Chapter 10

Question 1

dementia

Answer 1

loss of cognitive ability

Question 2

Alzheimer’s disease (AD)

Answer 2

• leading cause of dementia
• degeneration of the brain, especially the cortex and limbic system (hippocampus)
• sulci especially wide, indicating degeneration of the cortex

Question 3

preclinical AD

Answer 3

• no symptoms
• measurable brain changes

Question 4

mild cognitive impairment due to AD

Answer 4

• very mild symptoms that do not interfere with everyday activities
• measurable brain changes plus subtle problems with memory and thinking

Question 5

mild AD

Answer 5

• symptoms interfere with some everyday activities
• memory problems (especially new memories), word finding difficulties, trouble with planning/organization

Question 6

moderate AD

Answer 6

• symptoms interfere with many everyday activities
• memory problems (personal history), feeling moody and/or withdrawn, wandering/getting lost, personality changes (e.g., suspiciousness and delusions)

Question 7

severe AD

Answer 7

• symptoms interfere with most everyday activities
• loss of awareness (of recent events and surroundings), difficulty with communication, vulnerable to infections (especially pneumonia)

Question 8

dementia memory lapses

Answer 8

• not recognizing family members
• forgetting to serve meal just prepared
• substituting inappropriate words
• getting lost in own neighborhood

Question 9

key characteristics of AD

Answer 9

• cognitive deficits: profound memory loss (anterograde/retrograde), language (anomic, empty, circumlocutory), visuospatial disturbance
• behavioral deficits: no significant early changes in personality, unawareness or denial of illness, psychosis
• no sensory or motor deficits
• age of onset 70s-80s

Question 10

pathology of AD

Answer 10

• neurofibrillary tangles (tau protein)
• amyloid plaques (beta amyloid)

Question 11

beta-amyloid plaques (senile plaques)

Answer 11

• large amyloid precursor proteins (APP) are cut into fragments called beta-amyloid fragments via the enzyme beta-secretase
• the fragments clump into plaques outside of the cell and destroy dendrites, reducing dendritic branching affecting cognition
• they also initiate an immune response from the microglia that also increase the spread of plaques killing neurons

Question 12

neurofibrillary tangles

Answer 12

• inside of the neuron
• microtubules are bound together with tau proteins
• if tau proteins change their structure, the microtubules fall apart
• the tau proteins clumps together in tangles, killing the neuron

Question 13

cytoskeleton of neuron

Answer 13

• gives the neuron its shape
  “bones” are:
• microtubules: big, run longitudinally down neurites, made of tubulin, microtuble-associated proteins (MAPs) regulate microtuble assembly and function; changes in MAPs called tau implicated in AD
• microfilaments: solid, thinner, actin
• neurofilaments: intermediate filaments, individual long protein molecules

Question 14

microtubule-associated proteins (MAPs)

Answer 14

• tau/MAPs can function as cross-bridges connecting microtubules
• can affect microtubule rigidity
• brain uses a transport system to help move around the nutrients it needs; system is made of proteins like railroad tracks guiding trains guide nutrients where they need to go; proteins that keep the tracks straight are tau proteins

Question 15

causes of AD

Answer 15

• genetics (likely several genes)
• immune responses initiated by microglia
• sleep imbalance

Question 16

genetics of AD

Answer 16

• amyloid precursor protein (APP) (familiar early onset of AD)
• presenilin (PS) 1 and 2 (familial early onset of AD)
• Down’s Trisomy 21
• ApoE4 increases risk of late onset of AD

Question 17

microglia and AD

Answer 17

• microglia play a role in the immune system and in the brain
• release inflammatory proteins
• attempts to clean up damage caused by beta-amyloid plaques but may contribute to the spread

Question 18

treatment of AD

Answer 18

• cholinergic replacement: treats symptoms
• anti-amyloid agents: tries to reduce the disease

Question 19

cholinergic hypothesis

Answer 19

• loss of ACh activity correlates with the severity of AD
• acetylcholinesterase inhibitors: drugs used to treat Alzheimer’s disease, act by inhibiting acetylcholinesterase activity
• these drugs block the esterase-mediated metabolism of acetylcholine to choline and acetate; this results in: increased acetylcholine in the synaptic cleft, increased availability of acetylcholine for postsynaptic and presynaptic nicotinic (and muscarinic) acetylcholine receptors

Question 20

acetylcholine (ACh)

