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INTRODUCTION: Essential tremor (ET) patients may exhibit a variety of non-motor features, including cognitive decline and depressive symptoms. Studies of several neurodegenerative diseases link depression to cognitive decline, suggesting depression is an early marker of dementia. We examined whether baseline depressive symptoms predict incident dementia in elders with ET. METHODS: Hundred and forty-one ET cases aged 70 years or older at baseline, enrolled in a prospective study of cognitive performance, took part in evaluations at baseline and at 18, 36, 54, and 72 months. Participants completed the Geriatric Depression Scale (GDS), a 30-item self-report measure of depressive symptoms, and a battery of neuropsychological tests and functional assessments, from which we derived cognitive diagnoses at each evaluation. Cox proportional hazards regression equations determined incident dementia risk based on participants' baseline depression scores. RESULTS: Mean baseline age was 81.5 ± 6.7 years. Higher baseline GDS scores were associated with increased risk of dementia in an unadjusted model (hazards ratio [HR] = 1.11, 95% confidence interval [CI] = 1.02-1.20, p = 0.01) and after controlling for baseline age, education, number of medications, and tremor onset age (HR = 1.13, 95% CI = 1.02-1.25, p = 0.02). CONCLUSION: Baseline depression scores predicted incident dementia in elders with ET. With each one-point increase in baseline depression score, there was a 13% increase in incident dementia risk. Given the published data that reported depression may be twice as high in elders with ET compared to controls, this association is particularly worrisome in the ET population.
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BACKGROUND: Essential tremor (ET) is a chronic, progressive neurological disease that affects an estimated 7 million individuals in the United States (ie, 2.2% of the entire U.S. population). Despite its high prevalence, there are a few published studies on patterns of prescription medication use among patients. OBJECTIVE: The aim was to examine prescription drug medication use among ET patients. METHODS: This is a cross-sectional study of ET patients, age ≥40, with at least 1 prescription medication fill using the Optum's de-identified Clinformatics Data Mart Database from 2018 through 2019. We examined patterns of fills of key agents used to treat ET. RESULTS: The final sample comprised 36,839 ET patients in the United States; 89% had at least 1 prescription drug claim over a 2-year period, indicating that 9 of 10 ET patients take a medication to treat their disease. For each of the 3 most frequently prescribed medications, only a modest fraction (1/5 to 1/4) of patients were taking that medication. Adherence to these agents was 52% to 61%. A high percentage of patients had fills for more than 1 of the main agents we studied. CONCLUSION: These data illustrate a need for medication in the ET population. There is only 1 FDA-approved medication to treat ET, propranolol, and less than 25% of ET patients used this drug during our study period. At the same time, no single agent was utilized by more than one quarter of ET patients, adherence was low, and use of multiple agents was common. For such a common disease, the pharmacotherapeutic landscape is impoverished.
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INTRODUCTION: Sleep disturbances have been associated with essential tremor (ET). However, their pathophysiological underpinnings remain unknown. In this exploratory study, we examined the association between subjective sleep disturbances and the presence of Lewy pathology (LP) on postmortem brain examination in ET cases. METHODS: Fifty-two ET cases enrolled in a prospective, longitudinal study were assessed over an average period of 42 months. Cases completed the Pittsburgh Sleep Quality Index (PSQI), which yields seven component scores (e.g., sleep quality, sleep latency). For each component score, we calculated the difference between the last score and the baseline score. Brains were harvested at death. Each had a complete neuropathological assessment, including extensive α-synuclein immunostaining. We examined the associations between baseline PSQI scores and the change in PSQI scores (last - first), and LP on postmortem brain examination. RESULTS: ET cases had a mean baseline age of 87.1 ± 4.8 years. LP was observed in 12 (23.1%) of 52 cases; in 7 of these 12, LP was observed in the locus coeruleus (LC). Change in time needed to fall asleep (last - first sleep latency component score) was associated with presence of LP on postmortem brain examination - greater increase in sleep latency was associated with higher odds of LP (odds ratio = 2.98, p = 0.02). The greatest increase in sleep latency was observed in cases with LP in the LC (p = 0.04). CONCLUSION: In ET cases, increases in sleep latency over time could be a marker of underlying LP, especially in the LC.
