A multi-site study on sex differences in cortical thickness in non-demented Parkinson’s disease

Abstract

Clinical, cognitive, and atrophy characteristics depending on sex have been previously reported in Parkinson’s disease (PD). However, though sex differences in cortical gray matter measures in early drugnaïvepatientshavebeendescribed,littleisknownaboutdifferencesincorticalthickness(CTh)as the disease advances. Our multi-site sample comprised 211 non-demented PD patients (64.45% males; mean age 65.58±8.44 years old; mean disease duration 6.42±5.11 years) and 86 healthy controls (50% males; mean age 65.49±9.33years old) with available T1-weighted 3T MRI datafrom four international research centers. Sex differences in regional mean CTh estimations were analyzed using generalized linear models. The relation of CTh in regions showing sex differences with age, disease duration, and age of onset was examined through multiple linear regression. PD males showedthinner cortex than PD females in six frontal (bilateral caudal middle frontal, bilateral superior frontal, left precentral and right pars orbitalis), three parietal (bilateral inferior parietal and left supramarginal), andonelimbicregion(right posterior cingulate).In PDmales,lowerCThvaluesinnine outoftenregionswereassociatedwithlongerdiseasedurationandolderage,whereasinPDfemales, lower CThwasassociatedwith older agebut with longer disease duration only in one region. Overall, male patients show a more widespread pattern of reduced CTh compared with female patients. Disease duration seems more relevant to explain reduced CTh in male patients, suggesting worse prognostic over time. Further studies should explore sex-specific cortical atrophy trajectories using large longitudinal multi-site data