Spanish English Verbal Learning Test Research Articles

The association of insulin responses and insulin sensitivity with cognition in adults with pre-diabetes: The Diabetes Prevention Program Outcomes Study

ObjectiveDysglycemia is a significant risk factor for cognitive impairment. However, which pathophysiologic determinant(s) of dysglycemia, impaired insulin sensitivity (ISens) or the islet β-cell's response (IResp), contribute to poorer cognitive function, independent of dysglycemia is not established. Among 1052 adults with pre-diabetes from the Diabetes Prevention Program Outcomes Study (DPPOS), we investigated the relationship between IResp, ISens and cognitive function. Research design and methodsIResp was estimated by the insulinogenic index (IGI; pmol/mmol) and ISens as 1/fasting insulin from repeated annual oral glucose tolerance tests. The mean IResp and mean ISens were calculated over approximately 12 years of follow-up. Verbal learning (Spanish-English Verbal Learning Test [SEVLT]) and executive function (Digital Symbol Substitution Test [DSST]) were assessed at the end of the follow-up period. Linear regression models were run for each cognitive outcome and were adjusted for dysglycemia and other factors. ResultsHigher IResp was associated with poorer performance on the DSST (−0.69 points per 100 unit increase in IGI, 95 % CI: −1.37, −0.01). ISens was not associated with DSST, nor were IResp or ISens associated with performance on the SEVLT. ConclusionsThese results suggest that a greater β-cell response in people at high risk for type 2 diabetes is associated with poorer executive function, independent of dysglycemia and ISens.

Association Between Hypertensive Disorders of Pregnancy and Interval Neurocognitive Decline: An Analysis of the Hispanic Community Health Study/Study of Latinos.

To evaluate whether hypertensive disorders of pregnancy, including gestational hypertension, preeclampsia, and eclampsia, are associated with cognitive decline later in life among U.S. Hispanic/Latina individuals. The HCHS/SOL (Hispanic Community Health Study/Study of Latinos) is a prospective population-based study of Hispanic/Latino individuals aged 18-74 years from four U.S. communities. This analysis included parous individuals aged 45 years or older who participated in the HCHS/SOL clinic study visit 1 (2008-2011) neurocognitive assessment and subsequently completed a repeat neurocognitive assessment as part of the Study of Latinos-Investigation of Neurocognitive Aging ancillary study visit 2 (2015-2018). Hypertensive disorders of pregnancy were assessed retrospectively by self-report of any gestational hypertension, preeclampsia, or eclampsia. Cognitive functioning was measured at both study visits with the Brief Spanish-English Verbal Learning Test, Digit Symbol Substitution, and Word Fluency. A regression-based approach was used to define cognitive decline at visit 2 as a function of cognition at visit 1 after adjustment for age, education, and follow-up time. Linear regression models were used to determine whether hypertensive disorders of pregnancy or their component diagnoses were associated with standardized cognitive decline after adjustment for sociodemographic characteristics, clinical and behavioral risk factors, and follow-up time. Among 3,554 individuals included in analysis, the mean age was 56.2 years, and 467 of individuals (13.4%) reported at least one hypertensive disorder of pregnancy. Individuals with hypertensive disorders of pregnancy compared with those without were more likely to have higher mean systolic blood pressure, fasting glucose, and body mass index. After an average of 7 years of follow-up, in fully adjusted models, gestational hypertension was associated with a 0.17-SD relative decline in Digit Symbol Substitution scores (95% CI, -0.31 to -0.04) but not other cognitive domains (Brief Spanish-English Verbal Learning Test or Word Fluency). Neither preeclampsia nor eclampsia was associated with neurocognitive differences. The presence of preeclampsia or eclampsia was not associated with interval neurocognitive decline. In this cohort of U.S. Hispanic/Latina individuals, gestational hypertension alone was associated with decreased processing speed and executive functioning later in life.

Abstract MP44: Non-Genetic Component of Height as a Surrogate Marker for Childhood Socioeconomic Status and Its Association With Cardiovascular and Brain Health: Results From HCHS/SOL

Introduction: Childhood socioeconomic status (SES) has been recognized to have lifelong effects on health, but often studies rely on recollected information subject to bias. Several studies suggest taller adult height is a surrogate for favorable childhood SES, likely due to better nutrition during skeletal development. We aimed to parse out the non-genetic component of height as a refined surrogate marker of childhood SES. Hypothesis: We hypothesized that the higher non-genetic component of height is associated with higher childhood SES, and further, with better cardiovascular and brain health in adulthood. Methods: Self-reported information such as parental education, nativity (born in US 50 states/DC), age at migration, and economic hardship to pay for basic needs and access to household utilities during childhood were collected from US Hispanics/Latinos aged 18-74 years in HCHS/SOL (2008-2011). A non-genetic component of height (height non-pgs ) was estimated by subtracting genetically predicted height from the measured height, where a height genetic prediction model was fitted on sex-standardized height with Hispanic-specific height polygenic score (height pgs ), genetic ancestry components, and sex. The AHA-LE8 cardiovascular health (CVH) clinical score was derived. Neurocognitive function (6-item screener, Spanish English Verbal Learning Test, Word fluency test, Digit symbol substitution test) was assessed among >45 years. We examined the associations of height non-pgs with childhood environment and health outcomes by survey linear regressions. Results: A higher height non-pgs was associated with better childhood environment - younger generation (mean height non-pgs = 0.37 (SE=0.02) for born in 1980-1999 vs -0.45 (0.03) for born in 1930-1949), higher parental education (0.28 (0.02) for college vs -0.11 (0.02) for elementary), US born or migrated at younger age, and availability of plumbing, electricity, and phone during childhood - but not with childhood economic hardship. Further, height non-pgs was positively associated with better cognitive functions in all domains, adjusting for demographics, participants’ SES, and cardiovascular risk factors. These associations with height non-pgs were more pronounced than those with measured height. Height non-pgs showed positive associations with better clinical CVH score among 45+ aged people. Among <45 years, height non-pgs was negatively associated with clinical CVH score. Conclusions: We observed that height non-pgs reflects childhood SES, potentially through better nutrition and greater access to resources that promote growth. Stronger associations of height non-pgs and health, compared to associations with measured height, suggest that height non-pgs is a good proxy for childhood environment. The paradoxical association of height non-pgs with CVH among <45 years old needs further investigation.

