AUTHOR=Chen Jing , Zhao Danhua , Wang Qi , Chen Junyi , Bai Chaobo , Li Yuan , Guo Xintong , Chen Baoyu , Zhang Lin , Yuan Junliang 

TITLE=Predictors of cognitive impairment in newly diagnosed Parkinson’s disease with normal cognition at baseline: A 5-year cohort study

JOURNAL=Frontiers in Aging Neuroscience

VOLUME=Volume 15 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2023.1142558

DOI=10.3389/fnagi.2023.1142558

ISSN=1663-4365

ABSTRACT=Background and Objective: Cognitive impairment (CI) is a substantial contributor to the disability associated with PD. We aimed to assess the clinical features and to explore the underlying biomarkers as the predictors of CI in patients with newly diagnosed PD (NDPD) (less than two years). 
Methods: We evaluated the status of cognitive function using the Montreal Cognitive Assessment (MoCA) and a battery of neuropsychological tests at baseline and subsequent annual follow-up for five years from the Parkinson’s Progression Markers Initiative (PPMI) database. We assessed the baseline clinical features, apolipoprotein (APO) E status, β-glucocerebrosidase (GBA) mutation status, cerebrospinal fluid findings, and dopamine transporter imaging results. Using a diagnosis of CI (combined mild cognitive impairment and dementia) developed during the 5-year follow-up as outcome measures, we assessed the predictive values of baseline clinical variables and biomarkers. We also constructed a predictive model for the diagnosis of CI using logistic regression analysis. 
Results: A total of 409 patients with NDPD with 5-year follow-up were enrolled, 232 of them with normal cognitive function at baseline, and 94 patients developed CI during the 5-year follow-up. In multivariate analyses, age, current diagnosis of hypertension, baseline MoCA scores, Movement disorder society Unified PD Rating Scale part III (MDS-UPDRS III) scores, and APOE status were associated with the development of CI. Predictive accuracy of CI using age alone improved by addition of clinical variables and biomarkers (current diagnosis of hypertension, baseline MoCA scores, and MDS-UPDRS Ⅲ scores, APOE status) (AUC 0.80 [95% CI 0.74–0.86] vs 0.71 [0.64-0.77], p = 0.008). Cognitive domains that had higher frequencies of impairment were found in verbal memory (12.6% vs 16.8%) and attention/processing speed (12.7% vs 16.9%), however, no significant difference in the prevalence of CI at annual follow-up was found during the 5-year follow-up in NDPD patients.
Conclusions: In NDPD, the development of CI during the 5-year follow-up can be predicted with good accuracy using a model combining age, current diagnosis of hypertension, baseline MoCA scores, MDS-UPDRS III scores, and APOE status. Our study underscores the need for the earlier identification of CI in NDPD patients in our clinical practice.