Lectures 58, 60: Dementia and Alzheimer's Flashcards Preview

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Flashcards in Lectures 58, 60: Dementia and Alzheimer's Deck (58):
1

No pathology/abnormal cognition

Cognitively frail aging

2

Abundant pathology/normal cognition

Resilient aging

3

Cognitive changes associated with normal aging (3)

Mild decline in memory, impaired prefrontal fxns, decreased fine motor coordination

4

T/F: Normal aging due to neuronal death?

No!

5

Mild Neurocognitive Disorder

Modest cog decline in 1+ domains but deficits do not interfere w/ capacity for ind.

6

Mild Neurocognitive Disorder: % progress to dementia per year and % improve

10% progress per year; 30% improve

7

Dementia (def)

Clinical syndrome marked by progressive cognitive impairment in clear consciousness

8

DSM-V Major Neurocognitive Disorder Dx Criteria

Significant cognitive decline from a previous level of performance in 1 or more cognitive domains based on individual concern/informant and impaired performance

9

Risk factors for dementia (5)

Age, female, vascular, env't, genetics

10

Resilience for dementia (9)

Education, social networks, cognitive stim activities, leisure activities, exercising, conscientiousness, male, statins, control vascular factors

11

Why do we care about the behavioral/psychiatric symptoms of dementia?

Serious burden for caregivers and institution, associated with poor outcomes

12

Three broad categories of dementia, an example of each, and symptoms

Cortical (AD: memory impairment, language deficits, apraxia, agnosia, and visuospatial deficits) vs Subcortical (PD: motor signs, recall, decreased verbal fluency without anomia, bradyphrenia, depressed mood, affective lability, apathy, and decreased attention/concentration) vs Mixed (Lewy body)

13

List some of the varied etiologies of dementia and give an example of each (5)

Primary (AD), infections (HIV), vascular/traumatic (stroke), toxic-metabolic (B12), psychiatric (schizophrenia)

14

MOST COMMON CAUSE OF DEMENTIA and %

Alzheimer's Disease = 50-75%

15

Age of onset of AD

Typically after 65

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AD consists of (dx criteria)...Death when?

Memory impairment + 1 other cognitive deficit; 8 - 10 years after sx onset

17

Describe dementia with Lewy Bodies: 3 hallmarks and one way to distinguish from AD

1. Fluctuating cognition; 2. Visual hallucinations; 3. Spontaneous Parkinsoniasm; early frontal and visuospatial deficits before memory impairment

18

Vascular dementia. Dx requires?

Cognitive decline caused by ischemic or hemorrhagic injury to the brain; focal neurological symptoms/imaging

19

Etiology of vascular dementia (6)

Stroke, small vessel ischemic disease, hemorrhage, chronic hypoperfusion (i.e. lung disease), genetic conditions, cerebral amyloid angiopathy

20

Frontotemporal dementias have a proclivity for...What protein? Death?

Young people (onset 45-65 years old); tau-opathy; 3-5 years to death

21

Frontotemporal dementias associated with what symptoms?

Personality changes: disinhibition, executive dysfunction, frontal release sign, aphasia

22

Balloon or Pick cells associated with...

FTD

23

CJD is different from the other dementias why?

Very rapid (death 6-9 months from onset)

24

Reversible causes of dementia (6)

Normal pressure hydrocephalus, thyroid dysfunction, dietary deficiencies, infection (syphilis), depression, tumor

25

ADLs are...what's the other group called?

Basic (toilet); Instrumental Activities of Daily Living (IADLs)

26

Describe delirium (what is it NOT and what is required?)

Acute, fluctuating disturbance of consciousness with reduced ability to focus, sustain or shift attention NOT better accounted for by established dementia CAUSED by a medical condition

27

Everyone with delirium has...

Poor attention/vigilance

28

Where is delirium common?

Hospitals

29

T/F: Delirium often persists well after the precipitants have been successfully addressed and removed

True!

30

What is a good reason to diagnose delirium quickly?

Late diagnoses = worse outcomes

31

Description of gross and histo brain changes seen in normal aging

Widened sulci, larger ventricles that is greater in gray matter; loss of neurons, accumulation of lipofuscin pigment, more astrocytes, extra cellular plaques

32

T/F: Can you ever see neurofibrillary tangles in normal brains?

