Dementia & Neurodegeneration Flashcards
(25 cards)
What are the 3 ways in which axons can become degenerated?
Wallerian - distal degeneration of both axon and myelin (often by trauma - DAI)
Axonal - ‘dying back’ from cell body towards dendrite
Demyelination - loss of oligodendrocytes/Schwann cells (MS/GBS)
Outline PNS degenerative disorders
Diabetic Neuropathy - axonal degeneration from hyperglycaemia, nociceptive + neuropathic pain
MND - UMN and LMN lesions by degeneration of motor pathways affecting outflow from anterior horn cells
GBS - autoimmune demyelinating disorder
Outline CNS degenerative disorders
MS - autoimmune inflammatory demyelinating disorder
PD - degeneration of DA neurones in SN and Lewy Body accumulation intracellularly (inclusion)
HD - autosomal dominant CAG repeats, GABAergic neurone loss in striatum and reduced ACh transmission - shrunken caudate head
Prion diseases - CJD, vCJD, Spongiform encephalopathies by PrPc -> PrPsc transmissible or genetic
What are the different types of Dementia?
Alzheimer’s - loss of ACh transmission
Vascular - reduced cerebral blood flow
Dementia with Lewy Bodies - a-synuclein Lewy body inclusion
Frontal Temporal - atrophy of frontal/temporal lobes (Pick’s)
Normal Pressure Hydrocephalus - CSF build up without raised ICP
How is Normal Pressure Hydrocephalus characterised both by symptoms and on imaging?
Ventriculomegaly
Urinary incontinence, gait disturbance, cognitive decline, ocular changes sometimes
How are Parkinson’s disease and Dementia with Lewy Bodies different?
LBD a-synuclein deposits typically throughout cortex, symptoms present with Parkinsonism + hallucinations + memory loss/fluctuations in cognition
PD bradykinesia + tremor from reduced DA neurones from SNPC (a-synuclein inclusion) and memory loss/cognitive impairment not until later stages
How does Alzheimer’s present on imaging? What is the treatment?
First thing to degenerate is hippocampus and medial temporal lobes
FMRI shows hypometabolism in posterior cingulate and bilateral parietal-temporal regions
Post-mortem will confirm histology of B-amyloid plaques and Tau neurofibrillary tangles
Gross morphology is cerebral atrophy
Cholinesterase inhibitors for mild-moderate: Donepezil, Galantamine, Rivastigmine
Severe treated with NMDAr antagonists Memantine
What investigations can be used for Dementia?
History from patient but family member/friend too
Cognitive tests: MMSE, GPCOG
Neuroimaging: CT, MRI, fMRI
Bloods for B12/Folate/TFT/CRP
Dementia is characterised by global deterioration in…
Cognition - memory, orientation, concentration, speech
Behaviour
Personality
= affect work, social function and relationships
What’s a cerebrovascular cause of dementia?
Multi-infarct
Which types of dementia fall into the acute, subacute and chronic clinical courses?
Acute (weeks) - infective/encephalitis/paraneoplastic
Subacute (months) - Thiamine deficiency (Werncike’s), CJD, vCJD, Inflammatory (vasculature, sarcoidosis)
Chronic (years) - AD, multi-infarct, Pick’s disease, HD
What are some cortical types of dementia and their features?
Frontotemporal
CJD
Alzheimer’s
Higher cortical abnormalities
Dysphasia
Agnostic
Apraxia
What are some subcortical types of dementia and their features?
Normal pressure hydrocephalus
PD
HD
Apathetic Forgetful Slow Impaired visuospatial abilities Depression of mood
What are 2 types of subcortical AND cortical dementia?
Multi-infarct
Cortical Lewy body disease
What does imaging in Alzheimer’s disease show?
Early imaging will be normal
Later: neocortical/hippocampus atrophy, medial temporal lobe atrophy
Functional imaging: hypometabolism in posterior cingulate and bilateral parieto-temporal regions
What type of neurones are lost in DLB?
Dopamine and Acetylcholine
How can you tell fronto temporal dementia on imaging?
Focal atrophy of frontal or temporal lobes
What are the 3 cardinal features of normal pressure hydrocephalus? What’s its sign on imaging? How is it treated?
Gait disturbance
Cognitive decline
Urinary incontinence
Ventriculomegaly on imaging
CSF shunt inserted ventriculoperitoneal to drain CSF into abdomen, maybe third ventriculostomy
What are the two main classes of drugs used to treat dementia and in which cases are they used?
Anticholinesterases (AChE inhibitors to prolong ACh in cleft) used in mild-moderate dementia (Donepezil Galantamine, Rivastigmine)
Glutamate receptor antagonists (NMDAr to prevent neuronal excitability and cell death) for moderate-strong dementia (Memantine)
What are the three features of DLB? What class of drug for one of the symptoms is a problem?
Dementia + Parkinsonism + Hallucinations
Antipsychotics can’t be used to treat hallucinations in DLB as they will exacerbate the Parkinsonism symptoms (as they block DA pathways to slow hyperactivity/psychotic behaviours seen in Schiz)
What are the two forms memory can be divided into? Where are these different memories stored?
Procedural (expressed through motor functions) and Declarative (recognition/naming)
Procedural memory involved cerebellum, basal ganglia and pre motor cortex = long lasting and can be performed without conscious recollection
Declarative memories are rapidly learned and rapidly forgotten - rely on connection between hippocampus and cortex
What’s anterograde amnesia?
Inability to form new memories due to fault in consolidation of new experience into long term memory
Damage usually in temporal lobes - hippocampal gyrus
What’s retrograde amnesia?
Inability to recall events prior to precipitating event eg a car crash
Failure of long term memory
What’s episodic memory?
Remembrance of autobiographical information located in time and personal experience
