Research Summary

Study: Cognitive Frailty Affects Nearly 7% of Adults Over 50 With HIV

Edited by:
Ashton L. Stahl

Key Highlights

  • Cognitive frailty was identified in 6.8% of adults 50 years or older with HIV.
  • Older age, lower nadir CD4+ cell count, and polypharmacy were independently associated with cognitive frailty.
  • Individuals with cognitive frailty showed worse performance across all cognitive domains and higher inflammatory biomarkers.

Cognitive frailty, defined as the concurrent presence of physical frailty and cognitive impairment in the absence of dementia, was present in nearly 7% of older adults living with HIV, according to a study recently published in AIDS. The prevalence observed in this Italian cohort exceeded estimates reported in the general population over 65 years old, underscoring the relevance of aging-related syndromes in people with HIV aged 50 years and older.

The investigators aimed to characterize the prevalence of cognitive frailty and identify associated risk factors in people with HIV, a population increasingly affected by age-related multimorbidity. The study also explored the relationship between cognitive frailty, HIV-related factors, comorbidities, and medication burden.

This cross-sectional observational study included antiretroviral therapy-experienced adults aged 50 years or older attending the Modena HIV Metabolic Clinic in Italy between January 2016 and April 2023. Neurocognitive performance was assessed using the Cogstate battery across 6 cognitive domains, with impairment defined by a global deficit score of at least 0.5. Frailty was evaluated using a validated 37-item frailty index, categorizing individuals as frail or fit.

Participants were classified into 4 groups based on frailty and cognitive test impairment status. Multivariable generalized linear mixed models were used to identify factors independently associated with cognitive frailty, adjusting for relevant clinical and HIV-related variables.

Study Findings
Among 1,258 participants, 85 individuals met criteria for cognitive frailty, corresponding to a prevalence of 6.8%. The median age of the cohort was 58 years, and 73% were men. Individuals with cognitive frailty were older and had higher BMI as well as higher rates of obesity, smoking, multimorbidity, sarcopenia, and polypharmacy compared with other groups.

Cognitive frailty was associated with lower nadir CD4+ cell counts and a longer duration of HIV infection. Participants with cognitive frailty demonstrated significantly poorer performance across all 6 cognitive domains and had higher levels of inflammatory and metabolic biomarkers, including C-reactive protein, D-dimer, and insulin resistance.

In adjusted analyses, age per 5-year increase (odds ratio [OR], 1.27), lower nadir CD4+ cell count (OR, 0.81), and polypharmacy (OR, 3.47) were independently associated with cognitive frailty. These associations remained significant after adjustment for multimorbidity, depression, time since HIV diagnosis, and cumulative exposure to integrase inhibitors.

Clinical Implications
According to the study authors, the findings suggest that cognitive frailty is relatively common in people with HIV aged 50 years or older and may reflect both HIV-specific factors and aging-related processes. The association with nadir CD4+ cell count supports a potential role of historical immune suppression in the development of cognitive frailty.

The authors noted that identifying cognitive frailty may provide a broader clinical framework to assess vulnerability in aging people with HIV, complementing existing approaches focused solely on neurocognitive impairment or frailty alone.

Expert Commentary
“…CF prevalence in people with HIV > 50 years was higher to what was observed in the general population >65 years. Nadir CD4+ cell count was associated with CF, suggesting an HIV specific contribution along with chronic inflammation related to the development of this condition,” the researchers concluded.

Reference
Milic J, Calza S, Lazzarini L, et al. Prevalence and risk factors of cognitive frailty in people with HIV. AIDS. 2026;40(2):133-142. doi:10.1097/QAD.0000000000004352