Analysis of neurocognitive and cortical thinning patterns between early onset and late onset Parkinson's disease dementia

Abstract

Cognitive dysfunction in Parkinson’s disease (PD) is one of the most disabling features and occurs mainly in old age. Although aging is a risk factor of dementia in PD, the early onset form of Parkinson’s disease dementia (PDD) had not been researched. The present study included 116 patients with PDD and 121 patients with normal cognition, The subjects were divided into two groups based on a cutoff value of 70 years; 39 patients with onset age younger than 70 years (Early-onset PDD, EOPDD) and 77 patients with onset after 70 years of age (Late-onset PDD, LOPDD). All of these patients were assessed with a neuropsychological battery. Among the patients, 65 underwent three-dimensional T1-weighted MRI scans and analyses of cortical thickness. In addition, volumetry of substantia innominata (SI) was performed. The effects of diagnosis and age and their interaction on neuropsychological tests, cortical thickness, and volume of SI were assessed using analysis of covariance. The EOPDD group exhibited poorer performance in backward span (p=0.011) and visual recognition tests (p=0.002) after adjusting for the effect of aging. In cortical thickness analysis, the LOPDD group showed widespread cortical thickness. After adjusting for age, the EOPDD group exhibited greater cortical thinning in the left anterior cingulate gyrus and right mesial temporal area, with a lower threshold of uncorrected p<0.001. The normalized SI volume was decreased in the EOPDD group after adjusting for aging effects in volumetric analysis. Our data suggest that EOPDD may be a distinct phenotype different from LOPDD. EOPDD had a greater pathological burden in key structures responsible for PD-related cognitive decline, whereas LOPDD had a widespread pathological burden related to aging.