About

Dr. Dane B. Cook is a Professor in the Department of Kinesiology at the University of Wisconsin-Madison. He serves as the Director of the Exercise Psychology laboratories at the William S. Middleton Memorial Veterans Hospital and the University of Wisconsin-Madison. Additionally, he is the Director of the Marsh Center for Research in Exercise and Movement within the Department of Kinesiology. Dr. Cook's educational background includes a BS in Psychology from Arizona State University, an MA and PhD in Exercise Science from the University of Georgia, and a postdoctoral fellowship in Neuroscience at UMDNJ-NJMSA. His research focuses on exercise psychology, and he is actively involved in laboratory and center leadership roles dedicated to advancing understanding in exercise and movement sciences.

Research topics

• Medicine
• Internal medicine
• Psychology
• Bioinformatics
• Cardiology
• Endocrinology
• Biology
• Pathology
• Physical therapy
• Psychiatry
• Immunology

Selected publications

• Design and rationale of RECOVER-AUTONOMIC: A randomized platform trial evaluating interventions for Long COVID postural orthostatic tachycardia syndrome

  American Heart Journal · 2026-02-18

  articleOpen access

  BACKGROUND: Post‑acute sequelae of SARS‑CoV‑2 infection (Long COVID) affect a substantial proportion of individuals, and among the many reported symptom clusters, autonomic dysfunction, particularly postural orthostatic tachycardia syndrome (POTS), represents an important subset. The Researching COVID to Enhance Recovery Clinical Trials (RECOVER-CT) initiative developed by the National Institutes of Health included a platform trial (RECOVER-AUTONOMIC) designed to assess the safety, tolerability, and efficacy of 3 interventions-(1) coordinated nonpharmacologic care, (2) pharmacotherapy with intravenous immunoglobulin (IVIG), and (3) pharmacotherapy with ivabradine-in treating POTS in adults with Long COVID. METHODS: RECOVER-AUTONOMIC is a multicenter, randomized, double-blinded, placebo-controlled, platform trial employing a flexible, adaptive design. Participants are randomized to IVIG or ivabradine with matching placebo, and (in a factorial design) to either coordinated nonpharmacologic care or usual care. The primary endpoint is the change in orthostatic intolerance symptoms measured by the Orthostatic Hypotension Questionnaire/Orthostatic Intolerance Questionnaire from baseline to the end of intervention. Secondary endpoints include quality of life, functional performance, symptom burden, and safety. Exploratory endpoints include autonomic function testing, wearable sensor data, and longitudinal biomarker profiling. DISCUSSION: RECOVER-AUTONOMIC seeks to determine the benefits and risks of IVIG and of ivabradine, as well as of coordinated nonpharmacologic care, for the treatment of POTS in Long COVID. Results from this trial will offer the largest source of evidence to help guide the medical care of this population. TRIAL REGISTRATION: ClinicalTrials.gov-Platform: NCT06305780; Appendix A (intravenous immunoglobulin): NCT06305793; Appendix B (ivabradine): NCT06305806. Protocol available at https://trials.recovercovid.org/autonomic.

  PublisherDOI

• Sex modifies the association between cardiorespiratory fitness and insulin resistance in adults at risk for Alzheimer’s disease

  Applied Physiology Nutrition and Metabolism · 2025-01-01

  article

  This study examines whether sex modifies the association between cardiorespiratory fitness (CRF) and insulin resistance in adults at risk for Alzheimer’s disease (AD). This study included n = 1131 (791 females, 340 males; mean age 64.7 years) cognitively unimpaired, nondiabetic participants from the Wisconsin Registry for Alzheimer’s Prevention, a longitudinal observational cohort study enriched with persons with parental history of AD dementia. CRF was estimated using a validated equation, and the homeostatic model assessment for insulin resistance (HOMA-IR) quantified insulin resistance from blood samples. Cross-sectional linear regression models were assembled in a moderation framework to test the interaction between CRF and sex on HOMA-IR scores. Finally, sex-stratified analyses were performed to test within-group associations of CRF and HOMA-IR. CRF was negatively associated with HOMA-IR (β = −0.504, SE = 0.21, p = 0.018) and the interaction of CRF and sex was likewise significant (β = −0.849, SE = 0.18, p < 0.001). Stratified models showed that the magnitude of the association between CRF and HOMA-IR was over twice as strong among males than females (males: β = −0.837, SE = 0.26, p = 0.001; females: β = −0.400, SE = 0.19, p = 0.03). Among older adults at heightened risk for AD, CRF protects against insulin resistance; however, this association may be stronger in aging males than in females.

