The UF Deep Brain Stimulation Cognitive Rating Scale (DBS-CRS): Clinical Decision Making, Validity, and Outcomes.

To more efficiently communicate the results of neuropsychological assessment to interdisciplinary teams, the University of Florida Neuropsychology Service developed a Deep Brain Stimulation-Cognitive Rating Scale (DBS-CRS). This tool condensed results of a 3-h exam into a five-point scale ranging from 1 (least) to 5 (most) cognitive concern for DBS surgery. In this study, we evaluated the role of the DBS-CRS in clinical decisions by the interdisciplinary team to proceed to surgery, its relationship to objective neuropsychological scores, and its predictive utility for clinical outcome. We retrospectively examined 189 patients with Parkinson's disease who were evaluated for DBS candidacy (mean age 64.8 [SD 9.2], disease duration 8.9 years [SD 5.0], UPDRS-Part III off medication 38.5 [SD 10.5], Dementia Rating Scale-II 135.4 [SD 6.0]). Approximately 19% of patients did not proceed to surgery, with neuropsychological red flags being the most commonly documented reason (57%). Patients who underwent DBS surgery had significantly better DBS-CRS scores than those who did not (p < 0.001). The two strongest and unique neuropsychological contributors to DBS-CRS ratings were delayed memory and executive function, followed by language and visuoperception, based on hierarchical linear regression that accounted for 77.2% of the variance. In terms of outcome, DBS-CRS scores were associated with higher quality of life, less severe motor symptoms, and better daily functioning 6 months following DBS surgery. Together, these findings support the construct and predictive validity of the DBS-CRS as a concise tool for effectively communicating pre-DBS cognitive concerns to an interdisciplinary team, thereby aiding decision making in potential DBS candidates.

Sniffing Out Cognitive Decline in Patients with and without Evidence of Dopaminergic Deficit.

BACKGROUND: Depletion of dopamine is a major neuropathological feature of Parkinson's disease; however, 15% of patients with parkinsonian motor symptoms have neuroimaging evidence of intact dopaminergic function. Recent work has demonstrated that such patients without dopaminergic deficit are at a greater risk of cognitive impairment yet have intact olfaction relative to parkinsonian patients with dopaminergic deficit. OBJECTIVES: Given the high discriminatory power of olfaction assessments in movement disorders, the current study sought to determine whether olfaction dysfunction differentially predicted cognitive decline in patients with or without dopaminergic deficit. METHODS: Data were obtained from the Parkinson's Progression Marker Initiative. The total sample included 401 patients with and 51 patients without dopaminergic deficit, based on neuroimaging scans, and 175 healthy controls. Participants were categorized into non-impaired or impaired olfaction groups based on performance on the University of Pennsylvania Smell Identification Test. Participants were administered the Montreal Cognitive Assessment twice (baseline and two-year follow-up), and change scores were calculated to examine changes in cognition over time. RESULTS: Within the impaired olfaction groups, participants without dopaminergic deficit had lower cognitive scores than participants with dopaminergic deficit and healthy controls at baseline. Group differences were not significant at follow-up; rather, impaired baseline olfaction predicted cognitive decline across all study participants. CONCLUSIONS: Future studies are needed to assess whether the profile of motor and non-motor symptoms in patients without dopaminergic deficit, including olfaction, are deserving of their own syndrome, or whether individual patients may fit better under alternative, existing diagnoses.

Everyday functioning in Parkinson's disease: Evidence from the Revised-Observed Tasks of Daily Living (OTDL-R).

INTRODUCTION: Performance tasks are presumed to have greater validity than rating scales in assessing day-to-day behaviors in Parkinson's disease (PD). One such task is the revised Observed Tasks of Daily Living (OTDL-R), which has been used extensively in healthy older adults, and but not yet empirically examined in PD. Thus, the aims of the current study were to examine and determine the impact of cognitive, motor, and mood symptoms on OTDL-R performance in PD. METHOD: Nineteen non-demented PD patients and 18 healthy older adults (HC) were administered measures of mood and cognitive functioning, and the OTDL-R (subtests include medication and telephone use, and medication management). Clinical severity of PD was assessed using the H&Y stage, UPDRS, and Schwab and England functional disability scores. RESULTS: Mann Whitney U tests indicated the PD patients were significantly slower to complete the OTDL-R and performed worse on only the telephone use subtest, relative to the HC group. In the PD group, hierarchical regression analyses revealed memory, attention, and initiative/perseveration were uniquely associated with the financial management subtest, after controlling for motor severity (ps < .05). No other significant relationships were found. CONCLUSIONS: PD patients were slower to complete the OTDL-R, but only less accurate on the telephone use subtest. Poor performance on the telephone use subtest may be related to motor severity, while poor performance on the financial management subtest was related to attention and working memory. Overall, the findings warrant future investigation to determine the validity and reliability of the OTDL-R in PD.

