Cardiorespiratory Fitness and Brain Atrophy in Early Alzheimer Disease

Department of Neurology, Hoglund Brain Imaging Center, University of Kansas School of Medicine, 3599 Rainbow Blvd, MSN 2012, Kansas City, KS 66160, USA.
Neurology (Impact Factor: 8.29). 08/2008; 71(3):210-6. DOI: 10.1212/01.wnl.0000317094.86209.cb
Source: PubMed


To examine the correlation of cardiorespiratory fitness with brain atrophy and cognition in early-stage Alzheimer disease (AD).
In normal aging physical fitness appears to mitigate functional and structural age-related brain changes. Whether this is observed in AD is not known.
Subjects without dementia (n = 64) and subjects with early-stage AD (n = 57) had MRI and standard clinical and psychometric evaluations. Peak oxygen consumption (VO(2)(peak)), the standard measure of cardiorespiratory fitness, was assessed during a graded treadmill test. Normalized whole brain volume, a brain atrophy estimate, was determined by MRI. Pearson correlation and linear regression were used to assess fitness in relation to brain volume and cognitive performance.
Cardiorespiratory fitness (VO(2)(peak)) was modestly reduced in subjects with AD (34.7 [5.0] mL/kg/min) vs subjects without dementia (38.1 [6.3] mL/kg/min, p = 0.002). In early AD, VO(2)(peak) was associated with whole brain volume (beta = 0.35, p = 0.02) and white matter volume (beta = 0.35, p = 0.04) after controlling for age. Controlling for additional covariates of sex, dementia severity, physical activity, and physical frailty did not attenuate the relationships. VO(2)(peak) was associated with performance on delayed memory and digit symbol in early AD but not after controlling for age. In participants with no dementia, there was no relationship between fitness and brain atrophy. Fitness in participants with no dementia was associated with better global cognitive performance (r = 0.30, p = 0.02) and performance on Trailmaking A and B, Stroop, and delayed logical memory but not after controlling for age.
Increased cardiorespiratory fitness is associated with reduced brain atrophy in Alzheimer disease (AD). Cardiorespiratory fitness may moderate AD-related brain atrophy or a common underlying AD-related process may impact both brain atrophy and cardiorespiratory fitness.

