Relationship between skeletal mitochondrial function and digital markers of free-living physical activity in older adults.

This study examined the association between in vivo skeletal mitochondrial function and digital free-living physical activity patterns-a measure that summarizes biological, phenotypic, functional, and environmental effects on mobility. Among 459 participants (mean age 68 years; 55% women) in the Baltimore Longitudinal Study of Aging, mitochondrial function was quantified as skeletal muscle oxidative capacity via post-exercise phosphocreatine recovery rate (τPCr) in the vastus lateralis muscle of the left thigh, using 31P magnetic resonance spectroscopy. Accelerometry was collected using a 7-day, 24-h wrist-worn protocol and summarized into activity amount, intensity, endurance, and accumulation patterning metrics. Linear regression, two-part linear and logistic (bout analyses), and linear mixed effects models (time-of-day analyses) were used to estimate associations between τPCr and each physical activity metric. Interactions by age, sex, and gait speed were tested. After covariate adjustment, higher τPCr (or poorer mitochondrial function) was associated with lower activity counts/day (ß = - 6593.7, SE = 2406.0; p = 0.006) and activity intensity (- 81.5 counts, SE = 12.9; p < 0.001). For activity intensity, the magnitude of association was greater for men and those with slower gait speed (interaction p < 0.02 for both). Conversely, τPCr was not associated with daily active minutes/day (p = 0.15), activity fragmentation (p = 0.13), or endurance at any bout length (p > 0.05 for all). Time-of-day analyses show participants with high τPCr were less active from 6:00 a.m. to 12:00 a.m. than those with low τPCr. Results indicate that poorer skeletal mitochondrial function is primarily associated with lower engagement in high intensity activities. Our findings help define the connection between laboratory-measured mitochondrial function and real-world physical activity behavior.

Differences in Daily Physical Activity by Alzheimer's Risk Markers Among Older Adults.

BACKGROUND: Daily physical activity patterns differ by Alzheimer's disease (AD) status and might signal cognitive risk. It is critical to understand whether patterns are disrupted early in the AD pathological process. Yet, whether established AD risk markers (ß-amyloid [Aß] or apolipoprotein E-ε4 [APOE-ε4]) are associated with differences in objectively measured activity patterns among cognitively unimpaired older adults is unclear. METHODS: Wrist accelerometry, brain Aß (+/-), and APOE-ε4 genotype were collected in 106 (Aß) and 472 (APOE-ε4) participants (mean age 76 [standard deviation{SD}: 8.5) or 75 [SD: 9.2] years, 60% or 58% women) in the Baltimore Longitudinal Study of Aging. Adjusted linear and function-on-scalar regression models examined whether Aß or APOE-ε4 status was cross-sectionally associated with activity patterns (amount, variability, or fragmentation) overall and by time of day, respectively. Differences in activity patterns by combinations of Aß and APOE-ε4 status were descriptively examined (n = 105). RESULTS: There were no differences in any activity pattern by Aß or APOE-ε4 status overall. Aß+ was associated with lower total amount and lower within-day variability of physical activity overnight and early evening, and APOE-ε4 carriers had higher total amount of activity in the evening and lower within-day variability of activity in the morning. Diurnal curves of activity were blunted among those with Aß+ regardless of APOE-ε4 status, but only when including older adults with mild cognitive impairment/dementia. CONCLUSIONS: Aß+ in cognitively unimpaired older adults might manifest as lower amount and variability of daily physical activity, particularly during overnight/evening hours. Future research is needed to examine changes in activity patterns in larger samples and by other AD biomarkers.

Effect of Isocaloric, Time-Restricted Eating on Body Weight in Adults With Obesity : A Randomized Controlled Trial.

