The effects of aerobic exercise and transcranial direct current stimulation on cognitive function in older adults with and without cognitive impairment: A systematic review and meta-analysis.

BACKGROUND: Aerobic exercise (AE) may slow age-related cognitive decline. However, such cognition-sparing effects are not uniform across cognitive domains and studies. Transcranial direct current stimulation (tDCS) is a form of non-invasive brain stimulation and is also emerging as a potential alternative to pharmaceutical therapies. Like AE, the effectiveness of tDCS is also inconsistent for reducing cognitive impairment in ageing. The unexplored possibility exists that pairing AE and tDCS could produce synergistic effects and reciprocally augment cognition-improving effects in older individuals with and without cognitive impairments. Previous research found such synergistic effects on cognition when cognitive training is paired with tDCS in older individuals with and without mild cognitive impairment (MCI) or dementia. AIM: The purpose of this systematic review with meta-analysis was to explore if pairing AE with tDCS could augment singular effects of AE and tDCS on global cognition (GC), working memory (WM) and executive function (EF) in older individuals with or without MCI and dementia. METHODS: Using a PRISMA-based systematic review, we compiled studies that examined the effects of AE alone, tDCS alone, and AE and tDCS combined on cognitive function in older individuals with and without mild cognitive impairment (MCI) or dementia. Using a PICOS approach, we systematically searched PubMed, Scopus and Web of Science searches up to December 2021, we focused on 'MoCA', 'MMSE', 'Mini-Cog' (measures) and 'cognition', 'cognitive function', 'cognitive', 'cognitive performance', 'executive function', 'executive process', 'attention', 'memory', 'memory performance' (outcome terms). We included only randomized controlled trials (RTC) in humans if available in English full text over the past 20 years, with participants' age over 60. We assessed the methodological quality of the included studies (RTC) by the Physiotherapy Evidence Database (PEDro) scale. RESULTS: Overall, 68 studies were included in the meta-analyses. AE (ES = 0.56 [95% CI: 0.28-0.83], p = 0.01) and tDCS (ES = 0.69 [95% CI: 0.12-1.26], p = 0.02) improved GC in all three groups of older adults combined (healthy, MCI, demented). In healthy population, AE improved GC (ES = 0.46 [95% CI: 0.22-0.69], p = 0.01) and EF (ES = 0.27 [95% CI: 0.05-0.49], p = 0.02). AE improved GC in older adults with MCI (ES = 0.76 [95% CI: 0.21-1.32], p = 0.01). tDCS improved GC (ES = 0.69 [90% CI: 0.12-1.26], p = 0.02), all three cognitive function (GC, WM and EF) combined in older adults with dementia (ES = 1.12 [95% CI: 0.04-2.19], p = 0.04) and improved cognitive function in older adults overall (ES = 0.69 [95% CI: 0.20-1,18], p = 0.01). CONCLUSION: Our systematic review with meta-analysis provided evidence that beyond the cardiovascular and fitness benefits of AE, pairing AE with tDCS may have the potential to slow symptom progression of cognitive decline in MCI and dementia. Future studies will examine the hypothesis of this present review that a potentiating effect would incrementally improve cognition with increasing severity of cognitive impairment.

Age-dependent modulation of motor network connectivity for skill acquisition, consolidation and interlimb transfer after motor practice.

OBJECTIVE: Age-related differences in neural strategies for motor learning are not fully understood. We determined the effects of age on the relationship between motor network connectivity and motor skill acquisition, consolidation, and interlimb transfer using dynamic imaging of coherent sources. METHODS: Healthy younger (n = 24, 18-24 y) and older (n = 24, 65-87 y) adults unilaterally practiced a visuomotor task and resting-state electroencephalographic data was acquired before and after practice as well as at retention. RESULTS: The results showed that right-hand skill acquisition and consolidation did not differ between age groups. However, age affected the ability to transfer the newly acquired motor skill to the non-practiced limb. Moreover, strengthened left- and right-primary motor cortex-related beta connectivity was negatively and positively associated with right-hand skill acquisition and left-hand skill consolidation in older adults, respectively. CONCLUSION: Age-dependent modulations of bilateral resting-state motor network connectivity indicate age-specific strategies for the acquisition, consolidation, and interlimb transfer of novel motor tasks. SIGNIFICANCE: The present results provide insights into the mechanisms underlying motor learning that are important for the development of interventions for patients with unilateral injuries.

