The role of environmental/lifestyle related factors in Alzheimer's disease- Can we lower our risk?

Introduction/Note to researcher

As you are aware, there is no cure for Alzheimer's disease. Just as there is no cure, there is no magic potion guaranteed to prevent Alzheimer’s disease (that we know of!). On the other hand, there is compelling evidence that we can do certain things to delay the onset of the disease and even slow its progression. If we follow enough of this advice, perhaps we can avoid it altogether. It is becoming evident that lifestyle plays a big role in many diseases. What we eat, where we live, what we do with our leisure time: all of these are now known to play a very significant role in how likely we are to a number of our most feared diseases. The same is true of for preventing Alzheimer’s. Our genetics may be a big factor in whether or not we will eventually be affected by it, but our lifestyle and other environmental factors, factors we can control, are also potential contributors. We have organized the material gathered into 4 cohesive categories: Physical Fitness, Mental Fitness, and Diet and Environment. We hope you find our collection of sources a useful part of your research on this topic.

-Maria, Amal, and Yafet.

What is Alzheimer's Disease?

What is Alzheimer's Disease? (n.d.). Retrieved April 9, 2015, from

Alzheimer's Disease, also commonly referred to as AD, is the most common form of dementia, accounting for 60-80% of known dementia cases. AD is a neuro-degenerative disease, which affects the brain and breaks down its neuron structure. AD is commonly linked with old age, as most victims affected are over the age 65. Although this is true, AD is not a normal part of aging and in fact 5% of people diagnosed with AD are under the age of 50, which is known as early on-set Alzheimer's. This process is slow and the degeneration of the brain occurs over time. Once this process begins, it is irreversible, and as mentioned before, currently has no known cures. To reiterate, as well as elaborate on the basics of AD, we have included an informative TedTalk video on the subject.

Symptoms and Diagnosis

What is Alzheimer's Disease? (n.d.). Retrieved April 9, 2015, from

When dealing with a potential case of AD, it is important to keep an eye out for earlier symptoms to be able to tackle the problem as soon as possible. The first, most common symptom of AD is difficulty remembering newly learned information. Since AD deals with the destruction of brain cells, the short term memory loss will eventually worsen and effect the patients everyday task, such as forgetting important dates and asking for the same information repetitively. Other early symptoms are: challenges with problem solving, confusion with time or place, misplacing things, poor judgement and changes in mood or personality. As AD reaches the more advanced stages, the symptoms begin to worsen, such as extreme confusion and disorientation. This degenerative process will eventually worsen to the point of long term memory loss and death.


Physical Fitness

Physical Activity and Alzheimer's Disease: From Prevention to Therapeutic Perspectives.

Participating in daily physical activities is known to be a risk reduction factor in the development of AD in the elderly. A case study was conducted in 1990 testing the cognitive ability of the elderly and found those who reported higher levels of physical activity, on average scored higher on the cognitive test. Further epidemiological studies reported that low physical activity is associated with high rates of cognitive decline and dementia. Patients diagnosed with AD also found that physical activity help with their quality of life and cognitive abilities. Physical activity can also be a factor in the prevention of AD, through a reduction of different cardiovascular risk factors such as hypertension, diabetes, hypercholesterolemia, and obesity. Benefits of consistent physical activity are manifested in the brain, strengthening it to the point where it can help prevent symptoms of onset AD.

Rolland, Y., & Van Kan, G. (2008). Physical Activity and Alzheimer's Disease: From Prevention to Therapeutic Perspectives. Journal of the American Medical Directors Association, Volume 6, 390-405. Retrieved April 12, 2015, from

Functional connectivity: A source of variance in the association between cardiorespiratory fitness and cognition

Both default mode network (DMN) function and increased aerobic fitness have been associated with better cognitive performance and reduced incidence of Alzheimer’s disease among older adults. In this article we examine the association between aerobic fitness, functional connectivity in the DMN, and cognitive performance. Results showed significant age-related deficits in functional connectivity in both local and distributed DMN pathways. However, in a group of healthy elderly adults, almost half of the age-related disconnections showed increased functional connectivity as a function of aerobic fitness level. Finally, we examine the hypothesis that functional connectivity in the DMN is one source of variance in the relationship between aerobic fitness and cognition. Results demonstrate instances of both specific and global DMN connectivity mediating the relationship between fitness and cognition. We provide the first evidence for functional connectivity as a source of variance in the association between aerobic fitness and cognition, and discuss results in the context of neurobiological theories of cognitive aging and disease.

