Prospective, longitudinal analysis of medication use in a cohort of elderly essential tremor cases.

BACKGROUND: There are no prospective, longitudinal studies investigating patterns of medication use among essential tremor (ET) patients. Our goal was to fill this knowledge gap. We also had a unique opportunity to examine medication use patterns primarily among elders with longstanding ET. We hypothesized that by the time ET patients reach advanced ages, medication changes would be uncommon - that is, they may have reached some kind of equipoise. METHODS: A prospective, longitudinal cohort of ET cases was evaluated across three time points. Cases were not ascertained from a treatment setting, thereby removing important selection biases. Each reported current medications and dosages of each. RESULTS: There were 144 cases (mean baseline age = 76.1 ± 9.4 years). The mean observation period = 2.9 ± 0.2 years. Primidone and propranolol were the most commonly used medications, although almost one-half of cases (44.4%) reported using neither during this period. A third of primidone users (33.3%) and a quarter of propranolol users (24.6%) reported changes in use vs. nonuse during the observation period. The majority of our cases made some change in their daily medication dosage during the course of the study - 73.3% of primidone users and 57.9% of propranolol users. CONCLUSION: In this prospective, longitudinal study, use vs. nonuse and daily dosage of both primidone and propranolol fluctuated across time for a sizable proportion of ET cases. Even among elders with chronic, longstanding ET, there is considerable ongoing medication adjustment, underscoring the need to improve the medication situation for ET patients.

Distribution of rest tremor in patients with Essential Tremor: Does it lateralize with simple kinetic, postural, or intention tremors?

BACKGROUND: Essential tremor (ET) is characterized by action tremor, although rest tremor may also occur. Despite this, rest tremor has not been studied extensively. A dearth of studies compare the relationship of rest tremor to other types of tremors in ET. METHODS: Two-hundred-and-thirteen ET cases underwent detailed neurological examination, including evaluations of rest, simple kinetic, postural, and intention tremors. A movement disorders neurologist assessed the prevalence of each type of tremor. Each instance of tremor was classified as either symmetrical (present and equally severe on both sides of the body) or asymmetrical (only present on or more severe on one side of the body). Asymmetrical rest tremor that co-occurred with other types of asymmetrical tremors in a given case was further classified as either concordant (i.e., asymmetry on the same side of the body) or discordant (i.e., asymmetry on opposite sides of the body). Chi-square analyses examined the prevalence of concordant versus discordant pairings. RESULTS: Sixty-two cases (29.2%) had rest tremor while seated. Fifteen (7.4%) had rest tremor while standing. Among asymmetric tremor pairings, concordant pairings occurred 2-2.7 times more frequently than discordant pairings - for pairings involving rest tremor while seated, 73.2% were concordant and 26.8% discordant (p < 0.001); for pairings involving rest tremor while standing, 66.7% were concordant and 33.3% were discordant (p = 0.25). CONCLUSIONS: Rest tremor often lateralized with other tremor types. These data add to our knowledge of the phenotypic manifestations of ET.

Depressive symptoms predict memory decline in Essential Tremor.

INTRODUCTION: Essential tremor (ET), a common movement disorder, is characterized by motor, cognitive and psychiatric symptoms. Depressed mood, a symptom of ET, has historically been viewed as a psychological response to disability. However, depressive symptoms are emerging as a predictor of cognitive decline across several clinical populations. We examined if depressive symptoms predict decline in global cognition, memory, and executive functioning among older adults with ET. METHODS: 125 cognitively normal participants with ET completed three in-person assessments of cognition, mood, and motor symptoms at baseline, 18 months, and 36 months; baseline data were collected from July 2014-July 2016. Depressive symptoms were measured with the Geriatric Depression Scale. Cognitive functioning was measured via a 3-4 hour neuropsychological evaluation. Generalized linear regression models examined depressive symptoms as a predictor of decline in global cognition, executive functioning (EF), and memory. RESULTS: Participants were grouped according to a median split (GDS <5 versus ≥ 5) due to the bimodal distribution of the data. In unadjusted models, depressive symptoms did not predict change in global cognition (b = -0.002, p = .502) or EF (b = 0.000, p = .931), however individuals with GDS ≥ 5 demonstrated faster memory decline in unadjusted (b = -0.008, p = .039) and adjusted models (b = -0.009, p = .019). CONCLUSION: The presence of 5 or more depressive symptoms predicted mildly faster memory decline in cognitively normal older adults with ET over 36 months. We discuss potential mechanisms and clinical implications.

