Peak Aging: Shape Your Development

One-year aerobic exercise increases cerebral blood flow in cognitively normal older adults

The impact of aerobic exercise training (AET) on cerebral blood flow (CBF) regulation remains inconclusive. This study investigated the effects of one-year progressive, moderate-to-vigorous AET on CBF, central arterial stiffness, and cognitive performance in cognitively normal older adults. Seventy-three older adults were randomly assigned to AET or stretching-and-toning (SAT, active control) intervention. CBF was measured with 2D duplex ultrasonography. Central arterial stiffness, measured by carotid β-stiffness index, was assessed with the ultrasonography and applanation tonometry. Cerebrovascular resistance (CVR) was calculated as mean arterial pressure divided by CBF. A cognitive battery was administered with a focus on memory and executive function. Cardiorespiratory fitness was measured by peak oxygen consumption (V˙O2peak). One-year AET increased V˙O2peak and CBF and decreased CVR and carotid β-stiffness index. In the AET group, improved V˙O2peak was correlated with increased CBF (r = 0.621, p = 0.001) and decreased CVR (r = -0.412, p = 0.037) and carotid β-stiffness index (r = -0.478, p = 0.011). Further, increased Woodcock-Johnson recall score was associated with decreased CVR (r = -0.483, p = 0.012) and carotid β-stiffness index (r = -0.498, p = 0.008) in AET group (not in SAT group). In conclusion, one-year progressive, moderate-to-vigorous aerobic exercise training increased CBF and decreased carotid arterial stiffness and CVR which were associated with improved memory function in cognitively normal older adults.

Computational epidemiology study of homeostatic compensation during sensorimotor aging

The vestibulo-ocular reflex (VOR) stabilizes vision during head motion. Age-related changes of vestibular neuroanatomical properties predict a linear decay of VOR function. Nonetheless, human epidemiological data show a stable VOR function across the life span. In this study, we model cerebellum-dependent VOR adaptation to relate structural and functional changes throughout aging. We consider three neurosynaptic factors that may codetermine VOR adaptation during aging: the electrical coupling of inferior olive neurons, the long-term spike timing-dependent plasticity at parallel fiber - Purkinje cell synapses and mossy fiber - medial vestibular nuclei synapses, and the intrinsic plasticity of Purkinje cell synapses Our cross-sectional aging analyses suggest that long-term plasticity acts as a global homeostatic mechanism that underpins the stable temporal profile of VOR function. The results also suggest that the intrinsic plasticity of Purkinje cell synapses operates as a local homeostatic mechanism that further sustains the VOR at older ages. Importantly, the computational epidemiology approach presented in this study allows discrepancies among human cross-sectional studies to be understood in terms of interindividual variability in older individuals. Finally, our longitudinal aging simulations show that the amount of residual fibers coding for the peak and trough of the VOR cycle constitutes a predictive hallmark of VOR trajectories over a lifetime.

The comparison of the effects of physical activity and neurofeedback training on postural stability and risk of fall in elderly women: A single-blind randomized controlled trial

Study Design: This was a single-blind randomized controlled trial.Background: Fall and postural instability are common undesirable consequences of the elderly. Although the benefits of exercise for fall prevention have been demonstrated, the majority of the elderly are physically inactive due to several physical and mental limitations they may face. Another alternative treatment such as neurofeedback with providing additional sensory information may enhance movement performance and so decrease the risk of fall.Objectives: To compare the effects of physical activity and neurofeedback training on postural stability and risk of fall in elderly women.Methods: Forty-five physically independent women who were older than 65 years old, living in the Fereshtegan Elderly Care Center in Shiraz, were recruited and randomly divided into three groups including control, physical activity, and neurofeedback training (15 people in each group). Participants in experimental groups trained for 12 weeks (3 days per week/30 minutes per session). Fall risk and postural stability of participants in all three groups were evaluated before and after intervention using the Biodex Balance System.Results: A mixed model design ANOVA comparing neurofeedback training and physical activity exhibited a significantly greater improvement in both risk of fall and postural stability compared to control (P < .05). Results of post-hoc analysis further indicated that neurofeedback training compared to physical activity can be superior beneficial in reducing risk of fall (P = .005) and improving postural stability (P = .005). There were also significant interactions between group and time of fall risk (P = .0005, ηp2 = 0.97) and postural stability (P = .001, ηp2 = 0.79).Conclusion: Both neurofeedback and physical activity could be considered as useful alternative for postural stability and balance improvement in elderly women; however, neurofeedback training was more effective than physical activity.

Neurofeedback and the Aging Brain: A Systematic Review of Training Protocols for Dementia and Mild Cognitive Impairment

Dementia describes a set of symptoms that occur in neurodegenerative disorders and that is characterized by gradual loss of cognitive and behavioral functions. Recently, non-invasive neurofeedback training has been explored as a potential complementary treatment for patients suffering from dementia or mild cognitive impairment. Here we systematically reviewed studies that explored neurofeedback training protocols based on electroencephalography or functional magnetic resonance imaging for these groups of patients. From a total of 1,912 screened studies, 10 were included in our final sample (N = 208 independent participants in experimental and N = 81 in the control groups completing the primary endpoint). We compared the clinical efficacy across studies, and evaluated their experimental designs and reporting quality. In most studies, patients showed improved scores in different cognitive tests. However, data from randomized controlled trials remains scarce, and clinical evidence based on standardized metrics is still inconclusive. In light of recent meta-research developments in the neurofeedback field and beyond, quality and reporting practices of individual studies are reviewed. We conclude with recommendations on best practices for future studies that investigate the effects of neurofeedback training in dementia and cognitive impairment.

Does playing a musical instrument prevent dementia?

Neurofeedback and the Aging Brain: A Systematic Review of Training Protocols for Dementia and Mild Cognitive Impairment

Dementia describes a set of symptoms that occur in neurodegenerative disorders and that is characterized by gradual loss of cognitive and behavioral functions. Recently, non-invasive neurofeedback training has been explored as a potential complementary treatment for patients suffering from dementia or mild cognitive impairment. Here we systematically reviewed studies that explored neurofeedback training protocols based on electroencephalography or functional magnetic resonance imaging for these groups of patients. From a total of 1,912 screened studies, 10 were included in our final sample (N = 208 independent participants in experimental and N = 81 in the control groups completing the primary endpoint). We compared the clinical efficacy across studies, and evaluated their experimental designs and reporting quality. In most studies, patients showed improved scores in different cognitive tests. However, data from randomized controlled trials remains scarce, and clinical evidence based on standardized metrics is still inconclusive. In light of recent meta-research developments in the neurofeedback field and beyond, quality and reporting practices of individual studies are reviewed. We conclude with recommendations on best practices for future studies that investigate the effects of neurofeedback training in dementia and cognitive impairment.

