Alzheimer disease
Lecanemab slows cognitive decline in patients with early Alzheimer disease
Lecanemab is a humanized monoclonal antibody that binds with high affinity to amyloid-beta. In a multicenter, double-blind, phase 3 trial involving people ages 50 to 90 years with early Alzheimer disease (defined as mild cognitive impairment or mild dementia due to Alzheimer 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 edema or effusions.[199]
Applications for US FDA approval of intravenous lecanemab, and marketing authorizations 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.
Summary
Definition
History and exam
Key diagnostic factors
- memory loss
- disorientation
- nominal dysphasia
- misplacing items/getting lost
- apathy
- decline in activities of daily living and instrumental activities of daily living (IADLs)
- personality change
- unremarkable initial physical exam
Other diagnostic factors
- mood changes
- poor abstract thinking
- constructional dyspraxia
- prosopagnosia
- autoprosopagnosia
Risk factors
- advanced age
- family history
- genetics
- Down syndrome
- cerebrovascular disease
- lifestyle factors and medications
- less than high school education
- traumatic brain injury
- depression
- hearing loss
- hyperlipidemia
- female sex
- elevated plasma homocysteine level
- artificially sweetened soft drink consumption
Diagnostic investigations
1st investigations to order
- bedside cognitive testing
- CBC
- metabolic panel
- serum thyroid-stimulating hormone (TSH)
- serum vitamin B12
- urine drug screen
- CT
- MRI
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)
Emerging tests
- amyloid-PET
Treatment algorithm
all patients
Contributors
Authors
Judith Neugroschl, MD
Associate Professor of Psychiatry
Icahn School of Medicine at Mount Sinai
New York
NY
Disclosures
JN declares that she has no competing interests.
Acknowledgements
Dr Judith Neugroschl would like to gratefully acknowledge Dr Brandy R. Matthews, Dr Asif S. Bhutto, and Dr Julie K. Gammack, the previous contributors to this topic.
Disclosures
BRM, ASB, and JKG declare that they have no competing interests.
Peer reviewers
Roy J. Goldberg, MD, FACP, AGSF, CMD
Medical Director
Kings Harbor Multicare Center
New York
NY
Disclosures
RJG declares that he has no competing interests.
Philip Scheltens, MD, PhD
Professor of Neurology
Department of Neurology/Alzheimer Center
VU University Medical Center
Amsterdam
The Netherlands
Disclosures
PS declares that he has no competing interests.
Differentials
- Delirium
- Depression
- Vascular dementia
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