Weekly MSK Literature Review

Reflections from the APTA Graham Session: Adding Value Through Evidence-Informed Practice

Monday: Exercise Training and Mortality in Older Adults

Main Points

The Generation 100 study followed 1,567 adults aged 70-77 over five years, comparing high-intensity interval training, moderate-intensity continuous training, and standard physical activity guidelines. Overall five-year mortality was 4.6%, with no significant difference between supervised exercise groups combined and controls. However, HIIT showed a trend toward lower mortality at 3.0% compared to control at 4.7% and MICT at 5.9%, representing a hazard ratio of 0.63 for HIIT versus control. The HIIT group demonstrated the greatest improvements in peak VO₂ and quality of life measures across all timepoints. Notably, control participants performed more high-intensity activity than the MICT group, narrowing expected group differences. No significant differences emerged in cardiovascular events (approximately 15% across groups) or cancer incidence (approximately 12% across groups) after five years.

Clinical Significance

This trial demonstrates that older adults can safely perform structured high-intensity exercise for extended periods and suggests that exercise intensity, not just volume, may be the critical factor in longevity and functional outcomes. The convergence of mortality rates across groups due to control participants self-selecting higher-intensity activities reinforces that when older adults understand the benefits of vigorous exercise, they naturally gravitate toward it, challenging traditional conservative approaches to senior fitness programming.

Citation

Stensvold, D., Viken, H., Steinshamn, S. L., Dalen, H., Støylen, A., Loennechen, J. P., Reitlo, L. S., Zisko, N., Bækkerud, F. H., Tari, A. R., Sandbakk, S. B., Carlsen, T., Ingebrigtsen, J. E., Lydersen, S., Mattsson, E., Anderssen, S. A., Singh, M. A. F., Coombes, J. S., Skogvoll, E., Vatten, L. J., Helbostad, J. L., Rognmo, Ø., & Wisløff, U. (2020). Effect of exercise training for five years on all cause mortality in older adults: The Generation 100 study. BMJ, 371, m3485. https://doi.org/10.1136/bmj.m3485

Tuesday: Social Power and the Movement System

Main Points

This perspective article argues that social determinants of health are downstream manifestations of deeper social power hierarchies that fundamentally shape movement system health disparities. The authors apply Fundamental Cause Theory to demonstrate that socioeconomic status operates as a flexible resource that influences multiple diseases through multiple pathways, with inequalities persisting even as specific mechanisms change over time. Social power determines differential exposure to environmental hazards, susceptibility to movement system pathology through chronic stress and discrimination, experience of illness through biased clinical interactions and limited access, and recovery capacity based on ability to access and adhere to treatment. The paper introduces structural competency and structural humility as essential frameworks, arguing that physical therapists must understand how commodification of healthcare services, systemic discrimination, and chronic scarcity (devitalization) create barriers that simple resource provision cannot overcome. The authors emphasize that effective action requires engagement at individual, community, and societal levels, sometimes challenging the profession's own economic incentives.

Clinical Significance

This framework redefines the physical therapy profession's obligation from purely clinical intervention to addressing the structural and political determinants that render clinical care inaccessible or ineffective for marginalized populations. Understanding that power, not just resources, determines who benefits from musculoskeletal care should fundamentally reshape how we design delivery models, partner with communities, and advocate for policy change.

Citation

Davenport, T. E., Griech, S. F., VanDeCarr, T., Rethorn, Z. D., & Magnusson, D. M. (2023). Social power and the movement system: Why and how physical therapists might influence the upstream currents of health. Physical Therapy, 103(7), 1–10. https://doi.org/10.1093/ptj/pzad052

