Psychotherapy: 95b - Alzheimer's and other Neurodegenerative Diseases

Sensory areas

• Beta and/or gamma secretase don’t function properly

• Instead of making normal cleavages, they cut at the wrong spot and produce amyloid beta40 and amyloid beta 42

• ​These toxic structures result in microglial activation

• -> Inflammation/glutamatergic toxicity

• -> Phosphorylation of Tau proteins

• -> Neurofibrillary tangles

• NMDA Receptor Inhibitors (memantine)
  

  • Blocks cytotoxicity caused by amyloid

• Cholinesterase inhibitors
  

  • Increase ACh inthe brain

  • Slow progression; best if started early

Limbic system

Involved in retentive memory

In Demetia with Lewy Bodies, cholinesterase inhibitors will make patients better

Vs. Alzheimer’s disease, they will slow progression

Visual variant of Alzheimer’s Disease

• Delcine in visual processing

• Earlier onset than typical AD

• Memory and language remain intact

PT, OT, speech therapy, reward-based therapy

(Main pharmacoogical is SSRI)

• Constipation

• Violent dream eneactment

• Occasional dizziness
  

  • Followed by slowing of movements, impaired balance

• Older patient

• Frequent forgetfulness
  

  • Conversations, events sometimes

  • Repetitive in conversations

• Trouble with word finding

• Results in difficulty with some functions
  

  • Finances

• Weight control

• Exercise

• Mental and social engagement

• Control:
  

  • Blood pressure

  • Blood sugar

  • Cholestoral

  • Vitamin B12

• Normalize sleep

• Mediterranean diet

• Deterministic genes
  

  • APP

  • Presenilin 1

  • Presenilin 2

• Risk genes
  

  • APO E4

But <1% of AD is thought to be genetic

SSRIs

(Non-pharmacological include PT, OT, speech therapy, reward-based therapy)

• Language type: primary progressive aphasia

• Behavioral type: Behavioral type frontotemporal dementia(akaPick’s Disease)

• Motor type: Corticobasal syndrome, Progressive supranuclear palsy, or FTD-MND (Associated with ALS)

Decreased amyloid in the CSF

• It’s busy messing with the brain :(

• Amyloid:Tau index <1

• P-tau >60

PSP and CBD will both have problems with balance, vision, speech, swallowing, and memory

• Progressive supranuclear palsy (PSP)
  

  • Cannot look down voluntarily

• Corticobasal degeneration (CBD)
  

  • Asymmetric (compared with PSP)

  • Behavior deficits

• FTD-Motor Neuron Disease (FTD-MND)
  

  • ​Frontotemporal dementia + ALS

  • Muscle weakness, shrinkage, jerking

  • Fewer memory deficits, more language deficits compared with PSP, CBD

  • Behavior deficits (like CBD)

Lacunar strokes

-> vascular cognitive impairment

Pick’s disease = behavioral variant of frontotemporal dementia

Characterized by progressive deterioration of behavior and cognition

• Behavioral disinhibition

• Apathy or inertia

• Loss of sympathy or empathy

• Preservative, stereotyped, or compulsive/ritualistic behavior

• Hyperorality, dietary changes

• Memory and visuospatial reasoning are spared
  

  • vs. Alzheimers has loss of memory

  • vs. Dementia with Lewy Bodeis has visuospatial impairment

Alzheimer’s Disease

• 
  MAPT
  

  • -> FTLD-Tau

• PGRN
  

  • -> FTLD-TDP (Type A = language type)

• C9ORF72
  

  • -> FTLD-TDP (Type B = behavioral type)

Not 100% sure about the types - pls DM if you can shed some light!

Nucleus basalis of Meynert

• ACh is produced here

• Tau and amyloid deposits -> damage

• -> Whole brain is hypocholinergic, especially the limbic system
  

  • ​Typical Alzheimer’s Disease

Hypometabolism in the occipital lobe

(Vs decreased metabolism in the cingulate cortex in Alzheimer’s)

Working memory is usually intact

If you tell the patient 4 words, they will be able to repeat them back to you

(But will forget them when distracted due to limbic destruction)

Amyloid plaques

Neurofibrillary Tangles (NFTs)