Objective: This study investigates if PD patients with Brain-derived-neurotrophic-factor (BNDF) Met allele are more likely to have Mild behavioral impairment (MBI). And whether Met allele carriers have impairments in specific domains of MBI using the Mild Behavioral Impairment Checklist (MBI-C) as the MBI ascertainment tool.

Background: Neuropsychiatric symptoms are common in Parkinson’s disease (PD) (1). MBI is a validated syndrome describing sustained and emergent neuropsychiatric symptoms in older adults as a marker of potential cognitive decline and dementia (2). Val66Met a polymorphism in BDNF gene is associated with neuropsychiatric deficits (3). Further, Val66Met is linked to susceptibility to neuropsychiatric symptoms e.g. depression, anxiety (4).

Method: 136 PD patients, Hoehn & Yahr stages II-III, were screened for neuropsychiatric and cognitive impairments with the MBI-C and the Montreal Cognitive Assessment (MoCA). All participants were screened for BDNF Val66Met using the TaqMan Genotyping Assay C-11592758-10.

Results: The two groups had no significant differences in any of the demographic and clinical characteristics (Table1).
Met carriers (n=43) had a higher likelihood of being MBI positive than Val carriers (n=93) (Fisher’s exact test=0.017). Met carriers were also more likely to have higher MBI-C total scores compared to Val carriers. For domain analyses, Met carriers had greater impairments in the emotional dysregulation (mood/anxiety symptoms) and the abnormal thoughts/perception (psychotic symptoms) domains of MBI-C compared to Val carriers (Table2).

Conclusion: In our cohort, we found a robust association between the BDNF Met allele and MBI in PD patients, with greatest symptom burden in the emotional dysregulation and the abnormal thoughts/perception domains of MBI. These findings suggest a role for the BDNF Met allele and MBI pathology in PD patients.

References: 1-Gallagher, D.A. and A. Schrag, Psychosis, apathy, depression and anxiety in Parkinson’s disease. Neurobiol Dis, 2012. 46(3): p. 581-9. 2- Ismail, Z., et al., The Mild Behavioral Impairment Checklist (MBI-C): A Rating Scale for Neuropsychiatric Symptoms in Pre-Dementia Populations. J Alzheimers Dis, 2017. 56(3): p. 929-938. 3- Wang, Q., et al., Association between BDNF G196A (Val66Met) polymorphism and cognitive impairment in patients with Parkinson’s disease: a meta-analysis. Braz J Med Biol Res, 2019. 52(8): p. e8443. 4- Tsai, S.J., Critical Issues in BDNF Val66Met Genetic Studies of Neuropsychiatric Disorders. Front Mol Neurosci, 2018. 11: p. 156.

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