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INTRODUCTION: Older Black adults are at risk of cerebral small vessel disease (CSVD), which contributes to dementia risk. Two subtypes of CSVD, arteriolosclerosis and ischemic lacunar infarcts, have been independently linked to lower cognition and higher dementia risk, but their combined effects on cognition in older Black adults are unclear. METHODS: Mixed models were used to examine the associations of in vivo measures of arteriolosclerosis (ARTS) and ischemic lacunar infarcts to cognitive level and change in 370 older Black adults without dementia. RESULTS: Modeled together, higher ARTS load accounted for lower levels of global cognition, episodic memory, semantic memory, and perceptual speed, whereas higher infarct load accounted for lower levels of working memory. There were no associations with rate of cognitive change. DISCUSSION: Both arteriolosclerosis and ischemic infarcts impact the cognitive health of older Black adults, but arteriolosclerosis affects cognition more broadly and offers promise as an in vivo biomarker of dementia risk. Highlights: Older Black adults are at risk of cerebral small vessel disease (CSVD) and dementia.Examined magnetic resonance imaging‐derived measure of arteriolosclerosis (ARTS), infarcts, and cognition.ARTS load was widely associated with lower cognition after adjusting for infarct load.Infarct load was specifically associated with lower complex attention.More within‐Black in vivo studies of CSVD subtypes and cognition are needed. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Reproductive health history may contribute to cognitive aging and risk for Alzheimer's disease, but this is understudied among Hispanic/Latina women. METHODS: Participants included 2126 Hispanic/Latina postmenopausal women (44 to 75 years) from the Study of Latinos‐Investigation of Neurocognitive Aging. Survey linear regressions separately modeled the associations between reproductive health measures (age at menarche, history of oral contraceptive use, number of pregnancies, number of live births, age at menopause, female hormone use at Visit 1, and reproductive span) with cognitive outcomes at Visit 2 (performance, 7‐year change, and mild cognitive impairment [MCI] prevalence). RESULTS: Younger age at menarche, oral contraceptive use, lower pregnancies, lower live births, and older age at menopause were associated with better cognitive performance. Older age at menarche was protective against cognitive change. Hormone use was linked to lower MCI prevalence. DISCUSSION: Several aspects of reproductive health appear to impact cognitive aging among Hispanic/Latina women. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Few studies have examined the associations of psychosocial factors with cognitive change in Hispanics/Latinos. METHODS: Data from the Hispanic Community Health Study/Study of Latinos‐Investigation of Neurocognitive Aging (HCHS/SOL INCA) and Sociocultural studies were used (n = 2,155; ages ≥45 years). Psychosocial exposures included intrapersonal (ethnic identity, optimism, purpose in life), interpersonal (family cohesion, familism, social networks, social support), and social factors (ethnic discrimination, loneliness, subjective social status). Survey‐linear regression models examined associations between psychosocial exposures and 7‐year cognitive change (global cognition [GC], verbal learning, memory, word fluency [WF], and digit symbol substitution [DSS]). RESULTS: Familism predicted decline in GC, verbal learning, and memory; family cohesion predicted DSS decline; and loneliness predicted memory decline. Ethnic identity was protective against decline in GC and memory, optimism and social support were protective against decline in memory, and purpose in life was protective against WF decline. DISCUSSION: Psychosocial factors are differentially related to cognitive changes. Culturally relevant factors should be explored in Hispanic/Latino cognitive aging research. Highlights: Psychosocial factors are differentially related to cognitive changes in Latinos.Role of culturally relevant factors on cognition should be further explored.Familism predicted decline in global cognition, verbal learning, and memory.Ethnic identity predicted increase in global cognition and memory. [ABSTRACT FROM AUTHOR]

• What is the primary question addressed by this study? We investigated associations of the cortical thickness signature of Alzheimer's disease (AD) and white matter hyperintensity volumes with a composite index of health and financial literacy given that the ability to access, understand, and utilize health and financial information influences older adults' health outcomes. • What is the main finding of this study? For 303 participants without dementia from the Rush Memory and Aging Project, reduced AD signature cortical thickness was associated with baseline levels of and faster declines in literacy. White matter hyperintensities were associated with the level of but not change in literacy. • What is the meaning of the finding? Results support the assertion that biological vulnerability associated with AD may predict a broader spectrum of behavior than originally recognized, even in non-demented older adults. The cortical thickness "signature" of Alzheimer's disease (AD-CT) and white matter hyperintensity (WMH) burden have each been associated with cognitive aging and incident AD and related dementias. Less is known about how these structural neuroimaging markers associate with other critical behaviors. We investigated associations of AD-CT and WMH volumes with a composite index of health and financial literacy given that the ability to access, understand, and utilize health and financial information significantly influences older adults' health outcomes. Participants were 303 adults without dementia (age∼80 years; 74% women) from the Rush Memory and Aging Project. Baseline 3T MRI T1-weighted structural and T2-weighted FLAIR data were used to assess AD-CT and WMH volumes, respectively. Literacy was measured using questions designed to assess comprehension of health and financial information and concepts, yielding a total literacy score. Multivariable linear mixed effects regression models determined the relationship of each neuroimaging marker, first separately and then combined, with the level of and change in literacy. Reduced AD-CT and higher WMH at baseline were each associated with lower levels of literacy; only AD-CT was associated with the rate of decline in literacy over time. The association of AD-CT with change in literacy persisted when both neuroimaging markers were included in the same model. The cortical thickness signature of AD predicts changes in health and financial literacy in nondemented older adults suggesting that the multidimensional construct of health and financial literacy relies on specific brain networks implicated in AD. [ABSTRACT FROM AUTHOR]

Introduction: The projected growth of Alzheimer's disease (AD) and AD‐related dementia (ADRD) cases by midcentury has expanded the research field and impelled new lines of inquiry into structural and social determinants of health (S/SDOH) as fundamental drivers of disparities in AD/ADRD. Methods: In this review, we employ Bronfenbrenner's ecological systems theory as a framework to posit how S/SDOH impact AD/ADRD risk and outcomes. Results: Bronfenbrenner defined the "macrosystem" as the realm of power (structural) systems that drive S/SDOH and that are the root cause of health disparities. These root causes have been discussed little to date in relation to AD/ADRD, and thus, macrosystem influences, such as racism, classism, sexism, and homophobia, are the emphasis in this paper. Discussion: Under Bronfenbrenner's macrosystem framework, we highlight key quantitative and qualitative studies linking S/SDOH with AD/ADRD, identify scientific gaps in the literature, and propose guidance for future research. Highlights: Ecological systems theory links structural/social determinants to AD/ADRD.Structural/social determinants accrue and interact over the life course to impact AD/ADRD.Macrosystem is made up of societal norms, beliefs, values, and practices (e.g., laws).Most macro‐level determinants have been understudied in the AD/ADRD literature. [ABSTRACT FROM AUTHOR]

