Showing papers by "Anat Mirelman published in 2015"

Differential effects of severe vs mild GBA mutations on Parkinson disease

Abstract: Objective: To better define the genotype-phenotype correlations between the type of GBA (glucosidase, beta, acid) mutation, severe or mild, and the risk and age at onset (AAO), and potential mechanism of Parkinson disease (PD). Methods: We analyzed 1,000 patients of Ashkenazi-Jewish descent with PD for 7 founder GBA mutations, and conducted a meta-analysis of risk and AAO according to GBA genotype (severe or mild mutation). The meta-analysis included 11,453 patients with PD and 14,565 controls from worldwide populations. The statistical analysis was done with and without continuity correction (constant or empirical), considering biases that could potentially affect the results. Results: Among Ashkenazi-Jewish patients with PD, the odds ratios for PD were 2.2 and 10.3 for mild and severe GBA mutation carriers, respectively. The observed frequency of severe GBA mutation carriers among patients with PD was more than 4-fold than expected (4.4% vs 0.9%, respectively, p GBA mutation carriers and 9.92 and 21.29 for severe GBA mutation carriers ( p −6 for all analyses). Pooled analysis demonstrated AAO of 53.1 (±11.2) and 58.1 (±10.6) years for severe and mild GBA mutation carriers, respectively ( p = 4.3 × 10 −5 ). Conclusions: These data demonstrate that mild and severe heterozygous GBA mutations differentially affect the risk and the AAO of PD. Our results have important implications for genetic counseling and clinical follow-up.

Age-specific penetrance of LRRK2 G2019S in the Michael J. Fox Ashkenazi Jewish LRRK2 Consortium

Abstract: Objective: Estimates of the penetrance of LRRK2 G2019S vary widely (24%–100%), reflective of differences in ascertainment, age, sex, ethnic group, and genetic and environmental modifiers. Methods: The kin-cohort method was used to predict penetrance in 2,270 relatives of 474 Ashkenazi Jewish (AJ) Parkinson disease (PD) probands in the Michael J. Fox LRRK2 AJ Consortium in New York and Tel Aviv, Israel. Patients with PD were genotyped for the LRRK2 G2019S mutation and at least 7 founder GBA mutations. GBA mutation carriers were excluded. A validated family history interview, including age at onset of PD and current age or age at death for each first-degree relative, was administered. Neurologic examination and LRRK2 genotype of relatives were included when available. Results: Risk of PD in relatives predicted to carry an LRRK2 G2019S mutation was 0.26 (95% confidence interval [CI] 0.18–0.36) to age 80 years, and was almost 3-fold higher than in relatives predicted to be noncarriers (hazard ratio [HR] 2.89, 95% CI 1.73–4.55, p p = 0.44). In contrast, predicted noncarrier male relatives had a higher risk (0.15, 95% CI 0.11–0.20) than predicted noncarrier female relatives (0.07, 95% CI 0.04–0.10; HR male to female: 2.40, 95% CI 1.50–4.15, p Conclusion: Penetrance of LRRK2 G2019S in AJ is only 26% and lower than reported in other ethnic groups. Further study of the genetic and environmental risk factors that influence G2019S penetrance is warranted.

GBA mutations are associated with Rapid Eye Movement Sleep Behavior Disorder

Abstract: Rapid eye movement sleep behavior disorder and GBA mutations are both associated with Parkinson's disease. The GBA gene was sequenced in idiopathic rapid eye movement sleep behavior disorder patients (n = 265), and compared to controls (n = 2240). Rapid eye movement sleep behavior disorder questionnaire was performed in an independent Parkinson's disease cohort (n = 120). GBA mutations carriers had an OR of 6.24 (10.2% in patients vs. 1.8% in controls, P < 0.0001) for rapid eye movement sleep behavior disorder, and among Parkinson's disease patients, the OR for mutation carriers to have probable rapid eye movement sleep behavior disorder was 3.13 (P = 0.039). These results demonstrate that rapid eye movement sleep behavior disorder is associated with GBA mutations, and that combining genetic and prodromal data may assist in identifying individuals susceptible to Parkinson's disease.