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Encéfalo , Temblor Esencial , Trastornos del Sueño-Vigilia , Humanos , Temblor Esencial/patología , Femenino , Masculino , Trastornos del Sueño-Vigilia/patología , Trastornos del Sueño-Vigilia/epidemiología , Anciano de 80 o más Años , Estudios Longitudinales , Anciano , Encéfalo/patología , Estudios Prospectivos , Cuerpos de Lewy/patología , Estudios de Cohortes , alfa-Sinucleína/metabolismoRESUMEN
OBJECTIVE: Despite recent attention to cognitive impairment in essential tremor, few studies examine rates of conversion to diagnoses of mild cognitive impairment and dementia. Development of dementia in essential tremor is associated with loss of functional ability and a doubling of mortality rate. This prospective, longitudinal study comprehensively reports the prevalence and incidence of, and the annual rates of conversion to, mild cognitive impairment and dementia in an essential tremor cohort. METHODS: Patients underwent detailed cognitive assessments and were assigned diagnoses of normal cognition, mild cognitive impairment, or dementia. There were 222 patients at baseline (mean age = 79.3 ± 9.7 years), and 177 patients participated in follow-up evaluations at 18, 36, 54, and 72 months (mean years of observation = 5.1 ± 1.7). Data were compared to those of historical controls and Parkinson disease patients. RESULTS: The cumulative prevalence of dementia and average annual conversion rate of mild cognitive impairment to dementia were 18.5% and 12.2%, nearly three times higher than rates in the general population, and approximately one half the magnitude of those reported for Parkinson disease patients. The cumulative prevalence of mild cognitive impairment (26.6%) was almost double that of the general population, but less than that in Parkinson disease populations. INTERPRETATION: We present the most complete exposition of the longitudinal trajectory of cognitive impairment in an essential tremor cohort yet presented. The prevalence of and conversion rates to dementia in essential tremor fall between those associated with the natural course of aging and the more pronounced rates observed in Parkinson disease. ANN NEUROL 2024;95:1193-1204.
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Disfunción Cognitiva , Demencia , Progresión de la Enfermedad , Temblor Esencial , Humanos , Temblor Esencial/epidemiología , Disfunción Cognitiva/epidemiología , Femenino , Masculino , Anciano , Prevalencia , Estudios Longitudinales , Demencia/epidemiología , Anciano de 80 o más Años , Estudios Prospectivos , Estudios de CohortesRESUMEN
OBJECTIVE: Essential tremor is among the most prevalent neurological diseases. Diagnosis is based entirely on neurological evaluation. Historically, there were few postmortem brain studies, hindering attempts to develop pathologically based criteria to distinguish essential tremor from control brains. However, an intensive effort to bank essential tremor brains over recent years has resulted in postmortem studies involving >200 brains, which have identified numerous degenerative changes in the essential tremor cerebellar cortex. Although essential tremor and controls have been compared with respect to individual metrics of pathology, there has been no overarching analysis to derive a combination of metrics to distinguish essential tremor from controls. We asked whether there is a constellation of pathological findings that separates essential tremor from controls, and how well that constellation performs. METHODS: Analyses included 100 essential tremor brains from the essential tremor centralized brain repository and 50 control brains. A standard tissue block from the cerebellar cortex was used to quantify 11 metrics of pathological change. Three supervised classification algorithms were investigated, with data divided into training and validation samples. RESULTS: Using three different algorithms, we illustrate the ability to correctly predict a diagnosis of essential tremor, with sensitivity and specificity >87%, and in the majority of situations, >90%. We also provide a web-based application that uses these metric values, and based on specified cutoffs, determines the likely diagnosis. INTERPRETATION: These analyses set the stage for use of pathologically based criteria to distinguish clinically diagnosed essential tremor cases from controls, at the time of postmortem.