Wednesday: Addressing Access Disparities Through Public Health

Main Points

One in three people worldwide would benefit from rehabilitation, yet years lived with disability from rehabilitation-sensitive conditions increased 69% from 1990 to 2019, with musculoskeletal disorders representing the leading global cause of disability. Physical therapy practice currently operates at the top of Frieden's Health Impact Pyramid—focused on individual counseling and tertiary prevention—while the greatest population health impact occurs through contextual change and socioeconomic interventions at the pyramid's base. The authors present a four-step public health framework: surveillance to define target populations, identification of risk and protective factors, development and evaluation of scalable interventions, and iterative implementation. Digital health and telehealth represent catalytic opportunities for expansion, with evidence showing hybrid virtual-clinic models improve adherence and outcomes. A rural Wisconsin school district embedding physical therapy demonstrated 30% reduction in opioid prescriptions, 21% reduction in non-PT musculoskeletal expenses, 35% reduction in outpatient hospitalizations, and 50% reduction in emergency department visits and surgeries. Task-shifting to physical therapist assistants, aides, and community health workers, combined with embedding physical therapists in primary care and employer settings, can dramatically expand reach while maintaining quality.

Clinical Significance

This public health reframing positions physical therapists as essential population health actors rather than solely individual rehabilitation providers, offering a strategic roadmap for addressing the fundamental mismatch between mushrooming rehabilitation needs and constrained workforce supply. The Wisconsin example provides compelling economic justification for upstream integration of musculoskeletal care into primary and preventive services.

Citation

McKinney, J., Kelm, N., Windsor, B., & Keyser, L. E. (2024). Addressing health care access disparities through a public health approach to physical therapist practice. Physical Therapy, 104, pzae136. https://doi.org/10.1093/ptj/pzae136

Thursday: Exercise, Inflammation, and Motivational Circuitry

Main Points

This mechanistic review proposes that aerobic exercise reduces depressive symptoms, particularly anhedonia, fatigue, and subjective cognitive impairment, through a specific biological pathway: exercise reduces systemic inflammation, which restores dopamine transmission in ventral striatal circuits, which decreases effort sensitivity in reward-based decision-making, which increases motivated behavior and cognitive control allocation. Depression involves profound motivational dysfunction characterized by reduced reward sensitivity, impaired effort-based decision-making, and diminished willingness to exert effort for potential rewards, deficits strongly associated with poor treatment response to traditional antidepressants. Elevated inflammatory cytokines (IL-6, IL-1β, TNF-α) suppress dopamine synthesis, release, and signaling specifically in motivational circuits, with experimental inflammation reducing reward responsivity and increasing effort sensitivity in healthy volunteers. Aerobic exercise reliably reduces systemic inflammation, increases brain-derived neurotrophic factor, enhances fronto-striatal connectivity (particularly anterior mid-cingulate cortex and dorsolateral prefrontal cortex), and boosts dopamine transmission. The authors argue that cognitive impairment in depression may be partly motivational rather than purely cognitive—people avoid cognitively effortful tasks because the perceived effort cost is too high relative to expected reward.

Clinical Significance

This framework explains why exercise may be effective when selective serotonin reuptake inhibitors fail and provides a mechanistic rationale for prescribing aerobic exercise specifically for the interest-activity symptom cluster in depression. Understanding exercise as an intervention that restores the brain's capacity for effortful, rewarding action rather than simply "improving mood" should inform how we dose, progress, and measure outcomes in exercise-based mental health interventions.

Citation

Brellenthin, A. G., & Koltyn, K. F. (2016). Exercise as treatment for depression: Efficacy and dose response. American Journal of Lifestyle Medicine, 10(3), 196–210. https://doi.org/10.1177/1559827613508542

