Role of Cardiovascular Risk Factors on the Association Between Physical Activity and Brain Integrity Markers in Older Adults.

BACKGROUND AND OBJECTIVES: Physical activity has been associated with a decreased risk for dementia, but the mechanisms underlying this association remain to be determined. Our objective was to assess whether cardiovascular risk factors mediate the association between physical activity and brain integrity markers in older adults. METHODS: At baseline, participants from the Age-Well study completed a physical activity questionnaire and underwent cardiovascular risk factors collection (systolic blood pressure, body mass index [BMI], current smoker status, and high-density lipoprotein cholesterol, total cholesterol, and insulin levels) and multimodal neuroimaging (structural MRI, diffusion MRI, FDG-PET, and florbetapir PET). Multiple regressions were conducted to assess the association among physical activity, cardiovascular risk factors, and neuroimaging. Mediation analyses were performed to test whether cardiovascular risk factors mediated the associations between physical activity and neuroimaging. RESULTS: A total of 134 cognitively unimpaired older adults (≥65 years) were included. Higher physical activity was associated with higher gray matter (GM) volume (ß = 0.174, p = 0.030) and cerebral glucose metabolism (ß = 0.247, p = 0.019) but not with amyloid deposition or white matter integrity. Higher physical activity was associated with lower insulin level and BMI but not with the other cardiovascular risk factors. Lower insulin level and BMI were related to higher GM volume but not to cerebral glucose metabolism. When controlling for insulin level and BMI, the association between physical activity and cerebral glucose metabolism remained unchanged, while the association with GM volume was lost. When insulin level and BMI were entered in the same model, only BMI remained a significant predictor of GM volume. Mediation analyses confirmed that insulin level and BMI mediated the association between physical activity and GM volume. Analyses were replicated within Alzheimer disease-sensitive regions and results remained overall similar. DISCUSSION: The association between physical activity and GM volume is mediated by changes in insulin level and BMI. In contrast, the association with cerebral glucose metabolism seems to be independent from cardiovascular risk factors. Older adults engaging in physical activity experience cardiovascular benefits through the maintenance of a lower BMI and insulin level, resulting in greater structural brain integrity. This study has implications for understanding how physical activity affects brain health and may help in developing strategies to prevent or delay age-related decline. TRIAL REGISTRATION INFORMATION: EudraCT: 2016-002,441-36; IDRCB: 2016-A01767-44; ClinicalTrials.gov Identifier: NCT02977819.

Optoelectronic Study of Gait Kinematics in Sagittal Spinopelvic Imbalance.

OBJECTIVE: Degenerative processes induce loss of lumbar lordosis and anterior sagittal imbalance (ASI). Optoelectronic study provides kinematic analysis of movement and can also detect ASI. The aim of the present study was to assess gait kinematic modifications induced by ASI. METHODS: Thirty-five healthy male volunteers were subjected to reversible ASI induced by wearing a kyphotic thermoformed thoracolumbar corset. The deformation was assessed by C7 tilt on EOS (EOS Imaging, Paris, France) full-spine views. Ten optoelectronic gait recordings were made with corset and 10 without. Gait kinematic parameters (stride length, walking speed, rhythm), gait balance parameters (center of mass braking index, stride width, double support time) and spinal sagittal balance parameters (C7T10S1, C7´S1' and spinal angles) were averaged. Adjusted analysis distinguished direct ASI impact from locomotor factors. RESULTS: The corset-induced ASI produced +15° change in C7 tilt (P < 0.0001), -7.4° in C7T10S1 (P < 0.0001), +66.2 mm in C7´S1' (P < 0.0001), and +13.1° in spinal angle (P < 0.0001). Radiographic and optoelectronic data correlated significantly. Stride length (P < 0.0001) and rhythm (P = 0.0003) were significantly reduced, contributing to a reduction in walking speed (P < 0.0001), and strongly influencing double support time (ß = -0.38; 95% confidence interval [CI]: -0.69; -0.06). Center of mass braking index was significantly reduced (P < 0.0001) and significantly influenced by ASI (ß = -0.51; 95% CI: -0.78; -0.28). Stride width was significantly increased by ASI (P < 0.0001), independently of rhythm and stride length. CONCLUSIONS: ASI induced by a kyphotic corset was detectable on the optoelectronic system, leading to significant changes in gait kinematics. Locomotor parameters were significantly reduced. Balance parameters were significantly and directly altered by ASI.

Cardiopulmonary Exercise Testing to Assess Persistent Symptoms at 6 Months in People With COVID-19 Who Survived Hospitalization: A Pilot Study.