¿Desempeña un papel decisivo la excitabilidad corticoespinal ipsilateral en el efecto cruzado provocado por el entrenamiento de fuerza unilateral? Una revisión sistemática / Does ipsilateral corticospinal excitability play a decisive role in the cross-education effect caused by unilateral resistance training? A systematic review

Introducción: El entrenamiento de fuerza unilateral ha demostrado provocar aumentos de fuerza tanto en la extremidad entrenada como en la no entrenada. Una de las teorías actuales más aceptadas defiende que el origen de dicho aumento de rendimiento se encuentra en adaptaciones en el sistema nervioso, concretamente en la corteza motora primaria, siendo los aumentos en la excitabilidad corticoespinal (EC) medida con estimulación magnética transcraneal una de las principales adaptaciones observadas tras periodos crónicos de entrenamiento. Por ello, el principal objetivo es hacer un análisis de la literatura actual para determinar el grado de adaptación que se da en la EC y su posible relación funcional con el aumento de fuerza de la extremidad no entrenada.DesarrolloSe llevó a cabo una búsqueda sistemática en la literatura existente entre enero de 1970 hasta diciembre de 2016 en las bases de datos online Medline (vía PubMed), Ovid, Web of Science y Science Direct con la siguiente estrategia de búsqueda: (Transcranial magnetic stimulation OR excitability) Y (strength training OR resistance training or force) Y (cross transfer OR contralateral limb OR cross education). Finalmente se incluyeron un total de 10 artículos.ConclusionesExiste cierta inconsistencia en los resultados referentes al aumento de la EC. Aunque no se puede descartar que dicha inconsistencia se deba a aspectos metodológicos, los resultados parecen indicar que el aumento de fuerza y el incremento en la EC podrían no estar funcionalmente relacionados. (AU)

Introduction: Unilateral resistance training has been shown to improve muscle strength in both the trained and the untrained limb. One of the most widely accepted theories is that this improved performance is due to nervous system adaptations, specifically in the primary motor cortex. According to this hypothesis, increased corticospinal excitability (CSE), measured with transcranial magnetic stimulation, is one of the main adaptations observed following prolonged periods of training. The principal aim of this review is to determine the degree of adaptation of CSE and its possible functional association with increased strength in the untrained limb.DevelopmentWe performed a systematic literature review of studies published between January 1970 and December 2016, extracted from Medline (via PubMed), Ovid, Web of Science, and Science Direct online databases. The search terms were as follows: (transcranial magnetic stimulation OR excitability) AND (strength training OR resistance training OR force) AND (cross transfer OR contralateral limb OR cross education). A total of 10 articles were found.ConclusionResults regarding increased CSE were inconsistent. Although the possibility that the methodology had a role in this inconsistency cannot be ruled out, the results appear to suggest that there may not be a functional association between increases in muscle strength and in CSE. (AU)

Home-based exercise programmes improve physical fitness of healthy older adults: A PRISMA-compliant systematic review and meta-analysis with relevance for COVID-19.

