Eleven-Year Outcomes of Deep Brain Stimulation in Early-Stage Parkinson Disease.

OBJECTIVE: The deep brain stimulation (DBS) in early-stage Parkinson's disease (PD) pilot clinical trial randomized 30 patients (Hoehn & Yahr II off; medication duration 0.5-4 years; without dyskinesia/motor fluctuations) to optimal drug therapy (ODT) (early ODT) or bilateral subthalamic nucleus (STN) DBS plus ODT (early DBS+ODT). This study aims to report the 11-year outcomes of patients who completed the DBS in early-stage PD pilot clinical trial. MATERIALS AND METHODS: Attempts were made to contact all 29 subjects who completed the two-year trial to participate in an 11-year follow-up study. Mixed-effects models compared overall trend in outcomes for randomization groups (fixed-effects: assigned treatment, year, their interaction; random-effect: subject) to account for repeated measures. RESULTS: Twelve subjects participated in this 11-year follow-up study (n = 8 early ODT, n = 4 early DBS+ODT). Participating subjects were 70.0 ± 4.8 years old with a PD medication duration of 13.7 ± 1.7 years (early DBS duration 11.5 ± 1.3 years, n = 4). Three early ODT subjects received STN-DBS as standard of care (DBS duration 6.5 ± 2.0 years). Early ODT subjects had worse motor complications (Unified Parkinson's Disease Rating Scale [UPDRS]-IV) than early DBS+ODT subjects over the 11-year follow-up period (between-group difference = 3.5 points; pinteraction = 0.03). Early DBS+ODT was well-tolerated after 11 years and showed comparable outcomes to early ODT for other UPDRS domains, Parkinson Disease Questionnaire-39 (PDQ-39), and levodopa equivalent daily dose (LEDD). CONCLUSIONS: Eleven years after randomization, early DBS+ODT subjects had fewer motor complications than early ODT subjects. These results should be interpreted with caution because only 40% of pilot trial subjects participated in this 11-year follow-up study. The Food and Drug Administration has approved the conduct of a pivotal clinical trial evaluating DBS in early-stage PD (IDEG050016). CLINICAL TRIAL REGISTRATION: The Clinicaltrials.gov registration number for the study is NCT00282152.

Vanderbilt University Medical Center Ambulatory Teleneurology COVID-19 Experience.

Background: Telehealth has proliferated since the 1950s, but adoption and coverage of telehealth services for the U.S. public have been slow. In response to the coronavirus disease 2019 (COVID-19) pandemic, the federal government has implemented temporary policy changes that removed barriers and catalyzed the unprecedented adoption of telehealth. Methods: To assess ambulatory teleneurology satisfaction, we analyzed postvisit questionnaire data from patients and clinicians who completed teleneurology visits during the COVID-19 pandemic at Vanderbilt University Medical Center Department of Neurology (VUMC). Results: From March 18 to May 8, 2020, VUMC completed 3,935 teleneurology visits. More than 97% of patients were very highly or highly confident in the telehealth care they received, whereas almost 99% of clinicians were very likely or somewhat likely to recommend telehealth to other clinicians. Conclusions: Teleneurology satisfaction at VUMC has been positive, and going forward, we must advance upon this unprecedented adoption of telehealth and never revert to former restrictive policies.

Cerebrospinal fluid biomarkers of neurodegeneration, synaptic dysfunction, and axonal injury relate to atrophy in structural brain regions specific to Alzheimer's disease.

INTRODUCTION: Patterns of atrophy can distinguish normal cognition from Alzheimer's disease (AD), but neuropathological drivers of this pattern are unknown. This study examined associations between cerebrospinal fluid biomarkers of AD pathology, synaptic dysfunction, and neuroaxonal injury with two AD imaging signatures. METHODS: Signatures were calculated using published guidelines. Linear regressions related each biomarker to both signatures, adjusting for demographic factors. Bootstrapped analyses tested if associations were stronger with one signature versus the other. RESULTS: Increased phosphorylated tau (p-tau), total tau, and neurofilament light (P-values <.045) related to smaller signatures (indicating greater atrophy). Diagnosis and sex modified associations between p-tau and neurogranin (P-values<.05) and signatures, such that associations were stronger among participants with mild cognitive impairment and female participants. The strength of associations did not differ between signatures. DISCUSSION: Increased evidence of neurodegeneration, axonopathy, and tau phosphorylation relate to greater AD-related atrophy. Tau phosphorylation and synaptic dysfunction may be more prominent in AD-affected regions in females.