SMR/Theta Neurofeedback Training Improves Cognitive Performance and EEG Activity in Elderly With Mild Cognitive Impairment: A Pilot Study

Background: Neurofeedback (NF) training, as a method of self-regulation of brain activity, may be beneficial in elderly patients with mild cognitive impairment (MCI). In this pilot study, we investigated whether a sensorimotor (SMR)/theta NF training could improve cognitive performance and brain electrical activity in elderly patients with MCI. Methods: Twenty elderly patients with MCI were assigned to 20 consecutive sessions of sensorimotor (SMR)/theta NF training, during 10 weeks, on a basis of two sessions each week. Neuropsychological assessments and questionnaires, as well as electroencephalogram (EEG), were performed and compared between baseline (T0), after the last NF training session at 10 weeks (T1), and 1-month follow-up (T2). Results: Repeated measures ANOVA revealed that from baseline to post-intervention, participants showed significant improvement in the Montreal cognitive assessment (MoCa, F = 4.78; p = 0.012), the delayed recall of the Rey auditory verbal learning test (RAVLT, F = 3.675; p = 0.032), the Forward digit span (F = 13.82; p < 0.0001), the Anxiety Goldberg Scale (F = 4.54; p = 0.015), the Wechsler Adult Intelligence Score–Fourth Edition (WAIS-IV; F = 24.75; p < 0.0001), and the Mac Nair score (F = 4.47; p = 0.016). EEG theta power (F = 4.44; p = 0.016) and alpha power (F = 3.84; p = 0.027) during eyes-closed resting-state significantly increased after the NF training and showed sustained improvement at a 1-month follow-up. Conclusion: Our results suggest that NF training could be effective to reduce cognitive deficits in elderly patients with MCI and improve their EEG activity. If these findings are confirmed by randomized controlled studies with larger samples of patients, NF could be seen as a useful non-invasive, non-pharmacological tool for preventing further decline, rehabilitation of cognitive function in the elderly. Clinical Trial Registration: This pilot study was a preliminary step before the trial registered in www.ClinicalTrials.gov, under the number of NCT03526692

Diffusion tensor imaging of the corpus callosum in healthy aging: Investigating higher order polynomial regression modelling

Previous diffusion tensor imaging (DTI) studies confirmed the vulnerability of corpus callosum (CC) fibers to aging. However, most studies employed lower order regressions to study the relationship between age and white matter microstructure. The present study investigated whether higher order polynomial regression modelling can better describe the relationship between age and CC DTI metrics compared to lower order models in 140 healthy participants (ages 18-85). The CC was found to be non-uniformly affected by aging, with accelerated and earlier degradation occurring in anterior portion; callosal volume, fiber count, fiber length, mean fibers per voxel, and FA decreased with age while mean, axial, and radial diffusivities increased. Half of the parameters studied also displayed significant age-sex interaction or intracranial volume effects. Higher order models were chosen as the best fit, based on Bayesian Information Criterion minimization, in 16 out of 23 significant cases when describing the relationship between DTI measurements and age. Higher order model fits provided different estimations of aging trajectory peaks and decline onsets than lower order models; however, a likelihood ratio test found that higher order regressions generally did not fit the data significantly better than lower order polynomial or linear models. The results contrast the modelling approaches and highlight the importance of using higher order polynomial regression modelling when investigating associations between age and CC white matter microstructure.

Comparison of effects between SMR/delta-ratio and beta1/theta-ratio neurofeedback training for older adults with Mild Cognitive Impairment: a protocol for a randomized controlled trial

BACKGROUND: Older adults with Mild Cognitive Impairment (MCI) are at high risk of progressing to Alzheimer's disease (AD). Slowing down the effect of dementia by enhancing brain plasticity represents one of the most prominent challenges. Neurofeedback (NF) has shown promising results in improving working memory but has never been evaluated in people with MCI. We aim to examine whether NF training can decrease cognitive disorders, targeting memory, attention functions and brain electrical activity in elderly patients with MCI. METHODS: In this single-blind, randomized controlled trial (RCT) protocol, we will investigate the effects of two NF training protocols on cognitive performances and on brain electrical activity. Sixty MCI patients will be assigned either to an intervention program or to psycho-pedagogical care as a control condition. Participants in the intervention group will attend 30 sessions of sensorimotor/delta-ratio NF training or beta1/theta-ratio NF training. Neuropsychological assessment, questionnaires and electroencephalography (EEG) assessment parameters will be used as dependent variables in three periods: at baseline (T0), immediately after the last NF training session at 4 months (T1) and at 3-month follow-up (T2). The primary outcome will be the change in attention measured with the Trail Making Test B. Secondary outcome will be the changes in cognitive performance and in EEG activities. DISCUSSION: If the results of our study show improvement in cognitive performances of older adults with MCI, this non-invasive, low-cost technique may deserve better consideration as a therapeutic intervention to delay cognitive decline and dementia. Consequently, research in NF will need to review and develop the rigor of its application in gerontology. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT03526692 . Registered on 16 May 2018.