Changes in oxygenated hemoglobin link freezing of gait to frontal activation in patients with Parkinson disease: an fNIRS study of transient motor-cognitive failures

Abstract: Recent studies have suggested that deficits in executive function contribute to freezing of gait (FOG), an episodic disturbance common among patients with Parkinson’s disease (PD). To date, most findings provide only indirect evidence of this relationship. Here, we evaluated a more direct link between FOG and frontal lobe dysfunction. Functional, near infrared spectroscopy measured frontal activation, i.e., oxygenated hemoglobin (HbO2) levels in Brodmann area 10 before and during FOG. Eleven patients with PD and eleven healthy older adults were studied. Changes in frontal lobe activation before and during FOG that occurred during turns were determined. Altogether, 49 FOG episodes were observed—28 occurred during turns that were anticipated (i.e., the patient knew in advance that the turn was coming), 21 during unanticipated turns that were performed “abruptly”, according to the examiner’s request. During anticipated turns, HbO2 increased by 0.22 ± 0.08 µM (p = 0.004) before FOG and by an additional 0.19 ± 0.13 µM (p = 0.072) during FOG. In contrast, during unanticipated turns, HbO2 did not increase before or during FOG. HbO2 decreased by 0.32 ± 0.08 µM (p = 0.004) during turns without FOG; in healthy controls HbO2 did not change during turns. These findings support the existence of an association between FOG episodes and changes in frontal lobe HbO2. Increased activation in Brodmann area 10 before FOG, specifically during anticipated turns, highlights the connections between motor planning, information processing, and FOG. These results support the idea that alterations in executive control play a role in this debilitating motor disturbance.

Prediction of Freezing of Gait in Parkinson's From Physiological Wearables: An Exploratory Study

Abstract: Freezing of gait (FoG) is a common gait impairment among patients with advanced Parkinson's disease. FoG is associated with falls and negatively impacts the patient's quality of life. Wearable systems that detect FoG in real time have been developed to help patients resume walking by means of rhythmic cueing. Current methods focus on detection, which require FoG events to happen first, while their prediction opens the road to preemptive cueing, which might help subjects to avoid freeze altogether. We analyzed electrocardiography (ECG) and skin-conductance (SC) data from 11 subjects who experience FoG in daily life, and found statistically significant changes in ECG and SC data just before the FoG episodes, compared to normal walking. Based on these findings, we developed an anomaly-based algorithm for predicting gait freeze from relevant SC features. We were able to predict 71.3% from 184 FoG with an average of 4.2 s before a freeze episode happened. Our findings enable the possibility of wearable systems, which predict with few seconds before an upcoming FoG from SC, and start external cues to help the user avoid the gait freeze.

Higher frequency of certain cancers in LRRK2 G2019S mutation carriers with Parkinson disease: a pooled analysis.

Abstract: Importance Patients with Parkinson disease (PD) who harbor LRRK2 G2019S mutations may have increased risks of nonskin cancers. However, the results have been inconsistent across studies. Objectives To analyze pooled data from 5 centers to further examine the association between LRRK2 G2019S mutation and cancer among patients with PD and to explore factors that could explain discrepancies. Design, Setting, and Participants Clinical, demographic, and genotyping data as well as cancer outcomes were pooled from 1549 patients with PD recruited across 5 movement disorders clinics located in Europe, Israel, and the United States. Associations between LRRK2 G2019S mutation and the outcomes were examined using mixed-effects logistic regression models to estimate odds ratios (ORs) and 95% CIs. Models were adjusted for age and ethnicity (Ashkenazi Jewish vs others) as fixed effects and study center as a random effect. Main Outcomes and Measures All cancers combined, nonskin cancers, smoking-related cancers, hormone-related cancers, and other types of cancer. Results The overall prevalence of the LRRK2 G2019S mutation was 11.4% among all patients with PD. Mutation carriers were younger at PD diagnosis and more likely to be women (53.1%) and of Ashkenazi Jewish descent (76.8%) in comparison with individuals who were not mutation carriers. The LRRK2 G2019S mutation carriers had statistically significant increased risks for nonskin cancers (OR, 1.62; 95% CI, 1.04-2.52), hormone-related cancers (OR, 1.87; 95% CI, 1.07-3.26) and breast cancer (OR, 2.34; 95% CI, 1.05-5.22) in comparison with noncarriers. There were no associations with other cancers. There were no major statistically significant differences in the results when the data were stratified by Ashkenazi Jewish ethnicity; however, there was some evidence of heterogeneity across centers. Conclusions and Relevance This multinational study from 5 centers demonstrates that LRRK2 G2019S mutation carriers have an overall increased risk of cancer, especially for hormone-related cancer and breast cancer in women. Larger prospective cohorts or family-based studies investigating associations between LRRK2 mutations and cancer among patients with PD are warranted to better understand the underlying genetic susceptibility between PD and hormone-related cancers.