Prevalence of Comorbid Spasticity and Urinary Incontinence in Residents of a Long-Term Care Facility.

The current study evaluated the prevalence of comorbid spasticity and urinary incontinence (UI) in a long-term care facility. Medical history, presence of UI, and activities of daily living (ADL) dependency were obtained from medical records and Minimum Data Set 3.0. Quality of life was assessed with the EuroQoL-5D-5L (EQ-5D). Comorbid spasticity and UI presented in 29% of participants (14 of 49). Participants with spasticity and UI had higher ADL dependency and lower EQ-5D than participants without both conditions (4.9, 95% confidence interval [CI] [1.6, 80.], p = 0.003; -0.17, 95% CI [-0.33, 0.00], p = 0.044; respectively). More than one half of participants with lower limb spasticity had severe UI, compared to only 10% without lower limb spasticity (relative risk = 5.5; 95% CI [1.9, 15.9]; p = 0.006). Comorbid spasticity and UI may be common in the long-term care setting and negatively associated with ADL and quality of life. Further investigation is needed to confirm these findings. [Journal of Gerontological Nursing, 46(10), 35-42.].

Teleneurology service provided via tablet technology: 3-year outcomes and physician satisfaction.

INTRODUCTION: This study aimed to demonstrate that teleneurology consultations conducted via tablet technology are an efficient and cost-effective means of managing acute neurologic emergencies at community-based hospitals and that utilizing such technology yields high community physician satisfaction. METHOD: During a 39-month period, Vanderbilt University Medical Center in Tennessee USA, provided teleneurology services to 10 community-based hospitals that lacked adequate neurology coverage. Hospitalists at one community-based hospital were not comfortable treating any patient with a neurologic symptom, resulting in 100% of those patients being transferred. This facility now retains more than 60% of neurology patients. For less than US$1200, these hospitals were able to meet the only capital expenditure required to launch this service: the purchase of handheld tablet computers. Real-time teleneurology consultations were conducted via tablet using two-way video conferencing, radiologic image sharing, and medical record documentation. Community physicians were regularly surveyed to assess satisfaction. RESULTS: From February 2014 to May 2017, 3626 teleneurology consultations were conducted. Community physicians, in partnership with neurologists, successfully managed 87% of patients at the community-based hospital. Only 13% of patients required transfer to another facility for a higher level of care. The most common diagnoses included stroke (34%), seizure (11%), and headache/migraine (6%). The average time for the neurologist to answer a request for consultation page and connect with the community physician was 10.6 minutes. Ninety-one percent of community physicians were satisfied or somewhat satisfied with the overall service. CONCLUSION: In the assessment of neurology patients, tablets are a more cost-effective alternative to traditional telehealth technologies. The devices promote efficiency in consultations through ease of use and low transfer rates, and survey results indicate community physician satisfaction.

Motivational Sensitivities Linked to Impulsive Motor Errors in Parkinson's Disease.

OBJECTIVES: We investigated how broad motivational tendencies are related to the expression and suppression of action impulses in Parkinson's disease (PD). METHODS: Sixty-nine participants with PD completed a Simon response conflict task and Behavioral Inhibition System (BIS) and Behavioral Activation System (BAS) scales based on Gray's (1987) reinforcement sensitivity theory. Analyses determined relationships between BIS, BAS, and the susceptibility to making impulsive action errors and the proficiency of inhibiting interference from action impulses. RESULTS: BIS scores correlated positively with rates of impulsive action errors, indicating that participants endorsing low BIS tendencies were much more susceptible to acting on strong motor impulses. Analyses of subgroups with high versus low BIS scores confirmed this pattern and ruled out alternative explanations in terms of group differences in speed-accuracy tradeoffs. None of the scores on the BIS or BAS scales correlated with reactive inhibitory control. CONCLUSIONS: PD participants who endorse diminished predilection toward monitoring and avoiding aversive experiences (low BIS) show much greater difficulty restraining fast, impulsive motor errors. Establishing relationships between motivational sensitivities and cognitive control processes may have important implications for treatment strategies and positive health outcomes in participants with PD, particularly those at risk for falling and driving difficulties related to impulsive reactions. (JINS, 2018, 24, 128-138).

Parkinson's Disease Subtypes Show Distinct Tradeoffs Between Response Initiation and Inhibition Latencies.

