Cognitive Issues in Older Adults Part 1 Flashcards
list the neurocognitive domains that make up cognition
- complex attention
- executive function
- learning and memory
- language
- perceptual-motor function
- social cognition
what makes up perceptual-motor function?
- visual perception
- visuoconstructional reasoning
- perceptual-motor coordination
what makes up language?
- object naming
- word finding
- fluency
- grammar and syntax
- receptive language
what makes up learning and memory?
- free recall
- cued recall
- recognition memory
- semantic and autobiographical
- long-term memory
- implicit learning
what makes up social cognition?
- recognition of emotions
- theory of mind
- insight
what makes up complex attention?
- sustained attention
- divided attention
- selective attention
- processing speed
what makes up executive function?
- planning
- decision-making
- working memory
- responding to feedback
- inhibition
- flexibility
list the various types of memory
- sensory
- iconic (visual)
- echoic (auditory)
- haptic (touch)
- short-term
- working
- long-term
- implicit (procedural)
- explicit (declarative-semantic)
- explicit (declarative-episodic)
what factors help differentiate between delirium and dementia?
- onset → delirium has quicker onset
- duration → delirium has shorter duration
- attention
- consciousness
- speech
- cause → delirium is caused by something else
- other features
list the 3 types of delirium
- hyperactive
- hypoactive
- mixed
T/F: delirium is not associated with any complications
FALSE
associated with:
- increased LOS
- Prolonged recovery times
- institutionalized care
- increased morbidity and mortality rates
describe the pathophysiology behind delirium
- brain structural changes (cortical atrophy, white matter lesions, etc.)
- neurotransmitter disturbances in central cholinergic and adrenergic pathways
- elevated inflammatory cytokines (IL-6, IL-8)
- multifactorial in older adults
prevention and management of delirium
- at least 30-40% of cases are preventable
- determine cause and remediate ASAP
- drugs linked to delirium
- psychoactive agents
- narcotics
- anticholingerics
- nonpharmacologic interventions
- cognitive orientation
- early mobility
- enabling adequate hearing and vision
- promoting a normal sleep-wake cycle
- proper nutrition/hydration
define dementia
a global impairment impacting intellectual functioning, memory, and at least one of the following:
- abstract thinking
- judgement and language
- identification of people and objects
- personality changes
- ability to use object appropriately
how is dementia diagnosed?
diagnosed through a semi-structured interview, detailed medical and neurological examination, neurocognitive testing
how does the DSM-V define dementia?
a neurocognitive disorder
list the types of Dementia
- Alzheimer disease (AD)
- Vascular dementia (VaD)
- Dementia with Lewy bodies (DLB)
- Frontotemporal dementia (FTD)
- Mixed pathologies
list the levels of cognitive impairment associated with dementia
- subjective cognitive impairment
- mild cognitive impairment
- moderate cognitive impairment
- severe cognitive impairment
- amnestic vs nonamnestic cognitive impairment
vascular dementia accounts for _______
20-30% of cases
Key features of vascular dementia
- associated with cerebrovascular disease
- more often abrupt onset, but can be gradual with small vessel disease
- memory loss usually less severe than AD
- mood changes and apathy common
- can occur in conjunction with AD = mixed dementia
T/F: multi-infarct dementia has not relationship with vascular dementia
FALSE
it is a subset form
affected brain areas in vascular dementia
- medial temporal atrophy
- cortical and subcortical lesions
Clinical symptoms of vascular dementia
- impaired attention, planning
- difficulties with complex activities
- disorganized thought
dementia with Lewy Bodies accounts for ________
8% of dementia cases
accepted to be highly underdiagnosed and misdiagnosed
key features of DLB
- complex visual hallucinations
- Parkinsonism
- sleep disturbances
- autonomic symptoms (i.e. hypotension)
- fluctuating cognition
DLB can occur in conjunction with _______
Parkinson’s Disease
affected brain areas in DLB
- less severe medial temporal lobe atrophy than AD
- FDG-PET shows occipital hypoperfusion and hypometabolism
- loss of dopaminergic neurons in substantia nigra
- limbic
- brainstem
- neocortex
3 primary presentations of Lewy Body Disease
- Parkinson’s disease dementia (PDD)
- Dementia with Lewy Bodies (DLB)
- Neuropsychiatric symptoms → DLB
Frontotemporal dementia accounts for ______
3-10% of dementia
key features of FTD
- more common in younger groups (50-60 yo)
- memory often intact in early stage
- sig changes in behavior and personality
- disinhibition and impulsiveness are common
types of FTD
- Pick’s disease
- Progressive supranuclear palsy
- corticobasal degeneration
affected brain areas in FTD
- frontal and temporal lobes
- specific areas of atrophy dependent on type of variant
Alzheimer’s disease accounts for _______
50-60% of dementia cases
Key features of AD
- gradual loss of memory and function leading to total dependence on caregivers
- eventual inability to recognize family/friends/self
how is a diagnosis of AD made?
through interview/history, diagnostic testing
affected brain regions in AD
- entorhinal area
- hippocampus
- amygdala
- regions of neocortex
describe neurobiological changes of cognitive dysfunction in dementia
- these changes can occur before symptoms appear in AD and other dementia
- asymptomatic to mild cognitive impairment stages
- amyloid markers are most prominent changes
- shifts to more prominent structural changes once MCI stage begins
- the degree of atrophy of medial temporal structures can be a potential diagnostic marker for mild cog impairment stage of AD
how accurate are structural MRIs for diagnosing early dementia due to AD in people with MCI?
not very, a Cochrane review has inconclusive evidence
list the diagnostic markers for AD
how many must be present?