BACKGROUND: Time-restricted eating (TRE) lowers body weight in many studies. Whether TRE induces weight loss independent of reductions in calorie intake, as seen in rodent studies, is unknown. OBJECTIVE: To determine the effect of TRE versus a usual eating pattern (UEP) on body weight in the setting of stable caloric intake. DESIGN: Randomized, isocaloric feeding study. (ClinicalTrials.gov: NCT03527368). SETTING: Clinical research unit. PARTICIPANTS: Adults with obesity and prediabetes or diet-controlled diabetes. INTERVENTION: Participants were randomly assigned 1:1 to TRE (10-hour eating window, 80% of calories before 1 p.m.) or UEP (≤16-hour window, ≥50% of calories after 5 p.m.) for 12 weeks. Both groups had the same nutrient content and were isocaloric with total calories determined at baseline. MEASUREMENTS: Primary outcome was change in body weight at 12 weeks. Secondary outcomes were fasting glucose, homeostatic model assessment for insulin resistance (HOMA-IR), glucose area under the curve by oral glucose tolerance test, and glycated albumin. We used linear mixed models to evaluate the effect of interventions on outcomes. RESULTS: All 41 randomly assigned participants (mean age, 59 years; 93% women; 93% Black race; mean BMI, 36 kg/m2) completed the intervention. Baseline weight was 95.6 kg (95% CI, 89.6 to 101.6 kg) in the TRE group and 103.7 kg (CI, 95.3 to 112.0 kg) in the UEP group. At 12 weeks, weight decreased by 2.3 kg (CI, 1.0 to 3.5 kg) in the TRE group and by 2.6 kg (CI, 1.5 to 3.7 kg) in the UEP group (average difference TRE vs. UEP, 0.3 kg [CI, -1.2 to 1.9 kg]). Change in glycemic measures did not differ between groups. LIMITATION: Small, single-site study; baseline differences in weight by group. CONCLUSION: In the setting of isocaloric eating, TRE did not decrease weight or improve glucose homeostasis relative to a UEP, suggesting that any effects of TRE on weight in prior studies may be due to reductions in caloric intake. PRIMARY FUNDING SOURCE: American Heart Association.

Physical Activity Intensity and Risk of Dementia.

INTRODUCTION: Regular participation in aerobic physical activity is associated with a reduced risk of dementia. It is currently unclear whether this association is due to the total volume or intensity of physical activity. METHODS: This prospective cohort study analyzed 386,486 adults from the UK Biobank who were free of dementia and self-reported >0 minutes of moderate-to-vigorous intensity physical activity (MVPA) at baseline (2007-2010). Participants were categorized as performing 0%, >0%-30%, or >30% of their total MVPA in vigorous activity (VPA). Cox proportional hazards regression models were used to examine the associations between categories of VPA and incident dementia while adjusting for sociodemographic and lifestyle factors including total MVPA. Analyses were performed in 2022. RESULTS: Over an average follow-up of 12.0 (1.7) years, there were 5,177 (1.3%) cases of dementia. Compared to the group reporting 0% VPA, the hazard ratios (95% confidence intervals) of dementia for the groups reporting >0%-30% and >30% VPA were 0.73 (0.68-0.78) and 0.81 (0.75-0.87), respectively, in the fully adjusted model. In a joint analysis, reporting some VPA was associated with a reduced risk of dementia regardless of meeting the aerobic physical activity guidelines (HR=0.78 [0.72-0.85]) or not (HR=0.76 [0.60-0.98]), while meeting the aerobic physical activity guidelines alone without VPA was not associated with incident dementia (HR=0.98 [0.90-1.07]), compared to the group that did not meet the guidelines and reported no VPA. CONCLUSIONS: These results suggest that engaging in VPA as part of MVPA is associated with a lower risk of dementia.

Sensory and motor deficits as contributors to early cognitive impairment.

INTRODUCTION: Age-related sensory and motor impairment are associated with risk of dementia. No study has examined the joint associations of multiple sensory and motor measures on prevalence of early cognitive impairment (ECI). METHODS: Six hundred fifty participants in the Baltimore Longitudinal Study of Aging completed sensory and motor function tests. The association between sensory and motor function and ECI was examined using structural equation modeling with three latent factors corresponding to multisensory, fine motor, and gross motor function. RESULTS: The multisensory, fine, and gross motor factors were all correlated (r = 0.74 to 0.81). The odds of ECI were lower for each additional unit improvement in the multisensory (32%), fine motor (30%), and gross motor factors (12%). DISCUSSION: The relationship between sensory and motor impairment and emerging cognitive impairment may guide future intervention studies aimed at preventing and/or treating ECI. HIGHLIGHTS: Sensorimotor function and early cognitive impairment (ECI) prevalence were assessed via structural equation modeling. The degree of fine and gross motor function is associated with indicators of ECI. The degree of multisensory impairment is also associated with indicators of ECI.

