Dementia, Delirium, Depression Flashcards
1
Q
What are neuronal components of the normal aging process?
A
- Neurons decrease
- Glia increase in size and number
- Decline in nerves and nerve fibers
- Atrophy of brain and increase in cranial dead space
- Thickened leptomeninges in spinal cord
2
Q
What is the implication of the decreased number of neurons and increase in size and number of neuroglial cells in aging?
A
Increased risk for neurological problems or cerebrovascular accident
3
Q
What is the implication of the decline in nerves and nerve fibers during aging?
A
- Parkinsonism
- Slower conduction of fibers across the synapses
4
Q
What is the implication of the atrophy of the brain and increase in cranial dead space during aging?
A
- Modest decline in short-term memory
- Alterations in gait pattern: wide based, shorter stepped, and flexed forward
5
Q
What is the implication of thickened leptomeninges in spinal cord during aging?
A
- Increased risk of hemorrhage before symptoms are apparent
6
Q
What is the function of the glial cells?
A
- Support the neurons
- Remove pathogens
- Supply nutrients
7
Q
What is the function of ependymal cells?
A
- Control production and flow of CSF, brain metabolism, and waste clearance
8
Q
What is the function of astrocytes?
A
- Perform metabolic, structural, homeostatic and neuroprotective tasks including stabilizing and regulating the blood brain barrier
9
Q
What is the function of microglial cells?
A
- Specialized macrophages that remove damaged neurons and infections, maintaining the heal of the CNS
10
Q
What are oligodendrocytes?
A
- Myelinating cells of the CNS
- Proliferate, migrate, differentiate, and myelinate to produce the insulating sheath of the axon
11
Q
What happens to DNA during normal aging?
A
- DNA damage
- Malfunctioning DNA damage response (DDR)
12
Q
What does increased size and # of neuroglial cells lead to?
A
- Reduced microglia migration and activation –> chronic pain
- Oligodendrocytes reducing myelin –> leukodystrophy, MS, or neuromyelitis optics
- Reduced astrocyte function (supply nutrients)
13
Q
What does decreased # of neurons lead to?
A
ALS, parkinson’s disease, stroke, traumatic injury
14
Q
What is cerebral atrophy?
A
A loss of neurons and the connections between them
15
Q
What are the 2 types of cerebral atrophy?
A
Generalized and focal
16
Q
What diseases are associated with cerebral atrophy?
A
- Stroke and TBI
- Alzheimer’s disease, Pick’s disease, and fronto-temporal dementia
- Cerebral palsy (lesions may impair motor coordination)
- Huntington’s disease (genetic mutations)
- Leukodystrophies (destroys myelin sheath around axons)
- Mitochondrial encephalomyopathies (interferes with basic function of neurons)
- MS (inflammation, myelin damage, and lesions in cerebral tissue
- Infectious diseases (encephalitis, neurosyphilis, AIDS; infectious agents or the inflammatory reaction)
17
Q
What are symptoms of cerebral atrophy?
A
- Dementia
- Seizures
- Aphasia
18
Q
What is dementia?
A
- Progressive impairment of memory and intellectual function 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
19
Q
How can seizures due to cerebral atrophy present?
A
- Disorientation
- Repetitive movements
- Loss of consciousness
- Convulsions
20
Q
What are aphasias?
A
Disturbances in speaking and understanding language
21
Q
How does receptive aphasia present?
A
Impaired comprehension
22
Q
How does expressive aphasia present?
A
Odd choices of words, the use of partial phrases, disjointed clauses, and incomplete sentences
23
Q
What is a leptomeninge?
A
Arachnoid mater and pia mater (2 innermost meninges that cover brain and spinal cord)
24
Q
What are normal aging and cognitive function changes?
A
- Difficulty recalling names or locations of placed objects, often to remember at a later time without functional impairment
- Subtle deficits in memory function that are not severe enough to disturb/delay life
- Learning remains intact: 3 word recall
25
What is the spectrum of cognitive impairment in older adults?
Normal cognitive changes seen with aging --> mild cognitive impairment (MCI) pathology --> dementia
26
What is the goal of assessment of cognitive impairment?
Early identification of reversible causes
27
How should the history be obtained from cognitively impaired older adults?
From the patient and verified by a reliable source
28
What diagnostic labs can be performed for cognitive impairment in an elderly adult?
