Degenerative diseases - Alzheimer's, Dementia Flashcards
What is dementia?
A description of a set of symptoms which show an acquired decline in memory and other cognitive functions in an alert person sufficiently severe to cause functional impairment and present for more than 6 months.
- An acquired loss in multiple domains of higher mental function
- A progressive decline
- Occurs in clear consciousness
What are the major causes of dementia?
- Alzheimer’s disease
- Vacular dementia
- Dementia with lewy bodies
- Fronto-temporal dementia
- Parkinson’s disease + dementia
- Reversible dementias
Name some rare causes of dementia
Vit B12 deficiency,
hypothyroidism, infective (HIV, syphillis, CJD), intracranial mass (subdural haematoma, hydrocephalus, tumour), Huntington’s disease, alcohol/drug use
Major causes of late onset demntia (>65)
Alzeimer’s (55%), vascular (20%), lewy body (20%), others (5%).
Major causes of early onset dementia
Alzeimer’s (33%), vascular (15%), fronto-temporal (15%), Others (35%) - huntington’s, infection (HIV), infalmmatory (MS), toxic (alcohol)
What is Alzheimer’s disease?
A chronic neurodegenerative disease that usually starts slowly and worsens over time. It involes the build up of amyloid plaques and neurofibrillary tangles within brain tissue.
It is a primary degenerative cerebral disease
Pathology of alzheimer’s
Tempero-parietal dementia
- Neruofibrillary tangles
- Senile plaques (amyloid B protein)
- Apoliprotein E4
- Cerebral atrophy
What is the pathogenesis of amyloid plaques in Alzheimer’s disease?
Abnormal breakdown of membrane Amyloid precursor proteins (involed in neuronal growth and repair), meaning that previously soluble breakdwon products are no longer soluble (Amyloid-beta). Clumps (plaques) of beta-amyloid form in between neurons, which disrupt conduction mechanisms. Plaques also illicit an inflammatory response, and cause amyloid angiopathy, which weakens vessel walls and increase risk of haemorrhage
What is the pathogenesis of neurofibullary tangles in Alzheimer’s disease?
The presence of amyloid plaques leads to the activation of kinase, which adds phophate groups to Tau proteins in the microtubules inside the neuronal cells. This causes a conformational change in Tau protein structure, which causes them to stop supporting microtubules, break away and form neurofibrillary tangles
What macroscopic changes occur due to neuronal cell death in alzheimer’s disease?
-
Atrophy
- Narrowing gyri
- Widening sulci
- Increased ventricular volume
What are the symptoms of alzheimer’s disease?
Progresses slowly over years
- Memory disturbance - short term memory first
- Global cognitive decline with intact personality
- Decline in launguage,
- Decline in executive function (planning)
- Disorientation - temporal = visuospatial skills
- Progresses to broad, often global cognitive dysfunction, behavioural change (eg agitation, aggression or apathy) and functional impairment (BPSD)
O/E May be increased tone
What is vascular dementia?
Dementia caused by problems in the supply of blood to the brain, typically a series of minor strokes, leading to worsening cognitive decline that occurs step by step
What are risk factors for vascular dementia?
- DM
- Hypertension
- Smoking
- Other vascular disease
How does vascular dementia present?
Problems occur in a stepwise fashion
- Frontal lobe, extrapyramidal, pseudobulber and emotional lability is common
- Urinary incontinence and falls without other explanation
- Executive dysfunction may predominate
- Gait abnormalities
What would you see in neuroimaging in someone with vascular dementia?
- Multiple large vessel infarcts
- White matter infarcts/periventricular white matter changes
What is dementia with lewy bodies?
A dementia syndrome that is characterized by the development of abnormal collections of (alpha-synuclein) protein within the cytoplasm of neurons (known as Lewy bodies)
How does dementia with lewy bodies present?
General
- Deficits of attention, frontal executive, visuospatial.
Of the following, Two = probable, One = possible:
- Fluctuations in cognitive function and alertness
- Prominent auditory and visual hallucinations - often with paranoia and delusions
- Parkinsonism
Commonly presents with falls due to visuospatial impairment
What drugs can worsen confusion in dementia with lewy bodies?
