Dementia, Delirium, Depression Flashcards
what is the normal aging process?
- Cerebral atrophy - neurons decrease; loss of neurons and connections between them
- Thickened leptomeninges : glia cells increase in both size and #
- DNA damage
- malfunctioning DNA damage response (DDR)
what are nml signs of the aging neurologic system?
These changes are implications of what?
- Decreased # of neurons and increase in size and # of neuroglial cells = Increased risk for neurological problems: cerebrovascular accident
- decline in nerves and nerve fibers
- parkinsonism
- slower conduction of fibers - atrophy of brain and increase in cranial dead space
- decline in short-term mem
- changes in gait - thickened leptomeninges in spinal cord = increased risk of hemorrhage before sx show
how do glia cells support neurons?
insulation
remove pathogens
supply nutrients
name the 4 glia cells
- Ependymal – controls production and flow of CSF, brain metabolism and waste clearance
- Astrocytes – metabolic, structural, homeostatic and neuroprotective tasks- stabilizing and regulating BBB
- Microglial - macrophages that remove damaged neurons and infections
- Oligodendrocyte - myelinating cells of theCNS
Cerebral atrophy can either be _____ (brain shrinks) OR _____ (affecting only a limited area of the brain)
generalized or focal
associated dz of cerebral atrophy
- Stroke and TBI
- Alzheimer’s, Pick’s dz, and fronto-temporal dementia
- Cerebral palsy: lesions may impair motor coordination
- Huntington’s: genetic mutations
- Leukodystrophies: such as Krabbe disease; destroys the myelin sheath that protects axons
- Mitochondrial encephalomyopathies: Kearns-Sayre syndrome; interferes w/ basic neuron functions
- MS: inflammation, myelin damage, and lesions in cerebral tissue
- Infectious dz: encephalitis, neurosyphilis, and AIDS; infectious agents or inflammatory rxn
sx of cerebral atrophy
- Dementia:
- Progressive impairment of memory and intellectual function that is severe enough to interfere with social and work skills
- Memory, orientation, abstraction, ability to learn, visual-spatial perception, and higher executive functions such as planning, organizing, and sequencing may also be impaired
- Seizures:
- Aphasias:
- disturbances in speaking and understanding language
- Receptive aphasia: impaired comprehension
- Expressive aphasia: odd choices of words, the use of partial phrases, disjointed clauses, and incomplete sentences
in thickened leptomeninges, what are the two layers involved?
arachnoid
pia
nml aging findings of cognitive function
- Difficulty recalling names or locations of placed objects, often to remember at a later time
- Subtle deficits in memory function - not severe enough to disturb/delay life
- No functional impairment
- Learning remains intact: 3-word recall
Cognitive function in older adults is considered a ?
spectrum
nml changes with aging –> Mild cognitive impairment (MCI): pathology develops –> dementia
key hx info for cognitive impairment
- Duration and nature of progression
- Memory (recent and remote) and learning
- Language - word-finding problems, difficulty expressing self
- Visuospatial skills - hx of getting lost in familiar places
- Executive functioning - ex: balancing checkbook, overdraw account
- Apraxia - not able to do previously learned motor tasks, eg, slicing a loaf of bread
- Behavior or personality changes - easily missed dx as depression
- Psychotic sx
- Functional assessment: ADL’s, IADL’s
- Social support assessment
- PMHx, comorbidities, hx of head trauma
- Thorough medication review - easily reversible
- FHx
- ROS - screen for depression and alcohol/substance abuse
PE to assess for cognitive impairment
- Neuro: look for focal findings, extrapyramidal signs, gait and balance assessment
- CV examination
- Signs of abuse or neglect
- Screen hearing and vision
- Can’t recall info secondary to decreased visual or auditory acuity
Has to be alert - Can not rely on results if pt has altered LOC / delirium
diagnostics for cognitive impairment
- labs - VitB12, TSH
- additional: LFT, LP - imaging - noncontrast CT/MRI of brain
- r/o stroke, small vessel dz, tumor, SDH, normal pressure hydrocephalus
ddx for cognitive impairment
- Alzheimers Dementia
- Vascular dementia
- Dementia with Lewy body
- Frontotemporal dementia
- Depression (in mild cognitive changes)
- Chronic traumatic encephalopathy
- Drug induced
- Alcohol or drug abuse
- Vit B12 def - peripheral nerve changes/cognitive dysfunction
- Normal pressure hydrocephalus
- Toxic metabolic - DKA, hepatic encephalopathy
- CNS neoplasms
- Tertiary syphilis
- HIV-Associated Dementia
an intermediate state between normal cognition and dementia often seen in older adults
mild cognitive impairment (MCI)
Pt has
Difficulty remembering names and appointments
Difficulty solving complex problems.
