Mortality rate, main causes of death and factors associated with higher mortality hazard in late stage Parkinson's disease.

Alzheimer's disease (AD) and Parkinson's disease (PD) are prevalent among neurodegenerative disorders in aging populations, each contributing uniquely to cognitive and motor decline. While AD is primarily characterized by β-amyloid plaques and tau neurofibrillary tangles, PD is defined by dopaminergic neurodegeneration and the accumulation of α-synuclein aggregates. These pathologies often co-occur within the same individuals, particularly in older adults with PD who subsequently also develop dementia. Autopsy studies frequently reveal overlapping AD and PD pathology, suggesting a shared or compounding mechanism of neurodegeneration. Neuropathological data from the Arizona Brain and Body Donation Program (BBDP) indicates that over half of PD dementia cases exhibit significant comorbid AD pathology, evident by both amyloid plaque and tau pathology. Sex is an essential biological variable in both diseases. Men are more frequently affected by PD, while women are more likely to develop AD and may experience faster cognitive decline with more extensive tau and amyloid pathology. The mechanisms underlying these sex differences are complex, potentially involving hormonal and genetic factors. Despite known disparities in disease prevalence and progression, limited research has examined whether sex influences AD pathology in patients with PD. In this study, we analyzed clinical, cognitive, and neuropathological data from a large autopsy-confirmed cohort of PD patients, assessing differences in β-amyloid plaque and tau pathology burden, in relation to ApoE genotype, between males and females. This analysis aims to determine whether the well-documented pattern of increased AD pathology in women persists even in the context of comorbid PD, which could enhance clinical awareness and inform more nuanced models of disease progression.