Mixed exercise training for adults with fibromyalgia

BACKGROUND: Exercise training is commonly recommended for individuals with fibromyalgia. This review is one of a series of reviews about exercise training for fibromyalgia that will replace the review titled "Exercise for treating fibromyalgia syndrome", which was first published in 2002. OBJECTIVES: To evaluate the benefits and harms of mixed exercise training protocols that include two or more types of exercise (aerobic, resistance, flexibility) for adults with fibromyalgia against control (treatment as usual, wait list control), non exercise (e.g. biofeedback), or other exercise (e.g. mixed versus flexibility) interventions.Specific comparisons involving mixed exercise versus other exercises (e.g. resistance, aquatic, aerobic, flexibility, and whole body vibration exercises) were not assessed. SEARCH METHODS: We searched the Cochrane Library, MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), Thesis and Dissertations Abstracts, the Allied and Complementary Medicine Database (AMED), the Physiotherapy Evidence Databese (PEDro), Current Controlled Trials (to 2013), WHO ICTRP, and ClinicalTrials.gov up to December 2017, unrestricted by language, to identify all potentially relevant trials. SELECTION CRITERIA: We included randomised controlled trials (RCTs) in adults with a diagnosis of fibromyalgia that compared mixed exercise interventions with other or no exercise interventions. Major outcomes were health-related quality of life (HRQL), pain, stiffness, fatigue, physical function, withdrawals, and adverse events. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials for inclusion, extracted data, and assessed risk of bias and the quality of evidence for major outcomes using the GRADE approach. MAIN RESULTS: We included 29 RCTs (2088 participants; 98% female; average age 51 years) that compared mixed exercise interventions (including at least two of the following: aerobic or cardiorespiratory, resistance or muscle strengthening exercise, and flexibility exercise) versus control (e.g. wait list), non-exercise (e.g. biofeedback), and other exercise interventions. Design flaws across studies led to selection, performance, detection, and selective reporting biases. We prioritised the findings of mixed exercise compared to control and present them fully here.Twenty-one trials (1253 participants) provided moderate-quality evidence for all major outcomes but stiffness (low quality). With the exception of withdrawals and adverse events, major outcome measures were self-reported and expressed on a 0 to 100 scale (lower values are best, negative mean differences (MDs) indicate improvement; we used a clinically important difference between groups of 15% relative difference). Results for mixed exercise versus control show that mean HRQL was 56 and 49 in the control and exercise groups, respectively (13 studies; 610 participants) with absolute improvement of 7% (3% better to 11% better) and relative improvement of 12% (6% better to 18% better). Mean pain was 58.6 and 53 in the control and exercise groups, respectively (15 studies; 832 participants) with absolute improvement of 5% (1% better to 9% better) and relative improvement of 9% (3% better to 15% better). Mean fatigue was 72 and 59 points in the control and exercise groups, respectively (1 study; 493 participants) with absolute improvement of 13% (8% better to 18% better) and relative improvement of 18% (11% better to 24% better). Mean stiffness was 68 and 61 in the control and exercise groups, respectively (5 studies; 261 participants) with absolute improvement of 7% (1% better to 12% better) and relative improvement of 9% (1% better to 17% better). Mean physical function was 49 and 38 in the control and exercise groups, respectively (9 studies; 477 participants) with absolute improvement of 11% (7% better to 15% better) and relative improvement of 22% (14% better to 30% better). Pooled analysis resulted in a moderate-quality risk ratio for all-cause withdrawals with similar rates across groups (11 per 100 and 12 per 100 in the control and intervention groups, respectively) (19 studies; 1065 participants; risk ratio (RR) 1.02, 95% confidence interval (CI) 0.69 to 1.51) with an absolute change of 1% (3% fewer to 5% more) and a relative change of 11% (28% fewer to 47% more). Across all 21 studies, no injuries or other adverse events were reported; however some participants experienced increased fibromyalgia symptoms (pain, soreness, or tiredness) during or after exercise. However due to low event rates, we are uncertain of the precise risks with exercise. Mixed exercise may improve HRQL and physical function and may decrease pain and fatigue; all-cause withdrawal was similar across groups, and mixed exercises may slightly reduce stiffness. For fatigue, physical function, HRQL, and stiffness, we cannot rule in or out a clinically relevant change, as the confidence intervals include both clinically important and unimportant effects.We found very low-quality evidence on long-term effects. In eight trials, HRQL, fatigue, and physical function improvement persisted at 6 to 52 or more weeks post intervention but improvements in stiffness and pain did not persist. Withdrawals and adverse events were not measured.It is uncertain whether mixed versus other non-exercise or other exercise interventions improve HRQL and physical function or decrease symptoms because the quality of evidence was very low. The interventions were heterogeneous, and results were often based on small single studies. Adverse events with these interventions were not measured, and thus uncertainty surrounds the risk of adverse events. AUTHORS' CONCLUSIONS: Compared to control, moderate-quality evidence indicates that mixed exercise probably improves HRQL, physical function, and fatigue, but this improvement may be small and clinically unimportant for some participants; physical function shows improvement in all participants. Withdrawal was similar across groups. Low-quality evidence suggests that mixed exercise may slightly improve stiffness. Very low-quality evidence indicates that we are 'uncertain' whether the long-term effects of mixed exercise are maintained for all outcomes; all-cause withdrawals and adverse events were not measured. Compared to other exercise or non-exercise interventions, we are uncertain about the effects of mixed exercise because we found only very low-quality evidence obtained from small, very heterogeneous trials. Although mixed exercise appears to be well tolerated (similar withdrawal rates across groups), evidence on adverse events is scarce, so we are uncertain about its safety. We downgraded the evidence from these trials due to imprecision (small trials), selection bias (e.g. allocation), blinding of participants and care providers or outcome assessors, and selective reporting.

Spatial gradients of healthy aging: a study of myelin-sensitive maps

Protracted development of a brain network may entail greater susceptibility to aging decline, supported by evidence of an earlier onset of age-related changes in late-maturing anterior areas, that is, an anterior-to-posterior gradient of brain aging. Here we analyzed the spatiotemporal features of age-related differences in myelin content across the human brain indexed by magnetization transfer (MT) concentration in a cross-sectional cohort of healthy adults. We described age-related spatial gradients in MT, which may reflect the reversal of patterns observed in development. We confirmed an anterior-to-posterior gradient of age-related MT decrease and also showed a lateral-to-ventral gradient inversely mirroring the sequence of connectivity development and myelination. MT concentration in the lateral white matter regions continued to increase up to the age of 45 years and decreased moderately following a peak. In contrast, ventral white matter regions reflected life-long stable MT concentration levels, followed by a rapid decrease at a later age. We discussed our findings in relation with existing theories of brain aging, including the lack of support for the proposal that areas which mature later decline at an accelerated rate.