Self-report depressive symptoms are dissociated from tremor severity in essential tremor.

BACKGROUND: Depressive symptoms are associated with essential tremor (ET). However, the relationship between cognitive, functional, and motor measures with depressive symptoms in ET is not yet understood. METHODS: The following measures were cross-sectionally assessed in a group of 223 subjects with ET: the Montreal Cognitive Assessment (MoCA) Scale, the Lawton Independent Activities of Daily Living (IADL) Scale, a neurologist assessment of tremor severity, and the Geriatric Depression Scale (GDS). RESULTS: 20% (44) of the subjects met GDS criteria for depression (GDS ≥ 10). 43% (94) of the subjects showed at least some cognitive impairment (≤24 on the MoCA), and 15.3% (34) reported significant functional impairment (IADL score < 7). There was no significant association between GDS score and tremor scale score. The total GDS was negatively associated with the total MoCA score (Spearman's r = -0.15, p = 0.03). The total GDS was also negatively associated with the IADL score (Spearman's r = -0.19, p = 0.02), (logistic model odds ratio, OR = 4.91, p < 0.01). Over 60% of subjects who were depressed, per GDS cut-off score (≥10), were not receiving medical treatment for depression. CONCLUSIONS: There was a high point prevalence of depressive symptoms in subjects with ET. Self-report depressive symptoms are dissociated from tremor severity. Hence, these data do not support the hypothesis that depression in ET represents a psychological reaction to the tremor. There appears to be a clustering of cognitive, functional, and depressive symptoms in ET. Screening of depression in ET can improve our understanding and treatment of this disorder.

Perceived embarrassment and caregiver burden in essential tremor caregivers.

Essential tremor (ET) is a progressive neurological disease associated with functional disability, diminished quality of life and, in some individuals, poorer balance, cognitive impairment, depression and sleep dysregulation. Individuals with ET may rely on family members and friends to act as informal caregivers to assist with daily activities and provide emotional support. There is a high prevalence of embarrassment among individuals with ET, which may be a result of the outwardly visible nature of tremor. Studies in populations with outwardly visible disability have shown that perception by caregivers of a care-recipient's social distress can contribute to caregiver burden. We hypothesize that in ET, perception by caregivers of ET participant embarrassment is a predictor for caregiver burden. Data were collected from 57 ET participants and their caregivers. We measured ET participant embarrassment using the Essential Tremor Embarrassment Assessment (ETEA), and measured perception by caregivers of ET participant embarrassment using a modified version of the ETEA. The Zarit Burden Interview was used to measure caregiver burden. Perceived embarrassment was associated with ET participant embarrassment. In linear regression models, perceived embarrassment was a stronger predictor for caregiver burden than measures of ET participant cognitive and physical impairment. The results indicate that perception of ET participant embarrassment can be burdensome for caregivers. Clinicians may wish to address patient embarrassment and perceived embarrassment to better support caregivers and ET patients.

Psychological Suffering in Essential Tremor: A Study of Patients and Those Who Are Close to Them.

Background: Although the motor and non-motor features of essential tremor (ET) have been characterized in detail, it is not known whether ET patients suffer psychologically and whether those who are close to them consider them to be suffering in this way. Methods: Fifty ET patients and 50 "close others" (COs), identified by patients "as someone who knows you well and sees you often" and who can "provide a different perspective on your well-being", reported their own depressive symptoms, daily stress, and perceptions of patient psychological suffering and patient overall suffering with validated scales. ET patients' tremor severity, duration, disability, cognition, and number of medications were also assessed. Results: ET patients reported levels of psychological suffering within the range documented in arthritis and dementia patients from previous studies, and COs perceived significantly more psychological suffering in patients than patients reported themselves. Regression models, controlling for tremor severity, duration, and disability revealed that patients' greater psychological suffering was associated with greater patient depression. The greater perceptions of COs of patient psychological and overall suffering were associated with greater CO depression and daily stress. Sensitivity analysis showed that patients' cognitive status or number of medications did not affect the results. Discussion: Multidisciplinary teams caring for ET patients should look beyond simple clinical ET indicators. They should be aware of patient experiences and perceptions of COs of psychological and overall suffering. This will help guide the development of evidence-based, supportive interventions that improve communication about the needs of ET patients and those who are close to them.