Voss, M. W., Erickson, K. I., Prakash, R. S., Chaddock, L., Malkowski, E., Alves, H., … Kramer, A. F. (2010). Functional connectivity: A source of variance in the association between cardiorespiratory fitness and cognition? Neuropsychologia,48(5), 1394-1406. doi:

Semantic memory functional MRI and cognitive function after exercise intervention in mild cognitive impairment.
Mild cognitive impairment (MCI) is associated with early memory loss, Alzheimer’s disease (AD) neuropathology, inefficient or ineffective neural processing, and increased risk for AD. (Semantic, Pg 1) Physical exercise is often recommended for people diagnosed with MCI, primarily because of its widely reported cognitive benefits in healthy older adults. This study examines the effects of exercise training on semantic memory activation using an MRI. The study used participants affected by MCI as well as cognitively intact participants, who volunteered for a 12-week exercise intervention consisting of supervised treadmill walking. Both MCI and control participants significantly increased their cardiorespiratory fitness by approximately 10% on a treadmill exercise test. The findings that resulted from the MRI results conducted before and after suggest that exercise may improve efficiency during semantic memory retrieval in both MCI and cognitively intact older adults, and may lead to improvement in cognitive function. (Semantic, Pg 1) They do note that clinical trials are needed to determine if exercise is effective to delay conversion to AD.
Smith, J. Carson; Nielson, Kristy A.; Antuono, Piero; Lyons, Jeri-Annette; Hanson, Ryan J.; et al. Journal of Alzheimer's Disease37.1 (2013): 197-215.

Mental Fitness

Review of the memory bible: An innovative strategy for keeping your brain young.

In the book the author beings by defining memory and describes how it changes over time. It also gives a guide for people who have just gotten the diagnoses and ways to deal with it. It provides latest treatments and how to cope. The most interesting part of the book has to do with brain training and mental fitness. The authors writes about the importance of mental fitness and how it could delay or slow down Alzheimer’s disease. The author also talks about different types of mental fitness for example brain teasers and puzzles.

Ford, G. (2007). Review of the memory bible: An innovative strategy for keeping your brain young. American Journal of Electroneurodiagnostic Technology, 47(3), 227-228. Retrieved from

Educating the Brain to Avoid Dementia: Can Mental Exercise Prevent Alzheimer Disease? Margaret Gatz

In this article, Margaret Gatz discusses the interesting subject of the practice of actively exercising your brain in order to promote brain health, from a skeptical viewpoint. Her conclusion is that we have little evidence that mental practice will help prevent the development of AD, and that there is much better evidence that brain development early in life is what matters along with the fact that genetic influences are of great importance in accounting for individual differences in cognitive reserve and in explaining who develops Alzheimer disease and who does not. Gatz starts by stating that physicians now commonly advise older adults to engage in mentally stimulating activity as a way of reducing their risk of dementia and AD, pointing out that the recommendation is often followed by the acknowledgment that evidence of benefit is still lacking, but that it "can't hurt". She acknowledges Epidemiological studies that have shown the risk of Alzheimer disease is two to four times higher in those who have fewer years of education, as compared to those who have more years of education. She also acknowledges studies which have suggested that those who engage in more leisure activities, especially activities that are mentally stimulating, have a lower prevalence and incidence of Alzheimer disease, as well as studies that have found that older adults without dementia who participate in more intellectually challenging daily activities show less decline over time on various tests of cognitive performance. However, she is quick to point out problems with these studies - people cannot be randomly assigned to different levels of education, or to different kinds and levels of participation in leisure activities and consequently researchers must try to identify confounders and take them into account analytically. She continues to address other types of evidence suggesting that mental exercise may help to prevent Alzheimer disease and identifies the problems associated with them.
Gatz M (2005) Educating the brain to avoid dementia: Can mental exercise prevent Alzheimer disease? PLoS Med 2(1): e7.

