Dementia

Question 1

What are some genes associated with alzheimer’s?

Answer 1

ApoE4 (on chromosone 19)

Amyloid precursor protein gene mutations (Chr 21)

Presinilin 1 (Chr 14) and Presinilin 2 (Chr 1)

alpha-2 macroglobulin mutations (Chr 12)

Question 2

What results on CSF analysis might suggest AD?

Answer 2

elevated tau and low alpha,beta-42 levels in the CSF

Question 3

What result on MRI might suggest AD?

Answer 3

a reduction of hippocampus, amygdala and thalamic size

Question 4

What result on PET or SPECT may suggest AD?

Answer 4

bilateral temporoparietla hypometablism

Question 5

What are the major characteristics of AD pathology?

Answer 5

gross path: brain atrophy

micro path: senile plaques, neurofibrillary tangles

Question 6

What are the senile plaques made of?

Answer 6

extracellular deposits of amyloid surrounding dystrophic axons

Question 7

What are the neurofibrillary tangles made of?

Answer 7

intracellular accumulations of phosphorylated tau protein

Question 8

What are the medications we use for AD?

Answer 8

acetylcholinesterase inhibitors like donepezil or rivastigmine

NMDA receptor antagonists like memantine (not used at the VA bc it probably doesn’t work)

Vitamin E

Question 9

What is the average length of time from onset of symptoms to diagnosis in AD? What is the typical life-expectancy after a diagnosis of AD?

Answer 9

about 2-3 years

average duration from diagnosis to nursing home is 3-6 years

average life-expectancy after a diagnosis is 5-10 years

Question 10

What are the criteria for vascular dementia?

Answer 10

presence of dementia and two or more of the following: onset that is abrupt , stepwise progression, imaging with evidence of strokes, lacunes or extensive WM changes (Binswanger disease)

Question 11

Describe the typical clinical manifestations of dementia with lewy bodies.

Answer 11

cognitive impairment - particularly with visuospatial perception and visual memory

marked fluctuations in alertness

prominent visual hallucinations in up to 80% of cases

delusions

extrapyramidal symptoms

extraordinary sensitivity to neuroleptics

Question 12

What is a lewy body?

Answer 12

an eosinophilic intracellular inclusion of alpha synuclein

Question 13

Where are the lewy bodies found in dementia with lewy bodies vs parkinsons disease?

Answer 13

in dementia they’re found in the cortical neurons in addition to the basal ganglia neurons (unlike in PD where they’re more just in the basal ganglia)

Question 14

What is the diagnosis in someone who has an inability to look up, dyarthria, dysphagia, extrapyramidal rigidity, gait ataxia and dementia?

Answer 14

progressive supranuclear palsy

Question 15

What will gross pathology show in progressive supranuclear palsy?

Answer 15

atrophy of the dorsal midbrain, globus pallidus, and subthalamic nuclei

Question 16

How do we make the diagnosis of Huntington’s diasease?

Answer 16

more than 40 CAG repeats in the HD gene on chromosome 4

Question 17

What does pathology show in Huntington’s disease?

Answer 17

severe destruction of the caudate and putamen (striatal GABA-ergic neurons) and loss of neurons in layer 3 of the cerebral cortex

Question 18

How does frontotemporal dementia typically present?

Answer 18

personality changes early in the disease, then memory later

Question 19

Describe the typical presentation of CJD.

Answer 19

rapidly progressive dementia with pyramidal signs, MYOCLONUS, cerebellar or extrapyramidal signs

Question 20

What will be seen on the EEG in CJD?

Answer 20

periodic sharp waves

Question 21

What might MRI with DWI show in CJD?

Answer 21

evolving cortical and basal ganglionic abnormalities

Question 22

What do we look for in the CSF for diagnose CJD?

Answer 22

protein 14-3-3

Question 23

What is the expected life span after a CJD diagnosis?

Answer 23

1 year

Question 24

What are some of the ways HIV can affect the CNS?

Answer 24

the virus can produce an encephalitis by itself

can also predispose individuals to other CNS infections like toxoplasmosis, tuberculosis, syphilis, and JC virus

can also cause a dementia by itself

Question 25

What is the management for HIV-associated dementia complex?

Answer 25

HAART