This systematic review and meta-analysis aimed to examine the effects of home-based exercise programmes on measures of physical-fitness in healthy older adults. Seventeen randomized-controlled trials were included with a total of 1,477 participants. Results indicated small effects of home-based training on muscle strength (between-study standardised-mean-difference [SMD] = 0.30), muscle power (SMD = 0.43), muscular endurance (SMD = 0.28), and balance (SMD = 0.28). We found no statistically significant effects for single-mode strength vs. multimodal training (e.g., combined balance, strength, and flexibility exercises) on measures of muscle strength and balance. Single-mode strength training had moderate effects on muscle strength (SMD = 0.51) and balance (SMD = 0.65) while multimodal training had no statistically significant effects on muscle strength and balance. Irrespective of the training type, >3 weekly sessions produced larger effects on muscle strength (SMD = 0.45) and balance (SMD = 0.37) compared with ≤3 weekly sessions (muscle strength: SMD = 0.28; balance: SMD = 0.24). For session-duration, only ≤30 min per-session produced small effects on muscle strength (SMD = 0.35) and balance (SMD = 0.34). No statistically significant differences were observed between all independently-computed single-training factors. Home-based exercise appears effective to improve components of health- (i.e., muscle strength and muscular endurance) and skill-related (i.e., muscle power, balance) physical-fitness. Therefore, in times of restricted physical activity due to pandemics, home-based exercises constitute an alternative to counteract physical inactivity and preserve/improve the health and fitness of healthy older adults aged 65-to-83 years.

Does ipsilateral corticospinal excitability play a decisive role in the cross-education effect caused by unilateral resistance training? A systematic review. / ¿Desempeña un papel decisivo la excitabilidad corticoespinal ipsilateral en el efecto cruzado provocado por el entrenamiento de fuerza unilateral? Una revisión sistemática.

INTRODUCTION: Unilateral resistance training has been shown to improve muscle strength in both the trained and the untrained limb. One of the most widely accepted theories is that this improved performance is due to nervous system adaptations, specifically in the primary motor cortex. According to this hypothesis, increased corticospinal excitability (CSE), measured with transcranial magnetic stimulation, is one of the main adaptations observed following prolonged periods of training. The principal aim of this review is to determine the degree of adaptation of CSE and its possible functional association with increased strength in the untrained limb. DEVELOPMENT: We performed a systematic literature review of studies published between January 1970 and December 2016, extracted from Medline (via PubMed), Ovid, Web of Science, and Science Direct online databases. The search terms were as follows: (transcranial magnetic stimulation OR excitability) AND (strength training OR resistance training OR force) AND (cross transfer OR contralateral limb OR cross education). A total of 10 articles were found. CONCLUSION: Results regarding increased CSE were inconsistent. Although the possibility that the methodology had a role in this inconsistency cannot be ruled out, the results appear to suggest that there may not be a functional association between increases in muscle strength and in CSE.

Contralateral Effects of Unilateral Strength and Skill Training: Modified Delphi Consensus to Establish Key Aspects of Cross-Education.

BACKGROUND: Cross-education refers to increased motor output (i.e., force generation, skill) of the opposite, untrained limb following a period of unilateral exercise training. Despite extensive research, several aspects of the transfer phenomenon remain controversial. METHODS: A modified two-round Delphi online survey was conducted among international experts to reach consensus on terminology, methodology, mechanisms of action, and translational potential of cross-education, and to provide a framework for future research. RESULTS: Through purposive sampling of the literature, we identified 56 noted experts in the field, of whom 32 completed the survey, and reached consensus (75% threshold) on 17 out of 27 items. CONCLUSION: Our consensus-based recommendations for future studies are that (1) the term 'cross-education' should be adopted to refer to the transfer phenomenon, also specifying if transfer of strength or skill is meant; (2) functional magnetic resonance imaging, short-interval intracortical inhibition and interhemispheric inhibition appear to be promising tools to study the mechanisms of transfer; (3) strategies which maximize cross-education, such as high-intensity training, eccentric contractions, and mirror illusion, seem worth being included in the intervention plan; (4) study protocols should be designed to include at least 13-18 sessions or 4-6 weeks to produce functionally meaningful transfer of strength, and (5) cross-education could be considered as an adjuvant treatment particularly for unilateral orthopedic conditions and sports injuries. Additionally, a clear gap in views emerged between the research field and the purely clinical field. The present consensus statement clarifies relevant aspects of cross-education including neurophysiological, neuroanatomical, and methodological characteristics of the transfer phenomenon, and provides guidance on how to improve the quality and usability of future cross-education studies.

