Effects of Exercise and Weight Loss on Proximal Aortic Stiffness in Older Adults With Obesity.

BACKGROUND: Obesity may accelerate age-related increases in aortic stiffness. Although aerobic exercise training generally has favorable effects on aortic structure and function, exercise alone may not be sufficient to improve aortic stiffness in older adults with obesity. We determined the effects of aerobic exercise training with and without moderate- to high-caloric restriction (CR) on the structure and function of the proximal aorta in 160 older (65-79 years) men and women with obesity (body mass index=30-45 kg/m2). METHODS: Participants were randomly assigned to 1 of 3 groups: aerobic exercise training only (treadmill 4 days/week for 30 minutes at 65% to 70% of heart rate reserve; n=56), aerobic exercise training plus moderate CR (n=55), or aerobic exercise training plus more intensive CR (n=49) for 20 weeks. Aortic pulse wave velocity, aortic distensibility, and other measures of aortic structure and function were assessed by cardiovascular magnetic resonance imaging. Pearson correlation coefficients were examined to assess associations between changes in proximal aortic stiffness and changes in fitness, fatness, and other potential confounders. RESULTS: Weight loss in the aerobic exercise training plus moderate CR (-8.0 kg [95% CI, -9.17 to -6.87]) and aerobic exercise training plus more intensive CR (-8.98 kg [95% CI, -10.23 to -7.73) groups was significantly greater compared with the aerobic exercise training-only group (-1.66 kg [95% CI, -2.94 to -0.38]; P<0.017 for both). There were significant treatment effects for descending aorta distensibility (P=0.008) and strain (P=0.004) and aortic arch pulse wave velocity (P=0.01) with the aerobic exercise training plus moderate CR group having a 21% increase in distensibility (P=0.016) and an 8% decrease in pulse wave velocity (P=0.058). None of the aortic stiffness measures changed significantly in the aerobic exercise training-only or aerobic exercise training plus more intensive CR groups, and there were no significant changes in any other measure of aortic structure or function in these groups. Overall, increases in aortic distensibility were correlated with improvements in body weight and body fat distribution, but these associations were not statistically significant after adjustment for multiple comparisons. CONCLUSIONS: In older adults with obesity, combining aerobic exercise with moderate CR leads to greater improvements in proximal aortic stiffness than exercise alone. Registration: URL: https://clinicaltrials.gov; Unique identifier: NCT01048736.

Cognition, Physical Function, and Quality of Life in Older Patients With Acute Decompensated Heart Failure.

BACKGROUND: Older adults with acute decompensated heart failure have persistently poor clinical outcomes. Cognitive impairment (CI) may be a contributing factor. However, the prevalence of CI and the relationship of cognition with other patient-centered factors such a physical function and quality of life (QOL) that also may contribute to poor outcomes are incompletely understood. METHODS AND RESULTS: Older (≥60 years) hospitalized patients with acute decompensated heart failure were assessed for cognition (Montreal Cognitive Assessment [MoCA]), physical function (Short Physical Performance Battery [SPPB], 6-minute walk distance [6MWD]), and QOL (Kansas City Cardiomyopathy Questionnaire, Short Form-12). Among patients (N = 198, 72.1 ± 7.6 years), 78% screened positive for CI (MoCA of <26) despite rare medical record documentation (2%). Participants also had severely diminished physical function (SPPB 6.0 ± 2.5 units, 6MWD 186 ± 100 m) and QOL (scores of <50). MoCA positively related to SPPB (ß = 0.47, P < .001), 6MWD ß = 0.01, P = .006) and inversely related to Kansas City Cardiomyopathy Questionnaire Overall Score (ß = -0.05, P < .002) and Short Form-12 Physical Component Score (ß = -0.09, P = .006). MoCA was a small but significant predictor of the results on the SPPB, 6MWD, and Kansas City Cardiomyopathy Questionnaire. CONCLUSIONS: Among older hospitalized patients with acute decompensated heart failure, CI is highly prevalent, is underrecognized clinically, and is associated with severe physical dysfunction and poor QOL. Formal screening may reduce adverse events by identifying patients who may require more tailored care.