Admixture mapping of cognitive function in diverse Hispanic and Latino adults

AbstractBackgroundGenome‐wide association studies (GWAS) conducted primarily in populations of European ancestry have revealed the polygenic nature of cognitive abilities [1, 2] but genetic discoveries in other populations, including Hispanics/Latinos, are lagging. Genetically, US Hispanics/Latinos have uniquely admixed genomes, encompassing African, Amerindian, and European ancestries.[3] Admixture patterns in genomic regions (local ancestry) can be leveraged in gene mapping when frequencies of trait‐associated genetic variants located within these regions differ between ancestries.MethodWe conducted genome‐wide admixture mapping analyses followed by fine mapping to identify genetic variants associated with cognitive function in 7,140 Hispanic and Latino adults (mean age 55 years; 60.5% women) from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). Five measures of cognitive function were investigated: Six‐Item Screener (SIS), Brief Spanish English Verbal Learning Test (SEVLT), Word Fluency Test (WFT), Digit Symbol Substitution Test (DSST), and a measure of general cognitive function (PC1). We tested the identified variants for replication in independent samples with similar neurocognitive measures.ResultWe identified 9 significant local ancestry‐associated regions for the 5 cognitive tests. Counts of African ancestry on at 13q12.11, 4q14, 10p12.2 and 9p22.1 were associated with DSST, PC1, SIS, and WFT, respectively. Counts of Amerindian ancestry at 1q25.2 were associated with DSST; and at 12q14.2 and 12q15 with SIS. Counts of European ancestry at 8p22 were associated with SEVLT; and at 13q12.13 with, both, DSST and PC1. Fine mapping via SNP association testing in each region identified genetic variants that partially or totally explained the admixture signal. While statistical evidence of independent replication of the prioritized variants was generally weak, with only two replicated associations at chr8p22 and chr13q12.13, there was strong biological support for the observed associations to cognitive function. For example, the prioritized variant at 8q22 is an eQTL for CNOT7, which regulates synaptic plasticity and is essential for hippocampal‐dependent learning and memory [4].ConclusionOur admixture mapping analyses identified multiple novel loci associated with measures of cognitive function. This demonstrates the effectiveness of admixture mapping in complementing GWAS [5] and provides an opportunity to identify genetic loci that may be particularly relevant in underrepresented populations.

1 Social Support is Associated with Better Memory Performance among Hispanic/Latino, but not Non-Hispanic White Older Adults

Objective:Hispanic/Latino (H/L) older adults are at greater risk of developing Alzheimer’s disease and related dementias compared to non-Hispanic whites (NHW), and there is an urgent need to identify important factors that may help prevent and/or reduce age-related cognitive health disparities. Positive psychosocial factors, such as social support, may protect against cognitive impairment and decline. However, recent research has highlighted that the effect of social support on cognitive outcomes may differ across racial/ethnic groups. Given the emphasis placed on family relationships and support in H/L culture, the current study sought to clarify whether H/L ethnicity moderated the association between social support and cognitive functioning in a well-characterized sample of community-dwelling older adults residing in Texas.Participants and Methods:Participants included 766 NHW and 817 H/L (predominantly Mexican American) older adults (Mage = 66.25 ±8.64) without dementia enrolled in the Health and Aging Brain Study-Health Disparities. Participants completed study questionnaires and a comprehensive neuropsychological battery. Perceived social support was measured using the total sum score from the 12-item abbreviated version of the Interpersonal Support Evaluation List. Episodic memory performance was operationalized as the z-score composite of the immediate and delayed recall totals from the Spanish English Verbal Learning Test and the Weschler Memory Scale (WMS)-III Logical Memory 1 and 2. Executive functioning was operationalized as the z-score composite of scores from the WMS-III Digit Span, Verbal Fluency (FAS), and Trails B. Analyses of covariance were used to explore racial/ethnic group differences in self-reported levels of social support. Multiple linear regression models examined (1) ethnicity x social support interactions on cognition, and (2) ethnicity-stratified social support and cognition associations. Covariates included age, education, sex, yearly income, and depressive symptoms.Results:H/L older adults reported less perceived social support compared to NHWs (F = 41.16, p < .001). There were no significant ethnicity x social support interactions on episodic memory (ß = 0.04, p = .53) or executive functioning (ß = 0.004, p = .95). However, stratified models revealed that more social support was associated with better memory performance in H/Ls (ß = 0.08, p = .01), but not in NHWs (ß = 0.0004, p = .99). No significant associations between social support and executive functioning were observed amongst H/Ls (ß = -0.01, p = .60) or NHWs (ß = 0.04, p = .29).Conclusions:Although H/Ls reported lower levels of social support relative to NHWs, we observed that social support was linked to better memory performance within the H/L group only. Results suggest that culturally tailored interventions which encourage strong interpersonal relationships and caring for family could enhance social support in H/Ls and thus help to prevent memory decline. Future work should focus on the development of assessment measures that better characterize unique cultural elements of social support within H/Ls, such as multigenerational households, and explore the direct effects of social support on brain metrics.