Reorganization of corticostriatal circuits in healthy G2019S LRRK2 carriers

Abstract: Objective: We investigated system-level corticostriatal changes in a human model of premotor Parkinson disease (PD), i.e., healthy carriers of the G2019S LRRK2 mutation that is associated with a markedly increased, age-dependent risk of developing PD. Methods: We compared 37 asymptomatic LRRK2 G2019S mutation carriers (age range 30–78 years) with 32 matched, asymptomatic nonmutation carriers (age range 30–74 years). Using fMRI, we tested the hypothesis that corticostriatal connectivity in premotor PD shifts from severely affected to less affected striatal subregions, as shown previously in symptomatic PD. Specifically, we predicted that in premotor PD, the shift in corticostriatal connectivity would follow the same gradient of striatal dopamine depletion known from overt PD, with the dorsoposterior putamen being more affected than the ventroanterior putamen. Results: The known parallel topology of corticostriatal loops was preserved in each group, but the topography of putamen connectivity shifted. In LRRK2 G2019S mutation carriers, the right inferior parietal cortex had reduced functional connectivity with the dorsoposterior putamen but increased connectivity with the ventroanterior putamen, as compared with noncarriers. This shift in functional connectivity increased with age in LRRK2 G2019S mutation carriers. Conclusions: Asymptomatic LRRK2 G2019S mutation carriers show a reorganization of corticostriatal circuits that mirrors findings in idiopathic PD. These changes may reflect premotor basal ganglia dysfunction or circuit-level compensatory changes.

Effects of Aging on Arm Swing during Gait: The Role of Gait Speed and Dual Tasking

Abstract: Healthy walking is characterized by pronounced arm swing and axial rotation. Aging effects on gait speed, stride length and stride time variability have been previously reported, however, less is known about aging effects on arm swing and axial rotation and their relationship to age-associated gait changes during usual walking and during more challenging conditions like dual tasking. Sixty healthy adults between the ages of 30–77 were included in this study designed to address this gap. Lightweight body fixed sensors were placed on each wrist and lower back. Participants walked under 3 walking conditions each of 1 minute: 1) comfortable speed, 2) walking while serially subtracting 3’s (Dual Task), 3) walking at fast speed. Aging effects on arm swing amplitude, range, symmetry, jerk and axial rotation amplitude and jerk were compared between decades of age (30–40; 41–50; 51–60; 61–77 years). As expected, older adults walked slower (p = 0.03) and with increased stride variability (p = 0.02). Arm swing amplitude decreased with age under all conditions (p = 0.04). In the oldest group, arm swing decreased during dual task and increased during the fast walking condition (p<0.0001). Similarly, arm swing asymmetry increased during the dual task in the older groups (p<0.004), but not in the younger groups (p = 0.67). Significant differences between groups and within conditions were observed in arm swing jerk (p<0.02), axial rotation amplitude (p<0.02) and axial jerk (p<0.001). Gait speed, arm swing amplitude of the dominant arm, arm swing asymmetry and axial rotation jerk were all independent predictors of age in a multivariate model. These findings suggest that the effects of gait speed and dual tasking on arm swing and axial rotation during walking are altered among healthy older adults. Follow-up work is needed to examine if these effects contribute to reduced stability in aging.

Nonmotor symptoms in healthy Ashkenazi Jewish carriers of the G2019S mutation in the LRRK2 gene.