Associations of Early Kidney Disease With Brain Magnetic Resonance Imaging and Cognitive Function in African Americans With Type 2 Diabetes Mellitus.

BACKGROUND: Relationships between early kidney disease, neurocognitive function, and brain anatomy are poorly defined in African Americans with type 2 diabetes mellitus (T2DM). STUDY DESIGN: Cross-sectional associations were assessed between cerebral anatomy and cognitive performance with estimated glomerular filtration rate (eGFR) and urine albumin-creatinine ratio (UACR) in African Americans with T2DM. SETTING & PARTICIPANTS: African Americans with cognitive testing and cerebral magnetic resonance imaging (MRI) in the African American-Diabetes Heart Study Memory in Diabetes (AA-DHS MIND; n=512; 480 with MRI) and Action to Control Cardiovascular Risk in Diabetes (ACCORD) MIND (n=484; 104 with MRI) studies. PREDICTORS: eGFR (CKD-EPI creatinine equation), spot UACR. MEASUREMENTS: MRI-based cerebral white matter volume (WMV), gray matter volume (GMV), and white matter lesion volume; cognitive performance (Mini-Mental State Examination, Digit Symbol Coding, Stroop Test, and Rey Auditory Verbal Learning Test). Multivariable models adjusted for age, sex, body mass index, scanner, intracranial volume, education, diabetes duration, hemoglobin A1c concentration, low-density lipoprotein cholesterol concentration, smoking, hypertension, and cardiovascular disease were used to test for associations between kidney phenotypes and the brain in each study; a meta-analysis was performed. RESULTS: Mean participant age was 60.1±7.9 (SD) years; diabetes duration, 12.1±7.7 years; hemoglobin A1c concentration, 8.3%±1.7%; eGFR, 88.7±21.6mL/min/1.73m2; and UACR, 119.2±336.4mg/g. In the fully adjusted meta-analysis, higher GMV associated with lower UACR (P<0.05), with a trend toward association with higher eGFR. Higher white matter lesion volume was associated with higher UACR (P<0.05) and lower eGFR (P<0.001). WMV was not associated with either kidney parameter. Higher UACR was associated with lower Digit Symbol Coding performance (P<0.001) and a trend toward association with higher Stroop interference; eGFR was not associated with cognitive tests. LIMITATIONS: Cross-sectional; single UACR measurement. CONCLUSIONS: In African Americans with T2DM, mildly high UACR and mildly low eGFR were associated with smaller GMV and increased white matter lesion volume. UACR was associated with poorer processing speed and working memory.

Relationships between Cognitive Performance, Neuroimaging and Vascular Disease: The DHS-MIND Study.

BACKGROUND: Type 2 diabetes mellitus increases the risk of cognitive decline and dementia, and elevated burdens of vascular disease are hypothesized to contribute to this risk. These relationships were examined in the Diabetes Heart Study-MIND using a battery of cognitive tests, neuroimaging measures and subclinical cardiovascular disease (CVD) burden assessed by coronary artery calcified (CAC) plaque. We hypothesized that CAC would attenuate the association between neuroimaging measures and cognition performance. METHODS: Associations were examined using marginal models in this family-based cohort of 572 European Americans from 263 families. All models were adjusted for age, gender, education, type 2 diabetes and hypertension, with some neuroimaging measures additionally adjusted for intracranial volume. RESULTS: Higher total brain volume was associated with better performance on the Digit Symbol Substitution Task and Semantic Fluency (both p ≤ 7.0 × 10(-4)). Higher gray matter volume was associated with better performance on the Modified Mini-Mental State Examination and Semantic Fluency (both p ≤ 9.0 × 10(-4)). Adjusting for CAC caused minimal changes to the results. CONCLUSIONS: Relationships exist between neuroimaging measures and cognitive performance in a type 2 diabetes-enriched European American cohort. Associations were minimally attenuated after adjusting for subclinical CVD. Additional work is needed to understand how subclinical CVD burden interacts with other factors and impacts relationships between neuroimaging and cognitive testing measures.

Structural and functional assessment of the brain in European Americans with mild-to-moderate kidney disease: Diabetes Heart Study-MIND.

