Testing the structural disconnection hypothesis: Myelin content correlates with memory in healthy aging.

INTRODUCTION: The "structural disconnection" hypothesis of cognitive aging suggests that deterioration of white matter (WM), especially myelin, results in cognitive decline, yet in vivo evidence is inconclusive. METHODS: We examined age differences in WM microstructure using Myelin Water Imaging and Diffusion Tensor Imaging in 141 healthy participants (age 20-79). We used the Virginia Cognitive Aging Project and the NIH Toolbox® to generate composites for memory, processing speed, and executive function. RESULTS: Voxel-wise analyses showed that lower myelin water fraction (MWF), predominantly in prefrontal WM, genu of the corpus callosum, and posterior limb of the internal capsule was associated with reduced memory performance after controlling for age, sex, and education. In structural equation modeling, MWF in the prefrontal white matter and genu of the corpus callosum significantly mediated the effect of age on memory, whereas fractional anisotropy (FA) did not. DISCUSSION: Our findings support the disconnection hypothesis, showing that myelin decline contributes to age-related memory loss and opens avenues for interventions targeting myelin health.

Physical activity-related individual differences in functional human connectome are linked to fluid intelligence in older adults.

The study examined resting state functional connectivity (rs-FC) associated with moderate-to-vigorous physical activity (MV-PA), sedentary time (ST), TV viewing, computer use, and their relationship to cognitive performance in older adults. We used pre-intervention data from 119 participants from the Fit & Active Seniors trial. Multivariate pattern analysis revealed two seeds associated with MV-PA: right superior frontal gyrus (SFG; spanning frontoparietal [FPN] and ventral attention networks [VAN]) and right precentral (PrG) and postcentral gyri (PoG) of the somatosensory network (SN). A positive correlation between the right SFG seed and a cluster spanning default mode (DMN), dorsal attention (DAN), FPN, and visual networks (VIS) was linked to higher fluid intelligence, as was FC between the right PrG/PoG seed and a cluster in VIS. No significant rs-FC patterns associated with ST, TV viewing, or computer use were found. Our findings suggest that greater functional integration within networks implementing top-down control and within those supporting visuospatial abilities, paired with segregation between networks critical and those not critical to top-down control, may help promote cognitive reserve in more physically active seniors.

Corrigendum: Adaptive yoga versus low-impact exercise for adults with chronic acquired brain injury: a pilot randomized control trial protocol.

[This corrects the article DOI: 10.3389/fnhum.2023.1291094.].

Correlates of axonal content in healthy adult span: Age, sex, myelin, and metabolic health.

As the emerging treatments that target grey matter pathology in Alzheimer's Disease have limited effectiveness, there is a critical need to identify new neural targets for treatments. White matter's (WM) metabolic vulnerability makes it a promising candidate for new interventions. This study examined the age and sex differences in estimates of axonal content, as well the associations of with highly prevalent modifiable health risk factors such as metabolic syndrome and adiposity. We estimated intra-axonal volume fraction (ICVF) using the Neurite Orientation Dispersion and Density Imaging (NODDI) in a sample of 89 cognitively and neurologically healthy adults (20-79 years). We showed that ICVF correlated positively with age and estimates of myelin content. The ICVF was also lower in women than men, across all ages, which difference was accounted for by intracranial volume. Finally, we found no association of metabolic risk or adiposity scores with the current estimates of ICVF. In addition, the previously observed adiposity-myelin associations (Burzynska et al., 2023) were independent of ICVF. Although our findings confirm the vulnerability of axons to aging, they suggest that metabolic dysfunction may selectively affect myelin content, at least in cognitively and neurologically healthy adults with low metabolic risk, and when using the specific MRI techniques. Future studies need to revisit our findings using larger samples and different MRI approaches, and identify modifiable factors that accelerate axonal deterioration as well as mechanisms linking peripheral metabolism with the health of myelin.

Elevated Serum Levels of Soluble Transferrin Receptor Are Associated with an Increased Risk of Cardiovascular, Pulmonary, and Hematological Manifestations and a Decreased Risk of Neuropsychiatric Manifestations in Systemic Lupus Erythematosus Patients.