Abstract: Background The Asymptomatic carriers of the Leucine rich repeat kinase 2 (LRRK2) G2019S mutation represent a population at risk for developing PD. The aim of this study was to assess differences in non-motor symptoms between non-manifesting carriers and non-carriers of the G2019S mutation.

A Wearable Assistant for Gait Training for Parkinson’s Disease with Freezing of Gait in Out-of-the-Lab Environments

Abstract: People with Parkinson’s disease (PD) suffer from declining mobility capabilities, which cause a prevalent risk of falling. Commonly, short periods of motor blocks occur during walking, known as freezing of gait (FoG). To slow the progressive decline of motor abilities, people with PD usually undertake stationary motor-training exercises in the clinics or supervised by physiotherapists. We present a wearable system for the support of people with PD and FoG. The system is designed for independent use. It enables motor training and gait assistance at home and other unsupervised environments. The system consists of three components. First, FoG episodes are detected in real time using wearable inertial sensors and a smartphone as the processing unit. Second, a feedback mechanism triggers a rhythmic auditory signal to the user to alleviate freeze episodes in an assistive mode. Third, the smartphone-based application features support for training exercises. Moreover, the system allows unobtrusive and long-term monitoring of the user’s clinical condition by transmitting sensing data and statistics to a telemedicine service. We investigate the at-home acceptance of the wearable system in a study with nine PD subjects. Participants deployed and used the system on their own, without any clinical support, at their homes during three protocol sessions in 1 week. Users’ feedback suggests an overall positive attitude toward adopting and using the system in their daily life, indicating that the system supports them in improving their gait. Further, in a data-driven analysis with sensing data from five participants, we study whether there is an observable effect on the gait during use of the system. In three out of five subjects, we observed a decrease in FoG duration distributions over the protocol days during gait-training exercises. Moreover, sensing data-driven analysis shows a decrease in FoG duration and FoG number in four out of five participants when they use the system as a gait-assistive tool during normal daily life activities at home.

REM sleep behavior disorder, as assessed by questionnaire, in G2019S LRRK2 mutation PD and carriers

Abstract: Background Rapid eye movement sleep behavior disorder occurs with idiopathic Parkinson's disease (PD) and often precedes PD. Its frequency in LRRK2-PD and utility as a preclinical marker has not been established. Methods One hundred forty-four idiopathic PD, 142 LRRK2 G2019S mutation PD, 117 non-manifesting carriers, 93 related noncarriers, and 40 healthy controls completed the Rapid eye movement sleep Behavior Disorder Screening Questionnaire. Results Cut scores were met by 30.6% idiopathic PD, 19.7% LRRK2-PD, 6% nonmanifesting carriers, 20.4% related noncarriers, and 15% controls. The likelihood of abnormal scores was decreased in LRRK2-PD versus idiopathic PD (odds ratio = 0.55, P = 0.03), nonmanifesting carriers versus related noncarriers (OR = 0.25, P < 0.01), and PD of less than 3 years' duration, 1 of 19 LRRK2-PD versus 14 of 41 idiopathic PD (P < 0.05). Conclusions A lower frequency of abnormal questionnaire scores is seen in LRRK2-PD, especially in early LRRK2-PD, and in nonmanifesting carriers. Therefore, the Rapid eye movement sleep Behavior Disorder Questionnaire is unlikely to serve as a preclinical marker for phenoconversion to PD. © 2015 International Parkinson and Movement Disorder Society

Body-Fixed Sensors for Parkinson Disease

Abstract: Patients with Parkinson disease experience a complex array of both motor and nonmotor symptoms. The traditional motor hallmarks of Parkinson disease include rigidity, bradykinesia, resting tremor, postural instability, and freezing of gait. As the disease progresses, treatment-related motor response fluctuations and involuntary movements appear. In addition, cognitive disturbances, disautonomia, affective difficulties, and sleep disturbances are also common and further challenge the assessment and treatment of the progressive course of Parkinson disease. Treatment in Parkinson disease is traditionally based on periodic clinical evaluation, reporting of symptoms during the office visit, home-based diaries, and clinical scales assessing motor state, activities of daily living, cognitive and affective state and quality of life. These methods are able to track long-term changes, however, they generally have limitations related to recall bias, subjective reporting, and accuracy. These tools are also insensitive to subtle changes in motor and nonmotor function and the common daily and weekly fluctuations. Better tools are needed to accurately and objectively track disease symptoms, fluctuations, progression, and the effect of treatments.

