Th-214 CSF biomarkers of AD in PD patients with and without cognitive impairment suggest a subset with concomitant AD release_umc373v76fed5a6nintcarmqwy

Abstract

Objective: To determine if established CSF biomarkers of AD pathology could detect the presence of co-existing AD pathology in a subset of PD patients with and without cognitive impairment. Background: Up to 80% of elderly patients with Parkinson's disease (PD) develop meaningful cognitive impairment. The clinical profile is dominated by reduced cognitive processing speed and other measures related to subcortical and frontal lobe impairment. Decreased memory and cognitive functions that overlap with domains typically associated with AD may also be impaired. Additional overlap of these two late-life neurodegenerative conditions is documented by the coexistence of pathologic aggregations of synu-clein, neuritic plaques, and hyperphosphorylated tau in as many as 2 out of 3 patients with Parkinson's disease and dementia. Methods: Standardized clinical evaluations, including cognitive assessments and lumbar spinal fluid analysis were performed in 83 subjects; 38 PD, 7 PD dementia (PDD), and 38 elderly controls, participating in a longitudinal study of biomarkers of late-life neurode-generative dementia. CSF levels of total tau, p-taup181 and b-amyloid42 were determined using x-MAP Luminex technology. Results: Applying neuropathologically confirmed AD diagnostic CSF threshold values to the biomarkers in the PD subjects revealed that 31% had a CSF Ab42 level that was <192 pg/mL (consistent with a biomarker diagnosis of AD). The proportion was lower for p-tau181 and t-tau. There was no consistent relationship between the biomarker levels and global measures of cognitive function (DSM, MMS). Conclusions: In an overwhelmingly non-demented cohort of PD patients, CSF Ab42 levels associated with the diagnosis of AD was found in roughly one-third of PD patients. Global measures of cogni-tive function did not correlate with this finding, suggesting it may be possible to detect the presence of co-existing AD pathology in patients with PD prior to the expression of global cognitive impairment as measured by standard clinical tools. Expanding the study cohort, longitudinal follow-up, and the detection of amyloid using newly developed PET ligands may provide additional information. Th-215
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