  PublisherDOI

• Abnormal breathing patterns and hyperventilation are common in patients with chronic fatigue syndrome during exercise

  Frontiers in Medicine · 2025-11-10 · 3 citations

  articleOpen access

  Introduction Patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) experience symptoms of fatigue, dyspnea, mental fog, and worsening fatigue after physical or mental efforts. Some of these patients have been found to hyperventilate. In long COVID patients, many of whom also have ME/CFS, dysfunctional breathing (DB) has been described. Whether patients with ME/CFS, independent of COVID-19, experience dysfunctional breathing is unknown, as well as how it may relate to hyperventilation. Methods We performed serial 2-day cardiopulmonary exercise testing (CPET) in 57 patients with ME/CFS and 25 age- and activity-matched control participants. Peak oxygen consumption (VO 2 ), ventilatory efficiency slope (VE/VCO 2 ), O 2 saturation, end-tidal CO 2 (PetCO 2 ), heart rate, and mean arterial blood pressure were measured in all patients during upright incremental bicycle exercise. Ventilatory patterns were reviewed using minute ventilation (VE) versus time, respiratory rate, and tidal volume versus minute ventilation graphs. Chronic hyperventilation (HV) was defined as a PETCO 2 of <34 mm Hg that persisted during low-intensity exercise. Dysfunctional breathing was characterized by a 15% increase in oscillations in minute ventilation during at least 60% of the exercise duration or by a scatterplot pattern of respiratory rate and tidal volume plotted versus minute ventilation. Results The patients with ME/CFS had an average age of 38.6 ± 9.6 years, and a mean body mass index (BMI) of 24.1 ± 3.4, which was comparable to the sedentary controls. All participants performed maximal exercise, achieving a respiratory exchange ratio (RER) of >1.05. For the patients with ME/CFS, peak VO 2 averaged 22.3 ± 5.3 mL/kg/min, which was 79 ± 20% of predicted and comparable to that observed in the sedentary controls (23.4 ± 4.6 mL/kg/min; 81 ± 12%; p = NS). A total of 24 patients with ME/CFS (42.1%) met the criteria for dysfunctional breathing compared to four sedentary controls (16%) ( p < 0.02). In total, 18 patients with ME/CFS (32%) had hyperventilation compared to one sedentary control participant (4%) ( p < 0.01), and nine patients with ME/CFS had both hyperventilation and dysfunctional breathing, whereas no sedentary participant exhibited both. The patients with ME/CFS and hyperventilation had significantly higher VE/VCO 2 ratios (HV+: 34.7 ± 7.2; HV−: 28.1 ± 3.8; p < 0.001). A total of 15 of 18 patients with hyperventilation (83%) had either elevated VE /VCO 2 ratios ( n = 15) or dysfunctional breathing ( n = 9) compared to 44% ( n = 17) of the 40 non-hyperventilators ( p < 0.01). Conclusion Dysfunctional breathing and hyperventilation are common in patients with ME/CFS and could present a new therapeutic target for these patients.

