Individuals with the highest levels of cardiorespiratory fitness during middle age were significantly less likely to develop dementia in their senior years, a long-term prospective study suggested.
Among nearly 20,000 participants in the Cooper Center Longitudinal Study, those in the highest quintile of cardiorespiratory fitness at roughly age 50 were 36% less likely than those in the lowest quintile (adjusted hazard ratio 0.64, 95% CI 0.54 to 0.77) to be diagnosed with dementia after age 65, according to Laura F. DeFina, MD, of the Cooper Institute in Dallas, and colleagues.
The risk of all-cause dementia did not appear to be affected by whether participants had a stroke during follow-up, nor did educational attainment appear to make a difference, the researchers reported online in Annals of Internal Medicine.
Although the observational study could not prove that cardiorespiratory fitness actually prevents onset of dementia later on, DeFina and colleagues indicated that such a causal connection is plausible.
For example, greater fitness would reduce the incidence of other known risk factors for dementia such as diabetes and hypertension, the researchers noted. Fitness has also been linked to greater brain volume, and some evidence points to connections between physical activity and neural plasticity, neurotrophic factors, and beta-amyloid protein deposits.
"Future studies should address the dose-response relationship with physical activity needed to modify fitness levels to inform public health recommendations for dementia prevention," DeFina and colleagues wrote.
"In addition, studies on the effect of midlife physical activity and fitness levels on brain structure and function may further elucidate the mechanism(s) of the protective effect of fitness levels."
In an accompanying editorial, a prominent researcher in dementia agreed that a causal relationship was credible enough to warrant action by clinicians.
"Physical activity seems to be a reasonable prescription for dementia prevention," wrote Mary Sano, PhD, of Mount Sinai School of Medicine in New York City, given the weight of evidence to which the current study adds.
Another dementia expert, David Geldmacher, MD, of the University of Alabama at Birmingham, told MedPage Today that the potential benefit for dementia risk is worth bringing up with patients, even though recommendations of physical activity and fitness are familiar to everybody.
Compared with the benefit of exercise for cardiovascular health, "many physicians are not as clear that [the benefit] also translates to dementia risk," Geldmacher said.
"Many patients will [say] that, 'Well, it's not so bad if I die of a heart attack,' but they fear Alzheimer's disease very much. So knowing that fitness can reduce the Alzheimer risk may give them further motivation to follow through with an exercise and fitness plan."
The current study drew on data collected as part of the long-running Cooper Center study, begun more than 40 years ago under the leadership of Kenneth Cooper, MD, the famous advocate of aerobic exercise. It began with individuals who came to Cooper's wellness-oriented clinic, with later participation by people referred to it as part of employer-based programs.
DeFina and colleagues analyzed data on 19,458 participants, after excluding about 9,000 for whom later Medicare records were not available or with incomplete baseline data, those with a history of heart attack or stroke at baseline, those entering Medicare because of disability or a need for renal dialysis, and those with dementia or stroke prior to 2000 or at age 65 or younger (67 or younger for dementia).
All participants had a treadmill test when entering the study. Their mean age was 50. Fitness was calculated from time on the treadmill and the final speed and grade.
Participants' Medicare records were examined for diagnoses of dementia at ages 70, 75, 80, and 85. DeFina and colleagues calculated the risk for such a diagnosis according to quintiles of cardiorespiratory fitness, after adjusting for sex, age at baseline exam, year of exam, and other baseline factors including fasting glucose, cholesterol, body mass index, blood pressure, and smoking status.
Mean treadmill times for the five quintiles ranged from 8.1 maximal metabolic equivalents in the lowest to 13.3 in the highest.
Kaplan-Meier curves calculated in the study showed that, by age 92, about 52% of surviving participants in the two highest quintiles remained dementia-free, compared with 40% of those in the lowest quintile (P<0.001).
The risk did not appear to differ between participants with a stroke recorded prior to dementia diagnosis versus those without stroke (0.74 in both groups for the highest quintile relative to the lowest). This finding suggests "that the association between higher fitness level and risk for dementia is independent of intervening cerebrovascular disease," DeFina and colleagues wrote.
There was also no statistically significant relationship between dementia risk and educational level. But the authors cautioned that education data was available for only about 20% of the sample and, in those participants, the average attainment was relatively high (mean 15.7 years, SD 2.6).
Other limitations to the analysis included the reliance on Medicare data for dementia outcomes and the largely white, affluent, and healthy population represented in the Cooper Center study. DeFina and colleagues also pointed out that the baseline data did not cover all lifestyle factors that may correlate with fitness.
The study was funded by the University of Texas Southwestern Medical Center, the National Heart, Lung and Blood Institute, and the American Heart Association.
One co-author reported a relationship with Merck. Other study authors and Sano declared they had no relevant financial interests.
- Reviewed by Zalman S. Agus, MD Emeritus Professor, Perelman School of Medicine at the University of Pennsylvania and Dorothy Caputo, MA, BSN, RN, Nurse Planner
Annals of Internal MedicineSource Reference: DeFina L, et al "The association between midlife cardiorespiratory fitness levels and later-life dementia: A cohort study" Annals Intern Med 2013.
Annals of Internal MedicineSource Reference: Sano M "Never too fit for body and mind" Annals Intern Med 2013; 158: 213-214.