Dementia Flashcards
Describe Dementia.
Clinical syndrome, with multiple causes, defined by progressive acquired loss of higher mental function of sufficient severity to cause social or occupational impairment.
What percentage of those over 65 have Dementia?
• 10% > 65 years
What percentage of the over 80 have Dementia?
• 20% > 80 years
Outline the clinical features of dementia. List 5.
• Amnesia \+ • Aphasia • Apraxia • Agnosia • Executive function ∆ \+ • ∆ADL • Instrumental or Basic change
Give 3 other differentials of Dementia.
- Delirium (acute)
- Depression: Low mood/poor concentration
- MCI: Amnestic/ADLs intact
- Normal Ageing: WFD/Important things remembered and function preserved
What is the difference between forgetfulness (amnesia) and Dementia?
MCI amnestic ≠ Dementia
–> Dementia = Amnesia + Apraxia/Aphasia/Agnosia/Executive function + ∆ADL
What is Alzheimer’s disease?
Primary degenerative cerebral disease of unknown aetiology with characteristic pathological features: neuronal reduction, neurofibrillary tangles, argentophile plaques, largely of amyloid protein and granulovacuolar bodies.
Give 5 risk factors for Alzheimer’s Disease.
- Advanced age
- Physical inactivity
- Smoking
- High cholesterol
- Hypertension
- Poorly controlled diabetes
- FHx
- Education/social engagement
- Depression
- Head injury
- Hearing loss
Outline the key aspects of the pathophysiology of Alzheimer’s Disease.
- Degeneration of corticospinal tracts and hypoglossal nuclei: Reduced ACh + ∆Glutamate signaling
- Amyloid plaques (Aß peptide)
- Neurofibrillary Tangles (phosphorylated tau)
- Adipose inclusions + lipoid granules
Give 5 clinical features of Alzheimer’s Dementia.
- Insidious onset and steady progression
- Short-term memory loss
- Apathy: Slow disintegration of personality and intellect (apathy)
- Aphasia: Decline in language
- Visuospatial skills
- Apraxia (impaired ability to carry out skilled motor tasks)
- Agnosia (failure to recognize objects)
- Aphasia (cannot eat)
How would you diagnose Alzheimer’s disease?
What investigations might you order?
- Clinical diagnosis
- Mini Mental State Examination (MMSE): < 25/30
- MRI-Brain: Atrophy of mesial temporal lobe structures – hippocampic –> cerebral atrophy
- Emission Tomography: Reduced ACh signaling/Glutamate signaling in wrong palce/ Altered glucose metabolism
What is the pharmacological management for Dementia?
- ACEase-i: Donepezil/Rivastigmine/Galantamine –> increase cholinergic transmission
- NMDA antagonist: Memantine
A 67 year old ex Builder presents with amnesia which has had a slow onset. Additionally, he has recently begun to speak in reduced quality and volume as well as lose appetite. He has become a bit clumsy and recalls reduced ability to carry objects or perform tasks. His PMHx is a background of hypertension, dyslipidemia, poorly controlled diabetes and an MI in 2014.
His investigations are unremarkable and his MMSE is 18/30.
What other investigation might you order?
MRI-Head
CT-Head
FBC
U+E
A 67 year old ex Builder presents with amnesia which has had a slow onset. Additionally, he has recently begun to speak in reduced quality and volume as well as lose appetite. He has become a bit clumsy and recalls reduced ability to carry objects or perform tasks. His PMHx is a background of hypertension, dyslipidemia, poorly controlled diabetes and an MI in 2014.
His investigations are unremarkable and his MMSE is 18/30. The MRI shows cerebral atrophy.
What is your differential?
Outline your management
Alzheimer’s Disease
ACEase-i: Donepezil/Rivastigmine/Galantamine –> increase cholinergic transmission
NMDA antagonist: Memantine
What is Vascular Dementia?
Type of dementia following haemorrhage (TIAs/CVA).
Give 5 risk factors for Vascular Dementia.
- Advanced age (> 60 years)
- Hypertension
- FHx
- Physical inactivity
- Diet: High cholesterol
- Stress
Give 5 clinical features of Vascular Dementia.
- Amnesia (forgetful)
- Apraxia (poor coordination)
- Aphasia (impaired of speech)
- Agnosia (impaired interpretation of sensations)
- Apathy
- Poor attention
- Difficulty solving problems
- ∆ADL
Outline the management for Vascular Dementia.
- Aspirin: 50-325mg PO OD
- Carotid endarterectomy/Carotid angioplasty + Stenting (≥ 70% carotid stenosis)
- Galantamine/Rivastigmine (if concomitant Alzheimer’s Disease)
- Antihypertensives: CCB ± Diuretics/ACEi or ARBs
- Statins (elevated LDL Cholesterol)
A 68 year old Female presents with amnesia, apraxia and aphasia. She says she has become restless recently, showing poor attention. She doesn’t remember this, but her family have made her aware of it. Additionally, she has begun forgetting to do basic activities like getting clothes washed or washing the dishes.
She has previously had an MI in 2014 and a PACS stroke in 2018 with partial recovery. She has hypertension, diabetes mellitus type 2, dyslipidemia. She drinks 18 units per week and smokes regularly with a pack year of 30.
What investigations might you want?
