Cross-national comparisons of later-life cognitive function using data from the Harmonized Cognitive Assessment Protocol (HCAP): Considerations and recommended best practices.

The Harmonized Cognitive Assessment Protocol (HCAP) is a major innovation that provides, for the first time, harmonized data for cross-national comparisons of later-life cognitive functions that are sensitive to linguistic, cultural, and educational differences across countries. However, cognitive function does not lend itself to direct comparison across diverse populations without careful consideration of the best practices for such comparisons. This perspective discusses theoretical and methodological considerations and offers a set of recommended best practices for conducting cross-national comparisons of risk factor associations using HCAP data. Because existing and planned HCAP studies provide cognition data representing an estimated 75% of the global population ≥65 years of age, these recommended best practices will support high-quality comparative analyses of cognitive aging around the world. The principles described in this perspective are applicable to any researcher aiming to integrate or compare harmonized data on cognitive outcomes and their risk and protective factors across diverse populations.

A community-based study of reporting demographic and clinical information concordance between informants and cognitively impaired participants.

BACKGROUND: Understanding concordance between informants' and cognitively impaired participants' information reporting is crucial for Alzheimer's and Alzheimer's-related dementia studies. METHODS: The Brain Attack Surveillance in Corpus Christi-Cognitive is a community-based cohort study. Households in Nueces County, Texas, USA, were randomly identified. 330 dyads of participants and their named informants answered questions. Models were generated to examine which predictors, including age, gender, ethnicity, cognitive function, and relationship to informant, influenced answer discordance. RESULTS: For demographic items, female participants and participants with spouses/partners as informants had significantly less discordance, with incidence rate rations (IRRs) of 0.65 (CI = 0.44, 0.96) and 0.41 (CI = 0.23, 0.75), respectively. For health items, better cognitive function of the participant was associated with less discordance, with an IRR of 0.85 (CI = 0.76, 0.94). CONCLUSIONS: Demographic information concordance is most associated with gender and informant-participant relationship. Level of cognitive function is most associated with concordance for health information. CLINICALTRIALS: gov identifier NCT03403257.

Cognitive recovery trajectories 3 months following stroke in Mexican American and non-Hispanic white adults.

OBJECTIVES: We examined whether cognitive trajectories from 0-3 months after stroke differ between Mexican Americans (MAs) and non-Hispanic white (NHW) adults. MATERIALS AND METHODS: The sample included 701 participants with ischemic stroke (62% MA; 38% NHW) from the population-based stroke surveillance study, the Brain Attack Surveillance in Corpus Christi (BASIC) Project, between 2008-2013. The outcome was the modified Mini Mental State Examination (3MSE, range 0-100 lower scores worse). Linear mixed effects models were utilized to examine the association between ethnicity and cognitive trajectories from 0-3 months following stroke, adjusting for confounders. RESULTS: MAs were younger, had lower educational attainment, and fewer had health insurance than NHWs (all p< 0.01). A smaller proportion of MAs were rated by informants as exhibiting pre-stroke cognitive decline than NHW (p < .0.05). After accounting for confounders, MAs demonstrated lower cognitive performance at post-stroke baseline and at 3-months following stroke (-2.00; 95% CI =-3.92, -0.07). Cognitive trajectories from 0-3 months following stroke were indicative of modest cognitive recovery (increase of 0.034/day, 95% CI =0.030-0.036) and did not differ between MAs and NHWs (p = 0.68). CONCLUSION: We found no evidence that cognitive trajectories in the first three months following stroke differed between MAs and NHWs. MAs demonstrated lower cognitive performance shortly after stroke and at three months following stroke compared to NHWs. Further research is needed to identify factors contributing to ethnic disparities in cognitive outcomes after stroke.

Differential Impact of Stroke on Cognitive Impairment in Mexican Americans and Non-Hispanic White Americans.