(one of 3 must be present)
- medial temporal atrophy
- 75% sensitivity, 81% specificity
- temporoparietal hypometabolism
- abnormal neuronal CSF markers (tau and/or Abeta)
less common forms of dementia
- Creutzfeldt-Jakob disease
- HIV-related cognitive impairment
- Huntington’s chorea
- MS
- Normal pressure hydrocephalus
- Niemann-Pick disease Type C (NPC)
describe the normal aging brain
- recent memory for important events, affairs, and conversations not impaired
- does not get lost in familiar territory, may have to pause momentarily to remember way
- able to operate common appliances even if unwilling to learn how to operate new devices
- normal performance on mental status examinations, taking education and culture into account
describe a brain with dementia
- notable decline in memory for recent events, decline in ability to converse
- gets lost in familiar territory while walking or driving, may take hrs to eventually remember
- becomes unable to operate common appliances, unable to learn to operate even simple appliances
- abnormal performance on mental status exams not accounted for by education or cultural differences
how does the cellular environment differ between normal aging and dementia?
- normally there are diminished communication signals between brain cells diminish
- in dementia
- metabolism impaired with development of neurofibrillary tangles
- repair disabled by amyloid plaques
- plaques and tangles produce mistakes throughout the brain resulting in cell death
list AD diagnostic guidelines
- 2011 guidelines for diagnostic criteria
- disease progresses on a spectrum of 3 stages
- preclinical
- mild cognitive impairment (MCI)
- Alzheimer’s dementia
- potential use of biomarkers
- AB42
- tau and p-tau in the CSF
describe the Amyloid hypothesis
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
what is the connection between sleep and amyloid-beta?
sleep deprivation results in increased amyloid-beta build up and thus puts you at higher risk for developing AD
what is the function of amyloid-beta?
- 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)
Beneficial roles of amyloid-beta
- antimicrobial activity
- tumor suppression
- sealing leaks in the BBB
- promoting recovery from brain injury
- regulating synaptic function
what is the relationship between plaque burden and dementia?
- not all plaques are equal
- in some cases plaques appear to have protective function
- cognitive symptoms linked more closely to number/location of tau tangles
- post-mortem exams have shown tangles in absence of plaques
- beta amyloid appears to be driving force behind AD
list drugs that have undergone drug trials for treatment of dementia
- immunotherapy
- gamma-secretase inhibitor
- monoclonal antibody
- beta-secretase inhibitor
what do the results from drug trails mean in relationship to dementia?
- amyloid is a disease trigger for tau and inflammation to drive the disease
- drugs are being given at wrong point in progression of AD
- plaques can form decades before cognitive symptoms appear
- beta amyloid levels may have plateaued by time pt enters trial
- Beta amyloid is a match that starts bush fires of tau tangles, leading to a forest fire of inflammation in brain
- by the time the drug is given there is simply too much damage done
list biomarkers for dementia
- FDA-approved diagnostic tests for AD (PET neuroimaging scans)
- Amyvid
- Vizamyl
- Neuraseq
- FDA-approved at-home genetic test
- 23andME saliva swab to ID APOE gene variant
APOE4 affect on brain function
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
what is the purpose of Apolipoprotein E gene in the brain?
synthesized in the brain to regulate:
- level amyloid-beta
- brain lipid transport
- glucose metabolism
- neuronal signaling
- neuroinflammation
- mitochondrial function
describe drug treatment options for dementia
- emerging and not yet effective
- disease modifying drugs
- aim to slow or prevent onset of disease
- Current drugs on the market
- neurotransmitter-based drugs
- treat symptoms, attempt to delay progression
description the drug options that focus on neurotransmitter depletion
- Acetylcholine
- dramatic reduction from neuron degeneration
- loss of 60-90% of acetylcholine activity = memory impairment
- Other neurotransmitters
- serotonin, somatostatin, norepinephrine
- Symptomatic treatment
- blocking acetylcholinesterase
- meds targeting NMDA pathway
general drug treatment approach for mild dementia
cholinesterase inhibitor
general treatment approachs for moderate dementia
- cholinesterase inhibitor + memantine more likely to delay progression
- address behavioral and psychological symptoms
general treatment approaches for severe dementia
- consider if meds will provide a benefit, possibly do a med-free trial
- may continue cholinesterase inhibitor approved for late-stage disease or memantine
T/F: there is no cure for dementia
TRUE
can only attempt to delay progression
Alzheimer’s disease drug concerns
- Be aware of potential AE with meds
- cholinergic meds → GI issues most common
- Memantine → may cause dizziness, watch for falls
- communicate behavioral issues to healthcare providers
- Timing of PT
- provide structure to reduce behavioral issues
- reduce behavioral issues related to sun-downing
- utilize time of day when pt most alert
describe the drug option → Amyloid beta-directed antibody
aka aducanumb (Aduhelm)
approved under accelerated approval pathway
post-approval trial must verify clinical benefit or approval will be withdrawn
AEs of amyloid beta-directed antibody
- ARIA-edema
- HA
- ARIA-microhemorrhage
- ARIA-H superficial siderosis
- diarrhea
- confusion/delirium
- falling
ARIA = amyloid-related imaging abnormalities
downside of amyloid beta-directed antibody
VERY expensive
Controversy surrounding amyloid beta-directed antibody
- FDA advisory committee voted that there was insufficient evidence showing clinical efficacy
- does clearance of amyloid plaques actually slow disease progression?
- labeling does not match trial criteria
- may inhibit participation in needed post-trial
- may inhibit development of a better drug
