Case 4 Flashcards
What is Alzheimer’s?
50-80% of dementia cases
Gradual onset
What are symptoms of Alzheimer’s?
Memory loss
Language deficits
Rapid forgetting
Impaired visuospatial skills
Normal gait and neuro exam early on
What is the pathology of Alzheimer’s?
Generalised atrophy
Beta amyloid plaques
Neurofibrillary tangles
What is vascular dementia?
20-30% of dementia cases
Abrupt, stepwise progression
What are symptoms of vascular dementia?
Focal neurological signs
Signs of vascular disease
What is the pathology of vascular dementia?
Strokes
Lacunar infarcts
White matter lesions
Vulnerable to cerebrovascular events
What is Lewy body dementia?
10-25% of cases
Protein aggregates in nerve cells
Insidious, progressive onset (symptoms not obvious at first)
What are symptoms of Lewy body dementia?
Hallucinations
Fluctuating awareness
What is the pathology of Lewy body dementia?
Generalised atrophy
Lewy bodies in cortex and midbrain
What is frontotemporal dementia?
10-15% of cases
Frontal lobe (behaviour and speech) or temporal lobe (language and knowledge) affected
Insidious onset, rapid progression
What are symptoms of frontotemporal dementia?
Disinhibition
Behavioural changes
What is the pathology of frontotemporal dementia?
Frontal and temporal atrophy
Pick cells and pick bodies in cortex
How are amyloid plaques formed?
Amyloid precursor protein normally cleaved by alpha-secretase
In plaque formation, cleaved by beta- and gamma-secretase
Results in excessive amyloid beta peptides
AB peptides form oligomers and fibrils with beta-pleated sheet structures
Fibrils deposit in insoluble plaques outside neurones
How are neurofibrillary tangles formed?
Tau is a protein involved in microtubule formation
Microtubules are involved in neurone shape, development, transport inside cells, and communication between neurones
When Tau is hyperphosphorylated –> oligomers form
Oligomers aggregate into NFTs inside neurones
NFTs disrupt microtubule formation
Where are neurofibrillary tangles deposited?
Hippocampus
Medial temporal lobe
Frontal cortices
Lateral parietotemporal region
How can AB oligomers lead to NFT formation?
Microglial cells promote inflammation to clear amyloid plaques
Inflammation triggers Tau hyperphosphorylation
How does neuronal death lead to acetylcholine deficiency in Alzheimer’s?
Loss of neurones in nucleus of basalis of Meynert
These neurones are rich in acetylcholine
They supply the amygdala, hippocampus and neocortex
Neuronal death results in acetylcholine deficit in these regions
Acetylcholine involved in memory
What causes serotonin deficiency in Alzheimer’s?
Neuronal death in median raphe of brainstem
What causes noradrenaline deficiency in Alzheimer’s?
Neuronal death in locus coeruleus (small nucleus in brainstem)
What is cerebro-cortical atrophy?
Loss of neurones and synapses
Decrease in amount of brain tissue and brain size
What parts of the limbic system are affected in Alzheimer’s?
Cingulate gyrus
Hippocampus
Anterior thalamus
What is the cingulate gyrus involved in?
Orientation –> memory of time and place
What is the hippocampus involved in?
Short term memory
What is the anterior thalamus involved in?
Attention –> ability to focus on tasks