Effects of low- and high-intensity physical exercise on physical and cognitive function in older persons with dementia: a randomized controlled trial.

BACKGROUND: Potential moderators such as exercise intensity or apolipoprotein-E4 (ApoE4) carriership may determine the magnitude of exercise effects on physical and cognitive functions in patients with dementia (PwD). We determined the effects of a 24-week aerobic and strength training program with a low- and high-intensity phase on physical and cognitive function. METHODS: In an assessor-blinded randomized trial, 91 PwD (all-cause dementia, recruited from daycare and residential care facilities, age 82.3 ± 7.0 years, 59 women, Mini-Mental State Examination 20.2 ± 4.4) were allocated to the exercise or control group. In the exercise group, PwD participated in a walking and lower limb strength training program with 12 weeks low- and 12 weeks high-intensity training offered three times/week. Attention-matched control participants performed flexibility exercises and recreational activities. We assessed adherence, compliance, and exercise intensity for each session. We assessed physical (endurance, gait speed, mobility, balance, leg strength) and cognitive (verbal memory, visual memory, executive function, inhibitory control, psychomotor speed) functions with performance-based tests at baseline and after 6, 12, 18, 24, and 36 weeks (follow-up). ApoE4 carriership was determined post-intervention. RESULTS: Sixty-nine PwD were analyzed. Their mean attendance was ~ 60% during the study period. There were no significant effects of the exercise vs. control intervention on endurance, mobility, balance, and leg strength in favor of the exercise group (Cohen's d = 0.13-0.18). Gait speed significantly improved with ~ 0.05 m/s after the high-intensity phase for exercise participants (Cohen's d = 0.41) but declined at follow-up. There were no significant effects of the exercise vs. control intervention on any of the cognitive measures (Cohen's d ~ - 0.04). ApoE4 carriership did not significantly moderate exercise effects on physical or cognitive function. CONCLUSIONS: Exercise was superior to control activities for gait speed in our sample of PwD. However, the training effect provided no protection for mobility loss after detraining (follow-up). There were no beneficial effects of the exercise vs. control group on cognitive function. Exercise intensity moderated the effects of exercise on gait speed. ApoE4 carriership moderated the effect of exercise on global cognition only (trend level). TRIAL REGISTRATION: Netherlands Trial Register, NTR5035. Registered on 2 March 2015.

Do gait and muscle activation patterns change at middle-age during split-belt adaptation?

Advancing age affects gait adaptability, but it is unclear if such adaptations to split-belt perturbations are already affected at middle-age. Changes in neuromuscular control, that already start at middle-age, may underlie the age-related changes in gait adaptation. Thus, we examined the effects of age on adaptations in gait and muscle activation patterns during split-belt walking in healthy young and middle-aged adults. Young (23.3 ± 3.13 years) and middle-aged adults (55.3 ± 2.91 years) walked on an instrumented split-belt treadmill. Both age groups adapted similarly by reducing asymmetry in step length and double support time. Surface EMG was recorded from eight leg muscles bilaterally. Principal Component Analysis (PCA) was applied to the EMG data of all subjects, for the fast and slow leg separately, to identify muscle activation patterns. The principal components consisted of i.e. temporal projections that were analyzed with Statistical Parametric Mapping (SPM). The functional muscle groups, identified by PCA, increased activation during early adaptation and post-adaptation, and decreased activation over time similarly in both age groups. Extra activation peaks of the plantar- and dorsiflexors suggest a role in gait modulation during split-belt walking. Both young and middle-aged adults re-established gait symmetry and showed adaptation effects in the muscle activation patterns. Since the adaptation of muscle activation patterns parallels adaptation of gait symmetry, changes in muscle activation likely underlie the changes in step parameters during split-belt adaptation. In conclusion, split-belt adaptation, in terms of gait and muscle activation patterns, is still preserved at middle-age, suggesting that age-related differences occur later in the lifespan.

