Alzheimer's and Dementia Flashcards
Amnesia
impairment of ability to store new memories (anterograde) or recall previously stored memories (retrograde)
Aphasia
loss of ability to comprehend and/or produce language
Apraxia
impaired performance despite being physically able to do so
Agnosia
inability to recognize or identify objects despite intact sensory function
Executive dysfunction
abnormalities in one or more capacities including planning, organizing, decision-making, strategizing, cognitive flexibility, impulse control, sequencing, abstract reasoning, and social appropriate behavior
Describe the different types of memory
1) Short-term memory
2) Long-term memory:
Declarative
• Conscious, recollective, explicit
• Medial temporal lobe dependent
• Involves: event/fact learning; recall, recognition; episodic and semantic memory
Non-declarative • Implicit memory • Medial temporal lobe Independent Involves: • Repetition priming (perceptual and conceptual) • Sensorimotor adaptation • Classical conditioning • Skill learning
Describe the neuroanatomic substrates of memory
Neuroanatomical substrates:
Hippocampus
• Critical for consolidation of info into LTM
• Also for immediate coding of memory
Medial temporal lobe
PFC (lesions → less efficiently encoding and retrieval, impaired recall; problems with STM)
Cellular substrates
• Long-term potentiation = activity-dependent strengthening of synaptic connectivity = underlies formation and retention of memory
• Result from cascade of events → consolidation at cellular level
Correlate the neuropathological changes found in Alzheimer’s disease with its clinical manifestations, in particular, amnesia.
Cortical atrophy
o Widened sulci, narrowed gyri
o Most severe in frontal and temporal lobes
Hydrocephalus ex vacuo
o No increase in pressure, but increased size of ventricles & shrinkage of brain structures
Senile plaques
o Networks of fibrillary material in loose, disorganized arrangement
o From swollen, degenerated neuronal processes around a central amyloid deposit
Neurofibrillary tangles
o Accumulations of large numbers of paired helical filaments in neuron cytoplasm
o Birefringent under polarized light
o Seen with silver stains
Microglial activation
o Non-specific reaction to injury = low-grade inflammation
Amyloid angiopathy
Dementia Definition
Syndrome of acquired persistent decline in several areas of intellectual ability: o Impaired memory o Disturbed language o Visuospatial abnormalities o Decreased problem-solving, abstraction and other executive functions o Reduced attention o Apraxia o Agnosia
50% of dementia = caused by Alzheimer’s
Alzheimer’s: clinical features
Cognitive impairment:
Impaired encoding & recall of memory
o Memory loss occurs 2-3 years prior to onset
o Early: STM affected
o Eventually: LTM affected
o Progressive decline
Language: word-finding difficulties, reduced verbal fluency
Visuospatial: abnormal clock-drawing test
Functional impairment:
• Decreased ability to perform instrumental, then basic, activities of daily living (ADLs)
• Increased reliance on caregivers
Behavioral & psychological symptoms (BPSD)
• Depression, anxiety, irritability, apthay, insomnia, paranoid delusions, visual hallucinations, restlessness, yelling, swearing, physical aggression
Alzheimer’s: risk factors
• Age (most between 75-85)
- Genetics:
- Apolipoprotein e4 allele
- Down syndrome (trisomy 21)
- Family history
- TBI history
- Late-life depression
- Cardiovascular risk factors (HT, dyslipidemia, atrial fibrillation, obesity, smoking)
Alcohol use:
• Abstinence = slightly higher risk
• Mild-moderate use = lowest risk
• Excessive use: higher risk
Alzheimer’s: protective factors
- Genetics = Apo-e2
- Medication exposure: NSAIDs, statin
- Mild/moderate alcohol use
- Omega-3 fatty acids
- Physical exercise
- Cognitive stimulation
Vascular dementia
o Causes 8% of dementia
o Dementia due to cerebrovascular disease
• Symptoms depend on location of disease
Present with abnormal neurological exam