Researchers Believe Chess May Cure Alzheimer's
This video is a news report which talks about a scientific experiment involving the game of chess being conducted to determine if intellectual work can help to prevent the onset of Alzheimer's disease.


The significance of environmental factors in the etiology of Alzheimer's Disease.

Diet plays a primary risk factor in the development of AD. William Grant conducted an ecologic study, after noticing the difference in the occurrence of AD in immigrants as supposed to those in their respective native country. For example, Japanese-Americans living in Hawaii are 2.5x more likely to be diagnosed with AD than those living in Japan. Grant used data of AD prevalence and dietary supply from 11 different countries to help drive his research. Two main risk factors found by Grant were total fat consumption and total calorie consumption. Those diagnosed with AD had a higher caloric intake after the age of 60 than those who were healthy. Further research found that Polyunsaturated fatty acids, such as Linoleic acid, are known to be associated with cognitive impairment, and may speed the degenerative process of AD. Another dietary factor investigated is the correlation between cholesterol levels and the etiology of AD. The correlation is simple, in that the higher the cholesterol, the higher the risk of AD. Cholesterol is largely manipulated by dietary habits, such as the intake of sugars and fats. The cholesterol reducing drug Statin, also have the added affect of reducing the risk of AD.

Grant, W., Campbell, A., Itzhaki, R., & Savory, J. (2002). The significance of environmental factors in the etiology of Alzheimer's Disease. Journal of Alzheimer's Disease, Volume 4, 179-189. Retrieved April 10, 2015, from

Dietary Intake of Antioxidants and Risk of Alzheimer Disease.

The Rotterdam study gathered 5395 participants, no older than 55 and dementia free, to study their dietary habits over the course of several years. After six years of closely monitoring these patients, 197 participants developed dementia, of which 146 were diagnosed with AD. The main difference noticed between thosed who developed AD, and healthly participants was the intake of antioxidants and antioxidant supplements. The four main antioxidants which were found to have an affect were, beta-carotene, flavonoids, vitamins E & C. Emphasis can be placed on both vitamins C & E with AD prevention, while vitamin E also help slow the degenerative process in those who were already diagnosed with AD.

Engelhart, M., Geerlings, M., Ruitenberg, A., Van Swieten, J., Hofman, A., Witteman, J., & Breteler, M. (2002). Dietary Intake of Antioxidants and Risk of Alzheimer Disease. The Journal of the American Medical Association, Volume 287. Retrieved April 8, 2015, from

Mediterranean Diet and Alzheimer's Disease Mortality

The Mediterranean diet is characterized by high intake of vegetables, legumes, fruits, and cereals; high intake of unsaturated fatty acids (mostly in the form of olive oil), but low
intake of saturated fatty acids; a moderately high intake of fish; a low-to-moderate intake of dairy products (mostly cheese or yogurt); a low intake of meat and poultry; and a
regular but moderate amount of ethanol, primarily in the form of wine and generally during meals. Studies in support of Mediterranean diet as an optimal diet for prevention of cardiovascular and major chronic diseases has rapidly evolved. The authors of this journal article had reported that this diet (MeDi for short) is also related to a lower risk of Alzheimer's disease. In this subsequent study, they examined the association between MeDi and mortality in patients with AD by taking a relatively small sample of individuals, and following their adherence to the MeDi every 1.5 years. There were 192 individuals, all from New York. 44% of the patients died during the course of the study.What was discovered was that as compared with AD patients at the lowest MeDi adherence level, those in the middle had lower mortality risk, whereas subjects at the highest adherence level had an even lower risk. Based on these findings they were able to conclude that adherence to the Mediterranean diet may affect not only the risk for Alzheimer disease but also subsequent disease course: Higher adherence to the MeDi is associated with lower mortality in AD (Mediterranian, Pg 1.). The majority of their subjects were of nonwhite ethnicity. They did note that excluding the white subjects and repeating the analyses in only black and Hispanic patients did NOT change the associations. Compared with the patients who remained alive, those who died did not differ in any clinical–demographic characteristic, with the exception of being older and having lower MeDi scores (Mediterranean Pg 4). The data from this study is presented clearly, and they have included tables and graphs for illustrative purposes.

