Behavioral Science: Dementia 1-3 Flashcards
Age-associated cognitive changes
- Difficulty retrieving words and names
- Slower processing speed
- Difficulty sustaining attention when faced with competing environmental stimuli
- Learning new shit takes more effort
- No functional impairment
Mild cognitive impairment
- memory complaint corroborated by an informant
- objective memory impairment for age and education
- preserved general cognition
- normal ADL
- NOT demented
Amnestic MCI
- Memory loss not meeting criteria for dementia
- Progresses to AD at a rate of 10-15%/year (vs. 1-3% incidence in gen pop)
- May be earliest phase of AD
- Clinical dx (no formal test)
Dementia
Memory decline/impairment and at least one of the following:
- Aphasia
- Apraxia
- Impaired executive fxn
- Agnosia
Cognitive deficits must impact social and occupational function
Dx must be made in presence of a clear sensorium
Early onset AD
- ages 30-60
- rare, MC familial
- gene mutations: 1 (presenilin 2), 14 (presenilin 1), 21 (amyloid precursor protein) are abnormal
Late onset AD
- MC form
- After age 60
- Combination of factors
- Chromosome 19- apolipoprotein E4 gene implicated
Alzheimers disease
- MCC dementia, presents w/ deficits in recent memory, progressing to global impairment of cognition
- Usually sporadic and late onset
- AD
- Neuronal and synaptic loss affecting cortical and some subcortical areas (ex. nucleus basalis of Meynert)
Gross findings of AD
Cerebral atrophy especially affecting temporal, parietal, and frontal areas, with ventricular enlargement
Microscopic findings in AD
- Amyloid plaques consisting of extracellular deposits of beta-amyloid peptides, often associated w/ dystrophic plaques
- Amyloid Beta deposits in cortical and leptomeningeal arteries and arterioles
- Filamentous intracellular inclusions of tau protein called neurofibrillary tangles and neuropil threads
- Granulovacuolar degeneration
- Hirano bodies
Frontotemporal lobar degeneration
Types: Tau (MC), TDP, FUS
- Earlier onset than AD
- Lobar degeneration affects anterior frontal and superior temporal lobes, spares occipital and parietal lobes
- gross “knife edge” appearance
AD risk factors
- increasing age
- females
- family history of dementia
- less education, income, SES
- depression
- head injury
- low folate, B12
- elevated plasma homocysteine
- apolipoprotein E4 allele
- postoperative delirium
- alcohol abuse
Early symptoms of Ad
Cognitive: trouble keeping appointments, difficulty finding words, misplacing objects
Functional: difficulty driving, difficulty selecting clothes, missing appointments, problems at work
Behavioral: Subtle personality changes, social withdrawal, depression
Differences between depression v dementia
Depressed patients:
- demonstrate less motivation during cognitive testing
- Express cognitive complaints that exceed measured deficits
- Maintain language and motor skills
Brain imaging for AD
- Not routinely indicating, only considered when: focal findings on exam, rapid onset/decline, or Hx of falls/head trauma
- Nonspecific findings common in AD: lacunar infarcts, small vessel and white matter disease
Frontotemporal Dementia vs. Alzheimers
Frontotemporal dementia has:
- insidious onset, gradual progression
- early decline in social interpersonal conduct
- early impairment in regulation of personal conduct w/ lack of insight
- early emotional blunting
- characterized by behavioral abnormalities
- memory loss occurs LATER
Drugz for frontotemporal dementia
- No role for cholinesterase inhibitors
- Careful use of atypical antipsychotics
- Divalproex for behavioral control
- SSRIs for irritability, depression, impulsive behaviors
Drugz for Alzheimers
- Cholinergic therapy
- NMDA receptor antagonists
- Investigational agents
- Tx of neuropsychiatric sx
Why do anticholinesterases work in Alzheimers?
