The association of structural versus load-dependent large artery stiffness mechanisms with cerebrovascular damage and cortical atrophy in humans.

Large central arterial stiffness is a risk factor for cerebrovascular damage and subsequent progression of neurodegenerative diseases, including Alzheimer's disease and dementia. However, arterial stiffness is determined by both the intrinsic components of the arterial wall (structural stiffness) and the load (i.e., arterial blood pressure) exerted upon it by the blood (load-dependent stiffness). This study aimed to determine the degree to which structural and/or load-dependent mechanisms of central arterial stiffness are associated with cerebrovascular damage. Among 128 healthy individuals (aged 63±6, age range: 50-80 years, 42% men), aortic and carotid artery stiffness was measured via carotid-femoral pulse wave velocity and B-mode ultrasonography, respectively. Using participant-specific exponential models, both aortic and carotid artery stiffness were standardized to a reference blood pressure to separate their structural and load-dependent stiffness mechanisms. Magnetic resonance imaging was used to derive total, periventricular, and deep cerebral white matter lesion volume (WMLV) and global cortical thickness. After adjusting for common cardiovascular disease risk factors, a 1 m/s increase in structural aortic stiffness was associated with 15% greater total WMLV (95% confidence interval [CI] = 0.01, 0.27, P = 0.036), 14% greater periventricular WMLV (95%CI = 0.004, 0.25, P = 0.044) and 0.011mm lower cortical thickness (95%CI = -0.022, -1.18, P = 0.028). No association was observed between structural carotid stiffness and WMLVs (total, periventricular, and deep), and neither aortic nor carotid load-dependent stiffness was associated with WMLVs or cortical thickness. Structural, not load-dependent, mechanisms of aortic stiffness are related to cerebrovascular-related white matter damage.

Educational Attainment Moderates Task-State Control Network Connectivity Relations to Response Conflict Among Healthy Older Adults.

OBJECTIVES: Older adult executive function varies widely due to brain and cognitive aging. Variance in older adult executive function is linked to increased response conflict from cognitive and brain aging. Cognitive reserve (CR) is a theoretical protective mechanism that lessens brain aging's impact on cognition and is associated with greater educational attainment. Recent work in rest-state functional magnetic resonance imaging (fMRI) suggests CR proxies moderate the relationship between functional connectivity (FC) and cognitive performance. Brain network FC in "control networks," including the salience (SN), dorsal attention and frontoparietal networks, are associated with cognitive processes in older adults. CR is hypothesized to maintain cognitive processing in part through changes in how brain networks respond to cognitive demands. However, it is unclear how CR proxies like educational attainment are related to control network FC during performance when cognitive demands are increased relative to rest. Because CR is expressed more in those with higher education, we hypothesized stronger control network FC would relate to better performance, where this relationship would be strongest among the most educated. METHODS: We collected flanker task data during fMRI to assess the impact of a CR proxy (i.e., educational attainment) on response conflict among older adult subjects (n = 42, age = 65-80). RESULTS: Linear mixed-effects models showed more educated older adults with greater SN-FC had a smaller flanker effect (i.e., less influence of distractors; p < .001) during task performance. DISCUSSION: For the first time, we show that educational attainment moderates the relationship between task-state SN-FC and executive function among older adults.

The Effects of Computerized Cognitive Training in Older Adults' Cognitive Performance and Biomarkers of Structural Brain Aging.

OBJECTIVES: Cognitive training (CT) has been investigated as a means of delaying age-related cognitive decline in older adults. However, its impact on biomarkers of age-related structural brain atrophy has rarely been investigated, leading to a gap in our understanding of the linkage between improvements in cognition and brain plasticity. This study aimed to explore the impact of CT on cognitive performance and brain structure in older adults. METHODS: One hundred twenty-four cognitively normal older adults recruited from 2 study sites were randomly assigned to either an adaptive CT (n = 60) or a casual game training (active control, AC, n = 64). RESULTS: After 10 weeks of training, CT participants showed greater improvements in the overall cognitive composite score (Cohen's d = 0.66, p < .01) with nonsignificant benefits after 6 months from the completion of training (Cohen's d = 0.36, p = .094). The CT group showed significant maintenance of the caudate volume as well as significant maintained fractional anisotropy in the left internal capsule and in left superior longitudinal fasciculus compared to the AC group. The AC group displayed an age-related decrease in these metrics of brain structure. DISCUSSION: Results from this multisite clinical trial demonstrate that the CT intervention improves cognitive performance and helps maintain caudate volume and integrity of white matter regions that are associated with cognitive control, adding to our understanding of the changes in brain structure contributing to changes in cognitive performance from adaptive CT. CLINICAL TRIAL REGISTRATION: NCT03197454.

