Dementia

“An acquired disorder of cognitive function”

Causes

The potential causes of dementia are diverse, but the disorder is mainly due to neurodegenerative and/or vascular disease associated with increased age

• Alzheimer’s disease (60-80% of dementia cases)
• Cerebrovascular disease – vascular dementia (~20% of dementia cases)
• Parkinson’s disease
• Frontotemporal dementia (younger-onset, 40–60 years, memory generally remains intact)
• Dementia with Lewy bodies
• Huntington disease, Wilson disease

Risk Factors

• Age (>65 years)
• Family history
• Genetics (risk gene – apolipoprotein E-E4, deterministic gene – APP, PS-1, PS-2)
• Down Syndrome
• Alcohol consumption
• Smoking
• Diabetes
• Obesity
• Head trauma + repetitive injury (e.g. boxing)
• Cardiovascular disease

Clinical Presentation

• Memory impairment
• Cognitive impairment
  • Speech: aphasia, word-finding difficulties, semantic paraphasia
  • Intellectual capacities, reasoning, planning capabilities, and self-control
  • Spatial-temporal awareness (awareness of oneself remains stable for a long time)
  • Apathy
• Changes in personality, mood, and behaviour

• Early-stage – due to gradual onset, this stage is often overlooked
  • forgetfulness, losing track of the time, becoming lost in familiar places.
• Middle stage – at this stage, signs and symptoms become clearer and more restricting
  • becoming forgetful of recent events and names, becoming lost at home, increased difficulty with communication, needing help with personal care, behaviour changes, wandering and repeated questioning
• Late-stage – late-stage dementia entails total dependence and inactivity. Memory disturbances and physical signs and symptoms become more pronounced.
  • becoming unaware of the time/place, difficulty recognizing relatives and friends, increased need for assisted self-care, difficulty walking, behaviour changes that may escalate and include aggression

Pathophysiology

The reasons for this pathophysiology are still not fully understood

• Alzheimer’s disease:
  • Beta-amyloid plaques are derived from fragments of amyloid proteins
    • These fragments aggregate and clump to form plaques. These clumps of plaques interfere with neuron synapses and recruit immune cells → inflammation.
    • It is still not fully understood whether this process causes or is a result of the disease
  • Tau protein tangles (neurofibrillary tangles) are found inside of neurons. They are derived from the tau proteins on microtubules that support the inside of neurons.
    • In Alzheimer’s, these proteins are changed and aggregate to form tangles with the neuron microtubules → neurofibrillary tangles
    • These tangles reduce neuron communication → to cell death + neurodegeneration
  • Affect temporal lobe (learning + memory) → speaking + communication areas, as well as the frontal (thinking + planning) and parietal (sensory integration) lobe
    • ↑ progression through cortex → ­ neurodegeneration → cerebral atrophy/shrink

• Vascular dementia:
  • Reduced blood flow and oxygen delivery to the brain causes neuronal degeneration and cognitive dysfunction → vascular dementia

• Dementia with Lewy bodies:
  • Lewy bodies are abnormal protein structures derived from alpha-synuclein proteins found in terminal axons. They also feature in Parkinson’s disease.
  • If not processed correctly by the body → accumulation → harmful Lewy bodies
  • Symptoms include reduced cognitive abilities, problems with movement and trembling, hallucinations and sleepwalking/talking/ kicking

Investigations

• Patient and family history + physical examination
• Neurological examination, psychiatric evaluation
• Neuropsychological test – Mini-mental state examination (MMSE) with grading score, mini-cog test (name 3 objects → draw a clock → name the 3 objects)
• CT and MRI scans – differential diagnosis (type), rule out co-morbidities, monitor disease

Management

Target actions of acetylcholine + glutamate, manage comorbidities

• Cholinesterase inhibitors (donepezil, rivastigmine, galantamine)
  • Prevents Ach breakdown by acetylcholinesterase (AChE) → ↑ ­Ach concentration → ↑ improve memory and cognitive function
• NMDA receptor antagonist (memantine)
  • blocks overstimulation of NMDA by glutamate release as glutamate is released in excessive amounts in neuronal damage
• Medication may also be required for conditions related to dementia such as stroke, CVD, diabetes, HTN, depression
• Cognitive stimulation therapy may also be used

Complications

• Increased frailty → accidents and falls risk
• Memory loss → reduced nutrition and weight loss
• Dysphagia → aspiration pneumonia
• Reduced mobility → pressure sores and skin ulcers
• Comorbidities → co-existing illness