Disease-Modifying Therapies for Alzheimer's Dementia

Introduction to Anti-Amyloid Antibodies

The American Academy of Neurology recommends the use of anti-amyloid monoclonal antibodies, such as lecanemab and donanemab, as the first disease-modifying therapies for Alzheimer's disease, targeting the underlying pathology rather than just symptoms 1

The National Institute of Neurological Disorders and Stroke suggests that patients must have confirmed brain amyloid pathology using either amyloid PET imaging or cerebrospinal fluid testing before treatment initiation with anti-amyloid antibodies 1
Blood biomarker tests for amyloid pathology are emerging as more accessible alternatives, requiring sensitivity ≥90% with specificity ≥85% for primary care triaging or ~90% sensitivity and specificity for confirmatory testing, as recommended by the Alzheimer's Association 1

The American Geriatrics Society recommends that for patients not eligible for anti-amyloid antibodies or seeking symptomatic management, donepezil remains the preferred agent, initiated at 5 mg once daily and increased to 10 mg daily after 4-6 weeks if tolerated 2
The American Academy of Neurology suggests that cholinesterase inhibitors (donepezil, rivastigmine, galantamine) provide statistically significant but modest cognitive benefits without altering underlying disease progression, with a 1-3 point improvement on the ADAS-cog scale 4

The World Health Organization notes that the requirement for amyloid biomarker confirmation creates a diagnostic bottleneck, as 85% of dementia diagnoses are made by non-specialists who historically relied on clinical assessment alone 1
The National Institute on Aging recommends that blood biomarker tests meeting performance standards (sensitivity ≥90%, specificity ≥85-90%) could enable more accessible and scalable diagnostic pathways 1
The Alzheimer's Association suggests that without biomarker confirmation, 36% of patients evaluated by dementia specialists had their etiological diagnosis changed following amyloid PET scanning 1

The World Health Organization notes that demand for neurologists already exceeds supply throughout the United States, and access to specialist services is limited or absent in many low- and middle-income countries 1
The National Institute on Aging recommends that the growing population of older adults (55 million people worldwide with dementia, projected to exceed 139 million by 2050) will further strain diagnostic and treatment capacity 1