Soluble Intercellular Adhesion Molecule-1 (sICAM-1) as a Biomarker of Vascular Cognitive Impairment in Older Adults.

BACKGROUND: Endothelial dysfunction and subsequent inflammation contribute to the development of vascular cognitive impairment (VCI). Soluble intercellular adhesion molecule-1 (sICAM-1) is upregulated in endothelial dysfunction and promotes an inflammatory response; however, the relationship between sICAM-1 and VCI remains equivocal. OBJECTIVE: To determine whether sICAM-1 contributes to the prediction of VCI. METHODS: Community-dwelling older adults (n = 172) from the "Cohort of Obesity, Sarcopenia and Frailty of Older Mexican Adults" (COSFOMA) study were identified as VCI or controls using standard neuropsychological evaluations and neuroimaging. sICAM-1 was quantified using ELISA, and multivariate logistic regression determined the association between sICAM-1 and VCI. RESULTS: A total of 31 VCI cases were identified. sICAM-1 was higher in VCI (VCI: 450.7 [241.6] ng/mL vs. controls: 296.9 [140.9] ng/mL). sICAM-1 concentrations above the 90th percentile (464.1 ng/mL) were associated with VCI group membership in all models (OR: 6.9, 95% CI: 1.1-42.2). The final saturated model explained 64% of the variance in VCI group membership. CONCLUSION: High concentrations of sICAM-1 are independently associated with VCI group membership. Efforts to further characterize the relationship between indices of endothelial dysfunction and pathological changes to the aging brain should be further pursued.

Group-based exercise and cognitive-physical training in older adults with self-reported cognitive complaints: The Multiple-Modality, Mind-Motor (M4) study protocol.

BACKGROUND: Dementia is associated with cognitive and functional deficits, and poses a significant personal, societal, and economic burden. Directing interventions towards older adults with self-reported cognitive complaints may provide the greatest impact on dementia incidence and prevalence. Risk factors for cognitive and functional deficits are multifactorial in nature; many are cardiovascular disease risk factors and are lifestyle-mediated. Evidence suggests that multiple-modality exercise programs can provide cognitive and functional benefits that extend beyond what can be achieved from cognitive, aerobic, or resistance training alone, and preliminary evidence suggests that novel mind-motor interventions (i.e., Square Stepping Exercise; SSE) can benefit cognition and functional fitness. Nevertheless, it remains unclear whether multiple-modality exercise combined with mind-motor interventions can benefit diverse cognitive and functional outcomes in older adults with cognitive complaints. METHODS/DESIGN: The Multiple-Modality, Mind-Motor (M4) study is a randomized controlled trial investigating the cognitive and functional impact of combined physical and cognitive training among community-dwelling adults with self-reported cognitive complaints who are 55 years of age or older. Participants are randomized to a Multiple-Modality and Mind-Motor (M4) intervention group or a Multiple-Modality (M2) comparison group. Participants exercise for 60 minutes/day, 3-days/week for 24 weeks and are assessed at baseline, 24 weeks and 52 weeks. The primary outcome is global cognitive function at 24 weeks, derived from the Cambridge Brain Sciences computerized cognitive battery. Secondary outcomes are: i) global cognitive function at 52 weeks; ii) domain-specific cognitive function at 24 and 52 weeks; iii) mobility (gait characteristics under single and dual-task conditions and balance); and 3) vascular health (blood pressure and carotid arterial measurements). We will analyze data based on an intent-to-treat approach, using mixed models for repeated measurements. DISCUSSION: The design features of the M4 trial and the methods included to address previous limitations within cognitive and exercise research will be discussed. Results from the M4 trial will provide evidence of combined multiple-modality and cognitive training among older adults with self-reported cognitive complaints on cognitive, mobility-related and vascular outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT02136368.

Brain health and exercise in older adults.