* Vit B12 and TSH
* Additional labs on case-by-case basis: LFT, rapid plasma reagent (RPR-syphilis), HIV serology, paraneoplastic antibodies (autoimmune encephalitis)
* Lumbar puncture (R/O normal pressure hydrocephalus and CNS infections
29
What imaging can be performed for cognitive impairment in an elderly adult? Why?
Noncontrast CT/MRI
Helps rule out/in stroke, small vessel disease, tumor, subdural hematoma, normal pressure hydrocephalus
30
What are characteristics of mild cognitive impairment?
* Intermediate state between normal cognition and dementia
* Trouble remembering names and appointments
* Difficulty solving complex problems
* Testing shows abnormal memory but no functional impairment
* Subjective complaints of memory loss by family
* d/t age-related neurodegenerative disease
31
How is mild cognitive impairment managed?
* Look for reversible causes (medication side effects, sleep disturbances, depression, vitamin B12 deficiency, hypothyroidism)
* Identify and modify vascular risk factors
* Nonpharmacologic strategies
32
What nonpharmacological strategies can be used for mild cognitive impairment?
* Regular exercise
* Cognitive training: jigsaw puzzle, reading 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
33
What are types of dementia?
* Alzheimer's
* Vascular
* Lewy Body
* Frontotemporal
34
What is the definition of dementia?
* Conditions in which there are deficits in multiple areas of cognitive function resulting in impairment in daily functioning (at any level)
35
What is the epidemiology of dementia?
* 5 million people with dementia in 2014 and increasing
* Prevalence doubles every 5 years after 60
36
What is Alzheimer disease?
* Neurodegenerative disorder
* Uncertain etiology and pathogenesis
* Damage to hippocampus and entorhinal cortex that are essential in memory formation\
* As neurons die, brain begins to shrink
* By final stage, brain shrunk significantly
37
What is the pathophysiology of alzheimer disease?
* 2 types of cerebral cortex lesions: amyloid plaques and neurofibrillary tangles
* Unknown if lesions cause or result from AD
38
What is the pathophysiology of neurofibrillary tangles?
* Tau protein breakdown and adhere to each other instead of the microtubules
* Results in inadequate transport from the cell body to end of axon, preventing neuron communication
## Footnote
Tau proteins =glue that holds microtubules in place
Microubule = functions in transportation in axon
39
What is a amyloid precursor?
* Protein found on membrane of cells throughout the body and concentrated in synapse of neuron
* Enzymes cut these proteins
40
What is a beta amyloid protein?
Sticky fragment of the APP that is released when enzymes present
## Footnote
APP = amyloid precursor protein
41
What is a beta amyloid plaque?
* Lesion consisting of beta amyloid proteins that occurs between neurons and thought to affect neuronal communication
* Prevents dendrites from communicating with each other
42
What are risk factors for Alzheimer disease?
* Increasing age
* Female sex
* Apo e (epsilon)4 gene on chromosome 19
* Hx of head trauma
* Lower education level
* Vascular disease
* Diabetes
* Down syndrome
* Family history
## Footnote
chromosome 19 APO e4 gene helps with cholesterol transport
Down syndrome has extra APP gene on chromosome 21 --> make more proteins
43
What is the classic triad in Alzheimer's disease?
* Difficulty learning and recalling information
* Visuospatial problems
* Language impairment
44
In addition to the classic triad, what clinical presentation may be present in Alzheimer's disease?
* Disorientation to time --> place --> person
* Behavioral changes: early- depression, apathy, irritability; late- agitation and psychotic symptoms (delusion, hallucinations, paranoia)
* Slow progression
* Family often associate with normal aging
* Patients often lack insight into symptoms
* Interferes with social, occupational, or daily functioning
45
What is the clinical presentation of mild AD?
* Often first noticed by those close to individual
* Longer time to perform daily tasks
* Recognize familiar places
* Recall new names
* Paying bills or handling money
* Word recall
* Losing or misplacing items
* Planning or organizing
* Remember new reading material
46
What is the clinical presentation of moderate AD?
* Symptoms more pronounced
* Recalling demographics (phone #)
* Easily lost
* Disoriented to place/time
* Short attention span
* Disorganized thought processes
* Repetitive statements
* Difficulty recognizing family/friends
* Choosing appropriate clothing
* Loss of new learning
* Psychotic symptoms
* Behavioral changes
* Trouble reading, writing
47
What is the clinical presentation of severe AD?