OBJECTIVES: In unpredictable situations, individuals often show tradeoffs between response initiation and inhibition speeds. We tested the hypothesis that Parkinson's disease (PD) motor subtypes differentially impact tradeoffs between these two action-oriented processes. We predicted that, compared to tremor dominant (TD) patients, predominant postural instability and gait dysfunction (PIGD) patients would show exacerbated tradeoffs between response initiation and inhibition in situations requiring the sudden potential need to interrupt an action. METHODS: Fifty-one PD patients (subdivided into PIGD [n=27] and TD [n=24]) and 21 healthy controls (HCs) completed a choice reaction task to establish baseline response initiation speed between groups. Subsequently, participants completed a stop-signal task which introduced an occasional, unpredictable stop stimulus. We measured changes in initiation speed in preparation of an unpredictable stop (i.e., proactive slowing) and inhibition latency (i.e., stop-signal reaction time). RESULTS: Compared to HCs, PD patients showed slower response initiation speeds in the choice reaction task. All groups showed proactive slowing in the stop-signal task but the magnitude was considerably larger in PIGD patients, almost twice as large as TD patients. PD patients, irrespective of motor subtype, showed longer inhibition latencies than HCs. CONCLUSIONS: PIGD and TD subtypes both showed exacerbated response inhibition deficits. However, PIGD patients showed much more pronounced proactive slowing in situations with an expected yet unpredictable need to stop action abruptly. This suggests that PIGD is accompanied by exaggerated tradeoffs between response initiation and inhibition processes to meet situational action demands. We discuss putative neural mechanisms and clinical implications of these findings. (JINS, 2017, 23, 665-674).

The Impact of Pallidal and Subthalamic Deep Brain Stimulation on Urologic Function in Parkinson's Disease.

OBJECTIVE: Deep Brain Stimulation (DBS) is an established adjunctive surgical intervention for treating Parkinson's disease (PD) motor symptoms. Both surgical targets, the globus pallidus interna (GPi) and subthalamic nucleus (STN), appear equally beneficial when treating motor symptoms but effects on nonmotor symptoms are not clear. Lower urinary tract symptoms (LUTS) are a common PD complaint. Given prior data in STN-DBS, we aimed to further explore potential benefits in LUTS in both targets. METHODS: We performed a prospective, nonblinded clinical trial evaluating LUTS in PD patients in both targets pre and post DBS using validated urologic surveys. Participants were already slated for DBS and target selection predetermined before study entry. LUTS was evaluated using: the American Urological Association (AUA-SI), Quality of Life score (QOL), Overactive Bladder 8 Questionnaire (OAB-q), and Sexual Health Inventory for Men (SHIM). RESULTS: Of 33 participants, 20 underwent STN DBS and 13 had GPi DBS. Patients demonstrated moderate baseline LUTS. The urologic QOL score significantly improved post DBS (3.24 ± 1.77vs. 2.52 ± 1.30; p = 0.03). Analyzed by target, only the STN showed significant change in QOL (3.20 ± 1.61 vs 2.25 ± 1.33; p = 0.04). There were no other significant differences in urologic scores post DBS noted in either target. CONCLUSION: In PD patients with moderate LUTS, there were notable improvements in QOL for LUTS post DBS in the total sample and STN target. There may be differences in DBS effects on LUTS between targets but this will require further larger, blinded studies.

Curriculum Innovations: Inspiring Neurology Residents to Pursue Fellowship Training in Movement Disorders.

