Essential Tremor Parkinson's Disease Research Articles

Combined brain topological metrics with machine learning to distinguish essential tremor and tremor-dominant Parkinson's disease.

Essential tremor (ET) and Parkinson's disease (PD) are the two most prevalent movement disorders, sharing several overlapping tremor clinical features. Although growing evidence pointed out that changes in similar brain network nodes are associated with these two diseases, the brain network topological properties are still not very clear. The combination of graph theory analysis with machine learning (ML) algorithms provides a promising way to reveal the topological pathogenesis in ET and tremor-dominant PD (tPD). Topological metrics were extracted from Resting-state functional images of 86 ET patients, 86 tPD patients, and 86 age- and sex-matched healthy controls (HCs). Three steps were conducted to feature dimensionality reduction and four frequently used classifiers were adopted to discriminate ET, tPD, and HCs. A support vector machine classifier achieved the best classification performance of four classifiers for discriminating ET, tPD, and HCs with 89.0% mean accuracy (mACC) and was used for binary classification. Particularly, the binary classification performances among ET vs. tPD, ET vs. HCs, and tPD vs. HCs were with 94.2% mACC, 86.0% mACC, and 86.3% mACC, respectively. The most power discriminative features were mainly located in the default, frontal-parietal, cingulo-opercular, sensorimotor, and cerebellum networks. Correlation analysis results showed that 2 topological features negatively and 1 positively correlated with clinical characteristics. These results demonstrated that combining topological metrics with ML algorithms could not only achieve high classification accuracy for discrimination ET, tPD, and HCs but also help to reveal the potential brain topological network pathogenesis in ET and tPD.

Retinal Thickness in Essential Tremor and Early Parkinson Disease: Exploring Diagnostic Insights.

Essential tremor (ET) represents a heterogeneous condition which may overlap with Parkinson disease (PD) even at early stages, by sharing some subtle clinical aspects. Longstanding ET demonstrated also higher risk of developing PD, especially with a Tremor-dominant (TD-PD) phenotype. Therefore, differential diagnosis between ET and early PD could be quite challenging. Optical coherence tomography (OCT) has been recognized as a reliable tool to assess the retina as a proxy of neurodegeneration. We aimed to explore the possible role of retinal assessment in differential diagnosis between ET and early PD. Macular layers and peripapillary retinal nerve fiber layer (RNFL) thickness among ET, early PD, and healthy controls (HCs) were assessed using OCT. Forty-two eyes from 23 ET, 41 eyes from 21 early PD, and 33 eyes from 17 HCs were analyzed. Macular RNFL, ganglion cell layer, inner plexiform layer, and inner nuclear layer were thinner in PD as compared with ET and even more in HCs. Differences between ET and PD were more evident when considering the TD-PD subgroup, especially for RNFL. Among ET patients, thickness of the inner macular layers showed negative linear relationship with both age at onset and disease duration. Peripapillary temporal quadrant thinning was found in ET compared with HCs. Macular inner retina was thinner in patients with ET and early PD compared with HCs. These findings suggest that the retinal assessment may have a utility in the differential diagnosis between ET and PD.

Essential tremor-Parkinson's disease syndrome: clinical characteristics and subtypes using cluster analysis.

Essential tremor (ET) and Parkinson's disease (PD) are common movement disorders. ET-PD syndrome is characterized by the occurrence of PD in patients with a previous history of ET, which may be an independent phenotype distinct from PD. This study aims to identify clinical characteristics and subtypes in ET-PD. A total of 93 newly diagnosed ET-PD patients and 93 newly diagnosed PD patients matched for age, sex, education, and disease duration of PD were selected using propensity score matching analysis. The K-means cluster analysis was performed for 11 variables derived from the ET-PD group, and cluster profiles were established through statistical analysis of demographic and clinical variables. The ET-PD group consisted of a high number of patients with a family history of ET exhibiting evident tremor with milder hypokinesia and postural instability symptoms, as compared to the PD group. Through the cluster analysis, two clusters of ET-PD patients were identified. The ET-PD cluster 1 ( n = 34) had a shorter ET duration before PD onset, lower number of patients with a family history of ET, higher unified PD rating scale instability scores, higher non-motor symptoms scores (non-motor symptoms scale D1 scores, Hamilton depression scale scores, Hamilton anxiety scale scores, and PD sleep scale-2 scores), and higher Chinese version of the PD questionnaire-39 scores relative to the ET-PD cluster 2 ( n = 59). ET-PD patients had significantly different characteristics for motor symptoms as compared to PD patients, and may be distinctly divided into two clinical subtypes, namely, the ET-PD complex type and the ET-PD simple type.

