Brendan L. McNeish

Anti-myelin-associated glycoprotein (MAG) neuropathy is a rare autoimmune neuropathy that preferentially affects the myelin of distal fibers. This distal demyelination and secondary axon loss lead to its characteristic clinical features of distal sensory loss and weakness, upper limb tremor, and ataxia, leading to significant disability for the patient. Diagnosis is predicated on its distinct electrodiagnostic and serological profile of distally accentuated demyelination and high IgM anti-MAG antibody titers. Accurate diagnosis of anti-MAG neuropathy is critical, as standard CIDP therapies do not work, but some novel treatments like Bruton tyrosine kinase inhibitors may prove effective. Currently, rituximab is the most frequently used treatment, despite current evidence showing benefit in only a subset of patients. This review highlights the value of gait analysis in the clinical and research assessment of anti-MAG neuropathy, using existing quality of life-based data. The unique pathophysiology and clinical features of anti-MAG neuropathy create specific rehabilitation challenges, making awareness of this disorder critical for electromyographers and those treating neuropathies in all settings.

Introduction: Cancer is associated with accelerated aging, including changes in muscle composition and cognition. However, the relationship between myosteatosis and cognitive function has not been investigated in older cancer survivors. This study evaluated the association between myosteatosis and cognitive function in this population. Methods: The sample included 75 cancer survivors (age 76–85; 65% men; 31% Black; 41% prostate cancer; 21% breast cancer) from the Health ABC study who developed cancer within the first five years, completed CT imaging at Year 6, and cognitive testing at Year 10. Thigh intermuscular fat area (myosteatosis) was measured by CT at Year 6. Cognitive function was assessed using the Digit Symbol Substitution Test (DSST) and Modified Mini-Mental Status Exam (3MS) at Years 5 and 10. Multivariable models adjusted for demographics, education, cognitive function, and thigh muscle area at Year 5. Sensitivity analyses adjusted for leg strength, race, dementia risk factors, BMI, abdominal visceral fat, and thigh subcutaneous fat. LASSO regression identified key predictors of DSST and 3MS scores. Results: Greater thigh myosteatosis at Year 6 was associated with lower DSST (B = − 0.212, p < 0.05) and 3MS (B = − 0.145, p < 0.05) scores at Year 10. Associations remained significant after adjustment for strength, dementia risk, and adiposity. LASSO identified race, education, Year 5 cognition, and myosteatosis as key predictors for DSST as well as thigh muscle area and physical activity for 3MS. Discussion: Thigh myosteatosis is independently associated with lower cognitive performance in older cancer survivors and may represent a rehabilitation target to improve cognitive outcomes.

Cognitive impairment and dementia in older adults represent significant global health challenges. Although the bidirectional relationship between physical function and brain health is well established, the mechanistic drivers of this link remain poorly understood. Muscle function and quality are central to physical function, and muscle’s secretome is increasingly recognized for its systemic health effects—supporting the potential for muscle-to-brain crosstalk. This concept was explored at the 3rd International Research Symposium on Brain Health, jointly hosted by Vancouver Coastal Health and the University of British Columbia. We present the findings of this symposium, which reviewed the current state of the literature on muscle-to-brain crosstalk from multiple perspectives, spanning population studies to preclinical models. A key focus was the muscle secretome, particularly myokines and extracellular vesicles, as potential messengers influencing brain health. The symposium also identified critical takeaways and proposed next steps to further elucidate the underlying mechanisms of muscle-to-brain crosstalk and explore how these pathways might be harnessed through exercise or pharmacologic interventions to promote brain health in older adults.

Background: Prior research linking myosteatosis with cognition in older adults has been conducted in relatively homogenous populations with narrow age ranges. We evaluated if abdominal myosteatosis was associated with processing speed in a multiethnic cohort of middle aged and older adults. Methods: The analytical sample included 1,268 adults (46-86 years old, mean 63±9 years, 53% female of 41% White, 20% Black, 14% Chinese, and 25% Hispanic), a subset from the Multi-Ethnic Study of Atherosclerosis (MESA). Bivariate analyses were performed between abdominal computed tomography derived muscle densities (a myosteatosis measure) at year 3 with Digit Symbol Coding (DSC) with cytokines. Multivariable models were first adjusted for demographics, education, and general cognition, and further adjusted for other known predictors of dementia: APOE -4, physical activity, diabetes, cholesterol, smoking, and blood pressure. We further assessed whether central adiposity, general adiposity, and cytokines modified this association. We tested interactions by ethnicity, sex, and age. Results: Rectus abdominis myosteatosis was significantly associated with worse DSC (B= −0.247, 95% CI: 0.098,0.396, p=0.001) independent of demographics, education, general cognition, and dementia risk factors. Adjustment for central adiposity, and cytokines did not attenuate the associations. Tests for interactions by ethnicity, sex, and age were not statistically significant. Conclusions: Rectus abdominis myosteatosis is associated with worse processing speed in this middle and older aged multiethnic population of men and women, independent of other known predictors of cognition. Longitudinal studies should assess the interplay of myosteatosis with other markers of adiposity, inflammation, and circulating mediators and their combined impact on processing speed. Highlights: Abdominal myosteatosis correlated with lower cognitive processing speed in older adults. Myosteatosis links muscle density to cognitive function beyond dementia risk factors. Pro-inflammatory cytokines do not mediate the muscle-cognition association. Ethnicity, sex, and adiposity measures do not modify myosteatosis-cognition links. Abdominal CT scans could serve as diagnostic tools for cognitive health insights

Background: Myostatin, a cytokine produced by skeletal muscle, may influence Alzheimer’s disease (AD) pathogenesis, but sparse evidence exists in humans. We assessed the association between circulating levels of myostatin at Year 1 and plasma levels of β-amyloid 42/40 at Year 2, a marker of AD pathology, in a biracial cohort of older adults. Methods: We studied 403 community-dwelling older adults enrolled in the Health, Aging and Body Composition Study from Memphis, Tennessee, and Pittsburgh, PA. Mean age was 73.8 ± 3 years; 54% were female; and 52% were Black. Serum myostatin levels were measured at Year 1, plasma β-amyloid 42/40 levels in Year 2 (higher ratio indicating lower amyloid load). Multivariable linear regression analyses tested the association of serum myostatin with plasma levels of β-amyloid 42/40 adjusted for computed-tomography-derived thigh muscle cross-sectional area, demographics, APOe4 allele, and risk factors for dementia. We tested for 2-way.interactions between myostatin and race or sex; results were stratified by race and sex. Results: In multivariable models, myostatin was positively associated with plasma levels of β-amyloid 42/40 (standardized regression coefficient: 0.145, p = .004). Results were significant for white men and women (0.279, p = .009, and 0.221, p = .035, respectively) but not for Black men or women; interactions by race and gender were not statistically significant. Conclusions: Higher serum myostatin was associated with lower amyloid burden, independently of APOe4 alleles, muscle area and other established risk factors for dementia. The role of myostatin in AD pathogenesis and the influence of race should be further investigated.