Hector M. Gonzalez

Background and ObjectivesHispanic/Latino Americans are disproportionately affected by vascular risk factors (VRFs) linked to cognitive decline, yet they remain underrepresented in neuroimaging rese...

Background and ObjectivesHigh adherence to the Mediterranean diet (MeDi) has been associated with slower age-dependent cognitive decline and better cardiovascular health (CVH). We examined the asso...

INTRODUCTION: Research studying associations between plasma amyloid‐tau‐neurodegeneration (ATN) biomarkers and vascular factors, such as diabetes, is limited. We sought to examine associations between diabetes status and plasma ATN biomarkers in diverse Hispanic/Latino individuals. METHODS: We used data from the Hispanic Community Health Study/Study of Latinos and the Study of Latinos‐Investigation of Neurocognitive Aging ancillary studies. Our exposures included diabetes status and hemoglobin A1c (HbA1c) percentage. Outcomes included amyloid beta (Aβ) 42/40 ratio, phosphorylated tau 181 (p‐tau181), neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP). RESULTS: The final analytic sample was N = 6264. Diabetes, but not prediabetes, was associated with higher NfL and p‐tau181 and lower Aβ42/40 ratio. Elevated HbA1c percentage was associated with higher NfL, p‐tau181, and GFAP and lower Aβ42/40. DISCUSSION: Diabetes was associated with plasma biomarkers of Alzheimer's disease pathology and non‐specific neurodegeneration. Reducing diabetes prevalence could be beneficial for lowering dementia risk in this population.

Low life-course socioeconomic position (SEP) has been associated with worse cognitive function in older age. However, its association with brain structure remains unclear. We assessed whether SEP at 3 periods of the life-course and socioeconomic mobility are associated with later-life MRI-derived brain volumes. We used longitudinal data from the Hispanic Community Health Study/Study of Latinos and its Investigations of Neurocognitive Aging-MRI ancillary study. We determined childhood SEP using participant self-reports of their parent's educational attainment (z-scored brain volumes. We included 2,400 adults aged 50-85 years. Higher childhood SEP (TGMV 0.13; 95% CI 0.02-0.24) and higher height residuals (TGMV 0.17; 95% CI 0.09-0.24) were associated with larger brain volumes. Similarly, higher adult SEP at visit 1 (TGMV 0.18; 95% CI 0.05-0.31) and visit 2 (TGMV 0.16; 95% CI 0.04-0.29), upward socioeconomic mobility, and stable high SEP were associated with larger brain volumes. Higher adult SEP at visit 2 (log-WMHV -0.16; 95% CI -0.29 to -0.02) and upward mobility were also associated with smaller log-WMHV. This study highlights the contribution of higher life-course SEP to greater brain health as indexed by larger brain volumes in later life. Our results suggest that the effect of early-life socioeconomic disadvantages persists beyond socioeconomic conditions in adulthood.

Objective: Hispanic/Latino individuals have higher rates of type 2 diabetes and Alzheimer’s Disease and Related Dementia (ADRD) burden compared to non-Hispanic whites. Diabetes is a risk factor for ADRD, but the extent of its associations with brain markers in community-dwelling Hispanic/Latino individuals is unknown. We examined how glycemic dysregulation and diabetes associate with small vessel disease damage and neurodegeneration in Hispanic/Latino adults from a large and community-representative cohort study. Research design and methods: We used data from 2627 individuals, aged 35–85 years, from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL; 2008–2011) who underwent brain imaging through the SOL/Investigations of Neurocognitive Aging MRI (SOL-INCA MRI; 2018–2022) study. Exposures included diabetes status and HbA1c (%) levels. Outcomes included white matter hyperintensities, free water, fractional anisotropy, and volumetric regions including hippocampus, lateral ventricles, total brain, and cortical gray matter. Results: Diabetes status, compared to no diabetes, was associated with larger white matter hyperintensity volume, lower fractional anisotropy, and higher free water. Diabetes status was also associated with larger lateral ventricles as well as smaller total brain, frontal gray matter, and occipital gray matter volumes. The association between diabetes and brain MRI outcomes was stronger in middle-aged and older individuals (50 years and older) compared to younger individuals (35–49 years). Conclusion: Diabetes was associated with markers of small vessel disease (white matter micro and macrostructural damage) and neurodegeneration (smaller brain volumes). White matter hyperintensities have been associated with increased risk of stroke and cognitive decline. Other work has found that free water and fractional anisotropy may predict worse cognitive performance, even in normal-appearing white matter. Smaller brain volumes have also been associated with cognitive deficits. These findings highlight the additional ADRD burden this population faces due to their higher diabetes prevalence.

