Objective: In this study, we investigated whether [123I]FP-CIT single photon emission computed tomography (SPECT) imaging measures and CSF marker profiles predict CI in PD patients and provide a simple characteristic profile of those most at risk of CI.

Background: Cognitive impairment (CI) is an increasingly recognised complication of Parkinson’s disease (PD), with up to 80% of PD patients developing dementia during the course of the disease. Biomarkers provide a dynamic and powerful approach to understanding the spectrum of neurological disease with applications in observational and analytic epidemiology, randomized clinical trials, screening and diagnosis and prognosis.

Methods: 262 early-stage, de novo PD patients from the Parkinson’s Progression Markers Initiative database were stratified into two CI groups: Level 1 diagnosis included PD patients who had a MoCA score <26; Level 2 diagnosis included PD patients with Level 1 diagnosis, who also subjectively stated having cognitive decline and at least 2 test scores (of HVLT Total Recall, HVLT Recognition Discrimination, Benton Judgement of Line Orientation, Letter Number Sequencing, Semantic Fluency Test and/or Symbol Digit Modalities; irrespective of test domain) greater than 1.5 standard deviation below the age and education-standardized mean score in healthy controls. Predictive variables of CI were divided into deciles, providing us with ideal cut-off values for each variable.

Results: At the three-year follow-up, 108/262 (41.2%) PD patients had CI as defined by Level 1, of which 40/108 (37.0%) had CI as defined by Level 2. CSF Aβ42 (Hazard ratio [HR]=0.996, Wald: 5.035, Confidence Interval [CI]: 0.992-0.999, P=0.025), CSF total tau ([HR]:1.023, Wald: 4.680, [CI]: 1.002-1.044, P=0.031) and caudate [123I]FP-CIT-SPECT uptake ([HR]:0.332, Wald: 4.146, [CI]: 0.115-0.960, P=0.042 were predictors of cognitive decline. Patients with reduced CSF Aβ42 (<384.6 pg/mL), increased CSF total tau (>45.0 pg/mL) and reduced caudate [123I]FP-CIT-SPECT uptake (<1.82) had a 65% risk of developing CI at a 3-year follow-up.

Conclusions: Here, we report a characteristic profile (reduced CSF Aβ42, increased CSF total tau and reduced caudate [123I]FP-CIT-SPECT uptake) that provides the ability of identifying early PD patients most at risk of developing CI, which can be used as a surrogate end-point of clinical progression, therefore aiding the efficiency of clinical trials performed in PD patients with CI. 

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MDS Abstracts - https://www.mdsabstracts.org/abstract/predict-cognitive-decline-with-non-clinical-markers-in-parkinsons-disease/