Gait Measures as Predictors of Poststroke Cognitive Function Evidence From the TABASCO Study

Abstract: Background and Purpose—Patients with stroke are at risk for developing cognitive impairment. We tested whether the assessment of balance and gait can enhance the prediction of long-term cognitive outcome in stroke survivors. Methods—Participants were patients with first-ever, mild-moderate ischemic stroke or transient ischemic attack from the Tel Aviv Brain Acute Stroke Cohort (TABASCO) study, a large prospective cohort study, who underwent 3-T MRI and were followed for ≥2 years using neurological, neuropsychological, and mobility examinations 6, 12, and 24 months after the index event. Results—Data were available for 298 patients (age: 66.7±9.6 years). Forty-six participants (15.4%) developed cognitive decline (CD) over the 2 years of follow-up. The CD group and cognitively intact group did not differ in their neurological deficits or in their infarct volume or location. Nonetheless, 6 months after stroke, the Timed Up and Go test took longer in those who later developed CD (P<0.001). Additionally, the C...

Fall risk is associated with amplified functional connectivity of the central executive network in patients with Parkinson’s disease

Abstract: Falls are debilitating problems that markedly impact the health-related quality of life of many patients with Parkinson’s disease (PD). Numerous studies point to the role of executive function and attention in falls; however, the brain mechanisms underlying these relationships are less clear. Here, we aim to evaluate the brain mechanisms underlying the role of executive function in falls. Patients with PD who were fallers (n = 27) or non-fallers (n = 53) and 27 healthy older adults were examined in a cross-sectional study. Gray matter volumes of the caudate head and posterior putamen were evaluated, as these striatal regions play a role in the executive and the sensorimotor cortico-striatal networks, respectively. The functional connectivity of the central executive network and of the sensorimotor network was measured using intrinsic brain connectivity during resting state functional magnetic resonance imaging. Compared to non-fallers and healthy controls, fallers had lower gray matter volume in the caudate head, but not in the posterior putamen, and increased connectivity between posterior partial regions of the central executive network, with no difference within the sensorimotor network. Mediation analysis demonstrated that the relationships between caudate head gray matter volume and fall history and risk were mediated by increased connectivity within the central executive network, apparently via attentional changes. The above findings provide additional converging evidence for the involvement of executive-related brain changes in falls in PD and support the important role of attention and executive function in fall risk.

The Alzheimer Disease BIN1 Locus as a Modifier of GBA-associated Parkinson Disease

Abstract: GBA mutations are among the most common genetic risk factors for Parkinson disease (PD) worldwide. We aimed to identify genetic modifiers of the age at onset (AAO) in GBA-associated PD. The study included a genome-wide discovery phase, including a cohort of 79 patients with the GBA p.N370S mutation, and candidate validation and replication analyses of 8 SNPs in patients with mild (n = 113) and severe (n = 41) GBA mutations. Genotyping was performed using the Affymetrix human SNP 6.0 array and TaqMan assays. In the genome-wide phase, none of the SNPs passed the genome-wide significance threshold. Eight SNPs were selected for further analysis from the top hits. In all GBA-associated PD patients (n = 153), the BIN1 rs13403026 minor allele was associated with an older AAO (12.4 ± 5.9 years later, p = 0.0001), compared to patients homozygous for the major allele. Furthermore, the AAO was 10.7 ± 6.8 years later in patients with mild GBA mutations, (p = 0.005, validation group), and 17.1 ± 2.5 years later in patients with severe GBA mutations (p = 0.01, replication). Our results suggest that alterations in the BIN1 locus, previously associated with Alzheimer disease, may modify the AAO of GBA-associated PD. More studies in other populations are required to examine the role of BIN1-related variants in GBA-associated PD.

