Profiles of Normal Cognition in Essential Tremor

Abstract

Objectives:Patients with essential tremor exhibit heterogeneous cognitive functioning. Although the majority of patients fall under the broad classification of cognitively “normal,” essential tremor is associated with increased risk for mild cognitive impairment and dementia. It is possible that patterns of cognitive performance within the wide range of normal functioning have predictive utility for mild cognitive impairment or dementia. These cross-sectional analyses sought to determine whether cognitive patterns, or “clusters,” could be identified among individuals with essential tremor diagnosed as cognitively normal. We also determined whether such clusters, if identified, were associated with demographic or clinical characteristics of patients.Methods:Elderly subjects with essential tremor (age >55 years) underwent comprehensive neuropsychological testing. Domain means (memory, executive function, attention, visuospatial abilities, and language) from 148 individuals diagnosed as cognitively normal were partitioned using k-means cluster analysis. Individuals in each cluster were compared according to cognitive functioning (domain means and test scores), demographic factors, and clinical variables.Results:There were three clusters. Cluster 1 (n = 64) was characterized by comparatively low memory scores (p < .001), Cluster 2 (n = 39) had relatively low attention and visuospatial scores (p < .001), and Cluster 3 (n = 45) exhibited consistently high performance across all domains. Cluster 1 had lower Montreal Cognitive Assessment scores and reported more prescription medication use and lower balance confidence.Conclusions:Three patterns of cognitive functioning within the normal range were evident and tracked with certain clinical features. Future work will examine the extent to which such patterns predict conversion to mild cognitive impairment and/or dementia.

Prospective Longitudinal Study of Gait and Balance in a Cohort of Elderly Essential Tremor Patients

“…The neuropsychological evaluation at each assessment comprised a comprehensive in-person cognitive test battery in each participant's home, a telephone interview with an informant (a close family member or friend of the participant), and subjective written summaries from the trained research associates summarizing qualitative observations regarding cognitive and functional abilities for each participant. The cognitive test battery excluded tests whose scores relied on the accuracy of motor responses so as not to disadvantage participants with more severe tremor ( 31 , 32 ). The battery included two global cognitive screening measures [Mini-Mental State Examination (MMSE) ( 41 ) and Montreal Cognitive Assessment (MoCA) ( 42 )] as well as multiple tests per cognitive domain as follows: attention [Wechsler Adult Intelligence Scale (WAIS) Digit Span subtest ( 43 ) and Symbol-Digit Modalities test ( 44 )], executive function [Delis-Kaplan Executive Function System (D-KEFS) ( 45 ) Verbal Fluency, Color-Word Interference, Sorting, and Twenty Questions], language [Boston Naming test ( 46 ) and the Multilingual Aphasia Examination Token subtest ( 47 )], memory [California Verbal Learning Test – II ( 48 ), Wechsler Memory Scale (WMS) Verbal Paired Associates ( 49 ), and WMS Logical Memory subtest A ( 50 )], and visuospatial function [Judgement of Line Orientation ( 51 ), Benton Facial Recognition ( 52 ), and WAIS Visual Puzzles subtest ( 50 )].…”

“…During case conferences with collaborating expert neuropsychologists and neuropsychiatrists (E.D.H., S.C.), the neuropsychological evaluations were used to classify participants into cognitive groups ( 31 , 32 , 53 ). Classifications were assigned based on results from the clinical questionnaire, neuropsychological test battery, informant interview, and research associate impressions.…”

“…Participants were also assigned one of three primary cognitive diagnoses: normal cognition, mild cognitive impairment (MCI), or dementia. The criteria for assigning these three cognitive diagnoses has been described previously ( 31 ). Normal cognition included: No impairment (CDR 0, no impairment on any test); Impairment of unlikely clinical significance (CDR 0, impairment on 1 test); Impairment of possible clinical significance (CDR 0 or 0.5, impairment on ≥ 1 test but not meeting operational criteria for MCI); Questionable or isolated functional impairment (CDR 0.5, no impairment on any test).…”

“…The study, which began in July 2014, recruited participants through the International Essential Tremor Foundation (IETF) as well as other study websites. As described previously (31,32), participants who met the following eligibility criteria were recruited: (1) diagnosis of ET, (2) minimum age of 55 years, (3) no brain surgery for the treatment of ET, (4) willingness to participate in testing and enroll as a brain donor. All portions of the study were approved by the Yale University and Columbia University Internal Review Boards and all participants signed informed consent upon enrollment.…”

“…The neuropsychological evaluation at each assessment comprised a comprehensive in-person cognitive test battery in each participant's home, a telephone interview with an informant (a close family member or friend of the participant), and subjective written summaries from the trained research associates summarizing qualitative observations regarding cognitive and functional abilities for each participant. The cognitive test battery excluded tests whose scores relied on the accuracy of motor responses so as not to disadvantage participants with more severe tremor (31,32 (52), and WAIS Visual Puzzles subtest (50)]. Aggregate scores for each cognitive domain were calculated as an average of the z-scores for each test.…”