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Cerebelo , Temblor Esencial , Humanos , Temblor Esencial/diagnóstico , Anciano , Femenino , Masculino , Cerebelo/patología , Persona de Mediana Edad , Anciano de 80 o más Años , Algoritmos , Corteza Cerebelosa/patologíaRESUMEN
Background: Evaluating tremor severity is a critical component of diagnosing and clinically managing patients with essential tremor (ET). We examined the comparability of tremor severity ratings derived from two frequently used tremor rating scales: the Washington Heights-Inwood Genetic Study of Essential Tremor (WHIGET) rating scale and the Tremor Research Group Essential Tremor Rating Scale (TETRAS). Methods: A trained assistant administered and videotaped a neurological examination, including eight items assessing upper limb action tremor (arms outstretched, arms in the wingbeat position, finger-nose-finger maneuver, and drawing of Archimedes spirals). An experienced movement disorders neurologist reviewed the videos and assigned WHIGET and TETRAS ratings. We calculated associations between TETRAS and WHIGET ratings using Spearman rank order correlations. Subsequently, we collapsed these ratings into four tremor severity categories (absent, mild, moderate, severe) and then two broader tremor severity categories (absent/mild, moderate/severe). We calculated weighted Kappa coefficients to assess agreement between category assignments based on the TETRAS and the WHIGET. Results: Spearman's r' s were significant for all items (p's ≤ 0.001, mean r = 0.89). Weighted Kappa's revealed substantial to near perfect agreement for all eight items (mean k = 0.86, range = 0.64 to 1.00). Conclusion: Analyses revealed substantial strength of association and substantial to near perfect agreement between items rated with the WHIGET and TETRAS scales. These data indicated that ratings provided by each scale are highly comparable.
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Temblor Esencial , Temblor , Humanos , Temblor/diagnóstico , Temblor/genética , Temblor Esencial/diagnóstico , Washingtón , Examen Neurológico , Extremidad SuperiorRESUMEN
BACKGROUND: There is growing evidence that essential tremor (ET) patients are at high risk of cognitive impairment. Predictors of cognitive impairment have not been studied extensively. There is evidence from cross-sectional studies that sleep dysregulation is associated with cognitive dysfunction in ET, but longitudinal studies of the impact of sleep disruption on cognitive change have not been conducted. We investigated the extent to which sleep problems predict cognitive change in patients with ET. METHODS: ET cases enrolled in a prospective, longitudinal study of cognitive performance. Sleep quality was assessed using the Pittsburg Sleep Quality Index (PSQI). Cognitive abilities across five domains (memory, executive function, attention, language, and visuospatial ability), and a global cognitive score (mean of the domains) were extracted from an extensive neuropsychological assessment. Generalized estimated equations were used to examine the association between baseline sleep problems and cognitive changes over three follow-up assessments each spaced 18 months apart. RESULTS: The 188 non-demented ET cases had a mean age of 77.7 ± 9.5 years. Longer sleep latency was associated with longitudinal decline in executive function (p = 0.038), and marginally with longitudinal decline in global cognitive performance (p = 0.075). After excluding 29 cases with mild cognitive impairment, results were similar. CONCLUSION: Cognitively healthy people with ET who have longer sleep latency had greater declines in executive function during prospective follow-up. Early detection of, and possibly intervention for, abnormal sleep latency may protect against certain aspects of cognitive decline in ET patients.