Identifying feasible and effective interventions aimed at mitigating the effects of cognitive decline in older adults is currently a high priority for researchers, clinicians, and policy makers. Evidence suggests that exercise and cognitive training benefit cognitive health in older adults; however, a preferred modality has to be endorsed yet by the scientific community. The purpose of this review is to discuss and critically examine the current state of knowledge concerning the effects of aerobic, resistance, cognitive, and novel dual-task exercise training interventions for the preservation or improvement of cognitive health in older adults. A review of the literature suggests that the potential exists for multiple exercise modalities to improve cognitive functioning in older adults. Nonetheless current limitations within the field need to be addressed prior to providing definitive recommendations concerning which exercise modality is most effective at improving or maintaining cognitive health in aging.

The association between low cognitive reserve and subjective memory complaints in functionally independent older women.

BACKGROUND: Several factors have been found to defend against pathologic cognitive decline in aging (i.e., cognitive reserve [CR]); however, other factors, including subjective memory complaints (SMC) and decreased functionality are considered early indicators of underlying neurocognitive dysfunction. Despite these known associations, the relationship between the presence of CR and SMC remains equivocal. This study sought to determine the relationship between objectively measured CR and SMC in a sample of functionally independent older women. METHODS: This cross-sectional study recruited women aged ≥60 years who attended fitness or continuing education programs at the University for Seniors in Mexico City. Participants underwent a battery of physical and cognitive evaluations, including the Cognitive Reserve Questionnaire (CRQ), and were asked probing questions used to identify the presence of SMC. RESULTS: The 269 participants had a median age of 69 years; most were single (40.5 %), lived alone (32.7 %), retired (58.2 %), well-educated (≥12 years of education), and functionally independent (89.2 %). 62 % scored "high" on the CRQ, while 9.3 % scored "low". After adjusting for multiple covariates, an independent association between CRQ score and the probability to have SMC was found (adjusted OR = 0.87, 95% CI 0.80-0.95, p-value = 0.002). CONCLUSIONS: This study identified a relationship between low CR and the presence of SMC, independently of the cognitive function and motoric marker of muscle strength (i.e., low gait speed and handgrip strength) in functionally independent older women over 60y. This relationship remains independent of other variables such as age, symptoms of depression and instrumented activities of daily living.

Examining the Association between Life-Space Mobility and Cognitive Function in Older Adults: A Systematic Review.

PURPOSE: The purpose of this review is to investigate the relationship between life-space mobility and cognition in older adults. METHODS: MEDLINE, Embase, CINAHL, and PsycINFO were searched through December 2018 for studies containing measures of life-space mobility and cognitive function. Two independent reviewers screened studies. Eligible studies were combined using a random-effects model, and heterogeneity was assessed using the I 2. RESULTS: Thirty-five articles were identified for review. A moderate and statistically significant association (pooled r = 0.30, 95% confidence interval 0.19 to 0.40.) was observed between life-space mobility and cognition among nine studies. Life-space mobility demonstrated small-to-moderate associations with domain-specific cognitive functioning, particularly executive function, learning, memory, and processing speed. Furthermore, individuals who had restricted life-space mobility (Life-Space Assessment ≤ 40) experienced a steeper decline in cognition (ß = 0.56 and p = 0.0471) compared to those who did not (Life-Space Assessment ≥ 41). CONCLUSION: This review examined the association between life-space mobility and cognitive function in older adults. The results suggest that a moderate relationship between life-space mobility and cognition exists, whether adjusted or unadjusted for covariates such as sociodemographics, mental health, functional capacity, and comorbidities.

Monocyte chemoattractant protein-1 (MCP-1) and fibroblast growth factor-21 (FGF-21) as biomarkers of subclinical atherosclerosis in women.