Introduction: Studies suggest bilingualism may delay behavioral manifestations of adverse cognitive aging including Alzheimer's dementia. Methods: Three thousand nine hundred sixty‐three participants (unweighted mean population age ≈56 years) at Hispanic Community Health Study/Study of Latinos baseline (2008–2011) self‐reported their and their parents' birth outside the United States, Spanish as their first language, and used Spanish for baseline and comparable cognitive testing 7 years later (2015–2018). Spanish/English language proficiency and patterns of use were self‐rated from 1 = only Spanish to 4 = English > Spanish. Cognitive testing included test‐specific and global composite score(s) of verbal learning, memory, word fluency, and Digit Symbol Substitution (DSS). Survey linear regression models examined associations between baseline bilingualism scores and cognition. Results: Higher second‐language (English) proficiency and use were associated with higher global cognition, fluency, and DSS at follow‐up and better than predicted change in fluency. Discussion: The bilingual experience was more consistently related to 7‐year level versus change in cognition for Hispanics/Latinos. [ABSTRACT FROM AUTHOR]

Background: Everyday modifiable lifestyle factors play a crucial role in the development and maintenance of successful cognitive and neurodegenerative trajectories in later life. Although research has focused on independent associations of physical exercise (PE), diet, body mass index (BMI), and sleep, how all four factors simultaneously work in a larger multimodal association has not been studied. We examine the synergistic associations of all four risk factors to predict two markers of future white matter injury (cerebral free water [FW] content, a sensitive and early biomarker of white matter injury and white matter hyperintensities [WMH]) in Hispanic/Latino‐population. Method: We used cognitively normal older adults (n = 1386; mean age = 50.96(10.14) years; 66.2% female) with cross‐sectional data from the Study of Latinos‐Investigation of Neurocognitive Aging‐Magnetic Resonance Imaging (SOL‐INCA‐MRI). First, we applied path analyses to test independent associations of diet(Healthy‐Eating‐Index‐2010), PE(total activity), BMI, and sleep‐duration (measured 2008‐2015) on FW and WMH (measured 2018‐2022). Higher PE score represents lower exercise. Second, we tested mediations using significant independent predictors of FW and WMH. Third, we explored the best possible models that incorporated all six factors. We accounted for age, sex, and education in the final model. Result: First, lower PE predicted greater WMH (β = 0.171,SE = 0.064,p = 0.008) and FW (β = 0.004,SE = 0.002, p = 0.013). Higher BMI (β = 0.018,SE = 0.007, p = 0.017), and higher FW (β = 22.230,SE = 0.939, p<0.001) was associated with greater WMH. Second, we did not find that any of the three modifiable factors mediated the relationship between PE and FW. However, the association between PE and WMH was mediated by BMI (indirect model[borderline]:β = 0.012,SE = 0.006, p = 0.050) and by FW (indirect model:β = 0.066,SE = 0.025, p = 0.007). Third, the addition of diet and sleep in this double mediation model strengthened both mediations (PE→BMI→WMH:β = 0.012,SE = 0.006, p = 0.039; PE→FW→WMH:β = 0.065,SE = 0.025, p = 0.008) resulting in an overall indirect model (PE→BMI→WMH+ PE→FW→WMH:β = 0.077,SE = 0.025,p = 0.002) (Figure 1). Better diet was associated with lower BMI (β = ‐0.026,SE = 0.012,p = 0.029) and lower PE with more sleep (β = 0.190,SE = 0.061,p = 0.002). Conclusion: We observed that the association between PE and WMH is mediated by both BMI and FW, and the overall double mediation is clearer when diet and sleep are accounted for in the model. Our complex multimodal model provides a potential framework on how everyday modifiable risk factors synergistically predict WMH years later. [ABSTRACT FROM AUTHOR]

Background: Hispanics/Latinos are the largest and most diverse ethnoracial group at high risk for Alzheimer's disease and related dementias across the US. However, this population is largely understudied. We present preliminary findings on the association between cognitive profiles and brain morphometry measures in a large Hispanic/Latino cohort of older adults. Method: We used a longitudinal cohort of cognitively normal older adults (n = 2028; mean baseline age = 54.19 (6.75) years, 69.5% female) from the Study of Latinos‐Investigation of Neurocognitive Aging‐Magnetic Resonance Imaging (SOL‐INCA‐MRI). First, to establish a latent memory variable, we examined confirmatory factor analysis to test loadings of four manifest variables (Spanish‐English‐Verbal‐Learning Test learning and recall, digit symbol, word frequency) at the first (2008‐2015) and second (2015‐2021) cognitive visits. Second, we examined whether tertiles of our latent cognitive score were associated with two measures of brain integrity (white matter hyperintensities [WMH] and hippocampus) measured between 2018‐2022. The brain morphometry measures were regressed independently on cognitive tertiles at both visits. Age at each visit, sex, education, Hispanic/Latino background, and cognitive‐MRI lag time were included as covariates. Result: First, a two‐factor latent memory profile (episodic memory and working memory) best represented our four manifest variables at both visits 1 and 2. Each tertile corresponded to low (1), intermediate (2), and high (3) performing groups. Second, increase in cognitive tertile (from low to intermediate to high) on episodic memory (β = ‐0.157, SE = 0.040, p< 0.001) and working memory (β = ‐0.192, SE = 0.043, p< 0.001) at visit 1 was associated with lower WMH. Increase in cognitive tertile on episodic and working memory at visit 2 was associated with lower WMH (β = ‐0.241, SE = 0.036, p< 0.001 and β = ‐0.260, SE = 0.043, p< 0.001, respectively) and greater hippocampus (β = 0.051, SE = 0.015, p = 0.001 and β = 0.040, SE = 0.018, p = 0.025, respectively). Conclusion: Our preliminary findings showed that cognitive profiles and key brain integrity measures are associated years later in Hispanic/Latino adults. Careful monitoring of cognitive aging profiles in the Hispanic/Latino community may lead to early detection and intervention of older adults at high risk for future neurodegeneration. [ABSTRACT FROM AUTHOR]

Background: Cognitive decline in normal aging and Alzheimer's disease (AD) has been associated with changes in cerebral white matter tracts. Although women are at higher risk of developing AD, studies investigating the effect of sex on white matter integrity have been mixed. Decreased white matter integrity in limbic pathways including the fornix and cingulum have been reported in AD although underlying mechanisms and potential sex differences remain understudied. We explored sex as a moderator of the effect of age on myelin water fraction (MWF), a measure of myelin content, in older adults. Method: Fifty‐two older adults without dementia (mean age = 72; 61% female) underwent neuropsychological evaluation and 3T MRI at two research sites. Multicomponent driven equilibrium single pulse observation of T1 and T2 (mcDESPOT) quantified MWF in three a priori regions of interest including the fornix, cingulum in the hippocampal formation (CGH), and cingulum in the cingulate gyrus (CGC). The California Verbal Learning Test‐Second Edition assessed learning and long‐delay free recall. Separate multiple linear regressions assessed for (1) interactions between age and sex on regional MWF and (2) associations of regional MWF and memory. All models adjusted for APOE e4 allele frequency, vascular risk, and site; the second analysis additionally adjusted for age and sex. Result: (1) There was a significant ageXsex interaction for CGC MWF (p = 0.006) and fornix MWF (p = 0.016) (see Figure) but not CGH MWF (p = 0.443). Specifically, for both interactions, in women but not men, as age increased, MWF decreased. (2) Fornix MWF was associated with memory (p = 0.002), but MWF of the two cingulum regions were not (p>0.05). Results did not change when adjusting for hippocampal volume. Conclusion: Results suggest that the relationship between age and myelin content of limbic fiber pathways depends on sex, with women but not men showing age‐related decreases. Additionally, and consistent with previous studies, we observed an association between fornix MWF and learning and memory. Understanding sex differences in MWF may facilitate earlier detection of AD risk for women. Longitudinal study with larger samples is needed to further clarify the role sex plays in limbic system myelin integrity and potentially inform interventions. [ABSTRACT FROM AUTHOR]