Effects of acute and chronic unilateral resistance training variables on ipsilateral motor cortical excitability and cross-education: A systematic review.

OBJECTIVE: The increase in voluntary force of an untrained limb (i.e. Cross-education) after unilateral resistance training (RT) is believed to be a consequence of cortical adaptations. However, studies measuring neurophysiological adaptations with transcranial magnetic stimulation (TMS) found inconsistent results. One unexamined factor contributing to the conflicting data is the variation in the type and intensity of muscle contractions, fatigue, and the strategies of pacing the movement. Therefore, the purpose was to analyse how those unilateral RT variables affect the adaptations in ipsilateral M1 (iM1) and cross-education. METHODS: We performed a systematic literature review, with the following search terms with Boolean conjunctions: "Transcranial magnetic stimulation" AND "Ipsilateral cortex" AND "Resistance training". RESULTS: The 11 acute and 12 chronic studies included partially support the idea of increased cortical excitability and reduced intracortical inhibition in iM1, but the inconsistency between studies was high. CONCLUSIONS: Differences in type and intensity of contraction, fatigue, and strategies of pacing the movement contributed to the inconsistencies. The tentative conclusion is that high intensity eccentric or externally paced contractions are effective to increase iM1 excitability but cross-education can occur in the absence of such changes. Thus, the mechanism of the cross-education examined with TMS remains unclear.

Age-related changes in brain deactivation but not in activation after motor learning.

It is poorly understood how healthy aging affects neural mechanisms underlying motor learning. We used blood-oxygen-level dependent (BOLD) contrasts to examine age-related changes in brain activation after acquisition and consolidation (24 h) of a visuomotor tracking skill. Additionally, structural magnetic resonance imaging and diffusion tensor imaging were used to examine age-related structural changes in the brain. Older adults had reduced gray matter volume (628 ±â€¯57 ml) and mean white matter anisotropy (0.18 ±â€¯0.03) compared with young adults (741 ±â€¯59 ml and 0.22 ±â€¯0.02, respectively). Although motor performance was 53% lower in older (n = 15, mean age 63.1 years) compared with young adults (n = 15, mean age 25.5 years), motor practice improved motor performance similarly in both age groups. While executing the task, older adults showed in general greater brain activation compared with young adults. BOLD activation decreased in parietal and occipital areas after skill acquisition but activation increased in these areas after consolidation in both age groups, indicating more efficient visuospatial processing immediately after skill acquisition. Changes in deactivation in specific areas were age-dependent after consolidating the motor skill into motor memory. Young adults showed greater deactivations from post-test to retention in parietal, occipital and temporal cortices, whereas older adults showed smaller deactivation in the frontal cortex. Since learning rate was similar between age groups, age-related changes in activation patterns may be interpreted as a compensatory mechanism for age-related structural decline.

Effects of side-dominance on knee joint proprioceptive target-matching asymmetries.

AIMS: Right- and left-side-dominant individuals reveal target-matching asymmetries between joints of the dominant and non-dominant upper limbs. However, it is unclear if such asymmetries are also present in lower limb's joints. We hypothesized that right-side-dominant participants perform knee joint target-matching tasks more accurately with their non-dominant leg compared to left-side-dominant participants. METHODS: Participants performed position sense tasks using each leg by moving each limb separately and passively on an isokinetic dynamometer. RESULTS: Side-dominance affected (p < 0.05) knee joint absolute position errors only in the non-dominant leg but not in the dominant leg: right-side-dominant participants produced less absolute position errors (2.82° ± 0.72°) with the non-dominant leg compared to left-side-dominant young participants (3.54° ± 0.33°). CONCLUSIONS: In conclusion, right-side-dominant participants tend to perform a target-matching task more accurately with the non-dominant leg compared to left-side-dominant participants. Our results extend the literature by showing that right-hemisphere specialization under proprioceptive target-matching tasks may be not evident at the lower limb joints.

Spectral and temporal electroencephalography measures reveal distinct neural networks for the acquisition, consolidation, and interlimb transfer of motor skills in healthy young adults.

