Publications

BACKGROUND: Higher step width variability while walking is associated with poor physical function and falls. Sleep is an established modifiable risk factor for both gait and physical function impairments, but it remains to be examined whether sleep is also related to step width variability.

OBJECTIVE: This study aimed to evaluate the cross-sectional associations between objectively measured sleep quality, using cardiopulmonary coupling spectrograms, and step width variability during a preferred walking condition among middle-aged and older adults.

METHODS: This study included 72 adults (mean age 71, SD 8.3 y; n=37, 51% female; n=65, 90% non-Hispanic White) who had ≥2 nights of objectively measured sleep (cardiopulmonary coupling via SleepImage ring) and completed a 10-m walk at preferred speed while wearing inertial sensors (APDM Mobility Lab). Sleep measures included sleep duration, efficiency, fragmentation, stability, apnea-hypopnea index, percentage of time oxygen saturation level <90%, oxygen desaturation index, and respiratory disturbance index. Additional derived sleep variables were explored using least absolute shrinkage and selection operator models. Step width variability was defined by the asymmetry of lateral step variability and categorized as medial (≤-7.5 cm), minimal (within ±7.5 cm; reference), or lateral displacement (≥7.5 cm). Multinomial logistic regression models adjusted for age, sex, race, education, BMI, and usual gait speed evaluated cross-sectional associations between sleep and step width variability categories.

RESULTS: We found that a 1% higher sleep fragmentation was associated with a 6% higher probability of step width variability ≥7.5 cm (95% CI 1.01-1.11), while a 1% higher sleep stability was associated with a 5% lower probability of variability ≥7.5 cm (95% CI 0.91-0.99), compared to minimal variability. From the least absolute shrinkage and selection operator models, we found that a 1% higher sleep quality index, a 1% higher rapid eye movement sleep, a 1-second shorter apnea duration, and a 1-beat per minute slower mean heart rate were also associated with a lower probability of lateral compared to minimal displacement.

CONCLUSIONS: Poor sleep quality was associated with higher step width variability among middle-aged and older adults. This suggests that sleep may be a modifiable risk factor for maintaining postural stability while walking among middle-aged and older adults. Future studies are needed to examine whether intervening in these sleep measures also lowers the risk of falls.

Digital measures of walking and sedentariness may objectively quantify Parkinson's disease (PD) progression. We analyzed longitudinal wearable-sensor data to evaluate the sensitivity and specificity of digital walking and non-walking measures in ambulatory people with PD. We selected 26 individual and 6 composite measures with sufficient sensitivity and test-retest reliability in a development dataset (N = 171). Twenty measures showed significant within-participant changes, and 7 showed larger 2-year effect-size than gold-standard clinical measures in people with early-stage PD (N = 101, mean number of years since diagnosis [YSD], 2.2). Significant changes in non-walking and composite measures were detectable as early as 10 months. Twelve measures showed greater change in people with more advanced PD (N = 67; mean YSD 6.5) compared to matched non-PD individuals (N = 171). Sensitivity and specificity results indicate that measures capturing walking and especially non-walking behaviors hold promise as PD progression markers in early to mid-stage PD.

Limited information exists on incident dementia in individuals with Parkinson's disease (PD) in US community-based samples. We examined cognitive statuses and PD diagnoses of 183 individuals in the Framingham Heart Study (FHS) to establish incident dementia, mortality rates, associations with sex, age at PD onset, and education level. Annual incidence rates of dementia (5.0%, 95% CI [3.7%-6.4%]) and mortality (10.5%, 95% CI [8.7%-12.3%]), did not differ by sex or education level. Increased age at PD diagnosis was a significant risk factor for incident dementia and mortality. Sex may not be a significant risk factor for community-based PD dementia.

BACKGROUND: Essential tremor (ET) is a common movement disorder that affects the upper limbs in vital activities of daily living. Few studies have examined the impact of tremor severity on caregiving intensity.

METHODS: Clinic-based data were collected in the United States (US) from March 2021 to August 2021 through the Adelphi ET Disease Specific Programme (DSP). Linked data between physician and care partner/patient pairs were used to evaluate care partner-reported weekly hours of patient care. Tremor severity was assessed with the Essential Tremor Rating Assessment Scale (TETRAS) Performance and Activities of Daily Living subscales. Pearson chi-square, correlation and multivariate regression analyses were conducted to examine the relationships between tremor severity and hours of care partner assistance.

