Organophosphate pesticides and PON1 L55M in Parkinson's disease progression.
BACKGROUND
Parkinson's disease (PD) has motor and non-motor features that contribute to its phenotype and functional decline. Organophosphate (OP) pesticides and PON1 L55M, which influences OP metabolism, have been implicated in multiple mechanisms related to neuronal cell death and may influence PD symptom progression.


OBJECTIVE
To investigate whether ambient agricultural OP exposure and PON1 L55M influence the rate of motor, cognitive, and mood-related symptom progression in PD.


METHODS
We followed a longitudinal cohort of 246 incident PD patients on average over 5years (7.5years after diagnosis), repeatedly measuring symptom progression with the Mini-Mental State Exam (MMSE), Unified Parkinson's Disease Rating Scale (UPDRS), and Geriatric Depressive Scale (GDS). OP exposures were generated with a geographic information system (GIS) based exposure assessment tool. We employed repeated-measures regression to assess associations between OP exposure and/or PON1 L55M genotype and progression.


RESULTS
High OP exposures were associated with faster progression of motor (UPDRS β=0.24, 95% CI=-0.01, 0.49) and cognitive scores (MMSE β=-0.06, 95% CI=-0.11, -0.01). PON1 55MM was associated with faster progression of motor (UPDRS β=0.28, 95% CI=0.08, 0.48) and depressive symptoms (GDS β=0.07; 95% CI=0.01, 0.13). We also found the PON1 L55M variant to interact with OP exposures in influencing MMSE cognitive scores (β=-1.26, 95% CI=-2.43, -0.09).


CONCLUSION
Our study provides preliminary support for the involvement of OP pesticides and PON1 in PD-related motor, cognitive, or depressive symptom progression. Future studies are needed to replicate findings and examine whether elderly populations generally are similarly impacted by pesticides or PON1 55M genotypes.
['Paul|Kimberly C|KC|', 'Sinsheimer|Janet S|JS|', 'Cockburn|Myles|M|', 'Bronstein|Jeff M|JM|', 'Bordelon|Yvette|Y|', 'Ritz|Beate|B|']
D000368:Aged D000369:Aged, 80 and over D000383:Agriculture D043303:Aryldialkylphosphatase D002140:California D003071:Cognition D015331:Cohort Studies D003863:Depression D018450:Disease Progression D004781:Environmental Exposure D005260:Female D005838:Genotype D006801:Humans D008297:Male D008875:Middle Aged D009043:Motor Activity D010755:Organophosphates D010300:Parkinson Disease D010575:Pesticides
Organophosphates PON1 Parkinson's disease Progression Cognitive decline