Dementia And Degenerative Disorders Flashcards
What structure does Alzheimer disease affect? What does it cause?
Degenerative disease of the cortex which causes dementia.
What causes dementia? What causes movement disorders. How is it characterized?
Degeneration of the cortex leads to dementia and degeneration of the brainstem and basal ganglia lead to movement disorders. Characterized by loss of neurons within the gray matter, often due to accumulation of protein which damage neurons.
What are the clinical features of Alzheimer disease?
- slow onset memory loss and progressive disorientation.
- loss of learned motor skills and language.
- changes in behavior and personality
- patients become mute and bedridden
- focal neurological deficits are not seen in early disease
What is the risk profile of Alzheimer? Which alleles are associates with increased risk and decreased risk?
Risk increases with age (doubles every 5 years after 60 years). E4 allele of apolipoprotein E (APOE) is associated with increased risk. E2 allele with decreased risk.
What two situations is early onset Alzheimer disease seen in? Which mutations are involved?
- Familial cases associated with presellin1 and 2.
2. Down syndrome - commonly occurs by 40 years of age
What does the gross morphology of the brain look like in Alzheimer’s disease? What two histological structures are also present?
Cerebral atrophy with narrowing of the gyri and widening of the sulcci and dilation of the ventricles. Neuritic plaques and neurofibrillary tangles, loss of cholinergic neurons in the nucleus basalis of Meynert.
How is the diagnosis of Alzhemimers disease made?
Clinically after excluding other causes. Confirmed by histology at autopsy.
Where is Aß amyloid derived from? What kind of structures does it form when it Which chromosome is it coded on? What happens when it deposits around vessels?
Derived from amyloid precursor protein (APP) coded on chromosome 21. APP normqlly undergoes alpha cleavage, but beta cleavage results in Aß amyloid. Causes hemorrhage around vessels. They form neuritic plaques which is an extracellular core comprised of Aß amyloid with entangled neuritic processes.
What disease are neurofibrillary tangles present in? What are they made of?
They are intracellular aggregates of fibers composed of hyperphosphorylated twu protein which is a microtubule associated protein
What causes vascular dementia?
Multifocal infarction and injury due to hypertension, atherosclerosis or vasculitis. 2nd most common cause of dementia.
What lobes does Picks disease attack? What is it characterized by? What symptoms does it present with?
Frontal and temporal cortex. Characterized by round aggregates of tau protein (pick bodies) in neurons of the cortex. Behavioral and language symptome arise early and progress to dementia.
A 39 year old patient presents with chorea. His wife mentioned that he has been feeling depressed and has shown signs of dementia. What does he have and what is causing its? What is the common cause of death in these patients?
He has Huntington disease which is a degeneration of GABAergic neurons in the caudate nucleus of the basal ganglia. Average presentation age is 40 and suicide is a common cause of death.
What gene and which chromosome is affected in Alzheimer disease? How is it inherited? What do these mutations cause?
Autosomal dominant disorder on chromosome 4 characterized by expanded trinucleotide repeats (CAG) in huntingtin gene. Further expansion of repeats during spermatogenesis leads to anticipation.
A 57 year old mechanic comes in with his caretaker to your clinic. He presents with urinary incontinence , difficulty walking in a straight line and dementia. What does he have?how would you treat?
He has normal pressure hydrocephalus which is due to increased CSF resulting in dilated ventricles. Triad of wet, wobbly and wacky. Lumbar puncture improves symptoms. Tx is ventriculoperitoneal shunting.
