Dementia Flashcards
What is dementia?
The progressive decline in higher cortical function leading to global impairment of memory, intellect and personality which affects the person’s ability to cope with activities of daily living.
Is consciousness impaired in dementia?
No
What symptom is often first noted in dementia?
Memory loss
What types of irreversible dementia are there?
Alzheimer’s (60%) Vascular Dementia with Lewy bodies Fronto-temporal dementia Creutzfeldt- Jacob disease
What are some examples of reversible causes of dementia?
Depression Vitamin deficiency B12, folate, thiamine Alcohol Hypothyroid disorder Subdural haematoma Syphilis Brain tumour
Describe the memory deficits associated with dementia
Short term memory loss
Struggle to learn new information
What behavioural changes are seen in dementia?
Altered personality Disinhibition Labile emotions Wandering Restless Repetitive and purposeless activity
What physical challenges can occur in association with dementia?
Incontinence
Reduced oral intake
Difficulty swallowing
What speech changes occur with dementia?
Anomic aphasia - difficultly with word retrieval
Difficulty understanding language
What perceptual changes can occur with dementia?
Visual hallucinations
Illusions
Visuospatial disorder
What is apraxia?
Difficulty with motor planning - inability to perform learned purposeful movements
What investigations should be done?
Full history and collateral history MMSE Neurological examination Bloods - FBC, B12, TFTs CT/MRI to exclude tumour, stroke, hydrocephalus, subdural Memory clinic
What can be see on a CT with dementia?
Dilation of ventricles
Generalised atrophy
In vascular dementia, how would you describe the decline in cognitive status?
Stepwise - an event causes a drop
How would you describe the cognitive decline in Alzheimer’s?
Progressive decline
How would you describe the cognitive decline in Lewy body dementia?
General trend downwards, may have periods of time when they improve
Describe the macroscopic pathology seen in Alzheimer’s disease
Loss of cortical and subcortical white matter causing gyral atrophy and wide sulci.
Ventricular dilatation reflecting loss of white matter.
Describe the microscopic pathology of Alzheimer’s disease
The break down of amyloid precursor protein forms beta amyloid, which builds up and clumps together into plaques between neurons and disrupts cell functioning. The enzyme that cuts APP is not very precise - resulting in large beta amyloid strands that do not easily dissolve.
Inside cells, tau proteins detach from microtubules and stick to other tau molecules and eventually form tangles inside the cell. This disrupts the microtubule transport system inside the nerve cell. Can lead to cell apoptosis
What are the early stages of Alzheimer’s disease?
Loss of memory of recent events, forgetting names of places and objects, ask questions repetitively, poor judgement or harder to make decisions, less flexible and hesitant to try new things
Subtle changes in mood and behaviour- increasing anxiety or agitation, loss of interest and motivation
Does not majorly intrude into daily life ie can live on the whole independently
Insight maintained to a degree
Describe moderate Alzheimer’s disease
Memory problems more prominent and other cognitive difficulties start to emerge
Increasing confusion and disorientation
Difficulty expressing themselves, confusing words
Changes in behaviour e.g repetitive actions like tissue shredding
Changes to personality
Changes in sleep pattern
Complex activities difficult
Hallucinations
Reduced insight into disease
Describe late stage Alzheimer’s disease
Severe and pervasive memory problems - may not recognise themselves
Marked changes in behaviour and personality (may become violent, demanding, suspicious)
Difficulty communicating
Inability to control movement
Incontinence
Difficulty swallowing
Weight loss
Need extensive help with activities of daily living
In dementia with Lewy bodies, where are the Lewy bodies found in the brain?
Substantia nigra
Cortex
In Parkinson’s LBs found only in SN
What are some key clinical features of dementia with Lewy bodies?
Substantial fluctuations in the degree of cognitive impairment over time
In contrast to Alzheimer’s, early impairments in attention and executive function rather than just memory loss
Parkinson’s symptoms
Visual hallucinations
Frequent falls
What are the types of vascular dementia?
Post stroke dementia - blood flow in a large vessel cut off - death of brain tissue. Approx 20% who have a stroke develop post stroke dementia
Single and multi infarct dementia - caused by one or more smaller strokes
Small vessel dementia / subcortical dementia- small vessels deep in brain thicken and become stiffer, so blood flow reduces. Can cause small infarcts near base of brain.
What is the most common type of vascular dementia?
Small vessel/ subcortical dementia
What are the names of the cholinesterase inhibitors used in dementia?
Donepezil
Rivastigmine
Galantamine
How does Memantine work?
It is an NMDA receptor antagonist
Alzheimer’s can be classified into sporadic and familial. What are some characteristics of sporadic disease?
Late onset Genetic and environmental cause Accounts for vast majority of cases Risk increases with age Inheriting the e4 allele of apoprotein E gene (less effective at breaking down beta amyloid)
Describe the characteristics of familial Alzheimer’s disease
Cases where a dominant gene is inherited that speeds up progression of disease
5 to 10% of cases
Can be due to several gene mutations: PSEN-1 or PSEN-2 (change the way APP is cut) or trisomy 21 (Down syndrome) - the gene responsible for producing APP is located on this chromosome - increased expression of APP and therefore plaque build up.
In those with Down syndrome, by what age does familial Alzheimer’s likely to have developed?
Aged 40
Cholinesterase inhibitors are recommended for which stage of Alzheimer’s?
Mild to moderate disease
What do cholinesterase inhibitors do?
Increase the level of acetylcholine in the brain
What are some side effects of cholinesterase inhibitors?
Nausea
Diarrhoea
Trouble sleeping
Muscle cramps
Usually mild and temporary
Memantine is usually used for which stage of Alzheimer’s disease?
Severe
Maybe moderate
Can both cholinesterase inhibitors and memantine be used in the treatment of Lewy body dementia?
Yes
What drugs should be avoided in Lewy body dementia?
Neuroleptics
Extremely sensitive to side effects and may develop irreversible Parkinsonism
In Lewy body dementia what is the name of the protein that gets misfolded in the neurons?
Alpha synuclein - aggregates to form Lewy bodies
In Lewy body dementia, do the motor symptoms occur early or late?
Late
What symptoms are associated with vascular dementia?
Varies depending on region damaged
If stroke in temporal - difficulty with memory
Frontal - personality change
Appear suddenly and brain function decreases with each stroke
How is vascular dementia diagnosed?
Symptoms
Tests to confirm loss of brain function e.g MMSE
Imaging - CT or MRI to show infarcts
How is vascular dementia treated?
Focus on reducing repeated strokes
- manage BP, cholesterol, diabetes, stop smoking, diet and exercise improvements
What are 3 types of frontotemporal dementias?
Frontotemporal lobar degeneration with tau pathology
Pick’s disease
Familial tauopathies
What are the main symptoms seen in frontotemporal dementias?
Personality change and social conduct problems
Impaired judgement and insight
Speech output falls eventually to mutism
Insidious onset
Onset before 65
Relatively preserved memory and visuospatial skills
What is the most common type of frontotemporal dementia?
Pick’s disease
What are Pick bodies?
Spherical aggregations of tau protein
Should cholinesterase inhibitors or memantine be used in frontotemporal dementia?
No
Is a strong family link common in frontotemporal dementia?
Yes
Is dementia more common in men or women?
Women
What is the only way to make a definitive diagnosis of dementia?
Biopsy (post mortem)
