Alzheimer's and Other Dementias Flashcards
What is vascular dementia?
- Dementia induced from avascular blood supply to brain
- Blood supply to brain is interrupted by blocked/diseased vascular system
What are the features (causes) of vascular dementia?
- Reduced cerebral perfusion (strokes; ischaemia)
- Thromboembolism (stroke)
- Small blood vessel disease in brain
- Bleeding into the brain
How difficult is it to diagnose vascular dementia? How is it diagnosed?
- Easy diagnose, easily distinguishable from Alzheimer’s disease (vascular origin)
- MRI or CT scans; used to confirm lesions caused by vascular disease
How is vascular dementia treated?
No approved treatment currently:
• Clinical trials - cholinergic stimulants, vasodilators (treating cause), platelet aggregation inhibitors
• Preventative measures
What is Dementia w/Lewy Bodies (DLB)?
- Dementia as a result of Lewy body build-up (made up of α-synuclein)
- Build-up/deposits in dopaminergic (DA) neurones of substantia nigra
How is DLB diagnosed/features?
- Fluctuating cognition; varying attention and alertness (as w/most dementias)
- Visual hallucinations; form of psychosis
- Movement disorder (shared w/Parkinson’s Disease)
How is DLB distinguished from PDD (Parkinson’s disease dementia)?
• Severity of movement disorder:
- DLB; dementia precedes onset of movement disorder by 1 year (can have symptoms of movement problems but not established in 1st year)
- PDD; dementia occurs in the presence of existing movement disorder, pronounced bradykinesia (slowness of movement)
What is the three-pronged treatment approach to DLB?
• Cognitive:
- Cholinesterase inhibitors e.g. donepezil and rivastigmine (prevent ACh breakdown in cleft)
- NMDA receptor blocker; memantine (blocking Glu - implicated in DLB)
• Motor:
- Levodopa
- DA agonists (as per Parkinson’s)
• Psychiatric:
- Antipsychotics CONTRAINDICATED (exacerbate motor symptoms
What non-pharmacological treatments are associated w/DLB?
- Memory prompts (e.g. logbook of daily activities, post-its)
- Education of caregivers (debilitating condition; how to care for patient)
- Mobility aids (motor symptoms)
How does Fronto-temporal dementia present? How is it diagnosed?
- Loss of emotional warmth, apathy, selfishness etc. (frontal lobe affected)
- Decline in language, and memory (main symptom)
Diagnosis:
• Neuropsychological evaluation (specialist required)
What are the frontal and temporal lobes responsible for?
• Frontal:
- Part of cerebral cortex
- Personality; man impaled in frontal lobe and survived = completely different after, (reasoning, judgement) some motor coordination
• Temporal:
- Speech, language, memory
What are the pathophysiology/features of Frontal-temporal dementia?
- Mutation in tau protein
- Impact on neuronal processing, neuro-degeneration, normal nerve cell processes disrupted = cell death
What is the pathophysiology of Alzheimer’s disease?
- Formation of beta-amyloid plaques (main)
- Neurofibrillary tangles (knock-on effects)
How do beta-amyloid plaques form WRT Alzheimer’s?
- Normally, at the neuronal cell, gamma secretase and alpha secretase enzymes are implicated in the cutting/snipping of amyloid precursor protein (APP), which is embedded in the nerve cell membrane
- This usually produces a harmless P3 protein fragment as a result
- However, in Alzheimer’s; through mutation, alpha-secretase enzyme is replaced by beta-secretase (whilst gamma-secretase still remains)
- Thus when APP is cut now, a beta-amyloid fragment is produced instead of a harmless P3 protein fragment
- These beta-amyloid fragments clump up, eventually forming plaques
- Causing neurodegeneration and death of neurones, hence Alzheimer’s
How are neurofibrillary tangles implicated in the pathophysiology of Alzheimer’s disease?
- Affects microtubules; which have role in cell stability and the permitting of nutrient movement in the CNS
- Tau proteins in microtubules facilitate and support this process
- However, in Alzheimer’s: Tau protein becomes phosphorylated
- Leads to formation of neurofibrillary tangles
- These affect nutrient movement across microtubules; impeding movement
- Thus resulting in neurodegeneration of neuronal cells
»> Knock-on effect of beta-amyloid plaque formation
What is the main neurotransmitter are involved in Alzheimer’s disease?