OBJECTIVE: Plasticity of the central nervous system likely underlies motor learning. It is however unclear, whether plasticity in cortical motor networks is motor learning stage-, activity-, or connectivity-dependent. METHODS: From electroencephalography (EEG) data, we quantified effective connectivity by the phase slope index (PSI), neuronal activity by event-related desynchronization, and sensorimotor integration by N30 during the stages of visuomotor skill acquisition, consolidation, and interlimb transfer. RESULTS: Although N30 amplitudes and event-related desynchronization in parietal electrodes increased with skill acquisition, changes in PSI correlated most with motor performance in all stages of motor learning. Specifically, changes in PSI between the premotor, supplementary motor, and primary motor cortex (M1) electrodes correlated with skill acquisition, whereas changes in PSI between electrodes representing M1 and the parietal and primary sensory cortex (S1) correlated with skill consolidation. The magnitude of consolidated interlimb transfer correlated with PSI between bilateral M1s and between S1 and M1 in the non-practiced hemisphere. CONCLUSIONS: Spectral and temporal EEG measures but especially PSI correlated with improvements in complex motor behavior and revealed distinct neural networks in the acquisition, consolidation, and interlimb transfer of motor skills. SIGNIFICANCE: A complete understanding of the neuronal mechanisms underlying motor learning can contribute to optimizing rehabilitation protocols.

Relationship between drug burden and physical and cognitive functions in a sample of nursing home patients with dementia.

PURPOSE: The Drug Burden Index (DBI) is a tool to quantify the anticholinergic and sedative load of drugs. Establishing functional correlates of the DBI could optimize drug prescribing in patients with dementia. In this cross-sectional study, we determined the relationship between DBI and cognitive and physical functions in a sample of patients with dementia. METHODS: Using performance-based tests, we measured physical and cognitive functions in 140 nursing home patients aged over 70 with all-cause dementia. We also determined anticholinergic DBI (AChDBI) and sedative DBI (SDBI) separately and in combination as total drug burden (TDB). RESULTS: Nearly one half of patients (48%) used at least one DBI-contributing drug. In 33% of the patients, drug burden was moderate (0 < TDB < 1) whereas in 15%, drug burden was high (TDB ≥ 1). Multivariate models yielded no associations between TDB, AChDBI, and SDBI, and physical or cognitive function (all p > 0.05). CONCLUSIONS: A lack of association between drug burden and physical or cognitive function in this sample of patients with dementia could imply that drug prescribing is more optimal for patients with dementia compared with healthy older populations. However, such an interpretation of the data warrants scrutiny as several dementia-related factors may confound the results of the study.

Gender may have an influence on the relationship between Functional Movement Screen scores and gait parameters in elite junior athletes - A pilot study.

Aims The aim of this study was to examine the effects of gender on the relationship between Functional Movement Screen (FMS) and treadmill-based gait parameters. Methods Twenty elite junior athletes (10 women and 10 men) performed the FMS tests and gait analysis at a fixed speed. Between-gender differences were calculated for the relationship between FMS test scores and gait parameters, such as foot rotation, step length, and length of gait line. Results Gender did not affect the relationship between FMS and treadmill-based gait parameters. The nature of correlations between FMS test scores and gait parameters was different in women and men. Furthermore, different FMS test scores predicted different gait parameters in female and male athletes. FMS asymmetry and movement asymmetries measured by treadmill-based gait parameters did not correlate in either gender. Conclusion There were no interactions between FMS, gait parameters, and gender; however, correlation analyses support the idea that strength and conditioning coaches need to pay attention not only to how to score but also how to correctly use FMS.

Assessment of candidate immunohistochemical prognostic markers of meningioma recurrence.

