Dementia

Question 1

Stages of Alzheimer’s (8-10 years on average, but depends on individual)

Stage I = ____ disturbance - Progresses to poor__, carelessness in work habits & household chores, disorientation in space & time, get lost in familiar surroundings, apathy, irritability, suspicion, mild anomia. - Symptoms exacerbated by “challenges“ (e.g., illness, surgery, mild head injury, travel)

Stage II = ____ - Anomia, paraphasia, comprehension impaired. - Apraxia, acalculia (inability to do simple math), apathy worsens - Restlessness/pacing - Incontinence - Usually, care-givers are brought in at this stage

Stage III = all ____ functions affected - Worsening l___ function - Motor disturbances (rigidity, flexed posture) - Incontinence of urine and feces.

Answer 1

Stages of Alzheimer’s (8-10 years on average, but depends on individual)

Stage I = Memory disturbance - Progresses to poor judgement, carelessness in work habits & household chores, disorientation in space & time, get lost in familiar surroundings, apathy, irritability, suspicion, mild anomia. - Symptoms exacerbated by “challenges“ (e.g., illness, surgery, mild head injury, travel)

Stage II = aphasia- Anomia, paraphasia, comprehension impaired. - Apraxia, acalculia (inability to do simple math), apathy worsens - Restlessness/pacing - Incontinence - Usually, care-givers are brought in at this stage

Stage III = all intellectual functions affected - Worsening language function - Motor disturbances (rigidity, flexed posture) - Incontinence of urine and feces.

Question 2

Neuropathology of Dementia:

Early neuropathology: ___ loss in ____ structures

Interestingly, reduced___ levels in CSF are associated with an increased burden in brain –> senile _____ follow –> increase in ____ protein + neurofibrillary_____ follow

__ ___ is always affected in Alzheimer’s - time course of involvement of other areas varies!

Answer 2

Neuropathology of Dementia:

Early neuropathology: synaptic loss in limbic structures

Interestingly, reduced beta-amyloid levels in CSF are associated with an increased burden in brain –> senile plaques follow –> increase in tao protein + neurofibrillary tangles follow

Temporal lobe is always affected in Alzheimer’s - time course of involvement of other areas varies!

Question 3

The senile plaque is an ___ collection of protein. It’s a protein that is referred to as the amyloid-beta. It’s a fragment of a normal protein we all have called the ___ ___ ___ (___). It gets chopped into a smaller piece called __-___ that then collects, assembles outside of cells, and forms this aggregate mass that forms a ball between the neurons, between the interstices of the brain, which pushes aside all of the fine ramifications and connections of brain cells to form what we call a __-___ plaque.

The other hallmark of Alzheimer’s disease is the neurofibrillary tangle. That is made up of a different protein, a protein called ____, and in contrast to the plaque, the tangle forms ____ the cell. Now, there has been a debate for a long time about the primacy of the tangles or the plaques in the disease, and even more importantly what is the relationship between the two? We now know that fundamental fundamental pathogenesis of Alzheimer’s disease, is the__ and __deposition. Then, secondarily, the amyloid triggers this reaction in cells to form ___.

Answer 3

The senile plaque is an aggregate collection of protein. It’s a protein that is referred to as the amyloid-beta. It’s a fragment of a normal protein we all have called the amyloid precursor protein (APP). It gets chopped into a smaller piece called amyloid-beta that then collects, assembles outside of cells, and forms this aggregate mass that forms a ball between the neurons, between the interstices of the brain, which pushes aside all of the fine ramifications and connections of brain cells to form what we call a beta-amyloid plaque.

The other hallmark of Alzheimer’s disease is the neurofibrillary tangle. That is made up of a different protein, a protein called tao, and in contrast to the plaque, the tangle forms inside the cell. Now, there has been a debate for a long time about the primacy of the tangles or the plaques in the disease, and even more importantly what is the relationship between the two? We now know that fundamental fundamental pathogenesis of Alzheimer’s disease, is the plaque and amyloid deposition. Then, secondarily, the amyloid triggers this reaction in cells to form tangles.

Question 4

Risk Factors:

1. Age: 1/9 for ___ and older; nearly 1/3 for ___ and older
2. Gender – more common in ____
3. Head trauma
4. Depression “_____” – may be early marker for dementia
5. Excessive __ use (>___ per week)
6. Diabetes
7. Sedentary lifestyle?
8. +/- Lower educational attainment?