BACKGROUND: Advanced chronic kidney disease (CKD) is associated with altered cerebral structure and function. Relationships between mild-to-moderate CKD and brain morphology and cognitive performance were evaluated in European Americans (EAs). METHODS: A total of 478 EAs with estimated glomerular filtration rate (eGFR) >45 mL/min/1.73 m(2) and urine albumin:creatinine ratio (UACR) < 300 mg/g, most with type 2 diabetes (T2D), were included. Measures of total intracranial volume (TICV), cerebrospinal fluid volume, total white matter volume (TWMV), total gray matter volume (TGMV), total white matter lesion volume (TWMLV), hippocampal white matter volume (HWMV) and hippocampal gray matter volume (HGMV) were obtained with magnetic resonance imaging. Cognitive testing included memory (Rey Auditory Visual Learning Test), global cognition (Modified Mini-Mental State Examination) and executive function (Stroop Task, Semantic Fluency, Digit Symbol Substitution Test). Associations with CKD were assessed using log-transformed eGFR and UACR, adjusted for age, sex, body mass index, smoking, hemoglobin A1c, blood pressure, diabetes duration, cardiovascular disease and education. RESULTS: Participants were 55.2% female, 78.2% had T2D; mean ± SD age 67.6 ± 9.0 years, T2D duration 16.4 ± 6.5 years, eGFR 92.0 ± 22.3 mL/min/1.73 m(2) and UACR 23.8 ± 39.6 mg/g. In adjusted models, eGFR was negatively associated with TICV only in participants with T2D [parameter estimate (ß): -72.2, P = 0.002]. In non-diabetic participants, inverse relationships were observed between eGFR and HGMV (ß: -1.0, P = 0.03) and UACR and normalized TWMLV (ß: -0.2, P = 0.03). Kidney function and albuminuria did not correlate with cognitive testing. CONCLUSIONS: In EAs with mild CKD enriched for T2D, brain structure and cognitive performance were generally not impacted. Longitudinal studies are necessary to determine when cerebral structural changes and cognitive dysfunction develop with progressive CKD in EAs.

Kidney disease and cognitive function: African American-diabetes heart study MIND.

AIMS: Albuminuria and reduced estimated glomerular filtration rate (eGFR) are linked with poorer cognitive performance in European-ancestry populations with advanced nephropathy; relationships in African Americans (AAs) with type 2 diabetes (T2D) are less clear. Tests of cognitive performance, urine albumin:creatinine ratio (UACR), and CKD-EPI eGFR were performed in unrelated AAs with T2D to determine relationships. METHODS: Cross-sectional analysis of 263 unrelated AAs with T2D recruited in the African American-Diabetes Heart Study (AA-DHS) MIND. Global cognitive function (mini-mental state exam [3MSE] and Montreal Cognitive Assessment [MoCA]), memory (Rey Auditory Verbal Learning Test [RAVLT]), executive function (Stroop, verbal fluency for animals, and Digit Symbol Copy [DSC]), UACR, and eGFR were determined. Relationships between cognitive tests and renal parameters were assessed using multivariate models, adjusted for age, gender, body mass index, hemoglobin A1c, level of education, hypertension, and LDL cholesterol. RESULTS: Participants had a mean ± SD age of 60.2 ± 9.7 years, 62.7% were female, T2D duration was 14.3 ± 8.9 years, eGFR 86.0 ± 23.2 ml/min/1.73 m(2), and UACR 155.8 ± 542.1 (median 8.1) mg/g. In adjusted models, higher UACR was associated with worse 3MSE (p = 0.014), MoCA (p = 0.0089), DSC (p = 0.0004), Stroop performance time (p = 0.003), Stroop errors (p = 0.032), and Stroop interference (p = 0.026). Higher eGFR was associated with better performance on DSC (p = 0.0071). CONCLUSIONS: In AAs with T2D, albuminuria and eGFR were associated with cognitive function, even in mild kidney disease. These data stress the need for interventions to prevent cognitive decline well before the late stages of kidney disease.

Amyloid-ß Deposition Predicts Grocery Shopping Performance in Older Adults Without Cognitive Impairment.