Toward a Social Bioethics Through Interpretivism: A Framework for Healthcare Ethics.

Recent global events demonstrate that analytical frameworks to aid professionals in healthcare ethics must consider the pervasive role of social structures in the emergence of bioethical issues. To address this, the authors propose a new sociologically informed approach to healthcare ethics that they term "social bioethics." Their approach is animated by the interpretive social sciences to highlight how social structures operate vis-à-vis the everyday practices and moral reasoning of individuals, a phenomenon known as social discourse. As an exemplar, the authors use social bioethics to reframe common ethical issues in psychiatric services and discuss potential implications. Lastly, the authors discuss how social bioethics illuminates the ways healthcare ethics consultants in both policy and clinical decision-making participate in and shape broader social, political, and economic systems, which then cyclically informs the design and delivery of healthcare.

Shared and Distinct Associations of Manual Dexterity and Gross Motor Function With Brain Atrophy.

BACKGROUND: Poor motor function is associated with brain atrophy and cognitive impairment. Less is known about the relationship between motor domains and brain atrophy and whether associations are affected by cerebrovascular burden and/or physical activity. METHODS: We analyzed data from 726 Baltimore Longitudinal Study of Aging participants (mean age 70.6 ±â€…10.1 years, 56% women, 27% Black), 525 of whom had repeat MRI scans over an average of 5.0 ±â€…2.1 years. Two motor domains, manual dexterity and gross motor, were operationalized as latent variables. Associations between the latent variables and cortical and subcortical brain volumes of interest were examined using latent growth curve modeling, adjusted for demographics, white matter hyperintensities, and physical activity. RESULTS: Both higher manual dexterity and gross motor function were cross-sectionally associated with smaller ventricular volume and greater white matter volumes in the frontal, parietal, and temporal lobes (all p < .05). Manual dexterity was also cross-sectionally associated with parietal gray matter (B = 0.14; 95% CI: 0.05, 0.23), hippocampus (B = 0.10; 95% CI: 0.01, 0.20), postcentral gyrus (B = 0.11; 95% CI: 0.01, 0.20), and occipital white matter (B = 0.10; 95% CI: 0.01, 0.21) volumes, and gross motor function with temporal gray matter volume (B = 0.16; 95% CI: 0.05, 0.26). Longitudinally, both higher manual dexterity and gross motor function were associated with less temporal white matter and occipital gray matter atrophy (all p < .05). Manual dexterity was also associated with a slower rate of ventricular enlargement (B = -0.17; 95% CI: -0.29, -0.05) and less atrophy of occipital white matter (B = 0.39; 95% CI: 0.04, 0.71). CONCLUSIONS: Among cognitively normal middle- and older-aged adults, manual dexterity and gross motor function exhibited shared as well as distinct associations with brain atrophy over time.

Walking energetics and white matter hyperintensities in mid-to-late adulthood.

INTRODUCTION: White matter hyperintensities (WMHs) increase with age and contribute to cognitive and motor function decline. Energy costs for mobility worsen with age, as the energetic cost of walking increases and energetic capacity declines. We examined the cross-sectional associations of multiple measures of walking energetics with WMHs in mid- to late-aged adults. METHODS: A total of 601 cognitively unimpaired adults (mean age 66.9 ± 15.3 years, 54% women) underwent brain magnetic resonance imaging scans and completed standardized slow- and peak-paced walking assessments with metabolic measurement (V̇O2). T1-weighted scans and fluid-attenuated inversion recovery images were used to quantify WMHs. Separate multivariable linear regression models examined associations adjusted for covariates. RESULTS: Lower slow-paced V̇O2 (B = 0.07; P = 0.030), higher peak-paced V̇O2 (B = -0.10; P = 0.007), and lower cost-to-capacity ratio (B = .12; P < 0.0001) were all associated with lower WMH volumes. DISCUSSION: The cost-to-capacity ratio, which describes the percentage of capacity required for ambulation, was the walking energetic measure most strongly associated with WMHs.