28 Social Support, APOE Genotype, and Memory Associations in a Community-Based Sample of Older Adults in Texas

Objective:The apolipoprotein E (APOE) gene has been identified as a major risk factor for the development of Alzheimer’s disease in late life. Research has shown that APOE e4 allele carriers demonstrate poorer memory performance and accelerated cognitive decline relative to non-carriers, and there is a need to identify potential factors of resiliency against the negative effects of e4 on cognition. Social support may represent one potential mechanism given that higher levels of social support have been linked to better cognitive and functional outcomes in older adults. Thus, the current study sought to examine whether social support moderates the relationship between APOE e4 status and subjective and objective memory performance in a large community-based sample of Hispanic/Latino (H/L) and Non-Hispanic White (NHW) older adults residing in Texas.Participants and Methods:Participants included 1,564 (H/L = 808, NHW = 756) older adults (mean age = 66.36±8.68) without dementia that had enrolled in the Health and Aging Brain Study-Health Disparities. Participants completed study questionnaires and a comprehensive neuropsychological battery. Apolipoprotein e4 status (e4 carriers vs. non-carriers) was determined by possession of at least one e4 allele. Perceived social support was measured using the total score from the abbreviated 12-item version of the Interpersonal Support Evaluation List. Objective memory performance was assessed using a z-score composite of Story A and B from the Weschler Memory Scale (WMS)-III and immediate and delayed recall trials from the Spanish-English Verbal Learning Test. Subjective memory was assessed using the total score from the Subject Memory Complaints Questionnaire. Race stratified multiple linear regression models, controlling for age, sex, and years of education, examined APOE e4 positivity x social support interactions on subjective and objective memory performance.Results:There was a significant APOE e4 genotype x social support interaction on objective memory performance (ß = -1.10, p = 0.003) in H/Ls such that higher levels of social support were associated with better memory performance in non-e4 carriers (ß = 0.14, p < .001), but not in e4 carriers (ß = -0.13, p = 0.9). In contrast, no significant APOE e4 status x social support interaction was observed on subjective memory (ß = -0.39, p = 0.35) in H/Ls. Finally, results revealed no significant APOE e4 genotype x social support interactions on subjective memory (ß = 0.14 p = 0.77) or objective memory (ß = 0.67, p = 0.11) performance in NHWs. Conclusions: Findings revealed that social support did not mitigate against the negative effects of e4 on subjective and objective memory performance in H/Ls or NHWs. However, results demonstrate that higher levels of social support are associated with better objective, but not subjective memory performance in H/Ls without the e4 genotype. These findings suggest that social support may protect against cognitive decline and enhance cognitive reserve in non-e4 carriers. Future studies should explore other potential factors of resiliency (e.g., diet, exercise) and examine the association between genetic risk and social support on neural markers (e.g., cortical thinning, hippocampal atrophy).

5 Poorer Memory Outcomes are Observed in Underinsured Latino Older Adults with Metabolic Syndrome

Objective:Metabolic Syndrome (MetS) is a constellation of deleterious cardiometabolic health conditions (e.g., diabetes, hypertension) that have been linked to cognitive impairment and accelerated cognitive decline in older adults. Research has shown that Latinos are at increased risk for developing MetS relative to non-Latino Whites and the prevention, maintenance, and treatment of cardiometabolic risk factors are largely contingent upon health insurance status. Within the United States there are considerable state-based differences in eligibility and access to health insurance coverage. Although Texas has the second largest population of Latinos, they are one of the most underinsured groups within the state. There is some evidence to suggest that inconsistent healthcare is associated with cognitive impairment among underserved/underprivileged groups. The current study sought to examine whether insurance status moderates the association between MetS and cognitive functioning in an effort to inform public health policy initiatives vital to reducing age-related health disparities amongst Latino older adults residing in Texas.Participants and Methods:The study sample included 850 primarily Spanish-speaking (67.6%) Latino older adults (mean age = 63.1±7.81) largely of Mexican origin/descent (95%) enrolled in the Health and Aging Brain Study-Health Disparities. All participants completed neuropsychological testing, a health exam, and questions about health insurance coverage. MetS status (MetS+ vs. MetS-) was determined by abnormal clinical abdominal obesity, triglycerides, high-density lipoprotein, blood pressure, and fasting glucose values. Health insurance status was determined by current enrollment in any private or public insurance plan. Cognition was assessed with Digit Span, Logical Memory I and II, Trail Making Test (A and B), Spanish-English Verbal Learning Test, and Letter Fluency (FAS). Raw scores were converted to z-scores which were subsequently averaged into two distinct memory and executive functioning composite scores. ANCOVAs controlling for age, sex, education, APOE e4 positivity, annual income, and primary language status were used examine health insurance status x MetS interactions on cognitive composites.Results:Approximately 54.6% of the sample met clinical criteria for MetS+ and 23.6% endorsed having no health insurance. There were no significant group differences in the proportion of MetS+ and MetS- individuals with and without health insurance (X 2 = .002, p =.96). Results revealed there was a significant MetS x health insurance status interaction on the memory composite (F = 5.39, p = .02). Post-hoc comparisons revealed that Latino older adults without health insurance demonstrated poorer memory performance relative to those with health insurance in the MetS+ group (p=.02). In contrast, there were no significant differences in memory performance across insurance status in the MetS- group (p=.35). Finally, there was no significant MetS x health insurance interaction on executive functioning (p=.60).Conclusions:Findings revealed that health insurance coverage differentially impacts memory, but not executive functioning, amongst Latinos with MetS+. Underinsured Latinos with chronic cardiometabolic health conditions may be at risk for poor memory outcomes and increasing access to affordable healthcare could help mitigate the adverse effects of MetS+ on memory. Future studies examining the relationship between health insurance, MetS status, and neuroimaging markers may yield additional insight into mechanisms underlying age-related dementia disparities.

