Association between mid‐ to late life physical fitness and dementia: evidence from the <scp>CAIDE</scp> study

Kulmala, Jenni; Solomon, Alina; Kåreholt, Ingemar; Ngandu, Tiia; Rantanen, Taina; Laatikainen, Tiina; Tuomilehto, Jaakko; Kivipelto, Miia

doi:10.1111/joim.12202

Cited by 37 publications

(35 citation statements)

References 42 publications

(48 reference statements)

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“…There is growing evidence from retrospective studies that exercise at younger ages can have protective effects on brain aging (Rovio et al, 2005; Kulmala et al, 2014; Tolppanen et al, 2014). In older adults, self-reported early adult and mid-life exercise is correlated with enhanced global cognition (Gill et al, 2015), memory (Richards et al, 2003), and executive function (Sabia et al, 2009).…”

Section: Resultsmentioning

confidence: 99%

Differences in Resting State Functional Connectivity between Young Adult Endurance Athletes and Healthy Controls

Raichlen

Bharadwaj

Fitzhugh

et al. 2016

Front. Hum. Neurosci.

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Expertise and training in fine motor skills has been associated with changes in brain structure, function, and connectivity. Fewer studies have explored the neural effects of athletic activities that do not seem to rely on precise fine motor control (e.g., distance running). Here, we compared resting-state functional connectivity in a sample of adult male collegiate distance runners (n = 11; age = 21.3 ± 2.5) and a group of healthy age-matched non-athlete male controls (n = 11; age = 20.6 ± 1.1), to test the hypothesis that expertise in sustained aerobic motor behaviors affects resting state functional connectivity in young adults. Although generally considered an automated repetitive task, locomotion, especially at an elite level, likely engages multiple cognitive actions including planning, inhibition, monitoring, attentional switching and multi-tasking, and motor control. Here, we examined connectivity in three resting-state networks that link such executive functions with motor control: the default mode network (DMN), the frontoparietal network (FPN), and the motor network (MN). We found two key patterns of significant between-group differences in connectivity that are consistent with the hypothesized cognitive demands of elite endurance running. First, enhanced connectivity between the FPN and brain regions often associated with aspects of working memory and other executive functions (frontal cortex), suggest endurance running may stress executive cognitive functions in ways that increase connectivity in associated networks. Second, we found significant anti-correlations between the DMN and regions associated with motor control (paracentral area), somatosensory functions (post-central region), and visual association abilities (occipital cortex). DMN deactivation with task-positive regions has been shown to be generally beneficial for cognitive performance, suggesting anti-correlated regions observed here are engaged during running. For all between-group differences, there were significant associations between connectivity, self-reported physical activity, and estimates of maximum aerobic capacity, suggesting a dose-response relationship between engagement in endurance running and connectivity strength. Together these results suggest that differences in experience with endurance running are associated with differences in functional brain connectivity. High intensity aerobic activity that requires sustained, repetitive locomotor and navigational skills may stress cognitive domains in ways that lead to altered brain connectivity, which in turn has implications for understanding the beneficial role of exercise for brain and cognitive function over the lifespan.

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Section: Resultsmentioning

confidence: 99%

Differences in Resting State Functional Connectivity between Young Adult Endurance Athletes and Healthy Controls

Raichlen

Bharadwaj

Fitzhugh

et al. 2016

Front. Hum. Neurosci.

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“…, ; Kulmala et al. ). Moreover, as little as 2.5 h of “non‐vigorous” activity per week is associated with 19% reduced risk of mortality (Janssen ).…”

Section: Introductionmentioning

confidence: 98%

Molecular and metabolomic effects of voluntary running wheel activity on skeletal muscle in late middle-aged rats

