Cognitive subtypes in individuals with essential tremor seeking deep brain stimulation

Abstract

Objective: Essential tremor (ET) is a common neurological disorder that has been associated with 60% increased risk of developing dementia. The goals of the present study were to: (a) learn whether individuals with advanced ET symptoms seeking deep brain stimulation (DBS) surgery would fall into distinct cognitive subgroups, and (b) learn how empirically derived subgroups map onto criteria for mild cognitive impairment (MCI). Method: Patients with ET (N = 201; mean age = 68.9 ± 8.9 years) undergoing pre-surgical evaluation for DBS completed a multi-domain neurocognitive assessment consisting of memory, executive function, visuospatial skill, language, and processing speed. Two cluster analytic approaches (K-means, hierarchical) were independently conducted to classify cognitive patterns using domain composites. Demographics, clinical characteristics, and proportion of cases meeting neuropsychologically defined criteria for MCI were examined among clusters. Results: A three-cluster solution reflected a Low Executive group (N = 64), Low Memory Multi-Domain group (N = 41), and Cognitively Normal group (N = 96). The Cognitively Normal group was older and more educated, with a higher Dementia Rating Scale-2 score. In total, 27.4% of participants met criteria for MCI. Of the MCI cases, most were in the Low Executive (41.8%) or Low Memory Multi-Domain groups (49.1%). In the latter, 65.9% of its members were classified as MCI versus 35.9% in the Low Executive group. Conclusions: Our study identified three cognitive subtypes of ET patients presenting for DBS. Future work should examine the subgroups for progression to dementia, particularly the Low Memory Multi-Domain subgroup which may be at highest risk.

Keywords:

• Essential tremor
• cognition
• deep brain stimulation
• cluster analysis
• mild cognitive impairment

Disclosure statement

DB has received research grants, as PI or MPI, from the NIH (NINDS, NIMH, NIA), Parkinson’s Foundation, the McKnight Research Foundation, and the UF Foundation. MSO serves as a consultant for the Parkinson’s Foundation, and has received research grants from NIH, Parkinson’s Foundation, the Michael J. Fox Foundation, the Parkinson Alliance, Smallwood Foundation, the Bachmann-Strauss Foundation, the Tourette Syndrome Association, and the UF Foundation. MSO has received royalties for publications with Demos, Manson, Amazon, Smashwords, Books4Patients, Perseus, Robert Rose, Oxford and Cambridge (movement disorders books). MSO is an associate editor for New England Journal of Medicine Journal Watch Neurology. MSO has participated in CME and educational activities on movement disorders sponsored by the Academy for Healthcare Learning, PeerView, Prime, QuantiaMD, WebMD/Medscape, Medicus, MedNet, Einstein, MedNet, Henry Stewart, American Academy of Neurology, Movement Disorders Society and by Vanderbilt University. The institution and not MSO receives grants from Medtronic, Abbvie, Boston Scientific, Abbott and Allergan and the PI has no financial interest in these grants. MSO has participated as a site PI and/or co-I for several NIH, foundation, and industry sponsored trials over the years but has not received honoraria. Research projects at the University of Florida receive device and drug donations. KDF reports grants from NIH, and other funding from Donnellan/Einstein/Merz Chair; grants and non-financial support from Medtronic, grants from St Jude, Functional Neuromodulation, and Boston Scientific, and grants and other funding from Neuropace. Additionally, KDF has a patent US 8295935 B2 issued for a DBS cranial lead fixation device. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Notes

1 Cersonsky et al. (2020) included the following cognitive domains and measures: (1) Memory: California Verbal Learning Test II; Wechsler Memory Scale Revised: Logical Memory; Wechsler Memory Scale-IV: Verbal Paired Associates; (2) Executive Function: Wechsler Adult Intelligence Scale-IV: Digit Span Backward; Delis–Kaplan Executive Function System: Verbal Fluency Test, Color-Word Interference, Sorting, 20-Questions; (3) Attention: Oral Symbol-Digit Modalities Test; Wechsler Adult Intelligence Scale-IV: Digit Span Forward; (4) Visuospatial Abilities: Benton Judgment of Line Orientation; Benton Facial Recognition Test; Wechsler Adult Intelligence Scale-IV: Visual Puzzles; (5) Language: Multilingual Aphasia Examination: Token Test; Boston Naming Test.

Additional information

Funding

This work was supported in part by the NINDS under Grant T32-NS082168 (AR, FL, LK, DB) and by the University of Florida Movement Disorders Program of the Norman Fixel Institute for Neurological Diseases.