Introduction and Problem Statement: The aging US population has led to the increased prevalence of neurodegenerative diseases and the critical need for specialists with advanced training in the management of these conditions. Focus on Common Movement Disorders (FOCMD), a 2-day educational course hosted by Vanderbilt University, was started 16 years ago to provide neurology residents with exposure to the diagnosis and treatment of movement disorders. Objectives: The aim of the course was to provide early-career neurology residents with relevant exposure to the field of movement disorders, through which we hope to increase medical knowledge of movement disorders and common Food and Drug Administration (FDA)-approved therapies and inspire residents to pursue fellowship training in the field. Methods and Curriculum Description: FOCMD consists of lectures and small-group workshops that provide an overview of common movement disorders and approved therapies. All North American neurology residency program directors are invited to nominate a first-year or second-year resident. Attendees are administered standardized multiple-choice precourse and postcourse examinations to assess foundational knowledge of common movement disorders and FDA-approved therapies and to measure acquisition of the course material. Past participants are regularly surveyed to gauge their impression of the course's effect on fellowship selection and their utilization of therapies common in the treatment of movement disorders. Results and Assessment Data: Since 2008, FOCMD has trained 854 neurology residents from 113 programs. Between 2010 and 2020, 507 residents completed the precourse and postcourse examinations. There was an increase of 22.4 (95% CI 20.67-24.49; p < 0.001) percentage points between the precourse and postcourse examinations or an additional 3.8 questions were answered correctly. Follow-up surveys were sent to 414 past participants, and 116 were completed. Survey responses revealed that 84% of past attendees completed a fellowship, 44% of which were in the field of movement disorders. In addition, 82% of past participants reported that the course affected subspecialty selection and 63% reported treating patients with movement disorders in their current practice. Discussion and Lessons Learned: Experience with FOCMD has shown it to be successful in introducing neurology residents to the subspecialty early in their career and increasing medical knowledge on movement disorders. An educational program of this format may also positively influence fellowship selection.

The Efficacy of Hospice-In-Place Care Versus Traditional Inpatient Care.

Introduction: The hospice-in-place program at Vanderbilt University Medical Center (VUMC) is available to patients and families who elect for hospice benefits and are too unstable to be transported for hospice care. The goal of this study was to assess the satisfaction of family members of patients who died while hospitalized at VUMC and received hospice-in-place compared to the families of patients who did not receive hospice care. Methods: Next-of-kin satisfaction was measured through the administration of qualitative interviews and quantitative questionnaires. Semi-structured interviews were audio-recorded, and transcripts were analyzed using an iterative inductive-deductive approach to develop a conceptual framework. Participants were also asked to respond to a 10-question satisfaction questionnaire. Results: Forty participants were enrolled: 20 next-of-kin of patients who received hospice-in-place and 20 next-of-kin of patients who passed without hospice. Factors influencing satisfaction were organized into a conceptual framework with three categories: individual-level factors, systems-level factors, and modifying factors. For the questionnaires, the hospice-in-place group had a mean satisfaction score of 4.54 (0.76) out of five, while the non-hospice group had a mean score of 4.14 (1.00). A comparison of the two groups' responses did not show a statistically significant difference (P = 0.06). Discussion: Quantitative findings of this study showed improved satisfaction but were unable to show a significant difference in satisfaction with hospice-in-place compared to traditional care. Questionnaire results suggest that both types of care yield high satisfaction scores and are successfully supporting patients and families. The conceptual framework also adds to the understanding of end-of-life experiences at VUMC.

Long-term neuropsychological outcomes of deep brain stimulation in early-stage Parkinson's disease.

INTRODUCTION: The pilot trial of deep brain stimulation (DBS) in early-stage Parkinson's disease (PD) randomized 30 patients (medication duration 0.5-4 years; without dyskinesia or motor fluctuations) to receive optimal drug therapy alone (early ODT) or subthalamic nucleus (STN) DBS plus ODT (early DBS + ODT). This study reports long-term neuropsychological outcomes from the early DBS pilot trial. METHODS: This is an extension of an earlier study that examined two-year neuropsychological outcomes in the pilot trial. The primary analysis was conducted on the five-year cohort (n = 28), and a secondary analysis was conducted on the 11-year cohort (n = 12). Linear mixed effects models for each analysis compared overall trend in outcomes for randomization groups. All subjects who completed the 11-year assessment were also pooled to evaluate long-term change from baseline. RESULTS: There were no significant differences between groups in either the five- or 11-year analyses. Across all PD patients who completed the 11-year visit, there was significant decline in Stroop Color and Color-Word and Purdue Pegboard from baseline to 11 years. CONCLUSIONS: Previous significant differences between the groups in phonemic verbal fluency and cognitive processing speed showing more decline for early DBS + ODT subjects one year after baseline diminished as PD progressed. No cognitive domains were worse for early DBS + ODT subjects compared to standard of care subjects. There were shared declines across all subjects on cognitive processing speed and motor control, likely reflecting disease progression. More study is needed to understand the long-term neuropsychological outcomes associated with early DBS in PD.

Long-Term Care Resident Awareness and Interest in Spasticity Treatments.

