Classification of Mild Cognitive Impairment and Alzheimer's Disease Using Manual Motor Measures.

INTRODUCTION: Manual motor problems have been reported in mild cognitive impairment (MCI) and Alzheimer's disease (AD), but the specific aspects that are affected, their neuropathology, and potential value for classification modeling is unknown. The current study examined if multiple measures of motor strength, dexterity, and speed are affected in MCI and AD, related to AD biomarkers, and are able to classify MCI or AD. METHODS: Fifty-three cognitively normal (CN), 33 amnestic MCI, and 28 AD subjects completed five manual motor measures: grip force, Trail Making Test A, spiral tracing, finger tapping, and a simulated feeding task. Analyses included: 1) group differences in manual performance; 2) associations between manual function and AD biomarkers (PET amyloid ß, hippocampal volume, and APOE ε4 alleles); and 3) group classification accuracy of manual motor function using machine learning. RESULTS: amnestic MCI and AD subjects exhibited slower psychomotor speed and AD subjects had weaker dominant hand grip strength than CN subjects. Performance on these measures was related to amyloid ß deposition (both) and hippocampal volume (psychomotor speed only). Support vector classification well-discriminated control and AD subjects (area under the curve of 0.73 and 0.77 respectively), but poorly discriminated MCI from controls or AD. CONCLUSION: Grip strength and spiral tracing appear preserved, while psychomotor speed is affected in amnestic MCI and AD. The association of motor performance with amyloid ß deposition and atrophy could indicate that this is due to amyloid deposition in- and atrophy of motor brain regions, which generally occurs later in the disease process. The promising discriminatory abilities of manual motor measures for AD emphasize their value alongside other cognitive and motor assessment outcomes in classification and prediction models, as well as potential enrichment of outcome variables in AD clinical trials.

Efficacy of Corsi Block Tapping Task training for improving visuospatial skills: a non-randomized two-group study.

Even though impaired visuospatial abilities can negatively affect daily functioning, there are very few training programs that attempt to improve visuospatial abilities. The purpose of this study was to examine if a single training session with a computerized version of the Corsi Block Tapping Task could improve mental rotation skills. Fifty-three young adults were assigned to one of two groups: (1) control group (mean age = 21.4; 10 females), who had 20 min of rest after their baseline assessment, or (2) training group (mean age = 21.5; 17 females), who had 20 min of training on the Corsi Block Tapping Task after their baseline assessment. The primary outcome was reaction time on a computer-based mental rotation task, and it was assessed both before and after the rest or training. There was a significant interaction between time (pre vs. post) and group (control vs. training) on mental rotation performance (p = 0.04), with the training group performing on average 124 ms faster on accurate trials than the control group at post-test. This preliminary study suggested that improving mental rotation may be feasible through targeted cognitive training. Future studies will consider multiple sessions of Corsi Block Tapping Task training to maximize training benefits (i.e., dose-response), as well as longer term retention in cognitively intact and impaired individuals.

Age-related differences in functional tool-use are due to changes in movement quality and not simply motor slowing.

Age-related declines in fine motor control may impact tool-use and thereby limit functional independence. Most previous research has, however, focused on the effect of aging on gross motor tasks. Few studies have investigated the effects of aging on the strategy or quality of fine motor skills, especially in tool-use, which may better reflect how age impacts complex movement capability. Twenty-two young (ages 19-35) and 18 older adults (ages 58-87) performed a timed upper extremity task using a tool to acquire and transport objects to different locations. Overall task performance was divided into two phases based on 3-D position of the tool: a gross motor phase (object transport) and a fine motor phase (object acquisition). Overall, older adults took longer to complete the task. A linear model indicated that this was due to the duration of the fine motor phase more so than the gross motor phase. To identify age-related differences in the quality of the fine motor phase, we fit three-dimensional ellipsoids to individual data and the calculated the ellipsoid volume. Results demonstrated a significant volume-by-age interaction, whereby increased ellipsoid volume (space the tool occupied) related to increased mean dwell time for the older adult group only; younger adults did not demonstrate this relationship. Additionally, older adults with longer movement times during the fine motor phase also had lower cognitive scores. No age-related differences were observed for the gross motor phase, suggesting that age-related declines in tool-use may be due to changes in fine motor control and cognitive status.

