Cognitive Flashcards
Dementia screening
CBC, glucose, TSH, BMP with Cr/BUN, LFTs
-no VDRL/RPR or HIV screening anymore or LP
AD genes
ALL Autosomal dominant
Late onset AD - APOE4 increases risk -chr 19
(ApoE4 homozygous is a susceptibility gene not genetic mutation)
(apo E2 protective)
Early - APP- amyloid precursor - chr 21
presenilin 1 (most common) -chr 14
presenilin 2 -chr 1
TREM2 gene increase risk AD
-beta-amyloid plaques, tau fibrillary tangles
lecanemab - decreased B amyloid plaques, moderate effect on disease -
Risk: ARIA - rash, encephalopathy, superficial siderosis
Risk factors: FEMALE gender, low level education, repeated head trauma
IgLON5 Ab
Abnormal sleep movements, obstructive sleep apnea, bulbar Sx, central hypo ventilation, tauopathy
FDG PET patterns
AD dementia- low posterior temporoparietal activity (post cingulate low first)
-decreased glucose metabolism
LBD - lateral occipital cortex low, cingulate island sign = post cingulate preserved > temporoparietal hypometabolism
FTD - low frontal lobe, anterior temporal lobe
HD - low caudate, putamen
vascular dementia - scattered areas low update corresponding to infarcts
PSP - decreased glucose metabolism BG, thalamus, upper brainstem, ant cingulate
atypical AD
- parietaloccipital - Gerstmann
- logopenic - L temporoparietal function - repetition impaired
FTDegeneration
Pathology:
FT lobar degeneration
Primary progressive aphasias - semantic variant- FTD 43-
non fluent agrammatic variant - then hand involved (fine finger movements) -apraxia
-bvFTD - like a kid - loss empathy, apathy; FTD/ALS - C9orf72 TDP 43
-picks disease repeat expansion
-motor FTD - PSP - hummingbird
-motor FTD - CBD
tpd43 semantic variant
focal anterior temporal lobe atrophy - start asymmetric on left then right then orbitofrontal
Progranulin - TPD 43
MAPT - chr 17
3R repeats - Pick’s
4R - CBD and PSP
AD CSF
CSF pattern consistent with high risk of progression from MCI to Alzheimer’s:
High Tau, LOW beta-amyloid
-beta-amyloid plaques accumulate so low beta amyloid in CSF
minor cognitive impairment
1 or more domains
-doesn’t interfere with iADLs
-amnestic MCI->early AD
vs nonamnestic - language/executive/attn/visuospatial fxn
papez circuit, memory formation
entorhinal cortex->hippocampus->fornix->mamillary bodies->Anterior Nuc thalamus ->cingulate gyrus->entorhinal cortex
medial temp lobe: storage, retrieval (3 word recall first impairment ; episodic memory impaired vs immediate/remote memory; semantic spared until laterAD)
-BL medial temp lobe lesions - loss declarative/explicit memory
no specific lesions leading to loss of nondeclarative memory
AD histopathology, pathophys
-
early before Sx: amyloid deposition-cortex, leptomeningeal vessels**
neuritic plaques piles of sprinkles, neurofibrillary tangles-most specific -
-granulovacuolar degneration, Hirano bodies-less specific
(*Alzheimer’s type II astrocytes - hepatic encephalopathy)
-loss cholinergic neurons-nucleus basalis of Meynert
-loss AChtransferase acitivty-correlates with memory loss
MRI: hippocampal lumpy bumpy sign
Amyloid scan: grey + white matter light up, normal = just white matter lights up
Huntington’s disease
chromosome 4
FTD
inherited - chromosome 17 (backwards F)
tauopathy -histo: pick bodies (clumps of tau)
-behavioral variant FTD - Pick’s disease - least likely to be depressed vs HD- apathy, abulia, poor judgement, personality change, hyperphagia, OCD
-progresive nonfluent aphasia - preserve comprehension
-semantic dementia/progressive fluent aphasia - ~transcortical sensory aphasia, BL temp
Kluver-Bucy - BL anterior temporal lobe/amygdala - hyperphagia, hyperorality, and hypersexual, visual agnosia- HSV encephalitis
thalamic nuclei
anterior nuclei - Papez circuit memory formation
Dorsomedial nuc - abulia, anterograde amnesia, social disinhibition
pulvinar - visual, sensory integration
VPM-face and parvicellular potion = taste input
VPL-body
reticular nuc - sleep spindles
akinetic mutism
BL GPi
-BL ACA infarcts
-medial frontal lobe
TBI
altered personality interferes most with rehab
