Advances in Alzheimer’s Disease

Volume 11

Handbook of Intervention and Alzheimer’s Disease

Cyrus A. Raji, MD, PhD

Washington University, St. Louis, MO, USA

Yue Leng, PhD

University of California, San Francisco, CA, USA

J. Wesson Ashford, MD, PhD

VA Palo Alto Health Care System, Palo Alto, CA, USA

Stanford University, Palo Alto, CA, USA

Dharma Singh Khalsa, MD

Alzheimer’s Research and Prevention Foundation, Tucson, AZ, USA

The Handbook of Intervention and Alzheimer’s Disease includes articles on factors that can either inspire or inform future treatment and clinical trials. Such considerations are important in a era in which anti-amyloid immunotherapy is realigning the emphasis [1,2]. While such innovations present opportunities, there are also increased risks of brain bleeds and edema apparent on conventional neuroimaging [3] that can, in a small number, lead to adverse clinical outcomes. Concurrently, such findings and outcomes are more likely to occur in persons with poor brain health as evidenced in part by visually apparent lacunar infarcts, white matter hyperintense lesions from chronic small vessel ischemic changes, and brain bleeds prior to initiation of treatment [4]. To state the issue plainly, persons with better brain health through management of risk factors contributing to the Alzheimer’s disease ‘preventome’ are more likely to benefit from immunotherapies while minimizing adverse outcomes. Thus, especially as the quality of such novel therapies along anti-tau and anti-neuroinflammation mechanisms are innovated then optimal brain health in patients will take on critical importance. The papers in this volume can therefore be thought of as those that optimize brain health or provide key insights into interventions that may achieve such outcomes.

References

[1] van Dyck CH, Swanson CJ, Aisen P, Bateman RJ, Chen C, Gee M, Kanekiyo M, Li D, Reyderman L, Cohen S, Froelich L, Katayama S, Sabbagh M, Vellas B, Watson D, Dhadda S, Irizarry M, Kramer LD, Iwatsubo T (2023) Lecanemab in early Alzheimer’s disease. N Engl J Med 388, 9–21.

[2] Sims JR, Zimmer JA, Evans CD, Lu M, Ardayfio P, Sparks J, Wessels AM, Shcherbinin S, Wang H, Monkul Nery ES, et al. (2023) Donanemab in early symptomatic Alzheimer disease: The TRAILBLAZER-ALZ 2 randomized clinical trial. JAMA 330, 512–527.

[3] Cogswell PM, Barakos JA, Barkhof F, Benzinger TS, Jack CR, Poussaint TY, Raji CA, Ramanan VK, Whitlow CT (2022) Amyloid- related imaging abnormalities with emerging Alzheimer disease therapeutics: detection and reporting recommendations for clinical practice. AJNR Am J Neuroradiol 43, E19–E35.

[4] Cummings J, Aisen P, Apostolova LG, Atri A, Salloway S, Weiner M (2021) Aducanumab: appropriate use recommendations. J Prev Alzheimers Dis 8, 398–410.