95. Alzheimer's and Dementias

Question 1

Define Dementia (w/ 3 characteristics)

Answer 1

Major neurocognitive disorder caused by disease of the brain with

• decline from prior level of functioning in cognition, emotion, behavior
• progressive worsening over time
• interference with independence/daily activities

Question 2

What are the 5 main neurocognitive networks, symptoms of dysfx in each, and dz in each?

Answer 2

1. Spatial Attention (dorsal path)
   - sx: getting lost (spatial disorientation)
   - dz: DLB, Posterior Cortical Atrophy
2. Working Memory (frontal lobe)
   - sx: inattention, disinhibition, behavior change
   - dz: Frontal Type Dementia
3. Language (Broca’s/Wernicke’s)
   - sx: word finding hesitations (anomia, aphasia)
   - dz: Primary Progressive Aphasia
4. Object Recognition (Ventral Path)
   - sx: abnormal visual processing (visual agnosia)
   - dz: Semantic Aphasia/Dementia
5. Memory/Emotion (Limbic Network)
   - sx: forgetfulness (amnesia)
   - tx: Amnestic (alzheimer type) dementia

Question 3

Alzheimer’s Disease

• pathology
• risk factors
• pathogenesis

Answer 3

Path: amyloid plaques b/w nerve cells; neurofibrillary tangles inside nerve cells; Gross atrophy of cholinergic path (basal forebrain and cortex white/gray matter)

RF: AGE, FamHx, Genetics (AD, ApoE4, deterministic genes), Vascular RFs (DM, HTN, smoking), Head trauma, low education, lack of exercise

Pathogenesis: APP normally cleared by a-secretase, but mutations cause clearance by b-secretase/g-secretase = cause amyloid forming/aggregation
toxic aggregation: microglial activation (inflammation), fibrillation (neurofibrillary tangles), activates Fyn-kinase - phosphorylates NMDA = increase Ca influx = Glu excitotoxicity

Question 4

Alzheimer’s Disease

• imaging
• CSF profile
• Preventative measures
• Tx

Answer 4

Imaging: hippocampal atrophy, FDG-PET shows temporal-parietal hypometabolism, more amyloid in cortex on amyloid PET
CSF: high P-tau (secreted by dead brain cells), LOW amyloid (accumulates in brain cells)
Prevent: weight control, exercise, less loneliness, normal vitals/sleep, mediterranean diet

TX: cholinesterase inhibitors (Donepezil, Rivastigmine, Galantamine); Memantine (NMDA receptor inhibitor); sx tx

Question 5

Posterior Cortical Atrophy

• what is it
• sx
• onset age

Answer 5

Benson’s Syndrome - visual variant of AD

• decline in visual processing skills (intact memory/language in early stages)
• 50-65 years old (younger than AD)

Question 6

Lewy Body Disease (DLB)

• pathology
• sx triad
• imaging
• tx

Answer 6

Path: diffuse lewy bodies
sx: visual hallucinations, dementia, parkinsonism
Imaging: occipital lobe hypometabolism (cingulate eye preserved), DaT SPECT (loss of DA - looks like period instead of comma)

Tx: Cholinesterase inhibitors (Donepezil, rivastigmine)
Antipsychotics: Quetiapine (for psychosis sx)
Cognitive retraining/enviro. interactions like AD

Question 7

Vascular Cognitive Impairment

• RF
• other causes
• sx
• tx

Answer 7

RF: Age, HTN, AFib, Smoking, DM
Other: CAA/CADASIL
Sx: stepwise worsening in cognition due to repeated small strokes (more likely lacunar frontal lobe)

Tx: Cholinesterase inhibitors (Donepezil, Galantamine)
Tx RF (BP, HbA1c, Cholesterol)

Question 8

List the three types of Frontotemporal Lobar Degeneration

Answer 8

1. Behavioral Type (Pick’s Disease - bvFTD)
2. Primary Progressive Aphasia (PPA)
3. FTD - Motor Neuron Disease (FTD-MND)

Question 9

FTLD: bvFTD

• dx
• MRI
• Path

Answer 9

Dx: progressive deterioration of behavior +/- cognition with 3/6 of (early behavioral disinhibition; early apathy/inertia; early loss of sympathy; early compulsive behavior; hyperorality/diet changes; sparing of memory/visuospatial sx)

MRI: frontal hypometabolism
Path: frontal lobe atrophy
1. Tau inclusions in neurons (Picks bodies)
2. TDP inclusions in nuclear axons
3. FUS inclusions

Question 10

FTLD: bvFTD

• genetics
• tx

Answer 10

Genetics: more common than AD
MAPT gene: FTLD-tau
PGRN gene: FTLD-TDP (type a)
C9orf72 gene: FTLD-TDP (type b)

tx: depends on underlying pathology
SSRIs: citalopram
TCA: clomipramine
Antipsychotics: Quetiapine
Behavioral interventions: Reward based therapy

Question 11

FTLD: Primary Progressive Aphasia

• sx
• subtypes with path correlate

Answer 11

syndrome of progressive language decline due to neurodegeneration

1. Non-fluent (like broca’s) - FTLD
2. Semantic (anomic) - FTLD
3. Lopogenic (aphasic variant of AD)

Question 12

FTLD: FTD-Motor Neuron Disease

- sx

Answer 12

FTD + ALS
Changes in behavior and language
WITH muscle weakness, shrinkage, jerking