What does this recent landmark study mean for the prevention of cognitive decline and Alzheimer’s disease?
How can Functional Medicine, and specifically the Bredesen Protocol, prevent and treat cognitive decline?
An important article detailing findings from FINGER (The Finnish Geriatric Intervention Study to Prevent Cognitive impairment and Disability) was recently published in the prestigious JAMA Neurology Journal. This study and its findings are of great importance to those working to decrease the enormous medical, economic, and psychological burdens of cognitive decline and Alzheimer’s disease (AD). Yet even while we welcome this addition to the scientific evidence base, there are even more opportunities to address these debilitating neurological conditions.
Practitioners of Functional Medicine will not be surprised about the findings of the FINGER study—that even basic dietary and lifestyle adjustments can have positive impacts on cognitive health. We already know that optimizing multiple aspects of health simultaneously can effectively prevent and treat complex chronic conditions such as cognitive decline. Recently, we have been fortunate to have been able to learn about and use the Bredesen Protocol, which assesses and addresses multiple factors involved in cognitive health and cognitive decline simultaneously. Using this protocol allows us to not only stop further decline, but to reverse decline and improve cognitive function in patients with early onset dementia. This protocol also serves as a guide for preventing cognitive decline in those who are at high risk. More on that later…
Let’s first review the current state of our collective cognitive health, the study findings, and how they relate to a full Functional Medicine approach.
The landscape and burden of cognitive decline
It is estimated that 5.5 million Americans are living with AD in 2017, with 1 in 10 people 65 and older having AD. AD is the fifth-leading cause of death among those 65 or older, as well as a major cause of disability and poor overall health, not to mention the economic, health-related, and psychologic toll it takes on caregivers. Even more overwhelmingly, it is estimated that there are 8 million additional people out there living with mild cognitive impairment (MCI). In MCI, there are problems with cognitive function severe enough to be detected on testing and to be noticeable to others, but not enough to disrupt daily life or cause the inability to live independently. People with MCI often forget things, have trouble following conversations, books, and movies. They may also have difficulty planning out the steps needed to accomplish a task, or with interpreting complicated instructions. Sometimes they may have poor impulse control or exercise poor judgement. It is estimated that 15-20% of the US population over 65 are in this group. Estimates for the annual conversion rate for MCI developing dementia vary, mainly because the definition of MCI is still not agreed upon by all and testing methods vary. However, one major review of the topic estimated that 5-10% of those with MCI will go on to have dementia, also finding that more than 60% did not progress even after 10 years, many reverting to normal. While the relatively low conversion rate may be somewhat reassuring, just having MCI can be a huge burden on those suffering with it, as well as on their family and friends. Those with MCI may have to lighten up on their work schedule or use people or devices more than usual to remind them about events and tasks. So, it’s clear that whether we are talking about AD or MCI or any form of cognitive impairment or decline, it is imperative that we figure out what are the best ways to prevent or minimize these problems.
Genetic risk factors for Alzheimer’s disease
The ApoE ε4 genetic variant is associated with a 2-3 fold higher risk of AD in people with one APOE ε4 allele (heterozygous) and about a 12-fold higher risk in those with two APOE ε4 alleles (homozygous). For people who already know that they carry one or both apolipoprotein E ε4 alleles, the study’s findings are particularly motivating and useful. The presence of APOE ε4 varies by ethnicity and population, but in the United States it is estimated that approximately 30% of individuals carry at least one copy.
What is the FINGER study?
FINGER is an ambitious randomized controlled multimodal interventional trial, involving over 1000 older Finnish men and women (mean age 69, 46.3% female) with elevated risk of cognitive decline and dementia (based on CAIDE vascular and dementia risk score, for which there is an app available). Participants were randomized to an intervention group which included “usual health advice” or to a group which received fairly intensive counseling and activities including 1) nutritional guidance (individual and group), 2) exercise (aerobic, strength, and balance), 3) cognitive training (computer based program), and 4) vascular risk management (assessment and management of blood pressure, weight, blood sugar, cholesterol and other modifiable risk factors through lifestyle management and pharmacologic treatment as needed).
The intervention lasted for two years (ending in 2014), with initial results being published in 2015 in this Lancet article. The most recent article analyzed the data further based on ApoE allele status. Specifics of the interventions can be found in the study’s initial article. While not everyone may agree that the types of nutritional, exercise, and cognitive training used in the study were optimal for prevention of cognitive decline and dementia, it is fair to say that all the interventions were significant improvements over the standard nutritional, physical activity, and cognitive activity practices common among people in this age group. For example, nutritional counseling included recommending high consumption of fruits and vegetables, using whole grains for any cereal products, keeping sugar intake less than 50 grams daily, and eating fish twice per week. Participants were also advised to use “vegetable margarine and rapeseed [canola] oil instead of butter,” to use “low-fat options in milk and meat products.” Many of us would probably favor a much lower sugar and grain intake, and some of us might also disagree with the recommendation for low fat dairy, canola oil and margarine use. We would also probably recommend specific foods known to contain nutrients which have been shown to reduce inflammation and improve brain health, such as fish oil, nuts, rosemary, and turmeric. But in general, the advice was a definite improvement over the standard American/Western diet. The study intervention did not include recommendations for supplementation of nutrients other than vitamin D 800 IU/day and “fish oil supplements” for those not eating fish.