Download full-text


Available from: Jeffrey M Burns, Apr 09, 2014
  • Source
    • "Previous work from our lab suggests that effects of aerobic fitness and serum BDNF interact to support episodic recognition memory (Whiteman et al., 2014) in a task we have shown to recruit the hippocampus and perirhinal/EC (Schon et al., 2004, 2005). Additionally , increased cardio-respiratory fitness is associated with greater volume of the parahippocampal gyrus in Alzheimer's disease patients (Honea et al., 2009), and aerobic exercise consistently appears as one of the most effective interventions to attenuate cognitive decline in geriatric populations (Barnes & Yaffe, 2011; Burns et al., 2008). In younger cohorts, exercise-induced gains in cardio-respiratory fitness have been linked to better relational memory in children (Chaddock et al., 2010), and better learning of a virtual Morris Water Maze task in adolescents (Herting and Nagel, 2012). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Converging evidence supports the hypothesis effects of aerobic exercise and environmental enrichment are beneficial for cognition, in particular for hippocampus-supported learning and memory. Recent work in humans suggests exercise training induces changes in hippocampal volume, but it is not known if aerobic exercise and fitness also impact the entorhinal cortex. In animal models, aerobic exercise increases expression of growth factors, including brain derived neurotrophic factor (BDNF). This exercise-enhanced expression of growth hormones may boost synaptic plasticity, and neuronal survival and differentiation, potentially supporting function and structure in brain areas including but not limited to the hippocampus. Here, using voxel based morphometry and a standard graded treadmill test to determine cardio-respiratory fitness (Bruce protocol; VO2 max), we examined if entorhinal and hippocampal volumes were associated with cardio-respiratory fitness in healthy young adults (N = 33). In addition, we examined if volumes were modulated by recognition memory performance and by serum BDNF, a putative marker of synaptic plasticity. Our results show a positive association between volume in right entorhinal cortex and cardio-respiratory fitness. In addition, average gray matter volume in the entorhinal cortex, bilaterally, was positively associated with memory performance. These data extend prior work on the cerebral effects of aerobic exercise and fitness to the entorhinal cortex in healthy young adults thus providing compelling evidence for a relationship between aerobic fitness and structure of the medial temporal lobe memory system.
    Full-text · Article · Nov 2015 · NeuroImage
  • Source
    • "All studies employed a cross-sectional MRI design. Although three studies did not report a significant association (Bugg and Head, 2011; Burns et al., 2008; Tseng et al., 2013b), higher levels of PA were associated with greater global WM volumes in the two largest studies (Benedict et al., 2013; Gow et al., 2012). A meta-analysis of all five studies showed an overall small mean effect size of 0.22 (95% confidence interval (CI) = 0.10 to 0.34, p b 0.001) (Fig. 1). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Higher levels of physical fitness or activity (PFA) have been shown to have beneficial effects on cognitive function and grey matter volumes in older adults. However, the relationship between PFA and the brain's white matter (WM) is not yet well established. Here, we aim to provide a comprehensive and systematic review of magnetic resonance imaging studies examining the effects of PFA on the WM of the ageing brain. Twenty-nine studies were included in the review: eleven examined WM volume, fourteen WM lesions, and nine WM microstructure. While many studies found that higher levels of PFA were associated with greater WM volumes, reduced volume or severity of WM lesions, or improved measures of WM microstructure, a number of negative findings have also been published. Meta-analyses of global measures of WM volume and WM lesion volume yielded significant, but small, effect sizes. Overall, we found evidence for cautious support of links between PFA and WM structure, and highlighted key areas for future research including the extent to which the relationship between PFA and WM structure is anatomically specific, the influence of possible confounding factors, and the relationship between PFA, WM and cognition.
    Preview · Article · Oct 2015 · NeuroImage
    • "The PASE has previously been validated against physiological measures of physical activity including accelerometer (Washburn & Ficker, 1999), mini-logger (Harada et al., 2001), peak oxygen uptake and balance score (). The questionnaire is validated for completion by carers of dementia patients (Burns et al., 2008Burns et al., , 2010Honea et al., 2009). Cognitive activities were measured using the Florida Cognitive Activities Scale (FCAS;Schinka et al., 2005). "
    [Show abstract] [Hide abstract]
    ABSTRACT: To determine whether habitual physical activity status specifically influences executive function change in Alzheimer's disease (AD) over 1 year. In this longitudinal cohort study, 45 participants with AD were recruited and provided follow-up data approximately 1 year later. Executive function measures (map search task, digit symbol substitution task, controlled oral word association task, verbal fluency task) and habitual physical activity measures (Physical Activity Scale for the Elderly (PASE) and handgrip strength) were taken at baseline and follow-up. Individual composites were subsequently created. Additional demographic, lifestyle, and neuropsychiatric measures were also taken. In a structural equation model (χ(2)(26) = 9.84, p = .998, comparative fit index = 1.00, root mean square error of approximation = .00), a significant association was found between habitual physical activity and executive function change (β = .27, p = .04). In a cross-lagged panel analysis, a significant path was found between the PASE score and executive change (β = .22, p = .01). As higher habitual physical activity levels were associated with reduced executive function change, the promotion of low-intensity habitual physical activities in individuals with a diagnosis of AD may be warranted. Further research is needed, however, to explore the impact of habitual physical activity on the trajectory of change across cognitive domains, and how this relates to the progression of the underlying pathology associated with this disease.
    No preview · Article · Sep 2015 · Aging Neuropsychology and Cognition
Show more