Relation of forward and backward traveling pressure waves with subclinical carotid artery wall remodeling and central pulse pressure.

Central pulse pressure (PP) is the sum of forward and backward traveling pressure waves that have been associated with cardiovascular disease (CVD) risk. However, previous studies have reported differential findings regarding the importance of the forward versus the backward wave for CVD risk. Therefore, we sought to determine the degree to which the forward and backward pressure waves are associated with subclinical carotid artery wall remodeling and central PP in healthy adults. Using applanation tonometry, carotid pressure waveforms were acquired in 308 healthy individuals (aged 45 ± 17 years, range 19-80 years, 61% women), from which the time integral of the forward (PfTI) and backward (PbTI) pressure waves were derived via pressure-only wave separation analysis. Common carotid artery intima-media thickness (cIMT), a biomarker of subclinical CVD risk, was derived via B-mode ultrasonography measured ∼2 cm from the carotid bulb. Both PfTI (r = 0.31, P < 0.001) and PbTI (r = 0.40, P < 0.001) were correlated with cIMT. However, further analysis revealed that PbTI mediated the relation between PfTI and cIMT (proportion mediated = 156%, P < 0.001). The association between PbTI and cIMT remained after adjusting for age, sex, body mass index, blood glucose, low-density lipoprotein cholesterol, heart rate, brachial systolic pressure, and aortic stiffness (B = 0.02, 95% confidence interval = 0.01, 2.77, P < 0.001). Both PfTI (r = -0.58, P < 0.001) and PbTI (r = -0.50, P < 0.001) were correlated with central PP, however, PfTI fully mediated the association between PbTI and central PP (proportion mediated = 124%, P < 0.001). Although PfTI is correlated with higher central PP, it is PbTI that is directly associated with carotid artery wall remodeling.NEW & NOTEWORTHY The present study contributes to the growing body of evidence highlighting the physiological and clinical insight provided by the pulsatile hemodynamic components of central artery pulse pressure. The notable findings of this study are: 1) The reflected (backward) pressure wave is associated with carotid intima-media thickness independent of traditional cardiovascular risk factors, including systolic blood pressure and aortic stiffness. 2) The incident (forward) pressure wave, and not the reflected pressure wave, is associated with greater central pulse pressure.

Evaluating brain modularity benefits of an acting intervention: a discriminant-analysis framework.

Purpose: Aging is associated with a reduction in brain modularity as well as aspects of executive function, namely, updating, shifting, and inhibition. Previous research has suggested that the aging brain exhibits plasticity. Further, it has been hypothesized that broad-based intervention models may be more effective in eliciting overall gains in executive function than interventions targeted at specific executive skills (e.g., computer-based training). To this end, we designed a 4-week theater-based acting intervention in older adults within an RCT framework. We hypothesized that older adults would show improvements in brain modularity and aspects of executive function, ascribed to the acting intervention. Materials and methods: The participants were 179 adults from the community, aged 60-89 years and on average, college educated. They completed a battery of executive function tasks and resting state functional MRI scans to measure brain network modularity pre- and post-intervention. Participants in the active intervention group (n = 93) enacted scenes with a partner that involved executive function, whereas the active control group (n = 86) learned about the history and styles of acting. Both groups met two times/week for 75-min for 4 weeks. A mixed model was used to evaluate intervention effects related to brain modularity. Discriminant-analysis was used to determine the role of seven executive functioning tasks in discriminating the two groups. These tasks indexed subdomains of updating, switching, and inhibition. Discriminant tasks were subject to a logistic regression analysis to determine how post-intervention executive function performance interacted with changes in modularity to predict group membership. Results: We noted an increase in brain modularity in the acting group, relative to pre-intervention and controls. Performance on updating tasks were representative of the intervention group. However, post-intervention performance on updating did not interact with the observed increase in brain modularity to distinguish groups. Conclusion: An acting intervention can facilitate improvements in modularity and updating, both of which are sensitive to aging and may confer benefits to daily functioning and the ability to learn.