BACKGROUND: Atherosclerosis is a primary risk factor for cardiovascular disease (CVD). Proinflammatory biochemical factors can influence vascular health; monocyte chemoattractant protein-1 (MCP-1) is elevated in patients with CVD while fibroblast growth factor-21 (FGF-21) acts directly on cardiac tissue to reduce infarction damage. However, the relationship between plasma concentrations of MCP-1, FGF-21 and subclinical CVD indices remains equivocal. AIM: To determine the association between MCP-1, FGF-21 and subclinical atherosclerosis [i.e., carotid intima-media thickness (cIMT)] in women without clinical evidence of CVD. METHODS: A cross-sectional analysis of 140 women without history of CVD was performed. Anthropometrics were collected, serum concentrations of MCP-1 and FGF-21 were determined by enzyme-linked immunosorbent assay, and cIMT was quantified (B-mode ultrasonography). The correlations between MCP-1, FGF-21 and the presence of clinical and laboratory of subclinical atherosclerosis (i.e., cIMT ≥0.70 mm), comparison intergroup and odd ratio with multiple logistic regression were analyzed. RESULTS: MCP-1, but not FGF-21 correlated with some obesity indicators. In median comparison among groups, subclinical atherosclerosis showed higher serum concentrations of MCP-1and lower serum concentrations of FGF-21. In postmenopausal women, there were significant differences MCP-1 (p = 0.001), and FGF-21 (p = 0.010). Multiple logistic regression analysis in postmenopausal women with subclinical atherosclerosis, between MCP-1 (p = 0.001) and FGF-21 (p = 0.037) showed association with cIMT, along with age. CONCLUSIONS: MCP-1 and FGF-21 levels are associated with subclinical atherosclerosis disease severity (i.e., cIMT) in postmenopausal women without CVD. Further efforts focused on characterizing the relationship between novel blood-borne markers of early CVD pathology are warranted and should be pursued.

Multiple-modality exercise and mind-motor training to improve mobility in older adults: A randomized controlled trial.

OBJECTIVE: To investigate the effects of multiple-modality exercise with or without additional mind-motor training on mobility outcomes in older adults with subjective cognitive complaints. METHODS: This was a 24-week randomized controlled trial with a 28-week no-contact follow-up. Community-dwelling older adults underwent a thrice -weekly, Multiple-Modality exercise and Mind-Motor (M4) training or Multiple-Modality (M2) exercise with an active control intervention (balance, range of motion and breathing exercises). Study outcomes included differences between groups at 24weeks and after the no-contact follow-up (i.e., 52weeks) in usual and dual-task (DT, i.e., serial sevens [S7] and phonemic verbal fluency [VF] tasks) gait velocity, step length and cycle time variability, as well as DT cognitive accuracy. RESULTS: 127 participants (mean age 67.5 [7.3] years, 71% women) were randomized to either M2 (n=64) or M4 (n=63) groups. Participants were assessed at baseline, intervention endpoint (24weeks), and study endpoint (52weeks). At 24weeks, the M2 group demonstrated greater improvements in usual gait velocity, usual step length, and DT gait velocity (VF) compared to the M4 group, and no between- or within-group changes in DT accuracy were observed. At 52weeks, the M2 group retained the gains in gait velocity and step length, whereas the M4 group demonstrated trends for improvement (p=0.052) in DT cognitive accuracy (VF). CONCLUSIONS: Our results suggest that additional mind-motor training was not effective to improve mobility outcomes. In fact, participants in the active control group experienced greater benefits as a result of the intervention.

The Impact of Blood Pressure Dipping Status on Cognition, Mobility, and Cardiovascular Health in Older Adults Following an Exercise Program.

Objectives: To determine whether a dual-task gait and aerobic exercise intervention differentially impacted older adults with normal blood pressure (BP) dipping status (dippers) compared to those with nondipping status (nondippers). Methods: This study was a secondary analysis involving participants (mean age = 70.3 years, 61% women) who attended a laboratory-based exercise intervention over a 6-month period (40 min/day and 3 days/week). Participants were assessed in measures of cognition, mobility, and cardiovascular health at baseline, 3, 6, and 12 months (after a 6-month no-contact follow-up). Results: We observed improvements in cognition in both groups at 6 and 12 months, although no between-group differences were seen. Nondippers demonstrated superior improvements in usual gait velocity and step length after the exercise intervention compared to dippers. Dippers reduced daytime systolic BP at 6 and 12 months to a greater extent than nondippers. Discussion: BP dipping status at baseline did not influence exercise benefits to cognition but did mediate changes in mobility and cardiovascular health.