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Disfunción Cognitiva , Temblor Esencial , Trastornos del Sueño-Vigilia , Humanos , Anciano , Anciano de 80 o más Años , Estudios Longitudinales , Estudios Prospectivos , Temblor Esencial/complicaciones , Temblor Esencial/psicología , Estudios Transversales , Disfunción Cognitiva/complicaciones , Cognición/fisiología , Pruebas Neuropsicológicas , Trastornos del Sueño-Vigilia/psicologíaRESUMEN
Parkinson's disease (PD) is the fastest growing neurodegenerative disease, but at present there is no cure, nor any disease-modifying treatments. Synaptic biomarkers from in vivo imaging have shown promise in imaging loss of synapses in PD and other neurodegenerative disorders. Here, we provide new clinical insights from a cross-sectional, high-resolution positron emission tomography (PET) study of 30 PD individuals and 30 age- and sex-matched healthy controls (HC) with the radiotracer [11C]UCB-J, which binds to synaptic vesicle glycoprotein 2A (SV2A), and is therefore, a biomarker of synaptic density in the living brain. We also examined a measure of relative brain perfusion from the early part of the same PET scan. Our results provide evidence for synaptic density loss in the substantia nigra that had been previously reported, but also extend this to other early-Braak stage regions known to be affected in PD (brainstem, caudate, olfactory cortex). Importantly, we also found a direct association between synaptic density loss in the nigra and severity of symptoms in patients. A greater extent and wider distribution of synaptic density loss in PD patients with longer illness duration suggests that [11C]UCB-J PET can be used to measure synapse loss with disease progression. We also demonstrate lower brain perfusion in PD vs. HC groups, with a greater extent of abnormalities in those with longer duration of illness, suggesting that [11C]UCB-J PET can simultaneously provide information on changes in brain perfusion. These results implicate synaptic imaging as a useful PD biomarker for future disease-modifying interventions.
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OBJECTIVE: Postmortem examination of the essential tremor cerebellum has revealed a variety of pathological changes centered in and around Purkinje cells. Studies have predominantly focused on cerebellar neuronal connections. Bergmann glial morphology has not yet been studied in essential tremor. Among their many roles, Bergmann glia in the cerebellar cortex ensheath Purkinje cell synapses and provide neuroprotection. Specifically, the complex radial processes and lateral appendages of Bergmann glia are structural domains that modulate Purkinje cell synaptic transmission. In this study, we investigate whether Bergmann glia morphology is altered in the essential tremor cerebellum. METHODS: We applied the Golgi-Kopsch method and used computerized three-dimensional cell reconstruction to visualize Bergmann glia in the postmortem cerebellum of 34 cases and 17 controls. We quantified morphology of terminal structures (number of terminations and lateral appendage density) and morphology of radial processes (total process length, branch length, branch order, and branch volume) in each glial cell. We quantified number of branches and volume as well. RESULTS: Essential tremor cases had a 31.9% decrease in process terminations and a 35.7% decrease in lateral appendage density in Bergmann glia. Total process length and branch length did not differ between essential tremor cases and controls. We found also a reduction in number of secondary and tertiary branches and tertiary branches volume. INTERPRETATION: These findings suggest that Bergmann glia in essential tremor cases have more alterations in their terminal structures, with a relative preservation of radial processes, and highlight a potential role for these astrocytes in the disease pathophysiology.
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Temblor Esencial , Humanos , Neuroglía/fisiología , Células de Purkinje , Astrocitos , CerebeloRESUMEN
BACKGROUND: Although essential tremor (ET) is often divided into familial and sporadic cases, few data compare the evolution of clinical features in these groups over time. Leveraging data from a prospective, longitudinal study, we present analyses of the evolution of a broad range of cognitive, motor (i.e., tremor, tandem gait) and other features (e.g., disability) of ET. METHODS: Sixty-six familial and 23 sporadic ET cases completed in-home evaluations at baseline and 18, 36, and 54-month follow-ups. Assessments included detailed neuropsychological testing and videotaped neurological examinations. Analyses compared the longitudinal course of 16 clinical features in familial and sporadic cases. RESULTS: Baseline mean age was 75.2 ± 8.8 years and mean observation period was 4.7 ± 0.3 years. Tremor onset age was lower and childhood onset more common in familial than sporadic cases (p's = 0.02). Longitudinal analyses revealed no significant differences between clinical features displayed by familial and sporadic cases, or differences between the patterns of change in clinical features observed in these groups across time. Sporadic cases' daily activity skills declined significantly, whereas familial cases' did not, p's = 0.04 and 0.34, respectively; however, this finding was non-significant when controlling for false discovery rate. Several additional non-significant trends were noted. CONCLUSION: Familial and sporadic ET cases differed in onset age, and in the prevalence of childhood tremor onset. Although a number of interesting trends were observed, no significant differences in the evolution of clinical features over time in patients with and without a family history of ET were revealed.
