Physical Fitness Tied to a Nearly 90% Reduction in Dementia Risk

Damian McNamara

March 16, 2018

A high level of cardiovascular physical fitness in middle-aged women is associated with close to a 90% reduction in dementia risk in later life, results of a longitudinal study show.

Investigators followed a cohort of women for up to 44 years and found that compared with women who were moderately fit in midlife, those with high fitness levels had an 88% lower risk of developing dementia.

In addition, when the highly fit women did develop dementia, they developed the disease an average of 11 years later than women who were moderately fit, or at age 90 instead of age 79.

"I was surprised that the findings were so strong," study author Ingmar Skoog, MD, from the University of Gothenburg in Sweden, told Medscape Medical News.

"These findings are exciting because it's possible that improving people's cardiovascular fitness in middle age could delay or even prevent them from developing dementia," lead investigator, Helena Hörder, PhD, said in a statement.

The study was published online March 14 in Neurology.

Delayed Onset

Systematic reviews and meta-analyses of observational studies suggest a consistent link between physical activity and preserved cognitive function and decreased dementia risk. However, the investigators note these studies are limited by self-reported physical activity with no objective assessment of physical fitness.  

"Thus, it remains unclear whether the association between physical activity and dementia is mediated by social and cognitive stimulation rather than by level of physical fitness," they write.

Furthermore, most studies are conducted in people over age 60 at baseline and have a mean follow-up of 3 to 7 years.

Previous research includes a study that reported high midlife fitness on a maximal treadmill test was associated with a lower risk for dementia over a mean follow-up of 24 years (Ann Intern Med. 2013;158:162-168).

In another study among 18-year-old men in Sweden, low cardiovascular fitness on a bicycle ergometer test was associated with onset of dementia before age 60 years (Brain. 2014;137:1514-1523).

"This is interesting because the etiology of early-onset dementia is supposed to have strong genetic components," the researchers note. They also cited a population-based study in Finland showing that poor self-rated fitness in middle to late life was linked to increased risk for dementia over 25 years (J Intern Med. 2014;276:296-307).

To investigate whether greater cardiovascular fitness in midlife is associated with decreased dementia risk, the investigators measured maximal cardiovascular fitness of 191 participants (average age of 50 years) in a subsample of the Prospective Study of Women study, which began in 1968.

For measurement of peak cardiovascular capacity, the women performed physician-supervised stepwise-increased ergometer cycling testing to the point of exhaustion.

The average peak workload was measured at 103 W. A total of 40 women met criteria for a high fitness levels, or 120 W or higher.

A total of 92 women met criteria for medium fitness category, and 59 women were in the low fitness category, which was defined as a peak workload of 80 W or less, or who needed to stop because of high blood pressure, chest pain, or other cardiovascular problems.

Over the next 44 years, the women were tested for dementia six times by using Diagnostic and Statistical Manual of Mental Disorders, Third Edition, criteria, which relied on neuropsychiatric examinations, informant interviews, hospital records, and registry data up to 2012.

Results showed that 44 (23%) of the 191 women developed dementia during 5544 person-years of follow-up. Mean time to onset of dementia from initial examination was 29 years, and the mean age at time of onset was 81 years.

The mean time to dementia onset was 5 years longer for those with a high vs a medium peak workload. When the highly fit women did develop dementia, they did so an average of 11 years later than women who were moderately fit: age 90 vs age 79.

Compared with medium peak workload, the adjusted hazard ratio (HR) for all-cause dementia was 0.12 (95% confidence interval [CI], 0.03 - 0.54) among those with high fitness and 1.41 (95% CI, 0.72 - 2.79) among those with low fitness.

When researchers adjusted for body weight, they found that compared with medium peak fitness, the adjusted HRs for all-cause dementia were 0.35 (95% CI, 0.13 - 0.97) for those with high fitness and 1.37 (95% CI, 0.62 - 3.02) for low-fitness participants.

Table. Risk for Dementia According to Fitness Level

Fitness Level on Test Dementia Risk (%)
High 5
Medium 25
Low 32
Could not finish test 45


"It is noteworthy that the dementia incidence among those who interrupted the test at submaximal workload was 45%," the researchers note. "This indicates that adverse cardiovascular processes might be going on in midlife that seem to increase the risk for dementia."

Because of the study's observational design, the researchers point out that the reported association between cardiovascular fitness and subsequent dementia risk cannot be interpreted as cause and effect.

However, they note the results do suggest that "improved cardiovascular fitness might be a modifiable factor to delay or prevent dementia."

Heart, Brain Connection

In an accompanying editorial, Nicole L. Spartano, PhD, Boston University School of Medicine in Massachusetts, and Tiia Ngandu, MD, PhD, Karolinska Institutet Center for Alzheimer Research, Stockholm, Sweden, note that the findings raise important questions that need to be addressed in future studies.

"We must determine whether these associations are due solely to the influence of heart health on brain health or whether exercise influences the brain independently of cardiovascular effects.

"There is a need for longer-term intervention studies to understand whether exercise training, possibly even at modest does and intensity can improve dementia risk," they write.

Commenting on the findings for Medscape Medical News, Rong Zhang, PhD, from the UT Southwestern O'Donnell Brain Institute in Dallas, Texas, who was not involved in the study, said although a limitation of the study is its small sample size, it does provide "additional evidence that what's good for the heart is good for the brain. Engaging in exercise training early in midlife may protect brain from dementia in late life." 

"This finding is consistent with a study we recently published [J Alzheimers Dis.  2018;61:729-739] showing that lower fitness levels were associated with poor white matter fiber integrity, which in turn correlated with lower brain function," he said. "This suggests that lower fitness levels may lead to faster deterioration of vital brain nerve fibers with aging."

Zhang and his team are conducting a 5-year multicenter randomized controlled trial to determine whether exercise training and reduction in cardiovascular risk factors indeed will prevent or slow cognitive decline in middle- to old-aged adults (60 to 85 years) who have high risks of dementia.

The study was supported by the Swedish Forte Center on Aging and Health, the Swedish Research Council for Health, Working Life and Welfare, Alzheimer's Association Stephanie B. Overstreet Scholars, Alzheimer's Association Zenith Award, Sahlgrenska University Hospital, Bank of Sweden Tercentary Foundation, Swedish Brain Power, and several Swedish foundations. Skoog and Zhang have disclosed no relevant financial relationships.

Neurology . Published online March 14, 2018. Full text, Editorial

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