B - 82 Relations between Subjective and Objective Memory Functioning: Investigating Psychometric Equivalence across Race Using Structural Equation Models.

We assessed the relations between the Subjective Memory Complaints Questionnaire (SMCQ) and the Spanish English Verbal Learning Test (SEVLT) for equivalence across race. Secondary objectives include evaluating the SMCQ for measurement invariance across race. The current study accessed data from the University of North Texas Health Science Center's Health and Aging Brain Study - Health Disparities (HABS-HD). We used structural equation modeling (SEM) to test the SMCQ for measurement invariance across Black (n = 515), Hispanic (n = 1104), and White (n = 1096) Americans. We first specified a configural model to assess the fit of the underlying structure across groups, followed by a scalar model to determine whether scores reflect comparable levels of the latent construct. Next, we regressed the SEVLT on the SMCQ to test the relation between subjective and objective memory functioning. Lastly, we specified a multigroup SEM to compare unconstrained and constrained regression models across race. Full scalar invariance was tenable for the SMCQ (ΔCFI = 0.007, NCI = 0.023). There were significant negative relations between the SMCQ and the SEVLT for each group (Black: b = -2.31; Hispanic: b = -1.63; White: b = -2.72), but the relations were not equivalent across groups [χ2 diff (df) = 20.2.45 (2), p < 0.001]. Results suggest that the SMCQ can be administered to screen Black, Hispanic, and White individuals for memory functioning and that mean comparisons can be made. Differential regression coefficients suggest that clinical thresholds may need to be set independently across groups to promote clinical utility.

Evaluation of Neighborhood-Level Disadvantage and Cognition in Mexican American and Non-Hispanic White Adults 50 Years and Older in the US

Understanding how socioeconomic factors are associated with cognitive aging is important for addressing health disparities in Alzheimer disease. To examine the association of neighborhood disadvantage with cognition among a multiethnic cohort of older adults. In this cross-sectional study, data were collected between September 1, 2017, and May 31, 2022. Participants were from the Health and Aging Brain Study-Health Disparities, which is a community-based single-center study in the Dallas/Fort Worth area of Texas. A total of 1614 Mexican American and non-Hispanic White adults 50 years and older were included. Neighborhood disadvantage for participants' current residence was measured by the validated Area Deprivation Index (ADI); ADI Texas state deciles were converted to quintiles, with quintile 1 representing the least disadvantaged area and quintile 5 the most disadvantaged area. Covariates included age, sex, and educational level. Performance on cognitive tests assessing memory, language, attention, processing speed, and executive functioning; measures included the Spanish-English Verbal Learning Test (SEVLT) Learning and Delayed Recall subscales; Wechsler Memory Scale, third edition (WMS-III) Digit Span Forward, Digit Span Backward, and Logical Memory 1 and 2 subscales; Trail Making Test (TMT) parts A and B; Digit Symbol Substitution Test (DSST); Letter Fluency; and Animal Naming. Raw scores were used for analyses. Associations between neighborhood disadvantage and neuropsychological performance were examined via demographically adjusted linear regression models stratified by ethnic group. Among 1614 older adults (mean [SD] age, 66.3 [8.7] years; 980 women [60.7%]), 853 were Mexican American (mean [SD] age, 63.9 [7.9] years; 566 women [66.4%]), and 761 were non-Hispanic White (mean [SD] age, 69.1 [8.7] years; 414 women [54.4%]). Older Mexican American adults were more likely to reside in the most disadvantaged areas (ADI quintiles 3-5), with 280 individuals (32.8%) living in ADI quintile 5, whereas a large proportion of older non-Hispanic White adults resided in ADI quintile 1 (296 individuals [38.9%]). Mexican American individuals living in more disadvantaged areas had worse performance than those living in ADI quintile 1 on 7 of 11 cognitive tests, including SEVLT Learning (ADI quintile 5: β = -2.50; 95% CI, -4.46 to -0.54), SEVLT Delayed Recall (eg, ADI quintile 3: β = -1.11; 95% CI, -1.97 to -0.24), WMS-III Digit Span Forward (eg, ADI quintile 4: β = -1.14; 95% CI, -1.60 to -0.67), TMT part A (ADI quintile 5: β = 7.85; 95% CI, 1.28-14.42), TMT part B (eg, ADI quintile 5: β = 31.5; 95% CI, 12.16-51.35), Letter Fluency (ADI quintile 4: β = -2.91; 95% CI, -5.39 to -0.43), and DSST (eg, ADI quintile 5: β = -4.45; 95% CI, -6.77 to -2.14). In contrast, only non-Hispanic White individuals living in ADI quintile 4 had worse performance than those living in ADI quintile 1 on 4 of 11 cognitive tests, including SEVLT Learning (β = -2.35; 95% CI, -4.40 to -0.30), SEVLT Delayed Recall (β = -0.95; 95% CI, -1.73 to -0.17), TMT part B (β = 15.95; 95% CI, 2.47-29.44), and DSST (β = -3.96; 95% CI, -6.49 to -1.43). In this cross-sectional study, aging in a disadvantaged area was associated with worse cognitive functioning, particularly for older Mexican American adults. Future studies examining the implications of exposure to neighborhood disadvantage across the life span will be important for improving cognitive outcomes in diverse populations.

