Makindo Medical Notes.com

Related Subjects: |Dementias |Abbreviated Mental Test Score (AMTS) |Alzheimer disease |Dementia with Lewy bodies |Frontotemporal dementia |Corticobasal degeneration |Creutzfeldt Jakob disease |Vascular Dementia |Anti Dementia Drugs |AIDS Dementia Complex |Normal Pressure Hydrocephalus |Acetylcholinesterase inhibitors |Mental Capacity Act 2005 |Behavioural and Psychological Symptoms of Dementia

About

• Diagnosis: history from patient and family, cognitive testing, examination and imaging
• Progressive decline of cognitive function which affects 10% of those over 65.

Aetiology

• Increased in Down syndrome. Linkage to gene for apolipoprotein E4.
• Reduced cholinergic, noradrenergic and dopaminergic neurotransmission

Pathology

• Reduced Acetylcholine in the brain and CSF and senile plaques and neurofibrillary tangles
• Neurofibrillary tangles: composed of Paired helical filaments of the microtubule-binding protein tau found within the cytoplasm of neurons. Found in cortex in AD but not specific for AD.
• Senile plaques: composed of Beta-Amyloid protein and found in the hippocampus, basal forebrain and cortex.
• Beta Amyloid A4 protein forms a beta-pleated sheet tertiary form. It may accumulate and is locally toxic. It is formed during the processing of Amyloid precursor protein (APP)

Genetics

• Very rarely occurs as an autosomal dominant.
• Presenilin 1 and 2 genes. Lead to increased amyloid precursor protein
• Amyloid precursor protein gene on chromosome 21
• Homozygotes apolipoprotein E e 4

Increased Risks

• Age, Positive family history, Head trauma with concussion
• Diabetes mellitus, Hypertension, Cardiovascular disease
• Head trauma, Down syndrome

Clinical

• Diagnosis is mainly clinically supported by imaging
• Difficulty learning and retaining new information (anterograde amnesia).
• Episodic memory loss, reduced visuospatial ability and geographic orientation
• Motor problems (dyspraxias) and Language difficulties
• Constructional and Dressing apraxia, Agnosia - fails to recognise people/objects.
• Impaired Executive planning e.g. steps to make a cup of tea.
• Loss of insight. anxiety, irritability, depression

Investigations

• FBC, U&E, LFT, TFTs, B12, folate and probably VDRL to exclude treatable causes
• Head CT may show atrophy with advancing disease but its main role is to exclude differentials such as tumour , hydrocephalus, meningioma. In most cases, it is sufficient when the clinical picture fits.
• MRI: Marked atrophy of the hippocampus and indeed hippocampal volumes correlate progression. There are often T2W white matter changes of small vessel disease.
• EEG will show mild slowing but non-specific
• Post mortem histology (if done) - Neurofibrillary tangles are composed of the microtubule-binding protein tau which has been hyperphosphorylated. Senile plaques consist of beta-amyloid. Other findings include Hirano bodies which are rod liked eosinophilic bodies but are non-specific

Differential

• Dementia with Lewy bodies
• Depression
• Dementia caused by cerebrovascular disease

Management goals

• Maintain quality of life and Maximize function in daily activities
• Enhance cognition, mood and behaviour
• Foster a safe environment and promote social engagement, as appropriate

Management

• Diagnosis involves specialist assessment which may be through a memory clinic. Local policies on the use of agents should be followed with ongoing assessment. Medications are for mild to moderate dementia and may improve cognition for 6 months.
• Benefits are modest and should not be overstated. Monitor MMSE and side effects. These include nausea, vomiting, diarrhoea, muscle cramps, headaches, dizziness, fainting, appetite loss, and skin reddening
  • Donepezil (Aricept) Tablets and orodispersible tablets. Dosage 5 -10 mg daily
  • Galantamine (Reminyl XL) Tablets, capsules and liquid. Dosage 8mgs-24 mg once daily
  • Rivastigmine (Exelon) Tablets and liquid. Dosage 1.5mgs - 6mgs twice daily. Transdermal patches. Dosage 4.6mg or 9.5mg once daily
  • Memantine blocks NMDA channels
• Depression may be managed with a trial of SSRI which have low anticholinergic side effects. This needs support also from caregivers.
• Agitation may need low dose antipsychotic agents. Try non-pharmacological methods first. Consider when behavioural problems are significant with risks to the patient. Drugs used include quetiapine, olanzapine and risperidone. Check QT. Doses should be minimised and regularly reviewed and stopped if not needed. Recent reports suggest these drugs are overused.
• Social services support. Alzheimer society. Drug therapy is secondary to simply and reliable social support. A multidisciplinary team approach may be through psychogeriatricians most commonly involving social work, occupational therapy and physiotherapy. As the disease progresses and dependency increases then care becomes more medicalised and patients become bed-bound and require total nursing care. End-of-life care should be anticipated with plans made and decisions made in terms of palliation and the extent of medical input.
• Ongoing Mortality is about 10% per year