Skip to main content

Advertisement

SpringerLink
Log in

Cognitive functioning in essential tremor without dementia: a clinical and imaging study

  • Original Article
  • Published:
Neurological Sciences Aims and scope Submit manuscript

Abstract

Background and aims

To explore the cognitive functioning of ET patients without dementia and delineate its imaging counterpart.

Methods

We enrolled 99 subjects (49 non-demented ET patients and 50 education-matched healthy controls) that underwent neuropsychological and MRI evaluation. In order to identify the cognitive parameters that better reflect the profile of ET patients, we used a double statistical approach: (i) direct comparison between groups and (ii) machine learning approach with feature selection. Then, to evaluate the correlation between cognitive performances and the degree of brain atrophy in the ET group, we included the results derived from the uni- and multivariate analysis in whole-brain voxel-based morphometry (VBM) model.

Results

In ET patients, the univariate analysis showed differences in cognitive tests evaluating executive functions (FAB, MCST-CA), verbal memory-delayed recall (RAVLT-DR), and working memory (Digit Span B). The relative scores were significantly worse compared to controls, although within the normal range (subclinical dysfunctions). The machine learning approach also provided similar findings: tests exploring the executive functions, verbal memory, and language (RAVLT-DR, FAB, COWAT, RAVLT-IR, TOKEN) showed the highest importance rank in classification’s task. Regardless of the explored test, the MRI analysis revealed a correlation (p < 0.005 uncorrected, whole brain) between test scores and widespread areas including cerebellum, inferior and middle frontal cortices, cingulate cortices, and temporal cortex.

Conclusion

This study improves the knowledge on cognitive impairment in ET, as our findings demonstrate a heterogeneous pattern of cognitive dysfunction involving memory, executive function, and language domains in the ET group. This clinical profile relates with the deep involvement of the cerebellum and its connections with large-scale brain structures, suggesting that changes spreading in wide-ranging brain pathways may contribute to the physiopathology of cognitive dysfunction in ET.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Benito-León J, Louis ED, Mitchell AJ, Bermejo-Pareja F (2011) Elderly-onset essential tremor and mild cognitive impairment: a population-based study (NEDICES). J Alzheimer’s Dis 23(4):727–735

    Article  Google Scholar 

  2. Bermejo-Pareja F, Louis ED, Benito-León J (2007) Risk of incident dementia in essential tremor: a population-based study. Mov Dis: Off J Mov Disord Soc 22(11):1573–1580

    Article  Google Scholar 

  3. Thawani SP, Schupf N, Louis ED (2009) Essential tremor is associated with dementia: prospective population-based study in New York. Neurology 73(8):621–625

    Article  Google Scholar 

  4. Louis ED (2016) Non-motor symptoms in essential tremor: a review of the current data and state of the field. Parkinsonism Relat Disord 22:S115–S118

    Article  Google Scholar 

  5. Jhunjhunwala K, Pal PK (2014) The non-motor features of essential tremor: a primary disease feature or just a secondary phenomenon? Tremor and other hyperkinetic movements 4.

  6. Chandran V, Pal PK (2012) Essential tremor: beyond the motor features. Parkinsonism Relat Disord 18(5):407–413

    Article  Google Scholar 

  7. Sengul Y, Sengul HS, Yucekaya SK, Yucel S, Bakim B, Pazarcı NK et al (2015) Cognitive functions, fatigue, depression, anxiety, and sleep disturbances: assessment of nonmotor features in young patients with essential tremor. Acta Neurol Belg 115(3):281–287

    Article  Google Scholar 

  8. Benito-León J, Louis ED, Bermejo-Pareja F (2006) Elderly-onset essential tremor is associated with dementia. Neurology 66(10):1500–1505

    Article  Google Scholar 

  9. Gasparini M, Bonifati V, Fabrizio E, Fabbrini G, Brusa L, Lenzi GL et al (2001) Frontal lobe dysfunction in essential tremor. J Neurol 248(5):399–402

    Article  CAS  Google Scholar 

  10. Louis ED, Joyce JL, Cosentino S (2019) Mind the gaps: what we don’t know about cognitive impairment in essential tremor. Parkinsonism Relat Disord 63:10–19

    Article  Google Scholar 

  11. Schmahmann JD, Sherman JC (1998) The cerebellar cognitive affective syndrome. Brain J Neurol 121(4):561–79

    Article  Google Scholar 

  12. Tröster AI, Woods SP, Fields JA, Lyons KE, Pahwa R, Higginson CI et al (2002) Neuropsychological deficits in essential tremor: an expression of cerebello-thalamo-cortical pathophysiology? Eur J Neurol 9(2):143–151