BACKGROUND: The association between stroke and dementia is well established. Less is known about this association in underrepresented ethnic groups. In a large ethnically diverse cohort, we examined whether history of stroke was associated with cognitive impairment, and whether this relationship differed by ethnicity (Mexican American [MA] versus non-Hispanic White). METHODS: This was a population-based cohort study conducted in Nueces County, TX, a biethnic community with a large and primarily nonimmigrant MA population. Residents aged ≥65 were recruited door-to-door or by telephone between May 2018 and December 2021. The primary exposure was history of stroke, obtained by self-report. Demographic, medical, and educational histories were also obtained. The primary outcome was the Montreal Cognitive Assessment (MoCA), a scale that evaluates multiple domains of cognitive performance. Scores were divided into 3 ordinal categories, roughly corresponding to normal cognition (MoCA 26-30), mild cognitive impairment (MoCA 20-25), or probable dementia (MoCA 0-19). RESULTS: One thousand eight hundred one participants completed MoCA screening (55% female; 50% MA, 44% Non-Hispanic White, 6% other), of whom 12.4% reported history of stroke. Stroke prevalence was similar across ethnicities (X2 2.1; P=0.34). In a multivariable cumulative logit regression model for the ordinal cognition outcome, a stroke by ethnicity interaction was observed (P=0.01). Models stratified by ethnicity revealed that stroke was associated with cognitive impairment across ethnicities, but had greater impact on cognition in non-Hispanic Whites (cumulative odds ratio=3.81 [95% CI, 2.37-6.12]) than in MAs (cumulative odds ratio=1.58 [95% CI, 1.04-2.41]). Increased age and lower educational attainment were also associated with cognitive impairment, regardless of ethnicity. CONCLUSIONS: History of stroke was associated with increased odds of cognitive impairment after controlling for other factors in both MA and Non-Hispanic White participants. The magnitude of the impact of stroke on cognition was less in MA than in Non-Hispanic White participants.

Differential Relationships Between the Montreal Cognitive Assessment and Informant-Rated Cognitive Decline Among Mexican Americans and Non-Hispanic Whites.

OBJECTIVES: We compared the concurrent validity of the Montreal Cognitive Assessment (MoCA) with other cognitive screening instruments among Mexican Americans (MA) and non-Hispanic whites (NHW). METHODS: In a community-based study in Nueces county, Texas (5/2/18-2/26/20), participants 65+ with MoCA ≤25 completed the Harmonized Cognitive Assessment Protocol. Regressions examined associations between MoCA and: 1) Mini Mental State Examination (MMSE); 2) abbreviated Community Screening Interview for Dementia (CSI-D); 3) Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). RESULTS: MA (n = 229) and NHW (n = 81) differed by education but not age or sex. MoCA and cognitive performance associations (MMSE, CSI-D-Respondent) did not differ between MA and NHW (p's > .16). MoCA and informant rating associations (IQCODE, CSI-D-Informant) were stronger in NHW than MA (NHW R2 = 0.39 and 0.38, respectively; MA R2 = 0.30 and 0.28, respectively). DISCUSSION: Our findings suggest non-equivalence across cognitive screening instruments among MAs and NHWs.

Dementia care needs for individuals and caregivers among Mexican Americans and non-Hispanic Whites.

Mexican Americans (MA) are more likely to have cognitive impairment and dementia (CID), be diagnosed at an earlier age and live with CID longer, compared to non-Hispanic Whites (NHW). While studies have examined unmet needs of individuals with CID and their caregivers, few have focused on MA populations in the U.S. This paper examines the needs of community-residing individuals with CID and their caregivers in Nueces County, Texas, a county with one of the largest MA populations in the U.S., while exploring ethnic differences in needs identified.Using concept mapping, a mixed-method approach, qualitative input on perceived needs by informal caregivers and health professionals was collected. Participants then sorted and rated perceived needs. Using this information, multidimensional scaling and cluster analyses were conducted to map the relationship between perceived needs and determine their importance and priority.Five clusters were derived for caregivers and four for the health professionals. Themes across both caregivers and health professionals highlighted the need for specialized and team-based medical care, caregiver support and training, along with socio-economic and physical needs that help with day-to-day care of individuals with CID. Among caregivers, MA rated financial resources as more important and of higher priority compared to NHW. The health professionals' perspectives were aligned with those of all caregivers.By understanding the needs of caregivers and individuals with CID, we can help families deal with this disease and let caregivers thrive. This is especially important for minority populations like MAs.

