Cognitive Issues in Older Adults Part 1

Question 1

list the neurocognitive domains that make up cognition

Answer 1

1. complex attention
2. executive function
3. learning and memory
4. language
5. perceptual-motor function
6. social cognition

Question 2

what makes up perceptual-motor function?

Answer 2

1. visual perception
2. visuoconstructional reasoning
3. perceptual-motor coordination

Question 3

what makes up language?

Answer 3

1. object naming
2. word finding
3. fluency
4. grammar and syntax
5. receptive language

Question 4

what makes up learning and memory?

Answer 4

1. free recall
2. cued recall
3. recognition memory
4. semantic and autobiographical
5. long-term memory
6. implicit learning

Question 5

what makes up social cognition?

Answer 5

1. recognition of emotions
2. theory of mind
3. insight

Question 6

what makes up complex attention?

Answer 6

1. sustained attention
2. divided attention
3. selective attention
4. processing speed

Question 7

what makes up executive function?

Answer 7

1. planning
2. decision-making
3. working memory
4. responding to feedback
5. inhibition
6. flexibility

Question 8

list the various types of memory

Answer 8

1. sensory
   
   1. iconic (visual)
   2. echoic (auditory)
   3. haptic (touch)
2. short-term
   
   1. working
3. long-term
   
   1. implicit (procedural)
   2. explicit (declarative-semantic)
   3. explicit (declarative-episodic)

Question 9

what factors help differentiate between delirium and dementia?

Answer 9

1. onset → delirium has quicker onset
2. duration → delirium has shorter duration
3. attention
4. consciousness
5. speech
6. cause → delirium is caused by something else
7. other features

Question 10

list the 3 types of delirium

Answer 10

1. hyperactive
2. hypoactive
3. mixed

Question 11

T/F: delirium is not associated with any complications

Answer 11

FALSE

associated with:

1. increased LOS
2. Prolonged recovery times
3. institutionalized care
4. increased morbidity and mortality rates

Question 12

describe the pathophysiology behind delirium

Answer 12

1. brain structural changes (cortical atrophy, white matter lesions, etc.)
2. neurotransmitter disturbances in central cholinergic and adrenergic pathways
3. elevated inflammatory cytokines (IL-6, IL-8)
4. multifactorial in older adults

Question 13

prevention and management of delirium

Answer 13

1. at least 30-40% of cases are preventable
2. determine cause and remediate ASAP
3. drugs linked to delirium
   
   1. psychoactive agents
   2. narcotics
   3. anticholingerics
4. nonpharmacologic interventions
   
   1. cognitive orientation
   2. early mobility
   3. enabling adequate hearing and vision
   4. promoting a normal sleep-wake cycle
   5. proper nutrition/hydration

Question 14

define dementia

Answer 14

a global impairment impacting intellectual functioning, memory, and at least one of the following:

1. abstract thinking
2. judgement and language
3. identification of people and objects
4. personality changes
5. ability to use object appropriately

Question 15

how is dementia diagnosed?

Answer 15

diagnosed through a semi-structured interview, detailed medical and neurological examination, neurocognitive testing

Question 16

how does the DSM-V define dementia?

Answer 16

a neurocognitive disorder

Question 17

list the types of Dementia

Answer 17

1. Alzheimer disease (AD)
2. Vascular dementia (VaD)
3. Dementia with Lewy bodies (DLB)
4. Frontotemporal dementia (FTD)
5. Mixed pathologies

Question 18

list the levels of cognitive impairment associated with dementia

Answer 18

1. subjective cognitive impairment
2. mild cognitive impairment
3. moderate cognitive impairment
4. severe cognitive impairment
5. amnestic vs nonamnestic cognitive impairment

Question 19

vascular dementia accounts for _______

Answer 19

20-30% of cases

Question 20

Key features of vascular dementia

Answer 20

1. associated with cerebrovascular disease
2. more often abrupt onset, but can be gradual with small vessel disease
3. memory loss usually less severe than AD
4. mood changes and apathy common
5. can occur in conjunction with AD = mixed dementia

Question 21

T/F: multi-infarct dementia has not relationship with vascular dementia

Answer 21

FALSE

it is a subset form

Question 22

affected brain areas in vascular dementia

Answer 22

1. medial temporal atrophy
2. cortical and subcortical lesions

Question 23

Clinical symptoms of vascular dementia

Answer 23

1. impaired attention, planning
2. difficulties with complex activities
3. disorganized thought

Question 24

dementia with Lewy Bodies accounts for ________

Answer 24

8% of dementia cases

accepted to be highly underdiagnosed and misdiagnosed

Question 25

key features of DLB

Answer 25

1. complex visual hallucinations 2. Parkinsonism 3. sleep disturbances 4. autonomic symptoms (i.e. hypotension) 5. fluctuating cognition

