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Worse Brain Aging in PWH: factors - CVD,
Social Determinants, HCV, Viral Load, Unemployment
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These findings confirm the hypothesis that comorbid and socioeconomic factors are associated with brain aging alongside clinical metrics such as viral load. A broadened clinical perspective on healthy aging with HIV may require increased focus on such non-traditional determinants of health. Regional correlations between brain-age gap (BAG) and cortical or subcortical volumes.
The brain-age gap (BAG), defined as the difference between brain-predicted age and true chronological age, was modeled as a function of clinical, comorbid, and social factors for PWH and PWoH.
BAG was significantly elevated in PWH compared to PWoH (p=0.001).
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HIV CLINICAL, COMORBID, AND SOCIAL DETERMINANTS OF HEALTH ARE LINKED WITH BRAIN AGING
CROI 2023 Feb 20-23
Kalen J. Petersen, Tina Lu, Julie Wisch, June Roman, Nicolas Metcalf, Sarah Cooley, Beau Ances
Washington University in St. Louis, St. Louis, MO, USA
STUDY AIM: Identify factors beyond serostatus or viral load that best account for variability in brain aging, individually & in concert.
Background: Neuroimaging reveals brain changes linked with HIV infection and neurocognitive disorders. However, group-level differences between persons with HIV (PWH) and persons without HIV (PWoH) conceal substantial within-group heterogeneity in risk factor exposures. PWH experience elevated comorbidities such as cardiovascular disease and socioeconomic deprivation. However, the contribution of such factors to brain aging in PWH and PWoH remains to be quantified.
HIV is thought accelerate biological aging in multiple tissues including CNS- Aung et al., AIDS Behav 2020.
Cognitive impairment affects a large minority of persons with HIV (PWH) even in cART era - Heaton et al., Neurology 2010.
Complexity of aging for PWH increased by multiple prevalent co-morbidities: substance use, social determinants CVD, co-infections - all affect brain health.
Methods: PWH (n=379; age=44.8±15.5 yr.; 78.1% biologically male; 68.6% African-American; 77.8% undetectable viral load [< 50 copies/mL]) and PWoH (n=259; age=38.3±17.1 yr.; 49.8% male; 56.4% A.A.) were clinically characterized and underwent 3-Tesla T1-weighted magnetic resonance imaging (MRI).
DeepBrainNet, a publicly available machine learning algorithm, was applied to estimate brain-predicted age from MRI.
The brain-age gap (BAG), defined as the difference between brain-predicted age and true chronological age, was modeled as a function of clinical, comorbid, and social factors for PWH and PWoH separately using linear regression and variable selection.
To identify spatial patterns relevant to pathological aging, BAG values were correlated with regional brain volumes quantified with FreeSurfer v5.3.
Results:
BAG was significantly elevated in PWH compared to PWoH (p=0.001).
In PWH, BAG was positively associated with Framingham cardiovascular risk score (p=0.002), detectable viral load (p=0.006) and hepatitis C co-infection (p=0.006).
Over 10 years brain-age difference between minimum & maximum cardiovascular risk.
In PWH, hepatitis C-positive status was linked with older-appearing brain
Effect size = +4.2 years
Co-infection plays a known role in cognitive impairment
After variable selection, the model for PWH retained Framingham score and hepatitis C, and added early life stress and area deprivation index, a socioeconomic measure combining geospatial data on housing, employment, education, and income.
Employment: Unemployed or on-disability status associated with a greater brain-age gap in PWH only; Effect size: +3.1 years; Causality of this effect is unclear
SOCIAL DETERMINANTS of Health
Area Deprivation Index (ADI): is the aggregate measure of social determinants from tract-level data, reflects neighborhood socioeconomic factors (not participant specific):
income, education, housing quality.
Elevated BAG was associated with reduced regional gray matter volumes and larger ventricles, with distinct spatial patterns by serostatus. PWH showed more negative BAG-volume associations in cortical regions such as precuneus and posterior cingulate gyrus, and subcortical structures including putamen, globus pallidus, and cerebellum (see Figure).
Conclusion: These findings confirm the hypothesis that comorbid and socioeconomic factors are associated with brain aging alongside clinical metrics such as viral load. A broadened clinical perspective on healthy aging with HIV may require increased focus on such non-traditional determinants of health. Regional correlations between brain-age gap (BAG) and cortical or subcortical volumes. There is a High variability in brain aging for both PWH & PWoH.
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