Friday: Environmental Shaping of Brain and Gut Barriers

Main Points

The blood-brain barrier and gut barrier function as dynamic environmental sensors that translate social, structural, and physical exposures into immune, endocrine, and neural changes affecting cognition and behavior across the lifespan. These barriers are not passive walls but active signaling hubs formed by tight junction proteins (claudin-5, occludin, ZO-1), endothelial or epithelial cells, supporting cells (pericytes, astrocytes for blood-brain barrier; immune cells and enteric neurons for gut barrier), and are bidirectionally connected via the immune system, hypothalamic-pituitary-adrenal axis, and microbiota-gut-brain axis. Positive social environments reduce inflammatory markers (IL-6, E-selectin) and enhance tight junction expression, while social isolation and defeat stress increase systemic inflammation, reduce claudin-5 expression, alter microglial function, shift microbiome composition toward dysbiosis, and increase gut permeability. Environmental enrichment (novelty, complexity, sensory diversity) increases neurogenesis, vascular density, blood-brain barrier stability, microbiome diversity, and short-chain fatty acid production while reducing inflammatory signaling. Physical exercise represents one of the most potent modulators, increasing microbial diversity, boosting butyrate production, reducing TNF-α and IL-6, enhancing tight junction expression in both barriers, increasing cerebral blood vessel density, and improving astrocyte coverage. Barrier dysfunction has been documented in major depressive disorder, bipolar disorder, and schizophrenia, positioning these barriers as early mechanistic drivers of psychiatric disease and potential therapeutic targets.

Clinical Significance

This research establishes biological plausibility for why movement-based interventions affect mental health and cognitive function through pathways entirely independent of traditional neurotransmitter models, suggesting that current psychiatric treatments may be targeting downstream symptoms while exercise addresses upstream barrier integrity. For musculoskeletal clinicians, this positions physical activity prescription as a fundamental intervention for brain health, not merely a adjunctive treatment for comorbid depression.

Citation

Menard, C., Pfau, M. L., Hodes, G. E., & Russo, S. J. (2017). Immune and neuroendocrine mechanisms of stress vulnerability and resilience. Neuropsychopharmacology, 42(1), 62–80. https://doi.org/10.1038/npp.2016.90

Weekly Themes & Strategic Insights

1. Intensity Over Volume in Exercise Prescription

The Generation 100 study challenges conventional conservative approaches to senior fitness by demonstrating that high-intensity interval training produced the strongest trends toward reduced mortality (3.0% vs 4.7% control) and greatest improvements in cardiorespiratory fitness and quality of life. Remarkably, control participants who were simply advised to follow guidelines self-selected more high-intensity activity than the moderate-intensity continuous training group, suggesting that when older adults understand benefits, they naturally gravitate toward vigorous exercise. This converges with the inflammation-dopamine-motivation framework, which positions exercise intensity as the key variable for reducing systemic inflammation and restoring motivational circuitry.

2. Structural Barriers Trump Individual Interventions

Davenport and colleagues demonstrate that social determinants of health are merely symptoms of deeper power hierarchies, with commodification, discrimination, and devitalization creating barriers that resource provision alone cannot overcome. McKinney's public health framework reinforces this by showing that physical therapy operates too high on the health impact pyramid—focused on individual counseling rather than contextual change—while one in three people globally would benefit from rehabilitation and years lived with disability continue to rise. Together, these papers argue that even the most effective clinical interventions fail at the population level when access is structurally constrained by power differentials.

3. Digital Health as Access Equalizer and Economic Lever

McKinney presents digital health and telehealth not as mere conveniences but as once-in-a-generation catalysts for expanding access through task-shifting, community-based delivery, and new contracting models. The rural Wisconsin example—30% reduction in opioid prescriptions, 21% reduction in non-PT musculoskeletal expenses, 50% reduction in emergency department visits and surgeries—demonstrates that upstream integration of musculoskeletal care produces major cost savings and clinical benefits. This economic case becomes even more compelling when viewed through Davenport's structural lens: digital platforms can bypass some (though not all) power-based access barriers by reducing transportation requirements, time costs, and geographic constraints.

4. Exercise as Biological Psychiatry

The inflammation-dopamine-motivation pathway and barrier biology research establish that aerobic exercise operates through mechanisms entirely distinct from traditional psychiatric medications, reducing systemic inflammation, restoring dopamine transmission in motivational circuits, strengthening blood-brain and gut barriers, increasing microbiome diversity, and enhancing short-chain fatty acid production. Exercise addresses interest-activity symptoms (anhedonia, fatigue, cognitive impairment) that predict poor treatment response to selective serotonin reuptake inhibitors, positioning movement-based interventions as potentially superior first-line treatments for motivational dysfunction. The barrier research extends this by showing exercise protects against stress-induced barrier breakdown, age-related cognitive decline, and mood disorder vulnerability.

