Our cross-sectional study included 747 middle-age and older adults participating in a national longitudinal community study, 97.8% of whom had at least one CVDRF based on a combination of laboratory biomarkers and self-reported medical history. Older but not middle-age participants with various CVDRFs significantly differed in levels of executive function. Both age groups with various CVDRFs significantly differed in levels of inflammatory markers, but they were similar in their engagement in three types of leisure activities (mental, physical, and social). We failed to identify the mediating role of inflammatory markers between CVDRFs and cognitive function. However, across middle and late adulthood, engaging in more mental activities were significantly associated with better cognitive function, while engaging in more physical activities were significantly associated with lower levels of inflammation, considering the influence of demographic and health characteristics and number of CVDRFs. Furthermore, in the old age group, physical activities moderated the effect of CVDRFs on episodic memory, and cognitive activities moderated the effects of CVDRFs on IL-6.
Expanding from the findings of previous studies that the presence of individual CVDRFs influences cognitive function and inflammatory markers (Peters et al., 2008
; Raffaitin et al., 2011
; Wang et al., 2011
), our study found that the levels of inflammatory markers differed by the number of CVDRFs in both middle and old age, but the negative association between cognitive function and number of CVDRFs was only found in old age. The major difference occurred between groups with ≥2 CVDRFs and with single CVDRFs in both age groups. The finding is consistent with several studies that co-existing diabetes and hypertension increase the risk of developing dementia by six-fold (Posner et al., 2002
), while co-existing diabetes, hypertension, obesity, hypercholesterolemia, and smoking increase the risk of developing AD by 20-fold (Reitz et al., 2011
). The underlying mechanism is unclear, but it is likely that these CVDRFs share similar endothelial dysfunction and atherosclerosis, and co-existence CVDRFs may independently and/or interactively enhance inflammatory process, cerebral glucose and energy metabolism and cerebrovascular pathological changes that are related to cognitive decline (Kuczynski et al., 2009
; Panza et al., 2011
). However, such accumulated effect of CVDRFs on cognitive function would not start manifesting until old age.
Our findings extend our understanding of the relationship between CVDRFs and cognitive function in several ways. First, regardless of the number of CVDRFs, we found no difference in the frequency of engagement in leisure activities in neither middle- nor old-age group. This is surprising as it suggests that middle-age and older adults with CVDRFs may not be fully aware of the benefits of leisure activities on inflammation or cognitive function. Second, when considering the influence of demographic and health characteristics, number of CVDRFs, and other leisure activities, engaging in a higher frequency of mental activities was significantly associated with higher cognitive function, and higher frequency of physical activities was associated with lower levels of inflammatory markers. Further, in the old age group, mental activities moderated the effect of number of CVDRFs on levels of IL-6, and physical activities moderated the effect of CVDRFs on episodic memory. Evidence from meta-analysis of longitudinal cohort studies and randomized controlled trials support that there is a significant protective effect of mental activities on cognition in healthy older adults without cognitive impairment and those with mild cognitive impairment (Martin et al., 2011
; Valenzuela and Sachdev, 2009
; Valenzuela and Sachdev, 2006
). Our findings suggest that mental activities, along with physical exercise, may independently protect cognition or the inflammatory process, in middle- and old-age adults with various CVDRFs. The mechanisms that might link mental and physical activities to inflammatory markers and cognitive function are likely multifactorial. The first hypothesis may be applied in any aging group in addition to those with neurodegenerative or metabolic disorders. Engaging in mental and physical activities provides an enriched environment that enhances neural plasticity in terms of stimulating brain-derived neurotrophic factor (BDNF) and neuronal growth, and results in reserve against cognitive decline (Kramer et al., 2004
), while low levels of BDNF were found in patients with diabetes and obesity (Pedersen et al., 2009
). The second hypothesis may be specific to people with vascular risk. That is, stimulating activities may also enhance brain vascular health by enhancing endothelial function, while inflammatory markers are an important marker of endothelial function (Fratiglioni et al., 2004
). The third hypothesis is based on the stress theory. Leisure activities may help with relaxation, which reduces the secretion of corticosterone as well as alleviate inflammatory process. Chronic hypersecretion of corticosterone and inflammatory processes can cause permanent damage of neurons that lead to cognitive deficits and dementia. Moreover, a previous longitudinal study identified the protective effect of physical exercise (regular walking) on cognitive change over time in older women with at least 3 coronary risk factors (Vercambre et al., 2011
). Our data are in line with this observation with respect to the protective effect of exercise against high CVDRFs load.
What should be noticed is that physical exercise can influence various health conditions; thus, individuals with CVDRFs may recognize its importance even though they may not be aware of the possible relationship between physical exercise and cognitive decline. In contrast, mental activities have been theorized to have relatively specific protective effects on cognitive functioning (Stern, 2009
). Older adults with a large number of CVDRFs may not recognize the risk of developing cognitive deficits nor the relationship between mental activities and cognitive functioning; thus, they may not engage in mental behaviors. It may be equally important to develop strategies to facilitate their engagement in cognitive activities as well as to deliver cognitive training programs for older adults with CVDRFs.
As one of the strengths of this study, we defined CVDRFs using a combination of laboratory-based biomarkers and self-reported medical history to obtain an accurate profile of CVDRFs. Second, we included measures of peripheral concentrations of inflammatory factors (IL-6 and CRP). Our results showing an interaction between cognitively stimulating activities and CVDRFs in predicting IL-6 adds new evidence of a potential protective effect of cognitively stimulating activities on cognitive function, while previous studies focused on examining mental activities and cognitive tests results (Akbaraly et al., 2009
). Third, we comprehensively measured stimulating leisure activities covering physical, social, and cognitive types. Finally, we involved a sample across middle- and late-adulthood. It is interesting that the middle- and old-age groups did not differ in their engagement in mental activities. Although there was no significant association between number of CVDRFs and cognitive function in the middle-age group, using preventative strategies such as mental activities to slow cognitive decline in late life should be initiated as early as midlife.
A major limitation of this study relates to the cross-sectional nature of the design. Although mental and physical activities were found to be associated with inflammatory markers and cognitive function, we were not able to determine their causal relationships. Empirical literature on these relationships has been mixed. For example, one study found childhood cognitive abilities predicted late-life inflammation (Luciano et al., 2009
), and another study found participation of leisure activities was related to the level but not the change of cognitive function over time (Bielak et al., 2011). A future prospective design should be able to address the causal relationships between cognitive or physical activities on cognitive function as mediated by underlying inflammatory process in older adults with high CVDRFs load. Second, given the relatively small sample, the associations of individual CVDRFs and self-reported cognitive factors with objective cognitive factors were not explored further. The common co-existence of CVDRFs in old age, however, reduces the likelihood of the influence of individual CVDRFs on cognitive deficits. Third, this study included a relatively young old age group, while the risks of both CVDRFs and cognitive decline substantially increased in the old-old age group. However, because we included a relatively young age group, we were able to study a group that might be considered relatively free of overt dementia.
Middle-age and older adults with multiple CVDRFs may be at risk of impaired inflammatory circulation; further, older adults with multiple CVDRFs may also be at risk of cognitive decline. However, they may not engage in frequent physical and cognitive activities that may be protective against the effect of CVDRFs on cognitive function and inflammatory process. Given the high prevalence of CVDRFs in middle-age and older adults and the high likelihood of cognitive decline in older adults with CVDRFs, our findings help define areas for intervention in these individuals from midlife and lay the groundwork for future prospective studies.