Multiple-modality exercise and mind-motor training to improve cardiovascular health and fitness in older adults at risk for cognitive impairment: A randomized controlled trial.

BACKGROUND: The effects of multiple-modality exercise on arterial stiffening and cardiovascular fitness has not been fully explored. OBJECTIVES: To explore the influence of a 24-week multiple-modality exercise program associated with a mind-motor training in cardiovascular health and fitness in community-dwelling older adults, compared to multiple-modality exercise (M2) alone. METHODS: Participants (n=127, aged 67.5 [7.3] years, 71% females) were randomized to either M4 or M2 groups. Both groups received multiple-modality exercise intervention (60min/day, 3days/week for 24-weeks); however, the M4 group underwent additional 15min of mind-motor training, whereas the M2 group received 15min of balance training. Participants were assessed at 24-weeks and after a 28-week non-contact follow-up (52-weeks). RESULTS: at 52-weeks, the M4 group demonstrated a greater VO2max (ml/kg/min) compared to the M2 group (mean difference: 2.39, 95% CI: 0. 61 to 4.16, p=0.009). Within-group analysis indicated that the M4 group demonstrated a positive change in VO2max at 24-weeks (mean change: 1.93, 95% CI: 0.82 to 3.05, p=0.001) and 52-weeks (4.02, 95% CI: 2.71 to 5.32, p=0.001). Similarly, the M2 group increased VO2max at 24-weeks (2.28, 95% CI: 1.23 to 3.32, p<0.001) and 52-weeks (1.63, 95% CI: 0.43 to 2.83, p=0.008). Additionally, the M2 group decreased 24h SBP (mmHg) at 24-weeks (-2.31, 95% CI: -4.61 to -0.01, p=0.049); whereas the M4 group improved 24h DBP (-1.6, 95% CI: -3.03 to -0.17, p=0.028) at 52-weeks. CONCLUSION: Mind-motor training associated with multiple-modality exercise can positively impact cardiovascular fitness to the same extent as multiple-modality exercise alone.

Combined Dual-Task Gait Training and Aerobic Exercise to Improve Cognition, Mobility, and Vascular Health in Community-Dwelling Older Adults at Risk for Future Cognitive Decline1.

This 6-month experimental case series study investigated the effects of a dual-task gait training and aerobic exercise intervention on cognition, mobility, and cardiovascular health in community-dwelling older adults without dementia. Participants exercised 40 min/day, 3 days/week for 26 weeks on a Biodex GaitTrainer2 treadmill. Participants were assessed at baseline (V0), interim (V1: 12-weeks), intervention endpoint (V2: 26-weeks), and study endpoint (V3: 52-weeks). The study outcomes included: cognition [executive function (EF), processing speed, verbal fluency, and memory]; mobility: usual & dual-task gait (speed, step length, and stride time variability); and vascular health: ambulatory blood pressure, carotid arterial compliance, and intima-media thickness (cIMT). Fifty-six participants [age: 70(6) years; 61% female] were included in this study. Significant improvements following the exercise program (V2) were observed in cognition: EF (p = 0.002), processing speed (p < 0.001), verbal fluency [digit symbol coding (p < 0.001), phonemic verbal fluency (p < 0.001)], and memory [immediate recall (p < 0.001) and delayed recall (p < 0.001)]; mobility: usual & dual-task gait speed (p = 0.002 and p < 0.001, respectively) and step length (p = 0.001 and p = 0.003, respectively); and vascular health: cIMT (p = 0.002). No changes were seen in the remaining outcomes. In conclusion, 26 weeks of dual-task gait training and aerobic exercise improved performance on a number of cognitive outcomes, while increasing usual & dual-task gait speed and step length in a sample of older adults without dementia.