Background: A screening tool sensitive to Alzheimer's disease (AD) risk factors, such as amyloid-ß (Aß) deposition, and subtle cognitive changes, best elicited by complex everyday tasks, is needed. Objective: To determine if grocery shopping performance could differentiate older adults at elevated risk of developing AD (OAer), older adults at low risk of developing AD (OAlr), and young adults (YA), and if amount of Aß deposition could predict grocery shopping performance in older adults (OA). Methods: Twenty-one OAer (78±5 years), 33 OAlr (78±5 years), and 28 YA (31±3 years) performed four grocery shopping trials, with the best and worst performances analyzed. Measures included trial time, number of correct items, number of grocery note fixations, and number of fixations and percentage of time fixating on the correct shelving unit, correct brand, and correct shelf. Linear mixed effects models compared measures by performance rank (best, worst) and group (OAer, OAlr, YA), and estimated the effect of Aß deposition on measures in OA. Results: Relative to their best performance, OAer and OAlr exhibited more correct shelving unit fixations and correct brand fixations during their worst performance, while YA did not. Within OA's worst performance, greater Aß deposition was associated with a smaller percentage of time fixating on the correct shelving unit, correct shelf, and correct brand. Within OA, greater Aß deposition was associated with more grocery note fixations. Conclusions: OA with elevated Aß deposition may exhibit subtle working memory impairments and less efficient visual search strategies while performing a cognitively demanding everyday task.

Age and beta amyloid deposition impact gait speed, stride length, and gait smoothness while transitioning from an even to an uneven walking surface in older adults.

BACKGROUND: Capturing a measure of movement quality during a complex walking task may indicate the earliest signs of detrimental changes to the brain due to beta amyloid (Aß) deposition and be a potential differentiator of older adults at elevated and low risk of developing Alzheimer's disease. This study aimed to determine: 1) age-related differences in gait speed, stride length, and gait smoothness while transitioning from an even to an uneven walking surface, by comparing young adults (YA) and older adults (OA), and 2) if gait speed, stride length, and gait smoothness in OA while transitioning from an even to an uneven walking surface is influenced by the amount of Aß deposition present in an OA's brain. METHODS: Participants included 56 OA (>70 years of age) and 29 YA (25-35 years of age). In OA, Aß deposition in the brain was quantified by PET imaging. All participants completed a series of cognitive assessments, a functional mobility assessment, and self-report questionnaires. Then participants performed two sets of walking trials on a custom-built walkway containing a mixture of even and uneven surface sections, including three trials with a grass uneven surface and three trials with a rocks uneven surface. Gait data were recorded using a wireless inertial measurement unit system. Stride length, gait speed, and gait smoothness (i.e., log dimensionless lumbar jerk) in the anteroposterior (AP), mediolateral (ML), and vertical (VT) directions were calculated for each stride. Outcomes were retained for five stride locations immediately surrounding the surface transition. RESULTS: OA exhibited slower gait (Grass: p < 0.001; Rocks: p = 0.006), shorter strides (Grass: p < 0.001; Rocks: p = 0.008), and smoother gait (Grass AP: p < 0.001; Rocks AP: p = 0.002; Rocks ML: p = 0.02) than YA, but they also exhibited greater reductions in gait speed and stride length than YA while transitioning to the uneven grass and rocks surfaces. Within the OA group, those with greater Aß deposition exhibited decreases in smoothness with age (Grass AP: p = 0.02; Rocks AP: p = 0.03; Grass ML: p = 0.04; Rocks ML: p = 0.03), while those with lower Aß deposition exhibited increasing smoothness with age (Grass AP: p = 0.01; Rocks AP: p = 0.02; Grass ML: p = 0.08; Rocks ML: p = 0.07). Better functional mobility was associated with less smooth gait (Grass ML: p = 0.02; Rocks ML: p = 0.05) and with less variable gait smoothness (Grass and Rocks AP: both p = 0.04) in the OA group. CONCLUSION: These results suggest that, relative to YA, OA may be adopting more cautious, compensatory gait strategies to maintain smoothness when approaching surface transitions. However, OA with greater Aß deposition may have limited ability to adopt compensatory gait strategies to increase the smoothness of their walking as they get older because of neuropathological changes altering the sensory integration process and causing worse dynamic balance (i.e., jerkier gait). Functional mobility, in addition to age and Aß deposition, may be an important factor of whether or not an OA chooses to employ compensatory strategies to prioritize smoothness while walking and what type of compensatory strategy an OA chooses.

