PHAM1129: Alzheimer's Disease

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  • Created by: ni6477x
  • Created on: 29-03-19 12:50
What is dementia?
A state of cognitive impairment resulting from the progressive loss of previously acquired mental abilities i.e. daily tasks like dressing, cooking etc
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What is dementia?
A decline in memory and thinking making independent living impossible. A gradual loss of orientation in space and time. A decline in emotional control/motivation or a change in social behaviour
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What conditions cause dementia?
Alzheimer's, Parkinson's, Huntington's, Korsakoff's syndrome (alcohol related), vascular, Lewy bodies, brain tumours
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What is meant by 'dementia as an organic disease'?
A syndrome due to disease of the brain, usually of a chronic & progressive nature in which there is disturbance of multiple higher cortical functions, memory, thinking, orientation, comprehension, calculation, learning capacity, language & judgement
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What is the difference between delirium and dementia?
Delirium = clouding of consciousness. For someone with delirium, symptoms come on over a matter of hours or a few days. The symptoms of dementia come on slowly, over a period of months or even years.
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What classification guides are used in diagnosing dementia?
ICD 10 in the UK and DSM IV in the U.S
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What are the symptoms of Alzheimer's?
Amnesia (memory impairment) AND at least aphasia (language disturbance), apraxia (impaired motor abilities), agnosia (failure to recognise objects despite sensory function) or disturbance in executive function (e.g. planning, organising, sequencing)
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What brain regions are affected in Alzheimer's?
Temporal lobes: memory/attention/emotion/speech. Frontal lobes: behaviour and personality. Occipital lobes: understanding images and meanings of words. Parietal lobes: somatosensory integration, visuospatial dysfunction
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Alzheimer's is characterised by gradual onset and continuing cognitive decline. What are the risk factors?
Age - increases risk from 65+ (particularly >85). Gender. Low education. Family history. Apolipoprotein E 4/4 genotype. Systolic arterial hypertension
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Why is the risk of Alzheimer's higher with age?
Exaggerated brain shrinking and synaptic/neuronal loss. Decreased glucose uptake by neurones in cortical association areas. Loss of cholinergic neurones projecting from basal forebrain to cortex and hippocampus.
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What structural brain differences are seen in Alzheimer's?
enlarged sulci (and ventricles) indicative of neurodegenerative brain tissue loss. Loss of synaptic density = cognitive decline.
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How is Alzheimer's diagnosed?
1) Initial GP presentation. 2) referral to neurology - clinical history & testing. 3) medical diagnostic testing - MRI. 4) neuropsychological testing - cognitive test battery (MMSE). 5) diagnosis and 6-monthly pre-test
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What specific causes of dementia that may provoke full or partial recovery should be eliminated?
Depressive illness. Drug intoxication. CVD. Hydrocephalus. Infective illness. Neoplasia/subdural haematoma. Metabolic/endocrine systemic dementia causes
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What conditions impair general cognition in old age?
Infection (bronchopneumonia/UTI). Nutritional (vitamin deficiency). Endocrine (hypothyroidism, hypocalcaemia, DM). Cardio-respiratory (MI, CHF, AF). Neoplasia. Trauma
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What are Positron Emission Tomography (PET) scans used for in Alzhemier's?
They show the differences in brain activity b/t a normal brain and a brain affected by AD. Blue and black areas in images denote inactive areas.
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Name 3 Global Outcome Scales in AD.
CGIC, CIBIC(+), CDR
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How are the cognitive outcomes in AD measured?
MMSE, ADAS-cog, SIB
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The Mini-Mental State Exam (MMSE) is a neuropsychological diagnostic tool used in AD. How does it work?
5 cognitive domains tested. 1) orientation e.g. days of the week or location 2) memory - immediate word recalls 3) attention and calculation - counting backwards 4) memory - delayed recall 5) language writing and drawing - name 2 items, shape drawing
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Using the MMSE, what score will indicate AD onset?
Below 26 out of 30
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What are the drawbacks of MMSE?
Poor sensitivity (but good specificity). Cut off score is 24 = many cases of early dementia = undetected
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Why is diagnosing AD early beneficial?
Patient safety. Lessens family stress. Early education of caregivers. Advance EoL planning e.g. will, power of attorney, advanced directives. Promotes advocacy for research and development. Early treatment opportunities. Patient's right to know