Wrist-Worn Accelerometry, Aging, and Gait Speed in the Baltimore Longitudinal Study of Aging.

Wrist-worn accelerometry metrics are not well defined in older adults. Accelerometry data from 720 participants (mean age 70 years, 55% women) were summarized into (a) total activity counts per day, (b) active minutes per day, (c) active bouts per day, and (d) activity fragmentation (the reciprocal of the mean active bout length). Linear regression and mixed-effects models were utilized to estimate associations between age and gait speed with wrist accelerometry. Activity counts per day, daily active minutes per day, and active bouts per day were negatively associated with age among all participants, while positive associations with activity fragmentation were only observed among those ≥65 years. More activity counts, more daily active minutes, and lower activity fragmentation were associated with faster gait speed. There were baseline age interactions with annual changes in total activity counts per day, active minutes per day, and activity fragmentation (Baseline age × Time, p < .01 for all). These results help define and characterize changes in wrist-based physical activity patterns among older adults.

A Rapid Review of "Low-Threshold" Psychiatric Medication Prescribing: Considerations for Street Medicine and Beyond.

OBJECTIVE: No widely accepted clinical guidelines, and scant directly applicable pragmatic research, are available to guide the prescription of psychiatric medications in "low-threshold" outpatient settings, such as street outreach, urgent care, and crisis care, as well as walk-in, shelter, and bridge and transition clinics. Providers frequently prescribe medications in these settings without patients' having firm psychiatric diagnoses and without medical records to guide clinical decision making. Persons who receive medications in these settings often seek help voluntarily and intermittently for mental illness symptoms. However, because of structural and individual factors, such patients may not engage in longitudinal outpatient psychiatric care. The authors reviewed the literature on psychiatric medication prescribing in low-threshold settings and offer clinical considerations for such prescribing. METHODS: The authors conducted a rapid literature review (N=2,215 abstracts), which was augmented with up-to-date clinical prescribing literature, the authors' collective clinical experience, and DSM-5 section II diagnostic criteria to provide considerations for prescribing medications in low-threshold settings. RESULTS: For individuals for whom diagnostic uncertainty is prominent, a symptom-based diagnostic and treatment approach may be best suited to weigh the risks and benefits of medication use in low-threshold settings. Practical considerations for treating patients with clinical presentations of psychosis and trauma, as well as mood, anxiety, and substance use disorders, in low-threshold settings are discussed. CONCLUSIONS: An urgent need exists to invest in pragmatic research and guideline development to delineate best-practice prescribing in low-threshold settings.

Renewed calls for abortion-related research in the post-Roe era.

Nearly 50 years after Roe versus Wade, the United States Supreme Court's decision in Dobbs versus Jackson Women's Health Organization unraveled the constitutional right to abortion, allowing individual states to severely restrict or ban the procedure. In response, leading medical, public health, and community organizations have renewed calls for research to elucidate and address the burgeoning social and medical consequences of new abortion restrictions. Abortion research not only includes studies that establish the safety, quality, and efficacy of evidence-based abortion care protocols, but also encompasses studies on the availability of abortion care, the consequences of being denied an abortion, and the legal and social burdens surrounding abortion. The urgency of these calls for new evidence underscores the importance of ensuring that research in this area is conducted in an ethical and respectful manner, cognizant of the social, political, and structural conditions that shape reproductive health inequities and impact each stage of research-from protocol design to dissemination of findings. Research ethics relates to the moral principles undergirding the design and execution of research projects, and concerns itself with the technicalities of ethical questions related to the research process, such as informed consent, power relations, and confidentiality. Critical insights and reflections from reproductive justice, community engagement, and applied ethics frameworks have bolstered existing research ethics scholarship and discourse by underscoring the importance of meaningful engagement with community stakeholders-bringing attention to overlapping structures of oppression, including racism, sexism, and ways that these structures are perpetuated in the research process.

Validation of accelerometer placement to capture energy expenditure using doubly labeled water.