* Completely dependent on others for care
* All sense of "self" is gone
* Absent recognition of family/friend
* Weight loss
* Increased sleeping
* Increased infections: aspiration pneumonia MC
* Death often due to complicating illness
* Loss of bowel/bladder control
* Trouble swallowing
* Unable to communicate effectively
48
How is alzheimer disease diagnosed?
* R/O delirium and other causes of dementia
* Imaging: CT or MRI can r/o mass, monitor progression
49
What can be seen on CT or MRI of a patient with Alzheimer disease?
* Diffuse cortical and/or cerebral atrophy
* Greater degree of hippocampal atrophy
* Progressive atrophy of medial temporal lobes
50
What can be seen on CT/MRI of a patient with frontotemporal dementia? Vascular dementia?
* Frontotemporal = diffuse cortical or cerebral atrophy of frontal lobe
* Vascular pathology = vascular dementia
51
How is alzheimer disease managed?
* Acetylcholinesterase inhibitors = first line at any stage of disease
* If moderate-to-severe or unable to tolerate cholinesterase inhibitors, NMDA receptor antagonists
* Nonpharmacologic interventions
* Behavioral management
52
What is the MOA of acetylcholinesterase inhibitors?
Works as a neurotransmitter to increase acetylcholine at neuronal synapses
53
What is the effect of acetylcholinesterase inhibitors?
slows the progression of AD
54
What are the FDA approved acetylcholinesterase inhibitors?
* Donezepril
* Galantamine
* Rivastigmine
* Aricept and Razadyne (po only)
* Exelon (po and transdermal)
55
What are the MC side effects of acetylcholinesterase inhibitors?
* Nausea
* Anorexia
* Sleep disturbance
* Diarrhea; take with food
56
What are serious side effects of acetylcholinesterase inhibitors?
* Bradycardia
* AV nodal block
* Syncope
57
How should acetylcholinesterase inhibitors be dosed?
Start low and go slow! Titrate up q 2 months until therapeutic dose achieved
58
What is the mechanism of action of NMDA receptor antagonists?
* reduces the destruction of cholinergic neurons and may inhibit B-amyloid production, thereby preserving memory
59
What is the effet of NMDA receptor antagonists on AD?
Slows the progression of the disease
60
What is the name of the NMDA receptor antagonist?
Memantine
61
What is the combo NMDA/cholinesterase inhibitor?
* Namzaric
* Indicated for moderate to severe AD
62
What are nonpharmacologic interventions for AD?
* Physical activity and exercise
* Mentally stimulating activities
* Social activities
63
What is behavioral management for AD?
* Nonpharmacologic therapy --> music therapy, exercise, remove extraneous noise and clutter, simplify tasks, develop daily routine
* Pharmacologic therapy --> SSRI for depression, agitation, sexual inappropriateness; trazodone to improve sleep wake cycle
* Refer to geriatric psychiatrist if unable to control symptoms
64
What is patient (family) education for AD?
* Assess driving safety, pill box, electronic reminders
* Appropriate supervision or limited use of 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: NIA, Caring for AD, Communication strategies, legal and financial planning
* Respite care services and adult daycare: NIA
* Local support groups: alzheimer's association
65
What are complications of Alzheimer disease?
* Worsening of comorbid conditions due to treatment adherence issues
* Increased risk of developing delirium in response to medical illness or surgery
* Advanced AD leads to poor nutritional intake, urinary incontinence, skin breakdown, and infections
66
What should you know about the course of AD?
* Rate of progression depends on patient
* Discontinue AchEI and NMDA once patient unable to express their needs
67
What is the definition of vascular dementia?
* Gradual or acute cognitive dysfunction
* Clinical or radiographic evidence of cerebrovascular disease, often with AD
68
What is the pathophysiology of vascular dementia?
* Pathophysiologic, small, micro-ischemic changes in brain
* Not enough for focal deficits but lots can damage neuro function
69
What is the clinical presentation of vascular dementia?
* Memory impairment, often less severe than AD
* Difficulty of timed activities and executive functions (one minute semantic test)
* Behavioral and psychological symptoms as in AD
* Depression often more severe than AD
* Focal neuro deficits not commonly seen
70
What imaging can be performed and its result for vascular dementia?
MRI showing small infarcts **white matter lesions**
71
How is vascular dementia managed?
Same as AD
Cholinesterase inhibitors, memantine, nonpharmacological therapy
72
What are vascular risks to identify and treat with vascular dementia?