Association of Blood Pressure and Cognition after Stroke.

BACKGROUND AND AIM: It is unclear whether blood pressure (BP) is associated with cognition after stroke. We examined associations between systolic and diastolic BP (SBP, DBP), pulse pressure (PP), mean arterial pressure (MAP), and cognition, each measured 90 days after stroke. METHODS: Cross-sectional analysis of prospectively obtained data of 432 dementia-free subjects greater than or equal to 45 (median age, 66; 45% female) with stroke (92% ischemic; median NIH stroke score, 3 [IQR, 2-6]) from the population-based Brain Attack Surveillance in Corpus Christi (BASIC) project in 2011-2013. PRIMARY OUTCOME: Modified Mini-Mental Status Examination (3MSE; range, 0-100). SECONDARY OUTCOMES: Animal Fluency Test (AFT; range, 0-10) and Trail Making Tests A and B (number of correct items [range, 0-25]/completion time [Trails A: 0-180 seconds; Trails B: 0-300 second]). Linear or tobit regression adjusted associations for age, education, and race/ethnicity as well as variables significantly associated with BP and cognition. RESULTS: Higher SBP, lower DBP, higher PP, and lower MAP each were associated with worse cognitive performance for all 4 tests (all P < .001). After adjusting for patient factors, no BP measures were associated with any of the 4 tests (all P > .05). Lower cognitive performance was associated with older age, less education, Mexican American ethnicity, diabetes, higher stroke severity, more depressive symptoms, and lower BMI. Among survivors with hypertension, anti-hypertensive medication use 90 days after stroke was significantly associated with higher AFT scores (P = .02) but not other tests (P > .15). CONCLUSIONS: Stroke survivors' BP levels were not associated with cognitive performance at 90 days independent of sociodemographic and clinical factors.

Integrated cross-network connectivity of amygdala, insula, and subgenual cingulate associated with facial emotion perception in healthy controls and remitted major depressive disorder.

Emotion perception deficits could be due to disrupted connectivity of key nodes in the salience and emotion network (SEN), including the amygdala, subgenual anterior cingulate cortex (sgACC), and insula. We examined SEN resting-state (rs-)fMRI connectivity in rMDD in relation to Facial Emotion Perception Test (FEPT) performance. Fifty-two medication-free people ages 18 to 23 years participated. Twenty-seven had major depressive disorder (MDD) in remission (rMDD, 10 males), as MDD is associated with emotion perception deficits and alterations in rsfMRI. Twenty-five healthy controls (10 males) also participated. Participants completed the FEPT during fMRI, in addition to an 8-minute eyes-open resting-state scan. Seed regions of interest were defined in the amygdala, anterior insula and sgACC. Multiple regression analyses co-varied diagnostic group, sex and movement parameters. Emotion perception accuracy was positively associated with connectivity between amygdala seeds and regions primarily in the SEN and cognitive control network (CCN), and also the default mode network (DMN). Accuracy was also positively associated with connectivity between the sgACC seeds and other SEN regions, and the DMN, particularly for the right sgACC. Connectivity negatively associated with emotion perception was mostly with regions outside of these three networks, other than the left insula and part of the DMN. This study is the first to our knowledge to demonstrate relationships between facial emotion processing and resting-state connectivity with SEN nodes and between SEN nodes and regions located within other neural networks.

Decreased Fronto-Limbic Activation and Disrupted Semantic-Cued List Learning in Major Depressive Disorder.

