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Table 1.  

Cognitive Deficits Associated with Essential Tremor34

Box 1.  

Classic Concept of Essential Tremor

Box 2.  

Essential Tremor: New Findings

Box 3.  

Cognition in Patients with Essential Tremor


Essential Tremor -- A Neurodegenerative Disorder Associated With Cognitive Defects?

  • Authors: Félix Bermejo-Pareja, MD, PhD
  • CME Released: 4/12/2011
  • Valid for credit through: 4/12/2012, 11:59 PM EST
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Target Audience and Goal Statement

This activity is intended for primary care clinicians, family practitioners, and other health professionals caring for patients with benign essential tremor.

The goal of this activity is to review the evidence that essential tremor may be a slowly progressive neurodegenerative disorder.

Upon completion of this activity, participants will be able to:

  1. Describe cognitive and mood abnormalities in patients with essential tremor on the basis of review findings
  2. Describe evidence for cerebellar and other pathology in patients with essential tremor on the basis of review findings
  3. Describe recommended diagnostic workup in patients with essential tremor on the basis of review findings


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  • Félix Bermejo-Pareja, MD, PhD

    Department of Neurology, University Hospital "Doce de Octubre," Madrid, Spain


    Disclosure: Félix Bermejo-Pareja, MD, PhD, has disclosed no relevant financial relationships.


  • Heather Wood

    Chief Editor, Nature Reviews Neurology


    Disclosure: Heather Wood has disclosed no relevant financial relationships.

CME Author(s)

  • Laurie Barclay, MD

    Freelance writer and reviewer, Medscape, LLC


    Disclosure: Laurie Barclay, MD, has disclosed no relevant financial relationships.

CME Reviewer(s)

  • Nafeez Zawahir, MD

    CME Clinical Director, Medscape, LLC


    Disclosure: Nafeez Zawahir, MD, has disclosed no relevant financial relationships.

  • Sarah Fleischman

    CME Program Manager, Medscape, LLC


    Disclosure: Sarah Fleischman has disclosed no relevant financial relationships.

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Essential Tremor -- A Neurodegenerative Disorder Associated With Cognitive Defects?: New Classification of Essential Tremor


New Classification of Essential Tremor

Research conducted in the past decade has challenged the traditional view of essential tremor as a monosymptomatic movement disorder that has no known underlying pathology. These studies indicate that essential tremor might be a slowly progressing neurodegenerative disorder (or disorders) characterized by tremor, CNS pathology (mainly cerebellar) and neurological abnormalities,[58] including cognitive and neuropsychiatric deficits ( Box 2 ).[44] From a clinical, genetic and pathological point of view, some authors suggest that essential tremor could be considered as a heterogeneous disorder.[45]

Neurological Deficits

The neurological disorders that are associated with essential tremor include bradykinesia,[15,59,60] cerebellar dysfunction,[5,17] gait ataxia[1,10,18] and dysarthria;[61] however, these conditions are typically subtle in patients with this tremor. Dysfunctional ocular movements,[19] mirror movements[42] and deficits in hand-eye coordination20 have also been associated with essential tremor, as have deficits in olfaction[22,23] and hearing,[23,24] although controversy surrounds the association with these latter two conditions.[12] Some clinical series indicate that olfaction is not dysfunctional in patients with essential tremor,[62] whereas another study has indicated that essential tremor and hearing deficits might exist concomitantly in some patients as a consequence of a shared familial factor.[63] The pathological basis of these sensory deficits and their relationship to essential tremor are not known in detail and require further study.[12] The consistent finding of tandem gait abnormalities that are closely associated to aging, tremor duration and midline tremors in patients with essential tremor[1,10,18,61] suggests that cerebellar dysfunction might be an important underlying pathophysiological factor in this condition.[10,61,64]

Mild cognitive deficits, including deficits in attention, executive functions and memory, have also been associated with essential tremor (see below).[25-37,52] Whether these cognitive deficits worsen over time is a matter of debate; however, elderly patients with essential tremor are known to be at high risk of dementia (a well-established finding from population-based surveys).[36,37,65] When these cognitive deficits are mild, clinicians do not perceive them as troublesome.[66]