Mild cognitive impairment, dementia and risk of mortality in essential tremor: A longitudinal prospective study of elders.

BACKGROUND: There is evidence that the risk of mortality is increased in patients with essential tremor (ET), however, there are few longitudinal, prospective data on the predictors of mortality in ET. There is also evidence that ET is associated with cognitive impairment; yet, it is unknown whether this is associated with elevated risk of mortality. METHODS: In a longitudinal, prospective study of 194 elders with ET, an extensive neuropsychological test battery was performed at three time points: baseline, 18 months, and 36 months, and cognitive diagnoses (normal, mild cognitive impairment [MCI], and dementia) were assigned during consensus conferences. We used Cox proportional hazards models to estimate hazard ratios (HR) for death. RESULTS: The mean baseline age was 79.1 ± 9.7 years. During follow-up, 52 (26.8%) died. In initial univariate models, a variety of baseline factors were associated with increased risk of mortality, including demographic variables (i.e., older age), cognitive variables and gait and balance variables. In the final multivariate Cox model, baseline dementia (HR = 2.66, p = 0.006), older baseline age (HR = 1.18, p < 0.001), and more reported falls at baseline (HR = 1.10, p < 0.001) were independently associated with increased risk of mortality. Amnestic MCI was marginally associated with increased risk of mortality (HR = 1.93, p = 0.08) in primary analyses and significantly (p < 0.05) in several sensitivity analyses. CONCLUSIONS: In this longitudinal, prospective study, baseline dementia resulted in a 2- to 3-times increase in risk of mortality in ET, further highlighting the clinical significance of cognitive impairment, specifically dementia, in this population.

The Progression of Essential Tremors: Illustrative Videos.

Background: Essential tremor (ET) is a progressive neurological disease whose natural history is one of progressive increase in tremor severity over time; surprisingly though, there are no published videotape diaries that visually and tangibly portray this progression over time. Phenomenology: Progressive, stepwise increase in limb tremor severity over a ten-to-fifteen-year period in three patients with ET. Educational value: We hope that this brief visual diary will serve as a useful teaching tool for students, primary care physicians, and neurologists to "see with their own eyes" the extent of change that can occur in the ETs.

"ET Plus": Instability of the Diagnosis During Prospective Longitudinal Follow-up of Essential Tremor Cases.

Background: A recent consensus statement introduced the term "ET plus". Although investigators have quantified the prevalence of ET plus in cross-sectional studies, patients with ET plus have not been tracked longitudinally; hence, there is no understanding of its stability over time. Methods: We present prospective, longitudinal phenotypic data on an ET cohort that was followed regularly at 18-month intervals (T1, T2, T3, T4) for up to 64 months. We assigned an ET or ET plus diagnosis to each case at each time interval. Results: There were 201 participants at baseline. The proportion with ET plus increased from 58.7% at baseline to 72.1% at T4 (p = 0.046). Of 172 (85.6%) who received a diagnosis of ET plus at one or more time intervals, the diagnosis was unstable (e.g., with reversion) in 62 (36.0%). We also assessed the stability of the clinical features of ET plus. Rest tremor was the most unstable clinical feature of ET plus; it was present in 59 participants, among whom it reverted from present to absent in 23 (39.0%). By contrast, for "memory impairment" (i.e., either mild cognitive impairment or dementia), the proportion who reverted from present to absent was only 21.3%. Conclusion: These data support our two a priori hypotheses: (1) the prevalence of ET plus would increase progressively, as it likely represents a more advanced stage of ET, and (2) the ET plus diagnosis would not be stable over time, as cases would fluctuate with respect to their phenotypic features and their assigned diagnoses.