The aim of this study was to analyze the relationship between the serum levels of soluble transferrin receptor (sTfR) and interleukin 4 (IL-4), and the disease activity and organ manifestations in SLE patients. We studied 200 SLE patients and 50 controls. We analyzed disease activity, organ involvement, serum sTfR, IL-4 and interleukin-6 (IL-6) levels, and antinuclear and antiphospholipid antibody profiles. The median serum levels of sTfR (p > 0.000001) and IL-4 (p < 0.00001) were higher in the study group than in the controls. SLE patients, compared to the controls, had significantly lower HGB levels (p < 0.0001), a lower iron concentration (p = 0.008), a lower value of total iron-binding capacity (TIBC) (p = 0.03), and lower counts of RBC (p = 0.004), HCT (p = 0.0004), PLT (p = 0.04), neutrophil (p = 0.04), and lymphocyte (p < 0.0001). Serum sTfR levels were negatively correlated with lymphocyte (p = 0.0005), HGB (p = 0.0001) and HCT (p = 0.008), and positively correlated with IL-4 (p = 0.01). Elevated serum sTfR > 2.14 mg/dL was associated with an increased risk of myocardial infarction (OR: 10.6 95 CI 2.71-464.78; p = 0.001), ischemic heart disease (OR: 3.25 95 CI 1.02-10.40; p = 0.04), lung manifestations (OR: 4.48 95 CI 1.44-13.94; p = 0.01), and hematological manifestations (OR: 2.07 95 CI 1.13-3.79; p = 0.01), and with a reduced risk of neuropsychiatric manifestations (OR: 0.42 95 CI 0.22-0.80; p = 0.008). Serum IL-4 was negatively correlated with CRP (p = 0.003), and elevated serum IL-4 levels > 0.17 mg/L were associated with a reduced risk of mucocutaneous manifestations (OR: 0.48 95 CI 0.26-0.90; p = 0.02). In SLE patients, elevated serum levels of sTfR were associated with an increased risk of cardiovascular, pulmonary, and hematological manifestations, and with a decreased risk of neuropsychiatric manifestations. In contrast, elevated serum IL-4 levels were associated with a decreased risk of mucocutaneous manifestations.

Biopsychosocial Variables in Male Schizophrenic Patients: A Comprehensive Comparison with Healthy Controls.

OBJECTIVE: this study aims to comprehensively compare neuropsychological, psychopathological, anthropometric, biochemical, pharmacological, and lifestyle variables between 27 male schizophrenic patients (SZ group) and 30 age- and sex-matched healthy male controls (HC group). METHODS: participants underwent a battery of neuropsychological tests including the Trail Making Test (TMT), Stroop Color-Word Interference Test, and Verbal Fluency Test. Psychopathological symptoms in the SZ group were evaluated using the Positive and Negative Syndrome Scale (PANSS). Anthropometric measurements such as body weight, height, BMI, and waist circumference were taken. Biochemical markers measured included fasting glucose, total cholesterol, triglycerides, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and fasting insulin. Lifestyle factors were assessed through a questionnaire for the study of views and eating habits of people aged 16 to 65. RESULTS: the HC group outperformed the SZ group in the TMT_A test and the Stroop test, but no significant differences were observed in the TMT_B test or in phonemic fluency tests. No correlation was found between age and PANSS scores within the SZ group. Anthropometrically, the SZ group had higher body weight, waist circumference, and BMI, with no difference in height. Biochemically, the HC group had higher HDL cholesterol levels but lower insulin and insulin resistance indices. Pharmacological assessment showed a more significant impact on body weight among SZ patients taking second-generation antipsychotics. Lifestyle factors such as diet and screen time were comparable between groups, but the SZ group reported longer sleep duration and lower leisure time activity. CONCLUSIONS: our study highlights distinct neuropsychological, pharmacological, anthropometric, and biochemical differences between male schizophrenic patients and healthy controls. The results underscore the complexity of schizophrenia and point toward the need for a multi-faceted approach to its management and understanding.

Increased Serum Interleukin 10 Levels Are Associated with Increased Disease Activity and Increased Risk of Anti-SS-A/Ro Antibody Positivity in Patients with Systemic Lupus Erythematosus.

Interleukin 10 (IL-10) plays a role in inflammation and cell-type responses. The anti-SS-A/Ro antibody contributes to leucopenia, and cutaneous and neonatal lupus. OBJECTIVES: To evaluate the association between serum IL-10 levels and autoantibodies, disease activity and organ involvement in systemic lupus erythematosus (SLE) patients. PATIENTS AND METHODS: We studied 200 SLE patients and 50 controls. We analyzed organ involvement, disease activity, serum IL-10 and interleukin-6 (IL-6) levels, and antinuclear and antiphospholipid antibody profiles. RESULTS: Serum IL-10 and IL-6 levels were higher in SLE patients than in controls (all p < 0.00001). Serum IL-10 levels were positively correlated with IL-6 (p < 0.00001), CRP (p < 0.00001), fibrinogen (p = 0.003), and ESR (p < 0.00001), and negatively correlated with hemoglobin (p = 0.0004) and lymphocytes (p = 0.01). Serum IL-6 levels were positively correlated with CRP (p < 0.00001), fibrinogen (p = 0.001), and ESR (p < 0.00001); and negatively correlated with hemoglobin (p = 0.008) and lymphocytes (p = 0.03). Elevated serum IL-10 levels were associated with an increased risk of anti-SS-A/Ro antibody positivity (p = 0.03). Elevated serum IL-6 levels were associated with an increased risk of heart (p = 0.007) and lung (p = 0.04) involvement. CONCLUSIONS: In SLE patients, increased serum IL-10 levels were associated with increased disease activity and risk of anti-SS-A/Ro antibody positivity.