Scarmeas, Nikolaos; Luchsinger, Jose A.; Mayeux, Richard; Stern, Yaakov. Neurology69.11 (Sep 2007): 1084-1093.

Association Between the Mediterranean Diet and Cognitive Decline in a Biracial Population

This study is suggesting there may be a chance that stronger adherence to the Mediterranean diet may reduce the rate of cognitive decline in black adults, moreso than white adults. The researcher noted that studies on the link between cognitive decline and the mediterranean diet have been limited by a lack of diversity and suggested this may be contributing to the fact that evidence of a link between AD and this diet have been less consistent than the link between the diet and cardiovascular disease and cancer. In a population of initially well-functioning older adults, this study found a significant association between stronger adherence to the Mediterranean diet and a slower rate of cognitive decline among black, but not white older adults. Previous prospective studies investigating the association etween the Mediterranean diet and cognition decline or dementia have reported mixed results in predominately white populations, while studies including sizeable black populations have had more consistently positive results (Association, Pg. 5).

Koyama, Alain; Houston, Denise K.; Simonsick, Eleanor M.; Lee, Jung Sun; Ayonayon, Hilsa N.; et al. The Journals of Gerontology: Series A: Biological Sciences and Medical Sciences70.3 (Mar 2015): 352-357.

Where the actions of environment (nutrition), gene and protein meet: Beneficial role of fruit and vegetable juices in potentially delaying the onset of alzheimer's disease.

The article discusses from the perspective of dietary supplementation on Alzheimer's disease (AD). The manuscript is focused to how apple juice concentrate (AJC) modulates theexpression of the important AD-related protein presenilin (PS-1). This work shows that AJC attenuates PS-1 overexpression during dietary and genetically - induced oxidative stress and suggests that dietary factors are important for the oxidative stress and neurotoxic properties of A/9 involved in AD pathogenesis. The implication of the work can be assessed from four important angles: i) A/3-mediated oxidative stress, ii) PS-1 expression, iii) nutritional and dietary factors, and iv) role of methylation. Growing evidence suggests that oxidative damage caused by A/3 in the pathogenesisof AD may be hydrogen peroxide mediated. Two important results emerge from this work. First, AJC contained SAM levels comparable to those capable of suppressing PS-1 overexpression. Second, AJC may be able to provide neuroprotection by mechanisms in addition to its antioxidant potential. Overall, the authors present interesting data on the effect of dietary supplementation with apple juice concentrate on PS-1 expression. The subject matter is interesting with regard to gene regulation research in general as well as AD research in particular.

Lahiri, D. K. (2006). Where the actions of environment (nutrition), gene and protein meet: Beneficial role of fruit and vegetable juices in potentially delaying the onset of alzheimer's disease. Journal of Alzheimer's Disease, 10(4), 359-361.


Occupational exposure to pesticides increases the risk of incident AD: The Cache County Study.

These researchers acknowledge that few studies have examined the relationship of pesticide exposure and risk of dementia or Alzheimer disease (AD), and explain they have sought to examine the association of occupational pesticide exposure and the risk of incident dementia and AD in later life. Studies of this nature are important due to the fact that commonly used pesticides affect the nervous system, so naturally it would be prudent to examine whether any lasting effect may exist. The researchers who conducted this study noted that case-control studies in dementia research, which necessarily rely on informant reports, are likely to produce somewhat conservative estimates as proxy informants have been shown to underreport pesticide exposures. (Occupational, pg 6). Evaluations of data from studies have also shown that informant reports tend to underestimate exposures while reports from farmers themselves tend to be reliable. They used self-reported exposure as data in this study. The data showed that occupational pesticide exposure was associated with an increased risk of dementia. When the outcome was restricted to Alzheimer's Disease, the association remained. The risk of AD associated with certain pesticides strains over others was found to be nearly significant. The pesticides examined are the commonly used organophosphate and organochlorine pesticides. The findings of this study add to a small but growing literature suggesting that exposure to pesticides may have adverse long-term effects on the nervous system, thereby increasing the risk of AD in late life.
Hayden, K. M.; Norton, M. C.; Darcey, D.; Østbye, T.; Zandi, P. P.; et al. Neurology74.19 (May 11, 2010): 1524-1530.

