Alzheimer's & Dementia Flashcards
Define dementia.
Disturbance of multiple higher cortical functions including memory, thinking, orientation, language, judgement
Commonly accompanied by deterioration in emotional control, social behaviour or motivation
Give examples of non-cognitive symptoms of dementia.
Physical aggression
Agitation
Psychotic symptoms
Sleep disturbances
Describe the main characteristics of Alzheimer’s dementia.
Characterised by atrophy and significant loss of neurones in areas of the brain primarily associated with cognitive function and memory
Classic features are neuritic plaques and neurofibrillary tangles
Describe the features of vascular dementia.
Damage can be caused by small strokes or injury to vessels from high blood pressure
Affects neuronal networks involved in cognition, behaviour, execution and memory
Memory may be more intact than in some other forms depending on the area of the brain that is impaired
Describe the features of Lewy body dementia.
In Lewy body, cognitive signs start first
In Parkinson’s, motor symptoms of idiopathic Parkinson’s disease predate the dementia
Brain changes include clumping of the protein alpha-synuclein
Memory impairment is not necessarily prominent early feature
Which neurotransmitters/neurones are responsible for symptoms of dementia?
Loss of cholinergic neurones is thought to be involved in problems with cognition
Loss of dopaminergic neurones in substantia nigra is postulated to account for degeneration of motor control
What are the three core diagnostic features of Lewy body dementia?
Fluctuating cognition with pronounced variation in attention and alertness
Recurrent visual hallucinations
Spontaneous features of Parkinsonism
Describe the features of frontotemporal dementia.
Affects the front of the brain
Can present with disinhibitive, apathetic and language effects rather than memory loss
Primary progressive aphasia is the type where outward speech decreases
Semantic dementia causes failures in understanding language
What are the two main types of symptoms of dementia?
Cognitive deficits
Behavioural and Psychological symptoms
Give examples of BPSDs.
Depression Psychosis Agitation Apathy Insomnia Sexual disinhibition
How do Tau tangles contribute to disease?
Responsible for stabilisation of neurones
If hyper-phosphorylated they cause destabilisation
Briefly describe the amyloid cascade hypothesis in Alzheimer’s.
Processing by beta-secretase cleaves at ‘safe’ areas, producing a monomer
Further processing by y-secretase forms the β-amyloid monomer
The β- amyloid protein is extremely sticky, which can cause aggregation to form oligomers
Excess formation of this can be seen in genetic mutations which can lead to AD
Processing by a-secretase is anti-amyloidogenic
Describe the effects of neuroinflammation.
Response to abnormal presence within the brain
Inflammatory responses begin to vary in the elderly, often involving collateral damage
Glial cells are responsible for packaging and clearing amyloid (phagocytosis), however inflammatory response is slowed in elderly so this will impact the levels of amyloid accumulating
At some point, cells go from phagocytosing amyloid, to pro-inflammatory response, leading to neurones becoming target
Discuss the pathophysiology of Alzheimer’s around diagnosis.
Preclinical phase shows no obvious symptoms
CSF measurements and PET imaging however can begin to see abnormal amyloid activation
Abnormal concentrations of amyloid are more obviously seen in genetic AD
Many of the physiological changes are occurring in only mild cognitive impairment (MCI), thus have already occurred before diagnosis
Neuronal loss has already begun to occur based on volumetric MRI scans
Biomarker levels already at a high
What is resveratrol?
Found in red wine
Thought to bind to amyloid oligomers, preventing the binding to receptors and damage to neurones
Changed configuration of oligomers to prevent degeneration and neuronal toxicity