RESULTS: A quarter of 960 individuals with ET required care partners. Most care partners were spouses (61%), but other family members or friends also served as care partners. About 23% of care partners reported giving constant care, defined as 112 hours per week or more, while the remainder of care partners reported caregiving time averaging 24.5 hours per week. The probability of needing a care partner was significantly associated with tremor severity, and the association between care partner need and tremor severity was moderate (bivariate r = 0.32-0.37) and not substantially impacted by the inclusion of additional covariates (age, sex, race, comorbidity, relationship with patient, and living with patient).

DISCUSSION: Roughly 25% of patients with ET have care partner needs, and the number of care partner hours provided is correlated with tremor severity. Therefore, treatments that ameliorate tremor severity have the potential to reduce caregiving intensity in ET.

OBJECTIVE: Tremor is a common presenting concern and is associated with a wide range of potential etiologies. This article reviews the approach to the clinical evaluation of tremor, the diagnosis of essential tremor, differential diagnoses, and management options.

LATEST DEVELOPMENTS: Although new investigational drugs are being studied, no medication besides propranolol has been approved by the US Food and Drug Administration (FDA) as a treatment for essential tremor. Thalamic deep brain stimulation (DBS) has been approved for use since 1997, and refinement of the stimulation target is currently being investigated. Focused ultrasound thalamotomy was approved by the FDA in 2016, and some devices with FDA approval can administer noninvasive transcutaneous afferent patterned stimulation of the median and radial nerves to treat essential tremor. Finally, botulinum toxin injections have shown potential effectiveness for treating head and voice tremors, and methods are currently being refined for potential application in the treatment of upper limb tremors.

ESSENTIAL POINTS: Tremor is a common neurologic symptom and should be distinguished from other movement disorders that may superficially resemble tremor. In addition, essential tremor, a primary tremor disorder consisting of bilateral upper limb action tremor, is commonly misdiagnosed. A careful history and clinical examination for other neurologic findings, such as bradykinesia, dystonia, or evidence of peripheral neuropathy, can reveal potential alternative etiologies of tremor. Drug-induced tremor and metabolic disturbances should always be considered in patients with recent-onset tremor. Oral pharmacotherapies, including propranolol and primidone, are mainstays of treatment, whereas DBS and focused ultrasound thalamotomy can be offered to alleviate disabling, medication-refractory tremor. Novel oral pharmacologic agents, noninvasive stimulation for tremor, and botulinum toxin injections for hand and head tremor need further study but may serve as potential future treatment options.

BACKGROUND: Essential tremor (ET) affects nearly 7 million people in the United States and consists of upper limb tremor that can affect activities of daily living, including activities related to work. Research examining the effect of ET on work productivity is limited and there are no studies using validated work productivity instruments.

METHODS: Clinic-based data were collected between March 2021 and August 2021 from US physicians participating in the Adelphi ET Disease Specific Programme (DSP). Patients were evaluated with the Essential Tremor Rating Assessment Scale (TETRAS), Quality of Life in Essential Tremor (QUEST) questionnaire, and the Work Productivity and Activity Impairment (WPAI) questionnaire. Statistical associations between tremor severity and work productivity were examined.

RESULTS: A total of 1,003 ET patients were identified, and 420 patients completed the WPAI questionnaire and were included in this study. Activity impairment was independently associated with tremor severity, adjusting for age, full-time vs. part-time employment, household income, depression, and anxiety. Of those who were employed (n = 165), 133 (80.6%) were employed full-time, and 141 (85.5%) had some level of work impairment. Work impairment was also independently associated with tremor severity, adjusting for the same covariates. Among those patients for whom QUEST responses were available, 47% (64/135) of patients with ET working full-time and 88% (36/41) of those working part-time reported that tremor interfered with work.

DISCUSSION: Work impairment is significantly correlated with tremor severity. Although a minority of patients in this clinic-based cohort were identified as employed, nearly all reported a negative impact on work performance.