    Article  Google Scholar 

  13. Novellino F, Vasta R, Sacca V, Nistico R, Morelli M, Arabia G, et al (2020) Hippocampal impairment in patients with essential tremor: hippocampal changes in ET

  14. Prasad S, Shah A, Bhalsing KS, Kumar KJ, Saini J, Ingalhalikar M et al (2019) Abnormal hippocampal subfields are associated with cognitive impairment in essential tremor. J Neural Transm 126(5):597–606

    Article  Google Scholar 

  15. Saccà V, Sarica A, Novellino F, Barone S, Tallarico T, Filippelli E et al (2019) Evaluation of machine learning algorithms performance for the prediction of early multiple sclerosis from resting-state FMRI connectivity data. Brain Imaging Behav 13(4):1103–1114

    Article  Google Scholar 

  16. Rajagopalan V, Pioro EP (2015) Disparate voxel based morphometry (VBM) results between SPM and FSL softwares in ALS patients with frontotemporal dementia: which VBM results to consider? BMC Neurol 15(1):1–7

    Article  Google Scholar 

  17. Deuschl G, Bain P, Brin M, Committee AHS (1998) Consensus statement of the movement disorder society on tremor. Mov Disord 13(S3):2–23

    Article  Google Scholar 

  18. Novellino F, Bagnato A, Salsone M, Cascini GL, Nicoletti G, Arabia G et al (2010) Myocardial 123I-MIBG scintigraphy for differentiation of Lewy bodies disease from FTD. Neurobiol Aging 31(11):1903–1911

    Article  Google Scholar 

  19. Association AP, Association AP (2013) Diagnostic and statistical manual of mental disorders: DSM-5. Arlington, VA

  20. Dubois B, Feldman HH, Jacova C, DeKosky ST, Barberger-Gateau P, Cummings J et al (2007) Research criteria for the diagnosis of Alzheimer’s disease: revising the NINCDS–ADRDA criteria. Lancet Neurol 6(8):734–746

    Article  Google Scholar 

  21. Fahn S, Tolosa E, Marín C (1993) Clinical rating scale for tremor. Parkinson’s Dis Mov Disord 2:271–280

    Google Scholar 

  22. Team RC (2000) R language definition. Vienna, Austria: R foundation for statistical computing

  23. Lombardi WJ, Woolston DJ, Roberts JW, Gross RE (2001) Cognitive deficits in patients with essential tremor. Neurology 57(5):785–790

    Article  CAS  Google Scholar 

  24. Benito-León J, Louis ED, Bermejo-Pareja F (2006) Population-based case-control study of cognitive function in essential tremor. Neurology 66(1):69–74

    Article  Google Scholar 

  25. Cersonsky TEK, Kellner S, Chapman S, Huey ED, Louis ED, Cosentino S (2020) Profiles of normal cognition in essential tremor. J Int Neuropsychol Soc 26(2):197–209

    Article  Google Scholar 

  26. Tuokko H, Vernon-Wilkinson R, Weir J, Beattie BL (1991) Cued recall and early identification of dementia. J Clin Exp Neuropsychol 13(6):871–879

    Article  CAS  Google Scholar 

  27. Schoenberg MR, Dawson KA, Duff K, Patton D, Scott JG, Adams RL (2006) Test performance and classification statistics for the Rey Auditory Verbal Learning Test in selected clinical samples. Arch Clin Neuropsychol 21(7):693–703

    Article  Google Scholar 

  28. Estévez-González A, Kulisevsky J, Boltes A, Otermín P, García-Sánchez C (2003) Rey verbal learning test is a useful tool for differential diagnosis in the preclinical phase of Alzheimer’s disease: comparison with mild cognitive impairment and normal aging. Int J Geriatr Psychiatry 18(11):1021–1028

    Article  Google Scholar 

  29. Moradi E, Hallikainen I, Hänninen T, Tohka J (2017) Initiative ADN. Rey’s Auditory Verbal Learning Test scores can be predicted from whole brain MRI in Alzheimer’s disease. NeuroImage Clin 13:415–27

    Article  Google Scholar 

  30. Russo MJ, Campos J, Vázquez S, Sevlever G, Allegri RF, Weiner MW et al (2017) Adding recognition discriminability index to the delayed recall is useful to predict conversion from mild cognitive impairment to Alzheimer’s disease in the Alzheimer’s disease neuroimaging initiative. Front Aging Neurosci 9:46

    Article  Google Scholar 

  31. Argyropoulos GPD, van Dun K, Adamaszek M, Leggio M, Manto M, Masciullo M et al (2020) The cerebellar cognitive affective/Schmahmann syndrome: a task force paper. The Cerebellum 19(1):102–125

    Article  CAS  Google Scholar 

  32. Stoodley CJ, Schmahmann JD (2010) Evidence for topographic organization in the cerebellum of motor control versus cognitive and affective processing. Cortex 46(7):831–44

