3 - Alzheimers (IN PROGRESS) Flashcards

1
Q

Define Dementia

A
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2
Q

What is the diagnostic criteria for dementia?

A

The 5 A’s

Amnesia - Memory impairment

Aphasia - Deterioration of Language Function

Agnosia - Failure to recognize or identify objects

Apraxia - Impaired ability to execute motor activities

Anomia - Deficit in expressive language; speak around unknown words

Executive Function Disturbance

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3
Q

What is the difference between primary and secondary dementia?

A

Primary - Arises from brain degeneration; Alzheimer’s is a primary dementia

Secondary - Arises from physical injury or disease

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4
Q

What are the gross morphological indications of AD?

A

Severe global attrophy

Most pronouced in the hippocampus, temporal and frontal lobes

Narrowing of gyri, widening of the sulci

Enlarged lateral and 3rd ventricle

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5
Q

**What are three major brain areas impacted by AD and subsequent cognitive correlates that are impacted by AD?

A
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6
Q

What are the histological characteristics of AD?

A
  1. Global cerebral atrophy–narrow gyri, widening of sulci
  2. Enlarged lateral ventricles
  3. Amyloid plaques
  4. neurofibrillary Tangles
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7
Q

Non genetic risk factors for AD?

A

Getting old

Other neuro disease

Down Syndrome

Head Trauma

CVD

Diabetes

Smoking

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8
Q

Early What genes have been shows to correlate with early/late AD?

A

Early: Autosomal Dominant familial inheritance: Presenilin 1 / 2

Late: APOE (lipid transport, metabolism)

APOE4 = increased risk

APOE2 = reduced risk

ABCA7 = Increased risk (microglial phagocytosis and AB clearance)

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9
Q

What are some hallmarks of Normal aging?

A

Decrease brain volume, expansion of ventricles

Largest changes: Frontal/Temporal cortex, putamen, thalamus, and nucleus accumbens

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10
Q

What are the 5 A’s for aging and dementia?

A

Aphasia

Agnosia

Apraxia

Anomia

Amnesia

Executive Function Disturbance

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11
Q

Dementia Types:

Vascular

Lewy Bodies

Frontotemporal

Medication

Nutritional (B12)

A

Vascular - Neurlogical deficits, more stepwise, long standing hypertension

Lewy - Fluctuation mental status, Pakinsonism, hallucination

Frontotemporal - Disinhibition, loss of social awareness, early loss of site

Medication - Induced cognitive defects

Nutrition - B12

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12
Q

Vitamin B12 Deficieny

A

Must be obtained from diet

Production of neurotransmitters

Vegan, Weight Loss Surgery, Crohns

Symptoms: Agitation, confusion, disorientation, delisions, numbess, abnormal gait, weakness, fatigue, shortness of breath

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13
Q

Early vs Late Alzheimers?

A

Early < 65

Late > 65

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14
Q

Main causes of death from Alzheimers?

A

Infection/pneumonia

Brain hemorrhage due to impaired BBB function

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15
Q

Pathology of AD?

A

Frontal lob atrophy

Medial temporal lobe (hippocampal) atrophy

Loss of Cholinergic (ACh) neurons

Loss of Glutamatergic neurons

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16
Q

AD: Neuronal Loss

A
  1. Medial Frontal / Temporal Lobes (Limbic Systems - PAPEZ Circuits)
    - Hippocampus, Amygdala, Entorhinal Cortex
  2. Basal Temporal Cortex - Lateral Posterior Temporal Cortex
  3. Nucleus Basalis of Meynert

4. Nucleus Locus Coeruleus (ARAS)

17
Q

Major areas impacted by AD?

A

Limbis, Multimodal Association Cortex, ARAS

18
Q

Early Stage Cognitive Changes w/AD?

A

Episodic memory deficits (recent, new events)

Sumantic Memory Deficits - Aphasia, Agnosia, inability to have meaningful conversations

19
Q

Early-Mid Stafe Cognitive Changes w/AD?

A

Procedural memory loss (forget to wash hair, how to run dishwasher)

Apathy

Depression

Sundowning (angry as day goes on)

20
Q

Late Stage Cognitive Changes w/AD?

A

Lose abiliyt to respond to environment

Severe communication deficits

Inability to control movement

Paranoid

Weight loss (forget to eat)

21
Q

Common thing for all theories on pathophysiology of AD?

A

All cause: Neurdegeneration and Inflammation

22
Q

What two hallmarks of AD are distinct to alzheimers vs dementia etc?

A

Tau Neurofibrillary Tangles (NFT)

Amyloid-B Senile Plaques

23
Q

Tau and AD

A

AD = Taupathy

AD = hyperphosphorylation of TAU

Generates neurofibrillary tangles (NFT)

Stronger than Amyloid-B correlation!

Effects entorhinal cortex, hippocampus, then association coretx

24
Q

Granulovascular Degeneration?

A

Fluid filled space and grandular debris within neurons

25
Gliosis
Includes sporadic astrogliosis and localized microgliosis aroiund plaques ## Footnote **Microglio are mobile and can spread, astro can't**
26
Amyloid Precursor Protein (APP)
Contributes to **regulation of synaptic function** **AB builds up in the brain w/AD = plaques** Cause unknown, these are usually removed during sleep
27
How does AD get a compromised BBB?
Blood vessels are damaged by AB accumulation in brain
28
Astrocytes and role in BBB?
Aid in mx of BBB, their function changes w/AD Not removing AB
29
AD and Glutamatergic Dysregulation
Disruption of glutamatergic homeostasis Degeneration of glutametergic neurons and receptor expression
30
Where is APOE synthesized?
Liver, but also astrocytes
31
Alzheimers Treatmen
Acetylcholinesterase Inhibitors: **Donepezil, Galantamine, Rivastigmine** NMDA Receptor Antagonist: **Memantine**
32
DBS of what area helps w/AD?
Fornix
33