Although tumour recurrence is an important and not infrequent event in meningiomas, predictive immunohistochemical markers have not been identified yet. The aim of this study was to address this clinically relevant problem by systematic retrospective analysis of surgically completely resected meningiomas with and without recurrence, including tumour samples from patients who underwent repeat surgeries. Three established immunohistochemical markers of routine pathological meningioma work-up have been assessed: the proliferative marker Ki-67 (clone Mib1), the tumour suppressor gene p53 and progesterone receptor (PR). All these proteins correlate with the tumour WHO grade, however the predictive value regarding recurrence and progression in tumour grade is unknown. One hundred and fourteen surgical specimens of 70 meningioma patients (16 male and 54 female) in a 16 years' interval have been studied. All tumours had apparently complete surgical removal. On Mib1, PR and p53 immunostained sections, the percentage of labelled tumour cells, the staining intensity and the multiplied values of these parameters (the histoscore) was calculated. Results were statistically correlated with tumour WHO grade, (sub)type, recurrence and progression in WHO grade at subsequent biopsies. Our results confirmed previous findings that the WHO grade is directly proportional to Mib1 and p53 and is inversely proportional to the PR immunostain. We have demonstrated that Mib1 and p53 have a significant correlation with and predictive value of relapse/recurrence irrespective of the histological subtype of the same WHO grade. As a quantitative marker, Mib1 has the best correlation with a percentage of labelled cells, whereas p53 with intensity and histoscore. In conclusion, the immunohistochemical panel of PR, p53, Mib1 in parallel with applying standard diagnostic criteria based on H and E stained sections is sufficient and reliable to predict meningioma recurrence in surgically completely resected tumours.

Cognitive decline in dementia with Lewy bodies: a 5-year prospective cohort study.

OBJECTIVES: We report the cognitive decline in persons diagnosed with mild dementia with Lewy bodies (DLB) and mild Alzheimer's disease (AD) during 5 years of annual follow-ups. METHODS: Patients were recruited into the study from geriatric, psychiatric and neurology clinics in Western Norway during 2005-2013. They were diagnosed according to clinical consensus criteria, based on standardised clinical rating scales. Autopsy-based diagnoses were available for 20 cases. Cognitive decline for up to 5 years was assessed using the Clinical Dementia Rating (CDR) scale and the Mini-Mental State Examination (MMSE). Survival analysis including Cox regression (time to reach severe dementia) and linear mixed-effects (lme) modelling were used to model the decline on MMSE. RESULTS: At least one follow-up assessment was available for 67 patients with DLB and 107 patients with AD, with a median follow-up time of 4.3 years. The time to reach severe dementia was significantly shorter in DLB (median 1793 days) compared with AD (1947 days; p=0.033), and the difference remained significant in the multiple Cox regression analysis (HR=2.0, p<0.02). In the adjusted lme model, MMSE decline was faster in DLB (annual decline 4.4 points) compared with AD (3.2 points; p<0.008). CONCLUSIONS: Our findings show that from the mild dementia stage, patients with DLB have a more rapid cognitive decline than in AD. Such prognostic information is vital for patients and families and crucial for planning clinical trials and enabling health economic modelling.

Direct and crossed effects of somatosensory electrical stimulation on motor learning and neuronal plasticity in humans.

PURPOSE: Sensory input can modify voluntary motor function. We examined whether somatosensory electrical stimulation (SES) added to motor practice (MP) could augment motor learning, interlimb transfer, and whether physiological changes in neuronal excitability underlie these changes. METHODS: Participants (18-30 years, n = 31) received MP, SES, MP + SES, or a control intervention. Visuomotor practice included 300 trials for 25 min with the right-dominant wrist and SES consisted of weak electrical stimulation of the radial and median nerves above the elbow. Single- and double-pulse transcranial magnetic stimulation (TMS) metrics were measured in the intervention and non-intervention extensor carpi radialis. RESULTS: There was 27 % motor learning and 9 % (both p < 0.001) interlimb transfer in all groups but SES added to MP did not augment learning and transfer. Corticospinal excitability increased after MP and SES when measured at rest but it increased after MP and decreased after SES when measured during contraction. No changes occurred in intracortical inhibition and facilitation. MP did not affect the TMS metrics in the transfer hand. In contrast, corticospinal excitability strongly increased after SES with MP + SES showing sharply opposite of these effects. CONCLUSION: Motor practice and SES each can produce motor learning and interlimb transfer and are likely to be mediated by different mechanisms. The results provide insight into the physiological mechanisms underlying the effects of MP and SES on motor learning and cortical plasticity and show that these mechanisms are likely to be different for the trained and stimulated motor cortex and the non-trained and non-stimulated motor cortex.

