24-Month Exercise Fails to Improve Cognitive Function in 1635 Sedentary Older Adults

Multiple lines of evidence support the notion that exercise confers cognitive benefits.

Dr. Jeff Williamson et. al., at the Wake Forest School of Medicine, hypothesized that a 24-month physical activity program would result in improved cognitive function.

The authors also tested whether exercise would lower the risk of mild cognitive impairment (MCI) and/or dementia compared with a health education program. The study was conducted in 1635 sedentary adults aged 70-89 years.

Surprisingly, Dr. Williamson's LIFE study concluded that exercise failed to result in improvements in domain-specific or global cognitive function.

At 24 months, the authors reported that:

  • DSC task and HVLT-R scores were not different between groups (mean 46.26 for the physical activity group and 46.28 for the control)
  • Mean HVLT-R delayed recall score was 7.22 for the physical activity cohort vs. 7.25 for the control group
  • Participants in the physical activity group who were 80 years or older (n = 307) and those with poorer baseline physical performance (n = 328) had better changes in executive function composite scores compared with the health education group (P = .01 for interaction for both comparisons).
  • However, MCI or dementia was diagnosed in 98 participants (13.2%) in the physical activity group and 91 participants (12.1%) in the health education group

When interventions fail to benefit patients with neurodegenerative disease, researches have been tempted to explain away the data by suggesting that the patients enrolled were already past the point of no return. Or in other words, the intervention would have “worked” in the prodromal phase prior to the onset of frank dementia.

To control for this possibility, Williamson et. al. excluded participants from the study with a current diagnosis of dementia or significant cognitive impairment as determined by the Mini-Mental State Examination (3MSE).

Physical activity was measured objectively using an Actigraph accelerometer to measure the total minutes of at least moderate activity.

The use of the accelerometer precludes any biases introduced by self-reporting. Another merit of the actigraphy data is that it could be used to tease out a dose-dependent effect of exercise on cognitive function.

The authors remarked that despite epidemiological data supporting the pro-cognitive effects of exercise, the results of the LIFE study that exercise failed to improve cognitive function in older adults are consistent with some other recently published randomized trials.

Why Exercise Failed To Benefit

Williamson et. al. consider the following explanations for the lack of cognitive benefit of physical activity:

  • The assigned level of physical activity may have been insufficient to produce changes in the cognitive measures despite its effect on physical function”
  • Improvements in cognitive function in some shorter clinical trials, including the LIFE pilot study, may dissipate by 24 months and thus may have been missed, especially if adherence to the physical activity intervention wanes over time
  • The study population was not specifically selected for cognitive vulnerability, although poor physical function, especially gait speed, has been shown to be a risk for cognitive decline
  • the participants were well educated (>two-thirds went to college), and high cognitive reserve may have protected against cognitive decline over 2 years
  • The health education intervention may have benefited cognition.The health education group attended interactive seminars providing both cognitive and social stimulation. Both cognitive and social stimulation have been shown to preserve cognition in older adults.

The most compelling explanation for the results of the LIFE study may be that vigorous exercise is required to observe clinically meaningful benefits on cognitive measures, and older adults are often frail which limits exercise tolerance. This hypothesis could be tested by enrolling participants who are not seniors but have been identified as at-risk for the later development of dementia.


Kaycee M. Sink, Mark A. Espeland, Cynthia M. Castro, Timothy Church, Ron Cohen, John A. Dodson, Jack Guralnik, Hugh C. Hendrie, Janine Jennings, Jeffery Katula, Oscar L. Lopez, Mary M. McDermott, Marco Pahor, Kieran F. Reid, Julia Rushing, Joe Verghese, Stephen Rapp, Jeff D. Williamson. Effect of a 24-Month Physical Activity Intervention vs Health Education on Cognitive Outcomes in Sedentary Older Adults. JAMA, 2015; 314 (8): 781 DOI: 10.1001/jama.2015.9617

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