Mechanisms linking physical activity and the brain may be multi-dimensional

Mid- and late-life moderate-to-vigorous physical activity was associated with measures of cerebrovascular health, a prospective observational study found.

“Greater physical activity levels in both mid- and late-life were associated with less late-life brain damage, including fewer cerebrovascular lesions and better white matter integrity,” wrote Priya Palta, PhD, of Columbia University in New York City, and co-authors in Neurology. “The association between midlife physical activity levels and later life brain imaging features makes a much stronger case for causality than does the same relationship when measured only in late life.”

The analysis included 1,604 participants from the Atherosclerosis Risk in Communities (ARIC) study. The team assessed leisure-time moderate-to-vigorous intensity physical activity in mid- and late-life and related it to MRI results for cerebrovascular lesions, grey matter volume, white matter hyperintensities, and white matter integrity. Higher white matter integrity is implied by higher mean fractional anisotropy (FA) and lower mean diffusivity (MD).

Midlife moderate-to-vigorous physical activity assessments revealed none in 34% of participants, low in 11%, middle in 16%, and high in 39%.

High midlife moderate-to-vigorous physical activity, compared with no midlife moderate-to-vigorous activity, was associated with:

  • Better white matter integrity in late-life: mean FA difference 0.13 per standard deviation, 95% CI 0.004-0.26; mean MD difference −0.11 per SD, 95% CI −0.21 to −0.004.
  • Lower odds of lacunar infarcts (but not cortical infarcts or subcortical microhemorrhage) in late life: OR 0.68, 95% CI 0.46-0.99.

High moderate-to-vigorous physical activity in late life was associated with fewer cerebrovascular lesions, larger grey matter volumes, less white matter hyperintensities, and greater white matter integrity.

“The associations of greater levels of midlife physical activity with fewer lacunar (but not cortical) infarcts and greater white matter microstructural integrity suggest cerebrovascular mechanisms are primarily at play,” the researchers wrote. “We were unable to demonstrate consistent associations between midlife physical activity and brain volumetric losses, making it unlikely (though not definitively so) that physical activity directly affected upstream Alzheimer processes (amyloidosis and tauopathy).”

In an accompanying editorial, Nicole Spartano, PhD, of Boston University and Leonardo Pantoni, MD, PhD, of the University of Milan in Italy wrote, “As echoed in the current study by Palta, et al, the most consistent evidence for the protective effect of physical activity against dementia risk has been reported to be leisure time physical activity, and it is unclear whether there is benefit to other types of physical activity that may be less ’enriching.’”

It’s imperative that intervention studies are designed to target populations in whom a strong benefit is to be expected, they added. “It is possible that future work will uncover the requirement that physical activity interventions to reduce dementia risk actually have an enriching element, such as in leisure-time activities, rather than be strictly rote, mechanical movement,” they wrote. “We posit that it may not just be those with high vascular risk, but also those with lower levels of environmental enrichment who might benefit from leisure-time physical activity interventions.”

In a 2005 study of 1,449 patients, midlife leisure physical activity levels were linked to decreased risk of dementia in later life. In a study of 10,705 ARIC patients published by the authors in 2018, persistent moderate or high-level midlife leisure time physical activity was associated with reduced cognitive decline and dementia risk.

However, another 2018 study found no difference between control and exercise interventions on 12 month Alzheimer’s disease assessment scale-cognitive subscale scores, and an analysis of FINGER trial data found an intervention on diet, exercise, cognitive training, and vascular risk led to no difference in MRI measures of cortical and white matter lesion volume or cortical thickness, compared with controls.

One reason for inconsistent results in these studies “might be that intervention studies need to consider the type, dose, intensity, and timing of the prescribed physical activity,” the editorialists noted. “Another is that they need to target a high-risk population in order to develop a successful intervention for the prevention of cognitive decline.”

In their analysis, Palta and colleagues studied ARIC participants who had a midlife evaluation in 1987-1989 and a late life visit in 2011-2013. Only those with late life MRI were included.

Physical activity was assessed with the modified Baecke physical activity questionnaire, which collects self-reported activity in sport, work, and leisure activity. Weekly minutes at metabolic equivalents of task (METs) of 3 or more defined moderate to vigorous leisure activity, which were grouped as none; low (1-74 minutes/week); middle (75-149 minutes/week) and high (150 minutes per week or more).

Average age at the midlife visit was 51-52 across activity level groups. Females were 67.7%, 61.8%, 66.4%, and 55.6% of groups with no, low, middle, and high moderate-to-vigorous physical activity, respectively.

Sensitivity analysis may point to multiple mechanisms in this study, Spartano and Pantoni noted. “Adjusted for vascular risk factors (hypertension, diabetes mellitus, body mass index, and stroke), the relation of midlife physical activity to lacunar infarcts was attenuated,” they wrote.

This “suggests that the association of physical activity with vascular risk factors may be partially responsible for any potential effect on cerebrovascular injury. In contrast, adjusting for vascular risk factors did not have a major attenuating effect on the association with white matter microstructure,” they pointed out. “Therefore, evidence from this study supports a hypothesis that the mechanisms linking physical activity and the brain are likely multi-dimensional, including mechanisms other than simply improving cerebrovascular health,” they added.

Limitations include self-reported measures in this study. In addition, MRI was not systematically obtained.

  1. Mid- and late-life leisure time physical activity was associated with measures of cerebrovascular health in a prospective observational study.

  2. Better white matter integrity and fewer lacunar infarcts were seen for both mid- and late-life high physical activity, compared with no activity levels.

Paul Smyth, MD, Contributing Writer, BreakingMED™

The Atherosclerosis Risk in Communities Study is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute contracts. This study also was supported by the National Institute on Aging.

Palta reported no disclosures.

Spartano has received research support from the National Institutes of Health, the Alzheimer’s Association, and the American Heart Association. Pantoni serves on the editorial board for the journals Stroke, Cerebrovascular Diseases, European Stroke Journal, Acta Neurologica Scandinavica, Neurological Sciences.

Cat ID: 33

Topic ID: 82,33,282,404,485,494,730,33,361,255,925