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February 25, 2020; 94 (8) Article

Traumatic brain injury preceding clinically diagnosed α-synucleinopathies

A case-control study

Shemonti Hasan, Michelle M. Mielke, Pierpaolo Turcano, J. Eric Ahlskog, James H. Bower, View ORCID ProfileRodolfo Savica
First published January 28, 2020, DOI: https://doi.org/10.1212/WNL.0000000000008995
Shemonti Hasan
From the Alix School of Medicine (S.H.), Department of Health Sciences Research (M.M.M., R.S.), and Department of Neurology (P.T., J.E.A., J.H.B., R.S.), Mayo Clinic, Rochester, MN.
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Michelle M. Mielke
From the Alix School of Medicine (S.H.), Department of Health Sciences Research (M.M.M., R.S.), and Department of Neurology (P.T., J.E.A., J.H.B., R.S.), Mayo Clinic, Rochester, MN.
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Pierpaolo Turcano
From the Alix School of Medicine (S.H.), Department of Health Sciences Research (M.M.M., R.S.), and Department of Neurology (P.T., J.E.A., J.H.B., R.S.), Mayo Clinic, Rochester, MN.
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J. Eric Ahlskog
From the Alix School of Medicine (S.H.), Department of Health Sciences Research (M.M.M., R.S.), and Department of Neurology (P.T., J.E.A., J.H.B., R.S.), Mayo Clinic, Rochester, MN.
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James H. Bower
From the Alix School of Medicine (S.H.), Department of Health Sciences Research (M.M.M., R.S.), and Department of Neurology (P.T., J.E.A., J.H.B., R.S.), Mayo Clinic, Rochester, MN.
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Rodolfo Savica
From the Alix School of Medicine (S.H.), Department of Health Sciences Research (M.M.M., R.S.), and Department of Neurology (P.T., J.E.A., J.H.B., R.S.), Mayo Clinic, Rochester, MN.
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  • ORCID record for Rodolfo Savica
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Traumatic brain injury preceding clinically diagnosed α-synucleinopathies
A case-control study
Shemonti Hasan, Michelle M. Mielke, Pierpaolo Turcano, J. Eric Ahlskog, James H. Bower, Rodolfo Savica
Neurology Feb 2020, 94 (8) e764-e773; DOI: 10.1212/WNL.0000000000008995

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Abstract

Objective To determine the association between traumatic brain injury (TBI) and any clinically diagnosed α-synucleinopathy including Parkinson disease (PD), dementia with Lewy bodies (DLB), PD dementia (PDD), and multiple system atrophy (MSA).

Methods Using the medical records-linkage system of the Rochester Epidemiology Project, we identified incident cases of α-synucleinopathies in Olmsted County, Minnesota, from 1991 to 2010, matching by age (±1 year) at symptom onset and sex to controls. We reviewed records of cases and controls to detect TBI prior to clinical-motor onset of any α-synucleinopathies. We based severity (possible, probable, and definite) upon the Mayo Classification System for TBI Severity. Using conditional-logistic regression, we calculated the odds ratio (OR) of all α-synucleinopathies and type, adjusting for coffee intake and smoking.

Results TBI frequency was lower among cases (7.0%) than controls (8.2%). No association was found between TBI and all α-synucleinopathies in multivariable analyses (OR 0.90, 95% confidence interval [CI] 0.54–1.52). No association presented when examining the number of TBIs, TBI severity, time between TBI exposure and index date, age at index date, or sex. When stratifying by each individual α-synucleinopathy, we did not identify any associations between TBI and PD, DLB, or PDD. Among the MSA group, 1 (6.4%) and 0 controls experienced a TBI (OR could not be estimated).

Conclusions In this nested case-control population-based analysis, TBI was not associated with subsequent α-synucleinopathies in general or any individual α-synucleinopathy. This did not change based on the temporality or the severity of the TBI. Our findings may be limited by the study power.

Glossary

CDC=
Centers for Disease Control and Prevention;
CI=
confidence interval;
DLB=
dementia with Lewy bodies;
H-ICDA=
Hospital Adaptation of the International Classification of Diseases, Eighth Revision;
ICD-9=
International Classification of Diseases, Ninth Revision;
IQR=
interquartile range;
MSA=
multiple system atrophy;
OR=
odds ratio;
PD=
Parkinson disease;
PDD=
Parkinson disease dementia;
REP=
Rochester Epidemiology Project;
TBI=
traumatic brain injury

Footnotes

  • Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Editorial, page 335

  • Received March 22, 2019.
  • Accepted in final form September 1, 2019.
  • © 2020 American Academy of Neurology
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  • Reader response: Traumatic brain injury preceding clinically diagnosed α-synucleinopathies: A case-control study
    • Tomoyuki Kawada, Professor, Nippon Medical School
    Submitted April 12, 2020
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