Ryan J. Dougherty

Neural consequences of post-exertion malaise in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Post exertion malaise is one of the most debilitating aspects of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, yet the neurobiological consequences are largely unexplored. The objective of the study was to determine the neural consequences of acute exercise using functional brain imaging. Fifteen female Myalgic Encephalomyelitis/Chronic Fatigue Syndrome patients and 15 healthy female controls completed 30min of submaximal exercise (70% of peak heart rate) on a cycle ergometer. Symptom assessments (e.g. fatigue, pain, mood) and brain imaging data were collected one week prior to and 24h following exercise. Functional brain images were obtained during performance of: 1) a fatiguing cognitive task - the Paced Auditory Serial Addition Task, 2) a non-fatiguing cognitive task - simple number recognition, and 3) a non-fatiguing motor task - finger tapping. Symptom and exercise data were analyzed using independent samples t-tests. Cognitive performance data were analyzed using mixed-model analysis of variance with repeated measures. Brain responses to fatiguing and non-fatiguing tasks were analyzed using linear mixed effects with cluster-wise (101-voxels) alpha of 0.05. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome patients reported large symptom changes compared to controls (effect size ≥0.8, p<0.05). Patients and controls had similar physiological responses to exercise (p>0.05). However, patients exercised at significantly lower Watts and reported greater exertion and leg muscle pain (p<0.05). For cognitive performance, a significant Group by Time interaction (p<0.05), demonstrated pre- to post-exercise improvements for controls and worsening for patients. Brain responses to finger tapping did not differ between groups at either time point. During number recognition, controls exhibited greater brain activity (p<0.05) in the posterior cingulate cortex, but only for the pre-exercise scan. For the Paced Serial Auditory Addition Task, there was a significant Group by Time interaction (p<0.05) with patients exhibiting increased brain activity from pre- to post-exercise compared to controls bilaterally for inferior and superior parietal and cingulate cortices. Changes in brain activity were significantly related to symptoms for patients (p<0.05). Acute exercise exacerbated symptoms, impaired cognitive performance and affected brain function in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome patients. These converging results, linking symptom exacerbation with brain function, provide objective evidence of the detrimental neurophysiological effects of post-exertion malaise.

Relationships between cardiorespiratory fitness, hippocampal volume, and episodic memory in a population at risk for Alzheimer's disease

Cardiorespiratory fitness (CRF) has been shown to be related to brain health in older adults. In individuals at risk for developing Alzheimers disease (AD), CRF may be a modifiable risk factor that could attenuate anticipated declines in brain volume and episodic memory. The objective of this study was to determine the association between CRF and both hippocampal volume and episodic memory in a cohort of cognitively healthy older adults with familial and/or genetic risk for Alzheimers disease (AD).

Meeting physical activity recommendations may be protective against temporal lobe atrophy in older adults at risk for Alzheimer's disease

Physical activity (PA) is associated with brain health in older adults. However, it is unknown whether the current physical activity recommendations (PAR) impart substantive benefit. The objective of this study was to compare temporal lobe volumes between older adults who met PAR and those who did not.

Moderate Physical Activity is Associated with Cerebral Glucose Metabolism in Adults at Risk for Alzheimer’s Disease

The objective of this study was to investigate the relationship between accelerometer-measured physical activity (PA) and glucose metabolism in asymptomatic late-middle-aged adults. Ninety-three cognitively healthy late-middle-aged adults from the Wisconsin Registry for Alzheimers Prevention participated in this cross-sectional study. They underwent 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) imaging and wore an accelerometer (ActiGraph GT3X+) to measure free-living PA. Accelerometer data yielded measures of light (LPA), moderate (MPA), and vigorous (VPA) intensity PA. FDG-PET images were scaled to the cerebellum and pons, and cerebral glucose metabolic rate was extracted from specific regions of interest (ROIs) known to be hypometabolic in AD, i.e., hippocampus, posterior cingulate, inferior temporal cortex, and angular gyrus. Regression analyses were utilized to examine the association between PA and glucose metabolism, while adjusting for potential confounds. There were associations between MPA and glucose metabolism in all ROIs examined. In contrast, LPA was not associated with glucose uptake in any ROI and VPA was only associated with hippocampal FDG uptake. Secondary analyses did not reveal associations between sedentary time and glucose metabolism in any of the ROIs. Exploratory voxel-wise analysis identified additional regions where MPA was significantly associated with glucose metabolism including the precuneus, supramarginal gyrus, amygdala, and middle frontal gyrus. These findings suggest that the intensity of PA is an important contributor to neuronal function in a late-middle-aged cohort, with MPA being the most salient. Prospective studies are necessary for fully elucidating the link between midlife engagement in PA and later life development of AD.

