More than 5 million Americans today are affected by Alzheimer’s disease (AD). It is estimated that there will be more than 16 million people with AD in the United States and more than 60 million people with AD worldwide by 2050. In the past 25 years, only five symptomatic medications for AD have met their primary clinical endpoints in Phase III clinical trials and successfully come to market; of these, four are still available.

There is increasing evidence that multiple medical conditions increase the risk of neurodegeneration and subsequent development of dementia. It also is becoming clear that a majority of those risk factors acts in amyloid- and tau-independent ways. Since 2003, every symptom- and disease-modifying agent has failed in Phase II or III trials because of challenges with safety or efficacy, including trials testing the amyloid hypothesis, anti-inflammatory agents, and early-phase anti-tau therapies.

With disease-modifying treatment trials unsuccessful at the present time and only medications to treat symptoms available, what now?

Thinking « out-of-the-box, » a scientist has developed an innovative program called the « Dementia Prevention Initiative » (DPI), which abandons generalized methods used to research and treat AD. The program has a novel « N-of-1 design » that individualizes medicine down to a single patient. Instead of conducting a conventional trial of 100 people all getting the same treatment, the scientist is conducting 100 single trials personalized to the individual. The youngest patient enrolled is 61 and the oldest is 86.

The DPI is a two-year clinical trial aimed at developing a best-practice model of personalized care that looks at each individual as the sole unit of observation. The idea is to treat neurodegenerative diseases as a disorder that develops over a lifetime and individualize ways to build a better brain as we age. The ultimate goal is to prevent dementia from happening in the first place.

The approach follows a form of personalized treatment similarly used in cancer and delivers an individualized prevention plan, tailored to each patient’s risk profile based on their genetic traits, biomarkers (blood, imaging, and electrophysiology), socio-demographics, lifestyle choices, and co-existent medical conditions. This approach specifically targets the heterogeneity of AD by identifying person-specific risk factors and applying a customized intervention directed against this risk profile. The head scientist anticipates that this method will provide more rapid information on whether personalized prevention plans can improve person-centered outcomes.

Although the single greatest risk factor for AD is age, AD is not inevitable. It is estimated that at age 85 there is a 42 percent risk of developing AD, which means that 58 percent of older adults do not develop dementia, even if amyloid can be detected in the brain. The reasons are unknown, but may be explained in part by a host of modifiable and non-modifiable risk factors. Up to 30 percent of AD cases may be preventable through modification of risk factors and behavioral changes to mitigate the effect of those risk factors that can’t be modified.

Nationally, if the onset of AD and related disorders is delayed by five years, 25 years later there would be approximately 5.7 million fewer cases, collective family savings would approach $87 billion, and societal savings would approach $367 billion.

Paper: “Prevention of Alzheimer’s Disease: Lessons Learned and Applied”

Reprinted from materials provided by Florida Atlantic University.

février 5, 2018