- FBC
- U+E
- SCr and eGFR
- MRI-Head
A 68 year old Female presents with amnesia, apraxia and aphasia. She says she has become restless recently, showing poor attention. She doesn’t remember this, but her family have made her aware of it. Additionally, she has begun forgetting to do basic activities like getting clothes washed or washing the dishes.
She has previously had an MI in 2014 and a PACS stroke in 2018 with partial recovery. She has hypertension, diabetes mellitus type 2, dyslipidemia. She drinks 18 units per week and smokes regularly with a pack year of 30.
Her MRI-Head shows white matter hyper intensities and hypo intensities.
What is your differential?
Outline your Rx.
Vascular Dementia
- Aspirin: 50-325mg PO OD
- Carotid endarterectomy/Carotid angioplasty + Stenting (≥ 70% carotid stenosis)
- Galantamine/Rivastigmine (if concomitant Alzheimer’s Disease)
- Antihypertensives: CCB ± Diuretics/ACEi or ARBs
- Statins (elevated LDL Cholesterol)
What severity of carotid stenosis would you give a carotid endarterectomy?
50%
What severity of carotid stenosis would you give a carotid angioplasty + stenting?
70%
What is Dementia with Lewy Bodies?
Type of dementia characterized by fluctuating cognition with pronounced variation in attention and alertness.
Give 5 clinical features of Dementia with Lewy Bodies.
- Prominent or persistent memory loss
- Impairment in attention
- Frontal/subcortical/visuospatial ability prominent
- Depression
- Sleep Atonia/Sleep disorders occur
- Recurrent formed visual hallucinations
- Parkinsonism
- Transient loss of consciousness
• Memory relatively preserved
What is the management of Dementia with Lewy Body Disease?
ACE-asei: Donezepil/Galantamine/Rivastigmine (transdermal)
Dopamine agonist (?): Levodopa
A 67 year old male presents with prominent amnesia, impairment in attention and apathy. He says he has begun to find it difficult to manage normal daily activities.
O/E you notice an coarse tremor which stabilises when performing a task. Additionally, you notice muscle rigidity, cog wheeling and bradykinesia.
What investigations would you want to conduct?
- Bloods: FBC
- U+E
- TFTs
- eGFR
- MRI/CT-Head: Cerebral atrophy or ventriculomegaly?
A 67 year old male presents with prominent amnesia, impairment in attention and apathy. He says he has begun to find it difficult to manage normal daily activities.
O/E you notice an coarse tremor which stabilises when performing a task. Additionally, you notice muscle rigidity, cog wheeling and bradykinesia.
His MRI-Head shows cerebral atrophy and ventriculomegaly.
What is your differential?
Outline your management.
Dementia with Lewy Bodies
ACE-asei: Donezepil/Galantamine/Rivastigmine (transdermal)
Dopamine agonist (?): Levodopa
State the 3 subtypes of Frontotemporal Dementia.
- Frontal variant: Behaviour and personality ∆s
- Progressive non-fluent Aphasia: ∆ speaking
- Semantic Dementia: ∆ use and understanding of language
Outline the pathophysiology of Frontotemporal Dementia.
• HyperP of Tau –> NFTs + Pick Bodies (present cf Alzheimer’s) + Microvacuolatioon –> Neuronal loss
What is Frontotemporal Dementia?
Type of dementia involving heterogeneous group of conditions with prominent progressing coarsening of personality, social behaviour, self-regulation and language.
Give 3 clinical features of Frontotemporal Dementia.
- Coarsening of personality/social behavior/habits
- Loss of language fluency or comprehension (Broca’s Area; Fluency and Sequencing from Frontal; Language and Perception from Parietal)
- Amnesia (develops following change in personality, language, habits and activity
- Apraxias
- Self-neglect
What investigations may you want to determine Frontotemporal dementia?
CT/MRI: Cerebral atrophy
How would you manage a patient with Frontotemporal Dementia?
• Supportive
• Benzodiazepine (agitation/acute irritability): Lorazepam 1-2mg PO OD then 0.25mg 4-6 hours
–> Max 4mg/day
• Home-assistance/respite care
List 3 roles of the Frontal Lobe.
- Problem solving
- Attention
- Social skills
- Flexible thinking
List 3 roles of the Parietal Lobe.
- Perception
- Visuospatial awareness
- Language (L)
List 3 roles of the Temporal Lobe.
- Memory
- Language (L) - (Wernicke’s Area – understanding language)
- Facial recognition
List main role of the Occipital lobe.
• Vision
Give an example of another animal known to display Dementia.
- Killer whale
- Dolphin
- Wolverine
- Degu
Give a genetic example implicated in the pathogenesis of Dementia.
Genetics:
1. AP
• PSEN1: Presenilin –> Cleaves proteins
• PSEN2: Presenilin –> Cleaves proteins
• APP: Amyloid Precursor Protein –> Amyloid and synapse formation/function
• ADAM-10: ADAM –> Metalloproteinse cleaving ECM
- NFT
• FERMT2: Fermitin homolog 2 –> Regulate integrin activation
• CASS4: Cass scaffolding protein 4 –> Regulate interaction of FAK in ECM - Cholesterol
• APOE4: LDL transport
• ABCA7: Cholesterol transporter
Give two key molecular pathological finds in the pathogenesis of Dementia.
- Amyloid Beta
2. Tau protein
Outline the processing of Amyloid ß in Dementia.
• APP + (ß-secretase) –> C99 + (y-Secretase) –> Aß40** + Aß42** –> Enters Mt via Mt-associated membranes
