Dementia and associated disorders

Question 1

________ is a degenerative disease of the frontal and anterior temporal lobes (spares parietal and occipital lobes), and is characterized by round aggregates of Tau protein in neurons of the cortex

Answer 1

Pick disease, which is a subtype of Frontotemporal Lobar Degeneration FTLD-Tau type (there also exists a FTLD-TPD-43 type)
In Pick’s disease, you will see rounded aggregates of Tau (pick bodies), which is in contrast to Alzheimer’s Disease that has Tau forming in the shape of the neurons (neurofibrililary tangles)
Behavioral and language symptoms arise early; eventually progresses to dementia

Question 2

_________________presents with alterations in personality, social behavior, and/or language. There will be progressive deterioration of these faculties and eventual progression to a global dementia.

Answer 2

Frontotemporal dementia (Pick disease)causes pronounced atrophy of the frontal and temporal lobes with sparing of the posterior 2/3 of the superior temporal gyrus:

• Frontal lobe degeneration leads topersonality changes, abulia, and disinhibition.
• Temporal lobe degeneration leads toimpaired understanding of language.

Question 3

Certain mutations predispose to early-onset Alzheimer diseaseincluding what 3:

Answer 3

1. Amyloid β precursor protein (AβPP) gene on chromosome 21
2. Presenilin-1 gene on chromosome 14
3. Presenilin-2 gene on chromosome 1 (presenillin is part of a complex for gamma-secretase enzymes involved in degrading amyloid beta proteins)

Question 4

Down syndrome patients almost universally develop _________ by 40 years of age due to the extra copy of chromosome 21 leading to increased expression of _____ gene.

Answer 4

Alzheimer disease
AβPP

AβPP mutations lead to abnormal Aβ production. In addition, metabolizing enzymes like alpha-secretase are unable to degrade proteins leading to formation of neuritic “senile” plaques.

Question 5

Distinct alleles of the apolipoprotein E (ApoE) gene have different associations with the risk of developing late-onset Alzheimer disease, what are the high and low risk alleles?

Answer 5

ApoE2: decreased risk
ApoE4: increased risk

Question 6

_________ have an extracellular core comprise of Aβ amyloid with entangled neuritic processes

Answer 6

Neuritic plaques

Question 7

__________ have intracellular aggregates of fibers composed of hyperphosphorylated Tau protein

Answer 7

Neurofibrillary Tangles

Question 8

______ is derived from amyloid precursor protein (APP), which is coded on chromosome ____

Answer 8

Aβ amyloid
chromosome 21
APP normally undergoes alpha cleavage; beta cleavage is what results in Aβ amyloid

Question 9

What is the major class of drug used to treat AD?

Answer 9

Acetyocholinesterase inhibitors (donepezil)

The degeneration of cholinergic cells that project to the cortex from the basal forebrain, especially in the basal nucleus of Meynert is seen in patients with Alzheimer disease.

Question 10

__________areextracellular β amyloid core that may cause amyloid angiopathy.

Answer 10

Senile plaques

AβPP mutations lead to abnormal Aβ production. In addition, metabolizing enzymes like alpha-secretase are unable to degrade proteins leading to formation of neuritic “senile” plaques.

Question 11

_______ is anamyloid deposition around vessels leading to lobar intracranial hemorrhage.

Answer 11

Amyloid angiopathy

Question 12

________areintracytoplasmic proximal dendritic eosinophilic inclusions of actin.

Answer 12

Hirano bodies

Question 13

___________isatrophy of the hippocampus consisting of small vacuoles within the cell body, each vacuole having a small dense inclusion.

Answer 13

Granulovacuolar degeneration

Question 14

_______is a depression that mimics dementia with an abrupt onset, moderate memory loss, cognitive problems, no decrease in IQ, and previous psychiatric history (unlike in Alzheimer disease).

Answer 14

Pseudodementia

Question 15

__________ shows minor forgetfullness, reduced ability to learn new things quickly, no decrease in IQ (unlike in Alzheimer disease), and no disruption of normal life.

Answer 15

Normal aging

Question 16

__________ has an insidious onset, severe memory loss, cognitive problems, decrease in IQ, and disruption of normal life.

Answer 16

Alzheimer disease

Question 17

_______ is caused by multiple, small cerebral infarctions usually resulting from cardiovascular disorders such as HTN, or atherosclerosis.
How do you tx?

Answer 17

Vascular dementia, or vascular neurocognitive disorder (NCD).
You will see lacunar infarcts (small holes)
Tx: treat underlying CVD to prevent further infarcts from occurring (anticoags, antihypertensives)

Question 18

This is the 2nd most common cause of dementia, with symptoms that occur in a stepwise fashion

Answer 18

Vascular dementia
Step wise progression can be seen after CVA
Controlling vascular risk factors will help
Often subcortical predominance (tend to have depression, executive fcn reduced)

Question 19

What histologic structure is necessary for a diagnosis of Parkinsons Disease?

Answer 19

Lewy bodies must be present in the substantia nigra

Even if you find a loss of pigmentation in the substantia nigra but you do NOT find lewy bodies, then it is not PD

Question 20

Dementia with Lewy Bodies (DLB) is associated with Lewy bodies being found in what region of the brain?

Answer 20

Cortex (frontal, temporal, limbic, insular cortex)

The finding of lewy bodies in substantia nigra is characteristic of Parkinsons

Question 21

A stain for what protein is needed to diagnose lewy bodies in lewy body dementia?

Answer 21

alpha-synuclein is used to stain sections of cortex, since lewy bodies are much easier to see in substantia nigra (PD patients).

Question 22

Lewy Body Dementia (LBD) or Parkinson’s Disease (PD)

Onset of dementia within 12 months of PD diagnosis?

Answer 22

Lewy body dementia

With PD, you see onset of dementia >12mo after PD dx

Question 23

Lewy Body Dementia (LBD) or Parkinson’s Disease (PD)

Onset of dementia more than 12 months of PD diagnosis?

Answer 23

Parkinson’s Disease and dementia

With Lewy Body Dementia you will see the onset of dementia within 12 months of PD dx

Question 24

Vivid visual hallucinations are characteristic of Lewy body dementia or parkinsons diseasE?

Answer 24

Lewy body dementia

Question 25

a Patient presents with cogwheel rigidity and shuffling gate…what is the most likely dx?

Answer 25

Parkinson’s Disease
T-Tremor..pill rolling at rest that disappears with movement
R-rigidity-cogwheel rigidity
A-Akinesia/bradykinesia-slowing of voluntary movement
P-Postural instability and shuffling gate

Question 26

A patient presents with step-wise dementia..what is the dx?

Answer 26

Vascular dementia

Question 27

The mini mental status exam (MMSE) is a standardized 30point rating scale, what scores correlate with Normal, mild, moderate, or severe?

Answer 27

Normal: 27-30
Mild: 20-30
Moderate: 10-20
Severe: 10 or lower

Question 28

The Montreal Cognitive Assessment (MoCA) is a standardized 30 point rating scale, what scores correlate with normal, mild, moderate, or severe?`

Answer 28

Normal >26
Mild: 18-26
Moderate: 10-17
Severe: <10