o Course = “step-wise”
• Sudden changes in cognition and functioning
• Separated by periods of stability
o Often coexists with Alzheimer’s
o Age range: 65-75 years
o Vascular risk factors (high cholesterol, HT) = higher risk of cardiac disease, death
Lewy Body Disease
o Causes 5% of dementia
Types:
Parkinson’s disease dementia = onset of cognitive symptoms at least 1 year after onset of motor symptoms
• Impairment due to Lewy bodies throughout subcortical regions
Dementia with Lewy Bodies (DLB):
• Fluctuating symptoms
• Visual hallucinations
• Cognitive impairment
• Less severe parkinsonian symptoms than in Parkinson’s Disease
• Lewy bodies are found in cerebral cortex
Frontotermporal Dementia
o Causes 8% of dementia
Collection of syndromes:
• Presence of tau inclusion bodies
• Lobar degeneration of frontal and/or temporal lobe
• Behavioral disturbance and/or aphasia
o Onset: 50-65
o May be a family history of early onset dementia
Symptoms may be:
• Like MDD: apathy, amotivation, anergia
• Like mania: disinhibition, impulsivity, irritability
o Cognitive enhancing medications NOT helpful
o Course = more rapid; death occurring within average 5 years
List the treatments available for dementia, including psychotropic medications, psychosocial interventions and caregiver interventions.
Medications
o Cognitive enhancing medications: donepezil, galantamine, rivastigmine, memantine
o Delay cognitive decline
o Treat: alzheimer’s, vascular dementia, and dementia with Lewy bodies
o NOT effective for Frontaltemporal dementia
Behavioral interventions
o Treat depression, anxiety, psychosis, agitation
o Includes: redirection, distraction techniques, soothing music, etc.
If interventions fail or patient behavior is dangerous:
o SSRIs
o Atypical antipsychotics (caution because increase mortality in elders with dementia)
Caregiver interventions
o High risk of depression (33%) = support and education
Parkinson’s Disease
Symptoms: o Bradykinesia o Muscular rigidity o Resting tremor o Impaired balance o Some patients may have cognitive decline (Parkinson’s disease dementia)
5-10 year progression to rigid, akinetic state
Cause:
o Decrease in striatal dopamine levels (normally inhibitory)
o Result: unopposed striatal GABAergic neurons → excessive excitatory ACh release
Explain why certain antipsychotic drugs cause Parkinsonism and what drugs can be used to treat this iatrogenic condition.
• Effects = usually reversible
Includes:
Antipsychotics: Butyrophenone, phenothiazine
• Block brain dopamine receptors
Reserpine (at high doses)
• Depletes brain dopamine
MPTP (byproduct from synthesis of illegal designer drug MPPP)
• Irreversible
• Destroys dopaminergic neurons in nigrostriatal tract
• Treating with MOAIs = protective in animals
Describe the main antiparkinsonism mechanisms of action of levodopa, dopamine receptor agonists, selegiline, amantadine, and muscarinic blocking drugs.
Increase DA by stimulating DA synthesis
o Levodopa = enters brain, converted to dopamine
Increase DA by inhibiting DA metabolism
o Carbidopa = inhibits DOPA decarboxylase in periphery
o Entacapone = inhibits COMT → enhances L-DOPA accumulation
o Selegiline = inhibits MAO type B
Directly stimulate DA receptors with DA agonists
o Pramipexole = D2 and D3 full agonist
o Ropinirole = D2 and D3 full agonist
o Bromocriptine = D2 full agonist; D1 partial agonist
Block CNS ACh receptors with muscarinic antagonists
o Trihexyphenidyl
o Benztropine
o Diphenhydramine = H1 blocker (significant antimuscarinic effect)
o Amantadine = unknown mechanism
List the drugs that inhibit DOPA decarboxylase and COMT and describe their uses in Parkinsonism.
- Carbidopa = inhibits DOPA decarboxylase in periphery
- Entacapone = inhibits COMT → enhances L-DOPA accumulation
- Both: function to enhance amount of DA reaching brain (less metabolized in periphery)
Describe the two major pharmacological approaches used to treat Alzheimer’s disease: inhibition of acetylcholinesterase and antagonism of the NMDA receptor.
