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Scientific Review: Is a Healthy Lifestyle the Key To Preventing Alzheimer’s Disease?

By: Mariana Leporowski, Universidad Francisco Marroquín


Alzheimer’s disease (AD) has been a condition that has affected millions of people through time. Despite this, we haven’t been able to find a cure or an effective treatment, mostly because of the complexity of the mechanisms that work towards forming this disease. Nowadays it is known that many medical/ pharmacological treatments have been used but none of these have had positive results on the improvement of patients with AD. Using a more incorporative approach (diet, exercise) seems to be the path to follow to find better ways to treat AD. Under this context, we are looking more into the combination of a diet-exercise-cognitive lifestyle rather than focusing on these as separate solutions. This review has the intention to show the historical data to this day, of what AD prevention has been and to allow a different perspective that could result in better and more effective ways to improve the quality of life of people who suffers from this disease.

Keywords: Alzheimer disease, diet, exercise, supplement, lifestyle, prevention


Alzheimer’s disease (AD) is the leading cause of dementia in America and Europe, being this 50-70% of the cases of dementia (1,2). AD is a cognitive disorder that hinders the independence of people who suffer from it (3).

The risk of developing dementia or AD increases when people reach the age of 65, where the prevalence of their development is 7% and this increases as the age advances (3).

AD has become a worldwide problem since no cure or prevention has found and the elderly population is estimated to increase by 30% in 2060 (4).

AD pathology is known to occur by the development of extracellular senile plaques from amyloid-B peptide and intracellular neurofibrillary tangles formed from hyperphosphorylation of the protein tau (5). 

The manifestations of AD begin with a loss of memory of daily life, such as not being able to complete the daily assignments or nor being able to remember what day it is. These memory lapses can be accompanied by apathy, depression, and anxiety (3).  

It has been studied that oxidative stress and inflammation may occur in the early stages of AD, that been said antioxidant and anti-inflammatory agents in food and physical activity had been studied to prevent AD (6).

Much of the studies of lifestyle interventions to prevent AD have heterogeneous data (7). Currently, there are no therapies to prevent the development or progression of AD, which is why this review aims to compile relevant articles on how a healthy lifestyle can help prevent or delay the progression of AD.


It is now that exercise would impact the brain health via the neurotrophic, neurogenic and vascular mechanism, due to an increase in cerebral blood volume, less brain atrophy and a slower progression to AD it also helps the neurogenesis of the brain by giving the neurons longer life span (8,9). A Cochrane study performed in adults with a cognitive disability found that aerobic exercise helps motor function, attention, cognitive speed and visual attention (10).  Another study made of mouse models demonstrate that exercise promotes hippocampus neurogenesis, nevertheless,no study has been made in humans (9).

A randomized controlled trial evaluated 68 people with early phases of AD, where they performed aerobic exercise during 26 weeks versus nonaerobic exercise such as stretching and toning (8), an observational study evaluated 56 participants without AD where they assessed a survey of the history of physical activity during their lifetime (11). The first study found an association with gaining cognitive function in the intervention group of aerobic exercise (p=0.02) (8), where the second study found an association in persons who perform physical activity in their daily basis a delay of cognitive function and brain impairment in people with AD (11). Both studies concluded that physical activity has beneficial effects on people with early stages of AD where the physical activity increased the cardiorespiratory function and improves brain health (8,11).

A multicenter prospective randomized control trial evaluated 210 people with AD, where they evaluated two physical intervention, the first one personalized exercise at home, and the second one implement group exercises. A statistically significant difference was seen in patients who performed physical activity personalized at home (p = 0.03) compared to the group intervention, indicating a gain in cognitive function in patients with AD, however, the results were obtained 12 months after the intervention (10).

It has been seen that physical activity can benefit brain health and cognitive function in patients with AD, however an important limitation of the studies was that they were performed in patients with early stages AD, where this review aims to assess the prevention of AD development, in spite of it, the sample sizes of these studies were small, so the conclusion we can provide is physical activity helps the cognitive function in patients with early AD and more studies need to be made to recommend exercise as prevention for AD.

