The Alzheimer’s Murder Mystery

Alzheimer’s research resembles a television murder mystery. Detectives come up with seedy suspects for a series of murders, such as gang members. The District Attorney wants all gang members charged and the investigation wrapped up quickly, but there are too many unresolved questions getting in the way and the murder investigation continues. This is much like beta-amyloid plaques being accused of causing Alzheimer’s, as complications bog down the research for a cure.

The urgency behind wrapping up the investigation is driven by the urgency of the disease. Over five million Americans are afflicted with Alzheimer’s. The disease is always fatal, with absolutely no survivors to date. The disease robs much of who we are on the way towards unavoidable death. Those who would care for loved ones with the disease greatly increase the chance they will succumb to the disease as well. Alzheimer’s poses a unique trifecta of tragedy unmatched by other afflictions.

Every day, every week, I get Google Alerts listing articles that refer to beta-amyloid plaques as the cause for Alzheimer’s. Ah, but there’s a little problem with this ongoing murder investigation. Until now there were people considered to have Alzheimer’s without plaques, as well as people with plaques who did not have Alzheimer’s.

Despite billions of dollars already spent on targeting beta-amyloid plaques as the culprit causing Alzheimer’s, these petulant plaques have proven neither necessary nor sufficient in relation to the disease, at least as originally defined. None of the medications for combating the disease to date have been effective. They do not work for everyone and, even when they do, only slow down cognitive decline. A cure has yet to be found, no matter what defines Alzheimer’s.

Beta-amyloid plaques are suspects with alibis for too many cases. In an article titled “When there’s no amyloid, there’s no Alzheimer’s” a study reported that 25% of the subjects with the mild to moderate cognitive decline typical of Alzheimer’s symptoms do not have beta-amyloid plaques. If Alzheimer’s researchers were detectives what an assault on their closure rate that would have been! Yet the title provides the answer for tidying this investigation up: if there’s no amyloid, well then, let’s not call it Alzheimer’s.

Brilliant! Just make a caveat that investigators need to test subjects with Alzheimer’s, er, I mean cognitive decline, for beta-amyloid plaques before making them part of the research or treatment funding stream for Alzheimer’s. The other 25% with the same symptoms? A different problem to consider down the road. Here’s an idea. Rather than redefining Alzheimer’s to fit the investigation, perhaps the investigation should focus on a different primary suspect.

The ongoing Alzheimer’s murder mystery indeed features two other main suspects, neurofibrillary tangles and metabolic disorders. Both plaques and tangles cause mischief outside brain cells, along the synaptic pathways connecting them. Metabolic disorders is a generic term for abnormal chemical reactions inside a cell, with oxidative stress being the most notorious offender. The oxidative stress created by charged free radicals causes inflammatory reactions and many other afflictions, including cognitive decline. Inflammation, in turn, can induce oxidative stress in an escalating positive feedback loop that leads to dementia symptoms.

Oxidative stress makes the blood brain barrier (BBB) more permeable. The membrane that serves as the BBB serves as an intricate defense mechanism by using receptors to escort only select particles across the barrier. The increased permeability of the BBB allows more beta-amyloid to enter the brain than under normal conditions. However, amyloid appears to be an anti-inflammatory response to multiple sclerosis, which engages our own immune system to attack the myelin sheaths that protect neurons, creating oxidative stress. Recent research indicates that a faulty immunal response to inflammation is more the cause than effect of beta amyloid plaques for triggering Alzheimer’s.

Perhaps the most damning evidence that suggests beta-amyloid plaques are more of an Alzheimer’s effect than cause is a comparative study involving Vitamin E, a natural antioxidant, and memantine, a drug that reduces amyloid. Vitamin E slowed cognitive decline better than memantine (Brand name Namenda) by a factor of four, but the real kicker is when combined together the treatment was no more effective than memantine only. Memantine was not only much less effective than the antioxidant, it inhibited the antioxidant’s full potential to remedy cognitive decline caused by oxidative stress.

Aha! Murder mystery solved, right? Oxidative stress must be like the drug cartel responsible at a higher level than gang members (beta-amyloid plaques) for the violent drug culture. Well, hold on a second.  Recent research reveals a correlation between antioxidants and cancer, as well as a negative correlation between cancer and Alzheimer’s.  Apparently, antioxidants are just as effective at removing free radicals from cancerous cells as from normal ones. There also are other metabolic disorders that contribute to cognitive decline, such as zinc deficiency, diabetes and an unhealthy microbiome. Focusing on oxidative stress covers more ground than beta-amyloid in regards to cognitive decline, but perhaps not enough.

Just as oxidative stress creates many different afflictions, many different lifestyle factors create oxidative stress. Poor diet, inadequate exercise, smoking and stress are a few of the most common lifestyle conditions that create oxidative stress as well as other health problems. Isolating which quality of life factor avoids which health disorder for which person is problematic at best. The better preventative strategy is to cover all bases by maintaining a high quality of life overall. This holistic approach guided a study that resulted in the reversal of cognitive decline for nine out of the ten participants. Many of the tips in my Brain Health Checklist derive from this study.

Contrast the quality of life approach to all current Alzheimer’s drug treatments. None have yet proven as effective for brain health as maintaining a high quality of life. That’s the norm for any incurable disease; prevention trumps treatment. Even should brain health deteriorate, a high quality of life still provides benefits for overall health and happiness. Furthermore, nobody experiences harmful side effects from maintaining a high quality of life, unlike with the two common drugs from Alzheimer’s, donepezil or memantine. If oxidative stress is more the cause of dementia symptoms, a high quality of life the most practical solution to oxidative stress to date, then why do beta-amyloid plaques remain the prime murder suspects, to the point of redefining the disease?

Civilized society being what it is, there remains a purpose and need for expanded research into all tangential causes and effects for dementia symptoms. Medications will be the necessary alternative to improving the quality of life for some, the preferred alternative for many. There may come a time when medical treatments for removing beta-amyloid plaques prove the most effective way to prevent dementia for some … but never for all.

Removing beta-amyloid plaques will never treat the 25% for whom cognitive decline occurs without plaques. Even for those plagued by plaques, some of those then would experience cognitive decline by other means after the plaques are controlled. There’s also the chance for some that no medical means for removing plaques will keep up with the oxidative stress and lifestyle factors leading to their creation.  As long as beta-amyloid plaques remain the prime suspect in the Alzheimer’s murder mystery, this may remain one mystery that never gets solved.

The good news is you do not have to wait for the Alzheimer’s murder mystery to be solved in order to maximize your chance for maintaining brain health, if you are willing to adapt your lifestyle accordingly. Your goal would be to minimize oxidative stress, even if you have a genetic predisposition for beta-amyloid plaques. Towards this end the three most important factors are diet, exercise and minimizing stress in your life. Other factors also are important for enhancing brain health, but this is the necessary foundation for building your high quality of life.

I currently am working on a small book about understanding Alzheimer’s, er, cognitive decline, and maintaining brain health. Included will be caregiver lessons learned from my experiences with Cindy. What New Years Resolution is more important than taking the steps to improve brain health, overall health and well-being? Stay tuned for future installments throughout the year or “sign up” for a copy of the entire book when it’s done by subscribing to the blog (thus providing your email address).

May you be well for this coming year and many more.