Answer 4

Risk Factors:

1. Age: 1/9 for 65 and older; nearly 1/3 for 85 and older
2. Gender – more common in women
3. Head trauma
4. Depression “pseudodementia” – may be early marker for dementia
5. Excessive alcohol use (>14 per week)
6. Diabetes
7. Sedentary lifestyle?
8. +/- Lower educational attainment?

Question 5

Genetics of AD:
Most AD cases:___ genes, environmental factors

• Late onset associated with ____ allele (chromosome ____)
• ____ allele is protective

Early-onset AD:

• Autosomal ____
• Amyloid precursor protein (APP) on chromosome__ (Down)
• Presenilin ___ (PSEN__) on chromosome ___ - most severe
• Presenilin __ (PSEN_) on chromosome __

Answer 5

Genetics of AD:
Most AD cases: multiple genes, environmental factors

• Late onset associated with APOe4 allele (chromosome 19)
• APOe2 allele is protective

Early-onset AD:

• Autosomal dominant
• Amyloid precursor protein (APP) on chromosome 21 (Down)
• Presenilin 1 (PSEN1) on chromosome 14 - most severe
• Presenilin 2 (PSEN2) on chromosome 1

Question 6

Dx for Dementia:

Established by clinical exam & cognitive testing

• __ history is critical
• Deficits in memory & at 1 other cognitive domain
• Progressive ___ of cognition
• No disturbance of ____
• Functionally impaired
• Impaired _____ (IADLs)
• ____ of other brain disease

Answer 6

Dx for Dementia:

Established by clinical exam & cognitive testing

• Collateral history is critical
• Deficits in memory & at 1 other cognitive domain
• Progressive impaired of cognition
• No disturbance of consciousness
• Functionally impaired
• Impaired instrumental activies of daiy living (IADLs)
• absence of other brain disease

Question 7

Early AD

• Cardinal symptom: impaired learning of ___ information, reflecting earliest involvement of __ __ region
• ___ memory tests – most sensitive
• decreased ____ recall
• decreased immediate but NORMAL delayed recall is/is not likely dementia
• Impairment should be judged relative to estimated ___ status

Answer 7

Early AD

• Cardinal symptom: impaired learning of new information, reflecting earliest involvement of medial temporal region
• Verbal memory tests – most sensitive
• decreased immediate recall
• decreased immediate but NORMAL delayed recall is not likely dementia –> could be depression
• Impairment should be judged relative to estimated premorbid status

Question 8

Depression vs. Dementia

How to differentiate?

__ and __ is a lot of it…

1. Impaired ___ and ____ (poor immediate recall) is something that can happen in people that are depressed b/c there is that there is a lot occurring internally. There is internal processing of thoughts, which can interfere with reception and immediate recall.

With dementia, there is an additional loss of ___ recall. Someone may not register perfectly the first time, but there will be a big difference with delay. In ____, if someone can register it, they will hold onto it. There won’t be a big difference between ___ recall and ____ recall.

2. People with ____ may perform better on difficult tests
3. In ___, memory impairment is secondary to impaired attention. They have poor immediate memory, no additional loss with delay; and there is pronounced benefit of ___ (giving them a cue for recalling something)

Late-life depression = risk factor of ___ ____. It is important to differentiate ____ symptoms (avoiding challenge) from ___ symptoms (tearful, sadness)

Answer 8

Depression vs. Dementia

How to differentiate?

attention and effort is a lot of it…

1. Impaired attention and effort (poor immediate recall) is something that can happen in people that are depressed b/c there is that there is a lot occurring internally. There is internal processing of thoughts, which can interfere with reception and immediate recall.

With dementia, there is an additional loss of delayed recall. Someone may not register perfectly the first time, but there will be a big difference with delay. In depression, if someone can register it, they will hold onto it. There won’t be a big difference between immediate recall and delayed recall.

2. People with depression may perform better on difficult tests
3. In depression, memory impairment is secondary to impaired attention. They have poor immediate memory, no additional loss with delay; and there is pronounced benefit of cuing (giving them a cue for recalling something)

Late-life depression = risk factor of AD. It is important to differentiate cognitive symptoms (avoiding challenge) from affective symptoms (tearful, sadness)

Question 9

Vascular Dementia

A “___-____ progression” (KNOW THIS BUZZ WORD!)

Someone gets a hit, and their ____ goes down, it remains relatively stable, they get another hit, and these changes happen overnight and then are stable over time. This is typical for vascular dementia than the gradual progression of AD.

1. Must have evidence of ___ disease on neuro-imaging
2. Decline in cognitive function in 2+ domains (same in___)
3. Compromise in daily functioning NOT explicable by deficits from ___.