Neural correlates of within-session practice effects in mild motor impairment after stroke: a preliminary investigation.

While the structural integrity of the corticospinal tract (CST) has been shown to support motor performance after stroke, the neural correlates of within-session practice effects are not known. The purpose of this preliminary investigation was to examine the structural brain correlates of within-session practice effects on a functional motor task completed with the more impaired arm after stroke. Eleven individuals with mild motor impairment (mean age 57.0 ± 9.4 years, mean months post-stroke 37.0 ± 66.1, able to move ≥ 26 blocks on the Box and Blocks Test) due to left hemisphere stroke completed structural MRI and practiced a functional motor task that involved spooning beans from a start cup to three distal targets. Performance on the motor task improved with practice (p = 0.004), although response was variable. Baseline motor performance (Block 1) correlated with integrity of the CST (r = - 0.696) while within-session practice effects (change from Block 1 to Block 3) did not. Instead, practice effects correlated with degree of lesion to the superior longitudinal fasciculus (r = 0.606), a pathway that connects frontal and parietal brain regions previously shown to support motor learning. This difference between white matter tracts associated with baseline motor performance and within-session practice effects may have implications for understanding response to motor practice and the application of brain-focused intervention approaches aimed at improving hand function after stroke.

Challenging the relationship of grip strength with cognitive status in older adults.

OBJECTIVE: Grip strength is a widely used motor assessment in ageing research and has repeatedly been shown to be associated with cognition. It has been proposed that grip strength could enhance cognitive screening in experimental or clinical research, but this study uses multiple data-driven approaches to caution against this interpretation. Furthermore, we introduce an alternative motor assessment, comparable to grip dynamometry, but has a more robust relationship with cognition among older adults. DESIGN: Associations between grip strength and cognition (measured with the Montreal Cognitive Assessment) were analysed cross sectionally using multivariate regression in two datasets: (1) The Irish LongituDinal Study on Ageing (TILDA; N = 5,980, community-dwelling adults ages 49-80) and (2) an experimental dataset (N = 250, community-dwelling adults aged 39-98). Additional statistical simulations on TILDA tested how ceiling effects or skewness in these variables influenced these associations for quality control. RESULTS: Grip strength was significantly but weakly associated with cognition, consistent with previous studies. Simulations revealed this was not due to skewness/ceiling effects. Conversely, a new alternative motor assessment (functional reaching [FR]) had a stronger, more robust and more sensitive relationship with cognition compared to grip strength. CONCLUSIONS: Grip strength should be cautiously interpreted as being associated with cognition. However, FR may have a stronger and clinically useful relationship with cognition.

Generalizing the predictive relationship between 1-month motor skill retention and Rey-Osterrieth Delayed Recall scores from nondemented older adults to individuals with chronic stroke: a short report.

Motor learning is fundamental to motor rehabilitation outcomes. There is growing evidence from non-neurological populations supporting the role of visuospatial memory function in motor learning, but current predictive models of motor recovery of individuals with stroke generally exclude cognitive measures, thereby overlooking the potential link between motor learning and visuospatial memory. Recent work has demonstrated that a clinical test of visuospatial memory (Rey-Osterrieth Complex Figure Delayed Recall) may predict 1-month skill learning in older adults; however, whether this relationship persists in individuals with chronic stroke remains unknown. The purpose of this short report was to validate previous findings using Rey-Osterrieth Complex Figure Delayed Recall test scores to predict motor learning and determine if this relationship generalized to a set of individuals post-stroke. Two regression models (one including Delayed Recall scores and one without) were trained using data from non-stroke older adults. To determine the extent to which Delayed Recall test scores impacted prediction accuracy of 1-month skill learning in older adults, we used leave-one-out cross-validation to evaluate the prediction error between models. To test if this predictive relationship generalized to individuals with chronic ischemic stroke, we then tested each trained model on an independent stroke dataset. Results indicated that in both stroke and older adult datasets, inclusion of Delayed Recall scores explained significantly more variance of 1-month skill performance than models that included age, education, and baseline motor performance alone. This proof-of-concept suggests that the relationship between delayed visuospatial memory and 1-month motor skill performance generalizes to individuals with chronic stroke, and supports the idea that visuospatial testing may provide prognostic insight into clinical motor rehabilitation outcomes.

