In a recent study conducted by researchers at Fudan University in Shanghai, it was discovered that lower levels of testosterone, combined with higher levels of a protein called neurofilament light chain, significantly increase the risk of cognitive decline in older men. The paper was published in the journal Alzheimer’s & Dementia.
As people age, their cognitive abilities generally deteriorate. This deterioration can be subtle at first but may become quite pronounced in advanced age. However, cognitive decline does not affect everyone equally. Some individuals maintain good cognitive functioning well into their 70s, 80s, or even later years, while others experience a much faster decline.
When an individual experiences a severe and progressive deterioration of cognitive function that significantly interferes with daily life, it is referred to as dementia. Dementia encompasses various conditions caused by different neurological issues that impair the nervous system. The most common type is Alzheimer’s disease, characterized by a buildup of specific proteins in the brain that create plaques and tangles, progressively killing neurons in the affected areas.
Some forms of dementia can be prevented, or their progression slowed. This has led scientists to intensely research ways to predict who will develop dementia. Among the factors being investigated are sex hormones, which are believed to modulate the risk of cognitive decline. For example, a premature reduction in estrogen in women can indicate the potential development of dementia.
Another important marker of impending dementia is neurofilament light chain. This protein helps maintain the shape and structural integrity of nerve cells, acting as a cellular skeleton. Normally, neurofilament light chain molecules remain within neurons. However, if these proteins are found in elevated quantities in the blood, it indicates that neurons have been damaged, releasing these proteins into the bloodstream.
Study author Shuning Tang and his colleagues wanted to explore how precisely can future cognitive decline of older men be predicted based on information about testosterone and neurofilament light chain levels. They hypothesized that lower testosterone level will be associated with cognitive decline, and that predicting cognitive decline will be even more effective if based both on testosterone and neurofilament light chain levels.
The researchers analyzed data from 581 older men participating in the Shanghai Aging Study. This longitudinal, community-based cohort study began in 2010 to investigate the prevalence, incidence, and risk factors of cognitive impairment among older Chinese adults. All participants were residents of the Jingansi community in downtown Shanghai, aged 60 or above, and dementia-free at the start of the study. On average, participants were followed for 6.7 years.
At the study’s outset, participants provided blood samples, which allowed researchers to measure testosterone and neurofilament light chain levels. Participants also completed a series of neuropsychological tests to assess their cognitive functioning. Between 2014 and 2023, participants were re-tested at least once, enabling researchers to compare their cognitive functioning over time and determine if dementia was developing.
The results showed that 45 participants developed cognitive decline during the study period. Compared to those who did not develop cognitive decline, these men were older, had fewer years of education, and were more likely to have a history of coronary heart disease, stroke, and hypertension. They also tended to have lower testosterone levels and higher neurofilament light chain levels in their blood.
By combining data on testosterone and neurofilament light chain levels, the researchers categorized participants into three risk groups: high, medium, and low. Participants in the high-risk group experienced cognitive decline 5-6 times more often than those in the low-risk group.
“Our findings suggest that the combination of testosterone and neurodegenerative markers may provide reliable predictive insights into future cognitive decline,” the study authors concluded.
The study offers a new method to predict future cognitive decline in older men. However, there are several limitations. The dementia diagnosis in this study was based solely on cognitive performance measures without examining the specific types and causes of dementia. This approach does not differentiate between different forms of dementia, such as Alzheimer’s disease or vascular dementia.
Additionally, the study participants were all from urban areas with relatively high levels of education, which may limit the generalizability of the findings to other populations. Higher education is associated with a slower rate of cognitive decline, potentially influencing the results.
Future research should aim to replicate these findings in larger, more diverse populations and explore the mechanisms underlying the observed associations. Longitudinal studies with repeated measurements of testosterone and neurofilament light chain could provide more nuanced insights into how these factors interact over time to influence cognitive health. Understanding the specific biological pathways through which testosterone and neurofilament light chain affect cognition could lead to new preventive and therapeutic strategies for dementia.
The paper, “Joint effect of testosterone and neurofilament light chain on cognitive decline in men: The Shanghai Aging Study,” was authored by Shuning Tang, Zhenxu Xiao, Fangting Lin, Xiaoniu Liang, Xiaoxi Ma, Jie Wu, Xiaowen Zhou, Qianhua Zhao, Junling Gao, Qianyi Xiao, Ding Ding.