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• More fit KL‐VS heterozygotes have more favorable AD‐relevant biomarker profiles

  Alzheimer s & Dementia Translational Research & Clinical Interventions · 2025-07-01 · 1 citations

  articleOpen access

  Abstract INTRODUCTION Although hallmarked by β‐amyloid plaques (Aβ) and neurofibrillary tangles (tau), Alzheimer's disease (AD) is a multifactorial disorder that involves neuroinflammation, neurodegeneration, and synaptic dysfunction. AD‐associated biomolecular changes seem to be attenuated in carriers of the functionally advantageous variant of the KLOTHO gene (KL‐VS HET ). Independently, better cardiorespiratory fitness (CRF) is associated with better health outcomes related to AD pathology. Here we investigate whether the relationships between CRF (peak oxygen consumption (VO 2peak )) and cerebrospinal fluid (CSF) core AD biomarkers and those of neuroinflammation, neurodegeneration, and synaptic dysfunction differ for KL‐VS HET compared to noncarriers (KL‐VS NC ). METHODS The cohort, enriched for AD risk, consisted of cognitively unimpaired adults ( n = 136; Mean AGE (SD) = 62.5(6.7)) from the Wisconsin Registry for Alzheimer's Prevention and the Wisconsin Alzheimer's Disease Research Center. Covariate‐adjusted (age, sex, parental AD history, apolipoprotein E ( APOE) 4+ status, and age difference between CSF sampling and exercise test) linear models examined the interaction between VO 2peak and KLOTHO genotype on CSF core AD biomarker levels (phosphorylated tau 181 [pTau 181 ], Aβ 42 /Aβ 40 , pTau 181 /Aβ 42 ). Analyses were repeated for CSF biomarkers of neurodegeneration (total tau [tTau], α‐synuclein [α‐syn], neurofilament light polypeptide [NfL]), synaptic dysfunction (neurogranin [Ng]), and neuroinflammation (glial fibrillary acidic protein [GFAP], soluble triggering receptor expressed in myeloid cells [sTREM2], chitinase‐3‐like protein 1 [YKL‐40], interleukin 6 [IL‐6], S100 calcium‐binding protein B [S100B]). RESULTS The interaction between VO 2peak and KL‐VS HET was significant for tTau ( p = 0.05), pTau 181 ( p = 0.03), Ng ( p = 0.02), sTREM2 ( p = 0.03), and YKL‐40 ( p = 0.03), such that lower levels of each biomarker were observed for KL‐VS HET who were more fit. No significant KL‐VSxVO 2peak interactions were observed for Aβ 42 /Aβ 40 , pTau 181 /Aβ 42 , α‐syn, NfL, GFAP, IL‐6 or S100B (all P s>0.09). CONCLUSIONS We report a synergistic relationship between KL‐VS HET and CRF with pTau 181 , tTau, Ng, sTREM2 and YKL‐40, suggesting a protective role for both KL‐VS HET and better CRF against unfavorable AD‐related changes. Their potentially shared biological mechanisms require future investigations. Highlights KLOTHO KL‐VS HET and higher cardiorespiratory fitness (CRF) may protect against unfavorable Alzheimer's disease (AD)‐related changes. Higher CRF attenuates neurodegeneration and synaptic dysfunction in KL‐VS HET . More fit KL‐VS HET also has lower levels of pTau and less neuroinflammation.

  PublisherDOI

• The Association of Cardiorespiratory Fitness with Rates of Cognitive Decline in a Multiethnic Cohort at Risk for Alzheimer’s Disease