Deep brain stimulation (DBS) for essential tremor is remarkably effective, leading to over 80% reduction in standardized tremor ratings. However, for certain types of tremor, such as those accompanied by ataxia or dystonia, conventional DBS targets have shown poor efficacy. Various rationales for using cerebellar DBS stimulation to treat tremor have been advanced, but the varied approaches leave many questions unanswered: which anatomic target, stimulation settings, and indications seem most promising for this emerging approach. This article reviews the clinical experience published to date and explores some of the pre-clinical and human physiology data that might support a role for further systematic investigation of cerebellar DBS for clinical use. Four tremor disorders to date have been targeted with cerebellar DBS in humans: essential tremor, post-stroke tremor, dystonic tremor, and tremor associated with degenerative cerebellar ataxias, like spinocerebellar ataxia type 3. The dentate nucleus is the most frequently chosen target, but key stereotactic and imaging details are missing from many of the case reports. Interestingly, consensus on laterality has not been definitively established as there are conflicting models of the hypothesized mechanism of action of DBS of the dentate nuclei, and conflicting reports of benefit on the tremor ipsilateral to and contralateral toto the affected limb. Several points are highlighted, including the prediction from in vivo preclinical physiology studies and interventional studies, the remaining uncertainty regarding the preferred laterality of targets, and the lack of clear prioritization of tremor etiologies to be targeted in future rigorously designed interventional studies (e.g., preferably repeated n-of-1 or sham-controlled studies involving more than one patient).

BACKGROUND: Smartphone-based cognitive assessments have emerged as promising tools, bridging gaps in accessibility and reducing bias in Alzheimer disease and related dementia research. However, their congruence with traditional neuropsychological tests and usefulness in diverse cohorts remain underexplored.

METHODS AND RESULTS: A total of 406 FHS (Framingham Heart Study) and 59 BHS (Bogalusa Heart Study) participants with traditional neuropsychological tests and digital assessments using the Defense Automated Neurocognitive Assessment (DANA) smartphone protocol were included. Regression models investigated associations between DANA task digital measures and a neuropsychological global cognitive Z score (Global Cognitive Score [GCS]), and neuropsychological domain-specific Z scores. FHS participants' mean age was 57 (SD, 9.75) years, and 44% (179) were men. BHS participants' mean age was 49 (4.4) years, and 28% (16) were men. Participants in both cohorts with the lowest neuropsychological performance (lowest quartile, GCS1) demonstrated lower DANA digital scores. In the FHS, GCS1 participants had slower average response times and decreased cognitive efficiency scores in all DANA tasks (P<0.05). In BHS, participants in GCS1 had slower average response times and decreased cognitive efficiency scores for DANA Code Substitution and Go/No-Go tasks, although this was not statistically significant. In both cohorts, GCS was significantly associated with DANA tasks, such that higher GCS correlated with faster average response times (P<0.05) and increased cognitive efficiency (all P<0.05) in the DANA Code Substitution task.

CONCLUSIONS: Our findings demonstrate that smartphone-based cognitive assessments exhibit concurrent validity with a composite measure of traditional neuropsychological tests. This supports the potential of using smartphone-based assessments in cognitive screening across diverse populations and the scalability of digital assessments to community-dwelling individuals.

Most research using digital technologies builds on existing methods for staff-administered evaluation, requiring a large investment of time, effort, and resources. Widespread use of personal mobile devices provides opportunities for continuous health monitoring without active participant engagement. Home-based sensors show promise in evaluating behavioral features in near real time. Digital technologies across these methodologies can detect precise measures of cognition, mood, sleep, gait, speech, motor activity, behavior patterns, and additional features relevant to health. As a neurodegenerative condition with insidious onset, Alzheimer disease and other dementias (AD/D) represent a key target for advances in monitoring disease symptoms. Studies to date evaluating the predictive power of digital measures use inconsistent approaches to characterize these measures. Comparison between different digital collection methods supports the use of passive collection methods in settings in which active participant engagement approaches are not feasible. Additional studies that analyze how digital measures across multiple data streams can together improve prediction of cognitive impairment and early-stage AD are needed. Given the long timeline of progression from normal to diagnosis, digital monitoring will more easily make extended longitudinal follow-up possible. Through the American Heart Association-funded Strategically Focused Research Network, the Boston University investigative team deployed a platform involving a wide range of technologies to address these gaps in research practice. Much more research is needed to thoroughly evaluate limitations of passive monitoring. Multidisciplinary collaborations are needed to establish legal and ethical frameworks for ensuring passive monitoring can be conducted at scale while protecting privacy and security, especially in vulnerable populations.