Question 26

DLB can occur in conjunction with \_\_\_\_\_\_\_

Answer 26

Parkinson's Disease

Question 27

affected brain areas in DLB

Answer 27

1. less severe medial temporal lobe atrophy than AD 2. FDG-PET shows occipital hypoperfusion and hypometabolism 3. loss of dopaminergic neurons in substantia nigra 4. limbic 5. brainstem 6. neocortex

Question 28

3 primary presentations of Lewy Body Disease

Answer 28

1. Parkinson's disease dementia (PDD) 2. Dementia with Lewy Bodies (DLB) 3. Neuropsychiatric symptoms → DLB

Question 29

Frontotemporal dementia accounts for \_\_\_\_\_\_

Answer 29

3-10% of dementia

Question 30

key features of FTD

Answer 30

1. more common in younger groups (50-60 yo) 2. memory often intact in early stage 3. sig changes in behavior and personality 4. disinhibition and impulsiveness are common

Question 31

types of FTD

Answer 31

1. Pick's disease 2. Progressive supranuclear palsy 3. corticobasal degeneration

Question 32

affected brain areas in FTD

Answer 32

1. frontal and temporal lobes 2. specific areas of atrophy dependent on type of variant

Question 33

Alzheimer's disease accounts for \_\_\_\_\_\_\_

Answer 33

50-60% of dementia cases

Question 34

Key features of AD

Answer 34

1. gradual loss of memory and function leading to total dependence on caregivers 2. eventual inability to recognize family/friends/self

Question 35

how is a diagnosis of AD made?

Answer 35

through interview/history, diagnostic testing

Question 36

affected brain regions in AD

Answer 36

1. entorhinal area 2. hippocampus 3. amygdala 4. regions of neocortex

Question 37

describe neurobiological changes of cognitive dysfunction in dementia

Answer 37

1. these changes can occur before symptoms appear in AD and other dementia 2. asymptomatic to mild cognitive impairment stages 1. amyloid markers are most prominent changes 2. shifts to more prominent structural changes once MCI stage begins 1. the degree of atrophy of medial temporal structures can be a potential diagnostic marker for mild cog impairment stage of AD

Question 38

how accurate are structural MRIs for diagnosing early dementia due to AD in people with MCI?

Answer 38

not very, a Cochrane review has inconclusive evidence

Question 39

list the diagnostic markers for AD how many must be present?

Answer 39

(one of 3 must be present) 1. medial temporal atrophy 1. 75% sensitivity, 81% specificity 2. temporoparietal hypometabolism 3. abnormal neuronal CSF markers (tau and/or Abeta)

Question 40

less common forms of dementia

Answer 40

1. Creutzfeldt-Jakob disease 2. HIV-related cognitive impairment 3. Huntington's chorea 4. MS 5. Normal pressure hydrocephalus 6. Niemann-Pick disease Type C (NPC)

Question 41

describe the normal aging brain

Answer 41

1. recent memory for important events, affairs, and conversations not impaired 2. does not get lost in familiar territory, may have to pause momentarily to remember way 3. able to operate common appliances even if unwilling to learn how to operate new devices 4. normal performance on mental status examinations, taking education and culture into account

Question 42

describe a brain with dementia

Answer 42

1. notable decline in memory for recent events, decline in ability to converse 2. gets lost in familiar territory while walking or driving, may take hrs to eventually remember 3. becomes unable to operate common appliances, unable to learn to operate even simple appliances 4. abnormal performance on mental status exams not accounted for by education or cultural differences

Question 43

how does the cellular environment differ between normal aging and dementia?

Answer 43

1. normally there are diminished communication signals between brain cells diminish 2. in dementia 1. metabolism impaired with development of neurofibrillary tangles 2. repair disabled by amyloid plaques 3. plaques and tangles produce mistakes throughout the brain resulting in cell death

Question 44

list AD diagnostic guidelines

Answer 44

1. 2011 guidelines for diagnostic criteria 2. disease progresses on a spectrum of 3 stages 1. preclinical 2. mild cognitive impairment (MCI) 3. Alzheimer's dementia 3. potential use of biomarkers 1. AB42 2. tau and p-tau in the CSF

Question 45

describe the Amyloid hypothesis

Answer 45

amyloid beta derived from larger protein: amyloid precursor protein (APP) B-secretase and gamma-secretase cut APP in two places → create peptide fragment gene mutation causes longer fragments that are more likely to clump together amyloid beta aggregates forming tau-tangles resulting in inflammation and synapse dysfunction and cell death manifesting as dementia

Question 46

what is the connection between sleep and amyloid-beta?

Answer 46

sleep deprivation results in increased amyloid-beta build up and thus puts you at higher risk for developing AD

Question 47

what is the function of amyloid-beta?