  Alzheimer s & Dementia · 2025-12-01

  articleOpen access

  BACKGROUND: Cardiorespiratory fitness (CRF) has emerged as a potential moderator of cognition. Higher CRF may offer cognitive resilience to individuals at risk for Alzheimer's Disease (AD). This, however, may vary across populations. Therefore, we aimed to examine whether the relationship between CRF and rates of cognitive decline differ for under-studied research groups (URGs) compared to non-URGs in a cohort of older cognitively unimpaired adults, enriched for AD risk. METHODS: ±SD=5.6±5.2 years] enrolled in the Wisconsin Registry for Alzheimer's Prevention or the Wisconsin Alzheimer's Disease Research Center. CRF was derived from a validated estimation equation (eCRF) and participants were categorized into tertiles (low, average and high) for analysis. Two-sample t-tests assessed cross-sectional differences in eCRF between URGs and non-URGs. Linear mixed effects models adjusting for age, sex, education, family history of dementia, BMI, and APOE4+ carrier status evaluated the association between eCRF and age-related decline in global cognition, assessed by the Preclinical Alzheimer Cognitive Composite (PACC), in the entire sample and stratified by URG status. Secondary analyses were carried out on the three individual component tests of the PACC in stratified samples. RESULTS: eCRF was significantly lower in URGs (p <0.001). Average and high eCRF was associated with slower decline in global cognition (ps <0.001)) across the entire sample. In stratified analyses, average and high eCRF were associated with slower decline in global cognition among non-URGs (ps <0.001), but not URGs (ps >0.6). Secondary analyses of decline in performance on PACC's three component tests revealed significant associations with average and high eCRF in non-URGs (ps <0.015) but not URGs (ps >0.16). CONCLUSION: Average and high eCRF were associated with slower cognitive decline in non-URGs, but not in URGs. These group differences may reflect underlying health or lifestyle disparities that influence fitness and cognition. Additionally, the eCRF measure used in this study was developed using data from a predominantly white population; therefore, may not accurately capture fitness status among URGs. This potential limitation should be addressed in future research to improve the accuracy and applicability of eCRF estimates in diverse populations.

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• 16 weeks of moderate intensity resistance exercise improves strength but is insufficient to alter brain structure in Gulf War Veterans with chronic musculoskeletal pain: a randomized controlled trial

  Frontiers in Neuroscience · 2025-04-16

  articleOpen accessSenior authorCorresponding

  Introduction Chronic widespread musculoskeletal pain (CMP) is a primary condition of Veterans who were deployed to the Persian Gulf War. The mechanisms that underlie CMP in these Veterans are unknown and few efficacious treatment options exist. This study tested the effects of 16 weeks of resistance exercise training (RET) on gray matter (GM) volume and white matter (WM) microstructure in Gulf War Veterans (GWVs) with CMP compared to GWV waitlist controls (WLC). Methods Fifty-four GWVs were randomly assigned to 16 weeks of RET ( n = 28) or WLC ( n = 26). Training involved 10 resistance exercises to involve the whole body, was supervised and individually tailored, and progressed slowly to avoid symptom exacerbation. Outcomes assessed at baseline, 6, 11 and 17 weeks and 6- and 12-months post-intervention included GM volume (voxel-based morphometry), WM microstructure (diffusion tensor imaging), pain [short form McGill Pain Questionnaire (SF-MPQ) and 0–100 visual analog scale (VAS)], fatigue (0–100 VAS), and mood (Profile of Mood States). Muscular strength was assessed at baseline, 8 and 16 weeks, and training volume was tracked throughout the 16-week intervention. Primary analyses used linear mixed effects models with Group, Time, and the Group*Time interaction as fixed factors and subject and slope as random factors to test the differential effects of RET and WLC on brain structure and symptoms. All neuroimaging analyses used the False Discovery Rate to correct for multiple comparisons at an alpha of 0.05. Results Strength increased significantly across the trial for the RET group ( p &amp;lt; 0.001). There were significant Group*Time interaction effects for pain ratings (SF-MPQ total; p &amp;lt; 0.01) and the Profile of Mood States total mood disturbance score ( p &amp;lt; 0.01). There were no Group or Group*Time effects for GM volume or WM microstructure. There were no significant associations between strength, symptoms, and brain structure ( p &amp;gt; 0.05). Conclusion Sixteen weeks of low-to-moderate intensity RET (i) improved musculoskeletal strength and (ii) did not exacerbate symptoms, but (iii) was insufficient to alter brain structure in GWVs with CMP.

