Neurocognitive Disorders - Dementia Flashcards
dementia
cognitive DECLINE (AQUIRED deficit, not developmental)
- more than one cognitive domain affected
- social/occupational functioning impairment
- static or progressive
All patients w/ Alzheimer’s have _____
All patients w/ Alzheimer’s have DEMENTIA
but NOT all pts w/ dementia have Alzheimer’s.
Neurocognitive Disorders (NCDs), major and minor
include delirium, conditions involving substantial decline in a single cognitive domain, conditions affecting younger individuals (e.g. TBI, HIV) as well as previously described dementias
6 cognitive domains
- complex attention
- executive function
- learning and memory
- language
- perceptual - motor
- social cognition
Major Neurocognitive Disorder due to Alzheimer’s disease (DSM-V)`
- evidence of INSIDIOUS onset, GRADUAL progression of impairment, and significant cognitive DECLINE from a previous level of performance in 2 or more of the 6 cognitive domains, based upon:
- -> Concern of decline expressed by the individual/others
- -> Substantial impairment in cognitive performance (standardized testing, etc) - either evidence of gene mutation OR memory/learning affected domains
- cognitive deficits interfere w/ daily independence
- cognitive deficits do NOT occur exclusively in context of delirium
Mild Neurocognitive Disorder due to Alzheimer’s disease (DSM-V)
The cognitive deficits do NOT interfere with capacity for independence in everyday activities
NCD due to Alzheimer’s is the most common cause of _____ in the elderly.
NCD due to Alzheimer’s is the most common cause of PSYCHOSIS in the elderly.
MCD due to Alzheimer’s prominent behavioral sx
- depression
- apathy
- irritability
- paranoid
- visual hallucinations
- agitation
- sleep disturbance
- wandering
- combativeness
- misidentification sx (thinks husband is imposter)
Amyloid cascade hypothesis
Amyloid Precursor Protein (APP)
1. cleaved by alpha-secretase to a benign breakdown product in the non-amyloidogenic pathway
OR
2. cleaved by beta-secretase and then gamma-secretase to form beta amyloid/amyloid-beta/A-beta/Αβ –> AGGREGATION and NEUROTOXICITY
Strategies to reduce beta-amyloid
- reduce production, vaccinate, facilitate clearance, prevent aggregation of beta amyloid
recent: use of monoclonal Abs directed against beta amyloid very early in the course of the illness
MCD due to Alzheimer’s unmodifiable risk fx
- Advancing age
- Family history and genetics
- first degree relative affected
- Apolipoprotein E (APOE) genotype (4*)
- Rare autosomal dominant “deterministic” genes - Down’s syndrome –> highly increased risk
- Female gender (some disagreement)
- head trauma
- low educational levels
- vascular risk fx (sedentary/obesity/smoking/HTN etc.)
Apolipoprotein E (APOE) genotypes (which increases risk? neutral? protective?)
APOE-4 allele, esp. homozygous –> inc risk (earlier onset, possibly via impaired Beta amyloid clearance)
APOE-3 allele, neutral
APOE-2 allele, may be PROTECTIVE
MCD due to Alzheimer’s biomarkers
- Measures of brain beta-amyloid deposition
- diminished CSF beta-amyloid (not getting cleared)
- positive amyloid in PET imaging - Measures of neurodegeneration
- inc CSF tau (tangles)
- dec glucose uptake in parietal/temporal cortex (FDG PET)
- structural imaging (MRI)
- PET tau imaging
MCD due to Alzheimer’s:
FDA approved meds
Cholinesterase Inhibitors
N-methyl-D-aspartate (NMDA) Partial Receptor Antagonists
- blocks xs glutamate (excitatory)
In elderly pts w/ dementia, how are Behavioral and Psychological Symptoms of Dementia (BPSD) and caregiver burden reduced?
Anticholinergic burden reduction (by reducing or eliminating medications with CNS anticholinergic side effect)
Does beta-amyloid increase or decrease in CSF?
Decrease. Less clearance.
Major Frontotemporal Neurocognitive Disorder
previously Frontotemporal Dementia
- Symptomatology often dominated by PERSONALITY change:
- social inappropriateness
- behavioral disinhibition
- apathy
- impaired judgment and insight
- perseverative, compulsive behavior
- hyperorality, such as overeating - Onset before 65 y/o
- Decline often faster than Alzheimer’s
Major Neurocognitive Disorder with Lewy Bodies
formerly Lewy Body Dementia
- FLUCTUATING cognition, variations in attn/alertness
- VISUAL hallucinations early on
- Parkinson sx, marked sensitivity to antipsychotic medication side effects
- REM sleep disorder (dreams acted out)
- autonomic dysfunction (falls, syncope, orthostatic hypotension)
- Lewy bodoes (alpha-synuclein) cerebral cortex
differential dx of Major Neurocognitive Disorder with Lewy bodies
vs. Parkinson’s
in Parkinson’s, motor sx clearly PRE-date cognitive decline
Major Vascular Neurocognitive Disorder
formerly Vascular Dementia
- cognitive deficits may be related to one or more cerebrovascular events
- course sometimes uneven w/ decline followed by periods of stability and maybe some improvement
- Pathophys of NCD due to Alzheimer’s and Vascular disease may overlap
- Patients over 85 often have NCD due to Alzheimer’s and cerebrovascular disease
Other Major/Minor Neurocognitive Disorders can be due to…
traumatic brain injury, substance/medication use, HIV infection, Prion disease, Parkinson’s Disease, Huntington’s Disease, another medical condition, or multiple etiologies
The most common cause or form of dementia
Alzheimer’s disease
T/F
Pts w/ dementia-related apathy are also likely to be depressed and will respond well to antidepressants
FALSE
Which dementia often initially presents w/ vivid visual hallucinations?
Major Neurocognitive Disorder with Lewy Bodies
Which dementia often initially presents w/ personality change?
Major Frontotemporal Neurocognitive Disorder
Delirium or dementia includes fluctuating levels of consiousness?
DEMENTIA
triad of lewy of body dementia
- dementia
- parkonsonian sx
- visual hallucinations
amyloid plaques
neurofibrillary tangles
frontotemporal atrophy
^found in
Alzheimer’s
One of the most prominent changes (and thus potential drug target) in alzheimer’s is the loss of __ activity in the brain.
ACh
Impaired CSF absorption (communicating/nonobstructive hydrocephalus) may lead to normal pressure hydrocephalus (NPH).
The classical triad of clinical features of NPH is
wet (urinary incontinence)
wacky (cognitive dysfunction)
wobbly (ataxia)
Intracellular neurofibrillary tangles (hyperphosphorylated tau protein) is a histologic hallmark of
Alzheimer’s dementia
