Alzheimer's Disease Flashcards
Define Alzheimers Disease
Progressive and irreversible decline in memory and cognitive function (neurodegenerative disorder), greater than expected for that age, has a substantial affect on personality, communication and every day life.
Alzheimers Disease is the most common type of dementia 60-80% cases
What are the key neurological underpinnings to alzheimers disease
Amyloid precursor proteins (APP) found in the brain for neuron growth and repair, norm cleaved by alpha/gamma secretase to soluble fragments, when cleaved by beta/gamma secretase forms insoluble clumps of amyloid beta.
These group together forming plaques that interrupt communication between neurons and act as DAMPS trigger inflammation, may accumulate around arteries inc risk of haemorrhage
Amyloid beta triggers kinases to phosparhylate tau proteins found in microtubles in the neruon.
Accumulates and becomes dysfunction - diregulates cytoskeleton
Less acetylcholine transport
Apoptosis of the neuron.
Synapse loss
What is the natural progression of Alzheimer’s disease?
Memory Loss
Executive malfuncation - difficult to plan or organise, difficulty following a recipe (frontal association cortex problem)
Spatial disorientation and Constructional dyspraxia (hard to follow directions or copy drawing - pariteal association cortex )
Circumlocution (vague, many world when only a few needed)
More advanced - sloppy dressed, slow, apathetic, confused, disoriented, stooped posture
Terminal - bedridden, stiff, unresponsive, nearly mute, incontinent, neuropsychiatric (agitation, despression or psychosis), loss of muscle control (aspiration pneumonia, difficulty swallowing etc)
How can imaging assist the diagnosis?
First line: Neuroimaging - shows cortical atrophy (narrower gyri and larger sulci, ventricles appear larger) this can be shown on an MRI or CT
Hypometabolism shown on a PET scan with glucose analogue tracers
PET scan can also show elevated amyloid plaques using amyloid tracers.
What is the key epidemiology of Alzheimers Disease?
Most common type of dementia up to 80% cases
Peak incidence in 70+ years
Before 65yrs is early onset
What are some non-modifiable risk factors for Alzheimers disease?
Age - doubles every 5 years over 65yrs
Sex - female higher lifetime risk - longer life expectancy or hormones
Head injury - moderate to severe traumatic brain injury (disrupts neuronal networks and increased amyloid beta production)
APOE genes - three alleles E4 increase risk, E2 protective
EOFAD genes - PSEN1, PSEN2, Amyloid precursor protein (APP) increase risk
Vascular disease - HTN, DM, hypercholesterolemia,
What are some modifiable risk factors for Alzheimer disease?
Educational attainment - lower education - reduced cognitive reserve, early onset of symptoms
Vascular risk - smoking, obseity
Diet - high in saturated fats and card (western) in risk, Mediterraneae diet decrease risk
Physical activity - decrease risk with regular exercise, increase neuroplasticity nad reduce systemic inflammation
Chronic sleep derivation or sleep aponea - increase risk of AD by affecting amyloid beta clearance from brain during sleep.
What brain regions are mainly affected in Alzheimer disease?
Hippocampal region - medial temporal lobe - responsible for storing new memories - hence initial short term memory loss.
Tends to affect limbic lobe (amygdala) and olfactory region.
May spread to frontal, temporal and parietal regions.
What signs of congitive impairement tend to be present in Alzheimers disease?
Memory loss - generally affects recent events more than distant, difficult to learn new info, defer to family members when answ questions, vague with dates
Problems with reasoning and communication
Difficulity in making decisions/executive function
Nominal dysphasia
What are the behavioural and psychological symptoms of dementia?
Fluctuate in strength
Depression
Agitation
Psychosis
Apathy
Disinhibition
What difficulties with daily living do people with dementia tend to have?
Initially struggle with more difficult tasks often related to using kitchen appliances
With time also struggle with simpler tasks e.g washing, getting dressed become a problem.
What are the first line investigations in alzheimers disease?
Cognitive testing - MMSE or the Addenbrookes cognitive exam - assess cognitive domains over time
Blood test - FBC, LFT, TFT, Vb12 and folate - exclude reversible cause of cognitive impairment
Brain imaging - CT/MRI to rule out other pathologies
What are the key differential diagnosis for a patient with alzheimers disease?
How to differentiate?
Vascular dementia - stepwise deteriotation rather than gradual as seen in alzheimers, more cerebrovascular risk factors, focal neurological signs
Frontotemporal dementia -early behavioural/personaility changes, may loose word meanings, family history
Lewy body dementia - fluctuating cognition, parkinsonism, visual hallucination
What non-pharmacological management is recommended for patients with dementia?
NICE recommends offering:
Range of wellbeing activities tailored to persona preference.
Group cognitive stimulation therapy for mild and moderate
Should consider group reminiscence therapy and cognitive rehabilitation
What pharmacological management should be offered to patients with Alzhiemers?
Acetylcholinesterase inhibitors (donepezil, galantamine, rivastimine) for mild to moderate
Memantine (NMDA receptor antagonist) second line: moderate with intolerance/contrainidcation for ACHesterase inhibitors, monotherapy in severe, add in for mod or severe.
May also offer anti-depressants or anti-psychotics if needed.