Phenotypic Features of Isolated Essential Tremor, Essential Tremor Plus, and Essential Tremor-Parkinson’s Disease in a Movement Disorders Clinic

Background:Patients with essential tremor were initially considered to have isolated tremor, but additional motor and non-motor features have been increasingly recognized. The term “essential tremor plus” was adopted by the Task Force on Tremor of the International Parkinson and Movement Disorder Society to describe essential tremor patients with additional neurologic signs.Objectives:To characterize essential tremor patients and their phenotypes in a movement disorders clinic population in the context of the new tremor classification.Methods:Demographic, clinical, historical, treatment, and diagnostic data were retrospectively collected on 300 patients diagnosed by movement disorder experts with essential tremor. Patients were classified as having essential tremor, essential tremor plus, or essential tremor-Parkinson’s disease combination, and features between these groups were compared.Results:Of the 300 patients, 20.7% were classified as isolated essential tremor, 53.3% as essential tremor plus, and 26.0% as essential tremor-Parkinson’s disease. There was no significant difference in the duration of tremor symptoms. Essential tremor plus patients were more likely to have dystonia, tandem gait abnormalities, head tremor and greater tremor severity. Essential tremor-Parkinson’s disease patients were more likely to have RBD symptoms. There was no significant difference in cognitive impairment between essential tremor plus and essential tremor-Parkinson’s disease patients.Conclusions:Additional motor and non-motor features, including parkinsonism, are common in patients with essential tremor. Further studies are needed to clarify essential tremor phenotypes and to provide insights into possible subtypes.Highlights:300 patients with essential tremor from a movement disorders clinic were re-classified based on the Movement Disorder Society Consensus Statement on the Classification of Tremors. Additional motor and non-motor features, including parkinsonism, were common, and only 20.7% of patients remained classified as isolated essential tremor.

Clinical Characteristics and Electrophysiological Biomarkers of Parkinson's Disease Developed From Essential Tremor.

Background and Objective: Parkinson's disease developed from essential tremor (ET-PD) is a distinct clinical syndrome that is different from essential tremor (ET) and Parkinson's disease (PD). There is currently a lack of research on ET-PD. Tremor characteristics (amplitude and frequency) are primary quantitative indexes for diagnosing and monitoring of tremors. In this study, we aimed to explore specific clinical and electrophysiological biomarkers for the identification of ET-PD.Methods: The study included patients with ET-PD (n = 22), ET (n = 42), and tremor-dominant PD (t-PD, n = 47). We collected demographic data, clinical characteristics (including motor and non-motor symptoms), and tremor analysis. The frequency, amplitude, contracting patterns of resting tremor and postural tremor were collected. The analysis of ET-PD and ET/t-PD was compared. The receiver operating characteristic (ROC) curve was used to analyze the electrophysiological features in distinguishing ET-PD from ET or t-PD.Results: Compared with ET, hyposmia, bradykinesia, rigidity, postural abnormality, and resting tremor were more common in the ET-PD group (P = 0.01, 0.003, 0.001, 0.001, 0.019, respectively). The postural tremor frequencies of the head, upper limbs, and lower limbs were significantly lower in the ET-PD than in the ET (P = 0.007, 0.003, 0.035, respectively), which were the most appropriate variables for distinguishing ET-PD from ET (AUC: 0.775, 0.727, and 0.701, respectively). Compared with t-PD, bradykinesia, rigidity, postural abnormality (both P < 0.001), and resting tremor (P = 0.024) were less common in the ET-PD. The postural tremor amplitudes of the head and upper limbs were significantly higher in the ET-PD than in the t-PD (P = 0.022, 0.001, respectively), which were the most appropriate variables for distinguishing ET-PD from t-PD (AUC: 0.793 and 0.716).Conclusions: Hyposmia and electrophysiological biomarkers (postural tremor frequencies and amplitudes) help early recognition of ET-PD.

A double whammy: Essential tremor and Parkinson's disease

Background: Surprisingly little has been written about the combined clinical entity, essential tremor-Parkinson's disease (ET-PD), which is the result of a double disease hit. We carefully quantified tremor burden using a wide range of measures (tremor severity, tremor-related disability, tremor-related quality of life) and furthermore, studied additional motor and non-motor features in ET-PD.