Spasticity is common in long-term care settings (affecting up to one in three residents), yet it remains under-treated despite safe and effective, Food and Drug Administration (FDA)-approved therapies. One barrier to treatment may be lack of awareness of available therapies for long-term care residents living with spasticity. A standardized spasticity treatment awareness and interest interview was conducted with 18 nursing home residents and 11 veterans' home residents in this cross-sectional study. Veterans' home residents were also asked about potential barriers to receiving spasticity treatment. Many residents across both long-term care facilities were unaware of most of the treatment options for spasticity. Participants were most aware of physical/occupational therapy (83%, 95% CI: 65-93%) and least aware of intrathecal baclofen (21%, 95% CI: 9-39%). After learning about treatments, only 7% of participants (95% CI: 0-23%) were not interested in receiving any form of spasticity treatment. Among residents previously unaware of spasticity treatments, at least one quarter became interested in receiving treatment and at least one-fifth indicated possibly being interested in the treatment after learning about it. Potential barriers to receiving treatment included traveling to see a doctor and limited knowledge of insurance coverage of spasticity treatments. These results suggest that patient-centered approaches, including education and discerning patient preferences, may improve spasticity treatment in long-term care settings.

Early subthalamic nucleus deep brain stimulation in Parkinson's disease reduces long-term medication costs.

INTRODUCTION: Subthalamic nucleus (STN) deep brain stimulation (DBS) is recognized as a safe and effective treatment in mid- and advanced-staged Parkinson's disease (PD) that decreases the need for PD medications and their associated costs. This study reports medication costs from the only clinical trial to evaluate DBS in patients with early-stage PD and projects costs through advanced-stage disease. METHODS: The DBS in early-stage PD pilot was a prospective, single-blind clinical trial that randomized 30 patients with early-stage PD 1:1 to receive bilateral STN-DBS plus optimal drug therapy (ODT) or ODT alone. Subjects who completed the trial participated in an observational follow-up study and were evaluated annually for five years after randomization. PD medication data collected at each study visit were used to calculate and project medication costs (n = 28). RESULTS: Five-year cumulative medication cost reduction with early DBS+ODT was $28,246. Mean annual medication cost for early DBS+ODT subjects was 2.4 times lower than early ODT subjects (ß = 2.4, 95%CI:1.5-3.7, p = 0.0004). Early DBS+ODT is projected to reduce cumulative medication costs by $104,958 over 15 years of disease duration. CONCLUSION: DBS in early-stage PD may provide long-term medication cost reduction compared to standard care.

A Simple Bedside Screening Tool for Spasticity Referral.

BACKGROUND AND OBJECTIVES: Spasticity is common in long-term care facilities; however, this often-disabling condition is largely underdiagnosed in this setting and therefore left untreated. This study aimed to test the ability of a three-question flowchart used at the bedside by primary care providers in the long-term care setting to identify residents in need of referral to a specialist for spasticity consultation. METHODS: All residents of a single long-term care facility were approached for participation in this cross-sectional, observational study. Spasticity diagnostic evaluations by a movement disorders specialist neurologist (reference standard) were compared with referral determinations made by two primary care providers [a primary care physician (PCP) and a nurse practitioner (NP)] using the simple flowchart. RESULTS: The analysis included 49 residents (80% male, age 78.2±9.0 years) who were evaluated by the reference standard neurologist and at least one primary care provider. The bedside referral tool demonstrated high sensitivity and moderate specificity when used by the PCP (92% and 78%, respectively; AUC=0.84) and NP (80% and 53%, respectively; AUC=0.67). CONCLUSION: This simple tool may be useful for primary care providers to identify residents to be referred to a specialist for evaluation and treatment of spasticity. These results warrant further investigation of the potential utility of this screening tool across multiple long-term care facilities and various types of care providers.

Prevalence of Spasticity in Nursing Home Residents.