- Typical antipsychotics - haloperidol
- Levodopa
- Dopamine
How could you distinguish dementia with lewy bodies from delerium?
- Insidious onset
- No underlying illness found
- Complex hallucinations - not misrepresentation of stimuli
- Persistent delusions
- Antipsychotics worsen status
How would Parkinson’s disease with dementia present?
- Typical parkinsonian motor features
- Presentation variable - may resemble vascular, alzheimer’s or lewy body
- Often preceded by parkinson’s
What is frontotemporal dementia?
A group of disorders caused by progressive nerve cell loss in the brain’s frontal lobes or its temporal lobes. This invariably cause deterioration in behavior and personality, language disturbances, or alterations in muscle or motor functions.
There is frontal and temporal atrophy wihtout alzeimer’s histology.
What are the features of fronto-temporal dementia?
Early onset - insidious/slow
- Behavioural – personality change, often changes in eating habits (and eraly dysphasia)
- Speech disorder - altered output, stereotypy, echolalia, perseveration, mutism
- Neuropsychology - frontal dysexecutive syndrome. Memory, praxis and visuospatial function not severely impaired. Disinhibition.
- Lack of Insight - early on
Memory and visulo-spatial is relatively preserved
What are the core features of dementia syndrome?
A - activities of daily living
B - Behavioural and Psychiatric Symptoms of dementia
C - cognitive impairment
D - Decline
What are the cognitive features of dementia?
Memory
-
Dysmnesia (memory impairment), plus one of the following:
- Dysphasia - expressive/receptive
- Dyspraxia - inability to carry out motor tasks
- Dysgnosia - difficulty recognising objects
- Dysexecutive function
Functional
- ADL’s
What are the behavioural and psychiatric symptoms of dementia?
- Psychosis (hallucinations and delusions)
- Depression (and other mood disturbances) - in 30%
- Altered circadian rhythms
- Agitation/irritability
- Anxiety
- Agnosia
Personality change in 75%
What physical signs can be seen in dementia?
- Signs of vascular disease
-
Signs of late dementia
- Primitive reflexes
- Global hyperreflexia
When performing a mental state exam for someone with suspected dementia, what would you want to exclude as differential diagnoses?
- Delerium - Agitation, restlessness, poor attention, fluctuating consicousness
- Depression - low affect, poor motivation
What investigations would you do in someone with dementia to look for potetnially reversible causes?
- Bloods - FBC, U+E’s, B12, Folate, ESR, Calcium, LFT’s, TSH, CRP
- ECG
- CXR
- Consider EEG, Neuroimaging (vascular damage, haemorrhage or structural pathology?) or LP
When is neuroimaging indicated in the context of a presentation of dementia?
- Age < 60
- Sudden onset/brisk decline
- High risk of structural pathology
- Focal CNS signs
How does delerium differ from dementia in terms of mode of onset?
Delerium is acute
How does delerium differ from dementia in terms of fluctuation?
Diurnal/hourly fluctuation common in delerium
Can have deterioration in dementia in the evening
How does delerium differ from dementia in terms of hallucinations?
Common in delerium, whereas late sign in dementia (except lewy body dementia)
How does delerium differ from dementia in terms of fear, agitation and aggression?
This is common in delerium, and is uncommon in the early stages of dementia
How does delerium differ from dementia in terms of motor signs?
Tremor, myoclonus and asterixis common in delerium
Motor signs late in delerium
How does delerium affect speech?
- Dysarthric - slurred or slow speech that can be difficult to understand
- Dynomic - fluent type of aphasia where an individual has word retrieval failures and cannot express the words they want to say
How does delerium differ from dementia in terms of memory?
Short and long term affected in delerium, whereas long term memory is often spared until later on in dementia
How would you manage someone with dementia?
Modify reversible factors
Medications
- Cholinesterase inhibitors - mild to moderate
- Memantine - moderate to severe
- Antipsychotropics
Adequate care at home
- Support caregivers
- Provide extra care for ADLs
- Carer education
What is important to remember when managing someone with dementia?
Notify DVLA at diagnosis
If early dementia license may be yearly
“those with poor short term memory, disorientation or lack of insight should almost certainly not drive”
What are risks associated with dementia?