BOLD hemodynamic response function changes significantly with healthy aging

Functional magnetic resonance imaging (fMRI) has been used to infer age-differences in neural activity from the hemodynamic response function (HRF) that characterizes the blood-oxygen-level-dependent (BOLD) signal over time. BOLD literature in healthy aging lacks consensus in age-related HRF changes, the nature of those changes, and their implications for measurement of age differences in brain function. Between-study discrepancies could be due to small sample sizes, analysis techniques, and/or physiologic mechanisms. We hypothesize that, with large sample sizes and minimal analysis assumptions, age-related changes in HRF parameters could reflect alterations in one or more components of the neural-vascular coupling system. To assess HRF changes in healthy aging, we analyzed the large population-derived dataset from the Cambridge Center for Aging and Neuroscience (CamCAN) study (Shafto et al., 2014). During scanning, 74 younger (18-30 years of age) and 173 older participants (54-74 years of age) viewed two checkerboards to the left and right of a central fixation point, simultaneously heard a binaural tone, and responded via right index finger button-press. To assess differences in the shape of the HRF between younger and older groups, HRFs were estimated using FMRIB's Linear Optimal Basis Sets (FLOBS) to minimize a priori shape assumptions. Group mean HRFs were different between younger and older groups in auditory, visual, and motor cortices. Specifically, we observed increased time-to-peak and decreased peak amplitude in older compared to younger adults in auditory, visual, and motor cortices. Changes in the shape and timing of the HRF in healthy aging, in the absence of performance differences, support our hypothesis of age-related changes in the neural-vascular coupling system beyond neural activity alone. More precise interpretations of HRF age-differences can be formulated once these physiologic factors are disentangled and measured separately.

A game-based neurofeedback training system to enhance cognitive performance in healthy elderly subjects and in patients with amnestic mild cognitive impairment

Introduction: This study examines the clinical efficacy of a game-based neurofeedback training (NFT) system to enhance cognitive performance in patients with amnestic mild cognitive impairment (aMCI) and healthy elderly subjects. The NFT system includes five games designed to improve attention span and cognitive performance. The system estimates attention levels by investigating the power spectrum of Beta and Alpha bands. Methods: We recruited 65 women with aMCI and 54 healthy elderly women. All participants were treated with care as usual (CAU); 58 were treated with CAU + NFT (20 sessions of 30 minutes each, 2-3 sessions per week), 36 with CAU + exergame-based training, while 25 patients had only CAU. Cognitive functions were assessed using the Cambridge Neuropsychological Test Automated Battery both before and after treatment. Results: NFT significantly improved rapid visual processing and spatial working memory (SWM), including strategy, when compared with exergame training and no active treatment. aMCI was characterized by impairments in SWM (including strategy), pattern recognition memory, and delayed matching to samples. Conclusion: In conclusion, treatment with NFT improves sustained attention and SWM. Nevertheless, NFT had no significant effect on pattern recognition memory and short-term visual memory, which are the other hallmarks of aMCI. The NFT system used here may selectively improve sustained attention, strategy, and executive functions, but not other cognitive impairments, which characterize aMCI in women.

Aging and the Epidemiology of Epilepsy

BACKGROUND: Epilepsy is a chronic disorder affecting all ages but with a peak in the elderly. The association of epilepsy with age can be explained by the predominance of brain diseases with epileptogenic potential (mostly stroke and dementia) and by the effects of the aging process through a number of molecular mechanisms involving networks of neurons with focal or diffuse distribution. SUMMARY: The prevalence of active epilepsy is 6.4 per 1,000 and the lifetime prevalence is 7.6 per 1,000. The prevalence tends to increase with age, with peaks in the oldest age groups and in socially deprived individuals. The incidence of epilepsy is 61.4 per 100,000 person-years. Epilepsy has a bimodal distribution according to age with peaks in the youngest individuals and in the elderly. The increased incidence of seizures and epilepsy in the elderly can be attributed to the increase of age-related and aging-related epileptogenic conditions. Key Messages: As the world population is steadily growing with parallel increase in the number of aged subjects, in the future, epilepsy will represent a huge burden for the society. Measures must thus be taken to prevent seizures and epilepsy through the reduction of preventable epileptogenic factors.

SMR Neurofeedback Training Facilitates Working Memory Performance in Healthy Older Adults: A Behavioral and EEG Study

Cognitive aging has become a major concern because life expectancy has increased and elderly populations are socially and economically active. Neurofeedback is a technique of neuromodulation through operant conditioning paradigm that uses a computer interface to provide real-time information about brain activity to increase individual self-perception and assist in modulation. The sensorimotor rhythm (SMR) training protocol is known to enhance attention and has been applied to improve cognitive performance, primarily for attention and memory gains. The aim of this study is to test if the SMR protocol can improve working memory performance in an aging population and consequently favor cognitive reserve. Seventeen older adults (12 females) took part in a randomized placebo-controlled study. They completed a visual working memory test, Delayed Matching to Sample Task (DMTS), before and after the SMR neurofeedback protocol in order to compare their visual working memory performance. Moreover, a 19-channels EEG was collected while they perform the DMTS pre- and post-training. The experimental group showed an improvement in their working memory performance after the training with similar activation power, mainly in theta and beta frequency band at frontal and alpha at temporal regions. The sham group showed some variations in the score of working memory after the training, but were not statistically significant and their power spectrum demonstrate enhancement in alpha and beta band frontal and temporal. The group that did not receive neurofeedback training did not show a change in their working memory performance, neither in their EEG spectrum. The results suggest that neurofeedback can benefit brain reserve in an aging population because individuals enhanced their working memory performance after training and have their EEG activation changed according to expected in working memory tasks.

Visual biofeedback training reduces quantitative drugs index scores associated with fall risk

OBJECTIVE: Drugs increase fall risk and decrease performance on balance and mobility tests. Conversely, whether biofeedback training to reduce fall risk also decreases scores on a published drug-based fall risk index has not been documented. Forty-eight community-dwelling older adults underwent either treadmill gait training plus visual feedback (+VFB), or walked on a treadmill without feedback. The Quantitative Drug Index (QDI) was derived from each participant's drug list and is based upon all cause drug-associated fall risk. Analysis of covariance assessed changes in the QDI during the study, and data is presented as mean ± standard error of the mean. RESULTS: The QDI scores decreased significantly (p = 0.031) for participants receiving treadmill gait training +VFB (- 0.259 ± 0.207), compared to participants who walked on the treadmill without VFB (0.463 ± 0.246). Changes in participants QDI scores were dependent in part upon their age, which was a significant covariate (p = 0.007). These preliminary results demonstrate that rehabilitation to reduce fall risk may also decrease use of drugs associated with falls. Determination of which drugs or drug classes that contribute to the reduction in QDI scores for participants receiving treadmill gait training +VFB, compared to treadmill walking only, will require a larger participant investigation. Trial Registration ISRNCT01690611, ClinicalTrials.gov #366151-1, initial 9/24/2012, completed 4/21/2016.

