Predictive and Diagnostic Value of Tau and Beta-amyloid Markers in Cerebrospinal Fluid and Positron Emission Tomography in the Dementia of Parkinson's Disease

Detailed Summary

The PET tracer Fluoro-ethyl-methyl-amino-naphthyl-ethylidene-malononitrile (\[F18\]-FDDNP) has a specific affinity for lesions containing tau protein and beta-amyloid The study consists of two phases * In a first transversal phase, 8 neurologically unimpaired controls, 15 patients with PD and no dementia (PDND) and 8 with PD and dementia (PDD) will undergo lumbar puncture for study of tau, phospho-tau and beta-amyloid levels in cerebrospinal fluid (CSF), as well as positron emission tomography (PET) with (\[F18\]-FDDNP. Concentration of CSF markers and both the degree and topography of FDDNP-PET uptake will be compared among groups, along with correlation analysis between CSF and PET findings. * During the second phase (18 months follow-up), the PDND patients will undergo the same procedures, and cognitive changes including incident dementia will be assessed. The correlation between cognitive impairment and neurochemical and neuroimaging changes will be established to determine the predictive value of these markers. Since the pathological lesions observed in Alzheimer disease (AD) are common in the PD and the concentrations of tau and beta-amyloid are altered in AD and PET with \[F18\]-FDDNP is able to separate patients with AD and cognitive impairment from controls, we hypothesized that: 1. \- Patients with PD will show a biomarkers profile similar to the AD (decreased levels of beta-amyloid and increased phospho-tau and tau) in CSF, and an abnormal uptake of \[F18\]-FDDNP PET compared to PDND patients and controls. 2. -The distribution of cortical \[F18\]-FDDNP in the PD will be different from the AD and similar to dementia with Lewy bodies, predominantly in posterior cortical areas. 3. PDND patients will show a \[F18\]-FDDNP PET uptake and levels of protein markers in CSF intermediate between controls and patients with PD. 4. -In the subsequent follow-up, PDND patients will show cognitive impairment correlate to changes in the levels of protein markers in CSF and uptake of PET with \[F18\]-FDDNP 5. \- The predictive value for the development of dementia in PD of specific patterns of PET uptake and CSF proteins profile will be established.

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