How plasma biomarkers illuminate brain health in women with HIV | Image Credit: © angellodeco – © angellodeco –

Plasma biomarkers may be indicators of brain health among people living with HIV (PLWH), according to a recent study published in JAMA Network Open.


  1. The study suggests that plasma biomarkers may serve as indicators of brain health in people living with HIV (PLWH), emphasizing the potential of blood-based markers in understanding neurological conditions.
  2. Effective and timely prescription of ARTs has reduced the rates of HIV-associated neurocognitive disorders. However, older PLWH are still at risk of conditions such as Alzheimer’s disease (AD).
  3. Women, both with and without HIV, may be at risk of adverse brain outcomes over time. The study underscores the need to identify blood-based AD biomarkers for early diagnosis, especially in the context of the potential increased risk in women living with HIV.
  4. The cohort study investigates the association between changes in plasma AD biomarkers and neuropsychological performance in women aged 40 and older. This approach helps bridge the gap between biological markers and clinical outcomes, providing a comprehensive understanding of brain health.
  5. The study reveals that women living with HIV generally performed worse in memory, learning, verbal fluency, and overall neuropsychological function compared to women without HIV.

Effective antiretroviral therapies (ARTs) have increased life expectancies among PLWH, leading to chronic HIV. However, HIV is still a public health concern, with over 38 million cases worldwide.

PLWH can experience neurological disorders including peripheral neuropathy and cognitive impairment, as well as neuropsychiatric conditions such as depression. Effective and fast prescribing of ARTs have decreased the rates of HIV-associated neurocognitive disorders, but older PLWH remain at risk for Alzheimer disease (AD).

Over 50 million people worldwide experience AD, which is the seventh leading cause of death in the United States. As women living with HIV (WLWH) and women living without HIV (WLWOH) may be at risk of more adverse brain outcomes over time, it is important to determine blood-based AD biomarkers which can lead to early diagnosis.

Investigators conducted a cohort study to determine the association between 1-year change in plasma AD biomarkers and neuropsychological performance (NP) among WLWH and WLWOH aged 40 years and older. Data was obtained from the Women’s Interagency HIV Study (WIHS), prospective study evaluating HIV in US women.

Sociodemographic characteristics obtained included race and ethnicity, date of birth, annual income, educational level, hypertension characteristics, diabetes characteristics, and tobacco, marijuana, alcohol, and drug use. Clinical characteristics included weight, height, systolic blood pressure, and diastolic blood pressure.

Prescribed antihypertensive medication use was used to define hypertension, and fasting glucose of 126 mg/dL or more to define diabetes. HIV-status, HIV viral load, and CD4 T cell count were laboratory confirmed, with other HIV-related measures including ART use and AIDS diagnosis.

Depression was a neurological measure based on the Center for Epidemiological Studies-Depression (CES-D) scale, determined by CES-D scores of 16 or above 60. Other neurological measures included numb hands and feet, memory loss, and confusion and getting lost.

There were 7 NP domains evaluated: attention and working memory, executive function, processing speed, memory, learning, verbal fluency, and fine motor skills. These domains were measured using the Letter-Number Sequencing test, Trail Making Test Part B, Stroop test, Hopkins Verbal Learning Test-Revised, Symbol Digit Modalities Test, Controlled Oral Word Association Test, Category Fluency Test, and Grooved Pegboard Test.

The final analysis included 307 women, of whom 209 were WLWH and 98 were WLWOH. Of participants, 96% were aged over 50 years, 53% were Black, 70% had a high school education or higher, and 78% were current or former smokers.

WLWH had a mean learning NP score of 47.8, memory score of 48.3, verbal fluency score of 48.3, and global score of 49.2. For WLWOH, these scores were 51.4, 52.4, 50.7, and 51.1, respectively. No AD or dementia diagnosis was observed at baseline.

At baselin, WLWH had increased median plasma levels of Aβ40, GFAP, and NFL compared to WLWOH. WLWH with higher t-tau levels had improved learning performance, and WLWOH with a higher Aβ42 to Aβ40 ratio had improved attention.

Patients with a greater average increase in Aβ40 had reduced memory, motor performance, and learning, while those with a greater average increase in Aβ42 had worse learning and motor performance. A greater increase in p-tau231 was associated with worse motor performance and a greater increase in NFL with worse verbal fluency, processing speed, and motor performance.

WLWH performed worse overall on memory, learning, verbal fluency, and global NP compared to WLWOH. Overall, these results indicated certain plasma biomarkers can be used to predict brain health among WLWH and WLWOH.


Li X, Yucel R, Clervius H, et al. Plasma biomarkers of alzheimer disease in women with and without HIV. JAMA Netw Open. 2023;6(11). doi:10.1001/jamanetworkopen.2023.44194