The Experience of Essential Tremor Caregivers: Burden and Its Correlates.

BACKGROUND: Essential tremor (ET) is associated with physical and cognitive impairments, as well as embarrassment, avoidance of social settings, and related difficulties that negatively impact the lives of patients. In similar disease contexts, burden on friends and relatives acting as caregivers has been noted and has well-documented implications. There has been no study examining caregiver burden related to ET. METHODS: Data were gathered from 55 ET participants enrolled in a clinical study and their caregivers. The Zarit Burden Interview was used to assess caregiver burden. To assess clinical features that may be associated with burden, we collected several variables including the Montreal Cognitive Assessment, self-reported tremor disability, a videotaped neurological examination, questionnaires assessing ET participants' suffering, caregivers' perceptions of that suffering, and both caregiver and ET participant depressive symptoms. Spearman's correlations were performed between caregiver burden and clinical features, and we created a multivariate linear regression model predicting caregiver burden. RESULTS: Many ET caregivers provide little to no care and experience little to no burden. However, some caregivers (11%) provide over 25 h of care/week, and 13% experience high levels of burden. Caregivers most commonly provided assistance with writing and cooking. Increased burden was associated with the ET participants' decreased cognition, more caregiving tasks, more hours/week of caregiving activities, a longer duration of care, more ET participant falls/year, more medications taken by the ET participant, and more depressive symptoms in both the ET participant and the caregiver (all p < 0.05). ET participants' suffering and their caregivers' perceptions of suffering were both associated with increased burden. Neither tremor severity score nor self-reported tremor disability score was associated with increased caregiver burden. Using a multivariate linear regression model, we found that caregivers' increased perception of their partners' suffering was the best predictor of caregiver burden. CONCLUSION: While not all relatives and friends of ET patients provide extensive care or experience high burden, there is a group reporting high levels of caregiver burden that requires the attention and counseling of clinicians. This burden is associated with primarily non-tremor symptoms of ET and with caregivers' perception that their partners are suffering.

Cognitive Dysfunction Is Associated with Greater Imbalance and Falls in Essential Tremor.

BACKGROUND: Essential tremor (ET) is not exclusively a tremor disorder; it is also associated with cognitive and gait dysfunction. However, a gap in knowledge is that the relationship between cognitive and gait dysfunction has not been studied in detail in ET. We examined the relationship between cognition and balance and falls in ET and hypothesized that cognitive dysfunction in ET patients would be associated with greater problems with balance and more falls. METHODS: ET cases were recruited into the Clinical-pathological Study of Cognition in ET. A comprehensive cognitive assessment was performed. This included the Montreal Cognitive Assessment (MoCA) to measure global cognition, multiple motor-free tests comprehensively assessing performance in each cognitive domain, and an assignment of Clinical Dementia Rating (CDR) scores. We collected data on the number of reported falls in the past year, and balance confidence was assessed using the 6-item Activities of Balance Confidence Scale. These cross-sectional analyses utilized baseline data. RESULTS: There were 199 ET cases (mean age 78.6 years). In linear regression models that considered the effects of numerous confounding variables, lower global cognition (poorer cognition) was associated with greater number of falls and reduced balance confidence (p < 0.05). In similar adjusted linear regression models, higher CDR score (poorer functional cognition) was associated with greater number of falls and reduced balance confidence (p < 0.05). We also assessed whether number of falls and balance confidence was associated with performance in specific cognitive domains. Number of falls was most closely linked with performance on tests of executive function, and balance confidence, with executive function, attention, and memory. CONCLUSION: These data indicate that a correlate of poorer cognition in ET is greater number of falls and lower balance confidence. Cognition should enter the dialog with ET patients as an issue of clinical significance.

Awareness of cognitive impairment in individuals with essential tremor.