Sex Specific Associations of Sex hormone With Brain Volumes and Cerebral Blood Flow: A Cross Sectional Observational Study Within the Look AHEAD Type 2 Diabetes Cohort.

Background: Females have greater brain volume and cerebral blood flow than males when controlling for intracranial volume and age. Brain volume decreases after menopause, suggesting a role of sex hormones. We studied the association of sex hormones with brain volume, white matter hyperintensity volumes and cerebral blood flow in people with Type 2 Diabetes and with overweight and obesity conditions that accelerate brain atrophy. Methods: We analyzed data from 215 participants with overweight or obesity and Type 2 Diabetes from the Look AHEAD Brain Magnetic Resonance Imaging ancillary study (mean age 68 years, 73% postmenopausal female). Estradiol and total testosterone levels were measured with electrochemoluminescence assays. The ratio of brain measurements to intracranial volume was analyzed to account for body size. We analyzed sex hormones as quantitative measures in males, whereas in females we grouped those with detectable vs. undetectable hormone levels (Estradiol <73 pmol/L [20 pg/mL]: 79%; Total Testosterone < 0.07 mmol/L [0.02 ng/mL]: 37% undetectable in females). Results: Females with detectable total testosterone levels had higher brain volume to intracranial volume ratio (median [25th, 75th percentile]: 0.85 [0.84, 0.86]) as compared to those with undetectable Total Testosterone levels (0.84 [0.83, 0.86]; rank sum p=0.04). This association was attenuated after age and body mass index adjustment (p=0.08). Neither white matter hyperintensity volumes or cerebral blood flow in females, nor any brain measures in males, were significantly associated with Estradiol or Total Testosterone. Conclusions: In postmenopausal females with Type 2 Diabetes with overweight and obesity, detectable levels of total testosterone were associated greater brain volume relative to intracranial volume, suggesting a protective role for testosterone in female brain health. Our findings are limited by a small sample size and low sensitivity of hormone assays. Our suggestive findings can be combined with future larger studies to assess clinically important differences. Trial Registration: NCT00017953.

Association of physical function with connectivity in the sensorimotor and dorsal attention networks: why examining specific components of physical function matters.

Declining physical function with aging is associated with structural and functional brain network organization. Gaining a greater understanding of network associations may be useful for targeting interventions that are designed to slow or prevent such decline. Our previous work demonstrated that the Short Physical Performance Battery (eSPPB) score and body mass index (BMI) exhibited a statistical interaction in their associations with connectivity in the sensorimotor cortex (SMN) and the dorsal attention network (DAN). The current study examined if components of the eSPPB have unique associations with these brain networks. Functional magnetic resonance imaging was performed on 192 participants in the BNET study, a longitudinal and observational trial of community-dwelling adults aged 70 or older. Functional brain networks were generated for resting state and during a motor imagery task. Regression analyses were performed between eSPPB component scores (gait speed, complex gait speed, static balance, and lower extremity strength) and BMI with SMN and DAN connectivity. Gait speed, complex gait speed, and lower extremity strength significantly interacted with BMI in their association with SMN at rest. Gait speed and complex gait speed were interacted with BMI in the DAN at rest while complex gait speed, static balance, and lower extremity strength interacted with BMI in the DAN during motor imagery. Results demonstrate that different components of physical function, such as balance or gait speed and BMI, are associated with unique aspects of brain network organization. Gaining a greater mechanistic understanding of the associations between low physical function, body mass, and brain physiology may lead to the development of treatments that not only target specific physical function limitations but also specific brain networks.

Corrigendum: Examining the intersection of cognitive and physical function measures: Results from the brain networks and mobility (B-NET) study.

[This corrects the article DOI: 10.3389/fnagi.2023.1090641.].

