Clinical presentations of Dementia Flashcards
Define Dementia
Dementia is a clinical syndrome of progressive cognitive decline with impaired social or occupational functioning
In people over the age of 80 how many people will have dementia?
1 in 5 people
Much less common in younger people
What is the commonest in people over age of 65?
Alzheimer’s
Beyond Alzheimer;s what does the balance of disease change with?
Age of onset
What is extremely rare in younger people?
Lewy bodies
What is very important clinically?
Frontal temporal dementia
What does Dementia refer to?
Particular pattern of changes
What is the common pattern of cognitive impairment for AD?
- Episodic (and topographical) memory initially
- Early parietal deficits visuo-perceptual, visuo-spatial, calculation,praxis
- Later global cognitive impairment
What is the common pattern of cognitive impairment for DLB?
- Executive dysfunction
- Visual hallucinations
- Parietal lobe deficits/episodic memory
What is the common pattern of cognitive impairment for FTLD?
- Behavioural/personality changes
- Executive dysfunction
- Language-specific subtypes
What is the common pattern of cognitive impairment for VaD?
- Cognitive slowing
2. Executive dysfunction + can affect other lobes
What are the profiles seen on the neuropsychological tests mapped onto?
Particular hallmarks of atrophy
What does Alzheimer’s produce problems within?
Selective early hippocampi
- The medial temporal lobe
What do Semantic dementia produce problems within?
Understanding of speech
- The left temporal lobe
What does Primary progressive aphasia (PPA) affect?
The frontal lobe of the brain
What do profile on the scans go with?
Profile we see neuropsychologically
What does Neuroimaging contribute?
- Exclusion of surgically remediable lesion
- Diagnostic positive predictive value
- Detection and quantification of change
What is a framework for understanding (degenerative) dementias?
- Genetic/ other risk factors
- Abnormal protein deposited in the brain
- Loss of brain cells (brain atrophy)
- Altered neuro-transmitter function
- Symptoms and signs of the disease
What is a risk factor for the acceleration of the early onset of Alzheimer’s?
APOE4
not used clinically but mentioned dermatologically
What is the genetics of Alzheimer’s disease?
- APP
- PS1
- PS2
- ApoE4
What is the abnormal protein deposited in the brain for Alzheimer’s disease?
- Amyloid
2. Tau
What is the brain atrophy for Alzheimer’s disease?
Hippocampal atrophy initially then whole brain
What is the altered neuro-transmitter function of Alzheimer’s disease?
Cholinergic
What are the symptoms and signs of Alzheimer’s disease?
Episodic memory problems
later global deficits
What is serial scan used for?
Repeated Imaging
Look at brain shrinkage
What is the process of a serial scan?
Register the scans onto a common space and measure whether there has been a change in brain volume
Quantify the change by putting a colour on it
What is Alzheimer’s disease summary?
- The most common disease-causing dementia and most closely associated in the public mind
- Insidious onset, usually early memory impairment
- Later global cognitive deficits
- Neurological examination normal early in disease
- Amyloid plaques & (tau-positive) neurofibrillary tangles
- Deficiency of acetylcholine biochemically
- Initially hippocampal atrophy, later global cerebral atrophy
What does posterior cortical atrophy have (PCA)?
- Visual disorientation
- Led by visuospatial awareness
- Early prominent involvement of parietal cortex & occipital cortex
What is the abnormal protein deposited in the brain for dementia with Lewy bodies?
Alpha-synuclein
What is the brain atrophy for dementia with Lewy bodies?
Posterior or generalised
What is the altered neuro-transmitter function?
- Dopaminergic
2. Cholinergic
What are the symptoms and signs of Dementia with Lewy bodies?
- Visual hallucinations
- Cognitive decline
- Fluctuations
- Parkinsonism
Dementia with Lewy Bodies summary
• Extensive overlap (? continuum) with Parkinson’s disease
• Cognitive decline often includes prominent attentional, executive as well as posterior cortical deficits, memory variable
• Other key features:
- Visual hallucinations
- Fluctuations in cognition
- REM sleep disorder
- Parkinsonism
• Relative ‘absence’ of disproportionate hippocampal atrophy on MRI
What is the genetics for FTLD?