BMI, insulin sensitivity, and cognition in early type 2 diabetes: The Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study.

This study exploredthe association of BMI and insulin sensitivity with cognitive performance in type 2 diabetes. A cross-sectional analysis of data from the baseline assessment of the Glycemia Reduction Approaches in Diabetes: a Comparative Effectiveness Study (GRADE) was conducted. BMI was used as a surrogate of adiposity and the Matsuda index as the measure of insulin sensitivity. Cognitive tests included the Spanish English Verbal Learning Test, the Digit Symbol Substitution Test, and the letter and animal fluency tests. Cognitive assessments were completed by 5018 (99.4%) of 5047 participants aged 56.7 ± 10.0 years, of whom 36.4% were female. Higher BMI and lower insulin sensitivity were related to better performance on memory and verbal fluency tests. In models including BMI and insulin sensitivity simultaneously, only higher BMI was related to better cognitive performance. In this study, higher BMI and lower insulin sensitivity in type 2 diabetes were cross-sectionally associated with better cognitive performance. However, only higher BMI was related to cognitive performance when both BMI and insulin sensitivity were considered simultaneously. The causality and mechanisms for this association need to be determined in future studies.

342-OR: The Impact of Insulin Secretion and Insulin Sensitivity on Cognition in Adults with Prediabetes—The Diabetes Prevention Program Outcomes Study (DPPOS)

Dysglycemia is a significant risk factor for cognitive impairment. However, which pathophysiologic determinant of dysglycemia, impaired insulin sensitivity (ISens) or insulin secretion (ISecr), or both, contributes to poorer cognitive function is not established. Among 1,054 adults with prediabetes (PreD) from the DPPOS, who did not develop diabetes, we investigated the relationship between ISecr, ISens and cognitive function, hypothesizing that lower ISens and/or lower ISecr is associated with worse cognition. Early ISecr was estimated by the mean insulinogenic index (IGI; pmol/mmol) from repeated annual oral glucose tolerance tests and ISens was estimated by the mean 1/fasting insulin from repeated fasting blood draws. ISecr and ISens were calculated over approximately 12 years of follow-up. Verbal learning (Spanish-English Verbal Learning Test [SEVLT]) and processing speed (Digital Symbol Substitution Test [DSST]) were assessed at the end of the follow-up period. Separate linear regression models were run for each cognitive outcome. Models included both mean ISecr and mean ISens as the main predictor variables and were adjusted for demographic, lifestyle, cardiovascular factors, and medications. Contrary to our hypothesis and to prior studies, higher mean ISecr was associated with poorer performance on the DSST (-0.74 points per SD increase in IGI, 95% CI: -1.43, -0.05; p=0.03). Mean ISens was not associated with DSST, nor were mean ISecr or mean ISens associated with SEVLT. These results suggest that higher insulin secretion in people with longstanding PreD may negatively impact processing speed, a critical component of executive control. This relationship could reflect a compensatory response of insulin in people with worsening metabolic dysregulation, who may also have poorer cognition. Further study is needed to replicate these findings and to understand the role of insulin in cognitive function. Disclosure A. Shapiro: None. A.H. Tjaden: None. S. Edelstein: None. S.E. Kahn: Advisory Panel; Anji Pharmaceuticals, Bayer Inc., Boehringer Ingelheim Inc., Eli Lilly and Company, Merck &amp; Co., Inc. Other Relationship; Novo Nordisk. P. Srikanthan: None. W.C. Knowler: None. E.M. Venditti: None. S. Golden: Advisory Panel; Abbott Diabetes, Medtronic. O. Carmichael: Research Support; Eli Lilly and Company. Advisory Panel; Novo Nordisk. Research Support; Nestlé Health Science. K.M. Gadde: Research Support; BioKier, Inc., National Institute of Diabetes and Digestive and Kidney Diseases. J.A. Luchsinger: Consultant; Merck KGaA. Other Relationship; Wolters Kluwer Health. D. Research Group: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (UDK048489, UDK048339, UDK048377, UDK048349, UDK048381, UDK048468, UDK048434, UDK048485, UDK048375, UDK048514, UDK048437, UDK048413, UDK048411, UDK048406, UDK048380, UDK048397, UDK048412, UDK048404, UDK048387, UDK048407, UDK048443, UDK048400)

