To What Degree is Alzheimer's a Lifestyle Disease?

Type 2 diabetes is the archetypal lifestyle disease, a metabolic dysfunction run out of control to the point at which it disrupts the crucial mechanisms of insulin metabolism. Diabetes isn't accelerated aging, but it has many of the same consequences when viewed from the high level: more damage, more disease, higher mortality. The vast majority of type 2 diabetics have this condition as a result of the choices they made. It is easy to become fat in a world of low-cost calories and increasing wealth, but it is still a choice. We can turn a questioning eye to Alzheimer's disease, a progressive age-related dementia characterized by a range of changes in the biochemistry of the brain, such as amyloid and tau deposits, and ask to what degree it is a lifestyle condition, driven by visceral fat tissue, lack of exercise, and the like. When looking at lifestyle choices and risk, the answers are more ambiguous than is the case for type 2 diabetes, however. Consider cardiovascular disease, for example. You can lead a life that makes you much more likely to die young from a heart attack, but equally everyone will suffer cardiovascular failure if they live long enough - the processes that weaken the heart and corrode our blood vessels operate in everyone, just more rapidly in the obese.

Is Alzheimer's more like type 2 diabetes, 90% avoidable over a normal human life span for the diligent, or is it more like cardiovascular disease, inevitable for all of us, absent radical progress in medical science, but arriving sooner for the less diligent? You'll see arguments either way if you wander the literature, most of which lean in the direction of Alzheimer's as a lifestyle condition, but not to the same degree as type 2 diabetes. A good meta-analysis from last year puts some numbers to that summary: if nine-tenths of type 2 diabetes is self-inflicted, then one can argue for two-thirds of Alzheimer's to be self-inflicted by the same types of statistical approach. Being overweight is definitely on the list: the distortions of metabolism caused by excess visceral fat tissue impact the brain. There is even a faction within the research community who argue that Alzheimer's is a type 3 diabetes, in effect.

Perhaps a better measure of the degree to which a medical condition is a lifestyle condition is whether or not it can be effectively treated, reversed, or cured by lifestyle changes alone. This is the case for type 2 diabetes. Even fairly late in its progression, calorie restriction and consequent loss of fat tissue can turn things around for a majority of patients, to the point of a cure. It is somewhat amazing that so many people continue down the road of disability when they could turn back at any time. For cardiovascular disease, lifestyle interventions like increased regular moderate exercise are beneficial, but in the way of a delaying tactic. You can improve the present poor situation, but you can't choose your way to back to full health for your age given the tools available. When it comes to the option to turn back, is Alzheimer's disease more like type 2 diabetes or more like cardiovascular disease, once it has taken hold?

The publicity materials and paper I'll point out today add a little more data from a small set of patients to the present evidence on this topic, putting Alzheimer's more in line with what one might expect from comparing the risk factors. Note the date on the paper, two years ago, versus the date on the publicity, however, this week. These results have been languishing for a few years, and by the look of it the researchers involved are now attempting another angle to broaden support for their approach - whenever book publication is mentioned in a release, it's a fair guess that the forthcoming book is why the release exists. Pitching a strategy of lifestyle changes to the usual panoply of research funding sources has ever had the problem that lifestyle changes are a poor foundation for a for-profit business, and are in any case well outside the area of interest for most for-profit funding sources relevant to medical research. It took some years for the calorie restriction research community to figure out a way to get for-profit interests involved, for example. That sort of challenge may well be what is taking place behind the scenes here, but equally it could simply be a mundane case of business failure for reasons unrelated to the science.

Pre and post testing show reversal of memory loss from Alzheimer's disease in ten patients

Results from quantitative MRI and neuropsychological testing show unprecedented improvements in ten patients with early Alzheimer's disease (AD) or its precursors following treatment with a programmatic and personalized therapy dubbed metabolic enhancement for neurodegeneration (MEND). The study is the first to objectively show that memory loss in patients can be reversed, and improvement sustained, using a complex, 36-point therapeutic personalized program that involves comprehensive changes in diet, brain stimulation, exercise, optimization of sleep, specific pharmaceuticals and vitamins, and multiple additional steps that affect brain chemistry. "All of these patients had either well-defined mild cognitive impairment (MCI), subjective cognitive impairment (SCI) or had been diagnosed with Alzheimer's disease before beginning the program. Follow up testing showed some of the patients going from abnormal to normal."

All but one of the ten patients included in the study are at genetic risk for AD, carrying at least one copy of the APOE4 allele. Five of the patients carry two copies of APOE4 which gives them a 10-12 fold increased risk of developing AD. "We're entering a new era. The old advice was to avoid testing for APOE because there was nothing that could be done about it. Now we're recommending that people find out their genetic status as early as possible so they can go on prevention." Sixty-five percent of the Alzheimer's cases in this country involve APOE4; with seven million people carrying two copies of the ApoE4 allele. "The magnitude of improvement in these ten patients is unprecedented, providing additional objective evidence that this programmatic approach to cognitive decline is highly effective. Even though we see the far-reaching implications of this success, we also realize that this is a very small study that needs to be replicated in larger numbers at various sites."

