Abstract
ObjectivesTo investigate whether baseline [123I]FP-CIT SPECT and CSF markers can predict cognitive impairment (CI) in PD patients, and provide a profile of those most at risk.Methods262 de novo PD patients from the Parkinson’s Progression Markers Initiative database were stratified into two CI groups at the 36-month follow-up: MoCA-defined diagnosis: PD patients who had a MoCA score < 26; neuropsychological test-defined diagnosis: PD patients with MoCA-defined diagnosis and at least two test scores (of six; irrespective of test domain) greater than 1.5 standard deviation below the mean score in healthy controls. Predictive variables of CI were divided into deciles, providing us with ideal cutoff values for each variable.ResultsAt the 36-month follow-up, 108/262 (41.2%) PD patients had CI as defined by the MoCA, of which 40/108 (37.0%) had neuropsychological test-defined CI. Baseline CSF Aβ42 (hazard ratio [HR]: 0.996, confidence interval [CI]: 0.992–0.999, p = 0.025), CSF total tau ([HR]: 1.023, [CI]: 1.002–1.044, p = 0.031) and caudate [123I]FP-CIT SPECT uptake ([HR]: 0.332, [CI]: 0.115–0.960, p = 0.042) were predictors of CI. 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 36-month follow-up.ConclusionWe report a characteristic profile (reduced CSF Aβ42, increased CSF total tau and reduced caudate [123I]FP-CIT SPECT uptake) that enables identification of early PD patients at risk of developing CI. These findings confirm previous reports of low CSF Aβ42, elevated CSF total tau and reduced dopaminergic integrity being associated with cognitive decline in PD.
Highlights
Cognitive impairment (CI) is an increasingly recognised complication of Parkinson’s disease (PD), with significant impact including increased caregiver burden and mortality [1]
We found that the best cutoff for cerebrospinal fluid (CSF) Aβ42 was 384.6 pg/mL, 45 pg/mL for CSF total tau and 1.82 for caudate [123I]FP-CIT uptake
Patients who had a combination of two abnormal markers had 15.0–20.0% risk of CI development over a period of 36 months (Fig. 2). This pilot study demonstrated that a combined evaluation of biological and neuroimaging markers enables the identification of 65% of drug-naïve PD patients that will develop CI over a 36-month follow-up
Summary
Cognitive impairment (CI) is an increasingly recognised complication of Parkinson’s disease (PD), with significant impact including increased caregiver burden and mortality [1]. Mild cognitive impairment (MCI), in particular, is recognised as a distinct entity, and a probable prodromal state to PD dementia [1]. Up to 80% of Parkinson’s disease patients develop dementia during the course of the disease, presenting with heterogeneous cognitive profiles and underlying disease pathology [1]. It is crucial to identify CI at an early stage to determine cognitive prognosis, given that MCI is a key risk factor for dementia [15]. The implementation of suboptimal methods in refining prognosis, diagnosis and tracking disease progression continues to hamper patient management and, clinical research [27]. Validated biomarkers with a high degree of sensitivity and specificity represent an unmet need in PD, especially for the development of disease-modifying therapies
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