This study compared accelerometer-measured physical activity by body placement to daily total energy expenditure (TEE) and activity energy expenditure (AEE) measured using doubly labeled water (DLW). Forty-nine adult participants wore accelerometers placed on the nondominant wrist, dominant wrist, and chest while also undergoing DLW assessments. In adjusted models, wrist-measured physical activity (p < 0.05), but not chest-measured physical activity (p > 0.05), was associated with TEE and AEE and explained a significant amount of variance that was not explained by age, sex, height, or body composition (R2 change = 0.04-0.08; all p < 0.05). Accelerometer placement location is an important consideration when using accelerometry to provide information about energy expenditure.

Cardiorespiratory fitness and cognition in persons at risk for Alzheimer's disease.

Introduction: This study examined the relationship between cardiorespiratory fitness (CRF) and longitudinal cognitive functioning in a cohort enriched with risk factors for Alzheimer's disease (AD). Methods: A total of 155 enrollees in the Wisconsin Registry for Alzheimer's Prevention completed repeat comprehensive neuropsychological evaluations that assessed six cognitive domains. Peak oxygen consumption (VO2peak) was the primary measure of CRF. Random effects regression was used to investigate the effect of CRF on cognitive trajectories. Results: Higher CRF was associated with slower decline in the cognitive domains of verbal learning and memory (P < .01) and visual learning and memory (P < .042). Secondary analyses indicated that these effects were stronger among men than women, and for noncarriers of the apolipoprotein E ε4 allele. Discussion: Higher CRF was associated with a slower rate of the decline in episodic memory that occurs as a natural consequence of aging in a cohort enriched with risk factors for AD.

Pain, but not Physical Activity, is Associated with Gray Matter Volume Differences in Gulf War Veterans with Chronic Pain.

Chronic musculoskeletal pain (CMP) is a significant burden for Persian Gulf War Veterans (GWV), yet the causes are poorly understood. Brain structure abnormalities are observed in GWV, however relationships with modifiable lifestyle factors such as physical activity (PA) are unknown. We evaluated gray matter volumes and associations with symptoms, PA, and sedentary time in GWV with and without CMP. Ninety-eight GWV (10 females) with CMP and 56 GWV (7 females) controls completed T1 weighted magnetic resonance imaging, pain and fatigue symptom questionnaires, and PA measurement via actigraphy. Regional gray matter volumes were analyzed using voxel-based morphometry and were compared across groups using analysis of covariance. Separate multiple linear regression models were used to test associations between PA intensities, sedentary time, symptoms, and gray matter volumes. Family-wise cluster error rates were used to control for multiple comparisons (α=0.05). GWV with CMP reported greater pain and fatigue symptoms, worse mood, and engaged in less moderate-to-vigorous PA and more sedentary time than healthy GWV (all p<0.05). GWV with CMP had smaller gray matter volumes in the bilateral insula and larger volumes in the frontal pole (p<0.05adjusted). Gray matter volumes in the left insula were associated with pain symptoms (rpartial=0.26, -0.29; p<0.05adjusted). No significant associations were observed for either PA or sedentary time (p>0.05adjusted). GWV with CMP had smaller gray matter volumes within a critical brain region of the descending pain processing network and larger volumes within brain regions associated with pain sensation and affective processing which may reflect pain chronification.Significance Statement:The pathophysiology of chronic pain in Gulf War Veterans is understudied and not well understood. In a large sample of Gulf War Veterans, we report Veterans with chronic musculoskeletal pain have smaller gray matter volumes in brain regions associated with pain regulation and larger volumes in regions associated with pain sensitivity compared to otherwise healthy Gulf War Veterans. Gray matter volumes in regions of pain regulation were significantly associated with pain symptoms and encompassed the observed group brain volume differences. These results are suggestive of deficient pain modulation that may contribute to pain chronification.

Impact of Time in Motion on Blood Pressure Regulation Among Patients with Metabolic Syndrome.