Functional connectivity of the cerebellar vermis in bipolar disorder and associations with mood.

Purpose: Studies of the neural underpinnings of bipolar type I disorder have focused on the emotional control network. However, there is also growing evidence for cerebellar involvement, including abnormal structure, function, and metabolism. Here, we sought to assess functional connectivity of the cerebellar vermis with the cerebrum in bipolar disorder and to assess whether connectivity might depend on mood. Methods: This cross-sectional study enrolled 128 participants with bipolar type I disorder and 83 control comparison participants who completed a 3 T magnetic resonance imaging (MRI) study, which included anatomical as well as resting state Blood Oxygenation Level Dependent (BOLD) imaging. Functional connectivity of the cerebellar vermis to all other brain regions was assessed. Based on quality control metrics of the fMRI data, 109 participants with bipolar disorder and 79 controls were included in the statistical analysis comparing connectivity of the vermis. In addition, the data was explored for the potential impacts of mood, symptom burden, and medication in those with bipolar disorder. Results: Functional connectivity between the cerebellar vermis and the cerebrum was found to be aberrant in bipolar disorder. The connectivity of the vermis was found to be greater in bipolar disorder to regions involved in motor control and emotion (trending), while reduced connectivity was observed to a region associated with language production. In the participants with bipolar disorder, past depression symptom burden affected connectivity; however, no effects of medication were observed. Functional connectivity between the cerebellar vermis and all other regions revealed an inverse association with current mood ratings. Conclusion: Together the findings may suggest that the cerebellum plays a compensatory role in bipolar disorder. The proximity of the cerebellar vermis to the skull may make this region a potential target for treatment with transcranial magnetic stimulation.

Functional Connectivity of the Cerebellar Vermis in Bipolar Disorder and Associations with Mood.

Purpose: Studies of the neural underpinnings of bipolar type I disorder have focused on the emotional control network. However, there is also growing evidence for cerebellar involvement, including abnormal structure, function, and metabolism. Here, we sought to assess functional connectivity of the cerebellum with the cerebrum in bipolar disorder and to assess whether any effects might depend on mood. Methods: This cross-sectional study enrolled 128 participants with bipolar type I disorder and 83 control comparison participants who completed a 3T MRI scan, which included anatomical imaging as well as resting state BOLD imaging. Functional connectivity of the cerebellar vermis to all other brain regions was assessed. Based on quality control metrics of the fMRI data, 109 participants with bipolar disorder and 79 controls were used to in the statistical analysis comparing connectivity of the vermis as well as associations with mood. Potential impacts of medications were also explored. Results: Functional connectivity of the cerebellar vermis in bipolar disorder was found to differ significantly between brain regions known to be involved in the control of emotion, motor function, and language. While connections with emotion and motor control areas were significantly stronger in bipolar disorder, connection to a region associated language production was significantly weaker. In the participants with bipolar disorder, ratings of depression and mania were inversely associated with vermis functional connectivity. No effect of medications on these connections were observed. Conclusion: Together the findings suggest cerebellum may play a compensatory role in bipolar disorder and when it can no longer fulfill this role, depression and mania develop. The proximity of the cerebellar vermis to the skull may make this region a potential target for treatment with transcranial magnetic stimulation.

Sex-specific associations of reservoir-excess pressure parameters with age and subclinical vascular remodeling.