__ __disease most common, often producing this profile:

1. ___ ____ deficit
2. Reduced ___ fluency
3. ___ slowing
4. ____, __ or ___ often present in people who have had vascular disease in the past. Main targets to look for are the ___ ____ progression, and clear __ __

Answer 9

Vascular Dementia

A “step wise progression” (KNOW THIS BUZZ WORD!)

Someone gets a hit, and their cognition goes down, it remains relatively stable, they get another hit, and these changes happen overnight and then are stable over time. This is typical for vascular dementia than the gradual progression of AD.

1. Must have evidence of cerebrovascular disease on neuro-imaging
2. Decline in cognitive function in 2+ domains (same in AD)
3. Compromise in daily functioning NOT explicable by deficits from stroke

Small vessel disease most common, often producing this profile:

1. Executive function deficit
2. Reduced verbal fluency
3. Motor slowing
4. Depression, irritability, or apathy often present in people who have had vascular disease in the past. Main targets to look for are the step wise progression, and clear neuro imaging

Question 10

Lewey Body Dementia

Ø____ most common dementia: 15-20%

ØCore symptoms:

§_____ in cognition; attention, alertness, orientation

§_____ hallucinations (vivid, well-formed)

§_____ (bradykinesia/rigidity)

ØSuggestive symptoms:

Ø___ ____ problems - pretty prominant in LBD

ØAdverse reactions to ____/_____

ØSupportive features:

ØFalls, syncope

Ø____ dysfunction

LBD is an umbrella term for two related diagnoses. LBD refers to both Parkinson’s disease dementia and dementia with Lewy bodies.

What Are Lewy Bodies?

Lewy bodies are __, ____, neuronal cytoplasmic ___ composed of aggregates of ___, a synaptic protein. Lewy body dementia is chronic cognitive deterioration characterized by cellular inclusions called Lewy bodies in the__ of __ neurons. Parkinson disease dementia is cognitive deterioration characterized by Lewy bodies in the __ ___; it develops ___ in Parkinson disease.

Parkinson’s vs. Lewey Body?

• All in the ____!!!!
• _____ dementia diagnosed when motor symptoms precede cognitive symptoms by ___ yr and often longer!!!
• __ ___ diagnosed when cognitive symptoms COME FIRST or occur TOGETHER with motor symptoms
• Parkinson’s dementia: bradyphrenia, executive function deficits, spatial impairment, memory retrieval impaired early, other memory functions preserved until late.

Answer 10

Lewey Body Dementia

ØThird most common dementia: 15-20%

ØCore symptoms:

§Impairment in cognition; attention, alertness, orientation

§Visual hallucinations (vivid, well-formed)

§ Parkinsonism (bradykinesia/rigidity)

ØSuggestive symptoms:

ØREM sleep problems - pretty prominant in LBD

ØAdverse reactions to L-dopa/neuroleptics

ØSupportive features:

ØFalls, syncope

ØAutonomic dysfunction

LBD is an umbrella term for two related diagnoses. LBD refers to both Parkinson’s disease dementia and dementia with Lewy bodies.

What Are Lewy Bodies?

Lewy bodies are spherical, eosinophilic, neuronal cytoplasmic inclusions composed of aggregates of alpha-synuclein, a synaptic protein. Lewy body dementia is chronic cognitive deterioration characterized by cellular inclusions called Lewy bodies in the cytoplasm of cortical neurons. Parkinson disease dementia is cognitive deterioration characterized by Lewy bodies in the substantia nigra; it develops late in Parkinson disease.

Parkinson’s vs. Lewey Body?

• All in the timing!!!!
• Parkinson’s dementia diagnosed when motor symptoms precede cognitive symptoms by 1 yr and often longer!!!
• Lewey Body Dementia diagnosed when cognitive symptoms COME FIRST or occur TOGETHER with motor symptoms
• Parkinson’s dementia: bradyphrenia, executive function deficits, spatial impairment, memory retrieval impaired early, other memory functions preserved until late.

Question 11

FTLD

• ___ onset (__-__) than most AD, with exceptions
• May represent ___% of all cases <___ years of age seen in dementia clinic
• __x more common in men, positive FH in 1/3 cases
• Marked by___ changes, so: __ changes:___, irritability,___ inappropriateness
• Often misdiagnosed as ___ or as a psychiatric cond’n

1. Behavioral Variant FTLD (includes Pick Disease)

Behavioral disturbance: 3+ of:

• D___
• A____
• Diminished ___/___
• Perseverative, stereotyped, or compulsive behaviors
• Hyper-____
• Executive dysfunction ____ on testing: planning, ____ thinking
• Impaired ___ & __ attention
• Preserved ___ –> cued __ intact
• Intact __ abilities and memory.

