Greater burden of Alzheimer's Co-pathology in women with Parkinson's disease dementia

Abstract

Objective To investigate sex differences in Alzheimer's disease (AD) related pathology among autopsy-confirmed Parkinson's disease (PD) cases. Background AD and PD frequently co-occur in older adults, yet the influence of sex on AD pathology in the context of PD remains unexplored. Methods All subjects were enrolled in the Arizona Study of Aging and Neurodegenerative Disorders (AZSAND) and Brain and Body Donation Program (BBDP) and had annual standardized research clinical assessments by neuropsychologists, subspecialty behavioral and movement disorders neurologists, as well as comprehensive neuropathological examinations after death. Results Among 230 autopsy-confirmed PD cases, females exhibited greater amyloid plaque pathology burden than males, regardless of a co-occurring AD diagnosis. Specifically, females with PD had significantly higher mean cortical total plaque scores (mean 6.5/15 vs. 4.9/15, p = 0.045) and greater CERAD neuritic plaque density (mean 1.7/3 vs. 1.3/3, p = 0.035). Females were also more likely to have a higher cortical plaque burden (plaque total ≥ 5: 56.8% vs. 39.7%, p = 0.015). In multivariable logistic regression models, female subjects showed greater than twice the odds of having an amyloid plaque burden ≥5 compared to males (OR = 2.18; 95% CI = 1.17–4.06; p = 0.014), when controlling for ApoE ε4 status, Lewy body density score, and age at death. Conclusions Female sex is associated with increased amyloid plaque pathology in PD, independent of ApoE ε4 status. These findings highlight a sex-specific vulnerability to AD pathology in PD patients and support the need for sex-informed approaches to reseach in mixed neurodegenerative disease. Plain Language Summary Women with Parkinson's Disease Dementia have higher rates of Alzheimer's related brain pathology. This study explored whether the amount of Alzheimer's-related brain changes differs between males and females with Parkinson's disease. The brains of 230 deceased individuals who had Parkinson's disease were examined. Throughout their lives, these people received regular clinical evaluations by neurology specialists and, after their death, autopsies were performed. The study found that women with Parkinson's disease Dementia had a higher “burden” of Alzheimer's disease-associated amyloid pathology in their brains compared to men with Parkinson's disease Dementia. This was true even if they had not been formally diagnosed with Alzheimer's disease. In conclusion, these findings show that women with Parkinson's disease Dementia are more vulnerable to developing Alzheimer's-like brain changes than men with Parkinson's disease Dementia.