Links between nutrition and dementia

By Serena Shaw
Bachelor of Human Nutrition,
University of Canberra

“Dementia is a mental health disorder that is common in the elderly and has been associated with poor nutritional status”.

Dementia is a mental health condition defined by the deterioration in mental cognition with the onset usually occurring later in life1. The disease causes problems in the brain’s structure affecting memory, function and behaviour1. Alzheimer’s disease is the most common form of dementia and is experiencing a rise in prevalence due to an increasingly ageing population (1). The neurodegenerative pathological changes associated with the disease include an irregular accumulation of proteins in the brain tissue causing neurofibrillary tangles, as well as a large loss of neurons and synapses within the brain (1). Although genetics play a large role in the development of dementia, the precise aetiology is still unknown (1). Lifestyle behaviours have been identified as risk factors for developing dementia and multiple chronic diseases such as Type 2 diabetes, cardiovascular disease and obesity are also alarming risk factors for dementia (2). These diseases are all associated with a poor nutritional intake throughout life, leading to the development of otherwise preventable disease and enhancing the probability for developing dementia later in life (3). Other evidence suggests certain nutrients such as omega-3 fatty acids and antioxidants can be used as a preventative measure against developing dementia (4). Although research is somewhat limited, nutrition throughout life can help reduce major risk factors for developing chronic diseases associated with dementia (1,4).

An estimated 24 million people are currently suffering from Alzheimer’s disease on a global scale (1,4). This alarming figure is expected to rise due to the ageing population and prevalence of other diseases that are identified as major risk factors. Since the cause of dementia is unknown and untreatable, it is important to identify risk factors in order to reduce the number of potential future incidences (1). Anatomical changes in the brain that correspond to Alzheimer’s disease include synaptic damage, neurofibrillary tangles and an overabundance of amyloid-β proteins (5). The accumulation of amyloid-β proteins supports further damage to brain tissue such as inflammation and apoptosis leading to the loss of neurons and synapses (1,5). The apolipoprotein E4 alleles are considered a strong genetic factor causing the development of dementia (2). However, people without these alleles can still develop the disease and there is evidence that a large number of diabetes and overweight patients with Alzheimer’s disease do not carry this genetic component (2).

Body weight can be a reflection of someone’s nutritional intake (3). Overweight and obesity commonly represents someone with an incorrect energy balance and usually poor nutritional intake (1,3). A poor nutritional status can be considered a direct and indirect risk factor for dementia (1). A longitudinal cohort study of 6,583 subjects identified central obesity as the driving force behind dementia impairment (6). Those with a high sagittal abdominal diameter and body mass index in the obese category were 3.6 times more likely to develop dementia (CI, 2.85-4.55) (6). They recognised that visceral adipose tissue is associated with the development of stroke, cardiovascular disease, hypertension and type 2 diabetes, all of which are risk factors for dementia (2,4).

Type 2 diabetes substantially increases the risk of developing Alzheimer’s disease through multiple mechanisms causing the pathological brain disruption associated with dementia (1). Type 2 diabetes occurs when the body’s insulin response is inadequate (1). Since insulin is not working effectively, glucose cannot be metabolised properly, leading to the development of advanced glycosylation end products (AGEs) (1). AGEs facilitate damage caused by amyloid-β proteins (1). Hyperinsulinemia is associated with obesity and diabetes (1). It occurs when there is excess insulin in the blood stream. The excess insulin encourages amyloid-β accumulation by competing with it for degrading enzymes (1). The effects caused by the excess insulin in the blood as a result of diabetes increase the likelihood of these amyloid β proteins and therefore enhance cognitive damage (1).

It has been identified that a poor nutritional status is a major cause behind multiple vascular diseases such as cardiovascular disease and hypertension (3). The brain and heart relationship indicates a connection between cardiovascular disease and cognitive impairment (7). Hypertension caused by high blood pressure can be associated with increased cognitive damage by compromising the efficiency of the blood brain barrier (1). This causes the invasion of proteins into brain tissue (1). The protein extravasation causes other pathological neurological damage such as cell death, amyloid-β accumulation and synaptic damage (1). Multiple placebo-randomised controlled trials have supported the link between hypertension and cognitive damage, providing reliable evidence supporting the use of anti-hypertensive treatments to reduce the risk of dementia development (1). One study concluded the use of anti-hypertensive drugs, nitren-dipine, enalapril maleate and hydrochlorothiazide, on patients without dementia aged over 60 years caused a 55% reduction in the risk of developing dementia, compared to the placebo group (1). Another study identified the beneficial effects of perindopril, with a 34% reduction in the risk of developing dementia after suffering a stroke and 54% decreased risk of cognitive decline (1).