Interest in genetic testing in Ashkenazi Jewish Parkinson's disease patients and their unaffected relatives.

Abstract: Our objective was to explore interest in genetic testing among Ashkenazi Jewish (AJ) Parkinson’s Disease (PD) cases and first-degree relatives, as genetic testing for LRRK2 G2019S is widely available. Approximately 18 % of AJ PD cases carry G2019S mutations; penetrance estimations vary between 24 and 100 % by age 80. A Genetic Attitude Questionnaire (GAQ) was administered at two New York sites to PD families unaware of LRRK2 G2019S mutation status. The association of G2019S, age, education, gender and family history of PD with desire for genetic testing (outcome) was modeled using logistic regression. One-hundred eleven PD cases and 77 relatives completed the GAQ. Both PD cases and relatives had excellent PD-specific genetic knowledge. Among PD, 32.6 % “definitely” and 41.1 % “probably” wanted testing, if offered “now.” Among relatives, 23.6 % “definitely” and 36.1 % “probably” wanted testing “now.” Desire for testing in relatives increased incrementally based on hypothetical risk of PD. The most important reasons for testing in probands and relatives were: if it influenced medication response, identifying no mutation, and early prevention and treatment. In logistic regression, older age was associated with less desire for testing in probands OR = 0.921 95%CI 0.868–0.977, p = 0.009. Both probands and relatives express interest in genetic testing, despite no link to current treatment or prevention.

Increased Activation of the Frontal Lobe is associated with Freezing of Gait in Patients with Parkinson's disease: an fNIRS study (P6.074)

Abstract: OJECTIVE: To test the hypothesis that frontal brain activation changes are associated with freezing of gait (FOG) episodes using functional near-infrared spectroscopy (fNIRS). BACKGROUND: Recent sugges that deficits in executive function contribute to FOG. However, direct evidence of changes in frontal lobe activation before or during FOG episodes is lacking. DESIGN / METHODS: PD patients (H&Y 2-4) with FOG (mean age: 69±10.1 yrs) performed a protocol designed to provoke FOG while walking in the wearing off state. Frontal brain activation was assessed by measuring the oxygenated hemoglobin (HbO 2 ) levels using fNIRS. For every FOG episode during a turn, three intervals of 5 seconds were studied: the first two intervals reflect the level of frontal brain activation before FOG; and the third interval reflects the level of frontal brain activation during the FOG episode. RESULTS: 110 FOG episodes during turns, gait initiation and straight walking were annotated during the protocol. Comparison between two intervals, before and after FOG, showed a significant increase of 2.4[percnt] in HbO2 after FOG (p=0.029). In contrast, comparison between two intervals, before and after 48 turns, gait initiation and straight walking without FOG, showed significant decrease of 5.5 [percnt] in HbO2 after the event (p=0.008). CONCLUSIONS: These results are the first direct evidence of association between FOG and changes in frontal brain activation. Higher level of frontal brain activation before turn, gait initiation and straight walking is associated with motor planning, an executive function necessary to perform these tasks. The decrease in HbO2 after the task demonstrates that these areas are less activate after the task was completed. In contrast, when these tasks included FOG an additional increase in HbO2 was found showing increase in frontal brain activation during and after FOG episodes. Disclosure: Dr. Maidan has nothing to disclose. Dr. Bernad-Elazari has nothing to disclose. Dr. Gazit has nothing to disclose. Dr. Mirelman has nothing to disclose. Dr. Hausdorff has nothing to disclose. Dr. Giladi has received personal compensation for activities with Teva Neuroscience, Intec Pharma, NeuroDerm Inc., Teva-Lundbeck, Merz Pharma, and UCB Pharma.