OBJECTIVES: Individuals with major depressive disorder (MDD) demonstrate poorer learning and memory skills relative to never-depressed comparisons (NDC). Previous studies report decreased volume and disrupted function of frontal lobes and hippocampi in MDD during memory challenge. However, it has been difficult to dissociate contributions of short-term memory and executive functioning to memory difficulties from those that might be attributable to long-term memory deficits. METHODS: Adult males (MDD, n=19; NDC, n=22) and females (MDD, n=23; NDC, n=19) performed the Semantic List Learning Task (SLLT) during functional magnetic resonance imaging. The SLLT Encoding condition consists of 15 lists, each containing 14 words. After each list, a Distractor condition occurs, followed by cued Silent Rehearsal instructions. Post-scan recall and recognition were collected. Groups were compared using block (Encoding-Silent Rehearsal) and event-related (Words Recalled) models. RESULTS: MDD displayed lower recall relative to NDC. NDC displayed greater activation in several temporal, frontal, and parietal regions, for both Encoding-Silent Rehearsal and the Words Recalled analyses. Groups also differed in activation patterns in regions of the Papez circuit in planned analyses. The majority of activation differences were not related to performance, presence of medications, presence of comorbid anxiety disorder, or decreased gray matter volume in MDD. CONCLUSIONS: Adults with MDD exhibit memory difficulties during a task designed to reduce the contribution of individual variability from short-term memory and executive functioning processes, parallel with decreased activation in memory and executive functioning circuits. Ecologically valid long-term memory tasks are imperative for uncovering neural correlates of memory performance deficits in adults with MDD.

Age and gender modulate the neural circuitry supporting facial emotion processing in adults with major depressive disorder.

OBJECTIVES: Emotion processing, supported by frontolimbic circuitry known to be sensitive to the effects of aging, is a relatively understudied cognitive-emotional domain in geriatric depression. Some evidence suggests that the neurophysiological disruption observed in emotion processing among adults with major depressive disorder (MDD) may be modulated by both gender and age. Therefore, the present study investigated the effects of gender and age on the neural circuitry supporting emotion processing in MDD. DESIGN: Cross-sectional comparison of fMRI signal during performance of an emotion processing task. SETTING: Outpatient university setting. PARTICIPANTS: One hundred adults recruited by MDD status, gender, and age. MEASUREMENTS: Participants underwent fMRI while completing the Facial Emotion Perception Test. They viewed photographs of faces and categorized the emotion perceived. Contrast for fMRI was of face perception minus animal identification blocks. RESULTS: Effects of depression were observed in precuneus and effects of age in a number of frontolimbic regions. Three-way interactions were present between MDD status, gender, and age in regions pertinent to emotion processing, including frontal, limbic, and basal ganglia. Young women with MDD and older men with MDD exhibited hyperactivation in these regions compared with their respective same-gender healthy comparison (HC) counterparts. In contrast, older women and younger men with MDD exhibited hypoactivation compared to their respective same-gender HC counterparts. CONCLUSIONS: This the first study to report gender- and age-specific differences in emotion processing circuitry in MDD. Gender-differential mechanisms may underlie cognitive-emotional disruption in older adults with MDD. The present findings have implications for improved probes into the heterogeneity of the MDD syndrome.

Stress Response to the Functional Magnetic Resonance Imaging Environment in Healthy Adults Relates to the Degree of Limbic Reactivity during Emotion Processing.

BACKGROUND: Imaging techniques are increasingly being used to examine the neural correlates of stress and emotion processing; however, relations between the primary stress hormone cortisol, the functional magnetic resonance imaging (fMRI) environment, and individual differences in response to emotional challenges are not yet well studied. The present study investigated whether cortisol activity prior to, and during, an fMRI scan may be related to neural processing of emotional information. METHODS: Twenty-six healthy individuals (10 female) completed a facial emotion perception test during 3-tesla fMRI. RESULTS: Prescan cortisol was significantly correlated with enhanced amygdala, hippocampal, and subgenual cingulate reactivity for facial recognition. Cortisol change from pre- to postscanning predicted a greater activation in the precuneus for both fearful and angry faces. A negative relationship between overall face accuracy and activation in limbic regions was observed. CONCLUSION: Individual differences in response to the fMRI environment might lead to a greater heterogeneity of brain activation in control samples, decreasing the power to detect differences between clinical and comparison groups. © 2015 S. Karger AG, Basel.