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How common is Alzheimer's among all forms of dementia?
50-70%
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Alzheimer's can only be definitively confirmed at post-mortem. What are the cellular hallmarks of the disease?
Key 'tombstone' markers. B-amyloid plaques. Neurofibrillary tangles.
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B-amyloid is expressed in nerve and glia cell membranes. It is responsible for cell structure and cell-cell regulation. Describe its secretion.
It is produced & secretase enzymes sever **** chain to release AB peptides into extracellular space.
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How is B-amyloid related to Alzheimer's?
When there's too much AB or dysfunctional removal of it, it accumulates to form hard insoluble plaques unable to be broken down.
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What happens when AB plaques increase in size?
They stimulate an autoimmune inflammatory response and interfere w/ synaptic function and the regulation of transmitter reuptake.
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What happens when there is excess extracellular transmitter due to impaired reuptake?
This generates excitotoxicity and cells adjacent to the plaques die
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What does the autoimmune response generate?
Free radicals by the immunologically active cells
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What are the proposed aetiologies of Alzheimer's?
Environmental toxins. Protein abnormalities. Lipoproteins. Infectious agents. Vascular immune abnormalities. Lack of growth factor. Oxidative stress.
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Which faulty genes are associated w/ Alzheimer's?
Chromosome 21 (encodes APP); 19 (ApoE4 predisposes familial and sporadic late-onset); 1/14 (presenillin-2 and -1 responsible for metabolism of APP)
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What neurotransmitter changes occur in AD?
Considerable decrease in ACh, Serotonin, CRH. Same measurable decrease in DA/NA and GABA as well as glutamate.
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What does CRH stand for?
Corticotrophin Releasing Hormone - there is no change in this NT during normal ageing (along w/ glutamate and serotonin)
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AChE inhibitors are used to treat the symptoms of Alzheimer's. What are the common drugs used?
Tacrine, donepezil, rivastigmine, galantamine
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How do AChE inhibitors work?
They reduce severity of symptoms and slow the rate of symptom progression but do not cure AD or stop the essential pathological process
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Donepezil HCl (Aricept)
Reversible competitive inhibitor. 5mg ON but can increase to 10mg over 4 weeks. SE: n/v, insomnia, syncope
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Galantamine (Reminyl)
RCI and direct nicotinic agonist. 4mg twice daily for one month and then to 8mg bd (maintenance is b/t 8-12mg). SE: n/v, agitation, dizziness
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Rivastigmine (Exelon)
RCI. 1.5mg bd for two weeks and then increase to 1.5mg gradually. SE: n/v, tremor, confusion, agitation, angina
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When should someone stop taking a cholinesterase inhibitor?
Intolerable SE e.g. n/v/d/muscle cramps; deterioration of symptoms over the first 6 months; loss of response over time. Consider switching before discontinuation of CIs
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Memantine HCl (Ebixa) is an NMDA-receptor antagonist that affects glutamatergic neurotransmission Discuss the treatment regime.
Moderate/Severe AD. 5mg OM and up to 10mg BD gradually. SE: dizziness, confusion, anxiety, cystitis. Not to be used in renal impairment
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What future treatments for AD are available?
Drugs to prevent AB deposition and neurotoxicity. Anti-inflammatory agents. Antioxidants. Lipid-lowering strategies. Gene therapy - nerve growth factor
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What neuropsychiatric complications can occur in AD?
Delusions/hallucinations. Mood abnormalities. Behavioural disturbances (e.g. aggression and failure to perform desired behaviours)
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What drugs are used to treat behavioural problems in dementia?
Neuroleptics (haloperidol, chlopromazine, olanzepine, reisperidone), BZs, antidepressants, anticonvulsants and lithium
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What is dementia?

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A decline in memory and thinking making independent living impossible. A gradual loss of orientation in space and time. A decline in emotional control/motivation or a change in social behaviour

Card 3

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What conditions cause dementia?

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Card 4

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What is meant by 'dementia as an organic disease'?

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Card 5

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What is the difference between delirium and dementia?

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