Quantification of tremor severity with a mobile tremor pen

BackgroundAn objective evaluation of tremor severity is necessary to document the course of disease, the efficacy of treatment, or interventions in clinical trials. Most available objective quantification devices are complex, immobile, or not validated. New methodWe used the TREMITAS-System that comprises a pen-shaped sensor for tremor quantification. The Power of Main Peak and the Total Power were used as surrogate markers for tremor amplitude. Tremor severity was assessed by the TREMITAS-System and relevant subscores of the MDS-UPDRS and TETRAS rating scales in 14 patients with Parkinson's disease (PD) and 16 patients with Essential tremor (ET) off and on therapy. We compared tremor amplitudes assessed during wearable and hand-held constellations. ResultsWe found significant correlations between tremor amplitudes captured by TREM and tremor severity assessed by the MDS-UPDRS in PD (r = 0.638–0.779) and the TETRAS in ET (r = 0.597–0. 704) off and on therapy. The TREMITAS-System captured the L-Dopa-induced improvement of tremor in PD patients (p = 0.027). Tremor amplitudes did not differ between the handheld and wearable constellation (p > 0.05). Comparison with existing methodsWe confirm the results of previous studies using inertial based sensors that tremor severity and drug-induced changes of tremor severity can be quantified using inertial based sensors. The assessment of tremor amplitudes was not influenced by using a handheld or wearable constellation. ConclusionsThe TREMITAS-System can be used to quantify rest tremor in PD and postural tremor in ET and is capable of detecting clinically relevant changes in tremor in clinical and research settings.

Evaluation of retinal alterations in Parkinson disease and tremor diseases.

Optical coherence tomography (OCT) has been suggested as a method for detection of retinal alterations in neurodegenerative diseases. The usefulness of OCT as a diagnostic tool to differentiate Parkinson's disease (PD) from other tremor diseases, remains unknown. We aimed to evaluate morphological changes of the retina in patients with PD, essential tremor (ET), essential tremor-Parkinson's disease (ET-PD) using OCT. Forty-two eyes of 21 patients with PD, 24 eyes of 12 patients with ET, 24 eyes of 12 patients with ET-PD and 44 eyes of 22 age-matched healthy controls were included in the study. All participants underwent detailed neurological and ophthalmological examination. Measurements in all quadrants of macula and retinal nerve fiber layer (RNFL) thickness using OCT were recorded. There was no significant difference among the groups regarding age, sex. The average RNFL thickness was thinner in PD patients than that of ET (p = 0.032). The RNFL thickness in superior quadrant was lower in PD group compared with the ET and control group (p = 0.001, p = 0.016). Significant differences were observed in most of the macular thickness parameters excluding foveolar and foveal thickness (p = 0.865, 0.394). Correlations were found among several OCT parameters and disease duration or severity in all patient groups (p > 0.05). Retinal alterations were found in PD patients compared to ET. However, no significant retinal changes were detected by OCT in patients with ET and ET-PD compared to controls. According to our data, retinal assessments by OCT do not seem to be satisfactory for differentiation of these disorders.

The features of the pathogenesis and clinical picture of Parkinson's disease that has developed in essential tremor

In the past decades, there has been evidence on the relationship between Parkinson's disease (PD) and essential tremor (ET). In addition, PD frequently develops in already existing ET. The occurrence of PD in ET seems to be a problem of relevance, since the risk of PD is higher in patients with ET than that in the population. However, due to the lack of awareness about this nosological phenomenon among physicians, it can be difficult to formulate a diagnosis of PD that has developed in ET.This paper gives an update on the clinical, epidemiological, pathogenetic, and neuroimaging characteristics of ET concurrent with PD.

