A recent study by researchers at Fudan University in Shanghai found that low levels of testosterone and elevated levels of proteins called neurofilament light chains significantly increase the risk of cognitive decline in older men. Alzheimer’s and Dementia.
Generally, as we age, our cognitive abilities decline. This decline may not be noticeable at first, but can become quite noticeable as we get older. However, cognitive decline does not affect everyone equally. Some people maintain good cognitive function into their 70s, 80s, and beyond, while others experience a much more rapid decline.
Dementia is a condition characterized by a severe and progressive decline in cognitive function that significantly impairs daily life. Dementia includes a range of symptoms caused by a variety of neurological problems that damage the nervous system. The most common type is Alzheimer’s disease, which is characterized by the accumulation of certain proteins in the brain, forming plaques and neurofibrillary tangles, which cause the gradual death of neurons in the affected areas.
Some dementias can be prevented or their progression slowed, which is why scientists are actively researching ways to predict who will develop dementia. Among the factors being investigated are sex hormones, which are thought to modulate the risk of cognitive decline. For example, it has been suggested that an early decline in estrogen in women may lead to the development of dementia.
Another important marker of impending dementia is neurofilament light chain. This protein maintains the shape and structural integrity of nerve cells and acts as a skeleton for the cell. Normally, neurofilament light chain molecules remain within neurons. However, when these proteins are found in large amounts in the blood, it is an indication that neurons are being damaged and releasing these proteins into the bloodstream.
Study author Shuning Tan and his colleagues wanted to investigate how accurately future cognitive decline in older men could be predicted based on information about testosterone and neurofilament light chain levels. They hypothesized that declining testosterone levels are associated with cognitive decline and that predictions based on both testosterone and neurofilament light chain levels would be even more effective at predicting cognitive decline.
The researchers analyzed data from 581 older men who participated in the Shanghai Aging Study, a longitudinal, community-based cohort study launched in 2010 to investigate the prevalence, incidence, and risk factors for cognitive impairment among older people in China. All participants were residents of the Jing’an Temple community in central Shanghai, were aged 60 years or older, and were free of dementia at the start of the study. Participants were followed for an average of 6.7 years.
At the start of the study, participants provided a blood sample that allowed researchers to measure their levels of testosterone and neurofilament light chains. Participants also underwent a battery of neuropsychological tests to assess cognitive function. Between 2014 and 2023, participants were retested at least once, allowing researchers to compare cognitive function over time and determine whether dementia was progressing.
Results showed that 45 participants developed cognitive decline over the course of the study. Compared with 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 high blood pressure. They also tended to have lower levels of testosterone and higher levels of neurofilament light chains in their blood.
The researchers combined data on testosterone and neurofilament light chain levels to classify participants into three risk groups: high, medium, and low. Participants in the high-risk group were five to six times more likely to experience cognitive decline than those in the low-risk group.
“Our findings suggest that the combination of testosterone and neurodegenerative markers may provide reliable predictive insight into future cognitive decline,” the study authors concluded.
This study presents a new way to predict future cognitive decline in older men. However, it has some limitations. The diagnosis of dementia in this study was based solely on measures of cognitive ability, without looking at the specific type or cause of dementia. This approach does not distinguish between different forms of dementia, such as Alzheimer’s disease or vascular dementia.
Furthermore, all study participants were relatively well-educated and from urban areas, which may limit the generalizability of the findings to other populations. Higher education is associated with a slower rate of cognitive decline, which could influence the results.
Future studies should aim to replicate these findings in larger and more diverse populations and to investigate the mechanisms underlying the observed associations. Longitudinal studies with repeated measurements of testosterone and neurofilament light chains may provide more nuanced insights into how these factors interact over time to affect cognitive health. Understanding the specific biological pathways by which testosterone and neurofilament light chains affect cognitive function may lead to new prevention and treatment strategies for dementia.
Paper, “The joint effect of testosterone and neurofilament light chains on cognitive decline in men: the Shanghai Aging Study.” authors are Shuning Tang, Zhenxu Xiao, Fangting Lin, Xiaoniu Liang, Xiaoxi Ma, Jie Wu, Xiaowen Zhou, Qianhua Zhao, Junling Gao, Qianyi Xiao, and Ding Ding.