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• Perceptual And Metabolic Responses To Exercise In Chronic Multisymptom Illness

  Medicine & Science in Sports & Exercise · 2025-09-16

  articleSenior author

  Post-exertional malaise (PEM) is a general worsening of symptoms following physical or mental exertion and a characteristic of chronic multisymptom illnesses (CMI) including Gulf War Illness (GWI), Chronic Fatigue Syndrome (CFS), and Long Covid. Cardiopulmonary exercise testing (CPET) has been used to elicit PEM and the existing data suggest an altered, pro-inflammatory, albeit heterogeneous, peripheral response to exercise in CMI that is often unrelated to symptoms. The pathophysiological antecedents of PEM are still unclear; understanding the perceptual and cardiopulmonary responses during exercise may provide greater insight into the post-exertional consequences for those with CMI. The present data were collected as part of a larger protocol testing the neuroinflammatory response to exercise in CMI with the goal of furthering our understanding of the mechanisms underlying PEM. Purpose: To compare the perceptual and cardiopulmonary responses to a standardized submaximal exercise test in CMI. Methods: 14 individuals with CMI (6 Long COVID, 6 CFS, and 2 GWI) and 14 age- and sex-matched controls (CON) completed a 30-min, submaximal (70% heart rate reserve; HRR) cycle ergometer test. Continuous CPET data were collected during (time points 1-6, 5-min averages) and following the test during cool down (time point 7, 1-min average). Ratings of leg muscle pain intensity and overall fatigue were also collected every 5 min during the test and once during cool down. A doubly multivariate MANOVA was calculated with time (1-7) and group (CMI vs CON) as main effects and with fatigue, tidal volume, respiratory rate, work rate, and VE/VCO2 as the multivariate outcomes. Results: The groups did not differ on age (CMI = 40.7, CON = 39.6), sex (65% female for both), BMI (CMI = 26.0, CON = 27.8) or percent time spent in their prescribed HRR zone (CMI = 83.5, CON = 90.1). For the exercise test, there was a significant effect for time (p > 0.001), but not for group (p = 0.803) or group by time interaction (p = 0.431). Conclusion: Our results suggest CMI and CON have a similar response to a standardized bout of submaximal exercise. Further analysis is needed to identify how these factors are related to post-exercise perceptual (i.e., PEM) and physiological (i.e., neuroinflammation) responses.Funded by the University of Wisconsin-Madison. Supported by: University of Wisconsin – Madison

  PublisherDOI

• Differential DNA methylation in blood in nuclear genes that encode mitochondrial proteins in mild cognitive impairment and Alzheimer’s disease

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-06-20 · 1 citations

  preprintOpen access

  Abstract Background Altered mitochondrial function contributes to the pathogenesis of mild cognitive impairment (MCI) and late-onset dementia due to Alzheimer’s disease (AD). Objective To test for differential methylation in nuclear genes that encode proteins that participate in mitochondrial function between cognitively unimpaired participants (CU) and those with MCI and AD. Methods Recently published whole genome methylation sequencing (WGMS) in blood from CU participants ( N =174), and those with MCI ( N =99) and AD ( N =109) was used to test for differential methylation in 1,121 nuclear genes that encode proteins that participate in mitochondrial function in the Human Protein Atlas . Results Seventy-four nuclear genes that encode proteins that participate in mitochondrial function were differentially methylated between persons with MCI and CU. Seventy-one genes were differentially methylated between persons with AD and CU, and 132 genes were differentially methylated between persons with MCI and AD. Thirteen differentially methylated genes shared between the 3 comparisons support contributions from disrupted metabolism and oxidative stress pathways in AD pathogenesis. Conclusions Nuclear genes that encode proteins that participate in mitochondrial glucose metabolism, fatty acid metabolism and oxidative stress pathways are differentially methylated between persons who are CU and those with MCI and AD.