PURPOSE OF REVIEW: This review assessed recent evidence on the association between objectively measured physical activity from wearable accelerometers and blood pressure (BP) in participants with metabolic syndrome (MetS). RECENT FINDINGS: Results directly related to BP were mixed, with some studies showing positive associations and others showing null results. Importantly, several studies noted that participants with MetS demonstrated greater improvements in components of MetS after engaging in higher amounts of daily physical activity. Although this suggests greater volume of physical activity may be a means to partially mitigate hypertension in those with MetS, it remains unclear whether physical activity or inactivity (i.e., sedentary behavior) is more strongly associated with MetS. Although there may be benefit to greater volumes of daily PA among hypertensive patients with MetS, more research is needed to quantify and define the amount of daily activity needed to improve health and refine clinical recommendations. Moreover, although the evidence for improving components of MetS through engaging in physical activity is high, the amount and type(s) of physical activity needed to achieve these benefits is unclear.

Daily Physical Activity Patterns as a Window on Cognitive Diagnosis in the Baltimore Longitudinal Study of Aging (BLSA).

BACKGROUND: Gradual disengagement from daily physical activity (PA) could signal present or emerging mild cognitive impairment (MCI) or Alzheimer's disease (AD). OBJECTIVE: This study examined whether accelerometry-derived patterns of everyday movement differ by cognitive diagnosis in participants of the Baltimore Longitudinal Study of Aging (BLSA). METHODS: Activity patterns, overall and by time-of-day, were cross-sectionally compared between participants with adjudicated normal cognition (n = 549) and MCI/AD diagnoses (n = 36; 5 participants [14%] living with AD) using covariate-adjusted regression models. RESULTS: Compared to those with normal cognition, those with MCI/AD had 2.1% higher activity fragmentation (SE = 1.0%, p = 0.036) but similar mean total activity counts/day (p = 0.075) and minutes/day spent active (p = 0.174). Time-of-day analyses show MCI/AD participants had lower activity counts and minutes spent active during waking hours (6:00 am-5:59 pm; p < 0.01 for all). Also, they had lower activity fragmentation from 12:00-5:59 am (p < 0.001), but higher fragmentation from 12:00-5:59 pm (p = 0.026). CONCLUSION: Differences in the timing and patterns of physical activity throughout the day linked to MCI/AD diagnoses warrant further investigation into potential clinical utility.

Cardiopulmonary, metabolic, and perceptual responses during exercise in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): A Multi-site Clinical Assessment of ME/CFS (MCAM) sub-study.

BACKGROUND: Cardiopulmonary exercise testing has demonstrated clinical utility in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). However, to what extent exercise responses are independent of, or confounded by, aerobic fitness remains unclear. PURPOSE: To characterize and compare exercise responses in ME/CFS and controls with and without matching for aerobic fitness. METHODS: As part of the Multi-site Clinical Assessment of ME/CFS (MCAM) study, 403 participants (n = 214 ME/CFS; n = 189 controls), across six ME/CFS clinics, completed ramped cycle ergometry to volitional exhaustion. Metabolic, heart rate (HR), and ratings of perceived exertion (RPE) were measured. Ventilatory equivalent ([Formula: see text], [Formula: see text]), metrics of ventilatory efficiency, and chronotropic incompetence (CI) were calculated. Exercise variables were compared using Hedges' g effect size with 95% confidence intervals. Differences in cardiopulmonary and perceptual features during exercise were analyzed using linear mixed effects models with repeated measures for relative exercise intensity (20-100% peak [Formula: see text]). Subgroup analyses were conducted for 198 participants (99 ME/CFS; 99 controls) matched for age (±5 years) and peak [Formula: see text] (~1 ml/kg/min-1). RESULTS: Ninety percent of tests (n = 194 ME/CFS, n = 169 controls) met standard criteria for peak effort. ME/CFS responses during exercise (20-100% peak [Formula: see text]) were significantly lower for ventilation, breathing frequency, HR, measures of efficiency, and CI and significantly higher for [Formula: see text], [Formula: see text] and RPE (p<0.05adjusted). For the fitness-matched subgroup, differences remained for breathing frequency, [Formula: see text], [Formula: see text], and RPE (p<0.05adjusted), and higher tidal volumes were identified for ME/CFS (p<0.05adjusted). Exercise responses at the gas exchange threshold, peak, and for measures of ventilatory efficiency (e.g., [Formula: see text]) were generally reflective of those seen throughout exercise (i.e., 20-100%). CONCLUSION: Compared to fitness-matched controls, cardiopulmonary responses to exercise in ME/CFS are characterized by inefficient exercise ventilation and augmented perception of effort. These data highlight the importance of distinguishing confounding fitness effects to identify responses that may be more specifically associated with ME/CFS.