- MAPT
- Progranulin
- C9ORF72
- CHMP2B
- VCP
- TBK1
What is the abnormal protein deposited in the brain for FTLD?
- Ubiquitin (TDP-43)
2. Tau
What is brain atrophy for FTLD?
Fronto-temporal atrophy
What is altered neuro-transmitter function of FTLD?
- Serotonergic
2. Dopaminergic
What are the symptoms and signs of FTLD?
Behavioural or language deficits
What is the macroscopic pathology of FTLD?
- Classically ‘’knife-blade’’ frontotemporal atrophy but severity variable
- Variable involvement of parietal lobes
- Subcortical structures (amygdala, hippocampus, basal ganglia, thalamus) frequently involved
- They have loss of insight
What is progressive prosopagnosia?
a clinical syndrome characterized by a progressive and selective inability to recognize and identify faces of familiar people
What is the clinical feature of progressive prosopagnosia?
R temporal love atrophy overlap extensively with ‘frontal’ dementia
What is sementic dementia syndrome closely associated with?
Focal L temporal atrophy and this constellation predicts ubiquitin pathology
What is FTLD summary?
- Paradigmatic ‘focal’ dementias
- Genetically mediated in a significant proportion and this is likely to continue to expand
- Behavioural and/or language-based presentations
- Variable prominence of other neurological features (esp. parkinsonism)
- Asymmetric atrophy with antero-posterior gradient on MRI
- Some evidence for molecular imaging signatures
What is progressive supranuclear palsy (PSP) + corticobasal degeneration (CBD)?
Overlapping clinical syndrome with parkinsonism plus other neurological and cognitive features, and various histopathological substrates
what are features of PSP?
- Prominent executive deficits
- Gaze palsy (supranuclear)
- Early falls and parkinsonism esp affecting axial muscles
- May have midbrain atrophy on MRI
What are features of CBD?
- Prominent parietal deficits
- Asymmetric limb apraxia, ridgity +- ‘alien limb’
- May have asymmetric fronto-parietal atrophy on MRI
What signs does PSP: midbrain atrophy have on structural MRI?
- Mickey Mouse sign
2. Hummingbird sign
What are the causes of vascular dementia?
- Large artery disease (including inflammatory)
- Cardiac embolic events
- Small vessel disease
- Thrombophilias
- Haematologic factors
- Haemodynamic mechanims
- Specific arteriopathies
- Haemorrhages (primary and secondary)
- Hereditary e.g. CADASIL, cerebral amyloid angiopathies
What are the lesion types for vascular dementia?
- Arterial territorial infarct
- Distal field/watershed infarct
- Lacunar infarct
- Ischaemic white matter change
- Incomplete ischaemic injury
What is the summary of vascular dementia?
- A range of causes including both sporadic and genetic vasculopathies
- Atherosclerosis is the most common but vasculitis is esp important as treatable
- Many cases lack conventional risk factors or clinical history of stroke
- Several MRI patterns possible
- Vessel disease often coexist with primary degeneration
What are examples of the classification of Limbic encephalitis?
- Autoimmune
- Paraneoplastic
- Infections
- Connective tissue diseases/ vasculitides
- Mimic syndromes
What are examples of autoimmune limbic encephalitis?
- LGI1 most common
- GABABR,
- AMPAR
- CASPR2
- steroid responsive encephalopathies
What are examples of Paraneoplastic limbic encephalitis?
- Small cell lung
- Testis
- Lyphoma
- Ovary
- Breast
What is an example of infections in Limbic encephalitis?
- Herpesviruses (esp HSV2, HHV6/7)
What are examples of connective tissue diseases/vasculitides?
- Behcets
- Sjogren’s
- Sarcoid
- Relapsing polychondritis
What is an example of mimic syndrome?
Temporal lobe tumour
What are the Limbic encephalitis summary?
- Causes include paraneoplastic and inflammatory (autoimmune). Expanding range of associations
- Syndrome of subacute memory impairment with confusion, psychiatric features/ behavioural change (limbic dysfunction)
- Fluctuation with more protracted episodes of altered conscioussness, abnormal movements (e.g. LGI1)
- Seizures common
- Temporal lobe abnormalities on MRI
- May respond to immunosuppressive treatments
