Cognitive Impairment in Parkinson's Disease: Epidemiology, Clinical Profile, Protective and Risk Factors

Abstract

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.

Keywords: Parkinson’s disease; clinical profile; dementia; mild cognitive impairment; risk factors.

Figure 1

Protective and risk factors for cognitive impairment. Factors associated with cognitive impairment are classified as either protective or risk factors. Established factors in each category are shown in solid colors. Factors where the association remains uncertain are shown in light colors and emphasized with a question mark. Possible interactions and mechanisms of action are displayed by connecting arrows and brackets. APOE = Apolipoprotein E; BDNF = Brain-derived neurotrophic factor; BMI = body mass index; COMT = Catechol-O-methyltransferase; DM = diabetes mellitus; HTN = hypertension; MAPT = Microtubule-associated protein tau; REM = rapid eye movement; UA = uric acid. Created with BioRender.com.