Energetic Cost of Walking and Brain Atrophy in Mid-to-Late Life.

BACKGROUND: Higher energetic costs for mobility are associated with declining gait speed, and slow gait is linked to cognitive decline and Alzheimer's disease. However, the physiological underpinnings of gait and brain health have not been well explored. We examined the associations of the energetic cost of walking with brain volume in cognitively unimpaired adults from the Baltimore Longitudinal Study of Aging. METHODS: We used brain magnetic resonance imaging (MRI) data from 850 participants (mean baseline age 66.3 ± 14.5 years), of whom 451 had longitudinal MRI data (2.8 ± 1.0 MRI scans over 4.0 ± 2.0 years). The energetic cost of walking was assessed as the average energy expended (V̇O2) during 2.5 minutes of customary-paced overground walking. Multivariable linear mixed-effects models examined the associations between baseline energetic cost of walking and regional brain volumes adjusting for covariates. RESULTS: At baseline, higher energetic cost of walking was cross-sectionally associated with lower gray and white matter volumes within the frontal, parietal, and temporal lobes, as well as hippocampal, total brain, and larger ventricular volumes (all false-discovery rate [FDR] p < .05). A baseline energetic cost of walking × time interaction demonstrated that participants with higher energetic cost of walking had faster annual decline in hippocampal volume (FDR p = .02) and accelerated annual increase in ventricular volumes (FDR p = .02). CONCLUSIONS: The energetic cost of walking is associated with gray and white matter volumes and subsequent hippocampal atrophy and ventricular enlargement. Collectively, these data suggest the energetic cost of walking may be an early marker of neurodegeneration that contributes to the gait brain connection.

Long-term television viewing patterns and gray matter brain volume in midlife.

The purpose of this study was to investigate whether long-term television viewing patterns, a common sedentary behavior, in early to mid-adulthood is associated with gray matter brain volume in midlife and if this is independent of physical activity. We evaluated 599 participants (51% female, 44% black, mean age 30.3 ± 3.5 at baseline and 50.2 ± 3.5 years at follow-up and MRI) from the prospective Coronary Artery Risk Development in Young Adults (CARDIA) study. We assessed television patterns with repeated interviewer-administered questionnaire spanning 20 years. Structural MRI (3T) measures of frontal cortex, entorhinal cortex, hippocampal, and total gray matter volumes were assessed at midlife. Over the 20 years, participants reported viewing an average of 2.5 ± 1.7 h of television per day (range: 0-10 h). After multivariable adjustment, greater television viewing was negatively associated with gray matter volume in the frontal (ß = - 0.77; p = 0.01) and entorhinal cortex (ß = - 23.83; p = 0.05) as well as total gray matter (ß = - 2.09; p = 0.003) but not hippocampus. These results remained unchanged after additional adjustment for physical activity. For each one standard deviation increase in television viewing, the difference in gray matter volume z-score was approximately 0.06 less for each of the three regions (p < 0.05). Among middle-aged adults, greater television viewing in early to mid-adulthood was associated with lower gray matter volume. Sedentariness or other facets of television viewing may be important for brain aging even in middle age.

Five-year changes in objectively measured cardiorespiratory fitness, physical activity, and sedentary time in mid-to-late adulthood.

This study examined 5-year changes in cardiorespiratory fitness, physical activity, and sedentary time in mid-to-late aged adults. Fifty-seven participants completed baseline and follow-up treadmill exercise tests and physical activity monitoring. We observed a 14% decline in fitness (p < 0.001), 12% decrease in physical activity (p = 0.010), and non-significant increase in sedentary time (p = 0.196). Age was negatively associated with 5-year change in physical activity (r = -0.31; p = 0.02) and this decline was strongest among APOE ε4 carriers (g = -0.75). Novelty: Cardiorespiratory fitness and physical activity significantly declined from mid-to-late adulthood, these findings were most pronounced among older adults and those with genetic risk for Alzheimer's disease.