Visceral adipose tissue also increases the amount of inflammatory cells in the body promoting the formation of atherosclerosis (6). Atherosclerosis occurs when there is excess cholesterol and triglycerides that accumulate on the sides of arteries forming plaques (7). These plaques can cause reduced cerebral blood flow, which is responsible for the depletion in neural energy therefore causing cell death in brain tissue (7). High cholesterol levels above 6.5mmol/L during midlife have been recognised to increase the chance of developing dementia, with an odds ratio of 2.6 (CI, 1.2-6.0) (7). It potentially does so by assisting the formation of amyloid-β proteins (7). Although there are substantial links between heart and brain health, observational studies have failed to provide consistent evidence supporting the treatment of vascular risk factors as a preventative measure for dementia (7). It is still prudent to control cholesterol levels to prevent the development of further cardiovascular disease and ensure the cardiovascular system is working efficiently to provide the brain with a sufficient blood supply (7).

Nutritional status throughout life has been identified as an opportunity to delay the onset of dementia as a preventative measure (8). Specifically focusing on foods high in antioxidants and poly-unsaturated fatty acids might be able to reduce the destructive effects occurring in the brain, although many studies are inconclusive (4). According to the National Health and Medical Research Council (NHRMC) 2013 dietary guidelines there is growing evidence for health benefits from fish consumption (3). They reported a trend in people who regularly consumed diets high in fish having a lower risk of developing diseases such as cardiovascular disease, stroke and dementia (3). They have obtained grade C evidence to suggest omega-3 fatty acid consumption will reduce the risk of dementia. Grade C evidence indicates there is some support for the recommendations (3).

Eicosapentaenoic acid (EPA) and Docosahexaenoic acid (DHA) are omega-3 polyunsaturated fatty acids which are essential to the body and must be obtained from the diet (9). A major source of these fatty acids is oily fish (9). It has been identified via animal studies that these fatty acids may be beneficial in preventing dementia by reducing the cognitive damage such as amyloid-β protein build up and oxidative stress (9). DHA promotes healthy cognitive function as it makes up components of the phospholipids in neuron membranes of the brain’s cerebral cortex and grey matter (4). Through complex mechanisms DHA can produce neuroprotectin D1, which provides pro-inflammatory responses and neuroprotective activities to counteract the damage caused by amyloid-β proteins (5,10). Further animal studies link omega-3 fatty acids with enhanced neuron excitability, improved neural transmission and reduced oxidative damage (4). Animal studies are considered weak evidence and other epidemiological studies have found contradicting evidence (9). Devore et al conducted a long-term cohort study focusing on omega-3 polyunsaturated fatty acid consumption from fish and the development of dementia. Their results confirmed there was no association between high intakes of omega-3 polyunsaturated fatty acids and the long-term risk of developing dementia (9). Since there are such inconsistent results it is difficult to draw conclusions at this stage and future analysis is required.

Oxidative damage by free radicals is another mechanism that leads to neuronal damage (4,11). To counteract this damage, the use of antioxidants such as vitamin C and E has been hypothesised, but once again results are inconclusive (11). Galasko et al discussed the outcomes of multiple animal studies using antioxidants to improve neurological damage associated with dementia. These studies found the use of vitamin E before amyloid-β accumulates was beneficial to slow plaque formation and the combination of vitamin C and E showed a decline in oxidative stress (4,11). Other animal laboratory studies identified cognitive benefits such as decreased amyloid-β accumulation and decreased oxidative stress from the consumption of α-Lipoic acid by its antioxidant properties (11). Since these studies are conducted on animals, the findings can only indicate an area to explore and cannot be applied to humans. Galasko et al also conducted their own double-blinded randomised controlled trial to investigate antioxidant supplements effects on cerebrospinal fluid biomarkers to indicate their effectiveness in preventing neurological damage found with dementia. This type of research is considered strong evidence at level II under NHMRC standards (3). The 78 subjects were divided into three groups and either received a vitamin E, vitamin C and α-lipoic acid supplement, coenzyme Q supplement or a placebo (11). Their findings were inconclusive, as the cerebrospinal fluid biomarkers did not differ greatly among the three groups. It indicates an area where a longer-term trial is necessary to obtain sufficient evidence (11).

Other studies have provided evidence supporting certain nutritional combinations with beneficial properties against dementia (1). A prospective cohort study conducted by Gu et al identified a dietary pattern high in omega-3 and 6 polyunsaturated fatty acids, vitamin E and folate and low in saturated fatty acid consumption had protective properties against Alzheimer’s disease (12). This is reflective of what is considered good nutritional intake under NHMRC recommendations, representing a diet high in nuts, fish, poultry, variety of fruits and vegetables but low in high-fat dairy, red meat and butter (3,12). As mentioned above, these nutrients provide protective measures by counteracting the pathological effects presented in dementia including antioxidant effects (12).

The Mediterranean diet is another nutritional area speculated to reduce the risk of dementia (13). Traditionally a Mediterranean diet consists of high vegetable, fruit, legume and olive oil intake, moderate intake of fish and low intake of saturated fat and dairy products (13). This combination of foods provides cognitive protective nutrients such as monounsaturated fatty acids, folate, omega-3, vitamin B12, antioxidants such as vitamin E and carotenoid (13). The Mediterranean diet is very similar to the dietary pattern described above, indicating that overall good nutritional intake can help reduce the risk of dementia (3). Although there is conflicting research, some evidence suggests that a dietary combination like the Mediterranean diet can reduce neurological degeneration and is therefore beneficial as a protective measure and should be intervened before major cognitive impairment occurs (14).