OBJECTIVE: The aim of this pilot study was to assess physical fitness and its relationship with functional dyspnea in survivors of COVID-19 6 months after their discharge from the hospital. METHODS: Data collected routinely from people referred for cardiopulmonary exercise testing (CPET) following hospitalization for COVID-19 were retrospectively analyzed. Persistent dyspnea was assessed using the modified Medical Research Council dyspnea scale. RESULTS: Twenty-three people with persistent symptoms were referred for CPET. Mean modified Medical Research Council dyspnea score was 1 (SD = 1) and was significantly associated with peak oxygen uptake (VO2peak; %) (rho = -0.49). At 6 months, those hospitalized in the general ward had a relatively preserved VO2peak (87% [SD = 20]), whereas those who had been in the intensive care unit had a moderately reduced VO2peak (77% [SD = 15]). Of note, the results of the CPET revealed that, in all individuals, respiratory equivalents were high, power-to-weight ratios were low, and those who had been in the intensive care unit had a relatively low ventilatory efficiency (mean VE/VCO2 slope = 34 [SD = 5]). Analysis of each individual showed that none had a breathing reserve <15% or 11 L/min, all had a normal exercise electrocardiogram, and 4 had a heart rate >90%. CONCLUSION: At 6 months, persistent dyspnea was associated with reduced physical fitness. This study offers initial insights into the mid-term physical fitness of people who required hospitalization for COVID-19. It also provides novel pathophysiological clues about the underlaying mechanism of the physical limitations associated with persistent dyspnea. Those with persistent dyspnea should be offered a tailored rehabilitation intervention, which should probably include muscle reconditioning, breathing retraining, and perhaps respiratory muscle training. IMPACT: This study is the first, to our knowledge, to show that a persistent breathing disorder (in addition to muscle deconditioning) can explain persistent symptoms 6 months after hospitalization for COVID-19 infection and suggests that a specific rehabilitation intervention is warranted.

Association of quality of life with structural, functional and molecular brain imaging in community-dwelling older adults.

BACKGROUND: As the population ages, maintaining mental health and well-being of older adults is a public health priority. Beyond objective measures of health, self-perceived quality of life (QoL) is a good indicator of successful aging. In older adults, it has been shown that QoL is related to structural brain changes. However, QoL is a multi-faceted concept and little is known about the specific relationship of each QoL domain to brain structure, nor about the links with other aspects of brain integrity, including white matter microstructure, brain perfusion and amyloid deposition, which are particularly relevant in aging. Therefore, we aimed to better characterize the brain biomarkers associated with each QoL domain using a comprehensive multimodal neuroimaging approach in older adults. METHODS: One hundred and thirty-five cognitively unimpaired older adults (mean age ± SD: 69.4 ± 3.8 y) underwent structural and diffusion magnetic resonance imaging, together with early and late florbetapir positron emission tomography scans. QoL was assessed using the brief version of the World Health Organization's QoL instrument, which allows measuring four distinct domains of QoL: self-perceived physical health, psychological health, social relationships and environment. Multiple regression analyses were carried out to identify the independent global neuroimaging predictor(s) of each QoL domain, and voxel-wise analyses were then conducted with the significant predictor(s) to highlight the brain regions involved. Age, sex, education and the other QoL domains were entered as covariates in these analyses. Finally, forward stepwise multiple regressions were conducted to determine the specific items of the relevant QoL domain(s) that contributed the most to these brain associations. RESULTS: Only physical health QoL was associated with global neuroimaging values, specifically gray matter volume and white matter mean kurtosis, with higher physical health QoL being associated with greater brain integrity. These relationships were still significant after correction for objective physical health and physical activity measures. No association was found with global brain perfusion or global amyloid deposition. Voxel-wise analyses revealed that the relationships with physical health QoL concerned the anterior insula and ventrolateral prefrontal cortex, and the corpus callosum, corona radiata, inferior frontal white matter and cingulum. Self-perceived daily living activities and self-perceived pain and discomfort were the items that contributed the most to these associations with gray matter volume and white matter mean kurtosis, respectively. CONCLUSIONS: Better self-perceived physical health, encompassing daily living activities and pain and discomfort, was the only QoL domain related to brain structural integrity including higher global gray matter volume and global white matter microstructural integrity in cognitively unimpaired older adults. The relationships involved brain structures belonging to the salience network, the pain pathway and the empathy network. While previous studies showed a link between objective measures of physical health, our findings specifically highlight the relevance of monitoring and promoting self-perceived physical health in the older population. Longitudinal studies are needed to assess the direction and causality of the relationships between QoL and brain integrity.

White matter hyperintensities across the adult lifespan: relation to age, Aß load, and cognition.

