Diet And Lifestyle Affect Risk for Alzheimer’s Disease

Worldwide, nearly 50 million people are living with Alzheimer’s disease today (1), with about 500,000 of those being Canadians (2) and 5.5 million Americans (3).  Alzheimer’s disease (AD) is the sixth leading cause of death in the United States and the fifth leading cause of death among those of 65 years of age and older.  In 2017 the CDC (Centers for Disease Control and Prevention) in the US released data showing that the death rate from AD has risen by 55% between 1999 and 2014.  Possible reasons put forward for this increase are the growing population of older adults and the increase in diagnosis of AD at earlier stages (4).  In Canada, no recent increase in the incidence of AD has been observed.  However, AD is the eighth leading cause of death in Canada (5).  On average, a person with Alzheimer’s lives four to eight years after diagnosis, although they can live as long as 20 years, depending on other factors.   This devastating disease is robbing people all over the world of their quality of life and severely cutting short their lifetimes.

 

What is Alzheimer’s Disease? (6,7,8)

 AD is not a normal part of aging.  It is the most common cause of dementia and accounts for 60% to 80% of dementia cases.  AD causes brain cells to degenerate and die.  The earliest symptom of AD is forgetfulness of recent events.  As the disease progresses, the continuous decline in memory, thinking ability, communication and behaviour sabotages the ability of a sufferer to carry out everyday tasks and to function independently.  Ultimately, damage caused to the brain results in a cascade of toxic events that harm and kill neurons and eventually their host.

AD is characterized by the depositing of two harmful proteins in the brain:

• “Plaques” are numerous, tiny, dense deposits of a protein fragment called beta-amyloid that accumulate in the spaces between nerve cells in the brain
• “Tangles” are twisted fibers of a protein called tau that build up inside nerve cells in the brain

Almost everyone develops plaques and tangles as they age.  However, those with AD produce more of them, especially in areas important for memory.  Plaques and tangles seem to play a critical role in blocking communication among nerve cells and in the destruction and death of nerve cells.

For many decades, amyloid plaques and tau tangles could only be observed through autopsy after the death of an AD patient.  More recently, PET scans to detect amyloid plaques in the brains of living Alzheimer’s patients have become available (9) and, in May 2020, new research provided evidence that PET scans could be used safely in older adults to identify the presence of tau tangles with a high level of accuracy (10).  At the present time, such tests are very expensive and not covered under most medical plans.  Consequently, AD is generally diagnosed through a variety of testing that assesses memory impairment, thinking skills and changes in behaviour.  In addition, investigations are performed to rule out other possible causes of dementia.  As noted before, AD is only one cause of dementia.  Others, some of which can be reversed, include vascular changes in the brain, Parkinson’s Disease, Lewy Body Disease, vitamin deficiencies, thyroid gland problems, brain infections, severe depression and medications.  At the present time AD is considered irreversible.

 

 Can Alzheimer’s Disease Be Prevented?

 Scientists have been aware of the potential of lifestyle and diet changes to prevent AD for some time yet study designs to date have been widely variable and results inconsistent.  The Alzheimer’s Association in the US notes that AD develops as a result of complex interactions of many factors such as age, genetics, environment, lifestyle and coexisting medical conditions, a situation that makes pinpointing the cause of AD a challenging task (11).

Convincing evidence though suggests that key lifestyle changes may be powerful measures in the prevention of the disease.  Autopsy studies show that plaques and tangles can be present in the brains of people who show no cognitive symptoms.  Conversely, individuals with signs of vascular disease along with plaques and tangles are much more likely to display dementia symptoms.  Since vascular disease is preventable and even in some cases reversible, there is hope that taking steps to increase blood vessel health may also prevent AD (11).

Recent studies are shedding new light on the possibilities of AD prevention.

 

2018 Research into Diet and the Risk for Alzheimer’s Disease (12)

 In May 2018, the report on a three-year study employing brain imaging to study the effects on the brain of higher vs lower adherence to a healthy Mediterranean diet was published.  Participants included 70 cognitively-normal adults between the ages of 30 and 60 who had received at least twelve years of education during their lifetimes.  Researchers looked at two biomarkers of AD in the brains of the subjects, reductions in the metabolism of glucose (reflecting neuron dysfunction) and changes in the amount of amyloid present.  A MeDi (Mediterranean Diet) score was calculated for each participant based on their adherence to a healthy Mediterranean diet.

Points toward the MeDi scores were given for;

• Higher intake of beneficial food groups (fruits, vegetables, legumes, cereals and fish)
• Lower intake of detrimental food groups (dairy, meat, sweets and processed foods)
• Higher monounsaturated fat-to-saturated fat ratio
• Low alcohol intake.

Participants underwent clinical, neuropsychological, and dietary examinations along with brain imaging performed twice, at least two years apart.

Results showed that those with lower MeDi scores had higher deposition of amyloid plaques in their brains and declines in the metabolism of glucose in the brain.  In addition, faster rates of progression of both amyloid deposition and glucose metabolism problems were evident in participants with low MeDi scores.