A 200-m All-out Front-crawl Swim Modifies Competitive Swimmers' Shoulder Joint Position Sense.

We tested the hypothesis that an all-out-effort 200-m front-crawl swim trial affects competitive swimmers' shoulder joint position sense. On Day 1, we measured shoulder joint position sense before and after the swim trial, and on Day 2 before and after 2 min of seated rest. On both days, shoulder joint position sense was measured in the seated position using electromagnetic movement sensors in a position-matching paradigm. An investigator abducted participants' left (reference) shoulder joint in the frontal plane to test angles of 90°, 135°, and 180°. Participants then actively abducted the right (indicator) shoulder joint to match the position of the left, reference arm. After the 200-m all-out front-crawl swim trial, the indicator relative to the reference angle differed by 4.4° toward adduction at the 180° (vertical) testing position (P<0.05). Variation in absolute matching error was 3.2° or 2.2 times greater after swim compared with the no-swim control trial. An all-out 200-m front-crawl swim trial can selectively increase competitive swimmers' shoulder joint position sense error and increase variation in matching error in horizontal arm position.

Neuronal mechanisms of motor learning and motor memory consolidation in healthy old adults.

It is controversial whether or not old adults are capable of learning new motor skills and consolidate the performance gains into motor memory in the offline period. The underlying neuronal mechanisms are equally unclear. We determined the magnitude of motor learning and motor memory consolidation in healthy old adults and examined if specific metrics of neuronal excitability measured by magnetic brain stimulation mediate the practice and retention effects. Eleven healthy old adults practiced a wrist extension-flexion visuomotor skill for 20 min (MP, 71.3 years), while a second group only watched the templates without movements (attentional control, AC, n = 11, 70.5 years). There was 40 % motor learning in MP but none in AC (interaction, p < 0.001) with the skill retained 24 h later in MP and a 16 % improvement in AC. Corticospinal excitability at rest and during task did not change, but when measured during contraction at 20 % of maximal force, it strongly increased in MP and decreased in AC (interaction, p = 0.002). Intracortical inhibition at rest and during the task decreased and facilitation at rest increased in MP, but these metrics changed in the opposite direction in AC. These neuronal changes were especially profound at retention. Healthy old adults can learn a new motor skill and consolidate the learned skill into motor memory, processes that are most likely mediated by disinhibitory mechanisms. These results are relevant for the increasing number of old adults who need to learn and relearn movements during motor rehabilitation.

Direct and crossed effects of somatosensory stimulation on neuronal excitability and motor performance in humans.

This analytic review reports how prolonged periods of somatosensory electric stimulation (SES) with repetitive transcutaneous nerve stimulation can have 'direct' and 'crossed' effects on brain activation, corticospinal excitability, and motor performance. A review of 26 studies involving 315 healthy and 78 stroke and dystonia patients showed that the direct effects of SES increased corticospinal excitability up to 40% (effect size: 0.2 to 6.1) and motor performance up to 14% (effect size: 0.3 to 3.1) but these two features did not correlate. SES did not affect measures of intracortical excitability. Most likely, a long-term potentiation-like mechanism in the excitatory glutamatergic connections between the primary sensory and motor cortices mediates the direct effects of SES on corticospinal excitability and motor performance. We propose two models for the untested hypothesis that adding SES to unilateral motor practice could magnify the magnitude of inter-limb transfer. If tenable, the hypothesis would expand the evolving repertoire of sensory augmentation of cross-education using mirrors and add SES as an alternative to conventional rehabilitation strategies such as constraint-induced movement therapy.