Cardiovascular Risk and Ethnic Disparities in Cognition among Mexican Americans and Non‐Hispanic Whites: The Health and Aging Brain Study

AbstractBackgroundMexican Americans (MAs) may have increased risk for cognitive impairment and greater cardiovascular risk (CVR) compared to non‐Hispanic whites (NHWs). This disproportionate burden of CVR in MAs may be an important driver for ethnic differences in cognitive aging, although population‐based evidence is lacking. As part of the Health and Aging Brain Study, we investigated the contribution of CVR burden to ethnic differences in cognition.MethodsWe studied 1,320 MA and NHW participants without dementia (63% women, 57% MAs) aged 50‐74 years (2017‐2021, mean age 63.7±6.7 years) who underwent a cognitive battery of five tests: Trail Making Test Part A (attention) and B (executive function), Digit Symbol Substitution (processing speed), FAS and Animal Naming (verbal fluency), and Spanish English Verbal Learning Test 30‐minute delay (verbal memory). CVR burden was assessed using the Framingham Risk Score (FRS, range ‐2 to 25 in woman, ‐2 to 19 in men). We used linear regression to assess the association of CVR (intermediate/high: FRS ≥10 vs. low: FRS &lt;10) with cognitive function (z‐standardized) and its contribution to ethnic differences in cognition.ResultsMAs were on average four years younger but have higher FRS (1.8 points; 95% CI 1.5 to 2.2) compared to NHWs. In unadjusted models, intermediate/high CVR was associated with lower cognition in all domains. After adjusting for ethnicity, age, sex, education, and APOE ε4, intermediate/high CVR remained associated with lower cognition in two domains: processing speed (‐0.13, 95% Cl ‐0.23 to ‐0.03) and verbal memory (‐0.13, 95% Cl ‐0.23 to ‐0.03). The strength of the association in MAs was similar to NHW (p &gt;0.05 for interactions by ethnicity). In unadjusted models, intermediate/high CVR explained 4‐6% of ethnic differences in cognition in all domains. Results in multivariable‐adjusted models were similar, although FRS explained a greater portion of the ethnic differences in some domains: 10% in processing speed and 15% in verbal memory.ConclusionCompared to NHWs, MAs had greater CVR burden, which explained some of the ethnic differences in cognition. Efforts to lessen ethnic disparities in cognitive outcomes may benefit from a better understanding, prevention, and management of CVR in a population with growing number of ethnic minorities.

Sleep, self‐reported ocular health, and cognition in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) and SOL‐Investigation of Neurocognitive Aging (SOL‐INCA)

Abstract/ProposalBackgroundVisually impaired individuals may experience increased frequency of sleep/wake disorders, fragmented sleep, insomnia, and short sleep duration. Visual impairment and sleep disorders can have downstream effects on cognitive functioning.MethodSample included n = 590 (unweighted) HCHS/SOL Miami Field Center participants ages 45‐74 at baseline who returned for cognitive examination on average 7‐years later (SOL‐INCA). Participants completed validated ocular (National Eye Institute Visual Functioning Questionnaire; NEI‐VFQ), validated sleep questionnaires for sleepiness, insomnia, sleep duration and objective measures of sleep apnea visit‐1 (2008‐2011). They also completed a battery of neurocognitive tests for verbal episodic learning and memory (Brief Spanish English Verbal Learning Test), verbal fluency (Controlled Oral Word Association), processing speed and executive function (Digit Symbol Substitution) at visit‐1 and at SOL‐INCA. Two additional measures of processing speed/executive functioning were added at SOL‐INCA(Trails‐A, ‐B). We examined global cognitive performance and change using a regression‐based reliable change index, adjusting for the time lapse between visit 1 and SOL‐INCA (all measured in z‐score units). We used regression models to test whether (1) participants with sleep disorders have an increased risk for visual impairment, (2a) ocular health is associated with worse baseline and average 7‐years cognitive function and/or cognitive decline, and (2b) sleep attenuates any of these associations.ResultSleepiness (β = 0.04; p&lt;0.01) and insomnia (β = 0.03; p&lt;0.001) were linked to worse ocular health, and the associations were robust to adjustment for sociodemographic characteristics, acculturation, behavioral risk measures, and health conditions. Worse ocular health was linked to lower global cognitive function at baseline (β = ‐0.14; p&lt;0.001) and on average 7‐years later (β = ‐0.16; p&lt;0.01). The associations were consistent across all considered cognitive domains and robust to demographic adjustments. Ocular health was also associated with a change in verbal fluency (β = ‐0.17; p&lt;0.05), but no change was observed in other cognitive domains. Sleep disorders did not attenuate any of the reported associations.ConclusionSelf‐reported ocular health was independently associated with worse language, memory, and executive function and predicted 7‐year cognitive decline in the language domain.