Psychiatric Disorders

Neuropsychiatric disturbances such as depression and anxiety, personality changes, social phobias, and low measures of subjective health status or health-related quality of life are all frequently observed in patients with essential tremor.[38-40,58,67-77] Although the association between these disturbances and essential tremor is well-established, more information is needed regarding their initiation and evolution. Evidence suggests that depression might occur before the clinical symptoms of essential tremor manifest; in such situations this psychiatric disorder cannot be a secondary response to disability.[40,70,77] A study of premorbid personality in patients with essential tremor demonstrated that these patients had similar premorbid personality traits to patients with PD. Depressive, introverted, 'rigid' and 'lonely' traits were evident in both patient groups.[58] Furthermore, a comparative study of depression in patients with PD, dystonia or essential tremor showed that the frequency and intensity of depression was of similar magnitude in these three disorders.[38] Symptoms of depression and anxiety have been documented in population-based studies in which many of the participants had mild essential tremor, or were thought to have undiagnosed essential tremor.[70,71,77] In fact, over 30% of patients with essential tremor may have mild depressive symptoms. Depression in essential tremor and in primary affective disorders has different clinical manifestations: patients with essential tremor are more likely to have concentration difficulties and lassitude than patients with primary affective disorders.[76] The pathophysiological basis of depression and anxiety in patients with essential tremor is currently unknown and awaits prospective studies.

Pathological Findings

Early studies indicated that essential tremor was not associated with pathology within the brain, and consequently this condition was judged to be a functional disorder. Before 1991, however, only eight cases of essential tremor had been studied pathologically. During this year, Rajput et al.[78] reported the study of six additional patients with this condition, but they found no evidence of underlying neuropathological lesions. This situation changed with the utilization of neuroimaging to study this essential tremor. Two studies, by Bucher et al. and Jenkins and Frackowiak,[79,80] indicated that essential tremor was associated with activity in the cerebral hemispheres and brainstem structures, such as the olivary nucleus, and that the cerebellum had a possible role in several cognitive processes; for example, executive functioning, working memory, and others.

Further pathological and neuroimaging studies suggested that essential tremor is associated with atrophy within the cerebellum[43,81-85] and other areas of the brain, including the locus coeruleus and cerebral white matter.[86-88] Other neuroimaging studies, however, have not identified specific pathological changes in patients with essential tremor,[89,90] and neuropathological investigations conducted by Rajput and colleagues did not identify consistent cerebellar pathology in these patients.[91,92] Of note, these studies were performed mainly on individuals in the early stages of the disease.

Essential tremor has been associated with other conditions, such as migraine,[93] restless legs syndrome,[94] fragile X mutations[95] and several neurodegenerative disorders.[45] Although early studies did not find any correlation between essential tremor and PD,[1,96] large clinical series[4,5] identified an association between these two disorders, and patients with essential tremor, as well as their relatives, seem to have an increased risk of developing this neurodegenerative disorder.[96-99] The relationship between essential tremor and both Alzheimer disease (AD) and Lewy body dementia is more contentious, and is currently under debate.[44,100,101]

In summary, subtle neurological symptoms are associated with essential tremor.[11,15-20] Electrophysiological,[102] clinical[16,61] and neuroimaging studies[46,86-90] have indicated that patients with this disorder have cerebellar deficits. Moreover, pathological studies have shown that the majority of patients with essential tremor have cerebellar atrophy. A subset of these patients might have pathology suggestive of Lewy body disease (especially in the locus coeruleus) but no cerebellar degeneration.[44,45] The association between essential tremor and other neurodegenerative disorders such as PD (and possibly Lewy body dementia and AD),[44,100,101] and the slow progressive evolution of several essential tremor symptoms suggest that this condition might, in most cases, be a benign neurodegenerative disorder.[1,36,65,103,104] However, an alternative view is that essential tremor might be caused by genetic or other etiological factors that produce a "dynamic oscillatory disturbance of the motor system."[12]