Systematic Review on Resting-State EEG for Alzheimer's Disease Diagnosis and Progression Assessment

Alzheimer's disease (AD) is a neurodegenerative disorder that accounts for nearly 70% of the more than 46 million dementia cases estimated worldwide. Although there is no cure for AD, early diagnosis and an accurate characterization of the disease progression can improve the quality of life of AD patients and their caregivers. Currently, AD diagnosis is carried out using standardized mental status examinations, which are commonly assisted by expensive neuroimaging scans and invasive laboratory tests, thus rendering the diagnosis time consuming and costly. Notwithstanding, over the last decade, electroencephalography (EEG) has emerged as a noninvasive alternative technique for the study of AD, competing with more expensive neuroimaging tools, such as MRI and PET. This paper reports on the results of a systematic review on the utilization of resting-state EEG signals for AD diagnosis and progression assessment. Recent journal articles obtained from four major bibliographic databases were analyzed. A total of 112 journal articles published from January 2010 to February 2018 were meticulously reviewed, and relevant aspects of these papers were compared across articles to provide a general overview of the research on this noninvasive AD diagnosis technique. Finally, recommendations for future studies with resting-state EEG were presented to improve and facilitate the knowledge transfer among research groups.

Home-based Rehabilitation With A Novel Digital Biofeedback System versus Conventional In-person Rehabilitation after Total Knee Replacement: a feasibility study

In-person home-based rehabilitation and telerehabilitation can be as effective as clinic-based rehabilitation after total knee arthroplasty (TKA), but require heavy logistics and are highly dependent on human supervision. New technologies that allow independent home-based rehabilitation without constant human supervision may help solve this problem. This was a single-center, feasibility study comparing a digital biofeedback system that meets these needs against conventional in-person home-based rehabilitation after TKA over an 8-week program. Primary outcome was the change in the Timed Up and Go score between the end of the program and baseline. Fifty-nine patients completed the study (30 experimental group; 29 conventional rehabilitation). The study demonstrated a superiority of the experimental group for all outcomes. Adverse events were similar in both groups. This is the first study to demonstrate that a digital rehabilitation solution can achieve better outcomes than conventional in-person rehabilitation, while less demanding in terms of human resources.

Resting-state EEG power and connectivity are associated with alpha peak frequency slowing in healthy aging

The individual alpha peak frequency (IAPF) of the human electroencephalography (EEG) typically experiences slowing with increasing age. Despite this hallmark change, studies that investigate modulations of conventional EEG alpha power and connectivity by aging and age-related neuropathology neglect to account for intergroup differences in IAPF. To investigate the relationship of age-related IAPF slowing with EEG power and connectivity, we recorded eyes-closed resting-state EEG in 37 young adults and 32 older adults. We replicated the finding of a slowed IAPF in older adults. IAPF values were significantly correlated with the frequency of maximum global connectivity and the means of their distributions did not differ, suggesting that connectivity was highest at the IAPF. Older adults expressed reduced global EEG power and connectivity at the conventional upper alpha band (10-12 Hz) compared with young adults. By contrast, groups had equivalent power and connectivity at the IAPF. The results suggest that conventional spectral boundaries may be biased against older adults or any group with a slowed IAPF. We conclude that investigations of alpha activity in aging and age-related neuropathology should be adapted to the IAPF of the individual and that previous findings should be interpreted with caution. EEG in the dominant alpha range may be unsuitable for examining cortico-cortical connectivity due to its subcortical origins.

Toward Development of Sham Protocols for High-Definition Transcranial Direct Current Stimulation (HD-tDCS)

High-definition transcranial direct current stimulation (HD-tDCS) is a noninvasive cortical stimulation (NICS) technique that, due to the utilization of multi-electrode stimulation, may enable development of sham conditions characterized by indistinguishable scalp sensations compared to active conditions, with little or no cortical influence. We sought to contribute to the development of an optimal sham electrode configuration for HD-tDCS protocols by gathering ratings of overall sensation reported by participants during different electrode configurations and current intensities. Twenty healthy participants completed a magnitude estimation task during which they rated their “overall sensation” in 1-minute intervals during five 5-minute stimulation conditions. A 5 x 5 (Time x Stimulation condition) analysis of variance (ANOVA) was conducted to determine if sensation measurements differed over time, and how this varied by condition. Null hypothesis significance tests and equivalence tests were conducted to determine which sham conditions were statistically indistinguishable from the experimental condition. The ANOVA revealed main effects for Time and Stimulation condition. Planned comparisons, comparing each sham condition to the experimental condition (4x1 ring configuration, 2 mA), revealed differences in sensation ratings for all but one condition (Sham 1x1A); no sham conditions were found to be statistically equivalent to the experimental condition. Our HD-tDCS findings build upon previous NICS reports of differences in sensation ratings between sham versus experimental conditions when traditional “ramping down” approaches were used. Alternative multi-electrode configurations that manipulate electrode placement to shunt current across the scalp warrant further investigation as valid blinding methods.

The potential effects of meditation on age-related cognitive decline: a systematic review

With a rapidly aging society it becomes increasingly important to counter normal age-related decline in cognitive functioning. Growing evidence suggests that cognitive training programs may have the potential to counteract this decline. On the basis of a growing body of research that shows that meditation has positive effects on cognition in younger and middle-aged adults, meditation may be able to offset normal age-related cognitive decline or even enhance cognitive function in older adults. In this paper, we review studies investigating the effects of meditation on age-related cognitive decline. We searched the Web of Science (1900 to present), PsycINFO (1597 to present), MEDLINE (1950 to present), and CABI (1910 to present) to identify original studies investigating the effects of meditation on cognition and cognitive decline in the context of aging. Twelve studies were included in the review, six of which were randomized controlled trials. Studies involved a wide variety of meditation techniques and reported preliminary positive effects on attention, memory, executive function, processing speed, and general cognition. However, most studies had a high risk of bias and small sample sizes. Reported dropout rates were low and compliance rates high. We conclude that meditation interventions for older adults are feasible, and preliminary evidence suggests that meditation can offset age-related cognitive decline.

