Abstract and Introduction

Abstract

In the past decade, the hypothesis that essential tremor is a monosymptomatic tremorogenic disorder has been questioned. New clinical, neuroimaging, electrophysiological and pathological studies indicate that essential tremor is associated with subtle neurological deficits and could be considered a slowly progressive neurodegenerative disorder. The aim of this Review is to describe the nonmotor neurological symptoms that are commonly associated with essential tremor, and highlight the cognitive deficits associated with this condition. Several clinical studies have demonstrated that essential tremor is associated with mild deficits in attention, executive functions, memory and, possibly, other cognitive processes. Population-based surveys have confirmed that dysfunction in these cognitive domains affects patients both with severe and mild essential tremor. Clinical studies have also indicated that cognitive deficits associated with essential tremor are progressive and that patients with this condition have an increased risk of dementia. Mood and cognitive deficits commonly observed in patients with essential tremor are similar to symptoms of cerebellar cognitive affective syndrome. Further evidence is required from prospective studies to support the interpretation that essential tremor is a slowly progressive neurodegenerative disorder.

Introduction

In the late 20^th century, most of the early studies of essential tremor did not provide evidence that this disorder was associated with any cognitive deficits,^[1-5] although in one study conducted by Rajput et al. "psychoneuroses" were reported in 16% of cases.^[6] In fact, most of the clinical series and neurological texts published during this time period described essential tremor as a monosymptomatic, slowly progressive, benign movement disorder ( Box 1 ).^[7-9] Furthermore, research conducted during this period indicated that this condition was frequently familial in nature, infrequently associated with incapacitating tremor, and associated with disturbances in tandem gait ataxia in chronic cases.^{[1,3,5,10,11]} Although the etiology of essential tremor is still not fully understood, the condition is considered to be a functional (tremorogenic) disorder.^[2,11,12] Further research has showed that essential tremor is association with other movement disorders, such as Parkinson disease (PD), dystonia and myoclonus,^[4,5] but the Movement Disorders Society has defined essential tremor as a separate entity from these neurological disorders and secondary causes of tremor.^[13]

Over the past decade, contemporary, multidisciplinary studies that have evaluated patients with essential tremor^[14] have shown that these patients typically experience mild neurological^[12,15-24] and cognitive deficits,^[25-35] and indicate that patients with essential tremor have an increased risk of dementia.^[35-37] Neuropsychiatric manifestations such as mood disorders have also been associated with essential tremor.^[38-40] These findings, along with pathophysiological observations showing that patients with essential tremor have substantially more cerebellar atrophy than controls, indicate that essential tremor is associated with damage to the cerebellum or its connectivity to other brain regions.^[41-44] The fact that essential tremor is associated with pathophysiological changes within the brain, cognitive and neuropsychiatric disturbances, and other neurodegenerative disorders such as PD,^[44] and typically worsens with age, has led several authors to suggest that it could be a neurodegenerative disorder.^[45-47] This article provides an overview of the nonmotor and cognitive aspects of essential tremor, and describes but does not analyze in depth neuropsychiatric aspects that are associated with this condition.