Clinical, electrophysiological, and imaging study in essential tremor-Parkinson's disease syndrome

IntroductionEssential tremor-Parkinson's disease (ET-PD) syndrome is a clinical condition in which individuals with a long-lasting history of Essential tremor (ET) eventually develop Parkinson's disease (PD). The aim of the study was to investigate the accuracy performances of clinical, neurophysiological, and imaging biomarkers in differentiating patients affected by ET-PD syndrome from patients with ET or PD. MethodsNineteen patients affected by ET-PD syndrome, 48 ET patients, and 37 tremor-dominant PD (t-PD) patients were included. Electrophysiological studies, including blink-reflex recovery cycle and tremor parameters analyses, were performed in all groups. Nigro-striatal and cardiac sympathetic denervation were also investigated. Sensitivity, specificity and accuracy of clinical, electrophysiological, and radiological features in differentiating ET-PD syndrome from ET and PD were calculated. ResultsET-PD patients had significantly lower rigidity (p = 0.007) and higher postural/kinetic tremor (p = 0.007) scores, in comparison to t-PD patients. ET-PD patients, differently from PD patients, had a synchronous pattern of resting tremor and, differently from ET patients, had abnormal blink-reflex recovery cycle. ET-PD patients also showed reduced nigro-striatal and cardiac sympathetic uptakes, albeit to a lesser extent than in PD patients. The highest accuracy values were found for the synchronous pattern of resting tremor (97.1%) in distinguishing ET-PD from PD, and for presence of abnormal blink-recovery cycle (100%) in distinguishing ET-PD syndrome from ET. ConclusionOur study demonstrates that some electrophysiological parameters, such as a synchronous resting tremor pattern and the abnormal blink-recovery cycle were the most accurate biomarkers in distinguishing patient with ET-PD syndrome from those with ET or those with PD.

Heart rate variability in patients with essential tremor: A cross sectional study

ObjectiveTo investigate heart rate variability (HRV) in patients with Essential Tremor (ET) in comparison with patients with Parkinson's Disease (PD). MethodsThis is a cross sectional control study including 10 patients with ET, 10 patients with PD and 10 age-sex-matched controls. In patients and controls, we measured the components of HRV analysis in the frequency domain during a daytime period of 12-h. Selected HRV variables were low-frequency (LF) and high-frequency (HF), conventionally considered to be influenced by the sympathetic system and the parasympathetic system respectively. ResultsHRV variables, in patients with ET, were significantly different from those detected in PD patients and similar to those of controls while in PD patients, they were significantly different from those of controls. At cut off level of 654 ms2, LF component correctly distinguished ET patients versus PD with sensitivity, specificity, PPV and accuracy of 100%. By contrast, at cut off level of 737 ms2, HF component showed sensitivity, specificity, PPV and accuracy of 80%, 100%, 100%, and 86.67% respectively. DAT-SPECT and cardiac MIBG uptake were both normal in ET patients whereas they were markedly decreased in those with PD. ConclusionsIn our study, the LF component of HRV analysis distinguishes ET patients from those with PD on an individual basis, thus representing a valid help in everyday clinical practice for differentiation between these patients in absence of scintigraphic investigations.

Essential tremor-Parkinson's disease: A double whammy

BackgroundSurprisingly little has been written about the combined clinical entity, essential tremor-Parkinson's disease (ET-PD), which is the result of a double disease hit. We carefully quantified tremor burden using a wide range of measures (tremor severity, tremor-related disability, tremor-related quality of life) and furthermore, studied additional motor and non-motor features in ET-PD. MethodsIn this prospective, clinical-epidemiological study, we performed a standardized, structured clinical evaluation of 27 ET-PD patients, comparing them to age-matched samples of 35 PD and 109 ET patients. ResultsThe number of hours/day shaking was lowest in PD (median=3.0), intermediate in ET (median=10.0) and highest in ET-PD (median=14.0) (p<0.001). All measures of mobility and balance (Berg Balance test, Activities-specific Balance Confidence Scale, Timed Up and Go test) worsened across groups in a stepwise manner from ET to PD to ET-PD (p<0.05). Mini-mental state test scores worsened (p=0.002) and daytime sleepiness increased (p=0.002) across groups from ET to PD to ET-PD. ConclusionsThe ET-PD patient seems to be more than just a PD patient with a little more kinetic tremor. Aside from a significantly greater tremor burden, ET-PD patients exhibited more cognitive and sleep problems and more mobility and balance problems than patients with isolated PD.

