Precision diagnosis of cognitive impairment due to Alzheimer's disease for therapeutic interventions

Abstract

With the advent of anti-amyloid monoclonal antibody (AAMA) therapy, precision diagnosis is necessary for identifying appropriate patients with cognitive disorders due to Alzheimer's disease. Therapy with AAMAs requires that candidates be diagnosed with mild cognitive impairment or mild dementia, have elevated brain amyloid-β, have good physical, psychiatric, and medical health, and lack clinical or biomarker evidence of potentially impactful non-Alzheimer brain disorders. The first three diagnostic activities are the core of the Clinical Practice Guidelines, but the last element of the precision diagnosis requires new decision-making tools for recognizing multi-etiology cognitive impairment. Within the context of shared decision-making between clinician, patient, and family, proper diagnosis is essential. In addition to discussing the benefits and risks of AAMA therapy, the experienced clinician must empathetically assist in bridging the gap between expectations of benefit and the patient's overall diagnostic suitability for AAMA therapy. HIGHLIGHTS: In order to prescribe an anti-amyloid monoclonal antibody (AAMA) to the right patients, those selected for treatment should be diagnosed with mild cognitive impairment or mild dementia, have elevated brain amyloid-β (Aβ), and have good physical, psychiatric, or medical health. Persons with Alzheimer's biology as the primary etiology are the ideal AAMA treatment recipients. A novel activity necessary to optimize therapeutic response is to exclude persons with clinical or biomarker evidence of alternative contributory brain disorders. While mild clinical severity and elevated brain amyloid-β are essential elements for selecting patients for AAMA treatment, clinical judgment is required to weigh the implications of more advanced disease severity, other medical co-morbidities, and the presence of other contributory neuropathologies.

Keywords: Alzheimer disease; diagnosis; lecanemab; therapy.