Abstract
Multi-domain cognitive impairment (CI) has been frequently described in patients with essential tremor (ET). However, the exact neuroanatomical basis for this impairment is uncertain. This study aims to ascertain the role of the hippocampal formation in cognitive impairment in ET. Forty patients with ET and 40 age, gender and education matched healthy controls (HC) were enrolled. Cognition was assessed using a structured neuropsychological battery and patients were categorized as ET with CI (ETCI) and ET without CI (ETNCI). Automatic segmentation of hippocampal subfields was performed using FreeSurfer 6.0. The obtained volumes were correlated with scores of neuropsychological tests. Significant atrophy of the left subiculum, CA4, granule-cell layer of dentate gyrus, right molecular layer, and hypertrophy of bilateral parasubiculum, right hippocampus-amygdala-transition-area, bilateral hippocampal tail (HT) and widening of right hippocampal fissure was observed in ET. Trends toward atrophy of right subiculum, and widening of left HF was also observed. Comparison of HC and ETCI revealed atrophy of right subiculum, hypertrophy of bilateral parasubiculum, HT, and widening of left HF. ETCI showed a trend toward widening of right HF. ETNCI had isolated left parasubicular hypertrophy and in comparison, to ETNCI the ETCI subgroup had atrophy of bilateral fimbria. Significant correlations were observed between the volumes of HT, HF, fimbria and scores of tests for executive function, working and verbal memory. Patients with ET have significant volumetric abnormalities of several hippocampal subfields and these abnormalities may be important contributors for some forms of cognitive impairment observed in ET.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Bastos-Leite AJ, van Waesberghe JH, Oen AL, van der Flier WM, Scheltens P, Barkhof F (2006) Hippocampal sulcus width and cavities: comparison between patients with Alzheimer disease and nondemented elderly subjects. AJNR Am J Neuroradiol 27:2141–2145
Benito-Leon J, Labiano-Fontcuberta A (2016) Linking essential tremor to the cerebellum. Clin Evid Cereb 15:253–262. https://doi.org/10.1007/s12311-015-0741-1
Benito-Leon J, Louis ED, Bermejo-Pareja F, Neurological Disorders in Central Spain Study G (2006) Population-based case–control study of cognitive function in essential tremor. Neurology 66:69–74. https://doi.org/10.1212/01.wnl.0000192393.05850.ec
Benito-Leon J et al (2017) White matter microstructural changes are related to cognitive dysfunction in essential tremor. Sci Rep 7:2978. https://doi.org/10.1038/s41598-017-02596-1
Bermejo-Pareja F (2011) Essential tremor—a neurodegenerative disorder associated with cognitive defects? Nat Rev Neurol 7:273–282. https://doi.org/10.1038/nrneurol.2011.44
Bermejo-Pareja F, Louis ED, Benito-Leon J, Neurological Disorders in Central Spain Study G (2007) Risk of incident dementia in essential tremor: a population-based study. Mov Disord 22:1573–1580. https://doi.org/10.1002/mds.21553
Bhalsing KS, Upadhyay N, Kumar KJ, Saini J, Yadav R, Gupta AK, Pal PK (2014) Association between cortical volume loss and cognitive impairments in essential tremor. Eur J Neurol 21:874–883. https://doi.org/10.1111/ene.12399
Bhalsing KS, Kumar KJ, Saini J, Yadav R, Gupta AK, Pal PK (2015) White matter correlates of cognitive impairment in essential tremor. AJNR Am J Neuroradiol 36:448–453. https://doi.org/10.3174/ajnr.A4138
Chandran V, Pal PK (2012) Essential tremor: beyond the motor features. Parkinsonism Relat Disord 18:407–413. https://doi.org/10.1016/j.parkreldis.2011.12.003