Stress and glucocorticoid footprints in the brain—the path from depression to Alzheimer's disease.

Increasingly, stress is recognized as a trigger of depressive episodes and recent evidence suggests a causal role of stress in the onset and progression of Alzheimer's disease (AD) pathology. Besides aging, sex is an important determinant of prevalence rates for both AD and mood disorders. In light of a recent meta-analysis indicating that depressed subjects have a higher likelihood of developing AD, a key message in this article will be that both depression and AD arestress-related disorders and may represent a continuum that should receive more attention in future neurobiological studies. Accordingly, this review considers some of the cellular mechanisms that may be involved in regulating this transition threshold. In addition, it highlights the importance of addressing the question of how aging and sex interplay with stress to influence mood and cognition, with a bias towards consideration of neuroplastic events in particular brain regions, as the basis of AD and depressive disorders

Sotiropoulos, I., Cerqueira, J. J., Catania, C., Takashima, A., Sousa, N., & Almeida, O. F. X. (2008). Stress and glucocorticoid footprints in the brain—the path from depression to alzheimer's disease. Neuroscience and Biobehavioral Reviews, 32(6), 1161-1173. doi:

Impact of Metals

The significance of environmental factors in the etiology of Alzheimer's Disease

The concentration of transitional metals and Aluminum ions located in the brain of those who died of AD are elevated compared to those with AD. The lack of alkali metals in the brain can also be observed in those who died of AD. Aluminum is known to be neurotoxic to humans, and that neurotoxicity can contribute to the neurodegenerative process of AD. A study confirmed elevated levels of metal in the temporal cortex, parietal cortex, and the hippocampus of patients with AD with elevated Aluminum levels in the hippocampus. They also found that Aluminum concentration levels in the brain increase with age, which is very well known factor in the development of AD. Although connections between metal and AD are still primitive and have doubters in the scientific realm, the connection has enough ground to be considered. Exposure to metals and specifically Aluminum in the environment can prove harmful, and lead to the development of AD.

Grant, W., Campbell, A., Itzhaki, R., & Savory, J. (2002). The significance of environmental factors in the etiology of Alzheimer's Disease. Journal of Alzheimer's Disease, Volume 4, 179-189. Retrieved April 10, 2015, from

Environmental Enrichment

Environmental Enrichment Reduces Aβ Levels and Amyloid Deposition in Transgenic Mice

Lazarov, O., Robinson, J., Tang, Y., Hairston, I., Korade-Mirnics, Z., & Lee, V. (2005). Environmental Enrichment Reduces Aβ Levels and Amyloid Deposition in Transgenic Mice. Cell Press, Volume 120, 701-713. Retrieved April 13, 2015, from

The environment in which an AD patient is surronded by plays a significant role on how the patient is affect by their AD. Cerebral deposition of β-amyloid (Aβ) peptides in the brain is a trait shared by patients who are affected by AD, and the same can be said for mice. Mice who had elevated level of cerebral Aβ where tested on, placing a number of mice in an "enriched environment" and a control group placed in an average/normal environmental. These studies found that there was a significance decrease of cerebral Aβ levels in those mice who were placed in the enriched environmental as suppossed to those in a standard environmental. The enriched environment for the mice consisted of larger cages, running wheels, colored tunnels, toys and chewable materials, compared to just a normal cage in the average living conditions. In humans, this could transfer into an environment where the patient is confortable, in a familiar setting, and surronded by those who know and speak the same language as the patient.


Why wait the 20 more years of studies it will take to prove we can delay cognitive decline through our lifestyle choices? Dr. Gary Small, Director of the UCLA Longevity Center at the Semel Institute for Neuroscience & Human Behavior, talks about brain healthy longevity, cluster genetics, and healthy lifestyles that provide for brain health. This lecture is just under 1 hour, and the material he presents covers a seemingly comprehensive array of ways in which we might delay and avoid Alzheimer's and related diseases.

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