Exploring the relationship between visuospatial function and age-related deficits in motor skill transfer.

BACKGROUND: Generalizing learned information from one motor task to another is critical for effective motor rehabilitation. A recent study demonstrated age-related declines in motor skill transfer, yet findings from other motor learning studies suggest that visuospatial impairments may explain such aging effects. AIMS: The purpose of this secondary analysis was to test whether age-related deficits in motor skill transfer were related to low visuospatial ability. METHODS: Forty-two participants (mean ± SD age: 72.1 ± 9.9 years) were tested on an upper extremity dexterity task before and after 3 days of training on an upper extremity reaching task. Training and control data have been published previously. Prior to training, global cognitive status and specific cognitive domains (visuospatial/executive, attention, and delayed memory) were evaluated using the Montreal Cognitive Assessment. RESULTS: Backward-stepwise linear regression indicated that the Visuospatial/Executive subtest was related to motor skill transfer (i.e., the amount of change in performance on the untrained motor task), such that participants with higher visuospatial scores improved more on the untrained dexterity task than those with lower scores. Global cognitive status was unrelated to motor skill transfer. DISCUSSION: Consistent with previous studies showing a positive relationship between visuospatial function and other aspects of motor learning, this secondary analysis indicates that less motor skill transfer among older adults may indeed be due to declines in visuospatial function. CONCLUSIONS: The present study highlights the potential utility of assessing older patients' visuospatial ability within motor rehabilitation to provide valuable insight into the extent to which they may learn and generalize motor skills through training.

Predicting Motor Sequence Learning in People With Parkinson Disease.

BACKGROUND AND PURPOSE: Skill acquisition (ie, performance changes during practice) occurs in a nonlinear fashion. Despite this, motor learning is typically measured by comparing discrete timepoints. Thus, typical measures of motor learning do not detect skill acquisition characteristics that may be clinically meaningful. Reliable prediction of motor skill learning in people with Parkinson disease (PD) would allow therapists to more effectively individualize practice doses to fit specific patients' needs. The purposes of this study were to (a) characterize postural skill acquisition in people with PD, and identify factors (such as acquisition rate and practice dose to plateau) that predict learning, and (b) investigate whether levodopa medication (L-dopa) status during practice impacted learning. METHODS: Twenty-seven adults with PD practiced a postural motor task over 3 days, followed by 2 retention tests. Participants were randomized to practice either ON or OFF L-dopa. Data for repeating and random sequences were each analyzed using nonlinear curve-fitting and mixed-effects regressions. Learning was defined as pretest minus retention test performance. RESULTS: Participants with less physical impairment demonstrated less learning on the repeating and random sequence tasks compared with participants with more impairment. Participants who improved faster during practice demonstrated less learning on the repeating sequence task compared with participants who improved more slowly. Reaching plateau during practice was not related to learning. L-dopa did not impair learning. DISCUSSION AND CONCLUSIONS: Participants' skill acquisition characteristics were related to learning a postural motor task. Patient-specific factors, such as the rate of skill acquisition, level of physical function, and medication status, may influence how postural motor practice is delivered during balance rehabilitation.Video Abstract available for more insights from the authors (see the Video, Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A250).

Quantifying Caregiver Movement when Measuring Infant Movement across a Full Day: A Case Report.

