Hippocampal Response to a 24-Month Physical Activity Intervention in Sedentary Older Adults

Abstract

BACKGROUND Greater hippocampal volume is observed in healthy older adults after short-term structured exercise. Whether long-term exposure to real-world physical activity (PA) programs has similar effects for sedentary older adults with impaired mobility and comorbid conditions is not known. HYPOTHESIS A long-term moderate intensity regimen of PA is related to larger volume of the hippocampus in older adults at risk for mobility disability. We further explore whether these associations are modified by factors known to be related to dementia. METHODS Twenty-six sedentary adults at risk for mobility disability participated in a 24-month randomized intervention program of physical activity (PA, n=10, age: 74.9 years, 7 women) or health education (HE, n=16, age: 76.8 years, 14 women). Volumes of total hippocampus, dentate gyrus and cornu ammonis were measured at baseline and at 24-month follow-up using 7 Tesla MRI. Between-group volumetric differences at 24-months were adjusted for sessions attended and baseline volumes. The contribution of each dementia-related factor was tested separately for education, APOE, diabetes, cardiovascular diseases, white matter hyperintensities and brain atrophy. RESULTS Between-group differences were significant for left hippocampus, left cornu ammonis and right hippocampus. Adjustment for regional baseline volume attenuated the associations to statistically non-significant for right hippocampus and left conru ammonis; associations for left hippocampus were robust for all adjustments. Results were similar after adjustment for dementia-related factors. CONCLUSIONS In this group of sedentary older adults there was a hippocampal response to a long-term program of moderate-intensity PA. Future studies should examine whether hippocampal response could explain the beneficial effects of PA on cognition for vulnerable older adults.

Long-term changes in time spent walking and subsequent cognitive and structural brain changes in older adults

“…Specifically, we found that the average individual in our sample (aged 82.5 years at first MRI) demonstrated a 6.2% reduction in bilateral hippocampal volume over 3 years, whereas individuals who had maintained walking over the previous decade (based on a slope value 1 SD above the mean) demonstrated a 4.5% reduction in bilateral hippocampal volume. Although previous studies have shown that PA— including walking—might mitigate hippocampal atrophy, our study adds to the literature by showing that this mitigation effect is not restricted to individuals under the age of 80 (Bugg and Head, 2011; Erickson et al, 2011; Makizako et al, 2015; Rosano et al, 2016; Ten Brinke et al, 2014). Our results also add to the literature by suggesting that walking effects on hippocampal structure might primarily involve macro- rather than microstructural protection, as there was no evidence that regular walking had an impact on changes in hippocampal MD.…”

“…Intervention studies have shown that structured exercise training—e.g. in the form of walking programs—increases cortical and hippocampal gray matter volume (Colcombe et al, 2006; Erickson et al, 2011; Rosano et al, 2016; Ten Brinke et al, 2014) and that training-induced improvements in aerobic fitness correlate with improved microstructural integrity (Voss et al, 2013) among previously sedentary older adults. PA-related structural changes in the brain have also been associated with improved cognitive health, including memory performance (Erickson et al, 2011) and a lower risk of cognitive impairment (Erickson et al, 2010).…”

“…The primary analyses focused on the hippocampus, in light of evidence that it is especially sensitive to PA and physical fitness (Bugg and Head, 2011; Erickson et al, 2010; Erickson et al, 2009; Erickson et al, 2011; Rosano et al, 2016; Ten Brinke et al, 2014). We examined both hippocampal volume, which has been the focus of previous studies (Erickson et al, 2010; Erickson et al, 2011; Ten Brinke et al, 2014), and hippocampal MD, which has been examined infrequently (Tian et al, 2014a).…”

Sex-dependent effects of chronic exercise on cognitive flexibility in aging mice

“…People with a history of a physically active lifestyle are known to have some resilience to the effects of normal aging on cognition. In humans, the correlation between aerobic exercise and improved cognition is strong and exercise appears to be effective across the lifespan (Chaddock et al, 2010;Erickson et al, 2011;Herting & Nagel, 2012;Kleemeyer et al, 2016;Rosano et al, 2017;Stillman et al, 2018;Thomas et al, 2016). This has significant implications for older adults who face heightened risk of dementia (Erickson et al, 2011;Kleemeyer et al, 2016;Rosano et al, 2017).…”

“…The effects of exercise on cognition has been linked with hippocampal function (Rubin, Watson, Duff, & Cohen, 2014), which is important for spatial tasks and cognitive flexibility (Burghardt, Park, Hen, & Fenton, 2012). Although many studies highlight changes in the hippocampus volume and connectivity as the neural correlate for exercise effects in humans (Chaddock et al, 2010;Erickson et al, 2011;Herting & Nagel, 2012;Kleemeyer et al, 2016;Rosano et al, 2017), the molecular correlates are poorly understood. Rodent models have been useful in this regard and have provided additional insights.…”