Neurology >
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
- Beta-amyloid plaques are derived from fragments of amyloid proteins
- 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