There is interest in using wearable sensors to measure infant movement patterns and physical activity, however, this approach is confounded by caregiver motion. The purpose of this study is to estimate the extent that caregiver motion confounds wearable sensor data in full-day studies of infant leg movements. We used wearable sensors to measure leg movements of a four-month-old infant across 8.5 hours, during which the infant was handled by the caregiver in a typical manner. A researcher mimicked the actions of the caregiver with a doll. We calculated 7744 left and 7107 right leg movements for the infant and 1013 left and 1115 right "leg movements" for the doll. In this case, approximately 15% of infant leg movements can be attributed to background motion of the caregiver. This case report is the first step toward removing caregiver-produced background motion from the infant wearable sensor signal. We have estimated the size of the effect and described the activities that were related to noise in the signal. Future research can characterize the noise in detail and systematically explore different methods to remove it.

Concussion history is negatively associated with visual-motor force complexity: evidence for persistent effects on visual-motor integration.

OBJECTIVES: Long-term monitoring of concussion recovery requires time- and cost-effective methods. Physiologic complexity may be useful in evaluating visual-motor integration following concussion. The purpose of this study was to quantify the extent to which prior number of concussions influenced visual-motor tracking force complexity. METHODS: Thirty-five individuals with a self-reported concussion history (age: 20.92 ± 1.98) and 15 without (age: 20.92 ± 2.21) performed an isometric visual-motor tracking task, using index finger force to trace a straight line across a computer screen. Finger force root mean square error (RMSE), multi-scale complexity, and average power from 0 to 12 Hertz (Hz) were calculated. Individual multiple regressions were fit to these outcomes. RESULTS: Force complexity decreased linearly with an increasing number of concussions (R2 = 0.101). Males had more complex force overall (R2 = 0.219) and greater 4-8 Hz average power (R2 = 0.193). The 8-12 Hz average power decreased significantly for individuals with prior loss of consciousness (LOC) and increasing numbers of concussions (R2 = 0.143). CONCLUSION: Individuals exhibited linear decreases in visual-motor tracking force complexity with increasing numbers of concussions, influenced by both gender and a history of LOC. These findings indicate cumulative changes in the ways in which previously concussed individuals process and integrate visual information to guide behaviour.

Within-Session Practice Effects in the Jebsen Hand Function Test (JHFT).

The Jebsen Hand Function Test (JHFT) is a standardized assessment that has been used as a clinical outcome measure. To appropriately interpret the effects of an intervention on hand function (as measured by the JHFT), the extent to which this instrument shows significant practice effects must be quantified. The purpose of this study was to determine whether the JHFT is susceptible to within-session practice effects. The results showed that the dominant and nondominant hands significantly improved on the JHFT and many of its subtests over six consecutive trials. Although practice effects might complicate the interpretation of change due to intervention, we briefly relate our findings to emerging neuropsychological evidence that practice effects may indicate a person's motor learning potential or treatment responsiveness.

White Matter Microstructure Analysis in Subjective Memory Complaints and Cognitive Impairment: Insights from Diffusion Kurtosis Imaging and Free-Water DTI.

Background: Dementia is characterized by a cognitive decline in memory and other domains that lead to functional impairments. As people age, subjective memory complaints (SMC) become common, where individuals perceive cognitive decline without objective deficits on assessments. SMC can be an early sign and may precede amnestic mild cognitive impairment (MCI), which frequently advances to Alzheimer's disease (AD). Objective: This study aims to investigate white matter microstructure in individuals with SMC, in cognitively impaired (CI) cohorts, and in cognitively normal individuals using diffusion kurtosis imaging (DKI) and free water imaging (FWI). The study also explores voxel-based correlations between DKI/FWI metrics and cognitive scores to understand the relationship between brain microstructure and cognitive function. Methods: Twelve healthy controls (HCs), ten individuals with SMC, and eleven CI individuals (MCI or AD) were enrolled in this study. All participants underwent MRI 3T scan and the BNI Screen (BNIS) for Higher Cerebral Functions. Results: The mean kurtosis tensor and anisotropy of the kurtosis tensor showed significant differences across the three groups, indicating altered white matter microstructure in CI and SMC individuals. The free water volume fraction (f) also revealed group differences, suggesting changes in extracellular water content. Notably, these metrics effectively discriminated between the CI and HC/SMC groups. Additionally, correlations between imaging metrics and BNIS scores were found for CI and SMC groups. Conclusions: These imaging metrics hold promise in discriminating between individuals with CI and SMC. The observed differences indicate their potential as sensitive and specific biomarkers for early detection and differentiation of cognitive decline.