Sleep disorders associated with essential tremor and Parkinson's disease

To evaluate the sleep quality and explore the manifestations of sleep disorders for 62 essential tremor (ET) patients, 60 normal controls and 62 Parkinson's disease (PD) patients. A total of 62 ET patients, 60 normal controls and 62 PD patients from June 2009 to December 2013 were recruited. All of them were outpatients at Second Affiliated Hospital, Soochow University and Hospital of Changshu Hospital of Traditional Chinese Medicine. Sleep was assessed with Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS). The global PSQI score was 4.7 ± 2.5 in controls, 6.0 ± 4.0 in ET cases and 7.4 ± 3. 7 in PD cases. PD cases had the highest PSQI score, followed by ET (intermediate) and lowest scores in controls (F = 9.022, P = 0.000). A poor quality of sleep was observed in normal controls (23/62, 38.3%) compared to ET cases (34/62, 54.8%) and PD cases (40/62, 64.5%) (χ² = 8.555, P = 0.014 when comparing all three groups and χ² = 1.206, P = 0.272 when ET vs PD). The ESS score increased from normal controls (4.4 ± 2.5) to ET cases (6.3 ± 4.8) and PD cases (8.2 ± 4.2). An ESS score ≥ 10 (an indicator of greater than normal levels of daytime sleepiness) was observed in 6 (10.0%) normal controls, compared to ET cases (16, 25.8%) and PD cases (20, 32.3%) (χ² = 9.047, P = 0.011 when comparing all three groups and χ² = 0.626, P = 0.429 when ET vs PD). For normal controls, ET and PD patients, the factor scores of subjective sleep were 0.6 ± 0.7, 0.8 ± 0.8 and 1.1 ± 0.7; the factor scores of quality sleep latency 0.6 ± 0.7, 0.9 ± 0.9 and 1.1 ± 1.0; the factor scores of sleep duration 0.6 ± 0.8, 0.7 ± 1.0 and 1.0 ± 0.9; the factor scores of sleep efficiency 0.6 ± 0.8, 0.9 ± 0.9 and 1.0 ± 1.0; the factor scores of sleep disturbances 1.2 ± 0.6, 1.2 ± 0.5 and 1.7 ± 0.7; the factor scores of daytime dysfunction 1.2 ± 1.0, 1.3 ± 1.0 and 2.0 ± 1.1 respectively. There were inter-group statistical differences in subjective sleep (F = 7.709, P = 0.001), quality sleep latency (F = 4.414, P = 0.013), sleep duration (F = 4.464, P = 0.013), sleep efficiency (F = 3.201, P = 0.043), sleep disturbances (F = 12.594, P = 0.000) and daytime dysfunction (F = 9.022, P = 0.000) . However, no inter-group statistical differences existed in use of sleeping medication (F = 1.200, P = 0.304). There were statistical differences in subjective sleep (P < 0.05), sleep efficiency (P < 0.05) and daytime dysfunction (P < 0.05) between ET and PD patients. Some sleep scores in ET are intermediate between those of PD cases and normal controls. And it suggests that a mild form of sleep dysregulation may be present in ET.

Mini Review: linkages between essential tremor and Parkinson’s disease?

Essential tremor (ET) and Parkinson’s disease (PD) are two of the most common movement disorders. Tremors are the primary symptoms of ET and of some PD patients, the two are often mistaken for each other. Especially since there are no available differentiate tests for the tremor of ET or PD, the early diagnoses mainly based on clinical assessments of medical symptoms, family and medication history, and examination by physicians. There is increasing evidence suggesting an association between ET and PD, such as a similar tremor frequency, overlapping resting tremors (a typical PD tremor), postural tremors (mainly in ET patients) in both ET and PD patients, and many ET patients develop PD later in life. Although it is difficult to make a differential diagnosis of ET and tremor-dominant PD based on clinical assessment, recent developments of objective measurements, such as brain imaging, neuropathology, and genetic analysis, has opened a helpful window for distinguishing ET from PD. In this mini review, we included literatures of ET and PD studies and discussed various advanced methods for differential diagnosis between ET and PD such as neuroimaging, genetic markers, tremor intensity and frequency, and drug-responses.