The investigators concluded that high consumption of beneficial foods, especially plant-based foods, and minimal consumption of detrimental foods is linked to lower risks of dementia along with decreased risks of cardiovascular disease, insulin resistance and inflammation, all of which may contribute to accelerated brain aging and loss of neurons.  There also emerged evidence that a healthy diet may protect against dementia at least in part by supporting the health of the blood vessels supplying blood to the brain.   The researchers noted that modifiable risk factors such as diet account for 1 in every 3 cases of AD.  But they cautioned that more studies with larger numbers of participants and longer follow-up times are needed to corroborate their conclusion that dietary interventions can be an effective preventive measure against AD.

 

2020 Research into Diet and Lifestyle Changes and the Risk for Alzheimer’s Disease (13)

Scientists involved in some of the newest AD research, published in July 2020, worked towards the goal of producing a set of practical guidelines for the prevention of AD based on solid scientific evidence and taking into account both the benefits and the risks of the suggested actions.

Investigators conducted a systematic review and meta-analysis of 243 existing observational prospective studies and 153 existing randomized controlled trials that had examined the risk of AD and its possible prevention.  Sources of bias and robustness of evidence was thoroughly assessed for each study or trial to ensure objectivity and transparency of the results.

Each of the included studies and trials were rated for the quality of its evidence for outcomes, credibility and consistency.  Ratings were applied as follows:

• Level A – the strongest evidence of the highest quality
• Level B – moderate to good strength evidence
• Level C – low strength evidence

Within each level, the resulting recommendations were categorized according to their strength;

• Class 1 – strong recommendation
• Class II – weak recommendation
• Class III – not recommended

This analysis revealed compelling evidence for a large number of factors which appear to increase the risk of developing Alzheimer’s disease.  The research culminated in several lists of AD risk factors offering practical guidance for the prevention of the disease.

Researchers involved in this study point out that this meta-analysis encompassed observational studies as well as randomized controlled trials.  Observational studies cannot prove causality.  Future rigorous, evidence-based randomized controlled trials looking at each AD prevention strategy can and should be carried out to validate these results.

 

Ten risk factors for AD with level A class 1 evidence;

• High blood pressure in mid-life
• Orthostatic hypotension (drop in blood pressure when standing from a sitting or lying down position)
• Increased BMI in late life
• High homocysteine blood level
• Diabetes
• Head trauma
• Depression
• Stress
• Lack of education (less than 6 years of schooling)
• Low cognitive activity

 

Nine risk factors for AD with level B class 1 evidence;

• Obesity in mid-life
• Weight loss in late life
• Low levels of physical exercise
• Smoking
• Lack of sufficient good-quality sleep
• Cardiovascular disease
• Frailty
• Atrial fibrillation
• Low vitamin C intake

 

Two medication groups often used in AD therapy were rated to have class III evidence and were not recommended because their risks appear to outweigh any possible benefits;  

• Estrogen replacement therapy (level A evidence)
• Acetylcholinesterase inhibitors (level B evidence)

Discouraging use of the above two therapies for AD challenges generally accepted principles of AD treatment.  Higher incidence of AD in women has been commonly believed to be associated with menopause.  However, this study illustrated that estrogen replacement therapy does not reduce the risk of AD and, in fact, estrogen use was associated with an increase in the risk of dementia.  In addition, acetylcholinesterase inhibitors (for example, donepezil (Aricept), galantamine (Reminyl) and rivastigmine (Exelon)), commonly the first drugs prescribed for AD, only help with controlling AD symptoms and slightly delaying cognitive decline.  They do not reduce the risk of developing the disease.

 

 Six more risk factors were rated as Class C (low-strength evidence) and their relationships with AD need to be confirmed in future studies;

• Management of diastolic blood pressure
• Use of NSAID medications (Non-Steroidal Anti-Inflammatory medications).  Results of studies on NSAID use and the risk of AD have been conflicting.  It appears that some NSAID use may help reduce the risk of developing Alzheimer’s disease, but too much may actually increase the risk.
• Low amount of social activity
• Osteoporosis
• Pesticide exposure
• Silicon from drinking water

 

Final list of evidence-backed healthy lifestyle actions for the prevention of Alzheimer’s disease resulting from this meta-analysis;

Authors of this study noted that the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) trial from 2015 advised the use of a combination of multiple recommendations as the best approach to delay the onset of AD (14).  The conclusions of this 2020 study agree, counselling that acting on not just one or two factors, but on the whole comprehensive set of healthy lifestyle factors, may be key to the prevention of AD.  Taking these actions can also help to stave off major AD risk factors such as diabetes, cerebrovascular diseases, depression and stress.

