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Cognitive Disorders

Cognitive Disorders Cognitive Disorders
Types of memory Declarative = facts (episodic=events, semantic=language), procedural = motor, implicit = skills
Forgets meaning of a word. Type of memory? Semantic
Forgets what happened yesterday. Type of memory? Episodic
Implicit memory example Forgetting a non-motor skill. Motor skills = procedural memory
Fluctuating attention and cognitive deficits Delirium. Often reversible
Delirium treatment Antipsychotics are temporizing, but do not decrease duration of delirium. Avoid anticholinergics
TGA patient demographics 50-80yo, no sex preference, not necessary any comorbidities
TGA pathophysiology Unclear. But thought to be due to hypoperfusion of hippocampi. 7T MRI will show +DWI signal
Sudden memory loss, back to normal in 24 hours Transient Global Amnesia TGA
TGA vs Dissociative Fugue TGA = neurological = preserved awarness of self. Fugue = psychiatric = cannot recognize self
MCI definition Reduced memory (more than normal aging) but no deficits on ADLs and normal cognition
Risk factor for MCI progression to dementia Family history. Others like age etc have less evidence
Alzheimers patient demographics Black/hispanic more likely. Low education/socioeconomic status more likely
Alzheimers pathophysiology Microangiopathy from DM/HTN/HLD/Smoking -> buildup of Tau
Alzheimers histopathology Intracell Tau neurofibrillary tangles. Extracell APP beta-Amyloid senile plaques. Hirano bodies
Alzheimers CSF Has high Tau but low beta-Amyloid (frequently tested)
What molecule is used in Alzheimers FDG-PET scans? CompB
Alzheimers MRI 1st = medial parietal, posterior cingulate. Then parietotemporal atropy
FDG-PET \/metabolism in parietotemporal Alzheimers
FDG-PET \/metabolism in occipital Lewy-Body Disease
FDG-PET \/metabolism in frontotemporal Fronto-Temporal Dementia
What is the function of Tau? Microtubule transport. Dysfunction = impaired intracellular transport of proteins/neurotransmitters
Alzheimers genes Chrm 21 APP. Chrm 14 PSEN1. Chrm 1-PSEN2. Chrm 19 APOE epsilon 4
1st type of memory damaged in Alzheimers Recent memory. Then episodic -> semantic -> language
Alzheimers treatment ACEi (donepezil, galantamine, rivastigmine), NMDA-antag (memantine). New = Adacanumab
Adacanumab side-effect Diffuse cerebral edema
Alzheimers associated conditions Cerebral Amyloid Angiopathy CAA. Down syndrome
Best predictor of driving in Alzheimers dementia Cognitive test. 2nd is caregiver perception. Least reliable is what patient self-assesses
Where is Tau located? Where is beta-amyloid? Tau is intracellular. Beta-amyloid is extracellular
Hirano bodies Actin filaments. A/w Alzheimers
Early Onset Alzheimers Will affect multiple cognitive domains. Still non-hereditary is most common
Posterior Cortical Atrophy Occipital hypometabolism and atrophy. Largely visual memory loss (faces, people, driving, etc)
FTD gene C9orf72 and TDP42 if with ALS. Others include Chrm 17q21 MAPT, and PGRN
What chromosome is TDP43 located on? ALS + FTD. Located on chromosome 9
Personality changes, disinhibition, apathy, dementia Fronto-Temporal Dementia
Hyperphosphorylated Tau Fronto-Temporal Dementia
FTD histopathology Spherical hyperphosphorylated Tau. Unlike Alzheimers, FTD is not tangles and has no amyloid
What is ubiquitin? Protein tag. Tagged cells will undergo autophagocytosis
Picks dementia Variant of Fronto-Temporal Dementia. More apathy/abulia. A/w Kluver-Bucy
Primary Progressive Aphasia Variant of Fronto-Temporal Dementia. More temporal language deficits
MRI "knife-edge" sylvian fissure Temporal atrophy. Consider Primary Progressive Aphasia variant of FTD
Word-finding difficulties, parkinsonism, temporal atrophy Primary Progressive Aphasia -- Nonfluent = L anterior perisylvian fissue
Vocabulary/naming difficulties, temporal atrophy Primary Progressive Aphasia -- Semantic = L>R anterior temporal lobe
Word-finding difficulties, dysphasia, Alzheimers Primary Progressive Aphasia -- Logopenic = L posterior temporal and inferior parietal
Sneddon syndrome Slowly progressive blockages of small/medium arteries -> vascular dementia
Binswanger disease Traditional risk factors (DM/HTN/etc) -> white matter disease -> vascular dementia
Vascular dementia treatment Start Donepezil, not just control risk factors. Donepezil is FDA approved for vascular dementia.
CJD protein PrPsc prion protein from PRNP gene on Chromosome 20p
CJD inheritance Overwhelmingly due to spontaneous mutations in protein misfolding. Rarely genetic
Does immunosuppression increase risk of CJD? No. CJD is not autoimmune or infectious, it is spontaneous protein misfolding
Rapid dementia, hallucinations, myoclonus, ataxia Creutzfeldt-Jacob disease CJD = Prion disease
EEG 1Hz repetitive sharp-wave 1Hz is often seen in CJD
CJD CSF Often normal, can sometimes mimic Alzheimers (increased Tau, Hirano bodies)
14-3-3 Marker for CJD
Most sensitive test for CJD MRI showing cortical diffusion restriction ("cortical ribboning"), +basal ganglia and pulvinar
Most specific test for CJD RT-Quic PCR. More specific that 14-3-3 or EEG 1Hz findings
CJD histopathology Spongiform. Neuronal loss without any inflammation
Do you have to report CJD to public health authorities? No. It is generally not contagious unless tissues/organs are consumed in cannabalism
Fatal Familial Insomnia FFI Variant of CJD with intractable insomnia
CJD variants Fatal Familial Insomnia. Kuru. Mad cow
Subacute fluctuating dementia, seizures Check thyroid. Specifically TPO antibodies. Differential also autoimmune/paraneoplastic
Incontinence + gait difficulties + dementia "Wet, wobbly, wachy" of normal pressure hydrocephalus
Magnetic gait Normal pressure hydrocephalus
Normal pressure hydrocephalus test LP for CSF drainage. Assess gait pre- and 1-hour post-LP
Normal pressure hydrocephalus treatment Repeat LPs or shunt. Note: only helps gait/falls - no impact on cognition
Created by: amitchaudharimd
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