Reversal of cognitive decline in Alzheimer's disease

Effective treatment of Alzheimer's disease has been lacking, but recently a novel programmatic approach involving metabolic enhancement was described, with promising anecdotal results. This treatment is based on connectomic studies and previous transgenic findings as well as epidemiological studies of various monotherapeutic components of the overall program. The approach is personalized, responsive to suboptimal metabolic parameters that reflect a network imbalance in synaptic establishment and maintenance vs. reorganization, and progressive in that continued optimization is sought through iterative treatment and metabolic characterization.

Here we report the initial follow-up of ten patients who were treated with this metabolic programmatics approach. One patient had well documented mild cognitive impairment (MCI), with a strongly positive amyloid-PET (positron emission tomography) scan, positive FDG-PET scan (fluorodeoxyglucose PET scan), abnormal neuropsychological testing, and hippocampal volume reduced to 17th percentile; after 10 months on the MEND protocol, his hippocampal volume had increased to 75th percentile, in association with a reversal of cognitive decline. Another patient had well documented early Alzheimer's disease, with a positive FDG-PET scan and markedly abnormal neuro-psychological testing. After 22 months on the MEND protocol, he showed marked improvement in his neuropsychological testing, with some improvements reaching three standard deviations from his earlier testing.

The initial results for these patients show greater improvements than have been reported for other patients treated for Alzheimer's disease. The results provide further support for the suggestion that such a comprehensive approach to treat early Alzheimer's disease and its precursors, MCI and SCI, is effective. The results also support the need for a large-scale, personalized clinical trial using this protocol.


Alzheimer's disease is disease of memory. However, in addition to Alzheimer's there are numerous other factors that can negatively affect memory: depression, anxiety, alcohol, medications, insomnia and many others. When someone reports that they "cured Alzheimer's", the first question that must be answered is whether the diagnosis was correct. Unfortunately, the diagnostic accuracy of the reported cases - at least the way they were presented here - is questionable. Many patients in the report were diagnosed with MCI and this is by definition reversible. Depression is common among older patients but there are no data presented as to the prevalence of depression symptoms among the reported cases. Medications and alcohol are big factors affecting memory too but there are no data in the report what medications the patients were taking and for what. Did they stop drinking? That would do the trick! How was it possible that the patients who had "Alzheimer's disease" were still driving? For such solid research entities as Buck Institute and Easton Center to make sweeping claims about "curing Alzheimer's" these and other questions must be answered.

Posted by: Baskys at June 19th, 2016 10:25 AM

Word @Baskys. They also gave patients with high homocysteine or low B12 levels a form of vitamin B12; B12 deficiency can cause reversible cognitive impairment (as well as likely contributing to irreversible cognitive decline), so you would expect some cognitive improvement from such subjects even if "core AD" was unaffected. It won't matter to the perspective of the patient or his/her family in the short term, of course - a rapid improvement in cognitive function will be a blessing, even if the decline continues - but it's important to understand what is and isn't happening and what we still need to do to repair the aged brain from the structural damage of aging.

On the other hand, it's also important to remember that there is no such thing as "pure" Alzheimer's disease, or Lewy body dementia, or vascular dementia, or "sporadic" (age-related) frontotemporal lobar degeneration with tau inclusions, and so on: the aging brain is under assault from the reactive byproducts of multiple metabolic processes, each leaving characteristic cellular and molecular lesions in the aging brain, and cognitive decline and the ultimate progression to clinical dementia is the integrated sum of their collective impact. When one strongly dominates the others, there is a more or less distinct clinical and neuropathological phenotype, but the lesions and deficits of others are also present to greater or lesser degrees and contribute to the ravaging of the aging brain. We must repair, replace, remove, or render harmless all of the damage of aging to truly prevent, arrest, and reverse age-related cognitive decline: all else just buys time around the edges.

Posted by: Michael at June 19th, 2016 3:37 PM

Is anyone aware of any plans to use gene therapy to modify people with APOE3/4 to have APOE2 instead?

Posted by: Dennis Towne at June 20th, 2016 4:11 PM

@Dennis - that would just lower blood LDL levels leading to a slowing of the accumulation of damage (foam cells in the arterial walls filled with oxidised LDL). A better (and possibly easier) approach is the SENS one of focusing on removing this oxidised LDL using bacterial enzymes.

Posted by: Jim at June 21st, 2016 9:59 AM

I understand, however my impression was that the gene therapy approach would be possible now, whereas the SENS approach isn't. If I had double APOE4, I'd strongly consider getting such therapy to hopefully give me more time before it gets really bad.

Posted by: Dennis Towne at June 21st, 2016 12:01 PM
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