Omega-3 fatty acids

AD is associated with brain inflammation that´s why the anti-inflammatories properties of omega 3 are been studied to a better cognitive function in early AD or as a prevention.

Fatty acids provide energy to the brain to maintain brain function. Polyunsaturated fatty acids (PUFA) are needed for the structure on the neuronal membranes, this leads to a better synapse and neurotransmission (12).  Fatty acids cannot be produced by the body, that´s why omega 3 is considered an essential fatty acid and we need to get it from food consumption or supplementation (13).

Four randomized controlled trials were conducted to evaluate the supplementation of omega 3 on an intervention group compared to the placebo group (14–17). The first study evaluated 57 individuals, were 19 had already AD in early stages and the rest had cognitive impairment no dementia, they found that the individuals on the supplement group of omega 3 had no benefits in their cognitive mood. However, the participants were not tested if they were carriers of the APOE4 gene of AD and the study was made on people who already had AD or cognitive impairment. They suggest future studies to have a larger sample and longer supplementation period on people who do not have  AD or dementia (14). The second study evaluated 39 individuals were they supplement with omega 3 and omega 3 with alpha-lipoic acid (ALA) for 12 months, they did not found beneficial effects on omega 3 and LA compared to the placebo group, however the combination group of omega 3 and LA had benefits on slowing down the cognitive decline. Nevertheless, this study had a small sample size and the individuals had already mild to moderate AD (15). The third study evaluated 295 subjects with probable AD, where they found no evidence on the supplementation of docosahexaenoic acid (DHA) (16). The fourth study evaluated 165 individuals, where the supplementation was associated to increase omega 3 in plasma with the doses administrated of 2.3 g/d where the results preserve the cognitive function on patients with mild AD (17).

Two cohort studies evaluate the consumption of omega 3 and the benefits of subjects with AD (18,19).  They found significantly reduced risk of dementia and AD when concentrations of mercury and omega 3 were above the median and in persons who ate fish at least once a week (19), also when omega 3 was given with carotenoids a positive effect happens in the cognitive function in patients with AD (18). Analyzing the data provided by the previous studies, the randomized controlled trials, we can say that the studies need to be longer to provide the recommendation on supplementing or consuming omega 3 to prevent AD, also the subjects on the studies already have  AD so the prevention was not evaluated, and the sample of the studies was too small to draw conclusions (14–17), on the other hand, the cohort studies were longer and had people without AD, however, they did not found evidence statistically significant to provide any conclusions (18,19).

Insulin Resistance

Insulin resistance (IR) is an alteration of the cellular and systemic response to insulin (22). There has been new evidence that IR can increase the risk of AD, however, this does not cause AD (23) as IR and inflammation could explain the mechanism between type 2 diabetes and AD (24).

A controlled study for India evaluated 40 subjects, where they found a relationship between high insulin levels and the severity of dementia (25). Two longitudinal studies evaluated the association between IR and AD, where one study evaluates 50 postmenopausal women and their relationship between their body mass index (BMI) with hippocampal volume and cognitive performance, where the presence of the APOE-e4 allele did not alter the results of the study. They found that IR decreased hippocampal volume and cognitive function (26).  The second longitudinal study evaluates 1544 subjects, 80 developed AD. Where they found an inverse relationship between IR and AD, where they believe the brain insulin autophosphorylate the insulin receptors and affect synaptic plasticity (27).  

Two prospective cohort studies evaluate the relationship between IR and altered cognitive function (22,24). The first cohort study evaluates 126 subjects, where IR had an association with lower myelinization, this mechanism is unknown however in this study they speculate that this happens secondary to cholesterol metabolism may change the myelination mechanism (22). The second cohort study evaluates 840 subjects for 13 years, 125 develop AD, where they think adiponectin, a hormone derivate from visceral fat, is a potential factor for AD, IR, and mortality, that´s why they investigate plasma adiponectin, glucose, glycated albumin, and insulin, where they did not found and association with AD, however adiponectin level was an independent risk for AD in women where a study from Japan found that high levels of adiponectin where associated with mild cognitive impairment and AD (24).