You are looking more at __ and __ issues.

• Pick Disease (KNOW THIS!). Pick bodies are see on pathology. NO ___ PROBLEMS. IT IS PRESERVED!

_____ pts have a hard time with abstract thinking. E.G. If you asked them, “people in glass houses should not throw stones.” They will not be able to explain why, or they will say something bizarre.

• *Primary Progressive Aphasia - FTLD**
  1. Onset in ___’s & ___’s, a ____ rate of progression

2. __ is earliest sign
3. Memory may be preserved until middle stages, but we don’t know because their ___ is so impaired. It is very frustrating!
4. AD-related ~20% of time, with plaques & tangles in ___distribution

Answer 11

FTLD

• early onset (45-65) than most AD, with exceptions
• May represent 20% of all cases <65 years of age seen in dementia clinic
• 4x more common in men, positive FH in 1/3 cases
• Marked by behavioral changes, so: personality changes: withdrawal, irritability, social inappropriateness
• Often misdiagnosed as depression or as a psychiatric cond’n

1. Behavioral Variant FTLD (includes Pick Disease)

Behavioral disturbance: 3+ of:

• Disinhibition
• Apathy
• Diminished empathy/sympathy
• Perseverative, stereotyped, or compulsive behaviors
• Hyper-orality
• Executive dysfunction impaired on testing: planning, abstract thinking
• Impaired selective & divided attention
• Preserved memory –> cued memory intact
• Intact spatial abilities and memory.

You are looking more at attention and behavioral issues in FTLD.

• Pick Disease (KNOW THIS!). Pick bodies are see on pathology. NO MEMORY PROBLEMS. IT IS PRESERVED!

FTLD pts have a hard time with abstract thinking. E.G. If you asked them, “people in glass houses should not throw stones.” They will not be able to explain why, or they will say something bizarre.

• *Primary Progressive Aphasia - FTLD**
  1. Onset in 50’s & 60’s, a variable rate of progression

2. anomia is earliest sign
3. Memory may be preserved until middle stages, but we don’t know because their language is so impaired. It is very frustrating!
4. AD-related ~20% of time, with plaques & tangles in atypical distribution

Question 12

MCI

1. 80% of adults with amnestic MCI progress to ___ within 6 years
2. Best predictors of progression:
   - poor ___ performance
   - ____ genotype
   - ____ atrophy
   - existing __ disease

Answer 12

MCI

1. 80% of adults with amnestic MCI progress to AD within 6 years
2. Best predictors of progression:
   - poor memory performance
   - apoE4 genotype
   - hippocampal atrophy
   - existing metabolic disease

Question 13

Dementia caused by Normal Hydrocephalus

1. “Potentially ____”, makes up ~___% of all dementias
2. ___ disturbance, ___ incontinence, ____ deficits (wobbly, wet, & wacky)
3. Cognitive deficits involve attention & executive function. Very LARGE ___ on CT.
4. Shunting may improve some symptoms but ___ deficits usually persist

Answer 13

Dementia caused by Normal Hydrocephalus

1. “Potentially reversible”, makes up ~6% of all dementias
2. Gait disturbance, urinary incontinence, cognitive deficits (wobbly, wet, & wacky)
3. Cognitive deficits involve attention & executive function. Very LARGE ventricles on CT.
4. Shunting may improve some symptoms but cognitive deficits usually persist

Question 14

Alcohol Related Dementia

1. Long-term alcohol use increases risk of AD & vascular dementia
2. ____ deficiency associated with cognitive impairment - Wernicke’s Korsakoff
3. Persistent alcohol dementia: - Impairment in more than one area of cognition even with abstinence - Problems with visual scanning, visuo-spatial ability, eye- hand coordination, abstraction - Perseverations & ___ common

Answer 14

Alcohol Related Dementia

1. Long-term alcohol use increases risk of AD & vascular dementia
2. Thymine deficiency associated with cognitive impairment - Wernicke’s Korsakoff
3. Persistent alcohol dementia: - Impairment in more than one area of cognition even with abstinence - Problems with visual scanning, visuo-spatial ability, eye- hand coordination, abstraction - Perseverations & confabulation common

Question 15

Dementia caused by:

____thyroisidm- memory recall, visuospatial, psychomotor speed

____thyroidism: executive function impaired

Answer 15

Dementia caused by:

Hyperthyroisidm- memory recall, visuospatial, psychomotor speed

Hypothyroidism: executive function impaired