Answer 47

* it is present throughout lifespan in humans * found in all vertebrae with high degree of conservation in molecular sequence * suggests AB serves a beneficial role in human physiology * evidence shows that a depletion of endogenous AB has adverse consequences (in animal studies)

Question 48

Beneficial roles of amyloid-beta

Answer 48

1. antimicrobial activity 2. tumor suppression 3. sealing leaks in the BBB 4. promoting recovery from brain injury 5. regulating synaptic function

Question 49

what is the relationship between plaque burden and dementia?

Answer 49

1. not all plaques are equal 2. in some cases plaques appear to have protective function 3. cognitive symptoms linked more closely to number/location of tau tangles 4. post-mortem exams have shown tangles in absence of plaques 5. beta amyloid appears to be driving force behind AD

Question 50

list drugs that have undergone drug trials for treatment of dementia

Answer 50

1. immunotherapy 2. gamma-secretase inhibitor 3. monoclonal antibody 4. beta-secretase inhibitor

Question 51

what do the results from drug trails mean in relationship to dementia?

Answer 51

1. amyloid is a disease trigger for tau and inflammation to drive the disease 2. drugs are being given at wrong point in progression of AD 3. plaques can form decades before cognitive symptoms appear 4. beta amyloid levels may have plateaued by time pt enters trial 5. Beta amyloid is a match that starts bush fires of tau tangles, leading to a forest fire of inflammation in brain 1. by the time the drug is given there is simply too much damage done

Question 52

list biomarkers for dementia

Answer 52

1. FDA-approved diagnostic tests for AD (PET neuroimaging scans) 1. Amyvid 2. Vizamyl 3. Neuraseq 2. FDA-approved at-home genetic test 1. 23andME saliva swab to ID APOE gene variant

Question 53

APOE4 affect on brain function

Answer 53

increased risk of dementia thought to be linked to toxic “gain of function” * increased response to stress and injury * normal healthy brain function also appears to diminish

Question 54

what is the purpose of Apolipoprotein E gene in the brain?

Answer 54

synthesized in the brain to regulate: 1. level amyloid-beta 2. brain lipid transport 3. glucose metabolism 4. neuronal signaling 5. neuroinflammation 6. mitochondrial function

Question 55

describe drug treatment options for dementia

Answer 55

1. emerging and not yet effective * disease modifying drugs * aim to slow or prevent onset of disease 2. Current drugs on the market 1. neurotransmitter-based drugs 2. treat symptoms, attempt to delay progression

Question 56

description the drug options that focus on neurotransmitter depletion

Answer 56

1. Acetylcholine 1. dramatic reduction from neuron degeneration 2. loss of 60-90% of acetylcholine activity = memory impairment 2. Other neurotransmitters 1. serotonin, somatostatin, norepinephrine 3. Symptomatic treatment 1. blocking acetylcholinesterase 2. meds targeting NMDA pathway

Question 57

general drug treatment approach for mild dementia

Answer 57

cholinesterase inhibitor

Question 58

general treatment approachs for moderate dementia

Answer 58

1. cholinesterase inhibitor + memantine more likely to delay progression 2. address behavioral and psychological symptoms

Question 59

general treatment approaches for severe dementia

Answer 59

1. consider if meds will provide a benefit, possibly do a med-free trial 2. may continue cholinesterase inhibitor approved for late-stage disease or memantine

Question 60

T/F: there is no cure for dementia

Answer 60

TRUE can only attempt to delay progression

Question 61

Alzheimer's disease drug concerns

Answer 61

1. Be aware of potential AE with meds 1. cholinergic meds → GI issues most common 2. Memantine → may cause dizziness, watch for falls 2. communicate behavioral issues to healthcare providers 3. Timing of PT 1. provide structure to reduce behavioral issues 2. reduce behavioral issues related to sun-downing 3. utilize time of day when pt most alert

Question 62

describe the drug option → Amyloid beta-directed antibody

Answer 62

aka aducanumb (Aduhelm) approved under accelerated approval pathway post-approval trial must verify clinical benefit or approval will be withdrawn

Question 63

AEs of amyloid beta-directed antibody

Answer 63

1. ARIA-edema 2. HA 3. ARIA-microhemorrhage 4. ARIA-H superficial siderosis 5. diarrhea 6. confusion/delirium 7. falling ARIA = amyloid-related imaging abnormalities

Question 64

downside of amyloid beta-directed antibody

Answer 64

VERY expensive

Question 65

Controversy surrounding amyloid beta-directed antibody

Answer 65

1. FDA advisory committee voted that there was insufficient evidence showing clinical efficacy 2. does clearance of amyloid plaques actually slow disease progression? 3. labeling does not match trial criteria 4. may inhibit participation in needed post-trial 5. may inhibit development of a better drug