Can we trust the End of Alzheimer’s Programme?
Dr Dale Bredesen is a neurologist who created a program designed to prevent and reverse cognitive decline at any age, using a comprehensive approach known as The Bredesen Protocol (PreCODE for reducing Alzheimer’s risk, and ReCODE for the reversal of cognitive decline for people who are already living with Alzheimer’s disease). He explains this protocol in his book, The End of Alzheimer’s Programme.
Note that reversal of cognitive decline and reversal of disease itself are not the same, and that Alzheimer’s disease is just one of the many forms of dementia.
Rather than the reductionist method that is currently applied to medicine, which focuses on breaking a disease down to its individual parts then applying a treatment to “fix” that one component (e.g. anti-amyloid treatments that remove plaques from the brain), The Bredesen Protocol aims to take a comprehensive approach that incorporates discoveries of research across a multitude of disciplines.
While the Bredesen Protocol has no peer-reviewed, placebo-controlled science behind it, some of the key lifestyle interventions within the protocol are already believed to be beneficial in slowing Alzheimer’s progression by health care professionals. These include physical exercise, a healthy diet and social engagement.
Below is a summary of the main ideas shared in the book. Please see your health professional before implementing any of the ideas shared here.
The 7 Basics of the Bredesen Protocol:
The overall goal of the Bredesen Protocol is to "increase the contributors to synapoblastic (synapse-making) signalling and reduce the contributors to synaptoclastic (synapse-breaking) signalling". How Dr Bredesen suggests people do this is summarised below.
1. Reduce insulin resistance. According to Dr Bredesen, virtually everyone with Alzheimer’s has lost sensitivity to insulin and become resistant, “at least in the brain”. He suggests reducing insulin resistance by following what he has called the KetoFLEX 12/3 diet. The three components of KetoFLEX are:
(1) Diet: heavily plant-based, achieving mild ketosis. You're eating mostly non-starchy vegetables, moderate amounts of good quality protein such as meat and legumes, moderate amounts of good quality fats such as extra virgin olive oil, nuts and seeds, and small amounts of non-tropical fruits. You're also having small amounts of starchy vegetables with each meal.
(2) Fasting: no food for at least 12 hours overnight, beginning 3 hours before bed;
(3) Exercise: strength training and aerobic. Avoid sitting for extended periods, adopt a strength training program 3 to 4 times per week, and incorporate a daily walk for a minimum of 30 minutes. Bredesen states that exercise is "one of the best ways to protect cognition and is also an essential part of the protocol to reverse cognitive decline".
Other recommendations to reduce insulin resistance include optimising key nutrients such as zinc, which is involved in multiple steps of insulin secretion and effect, as well as reducing stress, treating sleep apnea if present, and taking certain supplements.
2. Optimise nutrient, hormone and trophic (growth factor) support. Bredesen states this will optimise our immune systems, support our mitochondria and begin to build our brain’s synaptic networks. He states that low levels of B1, B2, vitamin D, testosterone, oestrogen, and nerve growth factor are associated with cognitive decline. Bredesen’s view is that we shouldn’t just be bringing them to the low end of “normal”, but instead ensure there is enough for the best functioning of the nervous system. The book provides some (but not all) of the target values for vitamins, minerals and hormones.
3. Resolve and prevent inflammation. Bredesen states that the most common cause of chronic inflammation is “leaky gut”, which can be caused by stress, sugar, alcohol, processed foods, aspirin and related anti-inflammatories, soft drinks, and PPIs used to treat acid reflux or heartburn. For those who have inflammation but no leaky gut, Bredesen suggests considering if there is suboptimal dental hygiene, an infected root canal, chronic sinus infection, infection with a chronic pathogen such as Borrelia (Lyme disease), metabolic syndrome, or exposure to air pollution or mould toxins.
4. Treat chronic pathogens, if you have them. Bredesen says that even the brain may harbour bacteria, viruses, spiral bacteria, fungi, or parasites.
5. Identify and remove toxins. Bredesen states that metals such as mercury, organics like toluene and benzene, and biotoxins like mold toxins (mycotoxins) can lead directly or indirectly to cognitive decline.
6. Rule out sleep apnoea, and optimise sleep. If you suspect you have sleep apnoea, Bredesen advises that your doctor can lend you, or you can purchase, an oximeter to check your oxygen at night. Ideally, your oxygen saturation should be 96-98%. If it’s in the 70s or 80s, you can try a dental device to improve breathing, or a CPAP (Continuous Positive Airway Pressure) device. To optimise sleep, factors that will help include blocking blue light three hours before bed, keeping a regular sleep schedule, exercising earlier in the day, and avoiding caffeine past noon.
7. Socialise, and stimulate your brain. Prioritise social connection, as in actual meet-ups opposed to connecting through social media. Keep your brain active by learning a foreign language, learning to play a musical instrument, and doing challenging puzzles like sudoku and crosswords. Studies suggest that listening to music and dancing can also have a cognitive benefit.
Arguments against the Bredesen Protocol
According to Dr Joanna Hellmuth of the UCSF Memory and Aging Center, the issues with the Bredesen Protocol include the following: the study design of Bredesen’s paper is based on case studies rather than placebo-controlled clinical trials; his articles do not include a methods section on how the studies were conducted; there are no inclusion or exclusion criteria; and there is no data on any non-responders. It’s also not stated how tested measures were conducted or evaluated. (See full article here).
Bredesen addresses some of these issues in his book, stating that in 2011 he proposed a comprehensive trial for Alzheimer’s disease based on the research and findings his team has made so far, rather than employing the usual single-drug approach. He explains that the trial was denied by the US Institutional Review Board, which felt that the protocol was too complicated, and that it did not conform to the usual standard in which each trial evaluates only a single drug or treament.
Another issue is that not all the information required for people to follow the full protocol is provided in the book. For example, it emphasises the importance of optimising vitamins B1 and B2, yet the target values for these two vitamins aren't provided. To me, this suggests the book was not written with the intention of giving people full access to the protocol, but more as a marketing effort to encourage people to purchase his expensive paid program. When I reached out to Bredesen’s team to ask if the omitted information could be found elsewhere (e.g. online), they did not respond.
At the time of writing this review, there is a lack of scientific support behind the elements of the Bredesen Protocol that go beyond exercise, socialisation and a healthy diet. Thankfully, you don’t need to read the book or buy the expensive program in order to implement some or all of these cost-free elements.
