Parkinsonism and Related Disorders 24 (2016) 143e144

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Parkinsonism and Related Disorders

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Correspondence

Essential tremor is a risk factor for Parkinson's disease

Keywords:
Essential tremor
Parkinson's disease
Epidemiology
Lewy body

We read with interest the paper by Thenganatt and Jankovic [1]

on the relationship between essential tremor (ET) and Parkinson's
disease (PD). As noted in their paper, and as reviewed in greater
detail elsewhere [2], all of the epidemiological studies, of which
there are a considerable number [2], report an elevated odds or
elevated risk of PD in patients with ET. Indeed, there are no such
studies to the contrary. The estimated measures of association obtained from these epidemiological studies provide signicant
controlled, quantitative evidence that ET is associated with PD
and, more specically, that baseline ET seems to increase the risk
of developing PD by a factor of 4e5. They provide conrmation
for the widespread anecdotal sense, among practicing clinicians,
that ET patients commonly go on to develop PD.
In terms of the biological basis for this association, it is not
completely clear. Whether the common link is the Lewy body is
not clear, although there is some evidence. Several groups have
pointed to the increased odds of Lewy bodies in patients with ET
[3,4]. While this has wrongly been attributed by others to incidental Lewy bodies, this is not correct. In the more detailed of
the two aforementioned studies, moderate to severe Lewy bodies
(quantied as or ), which is well above what is typically
seen with incidental Lewy bodies, were observed in the locus ceruleus in 24.2% of ET brains [3]. One study, the Sun Health study, did
not nd an increase in Lewy bodies in ET cases vs. controls [5]; however, the nding is suspect. In addition to the several aws pointed
out by Thenganatt and Jankovic [1], we have pointed out in detail
elsewhere that that work is problematic for other reasons, with
one of the major ones being the case denition of ET and the
high probability that many of the ET cases had enhanced physiological tremor. In the Sun Health study, tremor was dened simply as
action tremor of the hand, voice, or isolated head tremor. This liberal denition does little to exclude enhanced physiological tremor,
which is an action tremor of the hands and is very common in the
elderly. Although the authors note that tremor had to have a rating
of 2 or higher, for their cases who had had tremor for 3 or more
years (i.e., most of their cases), a low-amplitude tremor (<2) was

deemed acceptable. Furthermore, the specic examination maneuvers that they performed to assess kinetic tremor were not explicitly delineated, further raising questions about the extent of the
clinical assessment and the stringency of the requirements for
the ET diagnosis (i.e., whether it required moderate or greater
amplitude kinetic tremor on several examination maneuvers).
Indeed, in the Arizona study, this liberal case denition is a considerable problem; they have reported that 177 of 753 enrolled subjects were diagnosed by study personnel as ET (i.e., 23.5%). The
mean age of the subjects enrolled and evaluated in their study
was 75 years. In other population-based studies, the expected prevalence of ET in this age group is on the order of 6e8%, which is 1/3
of that in their study. This raises the distinct possibility that the
large majority of their ET cases likely had other conditions such
as enhanced physiological tremor.
Leaving aside the issue of the Lewy bodies, one comes back to
the epidemiological studies. Adding quantitative data to what clinicians commonly observe, these studies furnish consistent scientic
support. The argument that there is no relationship is no longer
empirically tenable, as it would simply ignore a considerable
body of published evidence. It is not productive to cling to what
is now an outdated controversy. If we want to move forward, it behooves us to expend our energy on understanding the scientic
reasons for this association in order to provide a positive impact.
Funding
National Institutes of Health: NINDS #R01 NS039422. This funding body played no role in the design of the study, the collection,
analysis, and interpretation of data, or the writing of the manuscript. National Institutes of Health: NINDS R01 NS039422, R01
NS042859, R01 NS086736 and R01 NS088357.
Competing interests
Elan Louis has no conicts of interest and no competing nancial interests.
Julian Benito-Leon has no conicts of interest and no competing
nancial interests.
Phyllis Faust has no conicts of interest and no competing nancial interests.
Acknowledgments
None.
References
[1] M.A. Thenganatt, J. Jankovic, The relationship between essential tremor and

http://dx.doi.org/10.1016/j.parkreldis.2016.01.009
1353-8020/ 2016 Elsevier Ltd. All rights reserved.

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144

Correspondence / Parkinsonism and Related Disorders 24 (2016) 143e144

Parkinson's disease, Park. Relat. Disord. 22 (Supspl. 1) (2016) S162eS165.

[2] H. LaRoia, E.D. Louis, Association between essential tremor and other neurodegenerative diseases: what is the epidemiological evidence? Neuroepidemiology
37 (2011) 1e10.
[3] E.D. Louis, P.L. Faust, J.P. Vonsattel, L.S. Honig, A. Rajput, C.A. Robinson, et al.,
Neuropathological changes in essential tremor: 33 cases compared with 21
controls, Brain 130 (2007) 3297e3307.
[4] G.W. Ross, D. Dickson, M. Cerosimo, Pathological Investigation of Essential
Tremor Neurology, vol. 62, 2004, pp. A537eA538.
[5] H.A. Shill, C.H. Adler, T.G. Beach, Pathology in essential tremor, Park. Relat. Disord. 18 (Suppl. 1) (2012) S135eS137.

Elan D. Louis*
Department of Neurology, Yale School of Medicine, New Haven, CT,
USA
Department of Chronic Disease Epidemiology, Yale School of Public
Health, New Haven, CT, USA

Julian Benito-Leon
Department of Neurology, University Hospital 12 de Octubre,
Madrid, Spain
n Biom
Centro de Investigacio
edica en Red sobre Enfermedades
Neurodegenerativas (CIBERNED), Madrid, Spain
Department of Medicine, Complutense University, Madrid, Spain
Phyllis L. Faust
Department of Pathology and Cell Biology, Columbia University
Medical Center and the New York Presbyterian Hospital, New York,
NY, USA
*
Corresponding author.
E-mail address: elan.louis@yale.edu (E.D. Louis).

Center for Neuroepidemiology and Clinical Neurological Research,

Yale School of Medicine, New Haven, CT, USA

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18 December 2015