Differential prefrontal and subcortical circuitry engagement during encoding of semantically related words in patients with late-life depression.

OBJECTIVE: Verbal memory difficulties are common among individuals with late-life depression (LLD), though there is limited knowledge about disruptions to underlying cerebral circuitry. The purpose of this study is to examine aberrations to cerebral networks implicated in encoding novel verbal semantic material among older adults with LLD. METHODS: Twenty-four older adults with early-onset LLD and 23 non-depressed comparisons participated in the study. Participants completed a word list-learning task while undergoing functional magnetic resonance imaging. RESULTS: In the context of equivalent recall and recognition of words following scanning and similar hippocampal volumes, patients with LLD exhibited less activation in structures known to be relevant for new learning and memory, including hippocampus, parahippocampal gyrus, insula, and cingulate, relative to non-ill comparisons. An important region in which the LLD group displayed greater activation than the non-depressed comparison group was in left inferior frontal gyrus, an area involved in cognitive control and controlled semantic/phonological retrieval and analysis; this region may be critical for LLD patients to consolidate encoded words into memory. CONCLUSIONS: Functional irregularities found in LLD patients may reflect different modes of processing to-be-remembered information and/or early changes predictive of incipient cognitive decline. Future studies might consider mechanisms that could contribute to these functional differences, including hypothalamic-pituitary-adrenal axis functioning and vascular integrity, and utilize longitudinal designs in order to understand whether functional changes are predictive of incipient cognitive decline.

A Community-Based Study of Dementia in Mexican American and Non-Hispanic White Individuals.

BACKGROUND: Little information is available on the prevalence of cognitive impairment in Mexican American persons. OBJECTIVE: To determine the prevalence of mild cognitive impairment (MCI) and dementia in those 65 years and older among Mexican American and non-Hispanic white individuals in a community. METHODS: This was a population-based cohort study in Nueces County, Texas, USA. Participants were recruited using a random housing sample. The Harmonized Cognitive Assessment (HCAP) participant and informant protocol was performed after Montreal Cognitive Assessment (MoCA) screening. An algorithm was used to sort participants into diagnostic categories: no cognitive impairment, MCI, or dementia. Logistic regression determined the association of ethnicity with MCI and dementia controlling for age, gender, and education. RESULTS: 1,901 participants completed the MoCA and 547 the HCAP. Mexican Americans were younger and had less educational attainment than non-Hispanic whites. Overall, dementia prevalence was 11.6% (95% CI 9.2-14.0) and MCI prevalence was 21.2% (95% CI 17.5-24.8). After adjusting for age, gender, and education level, there was no significant ethnic difference in the odds of dementia or MCI. Those with ≤11 compared with ≥16 years of education had much higher dementia [OR = 4.9 (95% CI 2.2-11.1)] and MCI risk [OR = 3.5 (95% CI 1.6-7.5)]. CONCLUSIONS: Dementia and MCI prevalence were high in both Mexican American and non-Hispanic white populations. Mexican American persons had double the odds of mild cognitive impairment and this was attenuated when age and educational attainment were considered. Educational attainment was a potent predictor of cognitive impairment.

Exploring Pathways to Caregiver Health: The Roles of Caregiver Burden, Familism, and Ethnicity.