Examining the intersection of cognitive and physical function measures: Results from the brain networks and mobility (B-NET) study.

Background and objectives: Although evidence exists that measures of mobility and cognition are correlated, it is not known to what extent they overlap, especially across various domains. This study aimed to investigate the intersection of 18 different objective cognitive and physical function measures from a sample of unimpaired adults aged 70 years and older. Research design and methods: Canonical correlation analysis was utilized to explore the joint cross-sectional relationship between 13 cognitive and 6 physical function measures in the baseline visit of the Brain Networks and Mobility Function (B-NET) Study (n = 192). Results: Mean age of participants was 76.4 years. Two synthetic functions were identified. Function 1 explained 26.3% of the shared variability between the cognition and physical function variables, whereas Function 2 explained 19.5%. Function 1 termed "cognitive and physical speed" related the expanded Short Physical Performance Battery (eSPPB), 400-m walk speed, and Dual Task gait speed measures of physical function to semantic fluency animals scores, Digit Symbol Coding (DSC), and Trail Making Test B. Function 2 termed "complex motor tasks and cognitive tasks" related the Force Plate Postural Sway Foam Task and Dual Task to the following cognitive variables: MoCA Adjusted Score, Verbal Fluency L words, Craft story immediate and delayed recall, and Trail Making Test B. Discussion and implications: We identified groups of cognitive and physical functional abilities that were linked in cross-sectional analyses, which may suggest shared underlying neural network pathway(s) related to speed (Function 1) or complexity (Function 2). Translational significance: Whether such neural processes decline before measurable functional losses or may be important targets for future interventions that aim to prevent disability also remains to be determined.

Association Between Contrast Sensitivity and Physical Function in Cognitively Healthy Older Adults: The Brain Networks and Mobility Function Study.

BACKGROUND: To evaluate whether contrast sensitivity is associated with lower extremity physical function in cognitively intact older adults. METHODS: Cross-sectional analysis of the relationship of binocular and worse eye log contrast sensitivity (LCS) to expanded Short Physical Performance Battery (eSPPB) and its components (gait speed, narrow walking speed, chair stand pace, and balance) in 192 cognitively healthy older adults. The association of LCS with postural sway and gait was also tested with tasks that further challenged functional reserve. RESULTS: Mean age was 76.4 years with 56% identifying as female and over 98.5% having good corrected visual acuity. Lower LCS was significantly associated with worse performance on the eSPPB, 4-M gait speed, narrow walking speed, and balance time in unadjusted and adjusted models. The relationship between worse eye LCS and larger postural sway was 3 times greater on a foam surface (beta 1.07, 95% CI [0.35, 1.80]) than a firm surface (beta 0.35, 95% CI [0.05, 0.65]), and both were robust to adjustment for confounders; similar findings were observed with binocular LCS. Lower binocular LCS had a greater decremental effect on gait velocity during the fast pace (beta -0.58, 95% CI [-0.90, -0.27]) than the usual pace (Beta -0.39 [-0.63, -0.15]) gait task. CONCLUSIONS: These findings suggest that cognitively unimpaired older adults without significant visual acuity impairment can have subtle preclinical deficits in contrast sensitivity and physical function that could place them at risk of mobility and balance issues. Future studies should determine whether this subset of older adults may benefit from targeted intervention to prevent disability.

IMOVE: Protocol for a randomized, controlled 2x2 factorial trial of improvisational movement and social engagement interventions in older adults with early Alzheimer's disease.

