 |
|
|
| |
Effects of clinical, comorbid, and social determinants of health on brain ageing in people with and without HIV: a retrospective case-control study
|
| |
| |
February 07, 2023
Lancet HIV
Petersen et al.
Download the PDF here
Our findings indicate that comorbid and social determinants of health are associated with brain ageing in people with HIV, alongside traditional HIV metrics such as viral load and CD4 cell count, suggesting the need for a broadened clinical perspective on healthy ageing with HIV, with additional focus on comorbidities, lifestyle changes, and social factors.
People ageing with HIV exhibit altered brain structure and function compared with those without HIV, including morphological changes detectable on MRI.
However, group-level differences conceal substantial within-group heterogeneity. Although dementia is increasingly rare because of combination antiretroviral therapy (ART), more subtle forms of cognitive impairment persist in a subset of people with HIV, in some instances diminishing quality of life.
By use of neuroimaging, machine learning, and model selection, we have shown that a combination of clinical measures, comorbidities, and social determinants of health are associated with brain-predicted age in people with HIV and people without HIV. Cardiovascular disease burden, detectable HIV viral load, and hepatitis C co-infection were identified as the strongest univariate correlates of brain-age gap in people with HIV. Additionally, the effects of social factors such as unemployment and area socioeconomic deprivation were identified in multivariate regression. Differences in significant variables between univariate and multivariate analyses could have several causes. For example, two predictors with high colinearity, accounting for shared variance in the response variable, could both show significant effects on brain-age gap in independent univariate tests, but not in a multivariate model.
Summary
Background
Neuroimaging reveals structural brain changes linked with HIV infection and related neurocognitive disorders; however, group-level comparisons between people with HIV and people without HIV do not account for within-group heterogeneity. The aim of this study was to quantify the effects of comorbidities such as cardiovascular disease and adverse social determinants of health on brain ageing in people with HIV and people without HIV.
Methods
In this retrospective case-control study, people with HIV from Washington University in St Louis, MO, USA, and people without HIV identified through community organisations or the Research Participant Registry were clinically characterised and underwent 3-Tesla T1-weighted MRI between Dec 3, 2008, and Oct 4, 2022. Exclusion criteria were established by a combination of self-reports and medical records. DeepBrainNet, a publicly available machine learning algorithm, was applied to estimate brain-predicted age from MRI for people with HIV and people without HIV. The brain-age gap, defined as the difference between brain-predicted age and true chronological age, was modelled as a function of clinical, comorbid, and social factors by use of linear regression. Variables were first examined singly for associations with brain-age gap, then combined into multivariate models with best-subsets variable selection.
Findings
In people with HIV (mean age 44·8 years [SD 15·5]; 78% [296 of 379] male; 69% [260] Black; 78% [295] undetectable viral load), brain-age gap was associated with Framingham cardiovascular risk score (p=0·0034), detectable viral load (>50 copies per mL; p=0·0023), and hepatitis C co-infection (p=0·0065).
After variable selection, the final model for people with HIV retained Framingham score, hepatitis C, and added unemployment (p=0·0015). Educational achievement assayed by reading proficiency was linked with reduced brain-age gap (p=0·016) for people without HIV but not for people with HIV, indicating a potential resilience factor.
When people with HIV and people without HIV were modelled jointly, selection resulted in a model containing cardiovascular risk (p=0·0039), hepatitis C (p=0·037), Area Deprivation Index (p=0·033), and unemployment (p=0·00010). Male sex (p=0·078) and alcohol use history (p=0·090) were also included in the model but were not individually significant.
In people with HIV, 10-year Framingham scores, and lifetime alcohol, cocaine, and tobacco use were greater than in people without HIV (table). People with HIV lived in neighbourhoods with greater socioeconomic disadvantage as measured by the Area Deprivation Index, experienced more early life stressors, and had lower educational achievement on the Wide Range Achievement Test reading subtest. For people with HIV, mean viral load was 63·1 copies per mL, and mean CD4 T-cell counts were 588·0 cells per μL, with a mean nadir of 224·3 cells per μL. Of 379 people with HIV, 25 reported a history of hepatitis C.
Interpretation
Our findings indicate that comorbid and social determinants of health are associated with brain ageing in people with HIV, alongside traditional HIV metrics such as viral load and CD4 cell count, suggesting the need for a broadened clinical perspective on healthy ageing with HIV, with additional focus on comorbidities, lifestyle changes, and social factors.
Funding
National Institute of Mental Health, National Institute of Nursing Research, and National Institute of Drug Abuse.
|
| |
|
|
|
|
|
