Around 10% of older American adults, aged 65 and above, are currently living with Alzheimer's disease (AD), according to the Alzheimer's Association in 2019. This translates to approximately 5.8 million existing cases, with an additional 500,000 to 900,000 new cases reported each year. AD ranks as the sixth leading cause of death in the United States, as stated by the Alzheimer's Association in 2019. Despite numerous attempts, including over 400 failed trials with nearly 100 failures during Phase III (resulting in a failure rate of 99.6%), there is currently no effective treatment available for AD, as noted by Cummings, Morstorf, and Zhong in 2014 and Mehta, Jackson, Paul, Shi, and Sabbagh in 2017. Typically, monotherapy pharmaceutical interventions have been the standard approach, but recent research by Cummings, Tong, and Ballard in 2019 emphasizes the necessity of considering combination therapies that target multiple pathways of this complex disease.
Medications prescribed for Mild Cognitive Impairment (MCI) and AD, such as Aricept, Exelon, Namenda, and Razadyne, are advertised to slow down the progression of the disease. However, in 2018, the American Academy of Neurology (AAN) recommended that physicians explain the lack of evidence supporting these drugs' ability to slow cognitive decline before prescribing them. Instead, the AAN advocated for treating the behavioral and neuropsychiatric symptoms associated with AD, as mentioned by Petersen et al. in 2018.
Given the pharmaceutical industry's inability to find a cure for AD, the focus of treatment efforts has shifted towards multifactorial interventions that target risk factors in order to prevent or delay cognitive decline. Various factors contribute to an increased risk of developing AD, including genetic factors (e.g., APOE ε4 allele), medical conditions (e.g., diabetes, obesity, hypertension, hypercholesterolemia, cerebrovascular disease, sleep disordered breathing, head injury), psychological factors (e.g., depression, stress), demographic factors (e.g., older age, low education), and lifestyle factors (e.g., poor diet, smoking, alcohol abuse, low social engagement, insufficient physical activity). Multiple studies have indicated that up to 50% of dementia cases and 33% of AD cases could be attributed to modifiable risk factors, potentially making them preventable, as discussed by Cooper, Sommerlad, Lyketsos, and Livingston in 2015; Galvin in 2017; Hersi et al. in 2017; Larsson et al. in 2017; Pistollato et al. in 2016; and Rakesh, Szabo, Alexopoulos, and Zannas in 2017.
Interestingly, adopting a healthy lifestyle, including a nutritious diet, regular physical activity, quality sleep, positive social interactions, and effective stress reduction, has been shown to delay the onset of dementia. Postponing dementia onset by just 12 months could potentially reduce the annual number of AD cases by over 9 million, according to Brookmeyer, Johnson, Ziegler-Graham, and Arrighi in 2007. Therefore, effective prevention strategies are becoming increasingly important in public health, as noted by Rakesh et al. in 2017, and there is a need for high-quality studies that investigate the relationship between a combination of lifestyle factors and cognitive outcomes.
