Dementia Flashcards
Frontal lobe damage
Impaired judgement, abstract reasoning, strategic planning, emotional restraint, control of appetite and continence
Medial temporal lobe damage - hippocampus, amygdala, limbic - damage
Memory disorders
Hallucinations
Temporal neocortex damage
Receptive dysphasia and automatisms
Occipital lobe damage
Failure of visual sensory systems
Parietal lobe damage
Impairment of visuospatial skills, integration of sensory inputs, leading to sensory agnosias and apraxias
Neurodegenerative dementia types
Alzheimer's Lewy body dementia Frontotemporal dementia Huntington's disease + many others Vascular dementia Prion diseases
Dementia classification categories
Ant/post
Cortical/subcortical
Movement disorders examples
Parkinson’s
Parkinson plus syndromes
Huntington’s disease
Motor neuron disease
Neurodegenerative dementias
Alzheimer’s
Frontotemporal dementia
Dementia with lewy bodies
Tauopathies
Frontotemporal dementia
Alzheimer’s
Ubiquinopathies
Frontotemporal dementia
Synucleinopathies
Parkinson’s
Dementia with lewy bodies
MSA
Normal pressure hydrocephalus - presentation
Triad of: dementia, gait disturbance, urinary incontinence
Normal pressure hydrocephalus - types
NPH with preceding cause e.g. SAH, meningitis, trauma, radiation-induced
Idiopathic (50%)
What would show triphasic waves?
Transmissible spongiform encephalopathies
What does CBD stand for?
Corticobasal degeneration
What is CBD?
Tauopathy
MRI shows phospho-tau filaments within the neuron from a brain of CBD
What does VGKC Ab mean?
Voltage gated potassium antibodies
What does VGKC Ab indicate and present?
Subacute memory loss Psychiatric/behavioural disturbance Seizures Hyponatraemia 65 yo median age; 2:1 M:F Immunomodulation for treatment - if no tumours but a lot have tumours
What proteins are involved in dementia
B-amyloiad
Tau
a-synclein
Ubiquitin
What are amyloid proteins?
INsoluble fibrous protein aggregates sharing specific structural traits
What do tau proteins do?
A group of proteins that stabilise microtubules in neurons
Six isoforms - if defective, microtubules become unstable and dysfunctional
Amyloid cascade model
- a-secretase processing of APP is modulated by stimulation of ACh or 5HT receptors.
- Within the neuron, PS1 associated with APP and traffics it with an endosomal vesicle, generating AB1-42
- AB1-42 secreted and forms aggregates
- activate microglia + react excitotoxically with neurons, forming plaques via interaction with ApoE and deposition of AB amyloid as plaque
- Plaque formation degenerates neurons
- Active microglia make positive feedback loop + enhances plaque
a-Synuclein pathway
- Monomer folds badly
- forms b-sheet oligomer
- Forms lewy body
What is ubiquitin?
Small regulatory protein in almost all cells
Directs proteins to cell compartments
Can be attached to protein and label them for destruction
Pathogenesis
- Oxidative stress makes free radicals
- Excitotoxicity: glutamine stimulation
- Induction of apoptosis
Cytokines, genetic factors, ageing and unknown aetiology
Accumulation of abnormal proteins intracellular
Tau
a-Synuclein
Polyglutamine
Ubiquitin
Accumulation of abnormal proteins extracellular
Amyloid
Macroscopic neuropathological findings of AD
Brain weight decrease - (1300 -> 1000)
Atrophy in cerebral gyri (hippo, temp, parietal, frontal, cingulate - less so occipital)
Atrophy in white matter + thin corpus callosum + brain stem + cerebellum
Ventricular dilatation
Pale substantia nigra + locus ceruleus
Microscopic neuropathological findings of AD
Neuron loss from hippo,cerebral cortex
Microvacuolation in cerebral neocortex
Attenuation in white matter
Braak staging system what is it?
Shows mild to severe infiltration of abnormal proteins
Names of CERAD groups
Normal
Definitive AD
Probable AD
Possible AD
Macroscopic finding of dementia with lewy body (DLB)
Pale substantial nigra and LC???
Atrophy in amygdala, cingulate, temp, parietal, frontal
Microscopic finding of dementia with lewy body (DLB)
Neuronal loss from SN and LC
Accumulation of a-synuclein +ve bodies in neurons of SN, amygdala and later in the cerebral cortex
DLB under microscope you see
Red bodies
Vascular dementia features
Multi-infarct dementia (ischaemic damage to brain)
Binswanger’s dementia (pathology mainly in white matter - microinfarctions in white matter)
Arteriolosclerosis (high pressure and become sclerotic, collagen fibres replace smooth muscle, less able to supply local region so loss of neurons)
Frontotemporal dementia (pick’s disease) under microscope
Balloon cells and pick bodies - ubiquitin and tau positive
Abbreviations of major neuropathological diagnosis of dementias
Alzheimer’s Disease (AD) Frontotemporal lobar degeneration (FTLD) Dementia with Parkinsonism: Idiopathic Parkinson Disease (IPD) Dementia with Lewy Body (DLB) Corticobasal degeneration (CBD) Progressive Supranuclear Palsy (PSP) Vascular Dementia (VaD) Normal Pressure Hydrocephalus (NPH) Creutzfeldt-Jakob Disease (CJD)
