3 - Alzheimers (IN PROGRESS) Flashcards
Define Dementia
What is the diagnostic criteria for dementia?
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
What is the difference between primary and secondary dementia?
Primary - Arises from brain degeneration; Alzheimer’s is a primary dementia
Secondary - Arises from physical injury or disease
What are the gross morphological indications of AD?
Severe global attrophy
Most pronouced in the hippocampus, temporal and frontal lobes
Narrowing of gyri, widening of the sulci
Enlarged lateral and 3rd ventricle
**What are three major brain areas impacted by AD and subsequent cognitive correlates that are impacted by AD?
What are the histological characteristics of AD?
- Global cerebral atrophy–narrow gyri, widening of sulci
- Enlarged lateral ventricles
- Amyloid plaques
- neurofibrillary Tangles
Non genetic risk factors for AD?
Getting old
Other neuro disease
Down Syndrome
Head Trauma
CVD
Diabetes
Smoking
Early What genes have been shows to correlate with early/late AD?
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)
What are some hallmarks of Normal aging?
Decrease brain volume, expansion of ventricles
Largest changes: Frontal/Temporal cortex, putamen, thalamus, and nucleus accumbens
What are the 5 A’s for aging and dementia?
Aphasia
Agnosia
Apraxia
Anomia
Amnesia
Executive Function Disturbance
Dementia Types:
Vascular
Lewy Bodies
Frontotemporal
Medication
Nutritional (B12)
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
Vitamin B12 Deficieny
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
Early vs Late Alzheimers?
Early < 65
Late > 65
Main causes of death from Alzheimers?
Infection/pneumonia
Brain hemorrhage due to impaired BBB function
Pathology of AD?
Frontal lob atrophy
Medial temporal lobe (hippocampal) atrophy
Loss of Cholinergic (ACh) neurons
Loss of Glutamatergic neurons
AD: Neuronal Loss
- Medial Frontal / Temporal Lobes (Limbic Systems - PAPEZ Circuits)
- Hippocampus, Amygdala, Entorhinal Cortex - Basal Temporal Cortex - Lateral Posterior Temporal Cortex
- Nucleus Basalis of Meynert
4. Nucleus Locus Coeruleus (ARAS)
Major areas impacted by AD?
Limbis, Multimodal Association Cortex, ARAS
Early Stage Cognitive Changes w/AD?
Episodic memory deficits (recent, new events)
Sumantic Memory Deficits - Aphasia, Agnosia, inability to have meaningful conversations
Early-Mid Stafe Cognitive Changes w/AD?
Procedural memory loss (forget to wash hair, how to run dishwasher)
Apathy
Depression
Sundowning (angry as day goes on)
Late Stage Cognitive Changes w/AD?
Lose abiliyt to respond to environment
Severe communication deficits
Inability to control movement
Paranoid
Weight loss (forget to eat)
Common thing for all theories on pathophysiology of AD?
All cause: Neurdegeneration and Inflammation
What two hallmarks of AD are distinct to alzheimers vs dementia etc?
Tau Neurofibrillary Tangles (NFT)
Amyloid-B Senile Plaques
Tau and AD
AD = Taupathy
AD = hyperphosphorylation of TAU
Generates neurofibrillary tangles (NFT)
Stronger than Amyloid-B correlation!
Effects entorhinal cortex, hippocampus, then association coretx
Granulovascular Degeneration?
Fluid filled space and grandular debris within neurons
Gliosis
Includes sporadic astrogliosis and localized microgliosis aroiund plaques
Microglio are mobile and can spread, astro can’t
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
How does AD get a compromised BBB?
Blood vessels are damaged by AB accumulation in brain
Astrocytes and role in BBB?
Aid in mx of BBB, their function changes w/AD
Not removing AB
AD and Glutamatergic Dysregulation
Disruption of glutamatergic homeostasis
Degeneration of glutametergic neurons and receptor expression
Where is APOE synthesized?
Liver, but also astrocytes
Alzheimers Treatmen
Acetylcholinesterase Inhibitors: Donepezil, Galantamine, Rivastigmine
NMDA Receptor Antagonist: Memantine
DBS of what area helps w/AD?
Fornix