INTRODUCTION: Better cardiovascular health (CVH) is associated with better cognitive function, but limited data exist on its association with cerebrovascular disease (CVD) burden using the Life's Essential 8 (LE8) metric, particularly among Hispanic/Latino adults. METHODS: LE8 scores (range: 0 to 100) were calculated at baseline (2008 to 2011). Brain magnetic resonance imaging volumetric outcomes (2017 to 2022) included cerebral small vessel disease (cSVD) burden (infarcts, cerebral microbleeds, high white matter hyperintensity [WMH] burden, enlarged perivascular spaces), gray matter (GM), and WMH volumes. Survey‐weighted regression models examined associations between LE8, adjusting for demographic factors. RESULTS: Among 2211 participants (mean age [SE] = 57.6 [8.0] years, 58.5% female), higher LE8 score was associated with reduced cSVD burden and lower odds of infarcts and WMH burden. Higher LE8 scores were associated with greater total and frontal GM and lower WMH volumes. DISCUSSION: Better CVH was associated with reduced CVD burden and greater GM volume in Hispanic/Latino adults.

Background: The purpose of this study was to estimate the prevalence and number of cerebral microbleeds (CMBs) in a Hispanic and Latino cohort from various self‐identified backgrounds and test associations with age, vascular risk factors, APOE (apolipoprotein E), and cognitive function. Methods: The 3T brain magnetic resonance imaging exams were obtained on SOL‐INCA‐MRI (Study of Latinos‐Investigation of Neurocognitive Aging‐MRI) magnetic resonance imaging study participants, a community‐based study. CMB number was counted and categorized as: (1) any CMB, (2) lobar only, (3) deep only, (4) mixed, (5) deep+mixed, and (6) lobar+mixed. We examined whether prevalence of CMBs varied by age, sex, education, Hispanic background, cardiovascular risk factors (hypertension, diabetes, Framingham Risk Score), APOE genotype, and cognition. Results: A total of 2455 participants were included who were 63.0±8.4 years of age, 67.9% women, and 62.2% high school education or higher. CMBs prevalence was 11.7% (8.3% lobar only, 2.0% deep only, 1.4% mixed locations). After adjusting for age, sex, and education, a high Framingham Risk Score was associated with the presence of CMBs of all types, except lobar only. Prevalent stroke/transient ischemic attack was associated with higher likelihood of deep‐only CMBs. For participants with cognitive impairment, the adjusted prevalence of mixed CMBs (2.2% versus 1.1%, P =0.023) and deep‐only+mixed CMBs (5.2% versus 3.1%, P =0.010) was significantly higher compared with cognitively normal. Cognitive impairment was significantly associated with higher total CMB count (rate ratio, 1.46 [95% CI, 1.14–1.87]; P =0.003). No significant associations were found between diabetes, APOE4, and any CMB type. Conclusions: High vascular risk scores, self‐reported history of stroke/transient ischemic attack, and cognitive status were associated with a higher likelihood of CMBs, especially in deep regions.

BACKGROUND: Studies showed that hypertension predicts cognitive performance. It remains uncertain whether a bidirectional relationship exists. We investigated whether cognitive function predicts incident hypertension. METHODS: Data from the Hispanic Community Health Study/Study of Latinos were analyzed. Global cognitive score (GC) of nonhypertensive participants at baseline was derived by averaging z scores across 4 neurocognitive tests (brief Spanish-English verbal learning test sum and recall, word fluency, and digit symbol substitution test). Incident hypertension was investigated, on average, 6 years later. Sociodemographic characteristics and unhealthy behaviors (obesity, physical activity not at goal, low diet quality, smoking) were ascertained at baseline. Association of GC at baseline with incident hypertension (defined as blood pressure ≥130/80 mm Hg or on treatment) was investigated using logistic regression analyses adjusted for sociodemographic characteristics and time between visits. Multimodal analyses assessed whether unhealthy behaviors were pathway variables between GC and incident hypertension. RESULTS: A total of 6755 participants (mean [interquartile range] age, 53[48–59] years; 62% female) were included. At follow-up, 57% of individuals developed hypertension. In our final model, higher GC was associated with lower odds of incident hypertension (odds ratio, 0.85 [95% CI, 0.74–0.98]). In pathway analysis, indirect effects through unhealthy behaviors were small. Obesity was the only significant mediator (indirect odds ratio, 0.95 [95% CI, 0.90–0.99]). Smoking and physical activity not at goal were in the pathway of GC and obesity, but did not mediate GC-incident hypertension. CONCLUSIONS: Higher GC was associated with a lower incidence of hypertension 6 years later. Unhealthy behaviors may influence the association of cognitive function and incident hypertension.

