Lecanemab slows cognitive decline in patients with early Alzheimer's disease
Lecanemab is a humanised monoclonal antibody that binds with high affinity to amyloid-beta. In a multicentre, double-blind, phase 3 trial involving people aged 50 to 90 years with early Alzheimer's disease (defined as mild cognitive impairment or mild dementia due to Alzheimer's disease), intravenous lecanemab was associated with moderately less decline in cognition and function, as well as reduced brain amyloid burden, at 18 months, compared with placebo. Adverse effects of lecanemab included infusion-related reactions and amyloid-related imaging abnormalities with oedema or effusions.
Applications for US FDA approval of intravenous lecanemab, and marketing authorisations in Japan and Europe, are expected to be considered in 2023.
Further studies of lecanemab are ongoing, including a phase 1 study investigating subcutaneous dosing.
Alzheimer's disease (AD) is a chronic, progressive neurodegenerative disorder characterised by a global, non-reversible impairment in cerebral functioning.
AD is characterised by memory loss, loss of social and occupational functioning, diminished executive function, speech and motor deficits, personality change, and behavioural and psychological disturbance.
It has a deteriorating course over up to 8-10 years.
Brain lesions are marked by neurofibrillary tangles, senile plaques, neuronal loss and brain atrophy, with defects in acetylcholine synthesis at the cellular level.
Treatment requires a multidisciplinary approach with increasing emphasis on behavioural and psychological symptoms.
Psychosocial interventions and carer support are key to managing disease course. Carer support groups are beneficial to carers and should be considered, where available.
Alzheimer's disease (AD) is a chronic neurodegenerative disease with an insidious onset and progressive but slow decline. AD is the most common type of dementia. It often co-exists with other forms of dementia, particularly vascular dementia (mixed-type dementia). The histopathology of AD is characterised by senile plaques, neurofibrillary tangles, and neuronal loss. The hallmark symptoms are memory loss, impairment of daily activities, and neurobehavioural abnormalities. Definition of severity varies according to country, but a commonly accepted categorisation is mild, moderate, and severe. The Mini-Mental State Examination can be used as a guide to cognitive impairment, but education, language, and any other relevant factors must be taken into consideration when interpreting scores.
History and exam
Key diagnostic factors
- presence of risk factors
- memory loss
- nominal dysphasia
- misplacing items/getting lost
- decline in activities of daily living and instrumental activities of daily living (IADLs)
- personality change
- unremarkable initial physical examination
Other diagnostic factors
- mood changes
- poor abstract thinking
- constructional dyspraxia
- advanced age
- family history
- Down's syndrome
- cerebrovascular disease
- lifestyle factors and medications
- less than secondary school education
- traumatic brain injury
- hearing loss
- female sex
- elevated plasma homocysteine level
- artificially sweetened soft drink consumption
1st investigations to order
- bedside cognitive testing
- metabolic panel
- serum thyroid-stimulating hormone (TSH)
- serum vitamin B12
- urine drug screen
Investigations to consider
- cerebrospinal fluid (CSF) analysis
- serum rapid plasma reagin/Venereal Disease Research Laboratory (VDRL)
- serum HIV
- formal neuropsychological testing
- genetic testing
- fluorodeoxyglucose-PET (FDG-PET)
- single-photon emission CT (SPECT)
- electroencephalogram (EEG)
- Vascular dementia
- Clinical guidance in neuropalliative care: an AAN position statement
- Ethical considerations in dementia diagnosis and care: an AAN position statement
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