The concept of vascular contributions to cognitive impairment and dementia (VCID) derives from more than two decades of research indicating that (1) most older individuals with cognitive impairment have post mortem evidence of multiple contributing pathologies and (2) along with the preeminent role of Alzheimer's disease (AD) pathology, cerebrovascular disease accounts for a substantial proportion of this contribution. Contributing cerebrovascular processes include both overt strokes caused by etiologies such as large vessel occlusion, cardioembolism, and embolic infarcts of unknown source, and frequently asymptomatic brain injuries caused by diseases of the small cerebral vessels. Cerebral small vessel diseases such as arteriolosclerosis and cerebral amyloid angiopathy, when present at moderate or greater pathologic severity, are independently associated with worse cognitive performance and greater likelihood of dementia, particularly in combination with AD and other neurodegenerative pathologies. Based on this evidence, the US National Alzheimer's Project Act explicitly authorized accelerated research in vascular and mixed dementia along with frontotemporal and Lewy body dementia and AD itself. Biomarker development has been consistently identified as a key step toward translating scientific advances in VCID into effective prevention and treatment strategies. Validated biomarkers can serve a range of purposes in trials of candidate interventions, including (1) identifying individuals at increased VCID risk, (2) diagnosing the presence of cerebral small vessel disease or specific small vessel pathologies, (3) stratifying study participants according to their prognosis for VCID progression or treatment response, (4) demonstrating an intervention's target engagement or pharmacodynamic mechanism of action, and (5) monitoring disease progression during treatment. Effective biomarkers allow academic and industry investigators to advance promising interventions at early stages of development and discard interventions with low success likelihood. The MarkVCID consortium was formed in 2016 with the goal of developing and validating fluid‐ and imaging‐based biomarkers for the cerebral small vessel diseases associated with VCID. MarkVCID consists of seven project sites and a central coordinating center, working with the National Institute of Neurologic Diseases and Stroke and National Institute on Aging under cooperative agreements. Through an internal selection process, MarkVCID has identified a panel of 11 candidate biomarker "kits" (consisting of the biomarker measure and the clinical and cognitive data used to validate it) and established a range of harmonized procedures and protocols for participant enrollment, clinical and cognitive evaluation, collection and handling of fluid samples, acquisition of neuroimaging studies, and biomarker validation. The overarching goal of these protocols is to generate rigorous validating data that could be used by investigators throughout the research community in selecting and applying biomarkers to multi‐site VCID trials. Key features of MarkVCID participant enrollment, clinical/cognitive testing, and fluid biomarker procedures are summarized here, with full details in the following text, tables, and supplemental material, and a description of the MarkVCID imaging biomarker procedures in a companion paper, "MarkVCID Cerebral small vessel consortium: II. Neuroimaging protocols." The procedures described here address a range of challenges in MarkVCID's design, notably: (1) acquiring all data under informed consent and enrollment procedures that allow unlimited sharing and open‐ended analyses without compromising participant privacy rights; (2) acquiring the data in a sufficiently wide range of study participants to allow assessment of candidate biomarkers across the various patient groups who might ultimately be targeted in VCID clinical trials; (3) defining a common dataset of clinical and cognitive elements that contains all the key outcome markers and covariates for VCID studies and is realistically obtainable during a practical study visit; (4) instituting best fluid‐handling practices for minimizing avoidable sources of variability; and (5) establishing rigorous procedures for testing the reliability of candidate fluid‐based biomarkers across replicates, assay runs, sites, and time intervals (collectively defined as the biomarker's instrumental validity). Participant Enrollment Project sites enroll diverse study cohorts using site‐specific inclusion and exclusion criteria so as to provide generalizable validation data across a range of cognitive statuses, risk factor profiles, small vessel disease severities, and racial/ethnic characteristics representative of the diverse patient groups that might be enrolled in a future VCID trial. MarkVCID project sites include both prospectively enrolling centers and centers providing extant data and samples from preexisting community‐ and population‐based studies.With approval of local institutional review boards, all sites incorporate MarkVCID consensus language into their study documents and informed consent agreements. The consensus language asks prospectively enrolled participants to consent to unrestricted access to their data and samples for research analysis within and outside MarkVCID. The data are transferred and stored as a de‐identified dataset as defined by the Health Insurance Portability and Accountability Act Privacy Rule.Similar human subject protection and informed consent language serve as the basis for MarkVCID Research Agreements that act as contracts and data/biospecimen sharing agreements across the consortium. Clinical and Cognitive Data Clinical and cognitive data are collected across prospectively enrolling project sites using common MarkVCID instruments. The clinical data elements are modified from study protocols already in use such as the Alzheimer's Disease Center program Uniform Data Set Version 3 (UDS3), with additional focus on VCID‐related items such as prior stroke and cardiovascular disease, vascular risk factors, focal neurologic findings, and blood testing for vascular risk markers and kidney function including hemoglobin A1c, cholesterol subtypes, triglycerides, and creatinine.Cognitive assessments and rating instruments include the Clinical Dementia Rating Scale, Geriatric Depression Scale, and most of the UDS3 neuropsychological battery. The cognitive testing requires ≈60 to 90 minutes.Study staff at the prospectively recruiting sites undergo formalized training in all measures and review of their first three UDS3 administrations by the coordinating center. Collection and Handling of Fluid Samples Fluid sample types collected for MarkVCID biomarker kits are serum, ethylenediaminetetraacetic acid‐plasma, platelet‐poor plasma, and cerebrospinal fluid (CSF) with additional collection of packed cells to allow future DNA extraction and analyses.MarkVCID fluid guidelines to minimize variability include fasting morning fluid collections, rapid processing, standardized handling and storage, and avoidance of CSF contact with polystyrene. Instrumental Validation for Fluid‐Based Biomarkers Instrumental validation of MarkVCID fluid‐based biomarkers is operationally defined as determination of intra‐plate and inter‐plate repeatability, inter‐site reproducibility, and test‐retest repeatability. MarkVCID study participants both with and without advanced small vessel disease are selected for these determinations to assess instrumental validity across the full biomarker assay range.Intra‐ and inter‐plate repeatability is determined by repeat assays of single split fluid samples performed at individual sites. Inter‐site reproducibility is determined by assays of split samples distributed to multiple sites. Test‐retest repeatability is determined by assay of three samples acquired from the same individual, collected at least 5 days apart over a 30‐day period and assayed on a single plate. The MarkVCID protocols are designed to allow direct translation of the biomarker validation results to multicenter trials. They also provide a template for outside groups to perform analyses using identical methods and therefore allow direct comparison of results across studies and centers. All MarkVCID protocols are available to the biomedical community and intended to be shared. In addition to the instrumental validation procedures described here, each of the MarkVCID kits will undergo biological validation to determine whether the candidate biomarker measures important aspects of VCID such as cognitive function. Analytic methods and results of these validation studies for the 11 MarkVCID biomarker kits will be published separately. The results of this rigorous validation process will ultimately determine each kit's potential usefulness for multicenter interventional trials aimed at preventing or treating small vessel disease related VCID. [ABSTRACT FROM AUTHOR]

