The article “Early Menopause Linked to Cognitive Decline: A Study on Women’s Risk Factors” reveals a significant link between early menopause and cognitive decline in women. Researchers from Tohoku University Graduate School of Medicine and Tokyo Metropolitan Institute of Medical Science conducted a study that analyzed the English Longitudinal Study of Ageing, which included 4,726 women and 4,286 men. The team found that women who entered menopause before the age of 40 had worse cognitive outcomes compared to those who entered menopause after the age of 50.

The researchers were motivated by the disproportionate impact of dementia on women worldwide, as well as the association between early menopause and higher risk of depression in later life. The team controlled for modifiable risk factors for dementia and found that menopause at <40 years was significantly associated with worse cognitive function over a two-year follow-up period. Interestingly, the study also showed that hormone replacement therapy (HRT) did not have an association with cognitive function. This suggests that early menopause may be a direct risk factor for cognitive decline in women. The researchers concluded that understanding this relationship could potentially help design treatments to delay the onset of dementia in at-risk patients. The implications of this study are significant, as it highlights the importance of considering sex-specific factors when assessing the risk of developing dementia. Further research is warranted to elucidate the underlying mechanisms of the relationship between levels of female hormones and cognitive function.

In a groundbreaking study published in Neurology®, researchers have shed light on how age, sex, hormonal changes, and genetics influence certain biomarkers for dementia in the blood. The study, led by Hannah Stocker, PhD, MPH, of Heidelberg University in Germany, provides valuable insights into the roles these factors play in shaping an individual’s risk of developing dementia.

The researchers analyzed data from a larger 17-year study involving 513 people who developed dementia and 513 who remained free of the condition. The participants had an average age of 64 at the start of the study. By taking blood samples three times during the study, the researchers measured levels of three biomarkers: neurofilament light chain proteins, glial acidic proteins, and phosphorylated tau 181.

The findings revealed that older age was associated with higher levels of all three markers. For example, people aged 75 had an average of 25 picograms per milliliter (pg/ml) for neurofilament light chain proteins compared to those aged 50 who averaged 10 pg/ml. Similarly, glial acidic proteins were found at higher levels in older participants, with a significant difference between those aged 75 and those aged 50.

The study also showed that female participants had higher levels of glial acidic proteins, while male participants had higher levels of neurofilament light chain proteins. Furthermore, the researchers discovered that people who carried the APOEe4 gene had higher levels of tau and glial acidic proteins.

Notably, the study found that female participants who had not yet gone through menopause had higher levels of glial acidic proteins. This may be attributed to having higher levels of sex hormones, which have been linked to neuroinflammation in previous studies.

The findings of this study highlight the importance of further exploring these biomarkers, including during menopause, in the development of dementia. By gaining a better understanding of how age, sex, hormonal changes, and genetics interact with biomarker levels, researchers can improve their ability to test for dementia using simple blood tests.

Parkinson’s disease, a neurodegenerative disorder that affects over 10 million people worldwide, has long been shrouded in mystery. While some individuals carrying pathogenic variants that increase their risk of PD go on to develop the disease, others who also carry such variants remain unaffected. A new study from Northwestern Medicine has shed light on this enigma by identifying a set of key genes that contribute to the manifestation of Parkinson’s disease.

Using modern CRISPR technology, scientists at Northwestern Medicine systematically examined every gene in the human genome, leading them to identify a group of 16 proteins called Commander complex. This complex plays an important role in delivering specific proteins to the lysosome, a part of the cell responsible for recycling waste materials and old cell parts. Previous research has found that carrying a pathogenic variant in the GBA1 gene is the greatest risk factor for developing Parkinson’s disease and dementia with Lewy bodies (DLB). However, it was unknown why some individuals who carry these variants develop PD while others do not.

The study discovered that loss-of-function variants in Commander complex genes contribute to an increase in Parkinson’s disease risk. By examining genomes from two independent cohorts, the scientists found that people with PD had more loss-of-function variants in Commander genes compared to those without the disease. This breakthrough opens the door to previously untapped drug targets for treating PD.

The study reveals that lysosomal dysfunction is a common feature of several neurodegenerative diseases, including Parkinson’s disease. The Commander complex plays an important role in maintaining lysosomal function, suggesting that drugs targeting this complex could improve the cell’s recycling system and potentially lead to new treatments for PD.

Future research will determine the extent to which the Commander complex contributes to other neurodegenerative disorders with lysosomal dysfunction. If Commander dysfunction is observed in these individuals, drugs targeting Commander could hold broader therapeutic potential for treating such disorders. In this context, Commander-targeting drugs could also complement other PD treatments, potentially leading to combinatorial therapies.

The study was published in the journal Science and was funded by a Research Program Award (R35). The findings of this research have significant implications for understanding Parkinson’s disease and developing new treatments for this complex disorder.