* HTN
* Smoking
* DM
* Statins
* Antiplatelets (if hx of TIA or ischemic stroke)
73
What is the definition of dementia with lewy bodies?
* Dementia with lewy bodies on histopathology of brain tissue
74
What is the etiology of dementia with lewy bodies?
* Lewy bodies are deposits of alpha-synuclein
* Alpha-synuclein is naturally found at presynaptic terminals and plays role in neurotransmitter release
75
What is the pathophysiology of dementia with lewy bodies?
* Exact not understood
* Unknown if alpha-synuclein deposits cause damage or form as protective response
* Similar lesions in Parkinson's disease
76
What is the epidemiology of dementia with lewy bodies?
* Average age of onset is 75 but range from 50-80
* Slight male predominance
* Mostly sporadic- very rare occurance of family history
* Occur concomitantly with AD in 40% of patients
77
What is the core clinical presentation of dementia with lewy bodies?
* Insidious fluctuating cognitive impairment (day to day)
* Memory less affected than AD
* Visuospatial abilities, problem solving, and processing speed more severe than AD
* Spontaneous Parkinsonism
* Visual hallucinations (rare in AD)
* Delusional misidentification
78
What is the hallmark of dementia with lewy bodies?
Spontaneous parkinsonism
* Bradykinesia, bilateral limb rigidity, flat affect, postural instability, gait changes
* Less likely to involve tremors or respond to levodopa
79
What is often the first symptoms of dementia with lewy bodies that helps distinguish from AD?
delusional misinterpretation
80
What are additional presentations that may occur in dementia with lewy bodies?
* REM sleep disorder
* Vivid and scary dreams (may be acted out verbally or motorically)
* Sensitivity to antipsychotics (symptoms get worse, severe parkinsonism, NMS, life threatening rxn)
* Repeated falls
* Orthostatic hypotension, syncope, transient loss of consciousness
* Autonomic dysfunction
* Hypersomnia
* Hyposmia
* Apathy, anxiety, depression
## Footnote
hyposmia = decreased sense of smell
81
82
What diagnostics are used in dementia with Lewy bodies?
* R/o other causes
* MRI
* SPECT
83
What will be seen on MRI of DLB?
* Greater atrophy in basal ganglia structures and dorsal midbrain in DLB
* More pronounced cortical atrophy than PD
* Lewy bodies in pathohistological brain autopsy post mortem
## Footnote
Greater atrophy of medial temporal lobe in AD
Hippocampus atrophy more prominent in AD
84
What is the McKeith Criteria for DLB?
Probable DBL
* two or more clinical features of DLB are present, with or without indicative biomarkers
* OR only one core clinical feature is present, but with one or more indicative biomarkers
* Probable DLB should not be diagnosed on the basis of biomarkers alone
Possible DBL
* Only one core clinical feature of DLB is present, with no indicative biomarker evidence
* OR one or more indicative biomarkers are present, but there are no core clinical features
85
What is a SPECT and what are findings with dementia with lewy bodies?
* Nuclear imaging scan that integrates CT and radioactive tracer
* Reduction in dopamine uptake and perfusion
86
What is dementia with lewy bodies managed?
* Cholinesterase inhibitors
* +/- memantine - evidence mixed
* Atypical antipsychotics in very small doses only if psychosis severe
* SSRIs for depression
* Low doses of melatonin for REM disorders
* Parkinsonism treated same as PD: carbidopa-levodopa
* Fludrocortisone for orthostatic hypotension
87
What is the clinical course and prognosis of dementia with lewy bodies?
* Decrease in MMSE by 4-5 points per year
* Mean survival appx 10 years
* Risk factors for higher mortality include older age, hallucinations, greater degrees of fluctuation, and neuroleptic sensitivity
88
What is frontotemporal dementia?
* Umbrella term for clinical syndromes due to degeneration of the frontal and temporal lobes of the brain
* MC cause of early onset dementia (can begin in 40s)
* Often has family history
89
How is frontotemporal dementia diagnosed?
* MRI showing focal atrophy of frontal, insular, and/or temporal cortex
* Atrophy begins in one hemisphere and spreads to anatomically interconnected cortical and subcortical regions
90
What does behavioral variant FTD look like on MRI?
Medial and orbital frontal and anterior insula degeneration on MRI
91
What does non-fluent/agrammatic primary progressive aphasia look like on MRI?