OBJECTIVE: Central artery reservoir pressure and excess pressure (XSP) are associated with cardiovascular disease (CVD) events and mortality. However, sex differences in the trajectory of central reservoir pressure and XSP with advancing age and their relations with vascular markers of subclinical CVD risk are incompletely understood. Therefore, we tested the hypothesis that central reservoir pressure and XSP would be positively associated with advancing age and vascular markers of subclinical CVD risk in men and women. METHOD: Healthy adults ( n  = 398; aged 18-80 years, 60% female individuals) had central (carotid) artery pressure waveforms acquired by applanation tonometry. Reservoir pressure and XSP peaks and integrals were derived retrospectively from carotid pressure waveforms using custom written software. Carotid artery intimal-medial thickness (IMT) was measured by ultrasonography, and aortic stiffness was determined from carotid-femoral pulse wave velocity (cfPWV). RESULTS: Reservoir pressure peak, reservoir pressure integral and XSP integral were higher with age in both men and women ( P  < 0.05), whereas XSP peak was lower with age in men ( P  < 0.05). In women, both reservoir pressure peak ( ß â€Š= 0.231, P  < 0.01) and reservoir pressure integral ( ß â€Š= 0.254, P  < 0.01) were associated with carotid artery IMT, and reservoir pressure peak was associated with cfPWV ( ß â€Š= 0.120, P  = 0.02) after adjusting for CVD risk factors. CONCLUSION: Central artery reservoir pressure and XSP were higher with advancing age in men and women, and reservoir pressure peak was associated with both carotid artery wall thickness and aortic stiffness in women but not men. Central reservoir pressure peak may provide some insight into sex differences in vascular remodeling and subclinical CVD risk with advancing age in healthy adults.

Reshaping the path of mild cognitive impairment by refining exercise prescription: a study protocol of a randomized controlled trial to understand the "what," "for whom," and "how" of exercise to promote cognitive function.

BACKGROUND: Targeted exercise training is a promising strategy for promoting cognitive function and preventing dementia in older age. Despite the utility of exercise as an intervention, variation still exists in exercise-induced cognitive gains and questions remain regarding the type of training (i.e., what), as well as moderators (i.e., for whom) and mechanisms (i.e., how) of benefit. Both aerobic training (AT) and resistance training (RT) enhance cognitive function in older adults without cognitive impairment; however, the vast majority of trials have focused exclusively on AT. Thus, more research is needed on RT, as well as on the combination of AT and RT, in older adults with mild cognitive impairment (MCI), a prodromal stage of dementia. Therefore, we aim to conduct a 6-month, 2 × 2 factorial randomized controlled trial in older adults with MCI to assess the individual effects of AT and RT, and the combined effect of AT and RT on cognitive function and to determine the possible underlying biological mechanisms. METHODS: Two hundred and sixteen community-dwelling adults, aged 65 to 85 years, with MCI from metropolitan Vancouver will be recruited to participate in this study. Randomization will be stratified by biological sex and participants will be randomly allocated to one of the four experimental groups: (1) 4×/week balance and tone (BAT; i.e., active control); (2) combined 2×/week AT + 2×/week RT; (3) 2×/week AT + 2×/week BAT; or (4) 2×/week RT + 2×/week BAT. The primary outcome is cognitive function as measured by the Alzheimer's Disease Assessment Scale-Cognitive-Plus. Secondary outcomes include cognitive function, health-related quality of life, physical function, actigraphy measures, questionnaires, and falls. Outcomes will be measured at baseline, 6 months (i.e., trial completion), and 18 months (i.e., 12-month follow-up). DISCUSSION: Establishing the efficacy of different types and combinations of exercise training to minimize cognitive decline will advance our ability to prescribe exercise as "medicine" to treat MCI and delay the onset and progression of dementia. This trial is extremely timely as cognitive impairment and dementia pose a growing threat to global public health. TRIAL REGISTRATION: ClinicalTrials.gov NCT02737878 . Registered on April 14, 2016.

Aerobic exercise improves episodic memory in late adulthood: a systematic review and meta-analysis.

Background: Aerobic exercise remains one of the most promising approaches for enhancing cognitive function in late adulthood, yet its potential positive effects on episodic memory remain poorly understood and a matter of intense debate. Prior meta-analyses have reported minimal improvements in episodic memory following aerobic exercise but have been limited by restrictive inclusion criteria and infrequent examination of exercise parameters. Methods: We conducted a meta-analysis of randomized controlled trials to determine if aerobic exercise influences episodic memory in late adulthood (M = 70.82 years) and examine possible moderators. Thirty-six studies met inclusion criteria, representing data from 2750 participants. Results: Here we show that aerobic exercise interventions are effective at improving episodic memory (Hedges'g = 0.28; p = 0.002). Subgroup analyses revealed a moderating effect of age (p = 0.027), with a significant effect for studies with a mean age between 55-68 but not 69-85. Mixed-effects analyses demonstrated a positive effect on episodic memory among studies with a high percentage of females (65-100%), participants with normal cognition, studies reporting intensity, studies with a no-contact or nonaerobic physical activity control group, and studies prescribing >3900 total minutes of activity (range 540-8190 min). Conclusions: Aerobic exercise positively influences episodic memory among adults ≥55 years without dementia, with larger effects observed among various sample and intervention characteristics-the clearest moderator being age. These results could have far-reaching clinical and public health relevance, highlighting aerobic exercise as an accessible, non-pharmaceutical intervention to improve episodic memory in late adulthood.