Testing shows abnormal memory but no functional impairment
what is your dx?
mild cognitive impairment
cause/pathology of MCI
age-related neurodegenerative dz
management for MCI
- Look for reversible causes
- Med SE, Sleep disturbances, Depression, vit B12 def, Hypothyroidism - Identify and modify vascular RF
- Nonpharm strategies
- No studies point to improvement
- Regular exercise
- Cognitive training: jigsaw puzzle, playing cards, read and look up unfamiliar words, encourage activities that use senses, learn a new skill, teach a new skill, listen to or play music
A general term used to describe various conditions in which there are deficits in multiple areas of cognitive function resulting inimpairment in daily functioning (at any lvl)
dementia
types of dementia
- Alzheimer disease - MC
- Vascular dementia
- Dementia with Lewy bodies
- Frontotemporal dementia
A neurodegenerative disorder of uncertain etiology and pathogenesis, resulting in cognitive and behavioral impairment
Alzheimer Disease
cause/etiology of alzheimers
- damage starts in hippocampus and entorhinal cortex (essential in forming memories)
- As more neurons die, more of the brain are affected and begin to shrink
- By final stages, damage is widespread and brain tissue has shrunk significantly
alzheimers is associated with 2 types of cerebral cortex lesions:
- Amyloid plaques
- Neurofibrillary tangles
unknown if lesions are what cause AD or if they occur as a result of AD
reason/pathogenesis not fully understood
describe the normal neuron anatomy
- axon has microtubule that transport nutrients, organelles, and other messages from the cell body to the tip of the axon
- Tau proteins: glue that hold microtubules in place
- impulse comes down from cell body, follows along track and ends at point
pathophys of nerofibrillary tangles
- tau proteins breakdown and adhere to each other instead of adhering to microtubules
- Resulting in inadequate transport from the cell body to the end of axon, preventing nml neuron communication
a protein found on membrane of various cells throughout the body and concentrated in the synapse of the neuron
enzymes come in and cut these proteins
Amyloid precursor protein (APP)
aka senile plaques
a sticky fragment of the APP that is released when various enzymes are present
sticky and adhere to each other
Beta amyloid protein
a lesion consisting of beta amyloid proteins that occurs between neurons and thought to affect neuronal communication
prevents dendrites from communicating with each other
Beta amyloid plaque
RF for AD
- Increasing age
- Female sex
- Apo ε4 gene on chromosome 19 - help w/ cholesterol transport
- Hx of head trauma
- Lower educational level - “don’t use it you lose it”
- Vascular disease
- DM
- Down syndrome - (Trisomy 21) extra APP gene on chromosome 21 - make more proteins, develop same patho, but happens earlier
- FHx
classic triad of AD
- Difficulty learning and recalling info - memory impairment
- Visuospatial problems - gets lost in unfamiliar surroundings → familiar surroundings
- Language impairment - word retrieval issues → fluent aphasia → nonverbal
disorientation and behavioral changes are also common
Sx interfere with social, occupational, or daily functioning
early behavioral changes vs later changes associated with AD
early: depression, apathy, irritability
late: agitation and psychotic symptoms (delusions, hallucinations, paranoia)
- longer time to perform daily tasks
- recognizing familiar places
- paying bills, handling money
- recalling new names
- word recall
- losing or misplasing items
- pallning or organizing
- remember new reading material
This presents what type of AD?
mild AD
- recalling demographics
- easily lost
- disorientated to place/time
- short attention span
- disorganized thought processes
- choosing appropriate clothing
- difficulty recognizing family/friends
- repetitive statements
- loss of new learning
- behavioral changes
- psychotic sx
- trouble reading, writing
these are associated with which AD?
moderate AD
- absent recognition of family/friend
- wt loss
- increased sleep
- loss of bowel/bladder control
- Death often occurs due to a complicating illness (aspiration pneumonia)
- increased infections
- trouble swallowing
- unable to communicate effectively
these are associated with what type of AD?