OBJECTIVES: This study examines the associations of ethnicity, caregiver burden, familism, and physical and mental health among Mexican Americans (MAs) and non-Hispanic Whites (NHWs). METHODS: We recruited adults 65+ years with possible cognitive impairment (using the Montreal Cognitive Assessment score<26), and their caregivers living in Nueces County, Texas. We used weighted path analysis to test effects of ethnicity, familism, and caregiver burden on caregiver's mental and physical health. RESULTS: 516 caregivers and care-receivers participated. MA caregivers were younger, more likely female, and less educated compared to NHWs. Increased caregiver burden was associated with worse mental (B = -0.53; p < .001) and physical health (B = -0.15; p = .002). Familism was associated with lower burden (B = -0.14; p = .001). MA caregivers had stronger familism scores (B = 0.49; p < .001). DISCUSSION: Increased burden is associated with worse caregiver mental and physical health. MA caregivers had stronger familism resulting in better health. Findings can contribute to early identification, intervention, and coordination of services to help reduce caregiver burden.

Effect of Population-Level Blood Pressure Treatment Strategies on Cardiovascular and Cognitive Outcomes.

BACKGROUND: The large and increasing number of adults living with dementia is a pressing societal priority, which may be partially mitigated through improved population-level blood pressure (BP) control. We explored how tighter population-level BP control affects the incidence of atherosclerotic cardiovascular disease (ASCVD) events and dementia. METHODS: Using an open-source ASCVD and dementia simulation analysis platform, the Michigan Chronic Disease Simulation Model, we evaluated how optimal implementation of 2 BP treatments based on the Eighth Joint National Committee recommendations and SPRINT (Systolic Blood Pressure Intervention Trial) protocol would influence population-level ASCVD events, global cognitive performance, and all-cause dementia. We simulated 3 populations (usual care, Eighth Joint National Committee based, SPRINT based) using nationally representative data to annually update risk factors and assign ASCVD events, global cognitive performance scores, and dementia, applying different BP treatments in each population. We tabulated total ASCVD events, global cognitive performance, all-cause dementia, optimal brain health, and years lived in each state per population. RESULTS: Optimal implementation of SPRINT-based BP treatment strategy, compared with usual care, reduced ASCVD events in the United States by ≈77 000 per year and produced 0.4 more years of stroke- or myocardial infarction-free survival when averaged across all Americans. Population-level gains in years lived free of ASCVD events were greater for SPRINT-based than Eighth Joint National Committee-based treatment. Survival and years spent with optimal brain health improved with optimal SPRINT-based BP treatment implementation versus usual care: the average patient with hypertension lived 0.19 additional years and 0.3 additional years in optimal brain health. SPRINT-based BP treatment increased the number of years lived without dementia (by an average of 0.13 years/person with hypertension), but increased the total number of individuals with dementia, mainly through more adults surviving to advanced ages. CONCLUSIONS: Tighter BP control likely benefits most individuals but is unlikely to reduce dementia prevalence and might even increase the number of older adults living with dementia.

Trajectory of Cognitive Function After Incident Heart Failure.

Background: The size/magnitude of cognitive changes after incident heart failure (HF) are unclear. We assessed whether incident HF is associated with changes in cognitive function after accounting for pre-HF cognitive trajectories and known determinants of cognition. Methods: This pooled cohort study included adults without HF, stroke, or dementia from six US population-based cohort studies from 1971-2019: Atherosclerosis Risk in Communities Study, Coronary Artery Risk Development in Young Adults Study, Cardiovascular Health Study, Framingham Offspring Study, Multi-Ethnic Study of Atherosclerosis, and Northern Manhattan Study. Linear mixed-effects models estimated changes in cognition at the time of HF (change in the intercept) and the rate of cognitive change over the years after HF (change in the slope), controlling for pre-HF cognitive trajectories and participant factors. Change in global cognition was the primary outcome. Change in executive function and memory were secondary outcomes. Cognitive outcomes were standardized to a t-score metric (mean [SD], 50 [10]); a 1-point difference represented a 0.1-SD difference in cognition. Results: The study included 29,614 adults (mean [SD] age was 61.1 [10.5] years, 55% female, 70.3% White, 22.2% Black 7.5% Hispanic). During a median follow-up of 6.6 (Q1-Q3: 5-19.8) years, 1,407 (4.7%) adults developed incident HF. Incident HF was associated with an acute decrease in global cognition (-1.08 points; 95% CI -1.36, -0.80) and executive function (-0.65 points; 95% CI -0.96, -0.34) but not memory (-0.51 points; 95% CI -1.37, 0.35) at the time of the event. Greater acute decreases in global cognition after HF were seen in those with older age, female sex and White race. Individuals with incident HF, compared to HF-free individuals, demonstrated faster declines in global cognition (-0.15 points per year; 95% CI, -0.21, -0.09) and executive function (-0.16 points per year; 95% CI -0.23, -0.09) but not memory ( -0.11 points per year; 95% CI -0.26, 0.04) compared with pre-HF slopes. Conclusions: In this pooled cohort study, incident HF was associated with an acute decrease in global cognition and executive function at the time of the event and faster declines in global cognition and executive function over the following years.

