Neuro - Pathology (Dementia)

Question 1

What is dementia?

Answer 1

A decrease in cognitive ability, memory, or function with intact consciousness

Question 2

What is the most common cause of dementia in the elderly? Besides the elderly, which patient population has an increased risk of developing this?

Answer 2

Alzheimer disease; Down syndrome patients have an increased risk of developing Alzheimer

Question 3

What percentage of Alzheimer disease is associated with its familial form? With what kind of proteins is this form associated with in general, early onset, and late onset?

Answer 3

Familial form (10%) associated with the following ALTERED proteins (respective chromosomes in parentheses): EARLY ONSET - APP (Chr 21), presenilin-1 (Chr 14), presinilin-2 (Chr 1); LATE ONSET - ApoE4 (Chr 19)

Question 4

What protein is protective against Alzheimer disease, and on what chromosome is it found?

Answer 4

ApoE2 (Chr 19) is protective

Question 5

What are 2 gross findings in Alzheimer disease?

Answer 5

(1) Widespread cortical atrophy (2) Narrowing of gyri and widening of sulci

Question 6

Which neurotransmitter is decreased in Alzheimer disease?

Answer 6

Decreased ACh

Question 7

What are 2 histological findings characteristic of Alzheimer disease?

Answer 7

(1) SENILE PLAQUES (2) NEUROFIBRILLARY TANGLES

Question 8

What is the structure of Senile plaques? What is a complication that can arise from them? How are they synthesized?

Answer 8

SENILE PLAQUES: extracellular Beta-amyloid core; may cause amyloid angiopathy –> intracranial hemorrhage; ABeta (amyloid-Beta) synthesized by cleaving amyloid precursor protein (APP)

Question 9

What is the key structure/component of Neurofibrillary tangles? What clinical significance do they have?

Answer 9

NEUROFIBRILLARY TANGLES: intracellular, hyperphosphorylated tau protein = insoluble cytoskeletal elements; Tangles correlate with degree of dementia

Question 10

Name 4 major causes of dementia. What are 6 other causes?

Answer 10

(1) Alzheimer disease (2) Pick disease (frontotemporal dementia) (3) Lewy body dementia (4) Creutzfeldt-Jakob disease (Note - Other causes of dementia include: (1) multi-infarct, (2) syphilis, (3) HIV, (4) vitamins B1, B3, or B12 deficiency, (5) Wilson disease, and (6) NPH)

Question 11

What is another name for Pick disease? What 4 symptoms/aspects of the disease?

Answer 11

Pick disease (frontotemporal dementia); (1) Dementia (2) Aphasia (3) Parkisonian aspects (4) Change in personality

Question 12

What portion(s) of the brain is (are) spared in Pick disease?

Answer 12

Spares parietal lobe and posterior 2/3 of superior temporal gyrus (hence name frontotemporal dementia)

Question 13

What is a histological finding associated with Pick disease? What is its gross finding?

Answer 13

Pick bodies: spherical tau protein aggregates; Frontotemporal atrophy

Question 14

What is the initial presentation of Lewy body dementia and its progression of symptoms?

Answer 14

Initially dementia and visual hallucinations followed by parkisonian features

Question 15

What is the defect in Lewy body dementia?

Answer 15

alpha-synuclein defect

Question 16

What are the symptoms and time course of Creutzfeldt-Jakob disease?

Answer 16

Rapidly progressive (weeks to months) dementia with myoclonus (“startle myoclonus”)

Question 17

What is a gross finding associated with Creutzfeldt-Jakob disease? What is the underlying molecular change?

Answer 17

Spongiform cortex; Prions (PrP^c –> PrP^sc [Beta-pleated sheet resistant to proteases]

Question 18

What is the 2nd most common cause of dementia in elderly?

Answer 18

Multi-infarct