severe AD
MC infection associated with severe AD?
aspiration pneumonia
diagnostics for AD
r/o delirium
A clinical dx with evidence of cognitive dysfunction = functional impairment after r/o other causes of dementia
- imaging (not diagnostic) - CT/MRI, monitor progression, r/o mass
- shows diffuse cortical and/or cerebral atrophy
- greater degree of hippocampal atrophy = AD
- frontal lobe = frontotemporal dementia
- vascular pathology = vascular dementia
managment for AD
- Cholinesterase Inhibitors (1st line at any stage) - donepezil, galantamine rivastigmine, aricept and razadyne, exelon
- NMDA receptor antagonist - memantine, namzaric (combo NMDA/cholinesterase inhibitor)
- nonpharm - exercise, mental stimulation, social activities
- behavioral therapy
- nonpharm - music therapy, exercise, removing extra noise and clutter, easier tasks, having a daily routine
- pharm - SSRI, trazodone
- refer to geriatic psychiatrist if unableto control sx
Works as neurotransmitter
increases acetylcholine at the neuronal synapses in the brain
slows the progression of AD (no evidence of slowing MCI → AD)
what AD med is this
cholinesterase inhibitor
donepezil (Aricept), galantamine (Razadyne), rivastigmine (Exelon), Aricept and Razadyne (po only), Exelon (po & transdermal)
SE of AchEI
- MC: N/D, anorexia, sleep disturbance; take with food
- Serious: bradycardia, atrioventricular (AV) nodal block, and syncope
- Start low and go slow! Titrate up q 2 mo until therapeutic dose is achieved
reduces the destruction of cholinergic neurons and may inhibit β-amyloid production, thereby preserving memory
what AD med is this
NMDA receptor anatagonist
Memantine (Namenda)
indication for NMDA receptor antagonist?
moderate-to-severe AD, unable to tolerate AchEI
SE of NMDA receptor antagonist
Dizziness, HA, confusion, constipation
indication for namzaric
combo NMDA+AchEI
moderate-severe AD
pt & family ed for AD
- Assess - driving safety, pill box, electronic reminders
- Appropriate supervision or limited use - stove, woodworking equipment, firearms
- Medical alert systems
- 24-hour supervision if patient can’t identify what to do in an emergency
- Home care services to assist with ADL’s
- Caregiver Support
- Increased risk for depression, work absence, and health problems
- Educational resources
- National Institute on Aging
- Caring for AD
- Communication strategies
- Legal and financial planning - Respite care services & adult daycare - National Institute on Aging
- Local support groups - Alzheimer’s Association
Worsening of comorbid conditions of AD is due to ?
treatment adherence issues
complications with AD
- Increased risk of developing delirium in response to medical illness or surgery
- Advanced AD leads to - poor nutritional intake, UI, skin breakdown, infections
Course of the disease
1. Progression occurs at different rates
1. DC AchEI and NMDA once pt is unable to express their needs
A gradual or acute onset of cognitive dysfunction (not related to delirium) with clinical or radiographic evidence of cerebrovascular disease, often with AD
Vascular Dementia
cause of Vascular Dementia
- Pathophysiologic, small, micro-ischemic changes in brain
- Not enough for focal deficits, but lots of them can damage neurologic function
presentation of vascular dementia
- _Memory impairment _less severe than AD
- Difficulty of timed activities and executive functions - One-minute semantic test
- Same behavioral and psychological sx as in AD
- Depression more severe than AD
- Focal neurologic deficits are not seen
work-up and management for vascular dementia
- imaging - MRI = evidence of small infarcts (White matter lesions)
- management - same as AD = AchEI, memantine, nonpharms
vascular risks for vascular dementia
HTN
Smoking
DM
Statins
Antiplatelets (if hx of TIA or ischemic stroke)
cause of dementia with lewy bodies?