    Article  Google Scholar 

  33. Habas C, Kamdar N, Nguyen D, Prater K, Beckmann CF, Menon V et al (2009) Distinct cerebellar contributions to intrinsic connectivity networks. J Neurosci 29(26):8586–8594

    Article  CAS  Google Scholar 

  34. Krienen FM, Buckner RL (2009) Segregated fronto-cerebellar circuits revealed by intrinsic functional connectivity. Cereb Cortex 19(10):2485–2497

    Article  Google Scholar 

  35. Dosenbach NUF, Fair DA, Cohen AL, Schlaggar BL, Petersen SE (2008) A dual-networks architecture of top-down control. Trends Cogn Sci 12(3):99–105

    Article  Google Scholar 

  36. Quattrone A, Cerasa A, Messina D, Nicoletti G, Hagberg GE, Lemieux L et al (2008) Essential head tremor is associated with cerebellar vermis atrophy: a volumetric and voxel-based morphometry MR imaging study. Am J Neuroradiol 29(9):1692–1697

    Article  CAS  Google Scholar 

  37. Cerasa A, Messina D, Nicoletti G, Novellino F, Lanza P, Condino F et al (2009) Cerebellar atrophy in essential tremor using an automated segmentation method. Am J Neuroradiol 30(6):1240–1243

    Article  CAS  Google Scholar 

  38. Novellino F, Nicoletti G, Cherubini A, Caligiuri ME, Nistico R, Salsone M et al (2016) Cerebellar involvement in essential tremor with and without resting tremor: a diffusion tensor imaging study. Parkinsonism Relat Disord 27:61–66

    Article  Google Scholar 

  39. Jia L, Jia-lin S, Qin D, Qing L, Yan Z (2011) A diffusion tensor imaging study in essential tremor. J Neuroimaging 21(4):370–374

    Article  Google Scholar 

  40. Nicoletti G, Manners D, Novellino F, Condino F, Malucelli E, Barbiroli B et al (2010) Diffusion tensor MRI changes in cerebellar structures of patients with familial essential tremor. Neurology 74(12):988–994

    Article  CAS  Google Scholar 

Download references

Author information

Author notes

  1. Fabiana Novellino and Valeria Saccà contributed equally to this work.

Authors and Affiliations

  1. Neuroimaging Research Unit, Institute of Molecular Bioimaging and Physiology, National Research Council, Catanzaro, Italy

    Fabiana Novellino, Maria Salsone, Giuseppe Nicoletti & Aldo Quattrone

  2. Department of Pharmacology and Toxicology, School of Medicine, Universidad Complutense de Madrid (UCM), Av. Complutense s/n, 28040, Madrid, Spain

    Fabiana Novellino & José L. M. Madrigal

  3. Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain

    Fabiana Novellino & José L. M. Madrigal

  4. Instituto de Investigación Neuroquímica (IUINQ-UCM), Madrid, Spain

    Fabiana Novellino & José L. M. Madrigal

  5. Instituto de Investigación Sanitaria Hospital, 12 de Octubre (Imas12), Madrid, Spain

    Fabiana Novellino & José L. M. Madrigal

  6. Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, 02129, USA

    Valeria Saccà

  7. Institute of Neurology, University “Magna Graecia, Catanzaro, Italy

    Andrea Quattrone & Carmelina Chiriaco

  8. Neuroscience Center, Magna Graecia University, Catanzaro, Italy

    Aldo Quattrone

  9. Institute of Molecular Bioimaging and Physiology, National Research Council, Milan, Italy

    Maria Salsone

  10. Sleep Disorders Center, Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy

    Maria Salsone

Authors
  1. Fabiana Novellino
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Valeria Saccà
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Maria Salsone
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Giuseppe Nicoletti
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Andrea Quattrone
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Carmelina Chiriaco
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. José L. M. Madrigal
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Aldo Quattrone
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Fabiana Novellino or Aldo Quattrone.

Ethics declarations

Conflict of interests

The authors declare no competing interests.

Ethical approval

This study was performed in line with the principles of the Declaration of Helsinki. All study procedures and ethical aspects were approved by the institutional review board of Magna Graecia University, Catanzaro, Italy.

Consent to participate

Written informed consent was obtained from each participant included in the study.

Additional information

Publisher's note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Valeria Saccà performed the statistical analysis.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 824 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Novellino, F., Saccà, V., Salsone, M. et al. Cognitive functioning in essential tremor without dementia: a clinical and imaging study. Neurol Sci 43, 4811–4820 (2022). https://doi.org/10.1007/s10072-022-06045-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10072-022-06045-4

Keywords

Search

Navigation