In a recent study conducted by researchers at Fudan University in Shanghai, it was found 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 study was published in the journal Alzheimer’s disease and dementia.
As people age, their cognitive abilities typically decline. This decline may be subtle at first, but can become quite pronounced as they age. However, cognitive decline does not affect everyone equally. Some people maintain good cognitive functioning into their 70s, 80s, or even later, while others experience a much more rapid decline.
When a person experiences a severe and progressive deterioration in their cognitive functions that significantly interferes with daily life, it is called dementia. Dementia encompasses various conditions caused by different neurological problems 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, gradually killing neurons in the affected areas.
Some forms of dementia can be prevented or their progression can be slowed. That is why scientists have undertaken intensive research to determine who will develop dementia. Among the factors being studied are sex hormones, which are thought to modulate the risk of cognitive decline. For example, a premature decline in estrogen in women may 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 present in high amounts in the blood, this indicates that the neurons have been damaged, releasing these proteins into the bloodstream.
Study author Shuning Tang and colleagues wanted to know how accurately future cognitive decline in older men can be predicted based on testosterone and neurofilament light chain levels. They hypothesized that lower testosterone levels will be associated with cognitive decline and that prediction of cognitive decline will be even more effective if it is based on both testosterone and neurofilament light chain levels.
The researchers analyzed data from 581 older men participating in the Shanghai Aging Study. This community-based longitudinal cohort study began in 2010 to investigate the prevalence, incidence, and risk factors for cognitive impairment among older Chinese adults. All participants were residents of the Jingansi community in downtown Shanghai, aged 60 years or older and free of dementia at the start of the study. On average, participants were followed for 6.7 years.
At the start of the study, participants provided blood samples, which allowed researchers to measure levels of testosterone and neurofilament light chain. Participants also completed a series of neuropsychological tests to assess their cognitive functioning. Between 2014 and 2023, participants were retested at least once, allowing researchers to compare their cognitive functioning over time and determine whether 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 levels of neurofilament light chains in their blood.
By combining data on testosterone and neurofilament light chain levels, the researchers classified participants into three risk groups: high, medium, and low. Participants in the high-risk group experienced cognitive decline 5 to 6 times more often than those in the low-risk group.
“Our results suggest that the combination of testosterone and neurodegenerative markers may provide reliable predictive information about future cognitive decline,” the study authors conclude.
The study proposes a new method to predict future cognitive decline in older men. However, it has several limitations. The diagnosis of dementia in this study was based solely on measures of cognitive performance without examining the specific types and causes of dementia. This approach does not distinguish between different forms of dementia, such as Alzheimer’s disease or vascular dementia.
Additionally, study participants were all from urban areas with relatively high levels of education, which may limit the generalizability of the results to other populations. Higher education is associated with a slower rate of cognitive decline, which could influence 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 measures 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 novel preventive and therapeutic strategies for dementia.
The article titled “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.