Introduction: Apolipoprotein E (APOE) alleles are associated with cognitive decline, mild cognitive impairment (MCI), and Alzheimer's disease in Whites, but have weaker and inconsistent effects reported in Latinos. We hypothesized that this heterogeneity is due to ancestry‐specific genetic effects. Methods: We investigated the associations of the APOE alleles with significant cognitive decline and MCI in 4183 Latinos, stratified by six Latino backgrounds, and explored whether the proportion of continental genetic ancestry (European, African, and Amerindian) modifies these associations. Results: APOE ε4 was associated with an increased risk of significant cognitive decline (odds ratio [OR] = 1.15, P‐value = 0.03), with the strongest association in Cubans (OR = 1.46, P‐value = 0.007). APOE‐ε2 was associated with decreased risk of MCI (OR = 0.37, P‐value = 0.04) in Puerto Ricans. Amerindian genetic ancestry was found to protect from the risk conferred by APOE ε4 on significant cognitive decline. Discussion: Results suggest that APOE alleles' effects on cognitive outcomes differ across six Latino backgrounds and are modified by continental genetic ancestry. [ABSTRACT FROM AUTHOR]

Background: Health and financial literacy are central to older adults' well-being and financial standing, but the relation of literacy with mortality in advanced age remains unclear. Aims: To determine whether lower literacy, as reflected in measures of total literacy and subscales of health and financial literacy, was associated with an increased risk of mortality. Methods: Participants were 931 community-based older adults from the Rush Memory and Aging Project [age: mean (SD) = 80.9 (7.6), range 58.8–100.8], an ongoing, prospective observational cohort study of aging. Participants were without dementia at the time literacy was assessed. Proportional hazards models were used to determine whether literacy measures were associated with mortality. Results: During up to 8 years of follow-up, 224 (24.1% of 931) participants died. In models that adjusted for age, sex, and education, lower total, health, and financial literacy were each associated with an increased risk of mortality (total literacy: HR = 1.020, 95% CI 1.010–1.031, p < 0.001; health literacy: HR = 1.015, 95% CI 1.008–1.023, p < 0.001; financial literacy: HR = 1.013, 95% CI 1.003–1.023, p = 0.014). These associations persisted after additionally adjusting for income and indices of health status; however, only the association of lower health literacy with mortality persisted after further adjusting for a robust measure of global cognition. Discussion: We suspect that the current associations of lower literacy with mortality reflect the detrimental effect of early pathologic brain aging on literacy. Conclusions: Lower literacy, particularly lower health literacy, is associated with mortality in advanced age. [ABSTRACT FROM AUTHOR]

Introduction: We estimated the prevalence and correlates of mild cognitive impairment (MCI) among middle‐aged and older diverse Hispanics/Latinos. Methods: Middle‐aged and older diverse Hispanics/Latinos enrolled (n = 6377; 50–86 years) in this multisite prospective cohort study were evaluated for MCI using the National Institute on Aging–Alzheimer's Association diagnostic criteria. Results: The overall MCI prevalence was 9.8%, which varied between Hispanic/Latino groups. Older age, high cardiovascular disease (CVD) risk, and elevated depressive symptoms were significant correlates of MCI prevalence. Apolipoprotein E4 (APOE) and APOE2 were not significantly associated with MCI. Discussion: MCI prevalence varied among Hispanic/Latino backgrounds, but not as widely as reported in the previous studies. CVD risk and depressive symptoms were associated with increased MCI, whereas APOE4 was not, suggesting alternative etiologies for MCI among diverse Hispanics/Latinos. Our findings suggest that mitigating CVD risk factors may offer important pathways to understanding and reducing MCI and possibly dementia among diverse Hispanics/Latinos. [ABSTRACT FROM AUTHOR]

Introduction: Apolipoprotein E (APOE) is a susceptibility gene for late‐onset Alzheimer's disease neuropathology; less is known about the relationship between APOE and cerebrovascular disease (CVD) neuropathology. Methods: We investigated associations of APOE status with arteriolosclerosis, macroinfarcts and microinfarcts, and atherosclerosis in 1383 adults (65.9–108.2 years at death) with and without dementia. Excluding ε2/ε4 carriers, multivariable regressions for each CVD‐related neuropathology compared ε4 and ε2 carriers to ε3/ε3 carriers adjusting for confounders including age and Alzheimer's neuropathology. Results: Three hundred forty‐two individuals (24.7%; ∼87.7 years at death; 39.9% nondemented) were ε3/ε4 or ε4/ε4, and 180 (13.0%; ∼89.9 years at death; 66.6% nondemented) were ε2/ε3 or ε2/ε2. ε4 carriers had higher odds of macroinfarcts (odds ratio = 1.41, 95% confidence interval: 1.02–1.94, P =.03), whereas ε2 carriers had higher odds of moderate‐to‐severe arteriolosclerosis (odds ratio = 1.68, 95% confidence interval: 1.15–2.45, P =.006) compared to ε3/ε3 carriers. Age‐stratified analyses suggested that these relationships were driven by ε4 carriers <90 years at death and ε2 carriers ≥90 years at death, respectively. Discussion: APOE differentially affects type and timing of CVD‐related neuropathology. [ABSTRACT FROM AUTHOR]

Background: Composite scores may be useful to summarize overall language or visuospatial functioning. We generated composite scores for these domains from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and evaluated their validity. Method: We used item response theory to derive composite measures for language (ADNI‐Lan) and visuospatial functioning (ADNI‐VS). We performed multiple validation analyses comparing ADNI‐Lan and ADNI‐VS to individual test and global scores among participants with normal cognition (NC), mild cognitive impairment (MCI), and Alzheimer's disease (AD). We evaluated ability to detect change, strength of association with a priori selected structural brain imaging findings, association with risk of AD conversion for people with MCI, and differences in intercepts and slopes for people with MCI with vs. without the CSF AD biomarker signature. Result: There were 1,913 people with imaging data and age ³60. Single factor IRT models fit the data well for both composites. ADNI‐Lan outperformed MMSE language items, ADAS‐Cog language items, the Boston Naming Test (BNT), and fluency items in detecting change for MCI and AD. The clock score was modestly better than ADNI‐VS at detecting change for MCI and AD. ADNI Lan was the best at predicting MCI to AD conversion, while the clock score did slightly better than ADNI‐VS. Strength of association of language scores with structural MRI findings are shown in Table 1. ADNI‐Lan and the BNT had stronger associations than other scores for MCI in ADNI1, and also in ADNI2/ADNIGO except for BNT/temporal pole. For AD, ADNI‐Lan had strong associations with each region, similar to other scores except MMSE. Strength of association of visuospatial scores with structural MRI findings are shown in Table 2. ADNI‐VS and the clock had similar strong associations for most regions. People with MCI with the CSF AD biomarker signature had lower language intercepts, captured best by ADNI‐Lan, and more rapid decline, also captured best by ADNI‐Lan. Intercepts were not different for either visuospatial score, and ADNI‐VS and the clock score had similar slope terms. Conclusion: ADNI‐Lang and ADNI‐VS had good evidence of validity and may be useful composites for language and visuospatial functioning in ADNI. [ABSTRACT FROM AUTHOR]