Development and validation of the Michigan Chronic Disease Simulation Model (MICROSIM).

Strategies to prevent or delay Alzheimer's disease and related dementias (AD/ADRD) are urgently needed, and blood pressure (BP) management is a promising strategy. Yet the effects of different BP control strategies across the life course on AD/ADRD are unknown. Randomized trials may be infeasible due to prolonged follow-up and large sample sizes. Simulation analysis is a practical approach to estimating these effects using the best available existing data. However, existing simulation frameworks cannot estimate the effects of BP control on both dementia and cardiovascular disease. This manuscript describes the design principles, implementation details, and population-level validation of a novel population-health microsimulation framework, the MIchigan ChROnic Disease SIMulation (MICROSIM), for The Effect of Lower Blood Pressure over the Life Course on Late-life Cognition in Blacks, Hispanics, and Whites (BP-COG) study of the effect of BP levels over the life course on dementia and cardiovascular disease. MICROSIM is an agent-based Monte Carlo simulation designed using computer programming best practices. MICROSIM estimates annual vascular risk factor levels and transition probabilities in all-cause dementia, stroke, myocardial infarction, and mortality in a nationally representative sample of US adults 18+ using the National Health and Nutrition Examination Survey (NHANES). MICROSIM models changes in risk factors over time, cognition and dementia using changes from a pooled dataset of individual participant data from 6 US prospective cardiovascular cohort studies. Cardiovascular risks were estimated using a widely used risk model and BP treatment effects were derived from meta-analyses of randomized trials. MICROSIM is an extensible, open-source framework designed to estimate the population-level impact of different BP management strategies and reproduces US population-level estimates of BP and other vascular risk factors levels, their change over time, and incident all-cause dementia, stroke, myocardial infarction, and mortality.

Associations Between Stroke Type, Ischemic Stroke Subtypes, and Post-Stroke Cognitive Trajectories.

Background: It is unclear how post-stroke cognitive trajectories differ by stroke type and ischemic stroke subtype. We studied associations between stroke types (ischemic, hemorrhagic), ischemic stroke subtypes (cardioembolic, large artery atherosclerotic, lacunar/small vessel, cryptogenic/other determined etiology), and post-stroke cognitive decline. Methods: This pooled cohort analysis from four US cohort studies (1971-2019) identified 1,143 dementia-free individuals with acute stroke during follow-up: 1,061 (92.8%) ischemic, 82 (7.2%) hemorrhagic, 49.9% female, 30.8% Black. Median age at stroke was 74.1 (IQR, 68.6, 79.3) years. Outcomes were change in global cognition (primary) and changes in executive function and memory (secondary). Outcomes were standardized as T-scores (mean [SD], 50 [10]); a 1-point difference represents a 0.1-SD difference in cognition. Median follow-up for the primary outcome was 6.0 (IQR, 3.2, 9.2) years. Linear mixed-effects models estimated changes in cognition after stroke. Results: On average, the initial post-stroke global cognition score was 50.78 points (95% CI, 49.52, 52.03) in ischemic stroke survivors and did not differ in hemorrhagic stroke survivors (difference, -0.17 points [95% CI, -1.64, 1.30]; P=0.82) after adjusting for demographics and pre-stroke cognition. On average, ischemic stroke survivors showed declines in global cognition, executive function, and memory. Post-stroke declines in global cognition, executive function, and memory did not differ between hemorrhagic and ischemic stroke survivors. 955 ischemic strokes had subtypes: 200 (20.9%) cardioembolic, 77 (8.1%) large artery atherosclerotic, 207 (21.7%) lacunar/small vessel, 471 (49.3%) cryptogenic/other determined etiology. On average, small vessel stroke survivors showed declines in global cognition and memory, but not executive function. Initial post-stroke cognitive scores and cognitive declines did not differ between small vessel survivors and survivors of other ischemic stroke subtypes. Post-stroke vascular risk factor levels did not attenuate associations. Conclusion: Stroke survivors had cognitive decline in multiple domains. Declines did not differ by stroke type or ischemic stroke subtype.

