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. 2025 May 23;11(2):e70109.
doi: 10.1002/trc2.70109. eCollection 2025 Apr-Jun.

Psychosocial behavioral phenotypes of racially/ethnically minoritized older adults enrolled in HABS-HD differ on neuroimaging measures of brain age gap, hippocampal volume, and cortical thickness

Alexandra L Clark  1 , Makenna B McGill  1 , Alexandra J Weigand  2 , Julie K Wisch  3 , Kalen Petersen  3 , Beau Ances  3 , Meredith N Braskie  4 , Sid O'Bryant  5   6 , Kelsey R Thomas  7   8 ; HABS‐HD Study Team
Affiliations

Psychosocial behavioral phenotypes of racially/ethnically minoritized older adults enrolled in HABS-HD differ on neuroimaging measures of brain age gap, hippocampal volume, and cortical thickness

Alexandra L Clark et al. Alzheimers Dement (N Y). .

Abstract

Introduction: This study examined whether previously identified psychosocial behavioral phenotypes differed on structural neuroimaging markers.

Methods: Latent profile analysis (LPA) employed in a sample of 1820 community-dwelling older adults (1118 Hispanic and 702 Black) replicated previous Low Resource/Low Distress, High Resource/Low Distress, and Low Resource/High Distress phenotype classifications. Analyses of covariance (ANCOVAs) adjusting for relevant factors examined phenotype differences on neuroimaging outcomes of predicted brain age gap (BAG) (DeepBrainNet Predicted Age - Chronological Age), hippocampal volume, and cortical thickness of a meta-temporal region of interest.

Results: The Low Resource/Low Distress and Low Resource/High Distress phenotypes had significantly higher predicted BAGs relative to the High Resource/Low Distress phenotype, and the Low Resource/High Distress group displayed significantly lower hippocampal volumes and meta-temporal cortical thickness relative to High Resource/Low Distress phenotype.

Discussion: Results highlight there are neurostructural variations across psychosocial behavioral phenotypes and indicate the Low Resource/High Distress group may be at risk for ADRD.

Highlights: Brain age gap (BAG), hippocampal volumes, and cortical thickness differences were tested.The High Resource/Low Distress phenotype had the most favorable imaging outcomes.The Low Resource/High Distress phenotype demonstrated the poorest imaging outcomes.Risk for Alzheimer's disease and related dementias (ADRD) may differ across psychosocial behavioral phenotypes.

Keywords: brain age gap; health disparities; hippocampal volume; neurodegeneration; neuroimaging; phenotyping; psychosocial; risk and resilience to ADRD.

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Conflict of interest statement

The authors have no conflict of interest to report. Author disclosures are available in supporting information.

Figures

FIGURE 1
FIGURE 1
Identified psychosocial behavioral phenotypes in baseline HABS‐HD (Wave 5) data release. X‐axis depicts variables that were included in the psychosocial behavioral phenotypes and y‐axis depicts average levels for each variable included in the phenotype in a z‐score scale. GDS, Geriatric Depression Scale; HABS‐HD, Health and Aging Brain Study‐Health Disparities; OCC, occupational complexity composite; PSWQ, Penn State Worry Questionnaire. Class 1, Low Resource/Low Distress phenotype (depicted in red); Class 2, High Resource/Low Distress phenotype (depicted in blue); Class 3, Low Resource/High Distress group (depicted in green).
FIGURE 2
FIGURE 2
Forest plot of estimated marginal means for each neuroimaging metric by psychosocial behavioral phenotype. X‐axis depicts estimated marginal means and 95% confidence intervals across three neuroimaging metrics, and y‐axis depicts phenotypes labels. Brain age gap findings are depicted in red; left hippocampal volumes are depicted in green; right hippocampal volumes are depictured in blue. Note higher levels indicate larger brain age gaps, whereas lower values indicated smaller hippocampal volumes. Estimated marginal means are adjusted for age, sex/gender, race/ethnicity, scanner, and ICV (hippocampal volumes only). ICV, intracranial volume.
FIGURE 3
FIGURE 3
Violin plots of brain age gap (BAG) across the psychosocial behavioral phenotypes. X‐axis depicts phenotype labels, and y‐axis depicts residualized z‐scores for brain age gap that were adjusted for age, sex/, race/ethnicity, and scanner. Line on chart with asterisk indicates significant differences in brain age gap between the phenotypes. * = denotes significant differences between the High Resource/Low Distress and Low Resource/Low Distress groups at the p‐unadjusted = <0.001 level. ** = denotes significant differences between the High Resource/Low Distress and Low Resource/High Distress groups at the p‐unadjusted = 0.001 level.
FIGURE 4
FIGURE 4
Violin plots of left hippocampal volumes across the psychosocial behavioral phenotypes. X‐axis depicts phenotype labels, and y‐axis depicts residualized z‐scores for left hippocampal volumes that were adjusted for age, sex/gender, race/ethnicity, intracranial volume (ICV), and scanner. Line on chart with asterisk indicates significant differences in brain age gap between the phenotypes. * = denotes significant differences between the High Resource/Low Distress and Low Resource/High Distress groups at the p‐unadjusted = 0.005 level.
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