Symmetric data-driven fusion of diffusion tensor MRI: Age differences in white matter.

In the past 20 years, white matter (WM) microstructure has been studied predominantly using diffusion tensor imaging (DTI). Decreases in fractional anisotropy (FA) and increases in mean (MD) and radial diffusivity (RD) have been consistently reported in healthy aging and neurodegenerative diseases. To date, DTI parameters have been studied individually (e.g., only FA) and separately (i.e., without using the joint information across them). This approach gives limited insights into WM pathology, increases the number of multiple comparisons, and yields inconsistent correlations with cognition. To take full advantage of the information in a DTI dataset, we present the first application of symmetric fusion to study healthy aging WM. This data-driven approach allows simultaneous examination of age differences in all four DTI parameters. We used multiset canonical correlation analysis with joint independent component analysis (mCCA + jICA) in cognitively healthy adults (age 20-33, n = 51 and age 60-79, n = 170). Four-way mCCA + jICA yielded one high-stability modality-shared component with co-variant patterns of age differences in RD and AD in the corpus callosum, internal capsule, and prefrontal WM. The mixing coefficients (or loading parameters) showed correlations with processing speed and fluid abilities that were not detected by unimodal analyses. In sum, mCCA + jICA allows data-driven identification of cognitively relevant multimodal components within the WM. The presented method should be further extended to clinical samples and other MR techniques (e.g., myelin water imaging) to test the potential of mCCA+jICA to discriminate between different WM disease etiologies and improve the diagnostic classification of WM diseases.

Metabolic syndrome and adiposity: Risk factors for decreased myelin in cognitively healthy adults.

Metabolic syndrome (MetS) is a cluster of conditions that affects ∼25% of the global population, including excess adiposity, hyperglycemia, dyslipidemia, and elevated blood pressure. MetS is one of major risk factors not only for chronic diseases, but also for dementia and cognitive dysfunction, although the underlying mechanisms remain poorly understood. White matter is of particular interest in the context of MetS due to the metabolic vulnerability of myelin maintenance, and the accumulating evidence for the importance of the white matter in the pathophysiology of dementia. Therefore, we investigated the associations of MetS risk score and adiposity (combined body mass index and waist circumference) with myelin water fraction measured with myelin water imaging. In 90 cognitively and neurologically healthy adults (20-79 years), we found that both high MetS risk score and adiposity were correlated with lower myelin water fraction in late-myelinating prefrontal and associative fibers, controlling for age, sex, race, ethnicity, education and income. Our findings call for randomized clinical trials to establish causality between MetS, adiposity, and myelin content, and to explore the potential of weight loss and visceral adiposity reduction as means to support maintenance of myelin integrity throughout adulthood, which could open new avenues for prevention or treatment of cognitive decline and dementia.

Brain Structure and Function Predict Adherence to an Exercise Intervention in Older Adults.

INTRODUCTION: Individual differences in brain structure and function in older adults are potential proxies of brain reserve or maintenance and may provide mechanistic predictions of adherence to exercise. We hypothesized that multimodal neuroimaging features would predict adherence to a 6-month randomized controlled trial of exercise in 131 older adults (age, 65.79 ± 4.65 yr, 63% female), alone and in combination with psychosocial, cognitive, and health measures. METHODS: Regularized elastic net regression within a nested cross-validation framework was applied to predict adherence to the intervention in three separate models (brain structure and function only; psychosocial, health, and demographic data only; and a multimodal model). RESULTS: Higher cortical thickness in somatosensory and inferior frontal regions and less surface area in primary visual and inferior frontal regions predicted adherence. Higher nodal functional connectivity (degree count) in default, frontoparietal, and attentional networks and less nodal strength in primary visual and temporoparietal networks predicted exercise adherence ( r = 0.24, P = 0.004). Survey and clinical measures of gait and walking self-efficacy, biological sex, and perceived stress also predicted adherence ( r = 0.17, P = 0.056); however, this prediction was not significant when tested against a null test statistic. A combined multimodal model achieved the highest predictive strength ( r = 0.28, P = 0.001). CONCLUSIONS: Our results suggest that there is a substantial utility of using brain-based measures in future research into precision and individualized exercise interventions older adults.