Background
Definition
- Acquired cognitive decline that impairs activities of daily living (ADLs)
- Without impairment of ADLs, it is referred to as mild cognitive impairment (MCI)
- At least one cognitive domain affected (complex attention, executive function, learning and memory, language, perceptual-motor, social cognition), with poor ADLs and iADLs and no other cause identified
- Early-onset is prior to 65 years
Etiologies
- Alzheimer disease: insidious onset and gradual progression, usually starting with memory and learning but also behavioural and psychological manifestations
- Vascular dementia
- Multi-infarct
- Diffuse white matter disease (Binswanger's)
- Chronic alcohol use
- Parkinson disease
- Drug or medication intoxication
- Less common
- Vitamin deficiencies
- Thiamine (B1), causing Wernicke encephalopathy
- Cobalamin (B12), causing subacute combined degeneration
- Niacin (B3), causing pellagra
- Endocrinopathy
- Organ failure
- Renal failure
- Liver failure
- Pulmonary failure
- Chronic infections
- HIV
- Neurosyphilis
- JC virus, causing progressive multifocal leukoencephalopathy (PML)
- Tuberculosis, fungal infections, and protozoa
- Whipple disease
- Head trauma and diffuse brain damage
- Dementia pugilistica
- Chronic subdural hematoma
- Postanoxia
- Postencephalitis
- Normal pressure hydrocephalus
- Neoplastic
- Primary or secondary brain tumour
- Paraneoplastic limbic encephalitis
- Toxins
- Drug, medication, and narcotic overdose
- Heavy metal intoxication
- Dialysis dementia (aluminum)
- Organic toxins
- Psychiatric
- Depression (pseudodementia)
- Schizophrenia
- Conversion disorder
- Degenerative disorders
- Huntington disease
- Dementia with Lewy bodies
- Progressive supranuclear palsy
- Multisystem atrophy
- Hereditary ataxias
- Motor neuron disease, such as amyotrophic lateral sclerosis (ALS)
- Frontal lobe dementia
- Corticobasal degeneration
- Multiple sclerosis
- Adult Down syndrome with Alzheimer disease
- ALS Parkinson dementia complex of Guam
- Prion disease (Creutzfeld-jakob and Gerstmann-Straussler-Scheinker diseases)
- Miscellaneous
- Sarcoidosis
- Vasculitis
- Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)
- Acute intermittent porphyria
- Recurrent non-convulsive seizures
- Vitamin deficiencies
Epidemiology
- About 20% have a reversible cause (primarily depression, hydrocephalus, and alcohol abuse)
Clinical Manifestations
| Disease | Early symptoms | Mental status | Neuropsych | Neuro | Imaging |
|---|---|---|---|---|---|
| Alzheimer dementia | Memory loww | Episodic memory loss | Initially normal | Initially normal | Entorhinal cortex and hippocampal atrophy |
| Frontal-temporal dementia | Apathy, poo judgement/insight, speech and language, hyperorality | Frontal/executive, language; spares drawing | Apathy, disinhibition, hyperorality, euphoria, depression | May have vertical gaze palsy, axial rigidity, dystonia, alien hand, or MND | Frontal, insular, and/or temporal atrophy; spares posterior parietal lobe |
| Lewy body dementia | Visual hallucinations, REM sleep disorder, delirium, Capgras (imposter) syndrome, parkinsonism | Drawing and frontal/executive; spares memory; delirium-prone | Visual hallucinations, depression, sleep disorder, delusions | Parkinsonism | Posterior parietal atrophy; hippocampi larger than in AD |
| Creutzfeldt-Jakob disease | Dementia, mood, anxiety, movement disorder | Variable, frontal/executive, focal cortical, memory | Depression, anxiety | Myoclonus, rigidity, parkinsonism | Cortical ribboning and basal ganglia or thalamus hyperintensity on MRI |
| Vascular dementia | Often but not always sudden and stepwise; variable early symptoms; apathy, falls, focal weaknesses | Frontal/executive, cognitive slowing; can spare memory | Apathy, delusions, anxiety | Usually motor slowing, spasticity; can be normal | Cortical and subcortical infarcts, confluent white matter disease |
Physical Examination
- Mental status examination, including affect
- Full neurological examination
- Cranial nerves, including eye movements
- Motor exam, with axial and appendicular rigidity and rule out stroke and UMN signs (as would be seen in ALS)
- Sensory examination, first light touch before cortical sensory function
- Comment on signs of Parkinsonism
- Cerebellar examination
Investigations
- The goal is to rule out reversible causes
- Laboratory
- TSH to rule out hypothyroidism
- Vitamin B12 to rule out B12 deficiency
- CBC for anemia and occult infection
- Electrolytes
- Imaging
- CT or MRI brain to rule out strokes, NPH, and tumour(s)
- Age <60
- Rapid, unexplained decline (1-2 months)
- Short duration of dementia (<2 years)
- Recent head trauma
- New neurological symptoms
- History of cancer
- ...
- ...
- CT or MRI brain to rule out strokes, NPH, and tumour(s)
- Optional
- Laboratory
- Lumbar puncture
- Liver and renal function
- Urine toxicology
- HIV
- Apolipoprotein E
- Syphilis screen
- Parathyroid function
- Adrenal function
- Urine for heavy metals
- ESR
- Imaging
- Chest x-ray
- Angiogram
- PET or SPECT
- Other
- EEG
- Psychometric testing
- Brain biopsy
- Laboratory
Cognitive Testing
- Clock draw is the most sensitive for executive dysfunction, and also tests visuospatial and language domains
- MoCA is the only one with a clock, so MoCA tests executive function (also, abstraction)
- Diagnosis is based on clinical history, though, not from cognitive testing
Management
Behavioural and Psychological Symptoms of Dementia (BPSD)
- Symptoms include psychosis, aggression, agitation, mania, apathy
- History most important
- Triggers for behaviour
- Reversible causes
- Risks of harm to self or others
- Non-pharmacologic interventions
- Make the environment nice
- Caregiver education
- Try not to use drugs, but can try...
- Risperidone for severe behaviours, but increases risk of death
- Document their behaviours over several weeks to document benefit or harm, then reassess every three months if antipsychotics are used
