domain such as language or memory. |
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Term
| Distinguish mental retardation from dementia and delirium |
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Definition
All show cognitive impairment
1) Mental Retardation is congenital
2) Dementia is acquired (lasts months to year)
3) Delirium is acquired, time limited and reversible (fluctuates with severity of symptoms).
**Delirium and Dementia are same disorder on different time scales** |
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Term
| What major anatomical categories should be considered when "localizing" a lesion associated with delirium or dementia? |
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Definition
1) Small, but critical subcortical or cortical centers
2) DIffuse cortical lesions
- can involve Cholinergic and/or MAO (DA and hist) |
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Term
| What are the DSM IV criteria for Dementia (AD type)? |
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Definition
Gradual onset with continuing cognitive decline that MUST impair normal function.
1) Memory impairment (anterograde or retrograde)
2) 1 or more of
- Aphasia (inferior frontal or superior tempora)
- Apraxia (frontal/parietal connection)
- Agnosia (temporal)
- Disturbance in executive function (frontal)
**Aphasia/Apraxia cannot be due to other CNS conditions, systemic conditions or substance-induced conditions** |
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Term
| What are the DSM IV criteria for Delirium? |
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Definition
Disturbance of consciousness (alertness) with reduced ability to focus, sustain or shift attention.
1) Develops over short period of time (hours to days) and tends to fluctuate during course of day
2) Can be hypo-active (lethargic) or hyper-active (agitated)
3) Evidence from hist/physical/labs of direct physiological consequences of general medical condition. |
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Term
| What group of people are at the highest risk of developing Delirium? |
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Definition
- Post-surgical ICU subjects, particularly geriatric (80%)
- 14-56% of all hospitalized patients develop delirium |
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Term
| What is the evidence for a role of ACh in Delirium? |
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Definition
Mesopontine tegmentum loci (rostral pons) project to RN and intralaminal n. of thalamus
1) Attention, arousal, memory and REM sleep
- High in wakefulness and REM state, where EEG has low-amp, high-freq pattern.
- Delirious patients have high-amp, low-req pattern, characteristic of NREM.
2) Age-related decline in ACh neurons and decreased ox metabolism
- synthesis and degradation of ACh very sensitive to cerebral metabolic state (glycemic status) |
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Term
| What is the evidence for a role of DA in Delirium? |
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Definition
Important NT in reward and executive function
1) Hypoxia induces DA synthesis and delirium
2) In aging, DA-R decline and dementia with lewy bodies (DLB) is seen with delirium
3) People with hyper-active delirium have abnormal sense of signal-noise in reward processing.
**treatment is anti-DA agents, while cocaine and amphetamines induce it** |
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Term
| What is the functional anatomy of the DA system as it relates to Delirium? |
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Definition
2 major pathways
1) SNpc projects to BG
2) VTA projects to
-"mesolimbic system" (NA and amygdala)
-"mesocortical system" (frontal lobes). |
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Term
| What is the functional anatomy of the histamine system as it relates to Delirium? |
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Definition
Synthesized from amino acid L-histadine via histidine decarboxylase and found in tuberomamillary nucleus of hypothalamus.
1) Tuberomammillary nucleus of hypothalamus projects DIFFUSELY to entire brain and spinal cord.
2) High levels of histamine receptor in cortex promotes arousal
- Central histamine antagonism induces delirium. |
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Term
| What are the "hallmark" clinical features of Delirium? |
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Definition
1) Acute onset in alteration in attention and level of arousal with effects on circadian rhythms.
2) Often accompanied by fluctuations in symptoms and altered perception of external and internal stimuli |
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Term
What is the most important substrate for delirium?