A Six-Month Cognitive-Motor and Aerobic Exercise Program Improves Executive Function in Persons with an Objective Cognitive Impairment: A Pilot Investigation Using the Antisaccade Task.

Persons with an objective cognitive impairment (OCI) are at increased risk for progression to Alzheimer's disease and related dementias. The present pilot project sought to examine whether participation in a long-term exercise program involving cognitive-motor (CM) dual-task gait training and aerobic exercise training improves executive function in persons with an OCI. To accomplish our objective, individuals with an OCI (n = 12) as determined by a Montreal Cognitive Assessment (MoCA) score of less than 26 and older adults (n = 11) deemed to be cognitively healthy (i.e., control group: MoCA score ≥26) completed a six-month moderate-to-high intensity (65-85% maximum heart rate) treadmill-based CM and aerobic exercise training program wherein pre- and post-intervention executive control was examined via the antisaccade task. Notably, antisaccades require a goal-directed eye-movement mirror-symmetrical to a target and represent an ideal tool for the study of executive deficits because of its hands- and language-free nature. As well, the cortical networks mediating antisaccades represent regions associated with neuropathology in cognitive decline and dementia (e.g., dorsolateral prefrontal cortex). Results showed that antisaccade reaction times for the OCI group reliably decreased by 30 ms from pre- to post-intervention, whereas the control group did not produce a reliable pre- to post-intervention change in reaction time (i.e., 6 ms). Thus, we propose that in persons with OCI long-term CM and aerobic training improves the efficiency and effectiveness of the executive mechanisms mediating high-level oculomotor control.

Group-based exercise combined with dual-task training improves gait but not vascular health in active older adults without dementia.

BACKGROUND: Gait abnormalities and vascular disease risk factors are associated with cognitive impairment in aging. OBJECTIVE: To determine the impact of group-based exercise and dual-task training on gait and vascular health, in active community-dwelling older adults without dementia. METHODS: Participants [n=44, mean (SD) age: 73.5 (7.2) years, 68% female] were randomized to either intervention (exercise+dual-task; EDT) or control (exercise only; EO). Each week, for 26 weeks, both groups accumulated 50 or 75 min of aerobic exercise from group-based classes and 45 min of beginner-level square stepping exercise (SSE). Participants accumulating only 50 min of aerobic exercise were instructed to participate in an additional 25 min each week outside of class. The EDT group also answered cognitively challenging questions while performing SSE (i.e., dual-task training). The effect of the interventions on gait and vascular health was compared between groups using linear mixed effects models. RESULTS: At 26 weeks, the EDT group demonstrated increased dual-task (DT) gait velocity [difference between groups in mean change from baseline (95% CI): 0.29 m/s (0.16-0.43), p<0.001], DT step length [5.72 cm (2.19-9.24), p =0.002], and carotid intima-media thickness [0.10mm (0.003-0.20), p=0.04], as well as reduced DT stride time variability [8.31 coefficient of variation percentage points (-12.92 to -3.70), p<0.001], when compared to the EO group. CONCLUSIONS: Group-based exercise combined with dual-task training can improve DT gait characteristics in active older adults without dementia.

The Healthy Mind, Healthy Mobility Trial: A Novel Exercise Program for Older Adults.