All the evidence concluded that IR could increase the risk for AD, that been said we could prevent IR by eating healthy, reducing saturated fats, sugars, refined flours and doing physical activity to prevent type two diabetes.


They have been studying that oxidative stress and damage increase the risk of development and progression of AD, that has been said several nutrients like vitamin C, E and b-carotene have been studied to diminish the risk of AD (28).

Four randomized controlled trials evaluate the possible effects of different antioxidants nutrient on AD (29–32).

 The first study evaluates 212 subjects and the effect of a medical food that includes vitamins C, E, B12, B6, B9, selenium and other nutrients on cognitive function in patients with mild cognitive AD after 12 weeks. They found that subjects with mild AD who consume medical food improve statistically significant (p=0.026) their memory, however, they did not determine which nutrient specifically helps the most (29). The second study evaluates 613 subjects with mild to moderate AD, where they evaluate the supplementation with vitamin E and memantine where they did not found a significant association (30). The third and fourth study where they evaluate 4 circulating antioxidants modifiable by diet, this where ascorbate, b-carotene, retinol and, urate and ginkgo Biloba extract supplementation they did not found a protective incidence of AD (31,32)

On the other hand, a prospective cohort study evaluates 7525 subjects, where they evaluate the consumption on b-carotenoids, flavonoids, vitamin C and E. They found that a high intake of vitamin C and E from food may reduce the risk of getting AD after 6 years follow up, also that patients with genetic risk factors will decrease the risk of getting AD if they consume the four nutrients mentioned. They proposed that antioxidants may have a positive effect in decreasing oxidative stress-reducing DNA damage, neuronal cell death and the aggregation of b-amyloid within the brain and decreasing the risk of getting atherosclerosis by reducing the risk of getting AD diminishing the cardiovascular risk with antioxidants, however, randomized controlled trials need to be done to determine its causality or not (33).

A cross-sectional and longitudinal study evaluates 100 subjects with probable AD where they administer a functional drink that includes polyphenols, vitamins B and C. They studied the association between homocysteine levels and AD, where lower homocysteine levels reduce the risk of AD, where folic acid suppresses the accumulation of homocysteine. The study found that patients who were drinking the functional drink lower their homocysteine concentrations having an antioxidant an anti-inflammation effect reducing the risk of AD  (34).

Mixed evidence was found using antioxidants in the different studies but none of the studies where able to determine which antioxidant was the most beneficial for reducing the risk for AD, the need for more randomized controlled trials on specific antioxidants is important to make a concrete recommendation. It can be deduced that having a healthy diet involving fruits and vegetables is needed to get the antioxidant effect of food, however, a recommendation on portions or grams of these foods cannot be made.


In conclusion, even though conventional medicine hasn’t been very effective in treating AD, studies involving omega 3, exercise, antioxidants haven´t been effective as well. This doesn’t mean that a more incorporative approach is completely wrong or that this is a path completely closed in future trails, it means that the studies that have been made in the past aren’t significant enough to create accurate conclusions of whether this approach works. This is due to two primary facts. First, all the studies involving omega 3, antioxidants, and exercise were done on patients with early stages of AD, or already with a developed disease. So, it wasn’t possible to conclude whether these components are helpful in the prevention of AD. Second, statistically speaking there is not a big sampling that can be studied to provide sufficient evidence to sustain a solid recommendation that could apply to a large group of people. Where there has been a substantial outcome is with IR, where the evidence suggests that IR could attribute to a risk factor for AD, so a recommendation of a healthy lifestyle could be made.


1.          Shah R. The role of nutrition and diet in Alzheimer disease: A systematic review. J Am Med Dir Assoc [Internet]. 2013;14(6):398–402. Available from:

2.          Winblad B, Amouyel P, Andrieu S, Ballard C, Brayne C, Brodaty H, et al. Defeating Alzheimer’s disease and other dementias: A priority for European science and society. Lancet Neurol. 2016;15(5):455–532.

