Markers in other bodily fluids
In addition to markers in CSF, several other bodily fluids may provide potential markers for cognitive impairment and dementia in PD. These include plasma, serum, saliva, and urine. Examination of these fluids may be more practical, less expensive, or less stressful for patients. However, these fluids are more prone to be confounded by factors introduced by other organ systems and may therefore be considered as less attractive than CSF for the identification of cognitive biomarkers in PD. The number of studies examining these bodily fluids is still limited, yet some interesting candidates have been identified.
For example, lowered serum levels of uric acid, a potent antioxidant, have been associated with increased risk for PD in the general population and more rapid clinical decline in patients with symptomatic PD . One group also reported potential associations of serum and urine levels of uric acid with neuropsychological impairment in a small PD cohort [76, 77]. Another, probably even more promising, observation comes from a longitudinal study that examined 102 plasma proteins and their association with cognitive performance in PD, as measured by DRS-2. Baseline cognitive performance correlated with concentrations of 11 plasma proteins, of which epidermal growth factor (EGF) was identified as the strongest candidate. Importantly, low levels of EGF also predicted an eight-fold greater risk for progression to dementia during follow-up . This finding has been replicated in part in a more recent study that found serum EGF levels in early PD to correlate with frontal and temporal cognitive functioning and to predict cognitive performance after 2 years of follow-up
. However, additional longitudinal studies are needed to further validate these findings.
Genetic risk markers
Several epidemiological studies have shown an increased risk of PD-D or AD in first-degree relatives of patients with PD [80, 81], suggesting a possible role for genetic factors in PD-D. Indeed, research has revealed several genetic polymorphisms that have been proposed to influence cognitive function or dementia risk in PD.