Dementia Flashcards
Define dementia
A progressive, degenerative neurological disorder characterised by cognitive decline beyond what is expected from normal ageing.
Irreversible
Presents as memory loss, problems with reasoning, communication, change in personality among many others.
What are the most common types of Dementia?
Alzheimers Disease
Vascular Dementia
Lewy Body dementia
Frontotemporal dementia
Mixed
Young Onset
What is the prevalence of dementia?
Around 7% of older people in the UK have dementia.
This increase to 10% of 80-84yrs, and up to 41% of 95yrs+
Large numbers are estimated to be living with undiagnosed dementia or probably dementia in primary care settings.
Give an overview of the underlying pathology of Alzheimers disease
Atrophy of the cerebral cortex and formation of amyloid plaques and neurofibrillary tangles
This triggers neuroinflammation and reduction in neurotransmitters, particularly Acetylcholine.
Mainly in the parietal and temporal lobes.
Often co-exists with other dementia.
What is the detailed process of Alzheimer’s dementia?
Amyloid Precursor Protein (APP) in cell membrane - helps neuron grow and repair
Normally broken down by alpha and gamma secretase - creates soluble products that are disposed of.
1) If beta and gamma secretase break down - creates insoluble amyloid beta monomers
Aggregate to form beta amyloid plaques - accumulate between neurons - impaired signalling
-> trigger neuroinflammation
-> deposit around BV -> inc risk of haemorrhage
-> activates kinase (see next step)
2) Microtubules inside neurons contain tau, kinase enzymes phosphorylated tau leading to formation of neurofibrils tangles inside neuron -> leads to destruction of cytoskeleton -> unable to transport neurotransmitters.
What are some risk factors for Alzhiemers disease?
Genetics - APOE (allele ε4 is a risk, ε2 is protective), EOFAD (PSEN1?2 and APP) - around 50% of familial early onsey
Age - doubles every 5yrs after 65yrs
Sex - females, due to life expectance of hormones
Lower education attainment
Vascular risk factors - HTN, DM, obesity, hypercholesterolemia and smoking
Head injury
Diet - high in fats/simple carbs
Lack of regular physical activity
Sleep disorders or chronic sleep deprivation.
What does Alzheimers Disease look like on imaging?
Cortical atrophy - increased sulci and decreased gyri
Ventricle enlargement
Particularly enlargement of the temporal horn of the lateral ventricles due to atrophy of the hippocampus
How does alzheimer disease tend to present?
Develops insidiously over months/years
Cognitive - memorly loss (recent more than distant, struggle to learn more things, vague with dates or refer to family), decision making, reasoning and communication (not dysphasia)
Behavioural/psychological - fluctuate, depression, agitation, psychosis, apathy, disinhibition
Struggle with ADLS - kitchen appliances, washing, dressing etc
What are the first line investigations for Alzheimers disease?
Cogntive testing - MMSE, MoCA, Addenbrookes Cogntivie Examination 3
Bloods - FBC, electrolytes, LFTs, TTT, VB12 and folate - identify reversible causes.
Imaging - CT or MRTI head - exclude other cerebral pathology, pos may see atrophy of medial temporal lobe structures.
What further investgiations may be done on a patient with Alzheimers disease?
Cerebrospinal Fluid Analysis - AD likely if beta-amyloid reduced and total tau/phosphorylated tau are increase
Amyloid PET imaging - amyloid plaques in vivo
What is the non-pharmacological management for Alzheimers disease?
Range of activities to promote wellbeing tailored to the individual.
Group cognitive stimulation therapy is mild or moderate
Consider group reminiscence therapy and cog rehab
Advanced Care Planning
Signposting patient/family to charity support groups.
What is the pharmacological management for Alzheimer disease?
Acetylcholinesterase inhibitors - donepezil, galantamine, rivastigmine
Memantine (NMDA receptor antagonist) is second line.
When may memantine be used to treat Alzheimers disease?
Second line
->if moderate disease and intolerant or contraindicated for acetylcholinesterase inhibitors
-> as an add on to moderate or severe
-> monotherapy in severe
How should behavioural/psychologycal symptoms of dementia be managed?
Do NOT recommend antidepressant for mild to moderate
Antipsychotics are only given if risk of harm to themselves/others or if agitation/hallucination/delusion causing severe distress.
What are the drawbacks of donepezil in Alzheimers management?
Contraindicated in bradycardia
Adverse effects = insomnia
Define vascular dementia
A severe vascular cognitive impairment secondary to ischaemia or haemorrhage (from CVD).
Second most common type of dementia
Syndrome with a spectrum of presentations
What are the relevant risk factors for vascular dementia?
History of TIA
Atrial fibrillation
HTN
DM
Hyperlipidaemia
Smoking
Obesity
Coronary Heart Disease
FM of stroke or cardiovascular disease
Rarely inherited in CADASIL.
What are the different types of vascular dementia?
Stroke related - multiple or single infarct
Subcortical - small vessel disease
Mixed dementia - the presence of both VD and Alzheimers disease
What are the symptoms key to vascular dementia?
Sudden Stepwise deterioration of cognitive function - over months or years
Can have focal neurological deficits -> visual disturbance, sensory or motor deficits
Attention and concentration loss
Seizures
Memory loss
GAIT problems
Speech problems
Emotional disturbance
What criteria do NICE recommend is used to diagnose vascular dementia?
What is this?
NINDS-AIREN
1) cognitive decline so struggle with ADLs, cause is not due to secondary effect of CV event
2) Cerebrovascular disease
3) Relationship between 1+2 -> aka dementia within 3m stroke, sudden deterioration
What is the management plan for vascular dementia?
Mainly symptomatic - therapy targeted to neurological defect either focal or global decline in cognition
Detect and address cardiovascular risk factors - to slow down the progression.
What is frontotemporal dementia?
Primary neurodegenerative condition = 2% of dementia cases.
Progressive illness - behavioural changes and language problems.
Early onset compared to other dementias at around 50-60yrs
What is the aetiology of frontotemporal dementia?
Combination of genetics and lifestyle
50% have a positive family history
10% show autosomal dominant inheritance
Genes include:
MAPT - resulting in tau inclusion bodies
Progranuline (PGRN) - TDP-43 inclusion bodies
C90rf72 - uncertain
What is the pathophysiology of frontotemporal dementia?
Degeneration in the frontal and temporal lobes
Behavioural variant - mainly frontal lobes
Non-fluent/agrammatic variant - posterior frontal lobe, insular and temporal (including hippo)
Semantic - left-sided temporal and hippo, frontal lobes are relatively spared.
All tend to show axonal injury and inclusion bodies of tau (MAPT gene) or immunoreactive ubiquitin (PGRN)