AChE inhibitor
o Alzheimer’s = decrease in ACh and nicotinic receptors → goal is to increase ACh
o Also = AChE acts as molecular chaperone → forms stable complexes with Aβ → accelerates amyloid fibril formation
Includes:
• Donepezil
• Rivastigmine
• Galantamine
NMDA receptor antagonist
o Chronic glutamatergic activity may have role in Alzheimer’s pathogenesis
o Glutamate stimulates NMDA receptors → increased neuronal [Ca2+]
o Excessive Ca2+ can damage neurons
o Ex: Memantine
List methods used to assess cognition in patients suspected of having a neurocognitive disorder.
Mini-mental status exam (MMSE)
o Assess orientation to place and time
o Registration and recall of 3 small objects
o Attention, calculation, naming, repetition
o Reading comprehension, writing a sentence, copying a figure, following a 3-step command
St. Louis University Mental Status Exam (SLUMS) o Assess orientation to place and time o Registration and recall of 5 objects o Attention, calculation o Naming animals o Drawing a clock o Identifying a shape o Recalling a story
Animal naming test
o Name as many animals as possible in 1 minute
o Normal score is ≥15
o Tests executive function
Clock-drawing test
o Draw a clock and set hands to specific time
o Tests visuospatial and executive function
Min-Cog
o Combines clock-drawing test with 3-object recall
o A quick cognitive screen in primary care settings
Confusion Assessment Method (CAM) o 94% sensitive o 90% specific o 91% PPV Diagnoses deliria if met all criteria: • Acute change in mental status and fluctuating course • Impaired attention • Either disorganized thinking or altered level of consciousness
Delirium: Epidemiology
o Varies depending on setting: o Older adults in a community: 0.8% o Hospitalized with cancer: 25% o Nursing home residents >75 years: 60% o Terminally ill: 80%
Delirium: pathophysiology
o Multi-factorial
o Contributors: pain, constipation, dehydration, nutrition, sensory deprivation, changes in environment
Toxic causes:
- sedative-hypnotics
- anticholinergic drugs
- opiates
- steroids
- antibiotics (quinolones)
Metabolic causes:
- hyponatremia, hypernatremia, hypocalcemia, hypercalcemia
- hypoxemia, hypercapnia
- hypoglycemia, hyperglycemia
- renal failure (uremia), hepatic failure (hepatic encephalopathy)
Infectious causes:
-UTI (in older adults), pneumonia, meningitis, encephalitis, sepsis, CNS abscess
Other causes:
- traumatic brain injury
- stroke
- epilepsy
- cardiac ischemia or arrhythmia
Final common pathway = reticular activating system (RAS)
• Associated with arousal and attention
• Facilitates sensory input to cortex via cholinergic projections from brainstem to thalamus
• Projects to cerebral cortex
Delirium: risk factors
o Age o Cerebrovascular disease o Neurodegenerative disease o Chronic medical conditions o Recent surgery o Being in unfamiliar environment o Psychotropic medications (especially sedative-hypnotics or drugs with anticholinergic properties) o Malnutrition
Delirium: clinical presentation
o Delirium = acute change in mental status due to underlying medical condition
o Arise over short time (hours-days)
Features: • Waxing and waning symptoms • Impairment of attention • Altered level of consciousness o Associated symptoms: disorientation, disturbance of sleep-wake cycle, perceptual disturbances, paranoia, memory loss, emotional disturbances
Delirium: prognosis
o High mortality rate (May be marker for underlying disease)
o 15% elderly die within 1 month; 25% die within 6 months
Associated with: • Worse surgical outcomes • Increased surgical complications • Increased disability • Longer length hospital stay o Many do not return to premorbid cognitive and functional level
Describe the management of delirium.
• Treat underlying condition:
o Discontinue contributing medications
o Usually resolves within hours/days later
- May need to be hospitalized
- Antipsychotic if patient agitated
- Avoid benzodiazepines (except to treat delirium tremors in alcohol withdrawal)