  PublisherDOI

• P.026 Structural deficits with preserved kinematic performance after sport-related concussion

  Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques · 2025-06-01

  articleOpen accessSenior author

  Background: Identifying white matter abnormalities after acute concussion is challenging due to variable microstructural changes and individual imaging limitations. Combining diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) improves sensitivity to alterations. This study integrates neuroimaging and behavioural assessments to improve detection and characterization of abnormalities for clinical management. Methods: We recruited 12 recently concussed athletes (21 ± 2.1 years, 7 ± 4.6 days post-injury; 9 completed behavioural testing) and 24 controls. All participants underwent DTI and NODDI to assess white matter integrity. Kinematic performance was evaluated using the Kinarm exoskeleton robot’s Reverse Visually Guided Reaching (RVGR) task. Group differences in imaging and kinematic metrics were analyzed using permutation-based and parametric tests, controlling for age and sex. Results: Concussed athletes had elevated fractional anisotropy, reduced mean and radial diffusivity, and lower isotropic volume fraction in affected tracts. However, no group differences emerged in RVGR parameters, indicating intact sensorimotor function despite imaging abnormalities. Conclusions: Our findings reveal that acute concussion leads to measurable microstructural changes without corresponding functional deficits on a cognitive inhibition task. These findings highlight the clinical utility of neuroimaging for early and precise diagnosis, emphasizing its sensitivity over behavioural measures to detect subtle impairment for acute concussion management.

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• Characterising dysfunctional breathing seen in post-acute sequelae of SARS-CoV-2 using approximate entropy

  ERJ Open Research · 2025-02-13 · 1 citations

  articleOpen access

  Rationale Dysfunctional breathing (DB) is a commonly identified abnormality in post-acute sequelae of SARS-CoV-2 (PASC) patients undergoing cardiopulmonary exercise testing (CPET), and is potentially a contributor to ongoing symptoms. Currently, this oscillating, irregular breathing pattern is identified by visual observation of CPET data by an experienced interpreter, which is subjective. We hypothesise that approximate entropy (ApEn), a regularity statistic that quantifies the unpredictability of time-series data can reliably distinguish DB from normal breathing states. Methods Breath-by-breath CPET data were obtained for 82 PASC subjects and 25 controls. CPETs were visually analysed for DB prior to analysis. Minute ventilation ( V ′ E ), tidal volume ( V T ) and breathing frequency (BF) over time data were normalised with 100% considered as the ventilation at anaerobic threshold (AT) and detrended before ApEn was calculated. Analysis was initiated at 25 W and ceased at AT. Results The ApEn V ′ E of PASC subjects with visualised DB was 0.286±0.128 (mean± sd ), which was significantly different from control subjects (0.143±0.081) and PASC subjects without visualised DB (0.183±0.104); p&lt;0.05. Receiver operating characteristic curve analysis produced an optimal cut-off value of 0.17 for distinguishing DB, which resulted in a sensitivity of 81% and specificity of 72%. ApEn V T and ApEn BF were similar among all PASC patients despite visually recognised DB, but significantly greater than controls. Conclusions Identifying DB on CPET requires visual recognition, which has limitations. ApEn V ′ E is an objective metric that can reliably differentiate DB from normal breathing patterns on CPET. This can be a valuable addition to keen visual scrutiny of CPET data.

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Recent grants

• Impact of exercise training on pain and brain function in Gulf War Veterans

  NIH · 2011–2018

• NIH Grant R01AR050969

  NIH · $1.4M · 2011

• Post exertion malaise in GWI_Brain autonomic and behavioral interactions

  NIH · 2016–2026

Frequent coauthors

• Aaron J. Stegner

  Biostatistical Consulting (United States)

  171 shared

• Ozioma C. Okonkwo

  Geriatric Research Education and Clinical Center

  144 shared

• Jacob B. Lindheimer

  William S. Middleton Memorial Veterans Hospital

  124 shared

• Sterling C. Johnson

  Temple University

  114 shared

• Laura D. Ellingson

  Western Oregon University

  101 shared

• Sanjay Asthana

  Geriatric Research Education and Clinical Center

  83 shared

• Barbara B. Bendlin

  University of Wisconsin–Madison

  80 shared

• Michael J. Falvo

  VA New Jersey Health Care System

  78 shared

Education

• Ph.D., Kinesiology

  University of Wisconsin-Madison

  2005

• M.S., Kinesiology

  University of Wisconsin-Madison

  2001

• B.S., Kinesiology

  University of Wisconsin-Madison

  1999