OBJECTIVES: To determine the prevalence, rate of underdiagnosis and undertreatment, and association with activities of daily living dependency of spasticity in a nursing home setting. DESIGN: Cross-sectional study. SETTING AND PARTICIPANTS: This study is an analysis of a deidentified data set generated by a prior quality improvement project at a 240-bed nursing home for residents receiving long-term care or skilled nursing care services. METHODS: Each resident was examined by a movement disorders specialist neurologist to determine whether spasticity was present and, if so, the total number of spastic postures present in upper and lower limbs was recorded. Medical records, including the Minimum Data Set, were reviewed for neurologic diagnoses associated with spasticity, activities of daily living (ADL) dependency, and prior documentation of diagnosis and past or current treatments. Ordinary least squares linear regression models were used to evaluate the association between spasticity and ADL dependency. RESULTS: Two hundred nine residents (154 women, 81.9 ± 10.9 years) were included in this analysis. Spasticity was present in 22% (45/209) of residents examined by the neurologist. Only 11% of residents (5/45) had a prior diagnosis of spasticity and were receiving treatment. Presence of spasticity was associated with greater ADL dependency (χ2 = 51.72, P < .001), which was driven by lower limb spasticity (χ2 = 14.56, P = .006). CONCLUSIONS AND IMPLICATIONS: These results suggest that spasticity (1) is common in nursing homes (1 of 5 residents), (2) is often not diagnosed or adequately treated, and (3) is associated with worse ADL dependency. Further research is needed to enhance the rates of diagnosis and treatment of spasticity in long-term care facilities.

Deep brain stimulation in early-stage Parkinson disease: Five-year outcomes.

OBJECTIVE: To report 5-year outcomes from the subthalamic nucleus (STN) deep brain stimulation (DBS) in early-stage Parkinson disease (PD) pilot clinical trial. METHODS: The pilot was a prospective, single-blind clinical trial that randomized patients with early-stage PD (Hoehn & Yahr II off medications) to receive bilateral STN DBS plus optimal drug therapy (ODT) vs ODT alone (IDEG050016, NCT0282152, IRB040797). Participants who completed the 2-year trial participated in this observational follow-up study, which included annual outpatient visits through 5 years. This analysis includes 28 patients who were taking PD medications for 6 months to 4 years at enrollment. Outcomes were analyzed using both proportional odds logistic regression and linear mixed effects models. RESULTS: Early STN DBS + ODT participants required lower levodopa equivalent daily doses (p = 0.04, ß = -240 mg, 95% confidence interval [CI] -471 to -8) and had 0.06 times the odds of requiring polypharmacy at 5 years compared to early ODT participants (p = 0.01, odds ratio [OR] 0.06, 95% CI 0.00 to 0.65). The odds of having worse rest tremor for early STN DBS + ODT participants were 0.21 times those of early ODT participants (p < 0.001, OR 0.21, 95% CI 0.09 to 0.45). The safety profile was similar between groups. CONCLUSIONS: These results suggest that early DBS reduces the need for and complexity of PD medications while providing long-term motor benefit over standard medical therapy. Further investigation is warranted, and the Food and Drug Administration has approved the conduct of a prospective, multicenter, pivotal clinical trial of DBS in early-stage PD (IDEG050016). CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that DBS implanted in early-stage PD decreases the risk of disease progression and polypharmacy compared to optimal medical therapy alone.

Frailty Is Related to Subjective Cognitive Decline in Older Women without Dementia.

OBJECTIVES: Physical frailty (or loss of physiologic reserve) is associated with cognitive impairment and dementia. Subjective cognitive decline (SCD) may represent early pathologic changes of dementia. The association between these disease markers is unclear. DESIGN: Cross-sectional analysis. SETTING: Community-based participants from the Vanderbilt Memory & Aging Project. PARTICIPANTS: A total of 306 older adults with normal cognition (NC; n = 174) or mild cognitive impairment (MCI; n = 132). MEASUREMENTS: Frailty was measured using standard methods, and a composite frailty score was calculated. SCD was quantified using the Everyday Cognition Scale (ECog; total score and four domain scores). Objective cognition was assessed with the Montreal Cognitive Assessment (MoCA). Proportional odds models, stratified by sex, related the frailty composite to MoCA and total ECog score adjusting for age, education, body mass index, cognitive diagnosis, depressed mood, Framingham Stroke Risk Profile, apolipoprotein E (APOE ε4) carrier status, and height (for gait speed models). Secondary models related individual frailty components to SCD domains and explored associations in NC only. RESULTS: In women, frailty composite was related to MoCA (odds ratio [OR] = .56; P = .04), a finding attenuated in sensitivity analysis (OR = .59; P = .08). Frailty composite related to ECog total (OR = 2.27; P = .02), planning (OR = 2.63; P = .02), and organization scores (OR = 2.39; P = .03). Increasing gait speed related to lower ECog total (OR = .06; P = .003) and memory scores (OR = .03; P < .001). Grip strength related to lower ECog planning score (OR = .91; P = .04). In men, frailty was unrelated to objective and subjective cognition (P values >.07). Findings were consistent in the NC group. CONCLUSION: Frailty component and composite scores are related to SCD before the presence of overt dementia. Results suggest that this association is present before overt cognitive impairment. Results suggest a possible sex difference in the clinical manifestation of frailty, with primary associations noted in women. Further studies should investigate mechanisms linking early changes among frailty, SCD, and cognition. J Am Geriatr Soc, 1-9, 2019. J Am Geriatr Soc 67:1803-1811, 2019.