3.          Whalen RM. Alzheimer disease and other dementias. Fam Med Princ Pract. 2016;2:339–46.

4.          Vauzour D, Camprubi-Robles M, Miquel-Kergoat S, Andres-Lacueva C, Bánáti D, Barberger-Gateau P, et al. Nutrition for the ageing brain: Towards evidence for an optimal diet. Ageing Res Rev [Internet]. 2017;35:222–40. Available from:

5.          Schelke MW, Hackett K, Chen JL, Shih C, Shum J, Montgomery ME, et al. Nutritional interventions for Alzheimer’s prevention: A clinical precision medicine approach. Ann N Y Acad Sci. 2016;1367(1):50–6.

6.          Šeper V, Nešić N. Nutrition Patterns in Prevention and Treatment of Neurodegenerative Diseases : Alzheimer ’ s Disease 1. 2019;3(1).

7.          Vauzour D, Camprubi-Robles M, Miquel-Kergoat S, Andres-Lacueva C, Bánáti D, Barberger-Gateau P, et al. Nutrition for the ageing brain: Towards evidence for an optimal diet. Ageing Res Rev [Internet]. 2017;35(2017):222–40. Available from:

8.          Morris JK, Vidoni ED, Johnson DK, Van Sciver A, Mahnken JD, Honea RA, et al. Aerobic exercise for Alzheimer’s disease: A randomized controlled pilot trial. PLoS One. 2017;12(2):1–14.

9.          Vidoni ED, Van Sciver A, Johnson DK, He J, Honea R, Haines B, et al. A community-based approach to trials of aerobic exercise in aging and Alzheimer’s disease. Contemp Clin Trials [Internet]. 2012;33(6):1105–16. Available from:

10.        Öhman H, Savikko N, Strandberg TE, Kautiainen H, Raivio MM, Laakkonen ML, et al. Effects of Exercise on Cognition: The Finnish Alzheimer Disease Exercise Trial: A Randomized, Controlled Trial. J Am Geriatr Soc. 2016;64(4):731–8.

11.        Liang KY, Mintun MA, Fagan AM, Goate AM, Bugg JM, Holtzman DM, et al. Exercise and Alzheimer’s disease biomarkers in cognitively normal older adults. Ann Neurol. 2010;68(3):311–8.

12.        Jicha GA, Markesbery WR. Omega-3 fatty acids: Potential role in the management of early Alzheimer’s disease. Clin Interv Aging. 2010;5(1):45–61.

13.        Canhada Scheine, Castro Kamila, Schweigert Perry CVL. Omega 3 fatty acids supplementation in Alzheimer s disease A systematic review.pdf. Nutr Neurosci. 2018;21(8):529–38.

14.        Phillips MA, Childs CE, Calder PC, Rogers PJ. No effect of omega-3 fatty acid supplementation on cognition and mood in individuals with cognitive impairment and probable Alzheimer’s disease: A randomised controlled trial. Int J Mol Sci. 2015;16(10):24600–13.

15.        Shinto L, Quinn J, Montine T, Dodge HH, Woodward W, Baldauf-Wagner S, et al. A randomized placebo-controlled pilot trial of omega-3 fatty acids and alpha lipoic acid in Alzheimer’s disease. J Alzheimer’s Dis. 2014;38(1):111–20.

16.        Quinn JF, Raman R, Thomas RG, Yurko-mauro K, Nelson EB, Dyck C Van, et al. Docosahexaenoic Acid Supplementation and Cognitive Decline in Alzheimer Disease: A Randomized Trial. JAMA. 2012;304(February 2010):1903–11.

17.        Eriksdotter M, Vedin I, Falahati F, Freund-levi Y, Hjorth E. Plasma Fatty Acid Profiles in Relation to Cognition and Gender in Alzheimer ’ s Disease Patients During Oral Omega-3 Fatty Acid Supplementation : The OmegAD Study. 2015;48:805–12.

18.        Nolan JM, Mulcahy R, Power R, Moran R, Howard AN. Nutritional Intervention to Prevent Alzheimer ’ s Disease : Potential Benefits of Xanthophyll Carotenoids and Omega-3 Fatty Acids Combined. 2018;64:367–78.