Testing the hypothesis of accelerated cerebral white matter aging in schizophrenia and major depression

BACKGROUND: Elevated rate of aging-related biological and functional decline, termed "accelerated aging," is reported in patients with schizophrenia (SCZ) and major depressive disorder (MDD). We used diffusion tensor imaging derived fractional anisotropy (FA) as a biomarker of aging-related decline in white matter (WM) integrity to test the hypotheses of accelerated aging in SCZ and MDD. METHODS: The SCZ cohort comprised 58 SCZ patients and 60 controls (aged 20-60 years). The MDD cohort comprised 136 MDD patients and 351 controls (aged 20-79 years). The main outcome measures were the diagnosis-by-age interaction on whole-brain-averaged WM FA values and FA values from 12 major WM tracts. RESULTS: Diagnosis-by-age interaction for the whole-brain average FA was significant for the SCZ (p = .04) but not the MDD (p = .80) cohort. Diagnosis-by-age interaction was nominally significant (p<.05) for five WM tracts for SCZ and for none of the tracts in the MDD cohort. Tract-specific heterochronicity of the onset of age-related decline in SCZ demonstrated strong negative correlations with the age-of-peak myelination and the rates of age-related decline obtained from normative sample (r =-.61 and-.80, p<.05, respectively). No such trends existed for MDD cohort. CONCLUSIONS: Cerebral WM showed accelerated aging in SCZ but not in MDD, suggesting some difference in the pathophysiology underlying their WM aging changes. Tract-specific heterochronicity of WM development modulated presentation of accelerated aging in SCZ: WM tracts that matured later in life appeared more sensitive to the pathophysiology of SCZ and demonstrated more susceptibility to disorder-related accelerated decline in FA values with age. This trend was not observed in MDD cohort.

Common carotid flow velocity is associated with cognition in older adults

AIMS: To assess the relationship between carotid flow velocity and cognitive impairment in patients with mild-moderate (<50%) carotid artery disease. METHODS: We studied 407 participants with available carotid ultrasound and cognitive measures. We related peak systolic velocity (PSV) and end diastolic velocity (EDV) of internal carotid artery (ICA) and common carotid artery (CCA) and intimal medial thickness (IMT) to Mini Mental State Examination (MMSE), Clock Draw Test (CDT), Activities of Daily Living Scale (ADL)and Montreal Cognitive Assessment (MoCA). RESULTS: EDV of CCA was significantly different in higher and lower MoCA (MMSE) groups. Multiple regression analysis demonstrated that lower EDV was significantly associated with lower MoCA (+0.459 per standard deviation (SD), p<0. 01 for the left; +0.539 per SD, p<0. 01 for the right) and CDT (odds ratio (OR) 0.093, p< 0.05 for the left; OR) 0.120, p<0. 01 for the right) scores. PSV of left CCA (-0.205 per SD, p<0.05) and IMT (+42.536 per SD, p< 0.001) were associated with ADL. PSV of right CCA was associated with MMSE (+0.081 per SD, p<0.001). No significant relationship between ICA flow velocity and cognitive performance was observed. CONCLUSIONS: Our preliminary data show that common carotid artery flow velocity was associated with cognitive performance.

The Effects of Neurofeedback Training on Memory Performance in Elderly Subjects

Neurofeedback or electroencephalographic operant conditioning (EEG-OC) is an EEG biofeedback technique used to train individuals to control or modify their cortical activity through learned self-regulation. Initially used for treating a variety of pathologies, neurofeedback has been employed more recently to improve the physical or cognitive performance of human beings. The purpose of this study is to assess the hypothesis of the effect of neurofeedback (the ‘awakened mind’ model) on the memory performance of subjects aged over 65. 30 participants were shared equally between 3 groups: an experimental group that underwent 4 neurofeedback training sessions; a non-neurofeedback group trained at relaxation; and a ‘waiting list’ control group. Results showed that the members of the Neurofeedback group learned to increase the spectral power of the alpha frequency range as well as the alpha/thêta ratio, and that compared with the members of the two other groups, neurofeedback training resulted in a more pronounced decrease, albeit without any relation to changes in EEG activity and the level of stress and anxiety of participants undergoing such training. Yet contrary to expectations, no improvement of memory performance (differed recall of words and learning of lists of words) was observed. These mixed results, which suggest a wide range of applications, underline the need for a more systematic assessment of the potential applications of NFB training in elderly humans in order to be better able to specify the effects of the retained protocol on cognitive performance.

Transretinal degeneration in ageing human retina: a multiphoton microscopy analysis

AIM: Retinal cell remodelling has been reported as a consistent feature of ageing. However, the degree to which this results in transretinal degeneration is unclear. To address this, the authors used multiphoton microscopy to quantify retinal degeneration in post-mortem human eyes of two age groups. METHODS: Retinas from six young subjects (18-33 years old) and six older subjects (74-90 years old) were prepared as wholemount preparations. All retinas were stained with 4,6-diamidino-2-phenylindole and imaged by multiphoton confocal microscopy to quantify neuron densities in the retinal ganglion cell layer (RGCL), inner nuclear layer (INL) and outer nuclear layer (ONL). Neurons were counted using automated cell identification algorithms. All retinas were imaged hydrated to minimise tissue artefacts. RESULTS: In both groups, 56% of the area within the central 4 mm eccentricity and 27% of the area with eccentricity between 4 mm and 7 mm were imaged. Compared with young subjects, the peak RGCL neuron loss in the aged subjects (25.5%) was at 1 mm eccentricity. INL and ONL neuron densities significantly decreased at 1-2 mm eccentricity (8.7%) and 0.5-4 mm eccentricity (15.6%) respectively (P <0.05). The reduction in neuron density in the INL corresponded, spatially, to the region with the greatest neuron loss in the RGCL and ONL. CONCLUSIONS: This is the first study to correlate neurodegeneration in different populations of cells in the ageing retinas. These data confirm that the greatest neuronal loss occurs in the RGCL and ONL in human ageing retinas, whereas the INL is relatively preserved.

