Regular paperCardiorespiratory fitness is associated with atrophy in Alzheimer's and aging over 2 years
Introduction
The benefits of physical activity for brain health are receiving increased attention (Kramer et al., 2005). In animals, exercise increases neuronal survival and resistance to brain insults (Carro et al., 2001, Stummer et al., 1994), promotes vascularization (Black et al., 1990, Isaacs et al., 1992), stimulates neurogenesis (van Praag et al., 1999), and mobilizes gene expression profiles predicted to benefit brain plasticity (Cotman and Berchtold, 2002). Additionally, running increases brain-derived neurotrophic factor levels in the hippocampus and dentate gyrus and influences long term potentiation (Neeper et al., 1995, van Praag et al., 1999). In humans, several randomized controlled trials have examined the cognitive effects of increasing activity in healthy, older adults and found a beneficial impact on cognitive performance (Dustman et al., 1984, Hassmen and Koivula, 1997, Hill et al., 1993, Kramer et al., 1999, Williams and Lord, 1997). Several longitudinal studies report a positive relationship between self-reported physical activity and cognitive function (Laurin et al., 2001, Pignatti et al., 2002, Weuve et al., 2004, Yaffe et al., 2001).
There is an increasing interest in assessing the therapeutic role of exercise and physical activity in individuals with Alzheimer's disease (AD). Recently, greater physical activity and exercise in adults without dementia was associated with lower levels of AD biomarkers such as Pittsburgh Compound B binding (Liang et al., 2010). Additionally, a recent report showed that increased physical activity in those with dementia was associated with lower mortality risk (Scarmeas et al., 2010). Epidemiological studies suggest regular physical activity may prevent cognitive decline and dementia, and in midlife is associated with a reduced risk of developing mild cognitive impairment and AD (Friedland et al., 2001, Geda et al., 2010). One such study found that dancing, an aerobic activity, was associated with lower risk for developing dementia (Verghese et al., 2003). Others have demonstrated in randomized controlled trials that aerobic fitness training improves cognitive performance in mild cognitive impairment (Baker et al., 2010, Scherder et al., 2005).
Limitations to previous studies include a reliance on reported activity levels and a lack of standard objective measures of physical activity. Physical activity and exercise influence cardiorespiratory (CR) fitness, an objective measure of an individual's peak level of oxygen consumption during a graded exercise test. CR fitness is associated with lower rates of cognitive decline in nondemented older adults (Colcombe and Kramer, 2003) but there is a paucity of data on individuals with AD regarding the relationship of CR fitness with dementia progression and structural brain change (Rolland et al., 2008). We previously reported cross-sectional data suggesting that CR fitness relates to whole brain (Burns et al., 2008) and medial temporal lobe volume (Honea et al., 2009) in individuals with AD. Additionally, we reported that CR fitness levels were lower in those with AD compared with nondemented peers (Burns et al., 2008). We now extend these findings by reporting the results of a 2-year observational study of individuals with early-stage AD and nondemented controls. We hypothesized that individuals with AD would have greater CR fitness decline compared with nondemented control subjects and that CR fitness would be associated with progression of dementia severity and brain atrophy.
Section snippets
Sample
Participants were enrolled in the University of Kansas Brain Aging Project for baseline and follow-up evaluations (mean follow-up time 2.1 [SD 0.2] years). Data used in these analyses were from nondemented individuals (Clinical Dementia Rating [CDR] 0, n = 53) and individuals with early-stage AD (CDR 0.5 and 1, n = 37) aged 60 years and older. Study exclusions at baseline included neurologic disease other than AD with the potential to impair cognition (e.g., Parkinson disease), current or past
Demographics and cognition
AD and nondemented groups were not significantly different in age, gender, or race (p > 0.2, Table 1). All nondemented participants identified as white, with 1 reporting Hispanic ethnicity. Thirty-five participants with AD identified as white, 1 as African-American, and 1 as Native American. Individuals with AD had approximately 1 year less of formal education (p = 0.04). At baseline evaluation 34 participants with AD had Global CDR of 0.5 and 3 had a Global CDR of 1. At follow-up, 23
Discussion
Our data show that higher baseline CR fitness in individuals with AD was associated with attenuated progression of dementia severity, independent of age, gender, and baseline dementia severity. Additionally, decline in CR fitness over 2 years was most notably associated with greater rates of medial temporal atrophy. In nondemented older adults, lower baseline levels of CR fitness were marginally associated with cognitive decline (p = 0.06) and atrophy in temporal and posterior regions, whereas
Disclosure statement
The authors have no actual or potential conflicts of interest to disclose.
Informed consent was obtained from all participants or their legal representative as appropriate before enrollment into the study.
Acknowledgements
This study was supported by grant R03AG026374-01 from the National Institutes of Aging, grant K23NS058252 from the National Institute on Neurological Disorders and Stroke, and generous support from the University of Kansas Endowment Association, William and Carolie Hougland, and the Fraternal Order of Eagles. The University of Kansas General Clinical Research Center (M01RR023940) provided essential space, expertise, and nursing support. The Hoglund Brain Imaging Center is supported by grant C76
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