Evidence and sources of placebo effects in transcranial direct current stimulation during a single session of visuospatial working memory practice.

Transcranial direct current stimulation (tDCS) can be used to non-invasively augment cognitive training. However, the benefits of tDCS may be due in part to placebo effects, which have not been well-characterized. The purpose of this study was to determine whether tDCS can have a measurable placebo effect on cognitive training and to identify potential sources of this effect. Eighty-three right-handed adults were randomly assigned to one of three groups: control (no exposure to tDCS), sham tDCS, or active tDCS. The sham and active tDCS groups were double-blinded. Each group performed 20 min of an adapted Corsi Block Tapping Task (CBTT), a visuospatial working memory task. Anodal or sham tDCS was applied during CBTT training in a right parietal-left supraorbital montage. After training, active and sham tDCS groups were surveyed on expectations about tDCS efficacy. Linear mixed effects models showed that the tDCS groups (active and sham combined) improved more on the CBTT with training than the control group, suggesting a placebo effect of tDCS. Participants' tDCS expectations were significantly related to the placebo effect, as was the belief of receiving active stimulation. This placebo effect shows that the benefits of tDCS on cognitive training can occur even in absence of active stimulation. Future tDCS studies should consider how treatment expectations may be a source of the placebo effect in tDCS research, and identify ways to potentially leverage them to maximize treatment benefit.

Hemispheric specialization for movement control produces dissociable differences in online corrections after stroke.

In this study, we examine whether corrections made during an ongoing movement are differentially affected by left hemisphere damage (LHD) and right hemisphere damage (RHD). Our hypothesis of motor lateralization proposes that control mechanisms specialized to the right hemisphere rely largely on online processes, while the left hemisphere primarily utilizes predictive mechanisms to specify optimal coordination patterns. We therefore predict that RHD, but not LHD, should impair online correction when task goals are unexpectedly changed. Fourteen stroke subjects (7 LHD, 7 RHD) and 14 healthy controls reached to 1 of the 3 targets that unexpectedly "jumped" during movement onset. RHD subjects showed a considerable delay in initiating the corrective response relative to controls and LHD subjects. However, both stroke groups made large final position errors on the target jump trials. Position deficits following LHD were associated with poor intersegmental coordination, while RHD subjects had difficulty terminating their movements appropriately. These findings confirm that RHD, but not LHD, produces a deficit in the timing of online corrections and also indicate that both stroke groups show position deficits that are related to the specialization of their damaged hemisphere. Further research is needed to identify specific neural circuits within each hemisphere critical for these processes.

Assessment of upper extremity impairment, function, and activity after stroke: foundations for clinical decision making.

The purpose of this review is to provide a comprehensive approach for assessing the upper extremity (UE) after stroke. First, common UE impairments and how to assess them are briefly discussed. Although multiple UE impairments are typically present after stroke, the severity of one's impairment, paresis, is the primary determinant of UE functional loss. Second, UE function is operationally defined and a number of clinical measures are discussed. It is important to consider how impairment and loss of function affect UE activity outside of the clinical environment. Thus, this review also identifies accelerometry as an objective method for assessing UE activity in daily life. Finally, the role that each of these levels of assessment should play in clinical decision making is discussed to optimize the provision of stroke rehabilitation services.

Age and sex effects on Super G performance are consistent across internet devices.

