Prevention of Alzheimer's Disease: Lessons Learned and Applied

Abstract

Alzheimer’s disease (AD) affects over 5 million Americans with substantial consequences to patients, families and society that will only continue to be a significant cause of morbidity, mortality, and healthcare costs. With disease-modifying treatment trials unsuccessful at the present time and only symptomatic medications available, an emerging approach is the creation of prevention trials. Advances in diagnostic criteria, biomarker development and improved understanding of the biophysiological basis of AD make these initiatives feasible. Ongoing pharmacological trials using anti-amyloid therapies are underway in sporadic and genetic forms of AD. However, a large number of modifiable risk factors for AD have been identified in observational studies, many of which do not appear to exert effects via amyloid or tau. This suggests that prevention studies focusing on risk reduction and lifestyle modification may offer additional benefits. Rather than relying solely on large sample, long duration randomized clinical trial designs; a precision medicine approach using N-of-1 trials may provide more rapid results on whether personalized prevention plans can improve patient-centered outcomes. As there appear to be multiple pathways to develop AD, there may also be multiple ways to prevent or delay the onset of AD. Even if these precision approaches alone are not successful in preventing AD, they may greatly improve the likelihood of amyloid- or tau-specific therapies to reach their endpoints by reducing co-morbidities. Keeping this in mind, dementia may be as a disorder that develops over a lifetime, with individualized ways to build a better brain as we age.

Relationship Between Brain Amyloid Deposition and Instrumental Activities of Daily Living in Older Adults: A Longitudinal Study from the Multidomain Alzheimer Prevention Trial

“…Furthermore, this asymptomatic stage might be the only window of opportunity for antiamyloid therapies, which have failed to slow the progression of cognitive symptoms significantly, in individuals with symptomatic or prodromal AD. Better identification of individuals at risk of dementia might also be of great interest for intervention trials aiming to delay the onset of clinical symptoms …”

A mixed methods systematic review of multimodal non-pharmacological interventions to improve cognition for people with dementia

“…We have now shown that optimised and targeted interventions can help to address the underlying causes of cognitive decline. The role of neurotoxins, nutritional deficiencies, inflammation and the gut microbiome in neurodegenerative disease (Bland, 2016) can lead to a personalised care plan and enhanced precision of treatment decisions (Galvin, 2017). Moreover, a person's dementia has a unique etiology which must be understood individually to develop personalized treatment (Pomorska & Ockene, 2017).…”

Hypothetical Interventions on Risk Factors for Cognitive Impairment among Chinese Older Adults: An Application of the Parametric G-Formula

“…Cognitive interventions at the preclinical phases could be beneficial in delaying the onset of cognitive impairment [17][18][19]. Randomized control trials (RCTs) have offered some short-term impact of interventions that can improve cognitive function such as dance [20], exercise [21], physical activities [22], and psychological intervention [23].…”