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Physical Activity, Diet, and Risk of Alzheimer Disease: In this study, both higher Mediterranean-type diet adherence and higher physical activity were independently associated with reduced risk for AD.
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JAMA Aug 12 2009
Nikolaos Scarmeas, MD; Jose A. Luchsinger, MD; Nicole Schupf, PhD; Adam M. Brickman, PhD; Stephanie Cosentino, PhD; Ming X. Tang, PhD; Yaakov Stern, PhD
Author Affiliations: Taub Institute for Research in Alzheimer's Disease and the Aging Brain (Drs Scarmeas, Luchsinger, Schupf, Brickman, Cosentino, and Stern), Gertrude H. Sergievsky Center (Drs Scarmeas, Schupf, Brickman, Cosentino, Tang, and Stern), and Departments of Neurology (Drs Scarmeas, Brickman, Cosentino, and Stern) and Medicine (Dr Luchsinger), Columbia University Medical Center, New York, New York.
"Compared with physically inactive individuals, report of some physical activity was associated with a 29% to 41% lower risk of developing AD, while report of much physical activity was associated with a 37% to 50% lower risk."
"belonging to the middle diet adherence tertile was associated with a 2% to 14% risk reduction, while belonging to the highest diet adherence tertile was associated with a 32% to 40% reduced risk"
"Compared with individuals with low physical activity plus low adherence to diet (absolute AD risk, 19%), high physical activity plus high diet adherence was associated with a 35% to 44% relative risk reduction"
"This study suggests that more physical activity is associated with a reduction in risk for developing AD. The gradual reduction in risks for higher tertiles of physical activity also suggests a possible dose-response association. Elderly individuals are often quite physically inactive. High physical activity in this cohort of 77-year-old individuals corresponded to approximately 1.3 hours of vigorous physical activity per week, 2.4 hours of moderate physical activity per week, or 4 hours of light physical activity per week, or a combination thereof. Nevertheless, even this relatively small amount of physical activity was associated with a reduction in risk for developing AD."
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ABSTRACT
Context - Both higher adherence to a Mediterranean-type diet and more physical activity have been independently associated with lower Alzheimer disease (AD) risk but their combined association has not been investigated.
Objective - To investigate the combined association of diet and physical activity with AD risk.
Design, Setting, and Patients - Prospective cohort study of 2 cohorts comprising 1880 community-dwelling elders without dementia living in New York, New York, with both diet and physical activity information available. Standardized neurological and neuropsychological measures were administered approximately every 1.5 years from 1992 through 2006. Adherence to a Mediterranean-type diet (scale of 0-9; trichotomized into low, middle, or high; and dichotomized into low or high) and physical activity (sum of weekly participation in various physical activities, weighted by the type of physical activity [light, moderate, vigorous]; trichotomized into no physical activity, some, or much; and dichotomized into low or high), separately and combined, were the main predictors in Cox models. Models were adjusted for cohort, age, sex, ethnicity, education, apolipoprotein E genotype, caloric intake, body mass index, smoking status, depression, leisure activities, a comorbidity index, and baseline Clinical Dementia Rating score.
Main Outcome Measure - Time to incident AD.
Results - A total of 282 incident AD cases occurred during a mean (SD) of 5.4 (3.3) years of follow-up. When considered simultaneously, both Mediterranean-type diet adherence (compared with low diet score, hazard ratio [HR] for middle diet score was 0.98 [95% confidence interval {CI}, 0.72-1.33]; the HR for high diet score was 0.60 [95% CI, 0.42-0.87]; P = .008 for trend) and physical activity (compared with no physical activity, the HR for some physical activity was 0.75 [95% CI, 0.54-1.04]; the HR for much physical activity was 0.67 [95% CI, 0.47-0.95]; P = .03 for trend) were associated with lower AD risk. Compared with individuals neither adhering to the diet nor participating in physical activity (low diet score and no physical activity; absolute AD risk of 19%), those both adhering to the diet and participating in physical activity (high diet score and high physical activity) had a lower risk of AD (absolute risk, 12%; HR, 0.65 [95% CI, 0.44-0.96]; P = .03 for trend).
Conclusion - In this study, both higher Mediterranean-type diet adherence and higher physical activity were independently associated with reduced risk for AD.
INTRODUCTION
Previous research has shown that physical activity can slow down or prevent functional decline associated with aging and improve health in older individuals.1-2 However, regarding Alzheimer disease (AD) or dementia, the relationship is less clear, with many studies reporting exercise being associated with lower rates of cognitive decline1, 3 or dementia4-7 and others reporting no significant association.8-10 Dietary habits also may play an important role but epidemiological data on diet and AD have been conflicting.11 In this cohort, we previously found that higher adherence to a Mediterranean-type diet is associated with lower risk for AD12-13 and mild cognitive impairment.14
Nevertheless, it is important to know whether physical activity and diet confer independent associations because individuals who exercise often belong to higher educational-socioeconomic strata, are more health conscious, and in general tend to follow healthier eating habits. The magnitude of such potential associations with AD in individuals engaging in such activities is also of great interest from a public health point of view. To our knowledge, there is scarce literature examining diet and exercise combined.
In the current study, we first sought to examine the association between physical activity and risk of AD. We then investigated the extent to which physical activity and adherence to a Mediterranean-type diet had independent associations with AD risk. We hypothesized that both adherence to a Mediterranean-type diet and physical activity would be independently associated with development of AD and that individuals who ate healthfully and participated in physical activity would have additive benefits regarding development of AD.