OBJECTIVE: The extent to which individuals with ET who have clinically significant cognitive impairment are aware of their cognitive changes is unclear. Reduced awareness has important implications for everyday function and decision-making. METHODS: 150 individuals with ET (109 Normal Cognition (ET-NC group), and 30 with MCI and 11 dementia (ET-CI group)) completed self-ratings and objective assessments of memory, language, and executive functioning. Discrepancy scores were calculated to assess awareness of cognitive functioning. One sample t-tests evaluated whether mean discrepancy scores in each group were comparable to zero (i.e., accurate). Analyses of covariance (ANCOVA) compared discrepancy scores across two groups controlling for age and education. RESULTS: In the ET-NC group, discrepancy scores for language (M=-0.08, SD=1.10) and executive functioning (M=-0.01, SD=0.99) were comparable to zero. Memory discrepancy scores (M=0.32, SD=1.22) were greater than zero. In the ET-CI group, memory, (M=0.78, SD=1.01), language, (M=0.46, SD=0.95), and executive (M=0.39, SD=1.14) discrepancy scores were all greater than zero. Discrepancy scores were larger in ET-CI group than in ET-NC group for memory: F(1,148)=4.02, p=0.047, language: F(1,148)=6.16, p=0.014, and executive: F(1,148)=4.51, p=0.035. CONCLUSIONS: Individuals with ET and normal cognition accurately assessed their language and executive abilities, demonstrating mild overconfidence in memory function. Individuals with ET and cognitive impairment overestimated their performance in all domains of functioning. Since ET is linked to increased risk for cognitive impairment, and such impairment may not be accurately perceived, cognitive functioning should be proactively and regularly screened in ET.

Mild Cognitive Impairment Subtypes in a Cohort of Elderly Essential Tremor Cases.

OBJECTIVES: Individuals with essential tremor (ET) exhibit a range of cognitive deficits generally conceptualized as "dysexecutive" or "fronto-subcortical," and thought to reflect disrupted cortico-cerebellar networks. In light of emerging evidence that ET increases risk for Alzheimer's disease (AD), it is critical to more closely examine the nature of specific cognitive deficits in ET, with particular attention to amnestic deficits that may signal early AD. METHODS: We performed a cross-sectional analysis of baseline data from 128 ET cases (age 80.4±9.5 years) enrolled in a longitudinal, clinical-pathological study. Cases underwent a comprehensive battery of motor-free neuropsychological tests and a functional assessment to inform clinical diagnoses of normal cognition (ET-NC), mild cognitive impairment (MCI) (ET-MCI), or dementia (ET-D). ET-MCI was subdivided into subtypes including: amnestic single-domain (a-MCI), amnestic multi-domain (a-MCI+), non-amnestic single-domain (na-MCI), or non-amnestic multi-domain (na-MCI+). RESULTS: Ninety-one (71.1%) cases were ET-NC, 24 (18.8%) were ET-MCI, and 13 (10.2%) were ET-D. Within MCI, the a-MCI+ subtype was the most common (13/24; 54.2%) followed by a-MCI (4/24; 16.7%), na-MCI+ (4/24; 16.7%), and na-MCI (3/24; 12.5%). Cases with amnestic MCI demonstrated lower recognition memory Z-scores (-2.4±1.7) than non-amnestic groups (-0.9±1.2) (p=.042). CONCLUSIONS: Amnestic MCI, defined by impaired memory recall but associated with lower memory storage scores, was the most frequent MCI subtype in our study. Such impairment has not been explicitly discussed in the context of ET and may be an early hallmark of AD. Results have implications for the prognosis of specific cognitive deficits in ET. (JINS, 2017, 23, 390-399).

Daytime sleepiness and nighttime sleep quality across the full spectrum of cognitive presentations in essential tremor.

There is increasing evidence that essential tremor (ET) is a complex and heterogeneous disorder with nonmotor features including cognitive deficits and sleep problems. We are unaware of a study that has examined sleep deficits in ET across the full spectrum of cognitive presentations. Cross-sectional (baseline) data on self-reported nighttime sleep dysfunction and excessive daytime sleepiness were collected using the Pittsburgh Sleep Quality Index (PSQI) and the Epworth Sleepiness Scale (ESS) in 96 ET cases enrolled in a prospective study. Cases underwent a comprehensive neuropsychological assessment, and were classified as ET with normal cognition (ET-NC), ET with mild cognitive impairment (ET-MCI), and ET with dementia (ET-D). PSQI scores did not significantly differ across the three ET cognitive groups (p=0.22). ESS scores were highest (more daytime sleepiness) in the ET-MCI group, followed by the ET-D and ET-NC groups, respectively (p=0.016). We examined sleep dysfunction across the cognitive spectrum in ET. We demonstrate for the first time that excessive daytime sleepiness is greater in ET-MCI than ET-NC. Unpredicted low ESS scores in the dementia group raises two possibilities: a self-report bias related to cognitive impairment and/or the possibility that currently undefined pathological heterogeneity in ET may map onto multiple presentations of non-motor deficits.