Cerebral white matter structure is disrupted in Gulf War Veterans with chronic musculoskeletal pain

Abstract Chronic musculoskeletal pain (CMP) affects ∼25% of the 700,000 Veterans deployed during the Persian Gulf War (1990-1991). The cause of their pain is unknown, and there are no efficacious treatments. A small body of literature suggests that brain abnormalities exist in Gulf War Veterans (GVs), yet relationships between brain abnormalities and disease symptoms remain largely unexplored. Our purpose was to compare white matter (WM) integrity between GVCMP and matched, healthy Veteran controls (GVCO) and investigate relationships between cerebral WM integrity and symptoms. Thirty GVCMP and 31 controls completed magnetic resonance imaging with diffusion tensor imaging. Tract-based spatial statistics estimated WM fractional anisotropy, mean diffusivity, radial diffusivity, and axial diffusivity over the whole brain (P < 0.05) and were corrected using threshold-free cluster enhancement. GVCMP had greater pain symptoms and mood disturbance and lower quality of life and physical function compared with GVCO (P < 0.05). GVCMP had lower WM integrity across several brain regions implicated in chronic pain (P < 0.05) including the middle and inferior frontal gyrus, corpus callosum, corona radiata, precentral gyrus, external capsule, and posterior thalamic radiation. For GVCMP, WM integrity was associated with pain and mood symptoms in widespread brain areas that were found to be different between groups (P < 0.05). Results indicate widespread WM microstructure disruption across brain regions implicated in pain processing and modulation in chronic pain. The observed relationships between WM microstructure and symptoms encourage the testing of treatments designed to improve the brain health of affected Veterans.

An Objective Method to Accurately Measure Cardiorespiratory Fitness in Older Adults Who Cannot Satisfy Widely Used Oxygen Consumption Criteria

Cardiorespiratory fitness (CRF) is routinely investigated in older adults; however, the most appropriate CRF measure to use for this population has received inadequate attention. This study aimed to 1) evaluate the reliability and validity of the oxygen uptake efficiency slope (OUES) as a sub-maximal measurement of CRF; 2) examine demographic, risk-factor, and exercise testing differences in older adults who satisfied standardized criteria for a peak oxygen consumption (V̇O2peak) test compared to those who did not; and 3) determine the difference between directly measured V̇O2peak values and OUES-predicted V̇O2peak values. One hundred ten enrollees from the Wisconsin Registry for Alzheimers Prevention participated in this study. Participants performed a graded maximal exercise test and wore an accelerometer for 7 days. For each participant, the OUES was calculated at 75%, 90%, and 100% of exercise duration. V̇O2peak was recorded at peak effort, and one week of physical activity behavior was measured. OUES values calculated at separate relative exercise durations displayed excellent reliability (ICC = 0.995; p < 0.001), and were strongly correlated with V̇O2peak (rrange = 0.801-0.909; p < 0.001). As hypothesized, participants who did not satisfy V̇O2peak criteria were significantly older than those who satisfied criteria (p = 0.049) and attained a directly measured V̇O2peak that was 2.31 mL·kg·min-1 less than the value that was predicted by OUES V̇O2peak (p = 0.003). Older adults are less likely to satisfy V̇O2peak criteria, which results in an underestimation of their CRF. Without adhering to standardized criteria, V̇O2peak measurement error may lead to misinterpretation of CRF and age-related associations. Here, we conclude that OUES is a reliable, valid measurement of CRF which does not require achievement of standardized criteria.

Moderate intensity physical activity associates with CSF biomarkers in a cohort at risk for Alzheimer's disease

Alzheimers disease (AD) is characterized by the presence of amyloid β (Aβ) plaques, neurofibrillary tangles, and neurodegeneration, evidence of which may be detected in vivo via cerebrospinal fluid (CSF) sampling. Physical activity (PA) has emerged as a possible modifier of these AD‐related pathological changes. Consequently, the aim of this study was to cross‐sectionally examine the relationship between objectively measured PA and CSF levels of Aβ42 and tau in asymptomatic late‐middle‐aged adults at risk for AD.

