Home Mind & Brain New Study Shows Sex Differences in Dementia-Related Brain Changes

New Study Shows Sex Differences in Dementia-Related Brain Changes

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Lewy body dementia (LBD) is a complex neurodegenerative condition characterised by the progressive loss of substantia nigra neurons, a hallmark of Parkinson’s disease and dementia. Recent research, published in the journal Biology of Sex Differences, has highlighted significant differences in the clinical presentation and neuropathological correlates of substantia nigra neuron loss between males and females with Lewy body pathology.

The study, led by Ece Bayram and colleagues, delved into the depths of substantia nigra neuron loss and its clinical implications, focusing on sex-based differences. Utilising data from the National Alzheimer’s Coordinating Center, the team examined 159 female and 263 male participants, all diagnosed with brainstem, limbic, and neocortical Lewy body pathology.

Substantia nigra neuron loss is closely linked to parkinsonism in LBD, with its presence and degree playing a pivotal role in the disease’s progression and symptomatology. Despite similar levels of nigral loss and Lewy body pathology staging, the study found that females with Lewy body pathology tend to be older at death, exhibit higher levels of Braak tau staging, and are less likely to be diagnosed with clinical Lewy body disease during follow-up than their male counterparts.

Ece Bayram, researcher at the University of California San Diego, explained the motivation behind this study, “Lewy body dementia includes Parkinson’s disease dementia and dementia with Lewy bodies, which have underlying Lewy body pathology and cognitive impairment that affects daily life. Although LBD is very common and burdensome, we do not hear much about it, and there are a lot of unknowns.”

Bayram emphasised the importance of understanding sex differences in LBD, noting that “females do not get the pure Lewy body pathology as often as males and females have a higher risk than males for a wrong or delayed diagnosis at the clinic, which can make their experience in healthcare even more challenging.”

The research revealed notable differences in how substantia nigra neuron loss correlates with Lewy body pathology staging and core LBD features, such as cognitive fluctuations, visual hallucinations, rapid eye movement sleep behavior disorder, and parkinsonism, between males and females. More advanced Lewy body pathology staging was associated with more nigral neuron loss in males than in females. In addition, the loss of nigral neurons was more strongly associated with parkinsonism and clinical LBD diagnosis during follow-up in males.

“These findings have profound implications for the diagnosis and treatment of LBD. The observed sex differences suggest that females with Lewy body pathology may have a higher risk of underdiagnosis. The mechanisms underlying these differences need further elucidation to advance diagnostic and therapeutic efforts in LBD. Understanding these differences is crucial in improving clinical diagnostic accuracy and may lead to discoveries about disease pathogenesis,” Bayram further explained.

Bayram highlighted the key findings and implications of the study: “Using the National Alzheimer’s Coordinating Center data, we included 159 females and 263 males with pathological Lewy body disease. Compared to males, females lived longer, had more tau pathology but had similar levels of Lewy body pathology and substantia nigra neuron loss.”

Bayram underscored the challenges in diagnosing females with LBD: “Females with underlying Lewy body pathology do not show the LBD clinical profile we expect to see despite similar levels of Lewy body pathology, Alzheimer’s co-pathology, and substantia nigra neuron loss, based on traditional pathology staging.”

The study calls for further research to understand why these sex differences exist and how they can be better identified and treated in LBD. The data also underscores the need for sex-specific accuracy in biomarkers and clinical diagnostic criteria.

Bayram concluded by emphasising the future plans and the importance of this research: “Our work enhanced the story we were building with the traditional pathology staging using the National Alzheimer’s Coordinating Center data. But there is more to LBD than traditional pathology staging, and there is more to the research cohorts than the National Alzheimer’s Coordinating Center data.”

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