Autonomic function, as self-reported on the SCOPA-autonomic questionnaire, is normal in essential tremor but not in Parkinson's disease

ObjectiveTo compare autonomic function of subjects with Parkinson's disease (PD) and essential tremor (ET) relative to controls. BackgroundIt has been reported that patients with PD have autonomic dysfunction while no literature exists regarding autonomic function in ET. MethodsSubjects with PD, ET, and controls had autonomic function measured using the SCOPA-Autonomic questionnaire, with the total and domain scores transformed to a scale of 0–100 points. Results62 subjects with PD, 84 with ET, and 291 controls were included. Women were more prevalent in control (69%) compared to PD (44%) and ET (44%) groups, and mean age was significantly younger in PD (73 yrs) and older in ET (83) compared to controls (81). The mean SCOPA-Aut Total score in PD was significantly higher than controls, with no difference in ET. No autonomic dysfunction was found in any domain in ET but in PD there were significant abnormalities in gastrointestinal, cardiovascular, urinary, and thermoregulatory domains. Individual question data revealed a significantly higher percentage of subjects with dysfunction on 11/23 questions in the PD group but only 1 question (sialorrhea) in the ET group compared with controls. ConclusionAutonomic scores, particularly gastrointestinal, cardiovascular, urinary, and thermoregulatory were increased in patients with PD, as assessed by SCOPA-Aut. Patients with ET did not exhibit autonomic dysfunction, with the exception of sialorrhea.

Essential tremor is not dependent upon cerebellar Purkinje cell loss

The pathophysiology of essential tremor (ET) is unknown but recent studies report that the majority of ET cases has cerebellar Purkinje cell (PC) degeneration and its sequelae. ObjectiveTo perform PC counts in ET, and normal and Parkinson's disease (PD) controls to determine the relationship of PC loss to ET. MethodsAll ET cases and PD controls were followed at our clinic. Normal controls had no history of neurological disease and had normal standard neuropathological studies. The PC counts were done by a neuropathologist who was blinded to the clinical diagnosis. Three different methods were used for counting PC; section through any part of the PC, through any part of the PC nucleus, and through any part of PC nucleolus. The counts were done in five non-contiguous microscopic fields. Results59 brains were studied. These included 12 ET, 41 PD controls, and six normal controls. The mean age at death was 82.7 in ET, 79.1 in PD, and 75.7 years in the normal controls. The mean duration of symptoms was 34 years in ET and 15.7 years in the PD cases. The mean PC counts through any part of the neuron were 64.8 in ET, 56.2 in PD, and 58.0 in normal controls. Differences were not significant. ConclusionCerebellar PC loss does not distinguish ET from controls. It is concluded that PC loss is neither a pathological basis for, nor the distinctive feature of ET.

A new diagnostic test to distinguish tremulous Parkinson's disease from advanced essential tremor

Clinical distinction between advanced essential tremor and tremulous Parkinson's disease can be difficult. In selected power spectra of accelerometric postural tremor recordings on the more affected side of 41 patients with essential tremor and 39 patients with tremulous Parkinson's disease being indistinguishable by tremor frequency, peak power or number of harmonic peaks, waveform asymmetry (autocorrelation decay), and mean peak power of all harmonic peaks were computed. Cutoff for essential tremor-Parkinson's disease distinction was determined by receiver operating characteristics. Diagnostic yield was tested in 12 clinically unclear patients with monosymptomatic tremor, subsequently definitively diagnosed with essential tremor (n = 2) or Parkinson's disease (n = 10) by 123-I FP-CIT-single-photon emission computed tomography, fluorodopa-positron emission tomography, or clinical course. By autocorrelation decay 64%, by mean harmonic peak power 94% (Parkinson's disease > essential tremor) of patients with a definite clinical diagnosis, and 11 of 12 clinically unclear patients were classified correctly. Mean harmonic power is a useful measure to separate clinically difficult cases of advanced essential tremor from tremulous Parkinson's disease.

Olfactory tests in the diagnosis of essential tremor

Most patients with tremor-dominant Parkinson's disease (PD) have impaired smell function but it is unclear whether this is true for subjects with essential tremor (ET). If ET patients do not exhibit meaningful smell loss, then olfactory testing may help to distinguish PD from ET. We assessed olfactory function in 59 ET and 64 tremor-dominant PD patients using the University of Pennsylvania Smell Identification Test (UPSIT) and olfactory event-related potential (OERP). UPSIT scores were compared to those from 245 healthy controls, and OERPs were compared to those from 74 controls. Unlike the PD test scores, those of ET patients were indistinguishable from controls when the effects of age, age of onset, gender, and smoking were taken into account. ET patients with a family history of tremor scored significantly better than controls on the UPSIT, and their rate of decline with age was slower. The effect was not observed on OERP. Smell testing may help to distinguish between ET and tremor-predominant PD, and patients with family history of tremor may represent a subgroup whose olfactory function is enhanced by some unknown mechanism.