Background: Composite scores may be useful to summarize overall language or visuospatial functioning. We generated composite scores for these domains from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and evaluated their validity. Method: We used item response theory to derive composite measures for language (ADNI‐Lan) and visuospatial functioning (ADNI‐VS). We performed multiple validation analyses comparing ADNI‐Lan and ADNI‐VS to individual test and global scores among participants with normal cognition (NC), mild cognitive impairment (MCI), and Alzheimer's disease (AD). We evaluated ability to detect change, strength of association with a priori selected structural brain imaging findings, association with risk of AD conversion for people with MCI, and differences in intercepts and slopes for people with MCI with vs. without the CSF AD biomarker signature. Result: There were 1,913 people with imaging data and age ³60. Single factor IRT models fit the data well for both composites. ADNI‐Lan outperformed MMSE language items, ADAS‐Cog language items, the Boston Naming Test (BNT), and fluency items in detecting change for MCI and AD. The clock score was modestly better than ADNI‐VS at detecting change for MCI and AD. ADNI Lan was the best at predicting MCI to AD conversion, while the clock score did slightly better than ADNI‐VS. Strength of association of language scores with structural MRI findings are shown in Table 1. ADNI‐Lan and the BNT had stronger associations than other scores for MCI in ADNI1, and also in ADNI2/ADNIGO except for BNT/temporal pole. For AD, ADNI‐Lan had strong associations with each region, similar to other scores except MMSE. Strength of association of visuospatial scores with structural MRI findings are shown in Table 2. ADNI‐VS and the clock had similar strong associations for most regions. People with MCI with the CSF AD biomarker signature had lower language intercepts, captured best by ADNI‐Lan, and more rapid decline, also captured best by ADNI‐Lan. Intercepts were not different for either visuospatial score, and ADNI‐VS and the clock score had similar slope terms. Conclusion: ADNI‐Lang and ADNI‐VS had good evidence of validity and may be useful composites for language and visuospatial functioning in ADNI. [ABSTRACT FROM AUTHOR]

Background: Identifying people with MCI at greatest risk of AD conversion is an important research goal. Our objective was to determine whether changes in domain‐specific cognitive functioning over 6 months could identify people at greatest risk of AD conversion. Method: We used modern psychometric methods applied to the ADNI cognitive battery to develop composite scores for memory, executive functioning, language, and visuospatial functioning. We considered scores at baseline and 6‐month visits for the 809 participants who had prevalent MCI in ADNI1, ADNIGO, and ADNI2, and characterized people based on quartiles of 6‐month changes in each domain. We used Cox models to determine whether 6‐month changes for each domain associated with risk for conversion to AD. We compared 6‐month changes to APOE genotype and the AD CSF biomarker signature, controlling for age, sex, and years of education. Result: 305 participants (38%) had zero bottom quartile change scores (most decline); 296 (37%) had one; 138 (17%) had two; 60 (7%) had three; and 10 (1.2%) had all four. Cox model results for 6‐month changes in all four domains without and with APOE genotype are shown in Table 1. There were 173 people with CSF results to characterize the AD biomarker signature. Cox results are shown in Table 2. Compared to people in the top quartile for 6‐month language change (most learning), people in the bottom quartile (most decline) were at increased risk of AD conversion, independent of APOE genotype and the AD biomarker signature. For 6‐month memory change, the hazard ratio for the bottom quartile (most decline) was attenuated when APOE genotype was included in the model, and it was null when the CSF biomarker signature was included. 6‐month changes in executive functioning and visuospatial functioning were not associated with risk of AD conversion. Conclusion: 6‐month changes in language identify people with MCI at highest risk of AD conversion. This effect is not explained by APOE genotype or CSF biomarkers. 6‐month language scores may identify people to target in AD prevention trials. [ABSTRACT FROM AUTHOR]

Background: Lifetime risk for Alzheimer's disease is higher among women than men, and reproductive health factors may contribute to differential risk. Reproductive health and cognitive aging among Hispanic women/Latinas is understudied, so we examined such relationships in the Hispanic Community Healthy Study/Study of Latinos (HCHS/SOL) and the SOL‐Investigation of Neurocognitive Aging (SOL‐INCA). Method: The sample included Hispanic/Latina post‐menopausal women (n = 1,903, baseline age 44‐74 years). Exposures included oral contraceptive use, number of live births (parity), number of pregnancies, age at menarche, age at menopause, and reproductive span (years with menses). Outcomes included visit 2 cognitive performance (7‐years after baseline on average), 7‐year cognitive change (reliable change index), and NIA‐AA criteria mild cognitive impairment (MCI) prevalence. Cognitive measures included verbal learning and memory, verbal fluency, executive functioning (Trail B, higher scores = worse performance), and processing speed (Digit Symbol Substitution = DSS; Trail A, higher scores = worse performance), and a global composite (average of all individual z‐scores). Survey linear regressions were used to separately model the associations between reproductive health measures and outcomes, controlling for baseline age, education, language preference, Hispanic/Latina background, field center, income, birthplace, marital status, insurance status, and body mass index. Result: Performance at visit 2: Oral contraceptive use was associated with higher global cognitive performance (β = 0.129 [SE = 0.043], p<0.01), learning (β = 0.197 [SE = 0.062], p<0.01), and processing speed (βDSS = 0.147 [SE = 0.049], p<0.01 and βTrailA = ‐0.142 [SE = 0.071], p<0.05) than non‐use. Higher parity was associated with worse executive functioning (β = 0.035 [SE = 0.017], p<0.05) and processing speed (βDSS = ‐0.054 [SE = 0.015], p<0.001). 7‐year (average) cognitive change: Oral contraceptive use, higher parity, and higher pregnancies were each protective against change in learning (β = 0.147 [SE = 0.064], β = 0.040 [SE = 0.019], and β = 0.034 [SE = 0.014], respectively; all ps<0.05). Older age at menarche was protective against change in global cognition (β = 0.045 [SE = 0.016], p<0.01), learning (β = 0.035 [SE = 0.017], p<0.05) and memory (β = 0.037 [SE = 0.017], p<0.05). MCI: No exposures were associated with MCI. Conclusion: Reproductive health was linked to later life cognition among diverse Hispanic/Latina women. Future work should examine potential hormonal (e.g., estrogen) mechanisms. Although not associated with MCI In the present study, reproductive health may be linked to MCI status as the cohort ages and more women transition to MCI or dementia. [ABSTRACT FROM AUTHOR]

