In this large prospective study of women with preexisting CVD or vascular risk factors at higher risk of cognitive decline, greater physical activity was associated with substantially slower cognitive decline. Being in the two highest quintiles of physical activity was cognitively equivalent to being 5 to 7 years younger in age. Importantly, the association with total physical activity was not restricted to women engaged in vigorous exercise; higher levels of walking were significantly related to less cognitive decline.
Strong evidence supports the hypothesis that physical activity, including walking, may prevent cognitive decline in generally healthy older adults4–12
. However, studies of those at increased risk of cognitive impairment have been scarce. Some small clinical trials in participants with general cognitive impairments or complaints9, 11
or with severe congestive heart failure26
reported improvement or preservation of cognition in the physically active groups, but overall, the definitions of “high-risk” have been heterogeneous (e.g., general cognitive complaints rather than specific causes of cognitive complaints), yielding some inconsistent and inconclusive findings5, 7, 27, 28
. Thus, our findings provide important population-based long-term data that should be confirmed.
In our study, associations with change in category fluency were less consistent than those for memory and general cognition; this was also observed in a cohort of healthy women6
. Category fluency partially measures executive function, which is known to be affected by vascular disease24, 25
. One could speculate that the indirect vasculoprotective effects are weaker than the direct neuroprotective effects in preserving cognition, and thus, the domain most affected by vascular factors, such as executive function, may be less influenced than other domains. The potential differential associations with various cognitive domains are poorly understood. In addition, short-term intervention studies11, 29–31
and large observational cohorts4, 6, 10, 12
have revealed the possibility of differential effects with sex and different types of activities. These are all important issues that need evaluation in future studies.
Our study had several strengths. Four repeated cognitive assessments with high response rates were completed, maximizing information and minimizing biases due to loss to follow-up. Extensive health-related information was available, which allowed us to address confounding by baseline health status. Moreover, physical activity levels showed little variability according to baseline vascular disease, indicating low chance of confounding by severity of cardiovascular condition.
Some limitations should be considered. First, a telephone cognitive assessment might lack validity. However, both reliability and validity studies of our telephone instrument have provided convincing evidence of its utility to evaluate cognitive function in an epidemiologic study. Second, there may have been some misclassification of physical activity levels that were based on self-report. However, the physical activity questionnaire has been shown to reliably estimate physical activity levels19
, and misclassification would have led to biases towards the null. Most importantly, physical activity was assessed in late adulthood and may not reflect long-term exercise levels; it is also possible that inactivity/sedentary lifestyle may reflect pre-existing cognitive impairment rather than a risk factor for its future development32
. We addressed this possible bias in several ways; we imposed a mean 3.5-year lag between report of physical activity and the initial cognitive assessment, and we conducted several secondary analyses among women whose activity levels were stable over the two assessments before the cognitive assessment and among women at the top 90th
percentile at the first cognitive interview (i.e., after excluding those more likely to have reduced physical activity or have more errors in reporting activity due to cognitive impairment). We confirmed that overall, higher levels of physical activity were consistently and significantly associated with less cognitive decline. We were unable to adjust for other potential confounders (e.g., chronic kidney disease or other psychiatric disorders); thus, some residual confounding by other health or lifestyle factors is a possibility, and the results should be interpreted with appropriate caution. Finally, our study population, which was composed of female health professionals with vascular conditions, may not allow for direct generalizeability of the results to the general aging population. However, given that the majority of today’s elderly have prevalent cardiovascular disease (affecting over 70% of those aged ≥65 years in the US3
), our study provides some important evidence, which should be confirmed in other studies, of a modifiable risk factor for reducing cognitive impairment in this growing segment of the population.
Various biologic mechanisms may explain the positive relationship between physical activity and cognitive health33
. Exercise may directly preserve neuronal structures by stimulating brain-derived neurotrophic factor and neuronal growth34
, possibly providing reserve against cognitive decline and dementia35
. It may also have indirect effects by strengthening the underlying systems that support brain plasticity36, 37
and helping to sustain the brain’s vascular health38
by beneficially influencing cardiovascular risk factors, promoting endothelial function, improving glucose and insulin regulation, and ensuring adequate cerebral perfusion39
. Furthermore, physical activity reduces inflammation, which is higher in those with vascular disease40, 41
and impairs both systemic and brain-specific growth factor signaling. Physical activity may also improve psychological well-being42
, which, in turn, may protect against decline in cognitive functioning43
In summary, we found clear and strong associations between greater physical activity and reduced cognitive decline in this population of women with vascular disease or coronary risk factors. If confirmed in future studies, given the growing number of older persons with vascular disease or risk factors and their higher risk of cognitive impairment, physical activity recommendations could yield substantial public health benefits.