Association of Mediterranean Diet With Cognitive Decline Among Diverse Hispanic or Latino Adults From the Hispanic Community Health Study/Study of Latinos

The Mediterranean diet may reduce the burden of Alzheimer disease and other associated dementias in Hispanic or Latino people. To investigate the association of a Mediterranean diet with cognitive performance among community-dwelling Hispanic or Latino adults. This cohort study analyzed data from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) and the Study of Latinos-Investigation of Neurocognitive Aging (SOL-INCA), an HCHS/SOL ancillary study. Cognition tests were administered in the HCHS/SOL from March 2008 to June 2011 (visit 1) and in the SOL-INCA from October 2015 to March 2018 (visit 2). Participants included in the present study had completed a diet assessment at visit 1 and neurocognitive evaluations at visits 1 and 2. Data were analyzed from September 2021 to May 2022. Mediterranean diet adherence was ascertained using the Mediterranean diet score (MDS) and was categorized as low (MDS: 0-4 points), moderate (MDS: 5-6 points), or high (MDS: 7-9 points). The mean of two 24-hour dietary recalls was used to calculate the MDS. Cognitive change between visits 1 and 2 was calculated by subtracting the cognitive score at visit 2 from the cognitive score at visit 1 and adjusting by the time elapsed between visits and cognitive score at visit 1. Neurocognitive tests administered were Brief Spanish-English Verbal Learning Test (B-SEVLT) Sum, B-SEVLT Recall, word fluency, and Digit Symbol Substitution Test (DSST). Results of each test were z score-transformed and the means were averaged to create a global cognition score. Complex sample linear regression analysis was used to ascertain the association between MDS and neurocognitive performance at each visit and neurocognitive change. A total of 6321 participants (mean [SE] age, 56.1 [0.18] years at visit 1; n = 4077 women [57.8%]) were included. Mediterranean diet adherence weighted frequencies were 35.8% (n = 2112 of 6321) for the low adherence group, 45.4% (n = 2795) for the moderate adherence group, and 18.8% (n = 1414) for the high adherence group. In the fully adjusted model, z score-transformed cognitive scores at visit 1 in the high vs low adherence groups were higher for B-SEVLT Sum (β = 0.11; 95% CI, 0.02-0.20), B-SEVLT Recall (β = 0.16; 95% CI, 0.07-0.25), and global cognition (β = 0.10; 95% CI, 0.04-0.16) tests. In the mean follow-up time of 7 years, cognitive change in the high vs low adherence groups was less pronounced for B-SEVLT Sum (β = 0.12; 95% CI, 0.05-0.20) and B-SEVLT Recall (β = 0.14; 95% CI, 0.05-0.23), but not for word fluency, DSST score, or global cognition score. Results of this cohort study suggested that high adherence to a Mediterranean diet was associated with better cognitive performance and decreased 7-year learning and memory decline among middle-aged and older Hispanic or Latino adults. Culturally tailored Mediterranean diet may reduce the risk of cognitive decline and Alzheimer disease in this population.

The Laterality of Age-related Hearing Loss and Cognition.

To analyze the association between neurocognitive performance and age-related hearing loss in the right and left ear, individually. Subjects included 5277 participants (≥50 years) from the general Hispanic population who underwent audiometric testing in a US multicentered epidemiologic study. Linear regression was performed to assess the cross-sectional association between cognitive performance (Digit Symbol Substitution Test [DSST], Word Frequency Test, Spanish-English Verbal Learning Test [SEVLT] 3 Trials, SEVLT Recall, and Six-Item Screener) and hearing in each ear (4-frequency pure-tone average), adjusting for age, sex, education, cardiovascular disease, and hearing aid use. Mean age was 58.4 ± 6.2 years; 3254 (61.7%) were women. Mean pure-tone averages were 20.2 ± 11.7 dB (right ear) and 20.2 ± 12.3 dB (left ear). Multivariable regression demonstrated significant associations between all cognitive tests and hearing loss in both ears. Worsening hearing loss in the right and left ear was associated with decreased performance across all tests. No laterality in the association was demonstrated.

The Link between APOE4 Presence and Neuropsychological Test Performance among Mexican Americans and Non-Hispanic Whites of the Multiethnic Health & Aging Brain Study – Health Disparities Cohort

Introduction: The APOEε4 allele is the single strongest genetic risk for late-onset Alzheimer’s disease (AD). Prior work demonstrates that not only the APOEε4 allele varies by race/ethnicity but also the risk for AD and cognitive impairment conveyed by the APOEε4 allele varies by the racial/ethnic group as well as genetic ancestry. Here, we sought to examine the link between the APOEε4 and neuropsychological functioning among Mexican Americans (MAs). Methods: Data were examined from 1,633 (852 MAs and 781 non-Hispanic Whites [NHWs]) participants of the Health & Aging Brain Study – Health Disparities (HABS-HD) and were enrolled with all requisite data to be included into the current analyses. Results: The frequency of both ε4 and ε2 alleles was significantly lower among MAs as compared to NHWs. Among MAs, APOEε4 allele presence was associated specifically with poorer immediate and delayed memory (Wechsler Memory Scale – Third Edition [WMS-III] Logical Memory and Spanish-English Verbal Learning Test [SEVLT]). Among NHWs, APOEε4 allele presence was associated with poorer immediate and delayed memory as well as worse executive functioning (Trials B) and verbal fluency (Animal naming). Discussion/Conclusion: The APOEε4 allele was associated with poorer cognition across multiple domains among NHWs; however, allele presence was specifically associated with poorer memory performance among MAs. When combined with prior work, the current findings demonstrate that the risk factors associated with cognitive dysfunction differ among MAs as compared to NHWs and require additional investigation.