- Lewy bodies are deposits of alpha-synuclein
- A protein naturally found at the presynaptic terminals
- Alpha-synuclein plays a role in NT release
similar lesions in dementia with lewy bodies are found in what othr condition?
parkinson’s
DLB is MC in who
MC 75 y/o, range 50-80
Male
sporadic - rare with FHx
occurs with AD 40% of pt
presentation of DLB
- Insidious onset - fluctuating cognitive impairment (day-by-day)
- Memory affected < AD
- Visuospatial abilities, problem solving, and processing speed severe > AD early in course
- Spontaneous Parkinsonism - hallmark of DLB
- bradykinesia, bilateral limb rigidity, flat affect (mask-like facies), postural instability, gait changes
- less tremors or respond to levodopa
- visual hallucinations (60-85%) – rare in AD; Vivid, often animals, ppl, mystical
- Delusional misidentification often 1st sx that helps differ from AD
- REM sleep disorder
- sensitivity to antipsychotics
- Repeated falls – associated with parkinsonism
- Orthostatic hypotension, syncope, transient loss of consciousness
- Autonomic dysfunction
- Hypersomnia
- Hyposmia – decreased sense of smell
- Apathy, anxiety, depression
effects of antipsychotics in DLB?
- Sx often get worse
- Severe (sometimes irreversible) parkinsonism and impaired consciousness
- Features of neuroleptic malignant syndrome
- Life-threatening rxn to antipsychotic medications: fever, altered mental status, autonomic dysfunction
diagnostics for DLB
r/o other causes
- MRI - atrophy in basal ganglia structures and the dorsal midbrain in DLB
- pathohistological brain autopsy after death. - Lewy bodies
- McKeith criteria
- SPECT - decreased dopaine uptake and perfusion
criteria used for DLB
McKeith Criteria
-
probable DBL
- +2 core clinical features present w/ or w/o indicative biomarkers; OR
- only 1 clinical feature but with +1 indicative biomarkers
- probable DLB should not be dx on basis of biomarkers alone -
possible DBL
- only 1 clinical feature iwth no biomarkers OR
- +1 biomarkers but no clnical features
difference in findings on MRI with DBL vs PD vs AD
DBL - atrophy of basal ganglia structures + dorsal midbrain
AD - atropy of medial temporal lobe + hippocampus
PD - cortical atrophy + substantia nigra changes
a nuclear imaging scan that integrates computed tomography (CT) and a radioactive tracer
Single-photon emission computed tomography (SPECT)
management for DLB
- Cholinesterase inhibitors
- (+/-) Memantine - evidence of benefit is mixed
- Atypical antipsychotics in very small doses ONLY if psychosis is severe
- SSRIs - depression
- LD melatonin (3-15 mg) - REM disorders
- Parkinsonism is treated the same as PD: carbidopa-levodopa
- Fludrocortisone for orthostatic hypotension
RF for higher mortality of DLB
older age, hallucinations, greater degrees of fluctuation, and neuroleptic sensitivity
A group or umbrella term of clinical syndromes that results from degeneration of the frontal and temporal lobes of the brain
Frontotemporal Dementia (FTD)
MCC of early-onset dementia
Frontotemporal Dementia (FTD)
Onset <65 y/o
Sx can begin in 40’s
40-50% have FHx of FTD
imaging for FTD and findings
MRI
- FTD: Focal atrophy of frontal, insular, and/or temporal cortex - Atrophy begins focally in one hemisphere before spreading to anatomically interconnected cortical and subcortical regions
- Behavioral variant FTD: Medial and orbital frontal and anterior insula degeneration
- Semantic variant Primary Progressive Aphasia (PPA): Anterior temporal degeneration
- Non-fluent/agrammatic Primary Progressive Aphasia: Dominant hemisphere lateral frontal and precentral gyrus atrophy
presentation of FTD
3 clinical syndromes all insidious in onset
-
Behavioral variant (bvFTD) - MC
- Changes in personality, Apathy, disinhibition, compulsivity, loss of empathy, and overeating -
Semantic primary progressive aphasia variant
- Loss of ability to decode/recalling words, object, person-specific -
Primary progressive aphasia (non-fluent/agrammatic variant)
- Inability to produce words, often with prominent motor speech impairment
- Broca’s area
management for FTD
- Safety and driving as in AD
- Regular exercise
- Speech therapy in primary progressive aphasia variants
- Behavioral therapy
- Non-pharm 1st line: Distraction, redirection, offer simple choices, avoid overstimulation
- Pharm only if behavioral fails - SSRI or trazodone
Survival from sx onset: 8-10 yrs - shorter in behavioral variant of FTD
An accumulation of CSF that causes enlargement of the ventricles in the brain and compression of surrounding structures
Normal Pressure Hydrocephalus (NPH)
