Dementia

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
    • Hypothyroidism
    • Adrenal insufficiency and Cushing syndrome
    • Hypoparathyroidism and hyperparathyroidism
  • 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

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
    • ...
    • ...
• 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

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

Further Reading

• Canadian Dementia Guidelines CCCDTD4 2012