Association between cardiorespiratory fitness and cerebrovascular reactivity to a breath-hold stimulus in older adults: influence of aerobic exercise training.

Cerebrovascular reactivity (CVR) to a physiological stimulus is a commonly used surrogate of cerebrovascular health. Cross-sectional studies using blood oxygen level dependent (BOLD) neuroimaging demonstrated lower BOLD-CVR to hypercapnia among adults with high compared with lower cardiorespiratory fitness (CRF) in contrast to transcranial Doppler studies. However, whether BOLD-CVR changes following chronic aerobic exercise in older, cognitively intact adults is unclear. This study evaluated relations between BOLD-CVR with CRF (V̇o2peak) using a cross-sectional and interventional study design. We hypothesized that 1) greater CRF would be associated with lower BOLD-CVR in older adults (n = 114; 65 ± 6.5 yr) with a wide range of CRF and 2) BOLD-CVR would be attenuated after exercise training in a subset (n = 33) randomized to 3-mo of moderate- or light-intensity cycling. CVR was quantified as the change in the BOLD signal in response to acute hypercapnia using a blocked breath-hold design from a region-of-interest analysis for cortical networks. In the cross-sectional analysis, there was a quadratic relation between V̇o2peak (P = 0.03), but not linear (P = 0.87) and cortical BOLD-CVR. BOLD-CVR increased until a V̇o2peak ∼28 mL/kg/min after which BOLD-CVR declined. The nonlinear trend was consistent across all networks (P = 0.04-0.07). In the intervention, both the active and light-intensity exercise groups improved CRF similarly (6% vs. 10.8%, P = 0.28). The percent change in CRF was positively associated with change in BOLD-CVR in the default mode network only. These data suggest that BOLD-CVR is nonlinearly associated with CRF and that in lower-fit adults default mode network may be most sensitive to CRF-related increases in BOLD-CVR.NEW & NOTEWORTHY Earlier studies evaluating associations between cardiorespiratory fitness (CRF) and cerebrovascular reactivity (CVR) have demonstrated conflicting findings dependent on imaging modality or subject characteristics in individuals across a narrow range of CRF. This study demonstrates that CRF is nonlinearly associated with CVR measured by blood oxygen level dependent (BOLD) fMRI in a large sample of middle-aged and older adults across a wide range of CRF, suggesting that conflicting prior findings are related to the range of CRFs studied.

Getting Fit to Counteract Cognitive Aging: Evidence and Future Directions.

Physical activity has shown tremendous promise for counteracting cognitive aging, but also tremendous variability in cognitive benefits. We describe evidence for how exercise affects cognitive and brain aging, and whether cardiorespiratory fitness is a key factor. We highlight a brain network framework as a valuable paradigm for the mechanistic insight needed to tailor physical activity for cognitive benefits.

Hippocampal acidity and volume are differentially associated with spatial navigation in older adults.

The hippocampus is negatively affected by aging and is critical for spatial navigation. While there is evidence that wayfinding navigation tasks are especially sensitive to preclinical hippocampal deterioration, these studies have primarily used volumetric hippocampal imaging without considering microstructural properties or anatomical variation within the hippocampus. T1ρ is an MRI measure sensitive to regional pH, with longer relaxation rates reflecting acidosis as a marker of metabolic dysfunction and neuropathological burden. For the first time, we investigate how measures of wayfinding including landmark location learning and delayed memory in cognitively normal older adults (N = 84) relate to both hippocampal volume and T1ρ in the anterior and posterior hippocampus. Regression analyses revealed hippocampal volume was bilaterally related to learning, while right lateralized T1ρ was related to delayed landmark location memory and bilateral T1ρ was related to the delayed use of a cognitive map. Overall, results suggest hippocampal volume and T1ρ relaxation rate tap into distinct mechanisms involved in preclinical cognitive decline as assessed by wayfinding navigation, and laterality influenced these relationships more than the anterior-posterior longitudinal axis of the hippocampus.