Background: Neuropsychological assessment plays an important role in identifying mild cognitive impairment and dementia; demographically appropriate norms are essential for interpreting test performance and maximizing diagnostic accuracy. Limited availability of normative data for cognitive tests administered to older Hispanic/Latino adults can lead to diagnostic error. Executive functioning and information processing speed are crucial elements of neuropsychological assessment. To meet the needs of the Hispanic/Latino population, we investigated the associations of age, education, ethnic background, gender, and language on the Digit Symbol Substitution (DSS) test – a subtest of the WAIS‐R – and to provide demographically adjusted norms for a diverse group of Hispanics/Latinos. Method: The target population for the Study of Latinos‐Investigation of Neurocognitive Aging (SOL‐INCA; 2015–2018) included individuals from Central American, Cuban, Dominican, Mexican, Puerto Rican, and South American backgrounds (n = 6,172). Average age was 63.4±8.3 years, 54.5% were female, and mean education was 11.0±4.6 years. The DSS was administered as part of a larger cognitive protocol in participants' preferred language (English or Spanish). Lower scores on the DSS are associated with slower processing speed. Demographic adjusted DSS scores, and percentile cut‐points were created using survey‐adjusted regression and quantile regression models. Result: In covaried regression models, each year increase in age was associated with B = ‐0.54 (p<0.001) units decrease in DSS scores, and each additional year of education with B = 1.42 (p<0.001) units increase in performance. Males had, on average, lower DSS scores than females (B = ‐2.41; p<0.001), and individuals with English as their preferred language performed better than those preferring Spanish (B = 6.18; p<0.001). DSS performance varied significantly by Hispanic/Latino background with, predominantly, Mexicans scoring highest and Dominicans lowest on the DSS. Conclusion: While other norms for Hispanic/Latino populations exist, results from this study represent the largest and only norms for Hispanic/Latinos living in the US. Representative DSS test norms for diverse groups of US‐based Hispanics/Latinos will advance cognitive assessment and the accuracy of neurocognitive disorder diagnosis in this country. We have developed an online dashboard to facilitate potential clinical use and interpretation (https://solincalab.shinyapps.io/DSST/) [ABSTRACT FROM AUTHOR]

Background: Given mixed results regarding the role of bilingualism in cognitive aging, investigators are increasingly studying continuous measures of bilingualism (e.g., levels of language proficiency or use) as opposed to a dichotomous "yes/no" one, to better characterize the bilingual experience. We investigated associations of continuous measures of bilingualism and cognition. Method: Eligible Hispanic Community Health Study/Study of Latinos (HCHS/SOL) participants self‐reported their and their parents' birth outside the 50 United States and Spanish as their first language, and used Spanish for baseline cognitive testing at their HCHS/SOL visit (2008‐2011) and comparable cognitive testing 7‐years later as part of the SOL‐Investigation of Neurocognitive Aging (SOL‐INCA; 2015–2018). Composite scores for baseline self‐reported Spanish/English language proficiency (reading/speaking) and patterns of use (thinking/socializing) were rated using a Likert scale from 1 = only Spanish to 4 = English>Spanish. Cognitive testing at both visits included test‐specific and a global composite score(s) of verbal learning and memory, Word Fluency, and Digit Symbol Substitution (DSS). Survey linear regression models examined the associations between our two bilingualism scores (separately) and cognition (at follow‐up, and standardized measures of 7‐year change) adjusting for age, sex, education, depressive symptoms, income, Hispanic/Latino background, and field center. Result: There were 4,005 eligible participants (unweighted mean SOL‐INCA population age∼56 years, 56% female). Higher levels of second‐language (English) proficiency (β = 0.050, SE = 0.015, p<0.001) and patterns of use (β = 0.035, SE = 0.010, p<0.001) were associated with higher levels of global cognition at follow‐up (Figure), specifically, Fluency and DSS (p‐values<0.001). Only higher levels of second‐language proficiency were associated with better than predicted change in cognition, specifically, Fluency (β = 0.060, SE = 0.023, p<0.01). Conclusion: In an analytic sample of mid‐ to late‐life native Spanish speakers currently living in the US, second‐language (English) proficiency and patterns of use at baseline were associated with better cognitive outcomes over seven years of follow‐up. Associations of bilingualism composites and cognition suggest distinctions in the bilingual experience may differentially relate to level versus 7‐year change in cognition for Hispanics/Latinos. Investigations of foreign language learning on cognition in older adults, some of which have found no cognitive benefit, may be enhanced by using continuous measures of second‐language proficiency and, perhaps, patterns of language use. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study is to examine the association between verbal learning, fluency, and processing speed with anxious depression symptomatology (ADS) among diverse Hispanics. We hypothesized an inverse association of anxious depression with neurocognition among Hispanics of different heritage.Design: Data are from the Hispanic Community Health Study/Study of Latinos. The sample included 9,311participants aged 45-74 years (mean: 56.5 years). A latent class analysis of items from the Center for Epidemiological Studies for Depression scale and the Spielberger Trait Anxiety Inventory was used to derive an anxious depression construct. Neurocognitive measures included scores on the Brief Spanish English Verbal Learning Test (B-SEVLT, learning and recall trials), Word Fluency (WF), Digit Symbol Substitution (DSS) test, and a Global Cognitive Score (GCS). We fit survey linear regression models to test the associations between anxious depression symptomatology and cognitive function. We tested for effect modification by sex, Hispanic heritage, and age groups.Results: Among men, 71.6% reported low, 23.3% moderate, and 5.1% high ADS. Among women, 55.1% reported low, 33.2% moderate, and 11.8% high ADS. After controlling for age, sex, sociodemographic characteristics, cardiovascular risk factors and disease, and antidepressant use, we found significant inverse associations between moderate and high anxious depression (ref:low) with B-SEVLT learning and recall, DSS and GCS. Moderate, but not high, anxious depression was inversely associated with WF. Associations were not modified by sex, Hispanic heritage, or age.Conclusions: Increased anxious depression symptomatology is associated with decreased neurocognitive function among Hispanics. Longitudinal studies are needed to establish temporality and infer if negative emotional symptoms precede cognitive deficits. [ABSTRACT FROM AUTHOR]

We investigated whether midlife pulse pressure is associated with brain atrophy and cognitive decline, and whether the association was modified by apolipoprotein-E ε4 (APOE-ε4) and hypertension. Participants (549 stroke-free and dementia-free Framingham Offspring Cohort Study participants, age range=55.0 to 64.9 y) underwent baseline neuropsychological and magnetic resonance imaging (subset, n=454) evaluations with 5- to 7-year follow-up. Regression analyses investigated associations between baseline pulse pressure (systolic-diastolic pressure) and cognition, total cerebral volume and temporal horn ventricular volume (as an index of smaller hippocampal volume) at follow-up, and longitudinal change in these measures. Interactions with APOE-ε4 and hypertension were assessed. Covariates included age, sex, education, assessment interval, and interim stroke. In the total sample, baseline pulse pressure was associated with worse executive ability, lower total cerebral volume, and greater temporal horn ventricular volume 5 to 7 years later, and longitudinal decline in executive ability and increase in temporal horn ventricular volume. Among APOE-ε4 carriers only, baseline pulse pressure was associated with longitudinal decline in visuospatial organization. Findings indicate arterial stiffening, indexed by pulse pressure, may play a role in early cognitive decline and brain atrophy in mid to late life, particularly among APOE-ε4 carriers. [ABSTRACT FROM AUTHOR]