Background: In addition to cognitive impairment, people with Alzheimer's disease (PWAD) experience neuropsychiatric symptoms (e.g., apathy, depression), altered gait, and poor balance that further diminish their quality of life (QoL). Here, we describe a unique, randomized, controlled trial to test the hypothesis that both movement and social engagement aspects of a group dance intervention alter the connectivity of key brain networks involved in motor and social-emotional functioning and lead to improved QoL in PWAD. Methods: IMOVE (NCT03333837) was a single-center, randomized, controlled 2x2 factorial trial that assigned PWAD/caregiver dyads to one of 4 study conditions (Movement Group, Movement Alone, Social Group, or Usual Care control). The Movement Group participated in twice-weekly group improvisational dance (IMPROVment® Method) classes for 12 weeks. The Movement Alone intervention captured the same dance movement and auditory stimuli as the group class without social interaction, and the Social Group used improvisational party games to recapitulate the fun and playfulness of the Movement Group without the movement. The primary outcome was change in QoL among PWAD. Key secondary outcomes were functional brain network measures assessed using graph-theory analysis of resting-state functional magnetic resonance imaging scans, as well as neuropsychiatric symptoms, gait, and balance. Results: A total of 111 dyads were randomized; 89 completed the study, despite interruption and modification of the protocol due to COVID-19 restrictions (see companion paper by Fanning et al.). The data are being analyzed and will be submitted for publication in 2023.

Associations of physical function and body mass index with functional brain networks in community-dwelling older adults.

Deficits in physical function that occur with aging contribute to declines in quality of life and increased mortality. There has been a growing interest in examining associations between physical function and neurobiology. Whereas high levels of white matter disease have been found in individuals with mobility impairments in structural brain studies, much less is known about the relationship between physical function and functional brain networks. Even less is known about the association between modifiable risk factors such as body mass index (BMI) and functional brain networks. The current study examined baseline functional brain networks in 192 individuals from the Brain Networks and mobility (B-NET) study, an ongoing longitudinal, observational study in community-dwelling adults aged 70 and older. Physical function and BMI were found to be associated with sensorimotor and dorsal attention network connectivity. There was a synergistic interaction such that high physical function and low BMI were associated with the highest network integrity. White matter disease did not modify these relationships. Future work is needed to understand the causal direction of these relationships.

Virtual delivery of improvisational movement and social engagement interventions in the IMOVE trial during the COVID-19 pandemic.

Background: IMOVE evaluated the contributions of movement and social engagement to quality of life, brain network connectivity, and motor and social-emotional functioning in people with early-stage Alzheimer's disease participating with a caregiver. In response to COVID-19 restrictions, a pilot study was conducted to assess integrity of key elements of the intervention and feasibility of virtual intervention delivery. Methods: Participants in the parent study were randomized to one of 4 study conditions (Movement Group [MG], Movement Alone [MA], Social Group [SG], or Usual Care [UC; control]). To test virtual adaptations of each condition, groups of three participant-caregiver dyads (6 individuals) who had completed the parent trial participated in virtual adaptation classes. We adopted an engineering-inspired, rapid refinement model to optimize virtual interventions on the dimensions of social connectedness, fun, and physical exertion. After completing one iteration, participants gave feedback and adjustments were made to the intervention. This process was repeated until no further adjustments were needed. Results: The MA arm easily transitioned to virtual format. The virtual MG intervention required the most iterations, with participants reporting needs for additional technology support, higher level of physical exertion, and stronger social connection. The virtual SG intervention reported good social connection, but needed additional technology instruction and measures to promote equal participation. Conclusions: Our pilot study results underscore the feasibility of delivering remote social and/or dance interventions for older adults and provide a useful road map for other research teams interested in increasing their reach by adapting in-person group behavioral interventions for remote delivery.

Differences in arachidonic acid levels and fatty acid desaturase (FADS) gene variants in African Americans and European Americans with diabetes or the metabolic syndrome.