- Falls
- Wandering
- Aggression towards carers/family
- Self neglect
- Abuse towards patient
- Financial abuse
Name some of the acetylcholinesterase inhibitors used in dementia?
- Donepezil
- Rivastigmine
- Galantamine
What sort of drug is Memantine?
NMDA receptor blocker - reduces cholinergic neuron destruction
How would you manage agitation/aggression in a demented patient?
Non medical interventions
- Familiar environemtn
- Avoid precipitants
Medical interventions
- Benzodiazepines
- SSRI’s - if depression prominent
- Antipsychotics
How would you assess dementia severity?
- MMSE
- Montreal Cognitive assessment
What are classed as reversible causes of dementia?
- Hypothyroidism
- Intracerebral bleeds/tumours
- B12 deficiency
- Hypercalcaemia
- Normal pressure hydrocephalus
- Depression
Where are changes in alzheimer’s disease normally found in the brain?
Neocortex and hippocampus
What cholinesterase inhibitor is used to treat dementia with lewy bodies?
Rivastigmine
What cholinesterase inhibitor can be used to treat alzheimer’s disease?
Donepezil
What can galantamine be used for?
Mixed dementia
What is the triad of symptoms commonly seen in normal pressure hydrocephalus?
- Dementia
- Incontinence
- Gait disturbance (similar to parkinsons)
What is normal pressure hydrocephalus?
Reversible cause of demential seen in elderly patients. Secondary to reduced CSF absorption at the arachnoid villi. Could be caused by head injury, subarachnoid haemorrage or meningitis.
Symptoms typically develop over 3 months.
Management is ventriculoperitoneal shunting.
What is always important to remember to screen for when assessing someone with suspected dementia?
DEPRESSION
What is the defintion of capacity?
Ability to understand information relevant to a decision or action and to appreciate the reasonably forseeable consequences of taking or not taking that action or decison
What are the steps to assesing capacity?
- Presume capacity - always assume unless there is evidence to the contrary
- Maximise capacity - if lacking capcaity
- Bad decisions not necessarily incapable
- Mental disorder or severe communication disorder
What classes of mental disorders can lack capacity?
- Dementia
- Delerium
- Schizophrenia
- Aphasia
- Sensory impairment
What are the 5 aspects of decision making that need to be present in order for someone to be deemed to have capacity?
- Acting
- Making decision
- Understanding decisions
- Communicating decisions
- Retaining memory of decisions
What is power of attorney?
Power granted by person (when they have the capacity to do so) to make sure that their future decisions are safeguarded, even when they lode the ability to make these decisions themselves
What are the different types of power of attorney?
- Continuing - financial only
- Welfare - decisions about health and wellbeing
- Combined - both financial and decisions
What is guardianship?
Legal authority for someone to make decisions and act on behalf of a person who has lost capacity to make certain decisions.
May cover money, property, welfare and health
What are the 4 main areas of cognition tested in the MMSE?
- Orientation
- Memory/Registration and Recall
- Attention and calculation
- Language
What are disadvantages to using the MMSE?
- Biased against people with poor education due to elements of language and mathematical testing
- Bias against visually impaired
- Limited examination of visuospatial cognitive ability
- Poor sensitivity at detected mild/early dementia
Name some of the domains of cognition
Memory, attention/concentration, language, visuospacial, behaviour, emotion, executive functioning, problem solving, personality
Name 2 screening tests used for diagnosis of dementia
MMSE - orientation, registration, attention and calculation, recall, language, copying
MOCA
Speed of progression clues to diagnosis
Rapid - CJD, tumour, infection
Stepwise - vascular
Additional neruological signs linked to dementia
Abnormal movement - huntington’s
Parkinsonism - lewy body
Myoclonus - CJD
Differentials from presentation of dementia
Hydrocephalus
Tumour
Depression (pseudodementia)
What is agnosia?
Failure to recognise places, people etc
What is anosagnosia?
Lack of insight into the problems caused by the disease eg missed appointments, misunderstood plots, conversations, films, mishandling of money and clerical work
What is apraxia?
Inability to carry out skilled tasks