The neurological effects caused by dementia can be linked to unpreventable causes such as genetics, but lifestyle factors have also been associated with increased risk factors and the onset of the disease (1). Overweight and obesity represent poor nutritional intake throughout life and contributes substantially to the development of many otherwise preventable diseases (4). Since poor nutritional intake leads to the development of diseases such as cardiovascular disease, Type 2 diabetes and hypertension it can also be suggested as a major risk factor for the development of dementia by favouring mechanisms that cause cognitive damage (6). Environmental factors, such as lifestyle and nutritional intake, are the most modifiable and preventable risk factors for dementia1. There is some evidence suggesting dietary intake of omega-3 fatty acids and antioxidants can help reduce the neurological pathologies found with dementia (12).

Certain diet combinations, including the Mediterranean diet, have indicated potential positive effects from good nutritional intake on cognitive function and disease prevention (3,13,14). However the research for individual nutrients is very limited to animal studies and requires stronger human control trials to provide what is considered level I evidence by NHMRC standards (3).

Unfortunately results are inconsistent across the board for nutritional intervention as a means to reduce the risk for dementia, but opens up many areas for future investigation. Overall, people can benefit from healthy nutritional intake in regards to preventing disease and there is growing evidence that poor nutritional intake can be associated with dementia (3).

References
1. Reitz C, Brayne C, Mayeux R. Epidemiology of Alzheimer disease. National Review Neurology. 2011; 7(3): 137-152.

2. Naderali E, Ratcliff SH, Dale MC. Obesity and Alzheimer’s disease: A Link Between Body Weight and Cognitive Function in Old Age. American Journal of Alzheimer’s Disease and Other Dementias. 2009; 24(6): 445-449.

3. National Health and Medical Research Council. Australian Dietary Guidelines [Internet]. Canberra: National Health and Medical Research Council; 2013 [cited 2013 September 20]. Available from: http://www.nhmrc.gov.au/_files_nhmrc/publications/attachments/n55_australian_dietary_guidelines_130530.pdf

4. Morris MC. The role of nutrition in Alzheimer’s disease: epidemiological evidence. European Journal of Neurology. 2009; 16(1): 1-7.

5. Zhao Y, Calon F, Julien C, Winkler JW, Petasis NA, Lukiw WL, Bazan NG. Docosahexaenoic acid-derived neuroprotectin D1 induces neuronal survival via secretase- and PPARϒ-mediated mechanisms in Alzheimer’s disease models. 2011; 6(1): 1-15.

6. Whitmer RA, Gustafson DR, Barrett-Connor E, Haan MN, Gunderson EP, Yaffe K. Central obesity and increased risk of dementia more than three decades later. Neurology. 2008; 71: 1051-1065.

7. Muqtadar H, Testai, FD. The dementia of cardiac disease. Current Cardiology Reports. 2012; 14(6): 732-740.

8. Howes M-JR, Perry E. The role of phytochemicals in the treatment and prevention of dementia. Drugs and Aging. 2011; 28(6): 439-468.

9. Devore EE, Grodstein F, van Rooji FJA, Hofman A, Rosner B, Stampfer MJ, Witteman JCM, Breteler MMB. Dietary intake of fish and omega-3 fatty acids in relation to long term dementia risk. American Journal of Clinical Nutrition. 2009; 90(1): 170-176.

10. Lukiw WJ, Bazan NG. Docosahexaenoic acid and the aging brain. The Journal of Nutrition. 2008; 138(12): 2510-2514.

11. Galasko DR, Peskind E, Clark CM, Quinn JF, Ringman JM, Jicha GA, Cotman C, Cottrell B, Montine TJ, Thomas RG, Aisen P. Antioxidants for Alzheimer disease. Arch Neurology. 2012; 69(7): 836-841.

12. Gu Y, Nieves JW, Stern Y, Luchsinger JA, Scarmeas N. Food combination and Alzheimer disease risk: a protective diet. Arch Neurol. 2010; 67(6): 699-706.

13. Feart C, Samieri C, Rondeau V, Amieva V, Portet F, Dartigues J-F, Scarmeas N, Barberger-Gateau P. Adherence to a Mediterranean diet, cognitive decline, and risk of dementia. The Journal of the American Medical Association. 2009; 302(6): 638-648.

14. Arab l, Sabbagh MN. Are certain lifestyle habits associated with lower Alzheimer disease risk? Journal of Alzheimer’s Disease. 2010; 20(3): 785-794.

Want to read the other articles in this issue? SUBSCRIBE TODAY for as little as $99 to improve your practice and stay up to date on the latest in dementia research and training.