Dalton MA, Maguire EA (2017) The pre/parasubiculum: a hippocampal hub for scene-based cognition? Curr Opin Behav Sci 17:34–40. https://doi.org/10.1016/j.cobeha.2017.06.001
Daniels C et al (2006) Voxel-based morphometry shows no decreases in cerebellar gray matter volume in essential tremor. Neurology 67:1452–1456. https://doi.org/10.1212/01.wnl.0000240130.94408.99
Deuschl G, Elble R (2009) Essential tremor—neurodegenerative or nondegenerative disease towards a working definition of ET. Mov Disord 24:2033–2041. https://doi.org/10.1002/mds.22755
Deuschl G, Bain P, Brin M (1998) Consensus statement of the movement disorder society on tremor. Ad Hoc Sci Committee Mov Disord 13(Suppl 3):2–23
Draganski B, Gaser C, Busch V, Schuierer G, Bogdahn U, May A (2004) Neuroplasticity: changes in grey matter induced by training. Nature 427:311–312. https://doi.org/10.1038/427311a
Duane DD, Vermilion KJ (2002) Cognitive deficits in patients with essential tremor. Neurology 58:1706 (author reply 1706)
Duvernoy HM (2005) The human hippocampus functional anatomy, vascularization and serial sections with MRI, 3rd edn. Springer, Berlin
Duvernoy H, Cattin F, Risold P-Y (2013) Structure, functions, and connections. In: The human hippocampus. Springer, pp 5–38
Fahn S, Tolosa E, Marín C (1993) Clinical rating scale for tremor Parkinson’s disease and movement disorders. Williams and Wilkins, Baltimore, pp 271–280
Fang W et al (2015) Multiple resting-state networks are associated with tremors and cognitive features in essential tremor. Mov Disord 30:1926–1936. https://doi.org/10.1002/mds.26375
Farrell K et al (2019) Quantitative assessment of pathological tau burden in essential tremor: a postmortem study. J Neuropathol Exp Neurol 78:31–37. https://doi.org/10.1093/jnen/nly104
Fischl B (2012) FreeSurfer. Neuroimage 62:774–781
Gasparini M, Bonifati V, Fabrizio E, Fabbrini G, Brusa L, Lenzi GL, Meco G (2001) Frontal lobe dysfunction in essential tremor: a preliminary study. J Neurol 248:399–402
Higginson CI, Wheelock VL, Levine D, King DS, Pappas CT, Sigvardt KA (2008) Cognitive deficits in essential tremor consistent with frontosubcortical dysfunction. J Clin Exp Neuropsychol 30:760–765. https://doi.org/10.1080/13803390701754738
Iglesias JE et al (2015) A computational atlas of the hippocampal formation using ex vivo, ultra-high resolution MRI: application to adaptive segmentation of in vivo. MRI Neuroimage 115:117–137. https://doi.org/10.1016/j.neuroimage.2015.04.042
Janicki SC, Cosentino S, Louis ED (2013) The cognitive side of essential tremor: what are the therapeutic implications? Ther Adv Neurol Disord 6:353–368. https://doi.org/10.1177/1756285613489591
Kim JS, Song IU, Shim YS, Park JW, Yoo JY, Kim YI, Lee KS (2009) Cognitive impairment in essential tremor without dementia. J Clin Neurol 5:81–84. https://doi.org/10.3988/jcn.2009.5.2.81
La Joie R et al (2013) Hippocampal subfield volumetry in mild cognitive impairment. Alzheimer’s Dis Semant Dement Neuroimage Clin 3:155–162. https://doi.org/10.1016/j.nicl.2013.08.007
Lacritz LH, Dewey R Jr, Giller C, Cullum CM (2002) Cognitive functioning in individuals with “benign” essential tremor. J Int Neuropsychol Soc 8:125–129
Lenka A et al (2018) Hippocampal subfield atrophy in patients with Parkinson’s disease and psychosis. J Neural Transm (Vienna) 125:1361–1372. https://doi.org/10.1007/s00702-018-1891-3
Li X, Li D, Li Q, Li Y, Li K, Li S, Han Y (2016) Hippocampal subfield volumetry in patients with subcortical vascular mild cognitive impairment. Sci Rep 6:20873. https://doi.org/10.1038/srep20873
