Define dementia.
A chronic and progressive deterioration of behaviour and higher intellectual function due to organic brain disease. It is marked by memory disorders, changes in personality, deterioration in personal care, impaired reasoning ability, and disorientation.
List the different types of dementia.
Alzheimer's disease Vascular dementia Mixed dementia Lewy body dementia Frontotemporal dementia (Pick's disease) Other types
List the causes of dementia.
Alzheimer's disease Vascular dementia Drugs, depression, delirium Endocrine Metabolic Ethanol Neurological (e.g. Parkinson's disease) Trauma, toxins, tumours Infection Autoimmune
List some causes of reversible dementia.
Hypothyroidism Normal pressure hydrocephalus Drugs (e.g. opiates, alcohol) Tumours Neurosyphilis Chronic subdural haematoma Psychiatric disorders
List the common features of dementia.
- Cognitive dysfunction:
- –Memory impairment
- –Personality change
- –Multiple cognitive defects
- –Impaired intellectual ability
- –Interference with activities of daily life (ADLs) and social interactions - Neuropsychiatric symptoms (BPSD – behavioural and psychiatric symptoms of dementia):
- –Irritability
- –Delusions
- –Dysphoria/depression
- –Apathy/indifference
- –Agitation/aggression
- –Hallucinations
- –Motor behaviours
Describe the pathophysiology of Alzheimer’s disease.
- Structural brain changes:
a. Ventricular enlargement
b. Brain shrinking
c. Widening of sulci and gyral atrophy
d. Decreased brain weight - Neurotransmitter changes causing BPSD:
a. Reduced monoaminergic function
b. Cortical-subcortical behavioural circuit dysfunction
c. Areas of brain atrophy/neuronal loss
d. Cholinergic deficit in the striatum
e. Increased D2/D3 receptor availability in the striatum
f. Dysfunction of the sleep-wake cycle - Histological changes:
a. Amyloid plaques
b. Apolipoprotein E (i.e. the ApoE4 form)
c. Tau protein tangles
Describe the process of amyloid plaque formation.
- Amyloid precursor protein (APP) is broken down by alpha/beta/gamma secretases
- This forms 3 parts – the smallest is amyloid-beta4
a. NOTE: it is gamma secretase which cuts the APP at the cell membrane, causing beta amyloid to leave the cell - Amyloid-beta forms extracellular aggregates (plaques) in the brain
- Beta amyloid plaques are turned into ‘mature’ plaques by:
a. More protein degradation
b. Dystrophic neurons
c. Microglia
Describe the mutations in Alzheimer’s disease which increase amyloid plaque formation.
- Amyloid precursor protein (APP)
- Presenilin I and II enzymes (i.e. the subcomponent of gamma secretase which cuts APP)
- ApoE4
Describe the process of tau neurofibrillary tangle formation.
- Tau mutations cause the tau protein to become hyperphosphorylated
- Hyperphosphorylation leads to tau aggregation
a. These form soluble tau aggregates - Tau deposition occurs when there are too many tau aggregates
a. This forms tau fibrils and neuron tangles
Describe the pathophysiology of vascular dementia.
- Infarction (causes cystic gaps in the brain)
- Leukoaraiosis
a. White matter palor, caused by:
- –Loss of axons
- –Demyelination
- –Loss of oligodendrocytes
- –Perivascular tissue loss
- –Dilation of perivascular spaces
b. Capillary damage
c. Protein leakage and breakdown of the blood brain barrier - Haemorrhage
Describe structured cognitive testing for dementia.
- MMSE (mini-mental state examination)
a. Cut off for dementia diagnosis: 24 out of 30 - ACE-III (Addenbrooke’s cognitive examination)
a. Cut off for dementia diagnosis: 82-88 out of 100 - ADAS-Cog (Alzheimer’s Disease Assessment Scale-Cognitive section
- MDRS (Mattis Dementia Rating Scale)
- MoCA (Montreal Cognitive Assessment)
List the medications used to treat dementia.
- For cognitive dysfunction:
a. Cholinesterase inhibitors (donepezil, revastigmine, galantamine)
b. Memantine (partial glutamate antagonist) - For BPSD:
a. Antidepressants
b. Antipsychotics
c. Cholinesterase inhibitors
d. Memantine
Describe psychological treatment for dementia.
- Cognitive stimulation and reality orientation therapy
- Validation therapy
a. Based on the principal that even the most confused behaviour has some meaning for the patient - Behavioural therapy
a. Tries to find reasons for difficult behaviour
b. E.g. helps with wandering/restlessness
c. Used for many BPSD symptoms
Describe any other (i.e. not psychological or pharmacological) treatment options for dementia.
- Treatment of underlying conditions for reversible dementia
- Exercise/training programmes
- Environmental control measures (e.g. ID bracelets)
- Vascular risk reduction
- Social worker involvement
- Genetic counselling
Define delirium.
An acute disorder of the mental processes accompanying organic brain disease. It may be manifested by delusions, disorientation, hallucinations, or extreme excitement and occurs in metabolic disorders, intoxication, deficiency diseases, and infections
List the signs and symptoms of delirium.
- Acute onset
- Severe fluctuations
- Inattention (i.e. reduced awareness of the environment)
- Decreased focus
- Decreased ability to sustain or shift attention
- May be subtle at first:
a. Lethargy
b. Distractibility - Cognitive deficits
- Altered levels of consciousness
- Potentially life-threatening
How do you differentiate between dementia and delirium?
Dementia:
- Progressive development
- Consciousness preserved
- Primary CNS disease
- Lack of insight
- Memory impairment
- Normal sleep
- Worse in evening
- More settled
Delirium:
- Acute onset
- Impaired consciousness
- Secondary to underlying medical disease
- Disordered thinking
- Visual/tactile hallucinations
- Illusions
- Sleep disturbances
- Severe fluctuations throughout day
- Agitation, restlessness
Describe the advantages and disadvantages of the MMSE.
Advantages:
- Widely used
- Screening tool
Disadvantages:
- Doesn’t test PFC
- Minimal language testing
- Minimal visuospatial ability testing
- May be affected by language/education
Describe the advantages and disadvantages of the ACE-III.
Advantages:
1. Includes PFC tests
Disadvantages:
1. Strongly affected by poor education
