View in EDS

Uncovering Cognitive Subtypes in Essential Tremor: A Data-Driven Clustering Approach in Cognitively Normal Individuals.

Saved in:
Bibliographic Details
Title: Uncovering Cognitive Subtypes in Essential Tremor: A Data-Driven Clustering Approach in Cognitively Normal Individuals.
Authors: Sarica A; Neuroscience Research Center, University 'Magna Graecia', Catanzaro, Italy.; Department of Medical and Surgical Sciences, University 'Magna Graecia', Catanzaro, Italy., Calomino C; Neuroscience Research Center, University 'Magna Graecia', Catanzaro, Italy.; Department of Medical and Surgical Sciences, University 'Magna Graecia', Catanzaro, Italy., Nisticò R; Neuroscience Research Center, University 'Magna Graecia', Catanzaro, Italy.; Department of Medical and Surgical Sciences, University 'Magna Graecia', Catanzaro, Italy., Salsone M; Vita-Salute San Raffaele University, 20132 Milan, Italy.; IRCCS Policlinico San Donato, San Donato Milanese, 20097 Italy., Quattrone A; Neuroscience Research Center, University 'Magna Graecia', Catanzaro, Italy.; Institute of Neurology, Department of Medical and Surgical Sciences, Magna Graecia University, Catanzaro, Italy., Quattrone A; Neuroscience Research Center, University 'Magna Graecia', Catanzaro, Italy., Novellino F; Neuroscience Research Center, University 'Magna Graecia', Catanzaro, Italy.; Department of Medical and Surgical Sciences, University 'Magna Graecia', Catanzaro, Italy.
Source: Tremor and other hyperkinetic movements (New York, N.Y.) [Tremor Other Hyperkinet Mov (N Y)] 2025 Nov 05; Vol. 15, pp. 54. Date of Electronic Publication: 2025 Nov 05 (Print Publication: 2025).
Publication Type: Journal Article
Language: English
Journal Info: Publisher: Ubiquity Press Country of Publication: England NLM ID: 101569493 Publication Model: eCollection Cited Medium: Internet ISSN: 2160-8288 (Electronic) Linking ISSN: 21608288 NLM ISO Abbreviation: Tremor Other Hyperkinet Mov (N Y) Subsets: MEDLINE
Imprint Name(s): Publication: 2020- : East London Works, UK : Ubiquity Press
Original Publication: New York : Center for Digital Research and Scholarship
MeSH Terms: Essential Tremor*/physiopathology , Essential Tremor*/complications , Essential Tremor*/psychology , Cognition*/physiology , Cognitive Dysfunction*/physiopathology, Humans ; Male ; Female ; Middle Aged ; Cluster Analysis ; Aged ; Neuropsychological Tests ; Executive Function/physiology ; Attention/physiology ; Adult
Abstract: Competing Interests: The authors have no competing interests to declare.
Background: Different profiles of cognitive functioning have been demonstrated in ET subjects, also in patients with normal cognition. However, the prognostic significance of these profiles remains still debated. In this study, we aimed to explore different cognitive patterns among cognitively normal ET subjects and their relationship with the cognitive profiles of healthy subjects.
Methods: We enrolled 50 cognitively normal subjects (26 ET and 24 age-, sex-, and education-matched healthy subjects), which scored within normal ranges individually in all tests of a comprehensive neuropsychological battery covering memory, executive function, attention, visuospatial abilities, and language. Unsupervised clustering was applied separately within each group. Cluster membership was validated by post-hoc comparisons using ANOVA and Bonferroni-corrected pairwise tests to compare the variables among the clusters.
Results: All HC clustered together into a single high-functioning cognitive profile. On the contrary, we found two different clusters within ET, C1 (n = 14), showing high performance across all domains, and C2 (n = 12) which exhibited significantly poorer performances in the RAVLT-IR (p < 0.0001), RAVLT-DR (p = 0.0002), and Digit Span Forward (p = 0.015) than both ET-C1 and HC subjects. Other domains showed no significant differences across ET clusters.
Discussion: This study demonstrates a cognitive heterogeneity in ET and reveals a memory-impaired subgroup absent among HC. The ET cluster with lower memory performance likely reflects a pattern of vulnerability for longitudinal decline or progression to mild cognitive impairment. The identification of this profile has relevant translational implications for prognosis and identification of early intervention strategies.
Highlights: A data-driven clustering approach was applied to cognitive variables in HC subjects and ET patients. HC formed a homogeneous cluster. ET were divided into two cognitive subgroups: one cluster with high performance, and one memory-impaired cluster, significantly diverging from both the intact ET subgroup and HC. This may represent a cognitively vulnerable ET subgroup, with strong implications for targeted screening, early neuroprotective interventions and personalized clinical management.
(Copyright: © 2025 The Author(s).)