Because Alzheimers-associated degeneration of the basal nucleus of Meynert results in widespread Ach deficiency –> memory defects
Blocking degeneration of Ach leaves enough in synapse to slow progression of memory loss
Cholinesterase inhibitors for mild-moderate AD
- Tacrine (now obsolete)
- Donepezil
- Rivastigmine
- Galantamine
Glutaminergic tx for AD
- Memantine
Vascular dementia
- Multi-infarct dementia
- Cerebral amyloid angiopathy
- HTN-related small vessel disease
Hypertensive small vessel disease
- Arteriosclerosis of small arteries and arterioles supplying deep grey and white matter
- Lacunar infarcts
- Subcortical leukoencephalopathy
- Subcortical dementia: cognitive slowing, impaired problem solving, visuospatial abnormalities, disturbances of mood and affect
Vascular dementia sx
- “step-wise progression” - can be abrupt after CVA
- Usually seen w/ cardiovascular risk factors
- “Mixed” dementia with AD or Lewy Body is not unusual
- Emotional lability
Vascular Dementia tx
- Control cardiovascular risk factors: control BP, statins, stop smoking, control blood sugar, diet, exercise
- Cholinesterase inhibitors
Lewy bodies
Characterized by intracellular, fibrillar deposits of a presynaptic terminal protein called a-synuclein
Parkinsons Disease
- MC sporadic
- Resting tremor, akinesia, bradykinesia, rigidity, shuffling gait, postural instability
- Dopaminergic deficit
- Responsive to L-Dopa
Gross and microscopic neuropathology of PD
Gross: pallor of the substantia nigra
Microscopic: Degeneration and loss of the pigmented, dopaminergic neurons of the SNpc and other pigmented neurons of the brainstem, eg. locus coeruleus. Often contain 1+ eosinophilic inclusions called Lewy Bodies. Striatum, thalamus, and some cortical regions are FUNCTIONALLY AFFECTED by the loss of dopaminergic input.
Pathogenesis of PD
- a-synuclein is a pre-synaptic protein involved in regulation of synaptic vesicle trafficking
- Lewy bodies are composed primarily of fibrillar aggregates of a-synuclein (if in neural processes–> Lewy neurites)
- Aggregates are toxic and cause impairment of protein degradation, inhibition of oxidative phosphorylation, impairment of axonal transport, and cause oxidative stress
- Pesticide may be risk factor
Dementia with Lewy Bodies
- Sporadic, primarily late onset
- Memory frequently less affected than AD
- Frontal and subcortical features like deficits in attention and alertness are prominent
- Pronounced fluctuations and variations in symptoms
- Neuropsychiatric symptoms: visual hallucinations + delusions
- Motor symptoms of PD are variably present
Gross and microscopic neuropathology of Dementia w/ Lewy Bodies
Gross: Nigral pallor. Cortical atrophy is less severe than AD. Atrophy of limbic areas is often significant.
Microscopic:
- “Cortical”-type LBs in frontal, temporal, insular cortex, limbic areas
- Nigral LBs
- LNs, esp in hippocampus and striatum
- Plaques and tangles, dual dx of DLB and AD applies in most cases
Clinical Sx of LBD
- Short term memory loss, gradual onset
- Visual hallucinations
- Cognitive fluctuations
- REM sleep disorder
- Frequent falls
- Autonomic dysfunction
Drugz for LBD
- Cholesterase inhibitors for symptomatic support
- Trial of carbidopa/levodopa for severe movement sx
- AVOID antipsychotics (increased sensitivity)
- REM sleep disorder: clonazepam
Lewy Body dementia vs Parkinson’s dementia
LB: Onset of dementia WITHIN 12 months of parkinsonism
PD: Onset of dementia MORE THAN 12 months after Dx of
MMSE
- Standardized 30 point rating scale
- Screening tool, NOT diagnostic
- Not specific for dementia type
- Scoring can be impacted by age, education, ethnicity:
Normal 30-27
Mild 27-20
Moderate 20-10
Severe 10 or lower
MoCA
- Standardized 30 point rating scale
- Screening tool, NOT diagnostic
- Not specific for dementia type
- Scoring can be impacted by age, education, ethnicity:
Normal >26
Mild 18-26
Moderate 10-17
Severe
ADL vs IADL
ADL: walking, bathing, dressing, toileting, eating, etc.
IADL: cooking, driving, using computer, managing finances, managing medications
Adult home
- provides room and meals
- can add on assistance with daily activities
- no complex medical problems
- not always licensed or monitored by authorities
- cash only
Assisted living facility
- assistance with IADL
- can add on some basic ADL for extra fees
- No medical or nursing care onsite
- Cash only, not covered by medicaid/medicare
Skilled nursing facility
- Daily skilled nursing care, onsite medical care
- Dependent in all basic ADL
- Most patients have advanced dementia
- Cash until money is depleted
- Most residents on Medicaid
