UC San Diego

Cognitive impairment is a common non-motor symptom in Parkinson's Disease (PD) and an important source of patient disability and caregiver burden. The timing, profile and rate of cognitive decline varies widely among individuals with PD and can range from normal cognition to mild cognitive impairment (PD-MCI) and dementia (PDD). Beta-amyloid and tau brain accumulation, oxidative stress and neuroinflammation are reported risk factors for cognitive impairment. Traumatic brain injury and pesticide and tobacco exposure have also been described. Genetic risk factors including genes such as COMT, APOE, MAPT and BDNF may also play a role. Less is known about protective factors, although the Mediterranean diet and exercise may fall in this category. Nonetheless, there is conflicting evidence for most of the factors that have been studied. The use of inconsistent criteria and lack of comprehensive assessment in many studies are important methodological issues. Timing of exposure also plays a crucial role, although identification of the correct time window has been historically difficult in PD. Our understanding of the mechanism behind these factors, as well as the interactions between gene and environment as determinants of disease phenotype and the identification of modifiable risk factors will be paramount, as this will allow for potential interventions even in established PD.