et al. 2015

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We examined the molecular and metabolomic effects of voluntary running wheel activity in late middle-aged male Sprague Dawley rats (16–17 months). Rats were assigned either continuous voluntary running wheel access for 8 weeks (RW+) or cage-matched without running wheel access (RW−). The 9 RW+ rats averaged 83 m/day (range: 8–163 m), yet exhibited both 84% reduced individual body weight gain (4.3 g vs. 26.3 g, P = 0.02) and 6.5% reduced individual average daily food intake (20.6 g vs. 22.0 g, P = 0.09) over the 8 weeks. Hindlimb muscles were harvested following an overnight fast. Muscle weights and myofiber cross-sectional area showed no difference between groups. Western blots of gastrocnemius muscle lysates with a panel of antibodies suggest that running wheel activity improved oxidative metabolism (53% increase in PGC1α, P = 0.03), increased autophagy (36% increase in LC3B-II/-I ratio, P = 0.03), and modulated growth signaling (26% increase in myostatin, P = 0.04). RW+ muscle also showed 43% increased glycogen phosphorylase expression (P = 0.04) and 45% increased glycogen content (P = 0.04). Metabolomic profiling of plantaris and soleus muscles indicated that even low-volume voluntary running wheel activity is associated with decreases in many long-chain fatty acids (e.g., palmitoleate, myristoleate, and eicosatrienoate) relative to RW− rats. Relative increases in acylcarnitines and acyl glycerophospholipids were also observed in RW+ plantaris. These data establish that even modest amounts of physical activity during late middle-age promote extensive metabolic remodeling of skeletal muscle.

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“…Various longitudinal cohort studies have suggested that physical activity in middle age protects against cognitive decline and dementia in old age [2,3] and preserves the ability to perform activities of daily living (ADL) among older healthy subjects [4]. Moreover, a dose-response has been suggested in healthy subjects showing that higher levels of physical activity are associated with better cognitive performance [5].…”

Section: Introductionmentioning

confidence: 99%

Moderate-to-High Intensity Physical Exercise in Patients with Alzheimer’s Disease: A Randomized Controlled Trial

Hoffmann

Sobol

Frederiksen

et al. 2016

JAD

246

260

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Abstract.Background: Studies of physical exercise in patients with Alzheimer's disease (AD) are few and results have been inconsistent. Objective: To assess the effects of a moderate-to-high intensity aerobic exercise program in patients with mild AD. Methods: In a randomized controlled trial, we recruited 200 patients with mild AD to a supervised exercise group (60-min sessions three times a week for 16 weeks) or to a control group. Primary outcome was changed from baseline in cognitive performance estimated by Symbol Digit Modalities Test (SDMT) in the intention-to-treat (ITT) group. Secondary outcomes included changes in quality of life, ability to perform activities of daily living, and in neuropsychiatric and depressive symptoms. Results: The ITT analysis showed no significant differences between intervention and control groups in change from baseline of SDMT, other cognitive tests, quality of life, or activities of daily living. The change from baseline in Neuropsychiatric Inventory differed significantly in favor of the intervention group (mean: -3.5, 95% confidence interval (CI) -5.8 to -1.3, p = 0.002). In subjects who adhered to the protocol, we found a significant effect on change from baseline in SDMT as compared with the control group (mean: 4.2, 95% CI 0.5 to 7.9, p = 0.028), suggesting a dose-response relationship between exercise and cognition. * Correspondence to: Professor, DMSc, MD, Steen G. K. Hoffmann et al. / Aerobic exercise in Alzheimer's diseaseConclusions: This is the first randomized controlled trial with supervised moderate-to-high intensity exercise in patients with mild AD. Exercise reduced neuropsychiatric symptoms in patients with mild AD, with possible additional benefits of preserved cognition in a subgroup of patients exercising with high attendance and intensity.

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Association between mid‐ to late life physical fitness and dementia: evidence from the CAIDE study

Abstract: Abstract. Kulmala J, Solomon A, K areholt I, Ngandu T, Rantanen T, Laatikainen T, Soininen H, Tuomilehto J, Kivipelto M (University of Jyv€ askyl€ a, Jyv€ askyl€ a;

Cited by 37 publications

References 42 publications

Differences in Resting State Functional Connectivity between Young Adult Endurance Athletes and Healthy Controls

Differences in Resting State Functional Connectivity between Young Adult Endurance Athletes and Healthy Controls

Molecular and metabolomic effects of voluntary running wheel activity on skeletal muscle in late middle-aged rats

Moderate-to-High Intensity Physical Exercise in Patients with Alzheimer’s Disease: A Randomized Controlled Trial

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