Dementia, Delirium, Metabolic Encephalopathies Flashcards
Features of dementia
Impairment of intellectual/cognitive function of sufficient severity to interfere with social/occupational activities
- Impaired memory (short- or long-term) with at least 1 of: impaired abstract thinking, impaired judgment, or other disturbance (ex: aphasia, apraxia, agnosia); plus other criteria
- -> now re-named Major Neurocognitive Disorder to remove stigma
Features of delirium
Delirium is a symptom, not a disease!
Clouding of consciousness with reduced capacity to shift, focus, and sustain attention to environmental stimuli
*Disorientation and memory impairment, with at least 2: perceptual disturbance, incoherent speech, sleep-wake disturbance, inc/dec psychomotor activity; clinical features that develop over hours or days and show fluctuation
–> will usually have lab evidence of medical etiology, and not explained by preexisting or evolving dementia
Features of depression
aka pseudodementia
- date of onset is known, symptom duration is short, family often aware
- puts forth little/no effort on tasks
- no cortical signs
How to distinguish dementia, delirium, and depression
- DM is insidious onset and progressive deterioration over months to years; DL is acute/subacute deterioration over days to weeks
- DM is progressive, DL is fluctuating
- DM has no disorder of alertness, DL has altered level of consciousness, excitable, delusions, and hallucinations
- DL has hyperactive autonomic function
- DL IS REVERSIBLE
Causes of major NCD
- Alzheimer’s
- CV disease
- Frontotemporal lobe degeneration
- Lewy Body disease
- Huntington’s disease
- TBI
- HIV associated dementia
Causes of Dementia (partial list)
- neurodegenerative diseases (AD, DLB, FTD, PD, HD, WD, ALS, etc.)
- vascular dementia
- head trauma
- drugs/toxins/ethanol
- brain tumors
- normal pressure hydrocephalus
- infections
- metabolic disorders
- nutritional deficiencies
Alzheimer’s disease:
Clinical features
Progressive deficit in memory and 1/more other cognitive areas.
- insidious onset of memory loss, esp. short-term memory
- followed by deficits in attention, language, visual-spatial orientation, abstract thinking, judgment, and eventually personality/behavioral changes
- onset between ages 40-90, most after 65y
Alzheimer’s disease:
Pathological features
Diagnose the disease post-mortemly:
- loss of neurons
- neuritic plaques (dystrophic synapses containing tau protein) surrounding aggregates of B-amyloid
- neurofibrillary tangles (NFTs; which are pyramidal cells filled with aggregations of hyper-phosphorylated tau proteins)
- Parietal lobe has more plaques than tangles
Imaging:
- atrophic nucleus basalis (ACh center)
Alzheimer’s disease:
Inconsistent features
- sudden/acute onset
- focal neurologic findings
- seizures or gait disorder
Alzheimer’s disease:
Genetics
Early onset (AD) - 5-10%
- Chr 21 - APP (*tracks with Down’s syndrome)
- Chr 14 - Presenilin 1
- Chr 1 - Presenilin 2
Late Onset (sporadic) - 90-95%
- Chr 19 - ApoE4 (3 alleles, E4 is the worst)
- Chr 12 - a2-Macroglobulin (2 alleles)
- Chr 10 - others
- These are risk factor genes only, non-heritable
Alzheimer’s disease:
Risk factors
- age
- genetics (Chr 19, 12, 19)
- Down’s syndrome (Chr 21)
- weak ones include: mental inactivity, females, HCL, smoking
Alzheimer’s disease:
Treatment
Directed treatment:
- AChE and BuChE inhibitors
- immunotherapy against B-amyloid
- NMDA receptor blockers
Symptomatic treatment:
- anti-depression agents
- anti-anxiety agents
- tx delusions, hallucinations, insomnia
Dementia with Lewy Bodies (DLB)
- presents clinically similar to PD, btu differentiated by early onset of dementia too (with hallucinations, delusions, cognitive difficulties)
- Lewy bodies are eosinophilic, spherical inclusions with halo appearance in cytoplasm of neurons of SN, comprised of neurofilaments, a-synuclein, and ubiquitin
Tauopathies
- pathology with accumulations of hyper-phosphorylated tau proteins
- include: Pick’s disease (w/wo Pick bodies); FTD w/ Parkinsonism; Corticobasal ganglionic degen (CBD); PSP
Frontotemporal dementias (FTDs)
- degeneration of the frontal and temporal lobe that’s non-AD and non-vascular
- Clinical: prominent personality and behavioral changes early on, with no real memory impairment; behavior changes include loss of personal awareness, social comportment, disinhibition, impulsivity, distractibility, hyperorality, speech output change
- Path: NFTs and/or Pick bodies comprised of intracytoplasmic ubiquitin and hyper-phosphorylated tau protein