5. Movement System Health as Upstream Determinant

Across all five papers, movement emerges not as a downstream outcome but as an upstream determinant of longevity, mental health, barrier integrity, inflammation, and health equity. Generation 100 links movement to mortality reduction; the social power paper positions movement system access as a justice issue shaped by structural hierarchies; the public health framework identifies musculoskeletal disorders as the leading global cause of disability requiring population-level intervention; the motivation paper establishes movement as a biological treatment for psychiatric disease; and the barrier biology research shows physical activity as perhaps the most potent environmental modulator of brain and gut barrier integrity.

6. The Profession's Value Proposition Must Evolve

Davenport argues physical therapists must sometimes challenge their own professional self-interest to advance societal health, while McKinney demonstrates that traditional one-to-one clinic-based models cannot address the scale of global rehabilitation need. Together with the mechanistic evidence showing exercise operates through inflammation, dopamine, barrier biology, and microbiome pathways largely ignored by current medical paradigms, these papers suggest the physical therapy profession's value lies not in defending scope-of-practice boundaries but in becoming the essential architects of population-level movement interventions that address upstream determinants of both musculoskeletal and mental health.

Implications for MSK Care Delivery, Technology, and Strategy

Population Health Integration: The Wisconsin school district results (30% reduction in opioids, 50% reduction in emergency department visits) provide economic justification for embedding musculoskeletal care in primary care, employer settings, and community health systems rather than relegating it to tertiary episodic intervention.

Precision Exercise Prescription: Understanding that exercise reduces depression through inflammation-dopamine-motivation pathways suggests stratifying patients by inflammatory biomarkers and tailoring intensity, volume, and progression specifically to restore motivational circuitry rather than applying generic activity recommendations.

Technology as Equity Tool: Digital platforms should be designed not merely for convenience but explicitly to bypass structural access barriers including transportation requirements, time costs, geographic constraints, and provider availability, with recognition that technology alone cannot overcome power differentials related to digital literacy, device access, and broadband availability.

Reimbursement Model Transformation: The public health framework and structural power analysis both argue that fee-for-service models inherently limit access and perpetuate inequities; value-based arrangements that reward population health outcomes, prevention, and upstream integration align incentives with the evidence showing greatest impact occurs at the base of the health pyramid.

Barrier-Focused Biomarkers: Emerging understanding of blood-brain barrier and gut barrier dysfunction as mechanistic drivers of psychiatric and cognitive disorders suggests future musculoskeletal interventions should track inflammatory markers, microbiome composition, barrier integrity measures, and dopaminergic function alongside traditional physical performance outcomes.

Intensity as Therapeutic Variable: Generation 100's findings that high-intensity interval training showed strongest mortality reduction trends and that control participants self-selected higher intensity when informed challenges risk-averse exercise prescription patterns; protocols should systematically progress intensity as the primary therapeutic variable for both physical and mental health outcomes.

Advocacy as Professional Obligation: The social power framework positions policy advocacy—addressing commodification of services, discriminatory structures, and economic devitalization—as an essential professional competency rather than optional activism, requiring physical therapists to engage at individual, community, and societal levels simultaneously.

Bottom Line

The physical therapy profession stands at an inflection point where traditional clinic-based, one-to-one, tertiary intervention models are demonstrably insufficient to address the scale of global musculoskeletal need, the structural barriers that determine who accesses care, and the mechanistic evidence showing movement as an upstream biological determinant of mental health through inflammation, dopamine, barrier integrity, and microbiome pathways. Value creation in the next decade will come from professionals who architect scalable, digitally-enabled, population-level interventions that operate at the base of the health impact pyramid, explicitly address power-based access barriers, and leverage exercise intensity as a biological treatment for both musculoskeletal and psychiatric disease.