Chronotropic Response and Cognitive Function in a Cohort at Risk for Alzheimer’s Disease

The objective of this study was to examine the association of chronotropic response (CR) and heart rate (HR) recovery- two indices of cardiovascular function within the context of a graded exercise test- with cognitive performance in a cognitively healthy, late-middle-aged cohort at risk for Alzheimers disease (AD). Ninety participants (age = 63.52±5.86 years; 65.6% female) from the Wisconsin Registry for Alzheimers Prevention participated in this study. They underwent graded exercise testing and a comprehensive neuropsychological assessment that assessed the following four cognitive domains: Immediate Memory, Verbal & Learning Memory, Working Memory, and Speed & Flexibility. Regression analyses, adjusted for age, sex, and education, were used to examine the association between CR, HR recovery, and cognition. We found significant associations between CR and cognitive performance in the domains of Immediate Memory, Verbal Learning & Memory, and Speed & Flexibility. In contrast, HR recovery was not significantly associated with cognitive function. The association between CR and cognition persisted even after controlling for HR recovery. Together, these findings indicatethat, in a cognitively normal, late-middle-aged cohort, CR is a stronger correlate of cognitive performance than HR recovery. Overall, this study reinforces the idea that cardiovascular health plays an important role in cognitive function, specifically in a cohort at risk for AD; and that interventions that promote vascular health may be a viable pathway to preventing or slowing cognitive decline due to AD.

Symptom variability following acute exercise in myalgic encephalomyelitis/chronic fatigue syndrome: a perspective on measuring post-exertion malaise

ABSTRACT Background: Consensus for an operational definition of post-exertion malaise (PEM) and which symptoms best characterize PEM has not been established and may be due to variability within and between studies. Purpose: Determine the magnitude of the effect of maximal and submaximal physical exertion on multiple myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) symptoms that are associated with PEM and explore variability among two studies in which mood, fatigue, and pain symptoms were measured before and after exercise. Methods: Symptoms were measured before, and 48 and 72 hours after exercise in study 1 (ME/CFS = 13; Controls = 11) and before and 24 hours after exercise in study 2 (ME/CFS = 15, Controls = 15). Between-study variability was examined by comparing Hedges d effect sizes (95% CI) from studies 1 and 2. Within-patient group variability was examined via inspection of dot density plots. Results: In study 1, large increases in general fatigue (Δ = 1.05), reduced motivation (Δ = 0.93), feelings of fatigue (Δ = 0.90), feelings of confusion (Δ = 0.93), and total mood disturbance (Δ = 0.90) were found at 72 hours. In study 2, a large increase in affective/sensory pain (Δ = 0.79) was found at 24 hours. Dot density plots in both studies revealed substantial variability among people with ME/CFS relative to healthy control participants. Conclusions: PEM symptoms are variable among people with ME/CFS and several gaps in the literature need to be addressed before guidelines for measuring PEM in the clinical or research setting can be established.

EXERCISE TRAINING AND CEREBRAL BLOOD FLOW IN PRECLINICAL ALZHEIMER’S DISEASE: RESULTS FROM THE AEROBIC EXERCISE AND COGNITIVE HEALTH (REACH) STUDY

Cognition, z scores Global cognitive function .55 (.42 to .66) .48 (.37 to .6) .07 (–.11 to .22) .509 Executive function .33 (.13 to .52) .34 (.17 to .52) –.01 (–.28 to .24) .882 Processing speed .32 (.15 to .5) .19 (.03 to .35) .13 (–.1 to .37) .581 Memory .97 (.72 to 1.23) .88 (.64 to 1.1) .09 (–.25 to .44) .267 Verbal fluency .52 (.31 to .73) .55 (.36 to .75) –.13 (–.56 to 29) .822 Mobility Usual gait velocity, cm/s 1.77 (–3 to 6.6) 9.36 (4.94 to 13.78) –7.58 (–14.12 to –1.03) .024* Usual step length, cm .35 (–1.2 to 1.9) 3.36 (1.95 to 4.77) –3.01 ( – 5.10 to –.91) 006* Usual gait variability, CoV, % –.67 (–1.8 to .45) –.24 (–1.2 to .75) –.42 (–1.93 to 1.07) .574 DT gait velocity, cm/s 7.69 (1.5 to 13.9) 11.1 (5.4 to 16.7) –3.37 (–11.76 to 5) .424 DT step length, cm 2.11 (–.11 to 4.33) 3.81 (1.77 to 5.84) –1.69 (–4.71 to 1.31) .264 DT gait variability, CoV, % – 2.97 ( – 5.64 to .31) –.5 (–2.91 to 1.91) –2.47 (–6.07 to 1.12) .175