Dementia Flashcards
What is dementia?
A condition characterised by evidence of significant cognitive decline in at least 1 cognitive domain (attention, executive, learning and memory, language, perceptuo-motor (ie praxis) or social cognition, interfering with independence and unexplained by any other process
What is the main environmental risk factor of dementia?
Ageing
What are some genetic causes of dementia?
ApoE4 in Alzheimer’s increases risk
Huntington’s disease is a monogenetic inherited dementia
Autosomal dominant Alzheimers caused by Presenilin 1 and 2 mutations
Trisomy 21 increases Alzheimers risk between 3rd and 4th decade due to 3 copies of the APP gene on chromosome 21
What are some forms of potentially treatable dementia?
- Metabolic e.g. uraemia
- Toxic e.g. alcohol
- Vitamin deficiency - B12and thiamine
- Traumatic - severe or repeated brain injury
- Intracranial lesions e.g. subdural haematoma, tumours
- Infections e.g. HIV
- Endocrine e.g. hypothyroidism
- Psychiatric - depression causing ‘pseudodementia’
What are the main forms of dementia?
Alzheimer’s disease
Frontotemporal dementia
Vascular dementia
Lewy-body dementia
What is the most common form of dementia?
Alzheimers disease
How does having a 1st degree relative with AD increase risk of AD?
It doubles it
What is AD occurring in those under 65 known as?
Early onset AD (Possibly atypical or genetic)
What is AD occurring in those over 65 known as?
Sporadic AD (Mostly environmental)
What are the 2 main atypical sub-types of AD?
- Posterior cortical atrophy (Terry Pratchet)
- Progressive primary aphasia (Bruce Willis) - A form of frontotemporal dementia, but can cause an atypical form of AD
Describe the pathophysiology of AD
Alzheimer’s disease is a neurodegenerative proteinopathy, in which there is a build up of Amyloid-ß proteins
This causes the formation of:
- Extracellular amyloid plaques
- Intracellular neurofibrillary tangles
These cause disruption to cholinergic pathways in the brain and synaptic loss, causing cognitive impairment
What do extracellular amyloid plaques cause in the brain?
Disruption of normal cell functional and induced apoptosis
What do intracellular neurofibrillary tangles cause in the brain?
Disruption of the cell cytoskeleton leading to cell death
Describe the pathway that AD symptoms usually take?
Alzheimer’s disease usually presents initially with general forgetfulness, caused by degeneration of the medial hippocampus and later parietal lobes
This can then progress into apraxia and visuospatial difficulties
What are the main symptoms of AD?
- Gradual onset, decline of particularly short-term memory
- Autobiographical and political memory often well preserved
- Poor concentration, poor sleep, low mood
- Personality change - disinhibited, aggression, lack of self-care
What are some end stage symptoms of AD?
hallucinations, poor dentition, skin ulcers, loss of verbal communication
What is a symptom of posterior cortical atrophy (Sub-type of AD)?
Visuospatial disturbance
What investigations are required in AD?
- MRI: Atrophy of temporal / parietal lobes
- SPECT: temporoparietal ↓metabolism
- CSF : ↓amyloid : ↑ tau ratio
- Research: amyloid ligand imaging
How is AD managed?
Address vascular risk factors
ACh boosting treatments:
- Cholinesterase inhibitors (eg Rivastigmine / Donepezil)
- NMDA receptor blocker (eg Memantine)
- Amyloid monoclonal (Lecanemab – not NICE/SMC approved)
Describe the pathophysiology of frontotemporal dementia
Frontotemporal dementia is a neurodegenerative proteinopathy, in which there is a build up of Tau or TDP-43 proteins in the brain
Specific degeneration/atrophy occurs in the frontal and temporal lobes of the brain
What are the 3 syndromes of frontotemporal dementia?
Behavioural variant
Primary progressive aphasia
Semantic dementia
What are some symptoms of behavioural variant frontotemporal dementia?
Behavioural changes
Executive dysfunction
Disinhibition
Impulsivity
Loss of social skills
Apathy
Obsessions
Change in diet
What are some symptoms of primary progressive aphasia?
- Logopenic aphasia (repeating)
- Non-fluent aphasia (effortful)
Effortful non-fluent speech, speech sound/articulatory errors, lack of grammar, lack of words
What are some symptoms of semantic dementia?
Impaired understanding of meaning of words, fluent but empty speech
Difficulty retrieving names
What investigations are required in frontotemporal dementia?
- MRI: Atrophy of frontotemporal lobes
- SPECT: Frontotemporal ↓metabolism
- CSF: ↑ tau / normal amyloid
What are some management options for frontotemporal dementia?
- Trial of trazadone/antipsychotics to help behavioural features
- Safety management - controlled access to food/money/internet, structured activities
- Power of attorney
- Environmental / safety management
- Controlled access to food / money / internet
- Structured activities
- Support: MND nurse specialist if co-existent MND / CPN
What causes vascular dementia?
Brain damage due to cerebrovascular disease: either major stroke, multiple smaller unrecognised strokes (multi-infarct) or chronic changes in smaller vessels (subcortical dementia)
What are some symptoms of vascular dementia?
- Dysphasia
- Dyscalculia
- Frontal lobe symptoms
- Affective symptoms (more common than in Alzheimers)
Describe the pattern of decline in vascular dementia
Stepwise decline
What are some symptoms of subcortical (Small vessel) vascular dementia?
↓ attention, executive dysfunction, and slowed processing
What are the core criteria for vascular dementia diagnosis?
- Presence of cerebrovascular disease plus
- A clear temporal relationship between the onset of dementia and cerebrovascular disease
How is vascular dementia managed?
Manage vascular risk factors +/- cholineresterase inhibitor
What causes Lewy-body dementia?
Lewy-body dementia is a neurodegenerative proteinopathy, in which there is a build up of Alpha-synuclein proteins in the neurons of the brain stem and neocortex
How does alpha-synuclein cause dementia in Lewy-body dementia?
α-synuclein aggregates are insoluble and so lead to cell dysfunction and therefore cell damage
This leads to disruption of cholinergic and dopaminergic pathways
What are some early symptoms of Lewy-body dementia?
Common early involvement of reduced attention, executive function and visuospatial skills
What are some other symptoms of Lewy-body dementia?
- Visual hallucinations
- Fluctuating cognition (delirium-like)
- REM sleep behaviour disorder
- Extrapyramidal features (Parkinsonism) seen in 75% (Not more than 1 year prior to onset of dementia)
What are the core criteria for diagnosis of Lewy-body dementia?
- Fluctuating cognition plus
- Recurrent well-formed visual hallucinations +/-
- Presence of extrapyramidal features (seen in 75%)
What are some investigations for Lewy-body dementia?
DaT (dopamine transporter imaging) if atypical features
New (research) techniques: αsynuclein ligand imaging / αsynuclein in CSF
How is Lewy-Body dementia managed?
Small dose Levodopa /↓ acetylcholine (amongst other neurotransmitters) → trial cholinesterase inhibitors
Support: PD nurse specialist / CPN
What are some generalised investigations for suspected dementia?
CT (Standard)
MRI (If young or fast progressing)
Bloods (Dementia screen)
SPECT
DAT
What are some blood tests involved in the dementia screen?
B12, TFTs, syphilis, HIV, Ca2+
