An Innovation in Alzheimer's That Is Still Under Used

In November 2017, Bill Gates announced his significant investment of 100 million USD to support the efforts in finding the drugs that could help to understand Alzheimer’s disease. Gates pointed out that this investment would help to fund the analysis of the massive amounts of data that has been gathered on Alzheimer’s, thus helping to understand the new areas of research that some haven't even delve into yet. At present, there are about five million Americans living with Alzheimer’s, but if newer treatment or preventive measures are not developed this number could bloat to 16 million by 2050.

Alzheimer’s is one of the leading causes of dementia, a neurological disease characterized by proteinopathies leading to the slow destruction of brain neurons and other supporting cells. It is a highly debilitating condition due to the progressive fall in memory and various other cognitive capabilities.

The exact cause of Alzheimer’s has not been identified to date, probably because there isn’t any single cause, it develops as a result of the accumulation of several factors over the years. Making aging, poor health, infections, genetics, environmental factors, and auto-immunity all have their legitimate role in the development of Alzheimer’s. Whatever the cause of Alzheimer’s is, one thing is known for sure that various factors lead to the progressive deposition of amyloid protein that is damaging to brain cells.

Amyloid theory of Alzheimer’s was put forward in the mid-1980's, and since then it has become the most studied and widely accepted reason for the death of neurons in the brain. In the following years as brain scanning technology improved, it became evident that the formation of amyloid plaques is one of the earliest signs of Alzheimer’s. In fact, these plagues start forming several decades before the symptoms appear.

In recent times, amyloid proteins have become the focus of all the research for treatment, and more importantly prevention of Alzheimer’s. Researchers are trying to find the effective drugs that could either inhibit the formation of amyloid depositions in the brain or improve clearance of amyloid proteins.

However, a multitude of efforts in the direction has shown only limited results. Solanezumab, crenezumab, and aducanumab are monoclonal antibodies that have been tested to stop the formation of amyloid plaques in the brain with limited success.

Due to weaker results of the fight against amyloid protein deposition in the brain, researchers have started giving various questions to themselves. It is entirely possible that modalities aimed at amyloid plague dissolution failed because the chosen patients were in the advanced stage of Alzheimer’s. It is utterly possible for monoclonal antibodies or other drugs would give much better results in halting the progress of Alzheimer’s if they are given much earlier. Moreover, it is entirely possible that many of the participants in the trials did not have Alzheimer’s but were instead having dementia due to other causes. It seems that answer to all these problems could be found in a method of early detection of amyloid depositions.

If a method for early detection of early amyloid depositions could be found, it would help to conduct clinical trials in the much better way and help understand the disease processes. Finding a simple and minimally invasive method for early detection of the amyloid depositions is a must in our fight against Alzheimer’s. Fortunately, such method has already been devised, though it remains one of the most under-utilized tools in clinical neurology.

Revolution in early detection of Alzheimer’s

In 2012, Amyvid (Florbetapir F 18 Injection) became the first detection test for early diagnosis of amyloid plaques to be approved by FDA, and till date, it is the only authorized test that can be used for this purpose in humans.  It is a radio diagnostic agent for PET scan. Amyvid is an agent that is given intravenously before carrying out PET scan of the brain, and it can show the density of amyloid depositions in the very early stage. However, it remains as one of the most underutilized tools.

One of the reasons being that insurance services like Medicare and Medicaid have refused to reimburse the cost for diagnostic purposes, as they still have doubts about the role of this agent in preventing the progress of Alzheimer’s. There is also doubt about financial benefits from such an early detection of amyloid depositions.

The positive Amyvid test does not diagnose the Alzheimer’s, all it does is, provide information about the presence of amyloid depositions in the brain and their density. However, when used along with other tools and methods,it can significantly help in the early diagnosis not to mention the value it can bring to the clinical trial.

However, things may soon change as a trial to demonstrate the futility of PET scan along with Amyvid is in process. The Imaging Dementia—Evidence for Amyloid Scanning (IDEAS) has a primary objective to show the importance of early detection of amyloid plaques in Alzheimer’s. This study would also compare the group that has gone through early detection and treatment with those who did not participate in the study and thus, putting an end to the doubts about the usefulness of early detection and role of Amyvid test in Alzheimer’s treatment.

If this clinical trial is successful, thousands of people will get insurance or Medicare coverage for early detection of the reasons for dementia. It is vital as at present many of those being treated for dementia with monoclonal antibodies may not have amyloid depositions, and they may have dementia due to other factors. In fact, it could also help to explain why many drugs aimed at preventing amyloid deposition failed to provide the expected result, as it is suspected that many of those enrolled in trials were not having amyloid deposition (they probably had dementia due to other causes).

Additionally, it should be realized that even if IDEAS trial fails to show the futility of PET with Amyvid, it surely does not mean that early diagnosis has no value. Early diagnosis can at least give a person time to modify lifestyle, and plan ahead. It is no secret that Alzheimer’s is often diagnosed late or even misdiagnosed and Amyvid is going to change that all.

References

1. Lilly USA. AMYViD. https://amyvid.myregistrationp.com/amyvid/index.do. Published 2017. Accessed December 16, 2017.
2. Time. Bill Gates Just Made a Massive Investment in Alzheimer’s Disease Research. Time. http://time.com/5021339/bill-gates-alzheimers-research-dementia/. Accessed December 16, 2017.
3. Lilly. FDA Approves Amyvid™ (Florbetapir F 18 Injection) for Use in Patients Being Evaluated for Alzheimer’s Disease and Other Causes of Cognitive Decline | Eli Lilly and Company. https://investor.lilly.com/releasedetail2.cfm?ReleaseID=662647. Published 2012. Accessed December 16, 2017.
4. Imaging Dementia- Evidence for Amyloid Scanning. https://www.ideas-study.org/. Accessed December 16, 2017.
5. Jones DS, Greene JA. Is Dementia in Decline? Historical Trends and Future Trajectories. New England Journal of Medicine. 2016;374(6):507-509. doi:10.1056/NEJMp1514434.
6. Prince M, Ali G-C, Guerchet M, Prina AM, Albanese E, Wu Y-T. Recent global trends in the prevalence and incidence of dementia, and survival with dementia. Alzheimers Res Ther. 2016;8. doi:10.1186/s13195-016-0188-8.
7. Selkoe DJ, Hardy J. The amyloid hypothesis of Alzheimer’s disease at 25 years. EMBO Mol Med. 2016;8(6):595-608. doi:10.15252/emmm.201606210.