19.        Kröger E, Verreault R, Carmichael PH, Lindsay J, Julien P, Dewailly É, et al. Omega-3 fatty acids and risk of dementia: The Canadian Study of Health and Aging. Am J Clin Nutr. 2009;90(1):184–92.

20.        Zhang Y, Chen J, Qiu J, Li Y, Wang J, Jiao J. Intakes of fish and polyunsaturated fatty acids and mild-to-severe cognitive impairment risks: A dose-response meta-analysis of 21 cohort studies. Am J Clin Nutr. 2016;103(2):330–40.

21.        Barberger-Gateau P, Raffaitin C, Letenneur L, Berr C, Tzourio C, Dartigues JF, et al. Dietary patterns and risk of dementia. Neurology. 2007;69:1921–30.

22.        O’Grady JP, Dean DC, Yang KL, Canda C, Hoscheidt SM, Starks EJ, et al. Elevated Insulin and Insulin Resistance are Associated with Altered Myelin in Cognitively Unimpaired Middle‐Aged Adults. Obesity. 2019;

23.        Berger AL. Insulin resistance and reduced brain glucose metabolism in the aetiology of Alzheimer’s disease. J Insul Resist. 2016;1(1):7.

24.        Pylayeva-Gupta Y. Biomarkers for Insulin Resistance and Inflammation and the Risk for All-Cause Dementia and Alzheimer Disease: Results From the Framingham Heart Study. Bone. 2011;23(1):1–7.

25.        Thankappan S, Sen S, Subramanian S, Sinha P, Purushottam M, Bharath S. Insulin resistance in patients with Alzheimer’s dementia: A controlled study from India. Asian J Psychiatr [Internet]. 2018;38(2018):33–4. Available from:

26.        Rasgon NL, Kenna HA, Wroolie TE, Kelley R, Silverman D, Brooks J, et al. Insulin resistance and hippocampal volume in women at risk for Alzheimer’s disease. Neurobiol Aging [Internet]. 2011;32(11):1942–8. Available from:

27.        Lee TH, Hurwitz EL, Cooney R V., Wu YY, Wang CY, Masaki K, et al. Late life insulin resistance and Alzheimer’s disease and dementia: The Kuakini Honolulu heart program. J Neurol Sci [Internet]. 2019;403(June):133–8. Available from:

28.        Pizzorno, Joseph E., ND; Murray, Michael T. N. Textbook of Natural Medicine. In: Alzheimer´s Disease. 2013. p. 1189–99.

29.        Scheltens P, Kamphuis PJGH, Verhey FRJ, Olde Rikkert MGM, Wurtman RJ, Wilkinson D, et al. Efficacy of a medical food in mild Alzheimer’s disease: A randomized, controlled trial. Alzheimer’s Dement [Internet]. 2010;6(1):1-10.e1. Available from:

30.        Dysken MW, Guarino PD, Vertrees JE, Asthana S, Sano M, Llorente M, et al. Vitamin e and memantine in Alzheimer’s disease: Clinical trial methods and baseline data. Alzheimer’s Dement [Internet]. 2014;10(1):36–44. Available from:

31.        Williams DM, Hägg S, Pedersen NL. Circulating antioxidants and Alzheimer disease prevention: A Mendelian randomization study. Am J Clin Nutr. 2019;109(1):90–8.

32.        Vellas B, Coley N, Ousset PJ, Berrut G, Dartigues JF, Dubois B, et al. Long-term use of standardised ginkgo biloba extract for the prevention of Alzheimer’s disease (GuidAge): A randomised placebo-controlled trial. Lancet Neurol [Internet]. 2012;11(10):851–9. Available from:

33.        Engelhart MJ, Geerlings MI, Ruitenberg A, Van Swieten JC, Hofman A, Witteman JCM, et al. Dietary intake of antioxidants and risk of Alzheimer disease. J Am Med Assoc. 2002;287(24):3223–9.

34.        Morillas-Ruiz JM, Rubio-Perez JM, Albaladejo MD, Zafrilla P, Parra S, Vidal-Guevara ML. Effect of an antioxidant drink on homocysteine levels in Alzheimer’s patients. J Neurol Sci [Internet]. 2010;299(1–2):175–8. Available from:

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