AD drugs
memantine - NMDA antagonist (+5HT3 antagonist)
Donepezil - pure ACHE antagonist
Rivastigmine ACHE + butyrylcholinesterase antagonist “reverse the stigma” double punch to raise ACHE
Galantamine - ACHE antagonist + allosteric nicotinic modulator “Alzheimer’s Gala”
Histopathology
LBD - halo around Lewy body
Pick bodies - off center inclusion, fat (hyperphagia in FTD) - tau aggregates-silver staining
AD - 1st - amyloid angiopathy
neuritic plaques piles of sprinkles- like plaque psoriasis-Beta-amyloid
(B-secretase)
- neurofibrillary tangles - matted densehelix -hyperphosphylated tau
- granulovacuolar degeneration - vaculoles with intracytoplasmic granules- open spaces around cells
CJD - spongiform vacuoles - blank white spaces
PSP - tufted astrocytes (tufted eyebrows)
MSA - glial cytoplasmic inclusions
CBD - coiled bodies, ballooned neurons
Negri bodies - Rabies-little black dot (negro) perfect circle
ALS - Bunina bodies - buried dots at perimeter motor cell
Wernicke, Korsakoff vs psychogenic
psychogenic: lose autobiographical memory, +/- can learn new things
Wernicke - confusion, ataxia, ophthalmoplegia
CJD
familial - susceptibility-PRNP-Chr 20 twenty twerpy cows
Autosomal dominant
PrP alpha helix converts to B-pleted sheet
cortical ribbon
-increase T2 caudate, putamen, pulvinar
balint syndrome
Where disorders - dorsal stream (donde)
-simultanagnosia (can’t see more than one thing at one time)+ ocular apraxia + optic ataxia
BL parieto-occipital
agnosia types
prosopagnosia - BL fusiform gyri (temporo-occipital); +/- achromatopsia
topographagnosia - can’t navigate, read/draw maps - R posterior parahippocamcal/infracalcarine cortex
asomatognosia - can’t recognize body part - R superior parietal, supramarginal (somato = body)
-somatoparaphrenia - deny ownership of body parts + think they are stolen
misoplegia - severe hatred of limb
aphasias
pure word deafness/verbal auditory agnosia - can’t understand other people speaking but otherwise intact language; normal writing
-BL middle superior temporal gyri - disrupt connection to Heschl’s gyrus
-amusia - agnosia to music
nonverbal auditory agnosia - agnosia to sounds - BL anterior temporal lesions/R temporal lobe
anomia - recognize but can’t name - angular gyrus syndrome (finger agnosia-Gerstmann)
aphemia - pure word mutism - productive aphasia but can write, cannot repeat - dominant frontal operculum
conduction aphasia - cannot repeat, otherwise intact - internal arcuate fasciculus
amelodia/affective motor aprosodia - nondom posterior inferior frontal gyrus (R analog of Broca/s)
sensory/receptive aprosodia - inability to percieve/understand emotional contents of speech - R superior temp gyrus (R analog of Wernicke)
Foix-Chavany-Marie - anterior opercular syndrome
severe dysarthria, BL voluntary paralysis; preserved social smile/emotional innervation
BL anterior operculum
operculum
cover of insula - frontal, temp, parietal
pseudobulbar palsy
BL corticoBULBar pathways
Tx: dextromethorphan-quinidine
Lesions to OFC vs DLPFC vs DMPFC vs anterior cingulate
OFC -disinhibited, pressured speech, inappropriate jocularity (witzelsucht), echopraxia-imitate behavior
-Dorsomedial nuc thalamus- abulia, anterograde amnesia, social disinhibition
DMPFC - motor initiation, goal directed behavior, motivation
If severe->akinetic mutism + incontinence (paracentral lobule)
-BL DMPFC/anterior cingulate (ACA/pericallosal infarcts)
- BL GPi
DLPFC - disorganized, no multitasking, lose interest in hobbies, executive dysfunction
cognitive tests
pegboard test - finger texterity
trail making - processing, visual search, attention, WM, task set switching NOT visuospatial
random cancellation test - attention, processing
clock drawing - visuospatial
Wisconsin card sorting - prefrontal cortical function
delusional misidentification
Fregoli’s - same person exists in several disguises
intermetamorphosis - swap identity while maintaining appearance
reduplicate paramnesia - identical places/objects
Capgras - identical imposter
pseudocyesis - delusion that person is pregnant