Alzheimer's disease is not "brain aging": neuropathological, genetic, and epidemiological human studies

Human studies are reviewed concerning whether "aging"-related mechanisms contribute to Alzheimer's disease (AD) pathogenesis. AD is defined by specific neuropathology: neuritic amyloid plaques and neocortical neurofibrillary tangles. AD pathology is driven by genetic factors related not to aging per se, but instead to the amyloid precursor protein (APP). In contrast to genes involved in APP-related mechanisms, there is no firm connection between genes implicated in human "accelerated aging" diseases (progerias) and AD. The epidemiology of AD in advanced age is highly relevant but deceptively challenging to address given the low autopsy rates in most countries. In extreme old age, brain diseases other than AD approximate AD prevalence while the impact of AD pathology appears to peak by age 95 and decline thereafter. Many distinct brain diseases other than AD afflict older human brains and contribute to cognitive impairment. Additional prevalent pathologies include cerebrovascular disease and hippocampal sclerosis, both high-morbidity brain diseases that appear to peak in incidence later than AD chronologically. Because of these common brain diseases of extreme old age, the epidemiology differs between clinical "dementia" and the subset of dementia cases with AD pathology. Additional aging-associated mechanisms for cognitive decline such as diabetes and synapse loss have been linked to AD and these hypotheses are discussed. Criteria are proposed to define an "aging-linked" disease, and AD fails all of these criteria. In conclusion, it may be most fruitful to focus attention on specific pathways involved in AD rather than attributing it to an inevitable consequence of aging.

Are the Effects of rTMS in Parkinson's Disease Clinically Relevant?

Introduction. Earlier studies have shown that brain stimulation by means of repetitive Transcranial Magnetic Stimulation (rTMS) over the primary motor cortex can decrease the motor impairments in Parkinson's disease (PD). The present study focused on the clinical relevance of rTMS in the treatment of PD. Method. Thirteen PD patients received a minimum of 10 sessions of 2,000 pulses 5 Hz rTMS over the hand and leg area over the primary motor cortex, with a stimulation intensity of 120% of the motor threshold. In our analysis an effect could be considered as clinically relevant if the quality of life (QoL) improved with 30% or more. Results. Paired-sample t-tests revealed a significant improvement of Unified Parkinson's Disease Rating Scale score, walking speed, and mood. A minority of the patients (38%) who underwent rTMS showed an improvement in QoL of greater than 30%. The improvements on QoL correlated significantly to scores of motor improvements on the Unified Parkinson's Disease Rating Scale but not to improvements in mood as assessed by the Geriatric Depression Scale. The use of rTMS did not demonstrate any effects on tremor, freezing of gait, and activities of daily life, and rTMS had no effect on the stage of disease. It mainly improved rigidity, finger and hand movements, and leg agility. Conclusion. This study shows that although there can be significant group effects of rTMS on PD symptoms, these significant effects do not automatically imply that these are clinically relevant. Therefore we advise that future studies in the field of neuromodulation (rTMS, neurofeedback, etc.) also focus more on the clinical relevance of the treatment under investigation rather than only report “significant group differences.”

Biofeedback for training balance and mobility tasks in older populations: a systematic review

CONTEXT: An effective application of biofeedback for interventions in older adults with balance and mobility disorders may be compromised due to co-morbidity. OBJECTIVE: To evaluate the feasibility and the effectiveness of biofeedback-based training of balance and/or mobility in older adults. DATA SOURCES: PubMed (1950-2009), EMBASE (1988-2009), Web of Science (1945-2009), the Cochrane Controlled Trials Register (1960-2009), CINAHL (1982-2009) and PsycINFO (1840-2009). The search strategy was composed of terms referring to biofeedback, balance or mobility, and older adults. Additional studies were identified by scanning reference lists. STUDY SELECTION: For evaluating effectiveness, 2 reviewers independently screened papers and included controlled studies in older adults (i.e. mean age equal to or greater than 60 years) if they applied biofeedback during repeated practice sessions, and if they used at least one objective outcome measure of a balance or mobility task. DATA EXTRACTION: Rating of study quality, with use of the Physiotherapy Evidence Database rating scale (PEDro scale), was performed independently by the 2 reviewers. Indications for (non)effectiveness were identified if 2 or more similar studies reported a (non)significant effect for the same type of outcome. Effect sizes were calculated. RESULTS AND CONCLUSIONS: Although most available studies did not systematically evaluate feasibility aspects, reports of high participation rates, low drop-out rates, absence of adverse events and positive training experiences suggest that biofeedback methods can be applied in older adults. Effectiveness was evaluated based on 21 studies, mostly of moderate quality. An indication for effectiveness of visual feedback-based training of balance in (frail) older adults was identified for postural sway, weight-shifting and reaction time in standing, and for the Berg Balance Scale. Indications for added effectiveness of applying biofeedback during training of balance, gait, or sit-to-stand transfers in older patients post-stroke were identified for training-specific aspects. The same applies for auditory feedback-based training of gait in older patients with lower-limb surgery. IMPLICATIONS: Further appropriate studies are needed in different populations of older adults to be able to make definitive statements regarding the (long-term) added effectiveness, particularly on measures of functioning.

Brain Brightening: Restoring the Aging Mind

EEG neurofeedback: a brief overview and an example of peak alpha frequency training for cognitive enhancement in the elderly

Neurofeedback (NF) is an electroencephalographic (EEG) biofeedback technique for training individuals to alter their brain activity via operant conditioning. Research has shown that NF helps reduce symptoms of several neurological and psychiatric disorders, with ongoing research currently investigating applications to other disorders and to the enhancement of non-disordered cognition. The present article briefly reviews the fundamentals and current status of NF therapy and research and illustrates the basic approach with an interim report on a pilot study aimed at developing a new NF protocol for improving cognitive function in the elderly. EEG peak alpha frequency (PAF) has been shown to correlate positively with cognitive performance and to correlate negatively with age after childhood. The present pilot study used a double-blind controlled design to investigate whether training older individuals to increase PAF would result in improved cognitive performance. The results suggested that PAF NF improved cognitive processing speed and executive function, but that it had no clear effect on memory. In sum, the results suggest that the PAF NF protocol is a promising technique for improving selected cognitive functions.

