A recent synopsis from Science Daily based on information reported out of the University of Cambridge regarding Alzheimer’s disease presents some valid and important points along with, unfortunately, some misinformation and oversimplification. Here’s a brief rebuttal to some of the latter:
1. “It’s over a hundred years since the first case of Alzheimer’s disease was diagnosed. Since then we’ve learned a great deal about the protein ‘tangles’ and ‘plaques’ that cause the disease.”
It is no longer taken for granted and accepted unquestioningly that the beta-amyloid (Aβ) plaques and neurofibrillary tangles referred to here actually cause Alzheimer’s. While they certainly exacerbate cognitive decline and may increase the rate of progression, a growing number of researchers have called into question whether they play an initial causative role. If the Aβ plaques were a central causative factor, then pharmaceutical drugs that inhibit plaque formation should have beneficial effects on disease progression. However, drugs that target the amyloid plaques have failed time and again to result in any meaningful improvement. In fact, some of these drugs have actually resulted in worsening of signs and symptoms of the condition.
There is growing acknowledgement that the amyloid proteins may actually be the body’s defensive response—a protective measure—against physiological insults (specifically, oxidative stress). Dale Bredesen, MD, who has created a multi-pronged dietary and lifestyle protocol that has reversed Alzheimer’s disease and its precursor, mild cognitive impairment, in small-scale trials, has said, “The production of the amyloid is a protective response. […] The idea of just getting rid of the amyloid without understanding why it’s there actually makes very little biological sense.” (Emphasis added.)
The etiology of Alzheimer’s as described in the “amyloid hypothesis” fails to account for many of the metabolic and biochemical changes observed in the condition. First, there are patients who present with signs and symptoms of Alzheimer’s, yet who do not exhibit extensive plaque deposition, and there are individuals who do exhibit plaque buildup yet who do not have dementia. Second, one of the primary hallmarks of the condition—reduced cerebral glucose metabolism—begins years (decades, in some cases) before the accumulation of Aβ plaques. In many Alzheimer’s patients, extensive plaque deposition doesn’t occur until the very late stages of the illness, years after they have already been exhibiting signs and symptoms. So again, these problematic proteins may be contributing to a worsening disease state, but their accumulation is not the initial triggering event. Prominent Alzheimer’s researchers believe a mitochondrial hypothesis fits the data better than the amyloid hypothesis.
As some have written, “…the amyloid cascade hypothesis is no longer supported by the majority of experimental evidence,” and even more damningly, “…millions of research dollars, both private and public, are annually expended on anti-Aβ therapies that do not work and are based on a logically flawed hypothesis.”
2. “‘I don’t think we should talk of a cure,’ says Goedert [of the Medical Research Council Laboratory of Molecular Biology, and recipient of the 2014 European Grand Prix from the Paris-based Foundation for Research on Alzheimer’s Disease]. ‘At best, we will be able to halt the disease. Prevention will be much more important.” Part of the problem, he says, lies in the fact that there is no absolute way of identifying those at risk of developing Alzheimer’s disease.’”
It’s true that there’s no “absolute” way of identifying those at risk of developing Alzheimer’s disease, but it’s not as though researchers have no idea who may be at increased risk compared to the general population. It’s not for nothing that Alzheimer’s is now often referred to as “type 3 diabetes.” The links between metabolic syndrome, insulin resistance, and Alzheimer’s is so strong that researchers have also coined the phrase “metabolic-cognitive syndrome.” The link between chronic hyperinsulinemia and risk for Alzheimer’s is undeniable.
According to researchers, “Insulin resistance is usually at or near the top of the list of known lifestyle-related factors heightening the risk of declining cognition in the elderly.” In a prospective cohort, individuals with hyperinsulinemia had double the risk for developing Alzheimer’s compared to those without hyperinsulinemia. And this was true for individuals without diagnosed diabetes (i.e., their blood glucose levels were within “normal” ranges, likely solely due to chronically elevated insulin). In this study, “The risk of AD attributable to the presence of hyperinsulinemia or diabetes was 39%. The HR of AD for the highest quartile of insulin compared to the lowest was 1.7 (95% CI: 1.0, 2.7; p for trend = 0.009).” So blood glucose and/or insulin signaling dysfunction accounts for a nearly 40% risk of developing Alzheimer’s independent of other factors that may raise that even higher. Obviously, hyperinsulinemia is not the only risk factor, but it’s a powerful enough one that the public should be made aware of it, and perhaps insulin testing should become as routine as fasting blood glucose, cholesterol, and triglycerides.
We take it for granted now that diet and lifestyle are behind many chronic conditions of our time: type 2 diabetes, heart disease, NAFLD, the female athlete triad, osteoarthritis, infertility, and more. Why should we suspect Alzheimer’s is any different? As if the blood-brain barrier were an impenetrable shield that protects the brain from the ravages inflicted upon the rest of the body by the modern Western diet, high in refined carbohydrates and inflammation-inducing seed oils? Due to its high energy demands, micronutrient needs, and the preponderance of fragile polyunsaturated fatty acids in neuronal membranes, the brain may be even more susceptible to dietary insults than the periphery.
3. “Goedert doesn’t believe we will ever find a single ‘magic bullet’, but will need to use combination therapies – in the same way that we treat other diseases, such as HIV – with each drug targeting a particular aspect of the disease.”
This point is most certainly true: there will be no “magic bullet” for Alzheimer’s. The condition is a multifactorial situation, likely with many etiological factors. As such, monotherapies—single drugs targeting single pathways—are likely to continue being as disappointing as they’ve been in the past. “Combination therapies” will be required, but they need not be limited to pharmaceutical drugs. Dr. Bredesen’s extremely promising protocol is a multifaceted intervention strategy that addresses diet, sleep quality, micronutrient deficiencies, toxic burden, stress reduction, hormone balance, physical activity, and more. There may come a day when drugs prove effective for enhancing changes in these other areas, and they can be incorporated as adjuvants to other interventions, but if Alzheimer’s is yet another “disease of civilization,” caused primarily by an evolutionarily novel diet at odds with basic human physiology, then dietary changes should be fundamental to any strategy to combat this devastating condition—specifically, diets that reduce insulin resistance. (Diets that go even further—ketogenic diets that may nourish neurons that have lost the ability to harness energy from glucose—may be instrumental here, perhaps augmented by exogenous ketones, which have been shown to improve cognitive function in Alzheimer’s patients.)
Much remains to be elucidated regarding the etiology and pathological progression of Alzheimer’s disease. But it is time to start sharing some of what we do know with patients and their loved ones and caregivers.
Amy Berger, MS, CNS, NTP
Author of The Alzheimer's Antidote