Objective: To investigate the hypothesis that young veterans with (+) mTBI will show premature cognitive decline that is similar to executive functioning of Parkinson’s disease (PD) seniors suggesting a prodromal phenotype of PD.

Background: Fifty-percent of early stage PD patients experience mild cognitive symptoms, with 36% of PD patients experiencing memory and attention problems approximately 39-months prior to motor symptom onset. Veterans with (+) a mild traumatic brain injury (mTBI) have a 33-56% increased risk of developing PD.

Method: An exploratory, matched-control, cross-sectional study was conducted. Eligible subjects were age and IQ-matched (> 90) men and women veterans (+) mTBI and without (-) mTBI, non-veteran healthy controls (25-45-years-old), and PD seniors (60-90-years old) of all race/ethnicities. Non-English speaking, chronic unremitted/debilitating diseases or disorders, physical or sensory limitations and substance use were excluded. Veteran groups were or were not exposed to non-penetrating mTBI within the past 7-years. Healthy controls and PD subjects had no exposure to recent military service or mTBI. Seven domains of executive functioning were the primary outcomes analyzed using T-score transformations with comparisons made among groups.

Results: Out of 200 volunteers, 114 provided evaluable data [69% men, with a mean age of 32.7 yrs. (SD=3.8) for young subjects, 68.5 yrs. (SD=8.3) for PD seniors]. Multivariate analysis of covariance revealed veterans + mTBI performed worse than control groups and were more similar to PD subjects [F(21, 299) =3.09, p<0.000]. There were no significant main effects of mTBI grade levels [F(14,42) =.681, p=.779] nor interactions [F(7, 21) =.367, p=.911] on cognitive outcomes. Posttraumatic stress levels did not influence cognitive outcomes [F (21, 285) =.897, p=.596], nor was there an influence of depression [F (14,208) = .829, p=.637].

Conclusion: Non-age-related cognitive impairment is a prodromal signature of PD. These data show executive functioning in young veterans (+) mTBI is comparable to those with PD and provides the first compelling evidence suggesting that premature cognitive decline may be a prodromal phenotype of PD. Longitudinal matched-controlled studies with larger sample sizes are warranted to further substantiate these preliminary data.

References: [1]. R.C. Gardner, A.L. Byers, D.E. Barnes, Y. Li, J. Boscardin, K. Yaffe, Mild TBI and risk of Parkinson disease: A Chronic Effects of Neurotrauma Consortium Study, Neurology, 2018, 90, e1771-1779, doi.org/10.1212/WNL.0000000000005522. [2]. R. Durcan, L. Wiblin, R.A., Lawson, T. K. Khoo, A. J. Yarnall, G.W. Duncan, D. J. Brooks, et al., ICICLE-PD Study Group, Prevalence and duration of non-motor symptoms in prodromal Parkinson’s disease, Eur J Neurol 26 (2019) 979-985. [3]. S.J. Jafari, M. Etminan, F. Aminzadeh, A. Samii, Head injury and risk of Parkinson disease: A systematic review and meta‐analysis, Mov Disord, 2013, 28(9), https://doi.org/10.1002/mds.25458.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/premature-cognitive-decline-in-young-veterans-with-mtbi-a-possible-prodromal-signature-of-early-stage-parkinsons-disease/