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Temblor Esencial , Humanos , Anciano , Anciano de 80 o más Años , Temblor Esencial/diagnóstico , Temblor Esencial/epidemiología , Temblor Esencial/genética , Temblor , Estudios Prospectivos , Estudios Longitudinales , Edad de InicioRESUMEN
Essential tremor (ET) is a chronic, progressive neurological disease that may negatively affect patients' lives. While there has been considerable progress in ET research, some fundamental issues remain unaddressed. One such issue is disease staging. Staging schemes have inherent value and are part of the dialogue that clinicians have with other movement disorders patients. We highlight the value of and challenges with developing a staging system for ET and organize a discussion around the potential steps in developing such a system. Diseases for which there are staging schemes generally have a number of shared characteristics. ET has numerous features that would lend themselves to a staging scheme: emerging evidence supporting the existence of a premotor phase of disease, insidious onset, progressive worsening of arm tremor, spread of tremor to other body regions, the observation that patients seem to be at increased risk for other conditions within the same organ (i.e., emergence of Parkinson's disease and Alzheimer's disease in excessive numbers of ET patients), pathological changes in the cerebellum whose evolution can be ordered from (i) those that compromise the physical integrity and physiological function of Purkinje cells, (ii) subsequent changes that are reparative and regenerative, and (iii) eventual cell death. Challenges to formulating a staging scheme are the absence of both a biological marker and an "end stage" of disease. The sum of combined evidence suggests that a staging scheme would be of value. We provide initial thoughts as to how to begin to structure such a staging scheme.
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Temblor Esencial , Enfermedad de Parkinson , Humanos , Temblor , Cerebelo/patología , Células de PurkinjeRESUMEN
OBJECTIVE: Despite being one of the most prevalent neurological diseases, the pathophysiology of essential tremor (ET) is not fully understood. Neuropathological studies have identified numerous degenerative changes in the cerebellum of ET patients, however. These data align with considerable clinical and neurophysiological data linking ET to the cerebellum. While neuroimaging studies have variably shown mild atrophy in the cerebellum, marked atrophy is not a clear feature of the cerebellum in ET and a search for a more suitable neuroimaging signature of neurodegeneration is in order. Postmortem studies in ET have examined different neuropathological alterations in the cerebellum, but as of yet have not focused on measures of generalized synaptic markers. This pilot study focuses on synaptic vesicle glycoprotein 2A (SV2A), a protein expressed in practically all synapses in the brain, as a measure of synaptic density in postmortem ET cases. METHODS: The current study utilized autoradiography with the SV2A radioligand [18F]SDM-16 to assess synaptic density in the cerebellar cortex and dentate nucleus in three ET cases and three age-matched controls. RESULTS: Using [18F]SDM-16, SV2A was 53% and 46% lower in the cerebellar cortex and dentate nucleus, respectively, in ET cases compared to age-matched controls. CONCLUSION: In this pilot study, using in vitro SV2A autoradiography, we have observed significantly lower synaptic density in the cerebellar cortex and dentate nucleus of ET cases. Future research could expand on our sample size and focus on in vivo imaging in ET to explore whether SV2A imaging could serve as a much-needed disease biomarker.