BACKGROUND: White matter hyperintensities (WMH) are very frequent in older adults and associated with worse cognitive performance. Little is known about the links between WMH and vascular risk factors, cortical ß-amyloid (Aß) load, and cognition in cognitively unimpaired adults across the entire lifespan, especially in young and middle-aged adults. METHODS: One hundred and thirty-seven cognitively unimpaired adults from the community were enrolled (IMAP cohort). Participants underwent (i) a comprehensive neuropsychological assessment of episodic memory, processing speed, working memory, and executive functions; (ii) brain structural T1 and FLAIR MRI scans used for the automatic segmentation of total and regional (frontal, parietal, temporal, occipital, and corpus callosum) WMH; and (iii) a Florbetapir-PET scan to measure cortical Aß. The relationships of total and regional WMH to age, vascular risk factors, cortical Aß, and cognition were assessed within the whole sample, but also splitting the sample in two age groups (≤ or > 60 years old). RESULTS: WMH increased with age across the adult lifespan, i.e., even in young and middle-aged adults. Systolic blood pressure, diastolic blood pressure, and glycated hemoglobin were all associated with higher WMH before, but not after, adjusting for age and the other vascular risk factors. Higher frontal, temporal, and occipital WMH were associated with greater Aß, but this association was no longer significant when adjusting for age and vascular risk factors. Higher total and frontal WMH were associated with worse performance in executive functions, with no interactive effect of the age group. In contrast, there was a significant interaction of the age group on the link between WMH and working memory, which was significant within the subgroup of young/middle-aged adults only. Adding cortical Aß load in the models did not alter the results, and there was no interaction between WMH and Aß on cognition. CONCLUSION: WMH increased with age and were associated with worse executive functions across the adult lifespan and with worse working memory in young/middle-aged adults. Aß load was weakly associated with WMH and did not change the relationship found between WMH and executive functions. This study argues for the clinical relevance of WMH across the adult lifespan, even in young and middle-aged adults with low WMH.

Motivations and willingness of general practitioners in France to participate in primary care research as investigators.

BACKGROUND: Clinical research is mostly conducted among hospitalized patients, which restricts the generalizability of research results. The involvement of GPs in research has been consistently highlighted as a factor associated with successful study recruitment. OBJECTIVES: To assess GPs' motivations and willingness to participate in primary care research as investigators and to identify factors associated with their willingness. METHODS: We conducted an observational, cross-sectional study in Normandy, France, with a self-questionnaire sent to 3002 GPs. We collected data on GPs' socio-demographic characteristics, their experiences and their expectations regarding research, and their reasons for non-participation. RESULTS: Overall, 489 questionnaires were collected. Two hundred and forty-six GPs (50.3%) were interested in participating in clinical research as investigators. The two main conditions for participation as investigators were the relevance of the study topic for clinical practice (80.5%) and the feedback of study results (80.1%). The two main reasons for non-participation were lack of time (79.4%) and administrative burden (43.6%). Age between 27 and 34 years (adjusted odds ratio [AOR] = 2.86, P = 0.004) and GP trainer status (AOR = 2.41, P < 0.001) were associated with willingness to participate in primary care research. Age between 60 and 70 years (AOR = 0.53, P = 0.03) and locum status (AOR = 0.40, P = 0.04) were associated with non-participation in research. CONCLUSIONS: Based on our results, we were able to establish a profile of GPs willing to participate in primary care research as investigators. GPs' involvement should be based on their preferred areas of research. Different incentives such as a dedicated clinical research nurse or financial support could also be considered.

Impaired contrast sensitivity at low spatial frequency in cannabis users with early onset.

The regular use of cannabis generates pronounced cognitive disorders, especially in users who begin before the age of 15-16. However, less is known about the impact of regular cannabis on visual function, especially in the case of early onset. Cannabinoid receptors (CB1) are expressed in areas of the visual system, like the thalamus and primary cortex, which might originate sensory disorders. Hence, we measured contrast sensitivity (CS) in three groups, i.e. cannabis users with late onset of cannabis use (after 16 years old), cannabis users with early onset". We used a constant method which allowed us to control for biased responses. Stimuli were presented at high and low spatial frequencies and in both static and dynamic conditions (8Hz). As contrast sensitivity is measured behaviorally based on an explicit response and could thus be impacted by attentional or vigilance disorders, participants' attention and vigilance were carefully monitored by means of the D2 test, CPT-AX for attention and pupillography for vigilance. Cannabis users with early onset were significantly impaired only at low spatial frequency. This effect was independent of response bias, vigilance and attention. These results show for the first time that early cannabis use impacts contrast sensitivity at low spatial frequency.