White matter plasticity in healthy older adults: The effects of aerobic exercise.

White matter deterioration is associated with cognitive impairment in healthy aging and Alzheimer's disease. It is critical to identify interventions that can slow down white matter deterioration. So far, clinical trials have failed to demonstrate the benefits of aerobic exercise on the adult white matter using diffusion Magnetic Resonance Imaging. Here, we report the effects of a 6-month aerobic walking and dance interventions (clinical trial NCT01472744) on white matter integrity in healthy older adults (n = 180, 60-79 years) measured by changes in the ratio of calibrated T1- to T2-weighted images (T1w/T2w). Specifically, the aerobic walking and social dance interventions resulted in positive changes in the T1w/T2w signal in late-myelinating regions, as compared to widespread decreases in the T1w/T2w signal in the active control. Notably, in the aerobic walking group, positive change in the T1w/T2w signal correlated with improved episodic memory performance. Lastly, intervention-induced increases in cardiorespiratory fitness did not correlate with change in the T1w/T2w signal. Together, our findings suggest that white matter regions that are vulnerable to aging retain some degree of plasticity that can be induced by aerobic exercise training. In addition, we provided evidence that the T1w/T2w signal may be a useful and broadly accessible measure for studying short-term within-person plasticity and deterioration in the adult human white matter.

Sensor-measured sedentariness and physical activity are differentially related to fluid and crystallized abilities in aging.

Aerobic exercise and physical activity (PA) are known to benefit cognition in adulthood. However, a typical older adult spends most of the day sedentary or in light PA, behaviors that are typically poorly captured by questionnaires. To better understand the associations between time spent in different intensities of lifestyle PA and cognition, we measured average time spent daily in sedentariness, light, and moderate to vigorous PA using hip-worn sensors (ActiGraph accelerometers). We studied baseline data from 228 cognitively normal adults (Age 60-80) who took part in a clinical trial (clinical study identifier: NCT01472744). Fluid (processing speed, memory, and reasoning) and crystallized abilities (vocabulary knowledge) were assessed with the Virginia Cognitive Aging Battery. Adjusting for age, sex, and several modifiable socioeconomic, physical and functional health factors, time spent daily in moderate to vigorous PA was positively related with fluid abilities (perceptual speed and reasoning). Furthermore, we found that those spending more time sedentary performed better on vocabulary knowledge and reasoning tasks. In contrast, time spent in light PA was not related to either fluid or crystallized abilities. Our results add to the previous literature by providing the first sensor-based evidence that crystallized and fluid abilities in older age may be associated with engagement in different intensities of daily activity. Moreover, our findings suggest that the behavior of moderate to vigorous PA is at least as important in relation to cognition as the desirable long-term physiological effects of higher intensity PA and exercise. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Occupational Physical Stress Is Negatively Associated With Hippocampal Volume and Memory in Older Adults.

Our jobs can provide intellectually and socially enriched environments but also be the source of major psychological and physical stressors. As the average full-time worker spends >8 h at work per weekday and remains in the workforce for about 40 years, occupational experiences must be important factors in cognitive and brain aging. Therefore, we studied whether occupational complexity and stress are associated with hippocampal volume and cognitive ability in 99 cognitively normal older adults. We estimated occupational complexity, physical stress, and psychological stress using the Work Design Questionnaire (Morgeson and Humphrey, 2006), Quantitative Workload Inventory and Interpersonal Conflict at Work Scale (Spector and Jex, 1998). We found that physical stress, comprising physical demands and work conditions, was associated with smaller hippocampal volume and poorer memory performance. These associations were independent of age, gender, brain size, socioeconomic factors (education, income, and job title), duration of the job, employment status, leisure physical activity and general stress. This suggests that physical demands at work and leisure physical activity may have largely independent and opposite effects on brain and cognitive health. Our findings highlight the importance of considering midlife occupational experiences, such as work physical stress, in understanding individual trajectories of cognitive and brain aging.

Home-Based, Adaptive Cognitive Training for Cognitively Normal Older adults: Initial Efficacy Trial.