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The Archimedes spiral is a clinical tool that aids in the diagnosis and monitoring of essential tremor. However, spiral ratings may vary based on experience and training of the rating physician. This study sought to generate an objective standard model for tremor evaluation using convolutional neural networks. One senior movement disorders neurologist (Neurologist 1) with over 30 years of clinical experience used the Bain and Findley Spirography Rating Scale to rate 1653 Archimedes spiral images from 46 essential tremor patients (mild to severe tremor) and 75 control subjects (no to mild tremor). Neurologist 1's labels were used as the reference standard to train the model. After training the model, a randomly selected subset of spiral testing data was re-evaluated by Neurologist 1, by a second senior movement disorders neurologist (Neurologist 2) with over 27 years of clinical experience, and by our model. Cohen's Weighted Kappa 95% confidence intervals were calculated from all rater comparisons to determine if our model performs with the same proficiency as two senior movement disorders neurologists. The Cohen's Weighted Kappa 95% confidence intervals for the agreement between the reference standard scores and Neurologist 1's rerated scores, for the agreement between the reference standard scores and Neurologist 2's scores, and for the agreement between the reference standard scores and our model's scores were 0.93-0.98, 0.86-0.94, and 0.89-0.96, respectively. With overlapping Cohen's Weighted Kappa 95% confidence intervals for all agreement comparisons, we demonstrate that our model evaluates spirals with the same proficiency as two senior movement disorders neurologists.
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Temblor Esencial , Médicos , Humanos , Temblor Esencial/diagnóstico , Temblor/diagnósticoRESUMEN
Background: People with essential tremor (ET) can be subject to stigma, and some adopt avoidance behaviors. Characteristics associated with ET stigma and the relationship between perceived stigma and social dysfunction have not been studied. Objectives: To discern predictors of perceived stigma and social dysfunction in ET, and to identify potentially treatable psychological factors associated with social dysfunction. Methods: We surveyed ET patients (n = 158) on recalled stigma incidents and social dysfunction related to tremor, as well as clinical and demographic characteristics including tremor severity, and psychological constructs including anxiety, depression, mindfulness, resilience, and narcissism. Results: Worse tremor severity (Standardized beta [SB] 1.4, P < 0.001) especially among younger participants (interaction of age and tremor severity SB -0.9, P < 0.001) and presence of vocal tremor (SB 0.7, P = 0.002) predict perceived stigma. 53/157 (33.8%) participants met criteria for social dysfunction, employing maladaptive avoidance strategies. Scores for perceived stigma (Odds Ratio [OR] 1.2, P = 0.002), depression (OR 1.5, P = 0.004) and stigma psychological distress (OR 1.2, P = 0.001) as well as sex (OR 4.3 for females, P = 0.045) predicted social dysfunction. Conclusions: Depression and stigma psychological distress contribute to social dysfunction related to ET stigma. Treating these psychological factors may mitigate social avoidance behaviors prevalent among susceptible individuals: those who most perceive ET stigma, i.e. relatively younger patients with worse tremor or with vocal tremor, and in particular females who are more prone to social dysfunction than males with the same degree of perceived stigma.
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Essential tremor (ET) is a chronic and progressive neurologic disease. Its central and defining clinical feature is a 4-12Hz kinetic tremor, that is, tremor that occurs during voluntary movements such as drinking from a cup or writing. Patients may also exhibit a range of other tremors-postural, rest, intention, additional motor features (e.g., mild gait ataxia, mild dystonia), as well as nonmotor features. The disease itself seems to be a risk factor for other degenerative diseases such as Alzheimer's disease and Parkinson's disease. Both genetic and toxic environmental factors have been explored as etiologic factors. In addition to a growing appreciation of the presence of clinical, etiologic, and pathologic heterogeneity, there is some support for the notion that ET itself may not be a single disease, but may be a family of diseases whose central defining feature is kinetic tremor of the arms, and which might more accurately be referred to as "the essential tremors." Recent research has increasingly placed the seat of the disease in the cerebellum and cerebellar system and identified a host of neurodegenerative changes within the cerebellum, indicating that this progressive disorder is likely degenerative.