Background: Psychosocial factors including intrapersonal and interpersonal resources and social stressors are associated with changes in cognition in older non‐Hispanic whites and Blacks. Few studies have examined these associations in Hispanics/Latinos, the largest ethnic/racial group in the US, or evaluated ethnically‐based psychosocial factors that may be more relevant to this population. We examined whether psychosocial factors predict seven‐year cognitive changes among US Hispanics/Latinos. Method: Data from the parent HCHS/SOL, and Sociocultural and SOL‐Investigation of Neurocognitive Aging ancillary studies were used (n= 2,158; ages 45+). Baseline psychosocial factors included: intrapersonal factors (optimism; purpose in life), interpersonal factors (family cohesion; social network embeddedness; social support), social stressors (loneliness; subjective social status), and ethnically‐based factors (ethnic identity; familism; perceived ethnic discrimination). Outcomes were changes in individual test scores for episodic learning and memory (B‐SEVLT‐Sum and SEVLT‐Recall), word fluency (WF), and processing speed (Digit Symbol Substitution, DSS) derived using regressions adjusting for time between assessments. Survey linear regression models were used to examine the associations between each psychosocial factor (z‐scores) and 7‐year changes in cognitive outcomes adjusting for age, sex, education, income, Hispanic/Latino background, language preference, and depressive symptoms. Result: Mean age was 55.9±7.9 years; females 54% of target population. Higher (baseline) levels of familism [(βSEVLT‐Sum (SE))= ‐0.08 (0.03), P<0.05)] predicted seven‐year decline in verbal learning. Higher optimism [βSEVLT‐Recall= 0.09 (0.03), P<0.01], social support [βSEVLT‐Recall= 0.07 (0.03), P<0.05], and ethnic identity [βSEVLT‐Recall= 0.06 (0.03), P<0.05] each predicted increase in memory. Higher familism [βSEVLT‐Recall= ‐0.08 (0.03), P<0.05] and loneliness [βSEVLT‐Recall= ‐0.06 (0.03), P<0.05] each predicted decline in memory. Higher purpose in life [βWF= 0.07 (0.03), P<0.05] predicted increase in word fluency. Higher family cohesion [βDSS= ‐0.08 (0.03, P<0.01) predicted decline in processing speed. Social network embeddedness, subjective social status, and perceived ethnic discrimination were not associated with any outcome. Conclusion: Psychosocial factors differentially related to changes in cognition. Results confirm previous studies in non‐Hispanic whites on associations of optimism, purpose in life, social support, and loneliness with select cognitive tests. They also highlight that ethnic identity and familism are ethnically‐based psychosocial factors that should be considered when examining healthy cognitive aging in US Hispanics/Latinos. [ABSTRACT FROM AUTHOR]

Background: Hispanics/Latinos in the United States vary widely in their levels of acculturation (adoption of Anglo‐American culture) which may have implications for cognitive functioning in older age. We aimed to characterize the relationships of acculturation with cognition and cognitive change among diverse U.S. Hispanics/Latinos. Method: Selected Hispanics/Latinos (unweighted n=5,901; ages 50+ years) from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) were enrolled in the Study of Latinos ‐ Investigation of Neurocognitive Aging (SOL‐INCA) ancillary study. Three measures of acculturation were collected at baseline (Short Acculturation Scale for Hispanics (SASH) – Social and Language subscales (Marin et al., 1987) and MESA Acculturation score (Kandula et al., 2008). On all measures higher scores reflect greater acculturation. Cognition was measured at two time‐points, on average, 7‐years apart. Global cognition based on a composite measure from learning and memory, executive functioning, and processing speed tests at the second testing was the main outcome of interest in addition to change in global scores. Survey linear regressions were used to separately model the associations between acculturation measures (quartiles) and cognitive outcomes (z‐scores), controlling for baseline age, sex, education, Hispanic/Latino background, field center, income, marital status, and insurance status. Result: Average age of the target population was 63.3 ± 8.3(SD) years, 55% were female, 39% reported less than high school education, and 43% were currently uninsured. Adjusting for covariates, the least acculturated (lowest quartile) according to the SASH had lower global cognition compared to all other groups (all p‐values<0.01; Social subscale: b=0.10; SE=0.03, b=0.15; SE=0.03, and b=0.13; SE=0.03, for the 2nd, 3rd, and 4th quartiles respectively; Language subscale: b=0.15; SE=0.03, b=0.12; SE=0.03, and b=0.23; SE=0.03). Individuals with the lowest MESA acculturation quartile had lower global cognition relative to those with scores in the highest quartile only (b=0.13; SE=0.04; p<0.01). None of the acculturation indices were associated with global cognitive change. Associations with domain specific cognitive outcomes were largely similar in pattern. Conclusion: Acculturation may be indicative of baseline differences in cognition rather than risk for cognitive change. Alternatively, acculturation‐based distinctions in cognition may be related to differences in familiarity with testing environments or approaches to cognitive tasks. [ABSTRACT FROM AUTHOR]

Background: Latinos are 1.5 times as likely to develop Alzheimer's dementia as non‐Latino Whites. This health disparity may arise from multiple influences with culturally‐relevant factors receiving increasing attention. Models of acculturation stress the importance of considering acculturation‐related factors within the context of socioenvironmental factors to better capture the Latino experience in the US. Method: We measured 10 acculturation and contextually‐related variables in 199 Latinos (age∼69.7yrs) without dementia participating in Rush Alzheimer's Disease Center studies. We subjected these variables to Principal Component Analysis (PCA) to study their interrelationships; then investigated how the resulting components associated with level of and longitudinal change in domain‐specific cognition using separate linear mixed effects models adjusted for relevant confounders and their interactions with time. Result: The PCA revealed a 3‐factor unrotated solution (variance explained ∼70%). Factor 1, representing acculturation‐related aspects of nativity, language‐ and social‐based acculturation, was positively associated with level, but not change, in semantic memory and perceptual speed. Factor 2, representing contextually‐related socioenvironmental experiences of discrimination, social isolation, and social networks, was associated with lower levels of episodic memory and working memory and faster longitudinal decline in visuospatial ability (Figure 1). Factor 3 (familism only) did not associate with level or change in any cognitive outcome. We are actively investigating the role of cardiovascular health on these associations. Conclusion: Acculturation‐ and contextually‐related factors differentiated from each other and differentially contributed to cognition and cognitive decline in older Latinos. Providers should query multiple social determinants of health when evaluating older Latinos including acculturation‐ and contextually‐related lived experiences. [ABSTRACT FROM AUTHOR]