• Maintain a healthy BMI
• Adopt a heart healthy diet rich in whole fruits, vegetables and grains to prevent chronic diseases such as diabetes, high blood pressure, cardiovascular disease and obesity
• Manage atrial fibrillation using medication
• Regularly check blood homocysteine level and treat with vitamin B and/or folic acid
• Obtain sufficient vitamin C through the diet
• Enjoy regular physical exercise to avoid frailty and stay healthy and robust in later life
• Attain high-quality sleep throughout life
• Do not smoke and avoid environmental tobacco smoke
• Avoid head trauma and protect the brain during high risk activities
• Avoid stress or employ relaxation techniques to mitigate its effects
• Maintain good mental health to avoid depression.
• Ensure lifelong learning through obtaining as much education as possible in early life and participating in mentally stimulating activities in later years

 

What about genetic factors or a family history of dementia? (15,16)

The ApoE gene determines how effectively your body can remove harmful plaques from the brain.  There are three possible versions of the ApoE gene.  The most common one, ApoE3, is reasonably successful in removing plaques.  ApoE2, the least common version, is more effective at plaque removal and individuals with this version have a reduced risk of developing AD.  However, ApoE4 is less effective and individuals with this version have a significantly increased risk of developing AD.  If no preventative steps are taken, research has discovered that those with two versions of the ApoE4 gene (ie – have received the ApoE4 gene from both parents) have a 50% chance of developing AD.   So, it is even more important to take action to discourage the development of AD if you have a family history of dementia or have discovered that you have one or two copies of the ApoE4 gene in your genome.

On a positive note, just having the ApoE4 gene does not dictate that AD will develop.  Even those who have two copies of ApoE4 do not always develop AD and people without the ApoE4 gene can still have AD.  It appears that this gene affects AD risk but is not a cause. The risk can be reduced significantly by following a lifestyle associated with reducing AD risk as outlined in the above guidelines.

 

Final thoughts …

Long-term studies illustrate that amyloid plaques are present in the brain for at least fifteen years before any cognitive signs appear in the affected individual.  Once symptoms do appear, they begin insidiously and usually progress gradually.  No medication has been found to date that will significantly delay or reverse the development of AD, although the search for such a drug continues (17).

Scientists in the cognitive field are now recommending that steps to prevent AD need to be initiated very early in the progression of AD, in fact well before the onset of symptoms (16).  In particular, high-risk individuals, those with a family history of dementia or who bear the ApoE4 gene, would be wise to weave as many evidence-based AD preventative lifestyle practices into their lives as early as possible.

The majority of the preventive actions for AD elucidated by these recent studies are aimed at vascular risk factors, emphasizing the importance of keeping blood vessels throughout the body in good condition.  Reinforcing this is the knowledge that these same behaviour changes are backed by decades of evidence revealing their ability to reduce the risks of many other chronic diseases of our time.  With all these incentives in mind, adopting the suggested healthy lifestyle changes to prevent AD is the clear path to follow for a long and healthy life.

 

SOURCES:

 1 https://www.alzheimers.net/resources/alzheimers-statistics

2 https://alzheimer.ca/en/about-dementia/what-dementia/dementia-numbers-canada

3 https://www.nia.nih.gov/health/alzheimers-disease-fact-sheet

4 https://www.cdc.gov/media/releases/2017/p0525-alzheimer-deaths.html

5 https://www.statista.com/statistics/434435/death-rate-for-alzheimer-s-disease-in-canada

6  https://www.mayoclinic.org/diseases-conditions/alzheimers-disease/symptoms-causes/syc-20350447

7 https://alzheimer.ca/en/Home/About-dementia/Alzheimers-disease

8 https://www.alz.org/alzheimers-dementia/what-is-alzheimers

9 Rabinovici, G.D., Gatsonis, C., Apgar, C., et al. Association of Amyloid Positron Emission Tomography With Subsequent Change in Clinical Management Among Medicare Beneficiaries With Mild Cognitive Impairment or Dementia. JAMA. 2019; 321(13): 1286–1294. doi:10.1001/jama.2019.2000.

10  https://www.nia.nih.gov/news/first-tau-biomarker-approved-alzheimers-disease-diagnostic-tool

11  https://www.alz.org/alzheimers-dementia/research_progress/prevention

12 Berti, V., Walters, M., Sterling, J., Quinn, C.G., Logue, M., Andrews, R. et al.  Mediterranean diet and 3-year Alzheimer brain biomarker changes in middle-aged adults.  Neurology. 2018 May 15; 90(20): e1789–e1798.  doi: 10.1212/WNL.0000000000005527.

13 Yu, J., Xu, W., Tan, C., et al.  Evidence-based prevention of Alzheimer’s disease: systematic review and meta-analysis of 243 observational prospective studies and 153 randomised controlled trials.  Journal of Neurology, Neurosurgery & Psychiatry.  20 July 2020. doi: 10.1136/jnnp-2019-321913.

14 Ngandu, T., Lehtisalo, J., Solomon, A., et al. A 2 year multidomain intervention of diet, exercise, cognitive training, and vascular risk monitoring versus control to prevent cognitive decline in at-risk elderly people (FINGER): a randomised controlled trial.  Lancet .2015; 385: 2255–2263.

15  https://www.alzheimersorganization.org/alzheimers-gene-apoe4

16 https://www.mayoclinic.org/diseases-conditions/alzheimers-disease/in-depth/alzheimers-genes/art-20046552

17 Jack, C.R. Jr. Alzheimer Disease: New Concepts on Its Neurobiology and the Clinical Role Imaging Will Play.  Radiology. 2012 May; 263(2): 344–361.  doi: 10.1148/radiol.12110433.