Answer 20

an important neurotransmitter in areas of the brain involved in memory formation

Question 21

fronto-temporal dementia (FTD)

Answer 21

• FTD is an umbrella term that encompasses several types of dementia primarily affecting the frontal and temporal lobes of the brain
• includes various subtypes, such as behavioral variant FTD (bvFTD), primary progressive aphasia (PPA), and others

Question 22

Pick’s disease

Answer 22

• specific subtype of FTD
• characterized by presence of abnormal brain cells known as Pick bodies and Pick cells
• mainly affects the frontal and temporal lobes and typically presents with symptoms similar to behavioral variant FTD

Question 23

pathology of FTD

Answer 23

• can vary widely and may include tau protein inclusions, TDP-43 inclusions, or other forms of cellular degeneration
• does not always have Pick bodies

Question 24

pathology of Pick’s disease

Answer 24

characterized specifically by the presence of Pick bodies, which are abnormal clumps of tau protein inside neurons

Question 25

symptoms of FTD

Answer 25

- can vary depending on the subtype but typically include changes in personality, behavior, language, and sometimes motor skills - behavioral variant is most common and can cause disinhibition, apathy, and loss of empathy

Question 26

symptoms of Pick's disease

Answer 26

often similar to the behavioral variant of FTD with early behavioral and personality changes such as impulsivity and lack of social awareness; language difficulties may also be present

Question 27

age of onset of FTD

Answer 27

typically occurs in individuals under 65 years, most often in 50s or 60s but can occur earlier

Question 28

age of onset of Pick's disease

Answer 28

often appears in individuals in their 40s to 60s

Question 29

genetics of FTD

Answer 29

can have a genetic component, with 1/3 to 1/2 of cases linked to inherited mutations in genes such as MAPTm GRN, C9orf72

Question 30

genetics of Pick's disease

Answer 30

- less well-understood genetic basis, though it may occasionally run in families - not all cases genetically linked

Question 31

some neuropsychological tests used to evaluate executive functions

Answer 31

- Wisconsin card sorting task - Tower of Hanoi

Question 32

Wisconsin card sorting task

Answer 32

- cards may be sorted on the basis of color, shape, or number - patient not aware of the rules - use trial-and0error to infer the rule - after 10 accurate trials the rule will shift - different types of errors to report: total number errors, perseveration errors (when you keep applying the old rule), non-perseveration errors

Question 33

tower of Hanoi

Answer 33

- three pegs with three different colored rings on one end - goal: move the tower from one end of the board to the opposite side with as few moves as possible - rules: can only move one piece at a time, a larger piece is not allowed to be placed on top of a smaller piece

Question 34

vascular dementia

Answer 34

- multi-infarct - type of dementia caused by reduced blood flow to the brain, often due to strokes or other conditions that damage blood vessels, leading to brain cell death - reduced blood flow to the brain can lead to symptoms that impact memory, reasoning, and sometimes movement

Question 35

cause of vascular dementia

Answer 35

conditions that block or reduce blood flow to the brain, depriving brain cells of oxygen and nutrients - may happen due to stroke or small vessel disease

Question 36

small vessel disease

Answer 36

narrowing or blocking in the brain's smaller blood vessels can lead to gradual brain cell damage

Question 37

symptoms of vascular dementia

Answer 37

- vary depending on which parts of the brain are affected - memory loss - difficulty with problem-solving and organization - slowed thinking - difficulty with attention and concentration - changes in mood or personality - movement issues (e.g., unsteady gait)

Question 38

acute dementia

Answer 38

- intoxications: delirium - metabolic abnormalities: renal failure, substrate deficiencies (B12/folate deficiency) - hypothyroidism - depression (pseydodementia) - infectious agents: neurosyphilis/fungal meningitis/HIV

Question 39

delirium vs dementia

Answer 39

delirium and dementia often occur together in older hospitalized patients distinguishing signs of delirium: - acute onset - cognitive fluctuations over hours or days - impaired consciousness and attention - altered sleep cycles

Question 40

depression vs dementia

Answer 40

symptoms of depression and dementia often overlap, but patients with primary depression: - demonstrate decreased motivation during cognitive testing - express cognitive complaints that exceed measured deficits - maintain langauge and motor skills

Question 41

work-up of dementia

Answer 41

- careful history - complete mental status and neurological exam - blood studies CBC, electrolytes, LFTs, B12, folate levels, thyroid function tests, VDRL, FTA, HIV - lumbar puncture - EEG - MRI - PET