COMMENT
This study suggests that more physical activity is associated with a reduction in risk for developing AD. The gradual reduction in risks for higher tertiles of physical activity also suggests a possible dose-response association. Elderly individuals are often quite physically inactive. High physical activity in this cohort of 77-year-old individuals corresponded to approximately 1.3 hours of vigorous physical activity per week, 2.4 hours of moderate physical activity per week, or 4 hours of light physical activity per week, or a combination thereof. Nevertheless, even this relatively small amount of physical activity was associated with a reduction in risk for developing AD.
Although some studies have failed to detect an association between physical activity and cognition,8-10 our results are in accordance with many other studies in the literature that suggest a potentially beneficial role for physical activity regarding either rates of cognitive decline1, 3 or dementia.4-7 Cognitive benefits for physical activity have been demonstrated even in small preliminary intervention studies either in healthy elders34 or in those with cognitive impairment or dementia.35-36 Nevertheless, clinical trial evidence for a protective effect of physical activity is still insufficient overall.37
Evidence for connections between physical activity and brain biology is abundant. Cardiovascular fitness has been related to lower age-related brain atrophy in structural magnetic resonance imaging,38 to differential patterns of activation suggesting improved plasticity in functional magnetic resonance imaging,39 to increased cerebral blood flow,40 and to increased cerebral blood volume in the dentate gyrus (suggesting possibly increased neurogenesis).41 Animal studies have suggested that exercise may promote angiogenesis,42 neurogenesis, synaptic plasticity and learning,41 neuronal survival and resistance to brain insults,43 and may increase levels of brain-derived neurotrophic factor and expression of genes that could benefit plasticity.44-45 Higher physical activity also has been associated with reduction of inflammation,46 increased concentration of various neurotransmitters,47-48 and increased insulin growth factor.49 Physical activity has even been associated with AD pathological changes in mice; exercise has been shown to result in decreased cortical amyloid burden, possibly mediated by a change in the processing of amyloid precursor protein.50
Physical activity is only one of the factors constituting a healthy lifestyle. Another important one is dietary habits. More health-conscious individuals often follow not one but many aspects of healthy behavior. Therefore, the investigation of which particular dimensions of lifestyle are associated with disease risk is important. Nevertheless, many studies focus on specific individual factors. One of the reasons for the failure to consider diet in the past is the difficulty in summarizing dietary habits. This is particularly true in the neurological and dementia literature in which the methodological tool of dietary patterns has been underused. An exception to this is the Mediterranean-type diet pattern, which we previously reported to be associated with lower risk for AD,12-13 mild cognitive impairment,14 and lower mortality in AD.27
Dietary patterns reflect better everyday dietary habits (ie, foods or nutrients are not consumed in isolation but rather as components of an overall diet), and capture the diet's multidimensionality because they can integrate complex or subtle interactive effects of many dietary constituents and bypass problems generated by multiple testing and the high correlations that may exist among these constituents. In addition to this, as demonstrated in the present study, individuals' dietary habits can be effectively summarized in single scores that can be examined in terms of disease risk in the face of other potential predictors.
Because participating in physical activity and healthy eating are often related to each other (as shown in the present study), it could be argued that the association between physical activity and AD is just a manifestation of more physically active individuals eating healthier. Nevertheless, their association with lower rates of AD development was independent of each other. The highest tertiles for both physical activity and Mediterranean-type diet were associated with a 61% to 67% lower risk of AD, an association present after adjusting for multiple potential confounders. Therefore, it seems that both eating well and participating in physical activity may independently confer AD-related health benefits.
Study limitations relating to the construction of the Mediterranean-type diet score (use of an a priori dietary pattern score, equal weighting of underlying food categories, underestimating total food and caloric intake, etc) have been discussed.12-13 Physical activity was more weighted toward leisure-recreational type of activities, while the contribution of physical components of everyday activities was not recorded. Physical activity was based on reporting and not on physiological measurement of maximum oxygen consumption or other objective methods. Nevertheless, it correlated with objective measures of physical performance. To the extent that physical activity measurement error is unrelated to AD outcome, this may bias our results toward the null. Two different variants of the physical activity assessment instrument were used, but the associations remained in models adjusted for this or when we used only one of the physical activity variants.
Follow-up was relatively short and reverse causality or recall bias from persons with early subclinical cognitive deficits cannot be excluded. Both the dietary and physical activity measures demonstrated relative stability over time, but individuals who developed dementia reported somewhat higher decline in both physical activity and Mediterranean-type diet adherence. Nevertheless, adjusting for baseline CDR score and sensitivity analyses excluding individuals with mild cognitive impairment and/or considering a 2-year lag did not attenuate the associations.
Individuals not included in the present analyses because of either missing physical activity and dietary information or lack of follow-up did not differ in many characteristics but were slightly less educated, less likely to be smokers, younger, and had lower cognitive performance, higher caloric intake, higher BMI, and more comorbidities. The above characteristics have variable bidirectional associations with the outcome because low cognitive performance, low education,15 and higher caloric intake23 are risk factors for AD, while younger age and higher BMI are protective. Additionally, potential confounding was addressed by adjusting for all the above factors. Nevertheless, selection bias due to healthier individuals remaining in the cohort is possible. All observational epidemiology studies have residual confounding, in particular of the healthy person type, which cannot be excluded. This issue can only be definitively addressed by randomized controlled trials.
Confidence in our findings is strengthened by the following factors. The study is community-based and the population is multiethnic, increasing the external validity of the findings. Assessment instruments that have been previously validated and widely used in epidemiological studies were applied. The diagnosis of AD took place in a university hospital with expertise in dementia and was based on comprehensive assessments and standard research criteria. The patients were followed up prospectively at relatively short intervals. Measures for multiple potential confounders were carefully recorded and adjusted for in the analyses. Using a variety of sensitivity analyses, including conservative propensity analyses methods, the results were similar.
In summary, our results support the potentially independent and important role of both physical activity and dietary habits in relation to AD risk. These findings should be further evaluated in other populations.
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