Is Alzheimer's Prevention Possible Today?

In the absence of disease-modifying therapies, clinicians face an urgent need to be aware of potential interventions to reduce risk of, delay onset of, and at least in some cases prevent Alzheimer’s disease (AD). Although there is no “magic pill” to prevent AD, evolving evidence can assist in answering a common question from patients: “Is there anything that I can do to reduce my risk?” In The Prevention of Alzheimer’s Disease: Lessons Learned and Applied, Galvin eloquently and comprehensively provides a practical scientific overview for clinicians whose patients will inevitably ask how they can protect their brain health over time. Galvin appropriately makes the case that, while the field waits for successful pharmacological interventions, it is prudent to apply interventions that influence the multiple genetic, pathological, and biological pathways that may lead to AD while testing hypotheses related to risk reduction and mitigation. Based on the evidence to date, efforts to slow cognitive decline and prevent dementia may be more successful with multimodal interventions directed toward at-risk individuals based on their personal health profiles, rather than the more-common “one size fits all” approach. As Galvin makes clear, a common methodological constraint of randomized controlled trials, even those that have demonstrated positive outcomes, is their experimental focus on homogeneous study cohorts that make it difficult to generalize results to the individual sitting in front of a clinician. Confirmation studies in real-world clinic settings are needed to test the efficacy and ecological validity of modifiable risk factor–reduction strategies in at-risk individuals, especially those at the asymptomatic preclinical stage of AD. To this end, over the last few years, it has become more common for clinicians to practice in the field of AD prevention. Aligned with Galvin’s rigorous, evidencebased, comprehensive, personalized framework, there are several clinics in United States that focus on AD risk assessment and early intervention. In 2013, the Alzheimer’s Prevention Clinic (APC) at New York-Presbyterian Weill Cornell Medical Center was founded, providing direct clinical care to asymptomatic individuals with a family history of AD. In 2014, the Alzheimer’s Risk Assessment and Intervention Clinic at the University of Alabama in Birmingham was established, followed by the Alzheimer’s Prevention Program at Cedars Sinai Medical Center in Los Angeles in 2015, and the Alzheimer’s Prevention Clinic and Research Center in San Juan, Puerto Rico, in 2016 (in research collaboration with Weill Cornell). Similarly, the Cardiology Cognitive Clinic at the Rush Heart Center for Women in Chicago maintains the same philosophy of early care to protect brain health. These programs have applied the best available evidence in varied ways to provide care and educate people in the absence of definitive preventative treatments, and several have used novel strategies in an effectiveness-proven online AD prevention course (www.AlzU.org) to communicate a sound, balanced message to individuals and family members. From a practical clinical perspective, applying lessons learned from observational studies can help to target a range of modifiable risk factors. Population-attributable risk models estimate that one of every three cases of AD may be preventable (5). Considering that AD pathology begins in the brain decades before cognitive decline (1), pre-symptomatic risk factor management may be an important component of both primary and secondary AD prevention. In one report, the projected effect of risk factor reduction on AD prevalence found that a modest (10– 25%) reduction in seven risk factors (diabetes mellitus, midlife hypertension, midlife obesity, smoking, depression, cognitive inactivity or low educational attainment, and physical inactivity) could prevent as many as 1.1 million to 3.0 million AD cases worldwide and 184,000 to 492,000 cases in the United States. Clinicians and patients have two options: to face the challenges of AD passively or to intervene based on the mounting scientific evidence for a direct relationship between lifestyle and vascular-related risk factors and future dementia. Most of these changes are balanced in terms of risk versus benefit and, especially when under physician supervision, grounded in safety, yet there remains substantial confusion for practicing physicians. With each passing week, more studies are published on either side of the fence, which can help and hinder. Most commonly in medical practice, treatment plans are designed for the “average patient” based on the best-available evidence, incorporating a broad spectrum of data from heterogeneous cohorts that may, or may not, be directly applicable. It may be most practical to provide each person with an individualized, detailed plan (fortified with qualifiers) for reducing the risk of dementia after an extensive evaluation of his or her medical history, lifestyle factors, body composition, and laboratory and cognitive assessments. Physicians can apply this framework rather than adhere to the concept that AD prevention is not possible, which could be interpreted to mean, “There is This Editorial comments on the article by James E. Galvin