There have been recent advances in the application of online games that assess motor skill acquisition/learning and its relationship to age and biological sex, both of which are associated with dementia risk. While this online motor learning assessment (called Super G), along with other computer-based cognitive tests, was originally developed to be completed on a computer, many people (including older adults) have been shown to access the internet through a mobile device. Thus, to improve the generalizability of our online motor skill learning game, it must not only be compatible with mobile devices but also yield replicable effects of various participant characteristics on performance relative to the computer-based version. It is unknown if age and sex differentially affect game performance as a function of device type (keyboard versus touchscreen control). Thus, the purpose of this study was to investigate if device type modifies the established effects of age and sex on performance. Although there was a main effect of device on performance, this effect did not alter the overall relationship between performance vs. age or sex. This establishes that Super G can now effectively be extended to both computer and mobile platforms to further test for dementia risk factors.

Mediation Analysis of the Effect of Visuospatial Memory on Motor Skill Learning in Older Adults.

There is high inter-individual variability in motor skill learning among older adults. Identifying the nature of these individual differences remains challenging due to interactions between participant characteristics (e.g., age, cognition) and task-related factors (e.g., nature of task, level of skill pre-training), making it difficult to determine plausibly causal relationships. This study addresses these competing explanations by using mediation analysis to examine plausible causal inference between visuospatial memory and one-month retention of both gross and fine motor components of a functional upper-extremity task following training. Results suggest that better visuospatial memory results in more retention of fine but not gross motor skill, expanding on previous correlational studies in older adults and informing future interventions for maximizing motor learning in geriatric populations.

Placebo effects of transcranial direct current stimulation on motor skill acquisition.

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique used in neurorehabilitation to enhance motor training. However, its benefits to motor training can be difficult to reproduce across research studies. It is possible that the observed benefits of tDCS are not directly related to the intervention itself but rather to the brain-mind responses elicited by the treatment context, commonly known as a placebo effect. This study investigated the presence of a placebo effect of tDCS on motor training and explored potential underlying factors. Sixty-eight participants who were right-handed were randomly assigned to active tDCS, sham tDCS, or a no-stimulation control group. Double-blind active or sham tDCS was applied to the right primary motor cortex, while the unblinded control group received no stimulation. All participants completed 30 training trials of a functional upper-extremity motor task. Participants' beliefs of tDCS, along with their prior knowledge of tDCS, were also collected. There was no significant difference in the amount of improvement on the motor task between the active and sham tDCS groups; however, both active and sham tDCS groups improved more than the control group, indicating a placebo effect. More motor task improvement was also associated with higher beliefs of tDCS (regardless of whether active or sham tDCS was received). This demonstrates a measurable placebo effect of tDCS on motor training, driven at least in part by treatment expectations or beliefs. Future tDCS studies should control for beliefs and other placebo-related factors.

Establishing the Validity and Reliability of an Online Motor Learning Game: Applications for Alzheimer's Disease Research Within MindCrowd.

Objective: Motor practice effects (i.e., improvements in motor task performance with practice) are emerging as a unique variable that can predict Alzheimer's disease (AD) progression and biomarker positivity. However, the tasks used to study motor practice effects have involved face-to-face assessment, making them difficult to integrate into large internet-based cohorts that represent the next generation of AD research. The purpose of this study was to validate an online computer game against its in-lab version, which has been shown previously to characterize motor practice effects. Materials and Methods: This study leveraged young adult participants within the MindCrowd electronic cohort, a large nationwide cohort for AD research collected entirely through the internet. Validation compared performance on the online version among MindCrowd users against an age-matched cohort's performance on an in-lab version using a different controller (Xbox 360 controller joystick for in-lab sample versus keyboard arrow keys for online sample). Results: Data indicated that the rate of skill acquisition among MindCrowd users were not significantly different from those of the in-lab cohort. Furthermore, the contact-to-consent rate observed in this study (although low) was similar to that of other online AD cohorts. Conclusion: Overall, this study demonstrates that implementing online games designed to study and measure motor practice effects into online research cohorts is feasible and valid. Future research will explore how online game performance is associated with age and dementia risk factors that may help further an understanding of AD.