Treadmill-virtual reality combined training program to improve gait in multiple sclerosis individuals

Abstract: Gait disturbances are common in multiple sclerosis (MS) subjects. In particular, a non-physiological reduction of the walking speed and an increase of the gait variability is observed during a concurrent walking and cognitive challenge task. Virtual reality (VR) allows the delivery of challenging environments to train gait of MS individuals. This study aims to investigate the effects of two types of intensive treadmill-based interventions on gait of MS individuals. The two interventions share the same training protocol, except for the use of VR. Seventeen MS patients enrolled in the study were randomized in treadmill training (TT) group and treadmill training with VR (TT-VR) group. Assessments, performed before and immediately after the interventions, included gait analysis (single and dual-task conditions) and motor tests. Gait spatial-temporal parameters significantly improved in both groups. Ankle and hip kinetics improved in dual task only, for the TT-VR group. The preliminary results of this study suggest that TT-VR may significantly improve gait performance during complex conditions of MS individuals. The experimental research is still ongoing and more subjects will be recruited.

Accelerometer based free-living data: does macro gait behaviour differ between fallers and non-fallers with and without Parkinson's disease?

Abstract: [Poster] BACKGROUND AND AIM: Gait impairment and falls are frequent among older adults and people with Parkinson's disease (PD), and may lead to loss of functional independence and poor quality of life. Current approaches for evaluating falls risk are based on self-report or testing at a given time point and therefore may be suboptimal. Continuous monitoring of gait is emerging as a powerful tool to assess motor impairment and falls risk in real life using accelerometer-based technology, potentially providing an accurate and objective measure of risk [1]. Macro level gait behaviours (e.g., volume, pattern, and variability of walking bouts) are sensitive to PD pathology [2], however, there are conflicting reports about their association with falls risk. The aim of this study was to explore the association between physical activity (PA) and falls history by analysing whether macro level gait behaviour differs between fallers and non-fallers with and without PD using 7 day accelerometer-based free-living data. METHODS: 227 fallers (F: 106 elderly, 121 PD; age: 76±6 yrs, and 72±6 yrs, respectively) enrolled in the V-TIME study [3], who fell twice or more in the 6 months prior to assessment, together with 65 participants without a history of falls (NF: 50 elderly, 15 PD, age: 65±9 yrs, 70±7 yrs, respectively) enrolled into ICICLE-GAIT [2] were tested. Data were recorded continuously for 7 days with a tri-axial accelerometer (Axivity AX3, UK, 100Hz, ±8g) placed on the low back (L5). Macro level outcomes (MLO) representing the volume (% walking time, number of steps, mean bout length), pattern (alpha (α)), and variability (S2) of free-living activity were extracted in MATLAB® (R2012a) [2]. General linear modelling examined the effect of fall history (F vs NF) and pathology (PD vs elderly) on MLO, controlling for age, sex and BMI. RESULTS: Although the % walking time and number of steps was not related to fall history, F tended to walk in shorter bouts (p=.004) and had a less variable walking pattern (lower S2, p=.019) compared to NF. PD spent less time walking (p=.002), took fewer steps (p=.002), and accumulated proportionally more steps in shorter bouts (higher α) compared to the elderly (p=.006), regardless of falls history. There were no interactions between pathology and falls history for any of the outcomes. CONCLUSIONS: Our results showed that there is an association between falls history and PA. Volume-based MLO, pattern and variability of the walking bouts derived from free-living accelerometer-based data are independently associated with a history of falls and PD. These results support the use of a single accelerometer-based sensor to assess falls risk in free living settings, however, future work is needed to confirm if MLO can predict falls, potentially guiding clinical decision making. REFERENCES: [1] Lord S et al., Mov Disord, 2013; 28(11):1534-43 [2] Lord S et al., J Neurol, 2013; 260(12):2964-72 [3] Mirelman A et al., BMC Neurol, 2013;13:15

Differential neural activation in healthy older adults compared to subjects with Parkinson's disease during motor imagery of walking in virtual environments

Abstract: The neural correlates of locomotion in complex environments are unclear. Twenty healthy older adults and 20 patients with Parkinson's disease (PD) were asked to imagine walking in different virtual environments in MRI scanner. Whole brain analyses were performed. Between group comparisons revealed that patients with PD had a significantly higher activation already during imagined usual walk. However, comparisons between walking tasks showed increased activation during imagined complex walking tasks only in healthy older adults. This increased activation in patients with PD act as a compensatory strategy that limits the ability to recruit additional brain areas during more demanding walking tasks.