Li Y, Yan J, Zhu X, Zhu Y, Qin J, Zhang N, Ju S (2018) Increased hippocampal fissure width is a sensitive indicator of rat hippocampal atrophy. Brain Res Bull 137:91–97. https://doi.org/10.1016/j.brainresbull.2017.11.014
Lombardi WJ, Woolston DJ, Roberts JW, Gross RE (2001) Cognitive deficits in patients with. essential tremor. Neurology 57:785–790
Louis ED (2016) Non-motor symptoms in essential tremor: a review of the current data and state of the field. Parkinsonism Relat Disord 22(Suppl 1):S115-118 https://doi.org/10.1016/j.parkreldis.2015.08.034
Manto M, Marien P (2015) Schmahmann’s syndrome—identification of the third cornerstone of clinical ataxiology. Cereb Ataxias 2:2. https://doi.org/10.1186/s40673-015-0023-1
Mueller SG, Chao LL, Berman B, Weiner MW (2011) Evidence for functional specialization of hippocampal subfields detected by MR subfield volumetry on high resolution images at 4 T. Neuroimage 56:851–857. https://doi.org/10.1016/j.neuroimage.2011.03.028
Pan JJ, Lee M, Honig LS, Vonsattel JP, Faust PL, Louis ED (2014) Alzheimer’s-related changes in non-demented essential tremor patients vs. controls: links between tau and tremor? Parkinsonism Relat Disord 20:655–658. https://doi.org/10.1016/j.parkreldis.2014.03.003
Prasad S et al (2018a) DTI in essential tremor with and without rest tremor: two sides of the same coin? Mov Disord. https://doi.org/10.1002/mds.27459
Prasad S, Velayutham SG, Reddam VR, Stezin A, Jhunjhunwala K, Pal PK (2018b) Shaky and unsteady: dynamic posturography in essential tremor. J Neurol Sci 385:12–16
Sahin HA, Terzi M, Ucak S, Yapici O, Basoglu T, Onar M (2006) Frontal functions in young patients with essential tremor: a case comparison study. J Neuropsychiatry Clin Neurosci 18:64–72. https://doi.org/10.1176/jnp.18.1.64
Thawani SP, Schupf N, Louis ED (2009) Essential tremor is associated with dementia: prospective population-based study in New York. Neurology 73:621–625. https://doi.org/10.1212/WNL.0b013e3181b389f1
Troster AI, Woods SP, Fields JA, Lyons KE, Pahwa R, Higginson CI, Koller WC (2002) Neuropsychological deficits in essential tremor: an expression of cerebello-thalamo-cortical pathophysiology? Eur J Neurol 9:143–151
Wicking M, Nees F, Steiger F (2014) Neuropsychological measures of hippocampal function. Front Neurol Neurosci 34:60–70. https://doi.org/10.1159/000356425
Yuan P, Raz N (2014) Prefrontal cortex and executive functions in healthy adults: a meta-analysis of structural neuroimaging studies. Neurosci Biobehav Rev 42:180–192. https://doi.org/10.1016/j.neubiorev.2014.02.005
Funding
Symbiosis International University has received partial support from DST SERB (ECR/2016/000808) for setting up the computing facility.
Author information
Authors and Affiliations
Contributions
Research Project: conception: SP, JS, MI, PKP, organization: SP, KSB, KJK, JS, PKP, execution: SP, AS, KSB, MI, PKP. Statistical analysis: design: SP, AS, KSB, JS, MI, execution: SP, AS, KSB, MI, review and critique: AS, KSB, KJK, JS, MI, PKP. Manuscript: writing of the first draft: SP, review and critique: AS, KSB, KJK, JS, MI, PKP.
Corresponding author
Ethics declarations
Conflict of interest
None of the authors have any financial disclosure to make or have any conflict of interest.
Additional information
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Prasad, S., Shah, A., Bhalsing, K.S. et al. Abnormal hippocampal subfields are associated with cognitive impairment in Essential Tremor. J Neural Transm 126, 597–606 (2019). https://doi.org/10.1007/s00702-019-01992-3
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00702-019-01992-3