Audiometric Age-Related Hearing Loss and Cognition in the Hispanic Community Health Study

Studies associating age-related hearing loss (HL) with cognition have been limited by non-Hispanic cohorts, small samples, or limited confounding control. We overcome these limitations in the largest study of formal, audiometric HL and cognition to date using the multicentered Hispanic Community Health Study (n=5,277, mean age=58.4 [SD=6.2]). The main exposure was audiometric HL. The main outcome was neurocognitive performance. Adjusting for demographics, hearing aid use, and cardiovascular disease, a 20-dB increase (one-category worsening) in HL was cross-sectionally associated with worse performance in multiple neurocognitive measures: -1.53 (95% CI = -2.11, -0.94) raw score point difference on Digit Symbol Substitution Test, -0.86 (-1.23, -0.49) on Word Frequency Test, -0.76 (-1.04, -0.47) on Spanish-English Verbal Learning Test (SEVLT) 3 trials, -0.45 (-0.60, -0.29) on SELVT recall, -0.07 (-0.12, -0.02) on Six-Item Screener. Because HL is common and potentially treatable, it should be investigated as a modifiable risk factor for neurocognitive decline/dementia.

Association of Glycemia, Lipids, and Blood Pressure With Cognitive Performance in People With Type 2 Diabetes in the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE).

Type 2 diabetes is a risk factor for cognitive impairment. We examined the relation of glycemia, lipids, blood pressure (BP), hypertension history, and statin use with cognition in the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE). Cross-sectional analyses from GRADE at baseline examined the association of glycemia (hemoglobin A1c [HbA1c]), LDL, systolic BP (SBP) and diastolic BP (DBP), hypertension history, and statin use with cognition assessed by the Spanish English Verbal Learning Test, letter and animal fluency tests, and Digit Symbol Substitution Test (DSST). Among 5,047 GRADE participants, 5,018 (99.4%) completed cognitive assessments. Their mean age was 56.7 ± 10.0 years, and 36.4% were women. Mean diabetes duration was 4.0 ± 2.7 years. HbA1c was not related to cognition. Higher LDL was related to modestly worse DSST scores, whereas statin use was related to modestly better DSST scores. SBP between 120 and 139 mmHg and DBP between 80 and 89 mmHg were related to modestly better DSST scores. Hypertension history was not related to cognition. In people with type 2 diabetes of a mean duration of <5 years, lower LDL and statin use were related to modestly better executive cognitive function. SBP levels in the range of 120-139 mmHg and DBP levels in the range of 80-89 mmHg, but not lower levels, were related to modestly better executive function. These differences may not be clinically significant.

The cross-sectional association of renal dysfunction with tests of cognition in middle-aged adults with early type 2 diabetes: The GRADE Study.

The association of renal dysfunction with tests of cognition in type 2 diabetes has been examined in individuals with moderate and advanced renal disease. Here we examine the association of renal dysfunction with tests of cognition in a cohort of middle-aged adults with short duration diabetes (mean 4.0 ± 2.8 years). Baseline data were examined from the Glycemia Reduction Approaches in Diabetes (GRADE) study (n = 4998). Renal dysfunction was defined by the presence of albumin in the urine or by estimated glomerular filtration rate (eGFR). Cognition was assessed with the Spanish English Verbal Learning Test, Letter and Animal fluency tests, and the Digit Symbol Substitution Test. Participants with albuminuria or eGFR <60 ml/min/1.73 m2 had significantly lower test scores of information processing speed and perception, executive function and ability to categorize information, and of verbal learning and memory compared to participants without renal disease. Adjustment for hypertension, dyslipidemia, and waist circumference attenuated many of these findings but markers of impaired learning and executive function continued to remain lower in association with higher urine albumin levels. In type 2 diabetes of short duration, there are already subtle deficiencies in markers of cognition in association with renal disease in middle aged adults.

Normative data for the Brief Spanish-English Verbal Learning Test for representative and diverse Hispanics/Latinos: Results from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL).

IntroductionEpisodic learning and memory performance are crucial components of cognitive assessment. To meet the needs of a diverse Hispanic/Latino population, we aimed to provide normative data on the Brief Spanish‐English Verbal Learning Test (B‐SEVLT).MethodsThe target population for the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) included individuals 45+ years old from Central American, Cuban, Dominican, Mexican, Puerto Rican, and South American backgrounds. Average age was 56.5 years ± 9.92, 54.5% were female, and mean education was 11.0 years ± 5.6 (unweighted n = 9309). Participants were administered the B‐SEVLT in their preferred language (Spanish or English). Hispanic/Latino background adjusted B‐SEVLT scores and percentile cut‐points were created using survey‐adjusted regression models.ResultsHigher educational attainment, younger age, and being female were associated with higher learning and memory performance. Hispanic/Latino background groups differed in B‐SEVLT performance.DiscussionRepresentative learning and memory norms for Hispanic/Latinos of diverse backgrounds will improve cognitive assessment and accuracy of neurocognitive disorder diagnosis.