BACKGROUND: More evidence is needed to conclude that a specific program of exercise and/or cognitive training warrants prescription for the prevention of cognitive decline. We examined the effect of a group-based standard exercise program for older adults, with and without dual-task training, on cognitive function in older adults without dementia. METHODS: We conducted a proof-of-concept, single-blinded, 26-wk randomized controlled trial whereby participants recruited from preexisting exercise classes at the Canadian Centre for Activity and Aging in London, Ontario, were randomized to the intervention group (exercise + dual-task [EDT]) or the control group (exercise only [EO]). Each week (2 or 3 d · wk(-1)), both groups accumulated a minimum of 50 min of aerobic exercise (target 75 min) from standard group classes and completed 45 min of beginner-level square-stepping exercise. The EDT group was also required to answer cognitively challenging questions while doing beginner-level square-stepping exercise (i.e., dual-task training). The effect of interventions on standardized global cognitive function (GCF) scores at 26 wk was compared between the groups using the linear mixed effects model approach. RESULTS: Participants (n = 44; 68% female; mean [SD] age: 73.5 [7.2] yr) had on average, objective evidence of cognitive impairment (Montreal Cognitive Assessment scores, mean [SD]: 24.9 [1.9]) but not dementia (Mini-Mental State Examination scores, mean [SD]: 28.8 [1.2]). After 26 wk, the EDT group showed greater improvement in GCF scores compared with the EO group (difference between groups in mean change [95% CI]: 0.20 SD [0.01-0.39], P = 0.04). CONCLUSIONS: A 26-wk group-based exercise program combined with dual-task training improved GCF in community-dwelling older adults without dementia.

A model for determining baseline morphometrics of skeletal myofibres.

The minimum diameter method of morphometry (MDM) is used to measure and detect changes in myofibre diameters (FD). The MDM is used to identify pathology in skeletal muscle. In such studies, an assumption is made that the mean FD in a particular muscle in both limbs is essentially the same. This study explored this premise to determine the accuracy of MDM as a means of morphometric analysis. Muscle biopsies were obtained from the left (G1) and right (G2) tibialis anterior of four vervet monkeys and from the massaged left (G3) and untreated right (G4) tibialis anterior of four animals. Wax sections were prepared for MDM and FD was measured. Three specimens were re-measured on four occasions. The mean FD of each biopsy from G1 and G2 limbs were compared and the number of measurements necessary to produce a meaningful result determined. Repeated measurement showed a difference of < 3.0% in FD means between the first and three subsequent measurements. There was no significant difference of FD means between G1 and G2, whilst the difference between G3 and G4 was 11.2%. When > 175 FD were measured, the difference from the final mean was less than 2.0%. These data show that, (1) FD data derived from a muscle in an untreated limb can be used as a control for experiment mediated changes of FD in the other, (2) MDM is a reliable means of measuring FD and (3) 150-175 FD are needed to provide a dependable result.

A model for determining baseline morphometrics of the capillary bed in skeletal muscle.

Changes in capillary diameter (CD) have been used to detect the effect of pharmacological interventions, physical treatments and ischaemic reperfusion injury in skin and muscle. For comparison, CDs within similar structures in the untreated limb of the same subject have been used as the control, with the assumption that CDs are the same in both limbs. This study employs light microscopic morphometry (LMM) to explore this premise, investigates the repeatability of LMM and determines the number of CDs that should be measured to produce a reliable result. Muscle biopsies were obtained from the left (L) and right (R) vastus lateralis of four rabbits and the left and right tibialis anterior of three vervet monkeys. Thin (1-micro m) resin sections were prepared for LMM examination and CDs were measured using computerised image analysis. To determine the repeatability of measurement, two specimens were re-measured on five occasions at monthly intervals. The mean CD of each biopsy from L and R limbs were compared and the number of measurements necessary to produce a result with less than a 3% difference was determined. A minimum of 58 and a maximum of 175 CDs were measured from each specimen. Repeated measurement of the same biopsies showed a non-significant mean difference of less than 2% in CD means between the first measurement and each of the four subsequent measurements. There was a non-significant difference of 3.7% in CD means between R and L limbs in one animal, in which less than 70 CDs were measured on each side. When 100 CDs or more were measured, the difference was always less than 2.3%. When grouped, the difference in CD means between L and R limbs was 0.5% in rabbits and 2.0% in vervet monkeys. The results confirm that firstly, CD data derived from a muscle in an untreated limb can be used as a control for experiment-mediated changes of CD in the other; secondly, LMM appears to be a reliable means of measuring CD; and thirdly, while fewer measurements may suffice, ideally 75-100 CDs are needed to provide a dependable result.