- Cholinergic (ACh) pathways; cognition and memory
- Thus research focus = manipulating ACh
What are the other NTs involved in Alzheimer’s disease, and what are they responsible for?
Other NTs (behavioural symptoms):
- Glu; learning
- 5-HT; mood and psychosis
- GABA(a); anxiety + lethargy
- NA; aggression
Why is Alzheimer’s hard to treat?
- Neurotransmission is only impacted upon significant cell death
- Thus treatment is difficult given symptoms do not present until there is already massive cell death
What genetic elements are involved in the aetiology of Alzheimer’s disease?
• Coding variant on amyloid precursor protein gene
- Icelandic study; found in elderly w/this variant are protected against Alzheimer’s
• Familial Alzheimer’s
- Autosomal dominant mutations in chromosome 1, 14 and 21 in families displaying the disease
- Info. on CHR 21 derived from persons w/Down’s
• Late onset Alzheimer’s
- Isolated gene; apolipoprotein E (APOE)
- Synthesised in brain and liver, involved in lipid metabolism and tissue repair
- Allele APOε4 associated w/lower cognitive performance and mild cognitive impairment; progresses to dementia (Alzheimer’s)
What environmental factors are involved in the aetiology of Alzheimer’s disease?
• Head trauma:
- Survivors of head trauma observed to overexpress amyloid precursor protein (protective role)
- Increases probability of forming amyloid plaques
• Diet and malnutrition:
- Rabbits fed high cholesterol diet formed amyloid plaques
- Greater vitamin B12 deficiency observed in families w/AD and amyloid precursor mutation
What are the cognitive and behavioral symptoms of Mild AD?
• Cognitive (worsen w/AD stages):
- Short term memory impairment e.g. names of relatives
- Aphasia; inability to communicate in speech (start forgetting words, vocabulary decreases)
• Behavioural (common across AD stages):
- Reversal changes; previously social person may become introverted
- Depression (common across all stages of AD)
- Acute episodes of confusion, disorientation, hallucinations, agitation
> > > Person still able to day-to-day stuff
What are the cognitive and behavioral symptoms of Moderate AD?
• Cognitive (worse than mild)
- Poor retention of recent memories (short-term memory) but can be triggered by visual cues e.g. photo of family member for names
- Chronology of events severely affected; e.g. think they were married before they were born
- Effects on language; language learned most recently eroded first (short-term)
- Effects on comprehension
- Executive and intellectual function diminishes
- Reduced capacity for self-care; hygiene diminishes etc.
• Behavioural (similar to mild but slightly worse)
- Neurological alterations in brain
- 5-HT, DA, and NA implicated in aggression, agitation, psychoses
- Reduced function in frontal lobes impacts personality; apathy, depression, psychosis
- Sleep disturbance due to changes/detachment to the brainstem (medulla, pons, midbrain); pons involved in sleep/waking
What are the cognitive and behavioral symptoms of Late AD?
- Full-time care required
- Common stage of death e.g. pneumonia
- Almost irreversible (hard to treat)
• Cognitive:
- Memory function severely impaired ‘gone’
- Language skills; lost, speech is impoverished - can’t vocalise, child-like close to forming words
- Executive/intellectual function lost (can’t make decisions)
- Incontinence; self-care assistance/pads required
- Dysphagia (swallowing challenges; tube?); could inhale food into lungs instead - pneumonia risk
- Mobility diminishes; bed or chairbound
• Behavioural (similar to moderate):
- Aggression
- Agitation
- Sleep disturbance
- Psychoses
- Depression
> > > As functional impairment increases, physical function declines and eventually diminishes
What are the symptoms of Advanced AD?
- Most do not get to this stage; pass away at Late AD
- Completely dependent
- Mute
- Dysphagia; can’t swallow (pneumonia/flu)
- Incontinence; pads
- Cardiac
- Stroke
> > > Will die