A 78yo female has been diagnosed with mild to moderate dementia. What is an effect of a cholinesterase inhibitor?
Improvement in activities of daily living
Patients with Alzheimer’s disease have reduced production of choline acetyl transferase. What impact does this have on them biochemically?
Decreased choline acetyl transferase production leads to a decrease in acetylcholine synthesis and impaired cortical cholinergic functioning.
What is the role of cholinesterase inhibitors in Alzheimer’s disease?
- Provide some improvement in cognitive function and improve ADLs.
- There is no role for cholinesterase inhibitors in advanced Alzheimer’s disease.
Describe the genetics of Alzheimer’s Disease.
- Most cases are sporadic
- 5% of cases are inherited as an autosomal dominant trait.
- Mutations on Chromosomes 21, 14, and 1 are thought to cause an inherited form.
- Apoprotein E allele E4 - encodes a cholesterol transport protein
- RF = Down’s Syndrome
What are the macroscopic pathological changes seen in an Alzheimer’s brain?
Widespread cortical atrophy, particularly involving the cortex and hippocampus
What are the microscopic pathological changes seen in an Alzheimer’s brain?
- Cortical plaques due to deposition of type A-Beta-Amyloid protein and intraneuronal neurofibrillary tangles caused by abnormal aggregation of tau protein
- Hyperphosphorylation of the tau protein.
What are the biochemical pathological changes seen in an Alzheimer’s brain?
A deficit of acetylcholine from damage to an ascending forebrain projection.
What are ‘neurofibrillary tangles’?
- Paired helical filaments are partly made from tau.
- Tau interacts with tubulin to stabilise microtubules
- In AD, tau proteins are excessively phosphorylated, impairing the function.
What is the characteristic pathological feature of Lewy Body dementia?
Alpha-synuclein cytoplasmic inclusions (Lewy bodies) in the substantia nigra, paralimbic and neocortical areas.
What are the features of Lewy Body dementia?
1) Progressive cognitive impairment:
- > early impairments in attention and executive function, rather than just memory loss.
- > cognition may be fluctuating
2) Parkinsonism
3) Visual hallucinations (other features such as delusions and non-visual hallucinations may also be seen)
How is Lewy Body dementia diagnosed?
- Usually clinical diagnosis
- SPECT (Single-photon emission CT) is increasingly used. Commercially known as a ‘DaTscan’.
What is the Sensitivity and Specificity of a SPECT scan in diagnosing Lewy Body dementia?
Sensitivity = 90%
Specificity = 100%
What is the management of Lewy Body Dementia?
- Acetylcholinesterase inhibitors (Donepezil, Rivastigmine)
- Memantine
Why should neuroleptics be avoided in patients with Lewy Body dementia?
- Patients are extremely sensitive and may develop irreversible parkinsonism.
Note: questions may give a history of a patient who has deteriorated following the introduction of an antipsychotic agent.
What is the most common cause of Dementia in the UK?
Alzheimer’s Disease
followed by Vascular and Lewy Body dementia
Diagnosis of Dementia can be difficult and is often delayed. List 2 assessment tools recommended by NICE for the non-specialist setting in assessing for dementia.
1) 10-point cognitive screener (10-CS)
2) 6-item cognitive impairment test (6CIT)
What score on the Mini Mental State Examination implies dementia?
A MMSE score of 24 or less out of 30 suggests dementia.
Describe a patient’s pathway when they are en-route to getting a dementia diagnosis.
Primary Care: blood screen is usually sent to exclude reversible causes.
Refer to Memory Clinic / Old Age Psychiatry.
Secondary Care: Neuroimaging is performed to exclude reversible conditions (eg. subdural haematoma, normal pressure hydrocephalus), and to help provide information on aetiology to guide prognosis and management
Which bloods might a Primary Care Physician request in order to identify the reversible causes of Dementia?
FBC U&Es LFTs Calcium Glucose TFTs Vitamin B12 Folate
When and why might acetylcholinesterase inhibitors be contraindicated in a patient with Alzheimer’s?
SE of acetylcholinesterase inhibitors (Donepezil, Rivastigmine, Galantamine) = BRADYCARDIA (or SA block or AV block).
Hence, meds might be CI / started with caution in patients with conduction abnormalities or those taking beta blockers, rate-limiting CCBs, or Digoxin.
List some possible side effects of Acetylcholinesterase inhibitors.
- Neuroleptic Malignant Syndrome very rare!!
- GI: N&V, anorexia, diarrhoea
- Agitation
- Hallucinations
- Syncope
- EPSEs
Who prescribes Acetylcholinesterase inhibitors?
- Should be initiated by specialists with expertise in the area of prescribing these meds
eg. Psychiatrists, Elderly Care Specialists, Neurologists.
Note: GPs may be asked to take over the prescribing and monitoring under Shared Care Agreements.
List 5 factors favouring delirium over dementia.
- Impairment of consciousness
- Fluctuation of symptoms: worse at night, some periods of normality
- Abnormal perception (eg. illusions and hallucinations)
- Agitation, fear
- Delusions
Which factors might cause an ‘Acute Confusional State’?
- Physical: dehydration, constipation, UTI
- Medication changes / being in an unfamiliar environment
- Delirium is more common among elderly patients, especially those with poor hearing/eyesight or pre-existing memory problems.
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