What other causes contribute? |
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Definition
1) AGE
2) Hypoxia (in context of co-morbid conditions most commonly, such as COPD, CHF, OSA, pneumonia)
MANY OTHERS (co-morbidity is common cause) |
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Term
| What other clinical conditions may be confused with Delirium? |
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Definition
1) Focal strokes to posterior cortex (parietal) or ventral posterior and medial temporal lobes
2) If sub-acute, CNS infections, DLB, prion encepthalitis. |
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Term
| What is the most important reason to distinguish between delirium and dementia? |
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Definition
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Term
| What qualifies as a "Dementia" under the DSM IV regulations? |
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Definition
1) Loss of intellectual abilities sufficient enough to cause functional impairment
2) Memory impairment + at least 1 cognitive impairment
3) May be static, progressive or remitting. |
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Term
| What important epidemiological features define AD? |
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Definition
1) AGE
- after age 65, prevalence doubles every 5 years (40% at age 80)
2) Genetics
- Family history
-Apolipoprotein E polymorphism
- 5% autosomal dominant AD with amyloid protein processing genes
3) CV
- HTN
- Diabetes
- Obesity
4) Socioeconomic
- higher education and cognitively stimulating leisure are protective. |
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Term
| What clinical progressive that defines AD? |
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Definition
Insidiously progressive neuropsychiatric disorder with
1) Begins with episodic memory deficits (NFT in the entorhinal cortex and hippocampus)
2) Unimodal and Heteromodal spread leads to Aphasia (left), Visuospatial (right parieto-frontal) and/or Executive (bilateral parieto-frontal) issues. Mood disorders also possible.
3) Primary sensory cortices spared until later (early motor changes probably indicate a different dementia). |
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Term
Where do you find amyloid beta plaques in AD?
How are they most likely generated? |
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Definition
1) Limbic and associative/heteromodal cortices as clumps of beta-leated sheet of A-beta and dystrophic axons and dendrites.
- deposition begins 20 years before symptoms!
2) Differential cleavage of APP by alpha, beta and gamma secretases, with beta and gamma promoting plaque formation. |
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Term
| What is the role of Tau in AD? |
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Definition
Neurofibrillary tangles of mis-folded, hyperphoshorylated tau are deposited intracellulary, initially in cells in the temporal lobes (entorhinal cortex).
-Better correlated with clinical symptoms than A-beta plaques. |
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Term
| What is the role of ACh in AD? |
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Definition
Loss of central cortical ACh cells in nucleus basalis of Mynert (NBM) has been demonstrated.
AChE-i is only modestly effective in AD |
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Term
| How is AD typically diagnosed? |
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Definition
1) Clinical judgment (HPI, neuro exam, testing)
2) MRI- medial parietal atrophy
3) fMRI-bilateral parietal and lateral temporal hypometabolism
4) CSF- A-beta (decrease) and tau (increase) |
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Term
| What features define mild-cognitive impairment (MCI)? |
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Definition
Occurs between normal aging and dementia (high risk)
1) Recognition by subject or an informant of cognitive change
2) Near normal activities of daily living
3) Objective evidence of change by formal testing |
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Term
| What is the focus of treatment for AD and MCI? |
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Definition
| identifying reversible, or modifiable factors |
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Term
A patient appears parkinsonian and is experiencing visual hallucinations that began 3 months after the PD symptoms began. He explains that the hallucinations occur "minute-to-minute," but are worst at sleep-wake transitions.
The patient's partner complains that her husband have become "angry and violent" in their sleep, and that he has been experiencing ED as well.
What is the pathology of the condition described here? |
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Definition
1) PD with visual hallucinations makes you think Lewy Body Dementia (DLB) (especially since the hallucinations started within 1 year of the PD). The "minute-to-minute" description that are worst at "sleep-wake" transitions also support this diagnose. Finally, REM sleep disorder and autonomic disfunction (ED) are also characteristic.
2) Pathological aggregates of alpha-synuclein form Lewy Bodies in brainstem predominant, limbic predominant and diffuse cortex.
