Immunotherapies in Alzheimer's disease: state of the art and potential use in the elderly

Abstract

The recent positive results of phaseIII clinical trials evaluating the efficacy of anti-amyloid antibodies in Alzheimer's disease may give hope for an approbation in clinical practice soon. Indeed, lecanemab showed cognitive efficacy but also on functional status, quality of life and caregiver burden in the phaseIII CLARITY study. Aducanumab has already received marketing authorization in the United States in 2021 for the treatment of Alzheimer's disease. However, these clinical trials include mostly young participants without significant comorbidities who are not fully representative of the real elderly population. It is therefore necessary to examine the potential use of these treatments in routine care in the elderly population and to identify potential barriers to their use. The presence of cerebral microbleeds and anticoagulation, two frequent conditions in the elderly, could limit the use of anti-amyloid immunotherapy in the geriatric population. In this population, another limitation would be the unusually long diagnosis delays given that the anti-amyloid therapies target the earliest stages of the disease. However, the results of the phaseIII trials and in particular the subgroup analyses seem indicate a superior cognitive efficacy in elderly subjects, especially those over 75. European recommendations on the future use of these treatments are therefore awaited to clarify this situation, which will probably require a precise analysis of the benefit-risk balance. Age alone cannot be a contraindication to the administration of these treatments.