Over the past 50 years, increases in dietary n-6 PUFA, such as linoleic acid, have been hypothesised to cause or exacerbate chronic inflammatory diseases. The present study examines an individual's innate capacity to synthesise n-6 long-chain PUFA (LC-PUFA) with respect to the fatty acid desaturase (FADS) locus in Americans of African and European descent with diabetes or the metabolic syndrome. Compared with European Americans (EAm), African Americans (AfAm) exhibited markedly higher serum levels of arachidonic acid (AA) (EAm 7·9 (sd 2·1), AfAm 9·8 (sd 1·9) % of total fatty acids; P < 2·29 × 10⁻9) and the AA:n-6-precursor fatty acid ratio, which estimates FADS1 activity (EAm 5·4 (sd 2·2), AfAm 6·9 (sd 2·2); P = 1·44 × 10⁻5). In all, seven SNP mapping to the FADS locus revealed strong association with AA, EPA and dihomo-γ-linolenic acid (DGLA) in the EAm. Importantly, EAm homozygous for the minor allele (T) had significantly lower AA levels (TT 6·3 (sd 1·0); GG 8·5 (sd 2·1); P = 3·0 × 10⁻5) and AA:DGLA ratios (TT 3·4 (sd 0·8), GG 6·5 (sd 2·3); P = 2·2 × 10⁻7) but higher DGLA levels (TT 1·9 (sd 0·4), GG 1·4 (sd 0·4); P = 3·3 × 10⁻7) compared with those homozygous for the major allele (GG). Allele frequency patterns suggest that the GG genotype at rs174537 (associated with higher circulating levels of AA) is much higher in AfAm (0·81) compared with EAm (0·46). Similarly, marked differences in rs174537 genotypic frequencies were observed in HapMap populations. These data suggest that there are probably important differences in the capacity of different populations to synthesise LC-PUFA. These differences may provide a genetic mechanism contributing to health disparities between populations of African and European descent.

Corrigendum: Relationship between cerebrovascular reactivity and cognition among people with risk of cognitive decline.

[This corrects the article DOI: 10.3389/fphys.2021.645342.].

Associations between cognitive function and endogenous levels of estradiol and testosterone in adults with type 2 diabetes.

AIMS: To assess associations that endogenous estradiol and testosterone levels have with cognitive function in older adults with Type 2 diabetes mellitus (T2DM). METHODS: We use data from the Look AHEAD clinical trial of behavioral weight loss. Endogenous estradiol and total testosterone levels were determined using stored serum from 996 individuals, mean age 69 years, at two times (averaging 4 years apart) during years 8-18 of follow-up. One to four standardized assessments of attention, executive function, memory, and verbal fluency were collected during this follow-up. Mixed effects models and multiple imputation were used to assess associations that estradiol and total testosterone levels had with body mass index and cognitive function. RESULTS: Estradiol levels were not associated with cognitive function in either sex. Total testosterone levels were not associated with cognitive function in women, but greater total testosterone levels were associated with better verbal fluency in men (p < 0.001), most strongly among those carrying the APOE-e4 allele (interaction p = 0.02). The weight loss intervention left a legacy of relatively lower cognitive functioning among women, which was not mediated by current levels of sex hormones. CONCLUSIONS: Behavioral weight loss intervention does not affect cognitive functioning through mechanisms related to estradiol or testosterone. CLINICALTRIALS: gov Identifier: NCT00017953.

Gradient and Acceleration of Decline in Physical and Cognitive Functions in Older Adults: A Disparity Analysis.

BACKGROUND: Substantive previous work has shown that both gait speed and global cognition decline as people age. Rates of their decline, as opposed to cross-sectional measurements, could be more informative of future functional status and other clinical outcomes because they more accurately represent deteriorating systems. Additionally, understanding the sex and racial disparity in the speed of deterioration, if any, is also important as ethnic minorities are at an increased risk of mobility disability and dementia. METHOD: Data from 2 large longitudinal intervention studies were integrated. Rates of decline were derived from individual-level measures of gait speed of 400-m walk and scores on the Modified Mini Mental State Examination (3MSE). We also assessed age-associated declines and accelerations in changes across the ages represented in the studies (age range 53-90). RESULTS: The mean rate of decline in 400-m gait speed across individuals was 0.03 m/s per year, and multivariable analysis showed a significant acceleration in decline of -0.0013 m/s/y2 (p < .001). Both race and sex moderated the rate of decline. For global cognition, the mean rate of decline was 0.05 of a point per year on the 3MSE scale, and acceleration in the rate of decline was significant (-0.017 point/y2, p < .001), but neither sex nor race moderated the decline. CONCLUSION: Rate of decline in physical but not cognitive function appears moderated by sex and race. This finding, as well as rates and accelerations of decline estimated herein, could inform future intervention studies. CLINICAL TRIALS REGISTRATION NUMBER: NCT00017953 (Look AHEAD); NCT01410097 (Look AHEAD ancillary); NCT00116194 (LIFE).