A cultural neuropsychological approach to harmonization of cognitive data across culturally and linguistically diverse older adult populations.

OBJECTIVE: To describe a cultural neuropsychological approach to prestatistical harmonization of cognitive data across the United States (U.S.) and Mexico with the Harmonized Cognitive Assessment Protocol (HCAP). METHOD: We performed a comprehensive review of the administration, scoring, and coding procedures for each cognitive test item administered across the English and Spanish versions of the HCAP in the Health and Retirement Study (HRS) in the U.S. and the Ancillary Study on Cognitive Aging in Mexico (Mex-Cog). For items that were potentially equivalent across studies, we compared each cognitive test item for linguistic and cultural equivalence and classified items as confident or tentative linking items, based on the degree of confidence in their comparability across cohorts and language groups. We evaluated these classifications using differential item functioning techniques. RESULTS: We evaluated 132 test items among 21 cognitive instruments in the HCAP across the HRS and Mex-Cog. We identified 72 confident linking items, 46 tentative linking items, and 14 items that were not comparable across cohorts. Measurement invariance analysis revealed that 64% of the confident linking items and 83% of the tentative linking items showed statistical evidence of measurement differences across cohorts. CONCLUSIONS: Prestatistical harmonization of cognitive data, performed by a multidisciplinary and multilingual team including cultural neuropsychologists, can identify differences in cognitive construct measurement across languages and cultures that may not be identified by statistical procedures alone. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Harmonization of Later-Life Cognitive Function Across National Contexts: Results from the Harmonized Cognitive Assessment Protocols (HCAPs).

Background: The Harmonized Cognitive Assessment Protocol (HCAP) is an innovative instrument for cross-national comparisons of later-life cognitive function, yet its suitability across diverse populations is unknown. We aimed to harmonize general and domain-specific cognitive scores from HCAPs across six countries, and evaluate precision and criterion validity of the resulting harmonized scores. Methods: We statistically harmonized general and domain-specific cognitive function across the six publicly available HCAP partner studies in the United States, England, India, Mexico, China, and South Africa (N=21,141). We used an item banking approach that leveraged common cognitive test items across studies and tests that were unique to studies, as identified by a multidisciplinary expert panel. We generated harmonized factor scores for general and domain- specific cognitive function using serially estimated graded-response item response theory (IRT) models. We evaluated precision of the factor scores using test information plots and criterion validity using age, gender, and educational attainment. Findings: IRT models of cognitive function in each country fit well. We compared measurement reliability of the harmonized general cognitive function factor across each cohort using test information plots; marginal reliability was high (r> 0·90) for 93% of respondents across six countries. In each country, general cognitive function scores were lower with older ages and higher with greater levels of educational attainment. Interpretation: We statistically harmonized cognitive function measures across six large, population-based studies of cognitive aging in the US, England, India, Mexico, China, and South Africa. Precision of the estimated scores was excellent. This work provides a foundation for international networks of researchers to make stronger inferences and direct comparisons of cross-national associations of risk factors for cognitive outcomes. Funding: National Institute on Aging (R01 AG070953, R01 AG030153, R01 AG051125, U01 AG058499; U24 AG065182; R01AG051158).