3 - Alzheimers (IN PROGRESS)

Question 1

Define Dementia

Question 2

What is the diagnostic criteria for dementia?

Answer 2

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

Question 3

What is the difference between primary and secondary dementia?

Answer 3

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

Secondary - Arises from physical injury or disease

Question 4

What are the gross morphological indications of AD?

Answer 4

Severe global attrophy

Most pronouced in the hippocampus, temporal and frontal lobes

Narrowing of gyri, widening of the sulci

Enlarged lateral and 3rd ventricle

Question 5

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

Question 6

What are the histological characteristics of AD?

Answer 6

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

Question 7

Non genetic risk factors for AD?

Answer 7

Getting old

Other neuro disease

Down Syndrome

Head Trauma

CVD

Diabetes

Smoking

Question 8

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

Answer 8

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)

Question 9

What are some hallmarks of Normal aging?

Answer 9

Decrease brain volume, expansion of ventricles

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

Question 10

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

Answer 10

Aphasia

Agnosia

Apraxia

Anomia

Amnesia

Executive Function Disturbance

Question 11

Dementia Types:

Vascular

Lewy Bodies

Frontotemporal

Medication

Nutritional (B12)

Answer 11

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

Question 12

Vitamin B12 Deficieny

Answer 12

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

Question 13

Early vs Late Alzheimers?

Answer 13

Early < 65

Late > 65

Question 14

Main causes of death from Alzheimers?

Answer 14

Infection/pneumonia

Brain hemorrhage due to impaired BBB function

Question 15

Pathology of AD?

Answer 15

Frontal lob atrophy

Medial temporal lobe (hippocampal) atrophy

Loss of Cholinergic (ACh) neurons

Loss of Glutamatergic neurons

Question 16

AD: Neuronal Loss

Answer 16

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)

Question 17

Major areas impacted by AD?

Answer 17

Limbis, Multimodal Association Cortex, ARAS

Question 18

Early Stage Cognitive Changes w/AD?

Answer 18

Episodic memory deficits (recent, new events)

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

Question 19

Early-Mid Stafe Cognitive Changes w/AD?

Answer 19

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

Apathy

Depression

Sundowning (angry as day goes on)

Question 20

Late Stage Cognitive Changes w/AD?

Answer 20

Lose abiliyt to respond to environment

Severe communication deficits

Inability to control movement

Paranoid

Weight loss (forget to eat)

Question 21

Common thing for all theories on pathophysiology of AD?

Answer 21

All cause: Neurdegeneration and Inflammation

Question 22

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

Answer 22

Tau Neurofibrillary Tangles (NFT)

Amyloid-B Senile Plaques

Question 23

Tau and AD

Answer 23

AD = Taupathy

AD = hyperphosphorylation of TAU

Generates neurofibrillary tangles (NFT)

Stronger than Amyloid-B correlation!

Effects entorhinal cortex, hippocampus, then association coretx

Question 24

Granulovascular Degeneration?

Answer 24

Fluid filled space and grandular debris within neurons

Question 25

Gliosis

Answer 25

Includes sporadic astrogliosis and localized microgliosis aroiund plaques

Microglio are mobile and can spread, astro can’t

Question 26

Amyloid Precursor Protein (APP)

Answer 26

Contributes to regulation of synaptic function

AB builds up in the brain w/AD = plaques

Cause unknown, these are usually removed during sleep

Question 27

How does AD get a compromised BBB?

Answer 27

Blood vessels are damaged by AB accumulation in brain

Question 28

Astrocytes and role in BBB?

Answer 28

Aid in mx of BBB, their function changes w/AD

Not removing AB

Question 29

AD and Glutamatergic Dysregulation

Answer 29

Disruption of glutamatergic homeostasis

Degeneration of glutametergic neurons and receptor expression

Question 30

Where is APOE synthesized?

Answer 30

Liver, but also astrocytes

Question 31

Alzheimers Treatmen

Answer 31

Acetylcholinesterase Inhibitors: Donepezil, Galantamine, Rivastigmine

NMDA Receptor Antagonist: Memantine

Question 32

DBS of what area helps w/AD?

Answer 32

Fornix