Self-reported physical activity in essential tremor: Relationship with tremor, balance, and cognitive function.

BACKGROUND: Physical inactivity may be the result of medical comorbidities. Inactivity itself may also lead to important health consequences, especially in older patients. Essential tremor (ET) patients may have a variety of physical and cognitive problems that could detrimentally impact on level of physical activity. Yet, to our knowledge, there have been no studies of physical activity in these patients. METHODS: Self-reported physical activity was assessed using the Physical Activity Scale for the Elderly (PASE) in 100 ET cases (mean age 80.5years) enrolled in a clinical study. Additional clinical measures were the total tremor score, Montreal Cognitive Assessment (MOCA) score and number of steps taken off of the straight line during tandem gait (a measure of balance). RESULTS: Lower PASE score was associated with older age, more tandem gait difficulty, higher total tremor score and lower MOCA score (all p<0.05). In a linear regression model that included total tremor score, MOCA score, number of steps off of the straight line during tandem gait, and age, higher total tremor score (p=0.046) and more steps off of the straight line during tandem gait (p=0.014) were independently associated with reductions in physical activity. CONCLUSIONS: Several of the motor features of ET (tremor and imbalance) are independently associated with reductions in level of physical activity.

Defining the Treatment Gap: What Essential Tremor Patients Want That They Are Not Getting.

BACKGROUND: Patient-centeredness (i.e., providing care that is responsive to individual patient preferences) is increasingly recognized as a crucial element of quality of care. METHODS: A six-item patient-centeredness questionnaire was devised to assess the self-perceived needs of essential tremor (ET) patients. A link to the questionnaire was included in the monthly e-newsletter of the International Essential Tremor Foundation. The questionnaires were completed online and data were available in electronic format. RESULTS: There were 1,418 respondents. One in three respondents (i.e., 31.4%) indicated that the doctor was not even "moderately well-educated" about ET. Only 11.8% of respondents were satisfied with their care. Respondents raised a multiplicity of issues that were not being addressed in their current care. The top items were psychological services and support (33.9%), physical or occupational therapy (28.6%), handling embarrassment and social effects of tremor (15.8%), feelings of not being in control (13.7%), a detailed report and a more quantitative way of assessing tremor and tracking progression (12.7%), better counseling about current treatment and medications (11.9%), empathy, compassion and a feeling of being heard (11.6%), a treatment approach other than just medications and surgery (11.2%), and a discussion of all symptoms aside from tremor (e.g., cognition, balance). DISCUSSION: Patients with ET identified a broad range of issues that they felt were not addressed in their treatment; indeed, only one in 10 patients reported that they were satisfied with their care. It is hoped that patient-centered approaches such as this will lead to improved models for the care of patients with this common chronic disease.

Poorer Cognitive Performance in Patients with Essential Tremor-Parkinson's Disease vs. Patients with Parkinson's Disease.

BACKGROUND: Patients with essential tremor (ET) seem to be at increased risk of developing Parkinson's disease (PD). Surprisingly, little has been written about this clinical entity, ET-PD. Cognitive dysfunction is a well-known feature of PD, and can also be an issue in patients with ET. Whether the presence of the combined diagnosis, ET-PD, is associated with additive cognitive effects as compared with PD has not been studied. METHODS: Thirty ET-PD patients and 53 age-matched PD patients were enrolled in a clinical-epidemiological study. Two cognitive screens, the Telephone Interview for Cognitive Status (TICS, score = 0-41) and Folstein Mini-Mental State Examination (MMSE; range 0-30), were administered. RESULTS: The MMSE score was lower in ET-PD than PD [26.5 ± 3.1 (median 28.0) vs. 28.4 ± 2.2 (median 29.0), p = 0.001]. The TICS score was lower in ET-PD than PD [31.7 ± 3.9 (32.0) vs. 35.0 ± 2.0 (35.0), p < 0.001]. Subscores of these tests that related to orientation (p < 0.001), language (p < 0.001), and working memory (p = 0.001) were lower in ET-PD than PD, whereas the delayed memory subscore was only marginally lower in ET-PD than PD (p = 0.06), and the two groups did not differ with respect to the motor/construction subscore (p = 0.22). Both global cognitive scores were inversely correlated with disease duration (for MMSE score, Spearman's r = -0.46, p < 0.001; for TICS score, Spearman's r = -0.53, p < 0.001). CONCLUSION: The combined diagnosis, ET-PD, seemed to be associated with additive cognitive effects as compared with PD alone.