- Ascends from BG (SNpc) and basal forebrain (NBM) into limbic cortex (Medial temporal lobe and amygdala), and finally to unimodal and heteromodal associative cortex. |
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Term
| What clinical features are associated with each pathological stage of progression in Lewy body dementia (DLB) |
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Definition
In DLB, spreads from BG and Basal forebrain to Limbic cortex, and then to unimodal and heteromodal associative cortex.
1) Early involvement of Vagus (autonomic)
2)
- BG (SNpc and parkinsonian motor symptoms)
- NBM in basal forebrain (attentional fluctuations and visual hallucinations
3) Limbic
- Medial temporal cortex and amygdala (Executive Function/cortico-striatal-cotical loops and Memory) |
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Term
| What are the 2 different categories of Frontotemporal dementia and the 2 major pathological markers? |
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Definition
Defined by abnormal behaviors, dysexecutive problems and motor symptoms.
Cognitive features initially overshadowed by behavioral problems
1) Language predominant (semantic dementia)
2) Behavioral predominant (bvFTD)
1) Tau
2) Tar-DNA binding protein (TDP-43) |
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Term
| What are the 2 autosomal dominant forms of FTD? |
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Definition
Both on chromosome 17 and represent 10-20% of FTD patients.
1) Tau
2) Progranulin |
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Term
| What three brain regions are particularly important in the pathology of FTD? |
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Definition
Other common cause of FTD is TBI!
1) Orbitofrontal cortex
- EARLY in bvFTD and LATE in semantic dementia
- medial (insula, hypothalamus and braintsem connections)
- orbital/lateral (multi-sensory inter-cortical connections)
2) Dorsomedial PFC/Anterior Cingulate
- Decision making/Intentions into actions with DA connections to midbrain (action monitoring, reward and error detection)
- Lesions produce apathy and progressive non-fluent aphasia (dorsal and caudal aspects)
3) Anterior Temporal Lobes
- Amygdala (emotional valence to sensory information)
- Left (word/object meaning) and Right (social/facial-emotional)
- Effected in semantic dementia |
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Term
A patient presents with poor insight, disinhibited and socially inappropriate behavior, emotional blunting and OCD tendencies.
Their memory is fairly normal.
What is the pathology of the likely condition? |
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Definition
bvFTD (Pick's Disease)- association with ALS
- Defined by early disproportional behavior and/or language problems and executive deficiencies, with less conspicuous memory issues.
1) Symmetric, gross atrophy in frontal and temporal lobes (vs asymmetry in SD)
2) Intraneuronal Tau inclusions in frontal/temporal/limbic cortex (sometimes called Pick bodies) or intraneuronal TDP-43 inclusions. |
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Term
| How can you diagnose a case of bvFTD? |
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Definition
1) Exam- OCD-like, hyper-orality, emotional blunting, socially inappropriate behaviors
2) CSF
3) PET/SPECT |
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Term
| Which patients are at risk for Vascular Associated Cognitive Decline (VaD)? |
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Definition
can be caused by single stroke or series of "silent" infarcts in a stepwise progression.
1) Age
2) HTN, smoking, obesity, hyperglycemia (important during middle-age) |
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Term
| How can you diagnose a case of vascular associated cognitive decline? |
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Definition
Considered "sub-cortical" dementia.
-Look for cognitive symptoms characteristic of dementia, along with focal, lateralizing abnormalities that occur in step-wise progression.
- More apparent depression and apathy than AD |
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Term
| What is another term for multiple infarct demential syndrome? |
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Definition
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Term
| What are the important clinical and pathological features associated with VaD? |
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Definition
1) Damage usually occurs in cortical-striatal-thalamic-cortical loops (executive function and motor abnormalities).
2) Markers of atherosclerosis and arteriosclerosis of intracranial arteries |
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Term
A patient presents with abrupt cognitive decline, followed by stability and then further episodes of decline/stability.
What is most likely going on? |
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Definition
Probably a dementia, and given the "step-wise progression," you should think about VaD.
Look on MRI or CT for supportive evidence. |
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