True

33

Four physiologic changes of normal aging

1. Increased MHC antigens in brain; 2. Reduced synaptic plasticity; 3. Decreased hippocampal neurogenesis; 4. Increased BBB permeability

34

In 1907, these three characteristics of AD were described

Dementia, extracellular AB plaques and intracellular neurofibrillary tau tangles

35

Tangled tau proteins are...

Hyperphosphorylated

36

% of AD >80 years

35%

37

Probable Alzheimer's disease is diagnosed if either...

1. Genetic testing; 2. Clear evidence of memory decline, progressive, no evidence of mixed etiology

38

What do we have AD biomarkers for?

Amyloid beta deposition (low CSF AB42, PET amyloid) and Downstream neuronal injury (elevated CSF tau, PET, MRI of temporal atrophy)

39

Biological factors for AD

Genetic alterations, abnormal immune, medical problems (diabetes, HT, obesity, depression)

40

Environmental factors for AD

Traumatic injury, drugs, smoking, low education, low physical activity

41

Gross brain changes in AD

Cerebral cortical atrophy (frontotemporal); dilation of LVs; hippocampal atrophy

42

Microscopic changes in AD (3 + 3 "other")

Extracellular amyloid beta plaques; intracellular tau tangles; loss of hippocampal and cortical neurons, especially those involving diffuse cholinergic projections; other: synaptic loss, inflammation, oxidative stress

43

What's interesting about tangles?

Correlated with cognitive decline and length of illness (plaques are not like that)

44

Describe plaques (what's inside, what's outside)

Central core of Aβ4 protein that has a beta-pleated sheet configuration often surrounded by abnormal neurites

45

Genetics of AD are associated with...

Autosomal dominant mutations in one of three genes that are involved in amyloid protein

46

What's the most important genetic risk polymorphism factor for AD? Present in what % of AD patients? OR?

Abnormal ApoE gene (amyloid accumulation); 50%; 2 alleles, OR = 11

47

What is the Amyloid Hypothesis? Why is this hypothesis challenged?

Deposition of Aβ peptides in cortex, especially Aβ42, initiates a pathogenic cascade which ultimately leads to synaptic dysfunction, neurodegeneration (tangles, cell death) and cognitive/functional decline; Plaque load (unlike tangles) does NOT predict cognitive status decline in AD

48

What was the theory modification of the Amyloid Hypothesis

Pathological AB-oligomerization that leads to AD plaques (cannot be stained for) could be the actual problem

49

T/F: It seems that AB42 is better than tau to predict AD development from minor impairment

False! Tau appears to be a better predictor. It is sensitive, but maybe not very specific

50

Why are cortical-cortical circuits disrupted in AD? What does this disruption do?

Tangles and plaques thought to disrupt these circuits; breaks connection b/t association regions and hippocampus

51

Evidence for cholinergic deficiency in AD

Degeneration of cholinergic projections; loss of cell bodies in nucleus basalis; reduced CAT (makes ACh); anticholinegic drugs --> memory problems

52

AD Treatments and mechanism

ACHE inhib (donepezil, galantamiie, rivastigmine) and NMDA-receptor antagonist (memantine)

53

Why would a NMDA-receptor antagonist work?

Blocks excitotoxic effects of excess glutamate at NMDA receptor

54

Efficacy data for AD drugs (summary and what it does NOT do)

Small treatment effect sizes for cognitive function, activities of daily living and global assessment but does NOT modify disease course

55

Anti-amyloid targets for AD therapy include (2)

Immunotherapy (vaccine) and anti-aggregants via enzyme activity

56

Some other new targets for AD therapy are? (5)

Tau, cholinergic system, omega 3 fatty acids, inflammation, polyphenols (anti-oxidant)

57

What's a simple statement behind diet/lifestyle prevention for AD?

Good for heart = good for head

58

How would you distinguish cortical from subcortical dementia?

Cortical = memory impairment includes recognition and language impairment includes anomia; Subcortical = motor involvement, affective involvement (depression, lability)

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