OBJECTIVES: We examined whether a home-based, adaptive cognitive training (CT) program would lead to cognitive performance changes on a neuropsychological test battery in cognitively normal older adults. METHOD: Sixty-eight older adults (age = 70.0, SD = 3.74) were randomly assigned to either CT or an active control group (AC, casual computer games). Participants were instructed to train on their assigned programs for 42 min per day, 5 days per week, over 10 weeks (35 hr of total program usage). Participants completed tests of processing speed, working memory, and executive control before and after 10 weeks of training. RESULTS: Training groups did not differ in performance before training. After training, CT participants out-performed AC participants in the overall cognitive composite score, driven by processing speed and working memory domains. DISCUSSION: Our results show that a limited dose of home-based CT can drive cognitive improvements as measured with neuropsychological test battery, suggesting potential cognitive health maintenance implications for cognitively normal older adults.

Acute Exercise Effects Predict Training Change in Cognition and Connectivity.

PURPOSE: Previous studies report memory and functional connectivity of memory systems improve acutely after a single aerobic exercise session or with training, suggesting that the acute effects of aerobic exercise may reflect initial changes that adapt over time. In this trial, for the first time, we test the proof-of-concept of whether the acute and training effects of aerobic exercise on working memory and brain network connectivity are related in the same participants. METHODS: Cognitively normal older participants (N = 34) were enrolled in a randomized clinical trial (NCT02453178). Participants completed fMRI resting state and a face working memory N-back task acutely after light- and moderate-intensity exercises and after a 12-wk aerobic training intervention. RESULTS: Functional connectivity did not change more after moderate-intensity training compared with light-intensity training. However, both training groups showed similar changes in cardiorespiratory fitness (CRF) (maximal exercise oxygen uptake, V˙O2peak), limiting group-level comparisons. Acute effects of moderate-intensity aerobic exercise on connections primarily in the default network predicted training enhancements in the same connections. Working memory also improved acutely, especially after moderate-intensity, and greater acute improvements predicted greater working memory improvement with training. Exercise effects on functional connectivity of right lateralized frontoparietal connections were related to both acute and training gains in working memory. CONCLUSIONS: Our data support the concept of acute aerobic exercise effects on functional brain systems and performance as an activity-evoked biomarker for exercise training benefits in the same outcomes. These findings may lead to new insights and methods for improving memory outcomes with aerobic exercise training.

Cardiorespiratory fitness and hippocampal volume predict faster episodic associative learning in older adults.

Declining episodic memory is common among otherwise healthy older adults, in part due to negative effects of aging on hippocampal circuits. However, there is significant variability between individuals in severity of aging effects on the hippocampus and subsequent memory decline. Importantly, variability may be influenced by modifiable protective physiological factors such as cardiorespiratory fitness (CRF). More research is needed to better understand which aspects of cognition that decline with aging benefit most from CRF. The current study evaluated the relation of CRF with learning rate on the episodic associative learning (EAL) task, a task designed specifically to target hippocampal-dependent relational binding and to evaluate learning with repeated occurrences. Results show higher CRF was associated with faster learning rate. Larger hippocampal volume was also associated with faster learning rate, though hippocampal volume did not mediate the relationship between CRF and learning rate. Furthermore, to support the distinction between learning item relations and learning higher-order sequences, which declines with aging but is largely reliant on extra-hippocampal learning systems, we found learning rate on the EAL task was not related to motor sequence learning on the alternating serial reaction time task. Motor sequence learning was also not correlated with hippocampal volume. Thus, for the first time, we show that both higher CRF and larger hippocampal volume in healthy older adults are related to enhanced rate of relational memory acquisition.

Exercise and Hippocampal Memory Systems.

No medications prevent or reverse age-related cognitive decline. Physical activity (PA) enhances memory in rodents, but findings are mixed in human studies. As a result, exercise guidelines specific for brain health are absent. Here, we re-examine results from human studies, and suggest the use of more sensitive tasks to evaluate PA effects on age-related changes in the hippocampus, such as relational memory and mnemonic discrimination. We discuss recent advances from rodent and human studies into the underlying mechanisms at both the central and peripheral levels, including neurotrophins and myokines that could contribute to improved memory. Finally, we suggest guidelines for future research to help expedite well-founded PA recommendations for the public.