Impact of Tremor on Patients With Early Stage Parkinson's Disease.

Tremor is one of the most visible features of Parkinson's disease (PD), and the majority of PD patients experience tremor during the course of the disease. However, the distress caused by this cardinal motor feature for patients early in the course of their PD is commonly underappreciated. People living with early stage PD often experience intense embarrassment and difficulties due to their tremor that limit social interactions, and tremor frequently interferes with the ability to perform activities of daily living and simple tasks at home and work. Although tremor is primarily managed with medications, both tremor response and satisfaction with medical therapy are highly variable. This review offers an overview of reports of the patient experience of tremor in early stage PD and current management options for this cardinal motor feature.

The 12-Word Philadelphia Verbal Learning Test Performances in Older Adults: Brain MRI and Cerebrospinal Fluid Correlates and Regression-Based Normative Data.

BACKGROUND/AIMS: This study evaluated neuroimaging and biological correlates, psychometric properties, and regression-based normative data of the 12-word Philadelphia Verbal Learning Test (PVLT), a list-learning test. METHODS: Vanderbilt Memory and Aging Project participants free of clinical dementia and stroke (n = 230, aged 73 ± 7 years) completed a neuropsychological protocol and brain MRI. A subset (n = 111) underwent lumbar puncture for analysis of Alzheimer's disease (AD) and axonal integrity cerebrospinal fluid (CSF) biomarkers. Regression models related PVLT indices to MRI and CSF biomarkers adjusting for age, sex, race/ethnicity, education, APOE-ε4 carrier status, cognitive status, and intracranial volume (MRI models). Secondary analyses were restricted to participants with normal cognition (NC; n = 127), from which regression-based normative data were generated. RESULTS: Lower PVLT performances were associated with smaller medial temporal lobe volumes (p < 0.05) and higher CSF tau concentrations (p < 0.04). Among NC, PVLT indices were associated with white matter hyperintensities on MRI and an axonal injury biomarker (CSF neurofilament light; p < 0.03). CONCLUSION: The PVLT appears sensitive to markers of neurodegeneration, including temporal regions affected by AD. Conversely, in cognitively normal older adults, PVLT performance seems to relate to white matter disease and axonal injury, perhaps reflecting non-AD pathways to cognitive change. Enhanced normative data enrich the clinical utility of this tool.

Effects of deep brain stimulation on rest tremor progression in early stage Parkinson disease.

OBJECTIVE: To evaluate whether the progression of individual motor features was influenced by early deep brain stimulation (DBS), a post hoc analysis of Unified Parkinson's Disease Rating Scale-III (UPDRS-III) score (after a 7-day washout) was conducted from the 2-year DBS in early Parkinson disease (PD) pilot trial dataset. METHODS: The prospective pilot trial enrolled patients with PD aged 50-75 years, treated with PD medications for 6 months-4 years, and no history of dyskinesia or other motor fluctuations, who were randomized to receive optimal drug therapy (ODT) or DBS plus ODT (DBS + ODT). At baseline and 6, 12, 18, and 24 months, all patients stopped all PD therapy for 1 week (medication and stimulation, if applicable). UPDRS-III "off" item scores were compared between the ODT and DBS + ODT groups (n = 28); items with significant between-group differences were analyzed further. RESULTS: UPDRS-III "off" rest tremor score change from baseline to 24 months was worse in patients receiving ODT vs DBS + ODT (p = 0.002). Rest tremor slopes from baseline to 24 months favored DBS + ODT both "off" and "on" therapy (p < 0.001, p = 0.003, respectively). More ODT patients developed new rest tremor in previously unaffected limbs than those receiving DBS + ODT (p = 0.001). CONCLUSIONS: These results suggest the possibility that DBS in early PD may slow rest tremor progression. Future investigation in a larger cohort is needed, and these findings will be tested in the Food and Drug Administration-approved, phase III, pivotal, multicenter clinical trial evaluating DBS in early PD. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that for patients with early PD, DBS may slow the progression of rest tremor.