cause of Normal Pressure Hydrocephalus (NPH)
- CSF builds up inside the brain
- Idiopathic
- Secondary: underlying condition leads to inflammation and fibrosis at base of brain and/or arachnoid granulations, impairing CSF resorption
presentation of normal pressure hydrocephalus
- abnormal gait, UI, and dementia
- After intervention - gait improves, but dementia & incontinence does not
management for normal pressure hydrocephalus
-
Ventricular shunting
- MC shunting into abdomen (ventriculoperitoneal) - Fluid gets absorbed
- into the heart (ventriculoatrial) - Fluid filters into circulation
diagnostics for NPH
-
MRI/CT - Hallmark: ventriculomegaly in the absence of, or out of proportion to, sulcal enlargement
- Applies pressure to cerebral cortex = sx - High-volume LP
- Normal opening pressure
- Remove 30-50 cc of CSF
- Assess gait before and 30-60 mins after
- Improvement in gait = good prognostic for ventricular shunt placement
A disorder characterized by an acute change in attention and cognition due to an underlying illness, stressor or precipitant exposure
May be the only sign of an underlying illness in older patients
Delirium
greatest RF for delirium
preexisting cognitive impairment, specifically dementia
presentation of delirium
- Acute onset (hrs-d) of cognitive impairment and functional decline
- sx may fluctuate throughout the day
- Attention deficits - Reduced ability to direct, focus, sustain, shift attention
- Cognitive impairment - Memory deficit, disorientation, language, visuospatial ability, perception
3 concurrent approaches are involved in the treatment of delirium:
- Identification and tx of underlying
- Eradication or minimization of contributing factors of delirium
- Management of delirium sx
how to identify and tx underlying medical cause of delirium?
- A complete H&P should be performed
- Complete review of the medication history
- prescription, OTC, herbals, DDI - Kidney and liver function status should be assessed & medication dosage/frequency adjusted accordingly - Check for metabolic processes
- Selected laboratory and radiologic screening tests
- Evaluate for an occult infection
nonpharm management of delirium sx
- Frequent reorientation
- Environment optimization
- Sensory deficit correction
- Avoiding restraints
- Mobility/self-care
- Sleep hygiene
pharm strategies for delirium sx
- Reserve for severely agitated individuals whose behavior:
- Threatens medically necessary care (such as mechanical ventilation)
- Poses a safety hazard - Start at the lowest dose possible and for the shortest period due to risk of worsening confusion
- Goal: awake and manageable pt, not sedated
- meds
- typical antipsychotics: haloperidol
- atypical - olanzapine, quetinapine, risperidone/ziprasidone
- benzos
pros vs cons of typical antipsychotics for delirium
- Pros:Proven/tested, IV/IM/oral, oral formulation < QTc prolonging, pharmacokinetically optimal
- Cons:Sedation, hypotension, acute dystonia, extrapyramidal, anticholinergic SE, worsens Parkinson disease rigidity
pros vs cons of Olanzapine for delirium
- Pros:< extrapyramidal sx, dissolvable tabs
- Cons:Increased anticholinergic SE can worsen confusion, QTc prolongation
pros vs cons of quetiapine for delirium
- Pros:Sedating effect helps maintain sleep–wake cycle
- Cons:Oral formulation only, QTc prolongation
pros vs cons of risperidone/ziprasidone
- Pros:Sedating effect helps maintain sleep–wake cycle, oral and IM
- Cons: very sedating, QTc prolongation, tardive dyskinesia
pros vs cons of benzos for delirium
- Pros:Used for alcohol/sedative withdrawal; lorazepam is 1st choice bc of decreased half-life, no active metabolite, IV version
- Cons:Generally not recommended bc oversedating, worsens confusion
clinical course and prognosis for delirium
- Delirium is essentially a fully reversible condition, once underlying cause is identified and treated
- Pts who develop delirium have been found more likely to be dx w/ dementia later
delirium RF and tested interventions
- cognitive impairment - orienting communication, therapeutic activies
- immobilization - early mobilization, minimizing immobilizing equipment
- psychoactive meds - restricted use of PRN sleep and psychoactive meds, nonpharm for sleep and anxiety
- sleep deprivation - noise reduction strats, scheduling PM meds/procedures/nursing activities to allow uninterrupted period of sleep
- vision impairment - vision aids, adaptive equipment
- hearing impairment - amplifying devices, instruct staff in communication methods
- dehydration - early recognition and volume repletion