Background: Not everyone with mild cognitive impairment (MCI) progresses to Alzheimer's dementia (AD). Predicting who will decline is important. We previously reported that 6‐months change scores for language, but not for memory, executive functioning, or visuospatial functions, identified a high‐risk subgroup. Here we consider more specific language processes and consider AD fluid and imaging biomarkers. Methods: We used longitudinal data from 764 ADNI participants enrolled with MCI and still had MCI at 6 months, which was our baseline for Cox proportional hazards modeling of conversion to AD. We derived scores for four aspects of language: confrontation naming, animal fluency, letter fluency tests, and other language tests. We evaluated changes from enrollment to month 6 for each of these scores. We also adjusted models for APOE genotype, entorhinal thickness and hippocampal volume, and CSF amyloid and tau biomarkers. Results: The sample's mean age was 73.2 years, and 59% were male. From over 2918 total follow‐up years (mean 3.8), there were 287 conversions to AD. Cox models controlling for demographic characteristics, showed improvements in animal fluency scores associated with lower risk (HR=0.58, p=.005), but declines in confrontation naming were associated with higher risk (HR=1.74, p<.001). The animal fluency finding was somewhat attenuated when further controlling the Cox model for hippocampal volume (HR=0.64, p=0.10) and CSF biomarker findings (HR=0.61, p=0.12). Confrontation naming was not impacted by any of the imaging or fluid biomarkers we considered. Conclusions: In MCI, the association between six‐month changes in language, and the AD risk appears to be driven by animal fluency improvements and confrontation naming declines. Improvement in animal fluency may reflect still functional access to semantic networks. The attenuation of this signal when controlling for hippocampal volume and CSF biomarkers suggests inability to improve animal fluency may reflect processes associated with hippocampal volumes and CSF biomarkers. Declines in confrontation naming may represent impaired lexical access. The independence of this signal from hippocampal volumes and CSF biomarkers suggests declines in this network may act independently of these biomarkers. These findings suggest intriguing lines of research to further understand the importance of language abilities among people with MCI. [ABSTRACT FROM AUTHOR]

Background: Hispanics/Latinos have high prevalence of cardiovascular disease (CVD) risk factors which increases risk for stroke. However, the downstream impacts of CVD risk and stroke on brain structure in aging Hispanics/Latinos remains largely unknown. We compared Hispanic/Latino brain aging by CVD risk and stroke. Method: Hispanics/Latinos (nunweighted=1,156, 50‐85 years) from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) underwent magnetic resonance imaging (MRI) as part of the Study of Latinos ‐ Investigation of Neurocognitive Aging‐MRI (SOL‐INCA‐MRI) ancillary study. Outcomes included global (gray matter, total brain) and regional (lobar cortices, hippocampal) brain, lateral ventricle (log‐transformed), and total white matter hyperintensity (WMH; log‐transformed) volumes residualized for total cranial volume. Ten‐year CVD risk at visit 2 (before MRI) was determined by Framingham Risk Score and recoded into three groups (Low (<10%), Medium (10‐<20%) and High (20+%)). Stroke (yes, no) was based on self‐report of ≥1 strokes or transient ischemic attacks at visit 1 and/or 2. Linear regression models tested 1) whether CVD risk or presence of stroke modified the relationship between age and MRI outcomes, and 2) whether CVD risk or stroke related brain aging differed by sex. All models adjusted for height and Hispanic/Latino background. Result: Sample was 64.3± 7.1 years old on average (nunweighted=798 women). High CVD risk was inversely associated with total brain (standardized beta β=–0.26; p<0.001), total gray (β=‐0.23; p=0.006), frontal (β = ‐0.33; p<0.001) and parietal cortical gray (β =‐0.28; p=0.002) matter volumes and positively associated with (log) lateral ventricle (β log=0.23; p=0.006) and (log) WMH (βlog =0.42; p<0.001) volumes. Stroke/TIA (nunweighted=48) showed a similar profile of associations but only the associations with (log) lateral ventricle (βlog=0.27; p=0.049) and (log) WMH (βlog=0.44; p=0.001) reached significance. Accelerated brain aging (age slope modification) through CVD risk and stroke was evident for total brain volume but less so for other MRI outcomes, and equivalently so across sexes. Conclusion: Among Hispanics/Latinos, CVD risk and stroke are associated with poorer brain health across brain MRI indicators. Additionally, CVD risk and stroke may accelerate overall brain aging for both Hispanic/Latino men and women as determined by total brain volumes. [ABSTRACT FROM AUTHOR]

Background: The older Hispanic/Latino population in the U.S. is projected to grow faster than any racial/ethnic group in the country. Little is known about brain aging in this population, and we remain poorly equipped to detect and track brain changes in this population. We characterized brain aging in a sample of Hispanics/Latinos from diverse backgrounds and investigated differences by sex. Method: Nunweighted=1,389 Hispanics/Latinos (ages 39‐85 years; 66% female) from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) underwent brain magnetic resonance imaging (MRI) as part of the Study of Latinos ‐ Investigation of Neurocognitive Aging MRI (SOL‐INCA MRI) ancillary study. MRI outcomes of interest included global (gray matter, total brain) and regional (lobar cortices, hippocampus) brain volumes, lateral ventricle volume, and total white matter hyperintensity (WMH) volume. All MRI measures were residualized for total cranial volume prior to calculating brain aging trajectories using linear regressions that included sex, height, and Hispanic/Latino background as terms in the model. We also tested for effect modification by sex. Result: Mean age was 60.8± 10.3 years. Age was associated with decrements in total (βtotal=‐0.66; p<0.001) and hippocampal volumes (βhippocampus=‐0.20; p<0.001) as well as incremental enlargements in lateral ventricle and WMH volumes (βlog_lateralvent=0.48; p<0.001; βlog_WMH=0.54; p<0.001). Age was also inversely linked to total brain gray matter as well as all lobar cortical gray matter volumes. Age‐related decrements in total and regional brain volumes, but not lateral ventricle or WMH, were exacerbated in men relative to women (all p<0.05). Adjusting for height and background, women had larger total brain (standardized beta βtotal=0.27; p<0.001), frontal (βfrontal=0.27; p<0.001), and parietal (βparietal=0.17; p=0.025) volumes, smaller hippocampal and lateral ventricle volumes, and larger gray matter volumes, but did not differ in WMH as compared to men. Conclusion: These findings suggest that increasing age is associated with smaller regional MRI brain measures in Hispanic/Latino individuals. Aging patterns in gray matter volumes appeared to be exacerbated among men compared to women whereas age‐related differences in lateral ventricular volume and white matter hyperintensities were consistent between sexes. Our findings help establish the trajectories of brain aging among middle‐aged and older Hispanics/Latinos. [ABSTRACT FROM AUTHOR]

The article focuses on a study which utilized graph theory metrics to study brain connectivity in late-life depression and aging. Topics discussed include neuroimaging protocol, image analysis, and statistical analyses of data. Results in terms of demographics, sex differences, group differences and correlations with age are also mentioned.

The article reports on research which was conducted to investigate whether there was a link between vascular risk and depression in euthymic older adults. Researchers evaluated 57 older adults between the ages of 50 and 89. They found that there was an association between vascular risk and depression in euthymic older adults but concluded that their research had limitations.

The article reports on research which used graph theory and interregional correlations of cortical and subcortical volumes to investigate cortical subcortical structural network properties in subjects with later-life depression (LLD) compared with healthy comparison subjects. Researchers evaluated 73 healthy older subjects and 53 subjects with LDD. They found that cortical-subcortical network properties are altered in LLD and may reflect the underlying neuroanatomical vulnerabilities of the disorder.

The article reports on two techniques, diffusion tensor imaging and multi-component relaxometry techniques, which are used to provide images of brain white matter microstructure in the aging brain and discusses the benefits and limitations of both. A discussion of the role that both techniques will play in providing additional information on white matter structure and function and in providing information on the role that myelin and axonal integrity play in the aging of white matter, is presented.