What are the findings from the study so far?
- 2 years of the intervention (diet, physical activity, cognitive exercise, and vascular risk management) was associated with a 25% greater improvement in overall cognitive function (as measured by a Neuropsychological Test Battery (NTB) between the intervention group (NTB total Z score 0.20) and the control group (NTB total Z score 0.16)
- The degree of improvement in overall memory between the intervention and the control groups did not meet statistical significance, although there was a trend toward greater improvement and the authors stated that “post-hoc analyses showed [a positive] effect on more complex memory tasks.”
- Self-reported adherence to the intervention domains was high after 2 years with 100% reporting compliance with the diet, 90% with exercise, 85% with cognitive training and 87% with monitoring and treatment of vascular risk factors.
- No significant side effects were seen, other than mild musculoskeletal pain related to exercise.
- The study suggested that participants who were APOE ε4 carriers had just as much benefit from the intervention as non- APOE ε4 The authors state that this finding requires further study, but this is music to the ears of anyone who is an APOE4 carrier.
APOE ε4 carriers, who are otherwise at significant greater risk of cognitive decline and Alzheimer’s disease, should be motivated by the fact that they will derive the same impressive benefits from optimizing nutrition, physical activity, cognitive exercise, as non-APOE ε4 carriers. They can be equally successful at staving off cognitive decline and Alzheimer’s disease.
What about those who feel we need more evidence?
Despite this study’s results, some pessimistic scientists and clinicians out there may still say, hold on, there is not enough evidence to support use of intensive lifestyle changes to prevent dementia. But to them I say, what’s the harm? Helping people to start healthy habits like exercise, eating a healthy diet, and doing cognitive exercises is certainly not going to make anyone worse. And as far as return on investment is concerned, if our healthcare system spent just a fraction of what we spend on other later-stage, more expensive aspects of medical care on counseling people at increased risk of dementia and cognitive decline on how to make these lifestyle improvements, imagine the savings, both on outright medical spending and on increased productivity from people who would otherwise be unable to work.
Hopefully studies like FINGER will eventually convince funding sources to support more research on multi-modal treatment interventions for cognitive decline and AD, rather than searching for one drug that will prevent or cure Alzheimer’s disease. During the past 20+ years, experimental drugs have come and gone without any products showing the ability to slow or stop the disease. As the title of this recent editorial in Annals of Internal Medicine states, there is “No Magic Bullet” for prevention of late-life dementia. The author makes reference to a Lancet Commission about dementia that there is a clear need to “be ambitious about prevention,” including “1) the promotion of universal education to improve socioeconomic well-being, 2) increasing physical activity, 3) reducing or stopping smoking, and 4) maintaining social engagement, as well as 5) managing hypertension, obesity, hearing loss, depression and diabetes.”
How do the findings from FINGER relate to Functional Medicine?
Imagine what the results of FINGER study would have been if they had used a full Functional Medicine approach, that takes the multimodal intervention to a comprehensive, next level intervention. What if the authors had incorporated everything else we know about nutrition and cognitive health? What if the study had also included instructing participants to specifically use phytonutrients known to support cognitive health such as curcumin, resveratrol, rosmarinic acid, and therapeutic levels of omega-3 fatty acids? What if they had applied what we know about intermittent fasting and the benefits of adding high intensity interval training to moderate aerobic and resistance training? What if they had assessed and addressed high levels of homocysteine, elevated copper to zinc ratio, low magnesium, and other key nutrients? What if they had addressed the impaired gut-brain axis induced by dysbiosis, or neurotoxicity and oxidative stress caused by chronic infections, mycotoxins, and other inhalant related causes, as well as organo-pollutants, and toxic metals? What if they had addressed hormonal deficiencies such as those caused by thyroid dysfunction, menopause, and testosterone deficiency? We can predict that the outcomes would have been remarkably better than what was already achieved with the modest interventions in FINGER. In fact, based on case reports already published by Dr. Dale Bredesen, we know that cognitive decline in Alzheimer’s disease, even those with APOE ε4 carrier status, can be successfully arrested and reversed. Tremendous improvements have been achieved using his protocol, both clinically and radiologically. Patients have been able to return to work after being faced with retirement due to cognitive decline. MRIs have demonstrated that hippocampal volume (a neuro-radiological measurement of the severity of dementia) has returned to that of healthy normal ranges.
People at high risk of dementia and cognitive decline in Finland had improvement in cognitive function from relatively modest improvements in diet, exercise, vascular risk factors, and cognitive exercises. Imagine what could have been achieved if they had been able to take advantage of a Functional Medicine approach using the Bredesen Protocol, just like we are using currently in our practice! Get in touch with us to find out more.
We’d like to hear from you. Are you an individual living with or caring for someone with cognitive impairment or Alzheimer’s disease? Are you a practitioner working with this population? What has been your experience? Please comment below.