Reducing vascular variability of fMRI data across aging populations using a breathholding task

The magnitude and shape of blood oxygen level-dependent (BOLD) responses in functional MRI (fMRI) studies vary across brain regions, subjects, and populations. This variability may be secondary to neural activity or vasculature differences, thus complicating interpretations of BOLD signal changes in fMRI experiments. We compare the BOLD responses to neural activity and a vascular challenge and test a method to dissociate these influences in 26 younger subjects (ages 18-36) and 24 older subjects (ages 51-78). Each subject performed a visuomotor saccade task (a vascular response to neural activity) and a breathholding task (vascular dilation induced by hypercapnia) during separate runs in the same scanning session. For the saccade task, signal magnitude showed a significant decrease with aging in FEF, SEF, and V1, and a delayed time-to-peak with aging in V1. The signal magnitudes from the saccade and hypercapnia tasks showed significant linear regressions within subjects and across individuals and populations. These two tasks had weaker, but sometimes significant linear regressions for time-to-peak and coherence phase measures. The significant magnitude decrease with aging in V1 remained after dividing the saccade task magnitude by the hypercapnia task magnitude, implying that the signal decrease is neural in origin. These findings may lead to a method to identify vascular reactivity-induced differences in the BOLD response across populations and the development of methods to account for the influence of these vasculature differences in a simple, noninvasive manner.

Spontaneous low-frequency oscillations decline in the aging brain

It is well known that aging leads to a degeneration of the vascular system. Hence, one may hypothesize that spontaneous oscillations decrease in the cerebral microvasculature with aging. Accordingly, the authors investigated the age dependency of spontaneous oscillations in the visual cortex during rest and functional activation. Functional near-infrared spectroscopy was used because it is particularly sensitive to the microvasculature. Visual stimulation led to an increase of oxyhemoglobin, total hemoglobin, and a decrease of deoxyhemoglobin, without any influence of age. Peaks of normalized power spectral density were detected for spontaneous low-frequency (0.07 to 0.11 Hz) and very-low-frequency (0.01 to 0.05 Hz) oscillations, with a higher amplitude for oxyhemoglobin than for deoxyhemoglobin. Spontaneous low-frequency oscillations of oxyhemoglobin and deoxyhemoglobin declined strongly with aging during both rest and visual stimulation. Reduction of spontaneous low-frequency oscillations might indicate a declining spontaneous activity in microvascular smooth muscle cells, in conjunction with an increased vessel stiffness with aging.

Aging and the Simon task

A visual Simon task was used to study the influence of aging on visuospatial attention and inhibitory control processes. Responses were much slower for elderly than for young participants. The delay in trials in which stimulus and response side did not correspond as compared to when they did correspond (the Simon effect) was larger for older people, even after correcting for general slowing due to aging. The slowing of responses reflected a slowing of internal processing, as indicated by progressively larger delays of the peak latencies of the N1, the posterior contralateral negativity (PCN), and P3. A comparison between the amplitudes of the PCN and early lateralized readiness potential (pre-LRP) indicated that transmission from posterior sites (PCN) to the motor cortex may be affected by age. The data support the view that aging affects an inhibitory process that controls direct visuomotor transmission.

Cerebrospinal fluid production and dynamics in normal aging: a MRI phase-mapping study

Magnetic resonance imaging (MRI) phase mapping was used for non-invasive evaluation of the to-and-fro motion of cerebrospinal fluid (CSF) in the cerebral aqueduct, and to measure the supratentorial CSF production in vivo, in 13 healthy volunteers to determine whether normal aging affects these parameters. Eight young healthy volunteers (mean age 29.8 years) and five elderly healthy volunteers (mean age 69.0 years) were examined, all were normal on conventional MRI. Slightly higher aqueductal CSF peak flow velocities and peak volume flow in both the caudal and rostral directions were found in the group of elderly healthy volunteers, however, this was not statistically significant. The calculated mean supratentorial CSF production rates in the two groups were almost identical, corresponding to approximately 900-1000 ml per 24 h, we suggest that supratentorial CSF production in healthy humans in fact occurs at this relatively high rate. Our study further suggests that the differences found in human CSF production rates are caused by interindividual factors other than age.

The effects of processing of barley-based supplements on rumen pH, rate of digestion of voluntary intake of dried grass in sheep

1. In one experiment the effect on rumen pH of feeding with restricted amounts of whole or pelleted barley was studied. With whole barley there was little variation in rumen pH associated with feeding time, but with pelleted barley the pH decreased from about 7-0 before feeding to about 5-3, 2--3 h after feeding. 2. The rate of disappearance of dried grass during incubation in the rumens of sheep receiving either whole or pelleted barley was studied in a second experiment. After 24 h incubation only 423 mg/g incubated had disappeared in the rumen of sheep receiving pelleted barley while 625 mg/g incubated had disappeared when it was incubated in the rumen of sheep receiving whole barley. 3. The voluntary intake of dried grass of lambs was studied in a third experiment when they received supplements of either 25 or 50 g whole or pelleted barley/kg live weight 0-75. At the high level, pelleted barley reduced intake of dried grass by 534 g/kg but whole barley reduced it by only 352 g/kg. The digestibility of acid-detergent fibre was reduced more by pelleted barley than by whole barley but there was a tendency for a small increase in digestibility of the barley due to processing. 4. The implications of these findings on supplementation of roughages with cereals are discussed.

Z-score neurofeedback, heart rate variability biofeedback, and brain coaching for older adults with memory concerns

Background: The three-month, multi-domain Memory Boot Camp program incorporates z-score neurofeedback (NFB), heart rate variability (HRV) biofeedback, and one-on-one coaching to teach memory skills and encourage behavior change in diet, sleep, physical fitness, and stress reduction. Objective: This prospective trial evaluates the Memory Boot Camp program for adults ages 55 to 85 with symptoms of Mild Cognitive Impairment (MCI) and subjective memory complaints. Methods: Participants were evaluated via the Montreal Cognitive Assessment (MoCA), NeuroTrax Global Cognitive Score, measures of anxiety, depression, sleep, quality of life, quantitative electroencephalography (QEEG), and HRV parameters at four timepoints: baseline, pre-program, post-program, and follow-up. The trial included a three-month waiting period between baseline and pre-program, such that each participant acted as their own control, and follow-up took place six months after completion of the program. Results: Participants’ MoCA scores and self-reported measures of anxiety, depression, sleep quality, and quality of life improved after treatment, and these changes were maintained at follow-up. Physiological changes in HRV parameters after treatment were not significant, however, breathing rate and QEEG parameters were improved at post-program and maintained at follow-up. Finally, participants’ improvement in MoCA score over the treatment period was correlated with their improvement in two brain oscillation parameters targeted by the z-score NFB protocol: relative power of delta and relative power of theta. Conclusions: Trial results suggest that the Memory Boot Camp program is a promising treatment strategy for older adults with symptoms of MCI and subjective memory complaints.