S9 L1 Dementia, delirium and toxic insult Flashcards
Define dementia?
Progressive condition
Deterioration in cognition resulting in behavioural problems and impairment in the activities of daily living
Extensive affecting multiple domains of intellectual functioning
What are the different types of dementia?
- Alzheimer’s → most common (50-70%)
- Vascular → (25%)
- Lewy Body (15%)
- Frontotemporal
- AIDS-dementia complex
What is the pathophysiology of Alzheimer’s disease?
1- Global atrophy of brain lobes → Mostly frontal, parietal and temporal lobes 2- Macroscopic feature → Global cortical atrophy → Sulcus widening → Enlarged 3rd and 4th ventricles 3- Microscopic → Plaques - composed of amyloid beta → Tangles - hyperphosphorylated tau - Two hypothesis 1. The amyloid hypothesis 2. The tau theory
What is the amyloid hypothesis?
- Excess of interneuronal amyloid (Abeta) peptides, due to overproduction or diminished clearance of beta-amyloid
- Formation of dense amyloid oligomers, which are deposited as diffuse plaques
- Inflammatory process through microglial activation, cytokine formation, and activation of the complement cascade
- Formation of neuritic plaques, causing synpatic and neuritic injury and cell death
What is the tau theory?
Abnormal aggregation of tau protein, a microtubule-associated protein that stabilises microtubules in the cell
- Tau accumulates into interneuronal masses → neurofibrillary tangles and dystrophic neurites
- Abundance of tangles is roughly proportional to the severity of clinical disease and cognitive decline
What are the main neurones that are affected in AD?
- Cholinergic
- Noradrenergic
- Serotonergic
- Those expressing somatostatin
What are the risk factors for AD?
- Head injury
- ↑serum cholesterol and homocysteine levels pose a risk for development of AD
- Lifestyle factors
→ Smoking
→ Midlife obesity
→ Diet high in saturated fats
What is the history of someone with AD?
- Risk factors
- Memory loss → recent memory first (recall memory from long time ago)
- Disorientation to time and place → misplacing items/ getting lost
- Nominal dysphasia → proper names and low-frequency words decline first
- Apathy → emotional disturbances, ‘lack of care’
- Decline in activities of daily living
- Personality/mood changes
What is the pathophysiology of vascular dementia?
Cognitive impairment caused by cerebrovascular disease (multiple small strokes)
Common end point of many vascular pathologies intracranially
→ Infarction
→ Leukaraiosis → white matter disease - subcortical leukoencephalopathy - lack of blood supply due to deposition in the brain
→ Haemorrhage
→ Alzheimer’s disease → although not classified as a vascular pathology, AD has a strong vascular risk factor spectrum
What is the history of someone with vascular dementia?
- History of stroke
- Difficulty solving problems
- Apathy
- Disinhibition
- Slowed processing of information
- Poor attention
- Retrieval memory deficit
- Risk factors similar to IHD (idiopathic heart disease)
What is the pathology of Lewy body dementia?
- Accumulation of Lewy bodies in vulnerable sites of CNS
→ Substantia Nigra
→ Temporal lobe
→ Frontal lobe
→ Cingulate gyrus - Lewy bodies are composed of the proteins alpha-synuclein, a cytoplasmic protein and associated with synaptic vesicles
- Other proteins include neurofilament and ubiquitin
- The distribution and density of Lewy bodies are thought to be correlated with clinical symptoms
- Co-existing AD pathology is common
How can you tell if a patient PD or Lewy body disease?
Movement disorder followed by dementia call it PD
Dementia precede movement disorder we call it Lewy Bodies
What is the history of someone with Lewy body dementia?
- Risk factors → old age
- Cognitive fluctuations → fine for long periods of time, then deteriorate, then improve
- Hallucinations, typically visual and complex, up to 80% of patients
- Motor symptoms → Parkinsonian features present in >85% of patients
- Vivid dreams are accompanied by loss of associated atonia of REM sleep, ‘acting out’ dream
- Depression
- Repeated falls/syncope
- Urinary incontinence
- Constipation
What is the pathophysiology of someone with frontotemporal dementia?
- Focal neurodegeneration of the frontal or temporal lobes of the brain
- Dutch epidemiological study reported a positive family history in 43% of cases
- Definitive diagnosis depends on pathological examination of brain tissue and identification of patterns of neuronal injury and characteristic intra-neuronal and glial cell inclusion
→ FTD-tau
→ FTD-U (ubiquitin)
What is the classification of FTD?
Classification:
- Apathetic (not interested in anything)
- Disinhibited
- Stereotypic
Can be overlapping
Behavioural FTD v Primary Progressive aphasia
