Serum Neurofilament Light Chain and Cognitive Performance in Women with and without HIV: A Longitudinal Study Over Approximately 8 Years

Research Background

With the widespread use of highly active antiretroviral therapy (ART), the life expectancy of individuals infected with human immunodeficiency virus (HIV) has significantly increased. However, as they age, HIV-infected individuals face more health issues related to non-communicable diseases (NCDs), such as cognitive impairment, Alzheimer’s disease and related dementias (ADRD), and acquired brain injury. Serum neurofilament light chain (sNfL) is a biomarker widely used to assess the extent of neurodegeneration and neuronal damage. Although studies have shown the value of sNfL in male HIV-infected individuals, there is relatively less research on female HIV-infected individuals, especially regarding its relationship with cognitive performance. Therefore, this study aims to fill this knowledge gap by exploring the relationship between sNfL levels and cognitive performance among women living with HIV (WLWH) and women living without HIV (WLWOh).

Paper Source

This study was conducted by researchers from multiple institutions including SUNY Downstate Health Sciences University, Temple University, University of Gothenburg, UCL, Johns Hopkins University, and others. The paper was published in the journal EClinicalMedicine and was released online in October 2024, DOI: 10.1016/j.eclinm.2024.103052.

Research Process

Study Population

The data for this study came from the Women’s Interagency HIV Study (WIHS), which began in 1994 and is the largest prospective study of HIV in women in the USA. Researchers selected 417 participants (290 WLWH, 127 WLWOh) who completed baseline and follow-up cognitive assessments and had their serum sNfL levels measured between 2008 and 2019.

Study Methods

Sample Collection and Processing

Serum samples were collected using Becton Dickinson Vacutainer® CPT™ tubes and processed in a CLIA-certified laboratory. Subsequently, the serum was stored at -70°C to -80°C to ensure sample quality.

Data Collection

Researchers collected sociodemographic characteristics, behavioral factors, clinical data, and cognitive assessment results. Cognitive assessments included attention, working memory, executive function, processing speed, learning ability, memory, verbal fluency, and global cognition.

Laboratory Testing

The concentration of serum sNfL was measured using single molecule array (SIMOA) technology on an HD-X analyzer by Quanterix. All samples were tested in one round of experiments to minimize experimental error.

Statistical Analysis

Multivariable linear regression models were used to analyze the relationship between sNfL levels at baseline and follow-up with cognitive performance. Models were adjusted for age, income, BMI, depressive symptoms, estimated glomerular filtration rate (eGFR), diabetes, smoking, alcohol use, and other drug use. Additionally, for WLWH, models were further adjusted for CD4 count, HIV viral load, ART use, and AIDS history.

Research Results

Baseline Characteristics

At baseline, the average age of WLWH was 51.6 years, while that of WLWOh was 48.7 years. About half of the participants identified as African American or Black. Most participants had a high school education or higher, and most were current or former smokers. WLWH performed worse in cognitive tests, particularly in memory and global cognition.

Changes in sNfL Levels

At baseline, the median sNfL level was significantly higher in WLWH compared to WLWOh (p < 0.001). This difference persisted at follow-up (p < 0.0001). Over approximately 8 years, sNfL levels increased by 46.5% in WLWH, while in WLWOh, the increase was only 24.4%.

Relationship Between Cognitive Performance and sNfL Levels

In WLWH, higher baseline sNfL levels were associated with poorer processing speed, learning ability, memory, and verbal fluency. In WLWOh, higher baseline sNfL levels were associated with poorer executive function, processing speed, and verbal fluency. At follow-up, higher sNfL levels were linked to declines in executive function in WLWH, while in WLWOh, they were associated with declines in executive function, processing speed, attention, memory, and global cognitive performance. An increase in sNfL over approximately 8 years was related to declines in executive function, processing speed, memory, and global cognitive performance in WLWOh, and only executive function decline in WLWH.

Conclusion

This study found that higher sNfL levels and their approximate 8-year increase were closely related to declines in cognitive performance in both WLWH and WLWOh, but showed different association patterns at different time points and in different cognitive domains. Despite higher sNfL levels in WLWH, more pronounced cognitive declines were observed in WLWOh. This suggests that sNfL as a biomarker has potential applications in assessing cognitive health in both women with and without HIV.

Research Highlights

1. First Longitudinal Study: This is the first longitudinal study examining changes in sNfL levels over approximately 8 years and their relationship with cognitive performance in women with and without HIV.
2. Novel Biomarker: sNfL, as a blood-based biomarker, can reflect the degree of neuronal damage, providing a new tool for evaluating brain health in women with HIV.
3. Important Clinical Implications: The findings support using sNfL as an important indicator for monitoring neurodegenerative diseases and cognitive impairments, aiding early diagnosis and intervention.

Significance and Value of the Study

This study not only reveals the complex relationship between sNfL levels and cognitive performance in women with and without HIV but also provides important references for future research. By further exploring the application of sNfL in different populations, we can better understand the mechanisms of neurodegenerative diseases and develop more effective prevention and treatment strategies. Additionally, this study emphasizes the importance of using blood-based biomarkers to assess brain health in resource-limited settings, offering new ideas for public health activities.