Background: To examine preliminary associations between enlarged perivascular spaces (ePVS) and cerebrovascular small‐vessel disease, cortical atrophy, and cognitive impairment among a select cohort of Hispanic and Latino adults. The Hispanic and Latino population has a higher prevalence of dementia and vascular disease but is underrepresented in dementia research. This study addresses this gap by investigating ePVS in a large convenience cohort of Hispanic and Latino individuals. Methods: Brain magnetic resonance images from a convenience sample of 2161 participants, including 28.8% of individuals aged >50 years with cognitive impairment from the SOL‐INCA‐MRI (Study of Latinos–Investigation of Neurocognitive Aging Magnetic Resonance Imaging) study were analyzed. ePVS volume in the cerebral white matter was quantified using an automated method and then residualized with total cerebral volume. Associations between residualized mean ePVS volumes and demographic factors, magnetic resonance imaging measures, and cognitive impairment were assessed using regression models. Results: Residualized mean ePVS volume was significantly associated with age ( P P =0.03), white matter hyperintensity volume ( P P =0.009), cortical gray matter ( P P P =0.004). No significant sex differences in ePVS volume were observed when adjusting for head size. Conclusions: This convenience sample of Hispanic and Latino individuals demonstrates significant associations between ePVS volume and established markers of cerebrovascular small‐vessel disease, cortical atrophy, and cognitive impairment. These findings suggest that ePVS may be useful as an additional marker of vascular brain injury within this cohort.

Cerebral white matter hyperintensities (WMHs) on MRI are part of the spectrum of age-related brain vascular injury and are associated with increased risk of stroke and dementia. Genome-wide association studies (GWASs) conducted mostly in populations of European ancestry have identified several genetic loci. Although Hispanic/Latino adults have a greater burden of WMHs than their non-Hispanic White counterparts, they are vastly underrepresented in genetic studies. We sought to characterize the genetic architecture of WMHs in a Hispanic/Latino cohort by investigating the transferability of known WMH genetic loci and by leveraging Hispanic/Latino genetic diversity to map novel loci. We conducted genome-wide association and admixture mapping analyses of WMH volume in a sample of 2,159 diverse Hispanic/Latino adults (mean age: 62.4 years; 66% female). We investigated associations at 27 previously identified WMH loci. To identify additional loci, we meta-analyzed our genome-wide association results with those of the largest GWASs published to date. Accounting for population differences in linkage disequilibrium, we found some evidence of transferability of 20 of the 27 known WMH loci. Owing to power limitations, we could not exclude transferability of the remaining loci. Multiancestry meta-analysis combining our Hispanic/Latino genome-wide association results with those from a GWAS of non-Hispanic White (NHW) and African American (AA) populations identified a novel locus on 12q22 (p = 1.8 × 10⁻⁸) near NTN4 and tagged by rs10859915, which was previously associated with blood pressure and is an expression quantitative trait locus of AMDHD1. Admixture mapping identified a novel locus on 14q13.2, where higher counts of European ancestry at that locus were significantly associated with higher WMH volume (p = 4.9 x 10⁻⁷). This locus spans an 800-kilobase region containing RALGAPA1, with known impact on neuronal function and brain development. Aggregated rare coding variants in this gene were associated with WMHs in a previous analysis of 20,719 stroke-free and dementia-free adults. Our study suggests that WMH loci previously identified in NHW and AA individuals are relevant to Hispanic/Latino adults. It demonstrates the power of the diverse Hispanic/Latino population to fine-map known genetic loci and discover novel ones, augmenting our understanding of the genetic architecture of cerebral WMHs.