Dominant hemisphere lateral frontal and precentral gyrus atrophy
92
What are the 3 clinical syndromes in frontotemporal dementia?
* Behavioral variant
* Semantic primary progressive aphasia variant
* Primary progressive aphasia
93
What is the clinical presentation of behavioral variant frontotemporal dementia?
* Insidious onset
* Changes in personality, do things they wouldn't normally do
* Apathy, disinhibition, compulsivity, loss of empathy, overeating
94
What is the clinical presentation of semantic/primary progressive aphasia variant?
* Loss of ability to decode/recall words, object, person-specific
95
What is the clinical presentation of primary progressive aphasia FTD variant?
* Inability to produce words, often with prominent motor speech impairment
* Affects broca's area
96
How is frontotemporal dementia managed?
* Safety and driving as in AD
* Regular exercise
* Behavioral therapy
97
What are components of behavioral therapy for frontotemporal dementia?
* Non-pharm first line: distraction, redirection, offer simple choices, avoid overstimulation
* Pharmacologic only if behavioral modification fails with SSRI or trazodone (start low, go slow)
98
What is the prognosis of frontotemporal dementia?
* Survival from symptom onset is approximately 8-10 years
* Often shorter in patients with the behavioral variant FTD
99
What is the definition of normal pressure hydrocephalus?
* accumulation of CSF that causes enlargement of the ventricles in the brain and compression of the surrounding structures
100
What is the pathophysiology of normal pressure hydrocephalus?
* CSF build up inside the brain
* Idiopathic NPH: no cause identified
* Secondary NPH: underlying condition leads to inflammation and fibrosis at base of brain and/or arachnoid granulations, impairing CSF resorption
101
What is the clinical presentation of normal pressure hydrocephalus?
* Abnormal gait
* Urinary incontinence
* Dementia
* After intervention, gait often improves but dementia/incontinence do not
102
How is normal pressure hydrocephalus managed?
* Ventricular shunting into the abdomen (MC) --> fluid gets absorbed
* Into the heart to enter circulation (LC) --> fluid enters circulation
103
How is normal pressure hydrocephalus diagnosed?
* MRI/CT (MRI preferred)
* High-volume lumbar puncture
104
What are findings of normal pressure hydrocephalus on MRI/CT?
* Ventriculomegaly in absence of or out of proportion to sulcal enlargement
* Applies pressure to cerebral cortex causing symptoms
105
What are findings on high-volume lumbar puncture for normal pressure hydrocephalus?
* Normal opening pressure
* Remove 30-50 cc of CSF
* Assess gait prior to procedure and 30-60 mins after
* Improvement in gait is good prognostic sign for ventricular shunt placement
106
What is the definition of delirium?
* Acute change in attention and cognition due to underlying illness, stressor or precipitant exposure
* May be only sign of underlying illness in older patients
107
What is the greatest predisposing risk for delirium?
preexisting cognitive impairment, specifically dementia
## Footnote
many predisposing risk factors are present
108
109
What is the clinical presentation of delirium?
* acute onset of cognitive impairment and functional decline
* symptoms fluctuate throughout day
* Attenion deficits: reduced ability to direct, focus, sustain, and shift attention
* Cognitive impairment: memory deficit, disorientation, lagnuage, visuospatial ability, perception
110
How is delirium managed?
* 1. identification and treatment of underlying medical cause
* 2. eradication or minimization of contributing factors
* 3. management of delirium symptoms
111
how is the underlying cause of delirium identified and treated?
* H&P
* Review of meds
* Kidney and liver function assessment for metabolci processes
* Lab/radiologic screening tests such as TSH, B12, hepatic enzymes
* Evaluate for occult infection with CBC, UA, FO
112
How are delirium symptoms managed non-pharmacologically?
* Frequent reorientation
* Environment optimization
* Sensory deficit correction
* Avoiding restraints
* Mobility/self-care
* Sleep hygiene
113
How are delirium symptoms managed pharmacologically?
* Reserve for severely agitated individuals who threaten medically necessary care/pose a safety hazard
* Start at lowest dose possible and for shortest period d/t risk of worsening confusion
* Goal: awake and manageable, not sedated
* Antipsychotics used: haloperidol, olanzapine, quetiapine, risperidone
* Benzodiazepines (lorazepam is choice due to decreased half life)
114
What is the clinical course and prognosis of delirium?
* fully reversible once cause identified and treated
* Patients with delirium are more likely to be diangosed with dementia later