References: Sci Rep. 2025 Jul 2;15(1):23591. (PMID: 40603516)
Parkinsonism Relat Disord. 2025 Feb;131:107228. (PMID: 39673860)
Exp Neurol. 2017 Nov;297:50-61. (PMID: 28754506)
Neurology. 2009 Aug 25;73(8):621-5. (PMID: 19704081)
Mov Disord. 2007 Aug 15;22(11):1573-80. (PMID: 17516478)
Ital J Neurol Sci. 1987 Dec;Suppl 8:1-120. (PMID: 3330072)
Eur Neurol. 1996;36(6):378-84. (PMID: 8954307)
J Clin Exp Neuropsychol. 2004 Apr;26(2):246-50. (PMID: 15202543)
Mov Disord. 2013 Feb;28(2):196-200. (PMID: 23238868)
Parkinsonism Relat Disord. 2011 Aug;17(7):516-20. (PMID: 21486707)
Br J Med Psychol. 1959;32(1):50-5. (PMID: 13638508)
Arch Neurol. 1978 Jun;35(6):364-7. (PMID: 655909)
Neurol Sci. 2005 Jun;26(2):108-16. (PMID: 15995827)
Ther Adv Neurol Disord. 2013 Nov;6(6):353-68. (PMID: 24228071)
Science. 2007 Feb 16;315(5814):972-6. (PMID: 17218491)
Appl Psychol Health Well Being. 2025 Oct;17(5):e70072. (PMID: 40884072)
J Int Neuropsychol Soc. 2020 Feb;26(2):197-209. (PMID: 31581969)
Parkinsonism Relat Disord. 2020 Mar;72:56-61. (PMID: 32109738)
Tremor Other Hyperkinet Mov (N Y). 2019 Oct 18;9:. (PMID: 31709127)
Clin Park Relat Disord. 2022 Jan 23;6:100134. (PMID: 35146408)
Brain. 2011 Aug;134(Pt 8):2274-86. (PMID: 21747127)
Ann Neurol. 2024 Jun;95(6):1193-1204. (PMID: 38654628)
AJNR Am J Neuroradiol. 2015 Mar;36(3):448-53. (PMID: 25339653)
Cerebellum. 2022 Dec;21(6):1029-1051. (PMID: 34657271)
J Clin Neurol. 2009 Jun;5(2):81-4. (PMID: 19587814)
Clin Neuropsychol. 2022 Oct;36(7):1705-1727. (PMID: 33567972)
J Clin Med. 2025 Feb 11;14(4):. (PMID: 40004695)
Front Neurol. 2023 Aug 18;14:1224478. (PMID: 37662041)
Parkinsonism Relat Disord. 2024 Apr;121:106034. (PMID: 38382401)
Mov Disord. 2010 Apr 15;25(5):534-41. (PMID: 20175185)
Mov Disord. 2018 Jan;33(1):75-87. (PMID: 29193359)
Front Neurol. 2019 Apr 24;10:315. (PMID: 31068885)
Psychol Methods. 2019 Dec;24(6):735-753. (PMID: 31589062)
Neurol Sci. 2022 Aug;43(8):4811-4820. (PMID: 35511382)
Front Neurol. 2022 Mar 17;13:842732. (PMID: 35370922)
J Alzheimers Dis. 2011;23(4):727-35. (PMID: 21304183)
Eur J Neurol. 1996 May;3(3):198-202. (PMID: 21284770)
Contributed Indexing: Keywords: cluster analysis; essential tremor; memory; normal cognition
Entry Date(s): Date Created: 20251110 Date Completed: 20251112 Latest Revision: 20251112
Update Code: 20251113
PubMed Central ID: PMC12594078
DOI: 10.5334/tohm.1090
PMID: 41209541
Database: MEDLINE
Description
Abstract:Competing Interests: The authors have no competing interests to declare.<br />Background: Different profiles of cognitive functioning have been demonstrated in ET subjects, also in patients with normal cognition. However, the prognostic significance of these profiles remains still debated. In this study, we aimed to explore different cognitive patterns among cognitively normal ET subjects and their relationship with the cognitive profiles of healthy subjects.<br />Methods: We enrolled 50 cognitively normal subjects (26 ET and 24 age-, sex-, and education-matched healthy subjects), which scored within normal ranges individually in all tests of a comprehensive neuropsychological battery covering memory, executive function, attention, visuospatial abilities, and language. Unsupervised clustering was applied separately within each group. Cluster membership was validated by post-hoc comparisons using ANOVA and Bonferroni-corrected pairwise tests to compare the variables among the clusters.<br />Results: All HC clustered together into a single high-functioning cognitive profile. On the contrary, we found two different clusters within ET, C1 (n = 14), showing high performance across all domains, and C2 (n = 12) which exhibited significantly poorer performances in the RAVLT-IR (p &lt; 0.0001), RAVLT-DR (p = 0.0002), and Digit Span Forward (p = 0.015) than both ET-C1 and HC subjects. Other domains showed no significant differences across ET clusters.<br />Discussion: This study demonstrates a cognitive heterogeneity in ET and reveals a memory-impaired subgroup absent among HC. The ET cluster with lower memory performance likely reflects a pattern of vulnerability for longitudinal decline or progression to mild cognitive impairment. The identification of this profile has relevant translational implications for prognosis and identification of early intervention strategies.<br />Highlights: A data-driven clustering approach was applied to cognitive variables in HC subjects and ET patients. HC formed a homogeneous cluster. ET were divided into two cognitive subgroups: one cluster with high performance, and one memory-impaired cluster, significantly diverging from both the intact ET subgroup and HC. This may represent a cognitively vulnerable ET subgroup, with strong implications for targeted screening, early neuroprotective interventions and personalized clinical management.<br /> (Copyright: © 2025 The Author(s).)
ISSN:2160-8288
DOI:10.5334/tohm.1090