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Enfermedad de Alzheimer , Temblor Esencial , Humanos , Temblor Esencial/diagnóstico , Temblor/diagnóstico , Temblor/etiología , Cerebelo , MarchaRESUMEN
Objectives: The objective of this study was to study the interrelations of demoralization, depression, and resilience in patients with Parkinson disease, and, more specifically, to determine if higher resilience in patients with Parkinson disease is associated with lower demoralization, lower depression, or both. Methods: Outpatients with Parkinson disease (N = 95) were assessed for demoralization, depression, and resilience, as well as sociodemographic, clinical, and treatment-related variables. Bivariable associations, standard regressions, linear regression with copula correction, and correspondence analysis were used to analyze the data. Results: Although the bivariable association between resilience and depression was statistically significant, the association ceased to be significant when demoralization was taken into consideration in both standard regressions and linear regression with copula correction. By contrast, the association between resilience and demoralization was significant when depression was not taken into consideration and continued to be significant when depression was taken into consideration. Correspondence analysis revealed that low resilience was strongly related to demoralization combined with depression, whereas normal resilience was closely correlated with depression without demoralization. Conclusion: These results expand our understanding of resilience by suggesting that it is a mechanism evolved to reduce or prevent demoralization and not just depression. Reducing demoralization and strengthening resilience as part of a comprehensive treatment plan are likely to improve the prognosis of Parkinson disease.
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Essential tremor (ET) is a common neurological disorder, with clinical and pathophysiological links to the cerebellum. Inquiries into the etiology, pathophysiology, and nosology of ET stand to benefit from the identification of disease biomarkers. Serum neurofilament light chain (NfL) has emerged as a novel signature of conditions in which neuronal injury reflects an outcome of the ongoing disease process. We sought to investigate the concentrations of NfL in ET patients and healthy controls. In this case-control study, our powered study population of 41 ET patients and 40 age-matched healthy controls underwent clinical assessments and measurement of serum NfL concentration using Simoa technology. Serum NfL was elevated in ET patients - mean log-transformed serum NfL concentration = 1.23 ± 0.19 (95% confidence interval [CI] = 1.17-1.29) vs. 1.08 ± 0.15 (95% CI = 1.03-1.13), p = 0.0002. This difference persisted after accounting for age, sex and Montreal Cognitive Assessment score in a multiple linear regression model (p = 0.002) and in an age-matched sample subset of 35 ET cases and 35 controls (p = 0.006). There was no association between tremor severity and serum NfL levels (p = 0.73). In this sample of ET patients and controls, serum NfL concentrations were significantly higher in ET. Studies in additional cohorts of ET cases would be of value in attempting to replicate these results and assessing diagnostic utility.
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Background: Although essential tremor (ET) patients have greater odds of mild cognitive impairment (MCI) and dementia than age-matched controls, the functional consequences of these enhanced odds are unknown. We examined associations between cognitive diagnosis and the occurrence of near falls, falls, use of a walking aid or a home health aide, non-independent living, or hospitalizations within a prospective, longitudinal study of ET patients. Methods: A total of 131 ET patients (mean baseline age = 76.4 ± 9.4 years) completed a battery of neuropsychological tests and questions about life events and were assigned diagnoses of normal cognition (NC), MCI, or dementia at the baseline and at 18-, 36-, and 54-month follow-ups. Kruskall-Wallis, chi-square, and Mantel-Haenszel tests assessed whether the diagnosis was associated with the occurrence of these life events. Results: Patients with final diagnoses of dementia were more often reported as living non-independently than NC or MCI patients and more often used walking aids than NC patients, with a p-value of <0.05. Patients with a final MCI or dementia diagnosis more often employed a home health aide than NC patients, with a p-value of <0.05. Moreover, Mantel-Haenzsel tests revealed linear associations between the occurrence of these outcomes and the level of cognitive impairment, with a p-value of <0.001 (i.e., dementia > MCI > NC). Conclusion: Cognitive diagnosis was associated with reported life events of ET patients, including the use of a mobility aid, employment of a home health aide, and removal from an independent living situation. These data provide rare insights into the important role cognitive decline plays in the experiences of ET patients.