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IMPORTANCE: The magnitude of cognitive change after incident myocardial infarction (MI) is unclear. OBJECTIVE: To assess whether incident MI is associated with changes in cognitive function after adjusting for pre-MI cognitive trajectories. DESIGN, SETTING, AND PARTICIPANTS: This cohort study included adults without MI, dementia, or stroke and with complete covariates from the following US population-based cohort studies conducted from 1971 to 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. Data were analyzed from July 2021 to January 2022. EXPOSURES: Incident MI. MAIN OUTCOMES AND MEASURES: The main outcome was change in global cognition. Secondary outcomes were changes in memory and executive function. Outcomes were standardized as mean (SD) T scores of 50 (10); a 1-point difference represented a 0.1-SD difference in cognition. Linear mixed-effects models estimated changes in cognition at the time of MI (change in the intercept) and the rate of cognitive change over the years after MI (change in the slope), controlling for pre-MI cognitive trajectories and participant factors, with interaction terms for race and sex. RESULTS: The study included 30 465 adults (mean [SD] age, 64 [10] years; 56% female), of whom 1033 had 1 or more MI event, and 29 432 did not have an MI event. Median follow-up was 6.4 years (IQR, 4.9-19.7 years). Overall, incident MI was not associated with an acute decrease in global cognition (−0.18 points; 95% CI, −0.52 to 0.17 points), executive function (−0.17 points; 95% CI, −0.53 to 0.18 points), or memory (0.62 points; 95% CI, −0.07 to 1.31 points). However, individuals with incident MI vs those without MI demonstrated faster declines in global cognition (−0.15 points per year; 95% CI, −0.21 to −0.10 points per year), memory (−0.13 points per year; 95% CI, −0.22 to −0.04 points per year), and executive function (−0.14 points per year; 95% CI, −0.20 to −0.08 points per year) over the years after MI compared with pre-MI slopes. The interaction analysis suggested that race and sex modified the degree of change in the decline in global cognition after MI (race × post-MI slope interaction term, P = .02; sex × post-MI slope interaction term, P = .04), with a smaller change in the decline over the years after MI in Black individuals than in White individuals (difference in slope change, 0.22 points per year; 95% CI, 0.04-0.40 points per year) and in females than in males (difference in slope change, 0.12 points per year; 95% CI, 0.01-0.23 points per year). CONCLUSIONS: This cohort study using pooled data from 6 cohort studies found that incident MI was not associated with a decrease in global cognition, memory, or executive function at the time of the event compared with no MI but was associated with faster declines in global cognition, memory, and executive function over time. These findings suggest that prevention of MI may be important for long-term brain health.

IMPORTANCE: Higher educational attainment is associated with reduced dementia risk, but the role of educational quality is understudied, presenting a major evidence gap, especially as it may contribute to racial inequities. OBJECTIVE: To evaluate the association between state-level educational quality during childhood and dementia risk. DESIGN, SETTING, AND PARTICIPANTS: This cohort study analyzed longitudinal data collected from January 1, 1997, through December 31, 2019 (23-year follow-up period). The sample comprised members of Kaiser Permanente Northern California (KPNC), a large integrated health care delivery system, who completed an optional survey during 1964-1972. Eligible individuals were US born; non-Hispanic Black or non-Hispanic White; aged 65 years or older as of January 1, 1996; were still alive; and did not have a dementia diagnosis or lapse in KPNC membership greater than 90 days between January 1 and December 31, 1996. EXPOSURES: Historical state-level administrative indicators of school quality (school term length, student-teacher ratio, and attendance rates) linked to participants using birth state and birth year (with a 6-year lag) and divided into tertiles using the pooled sample. MAIN OUTCOMES AND MEASURES: Dementia diagnoses from electronic health records between 1997 and 2019 were analyzed between March 1 and August 31, 2022. The associations of educational quality with incident dementia were estimated using Cox proportional hazards regression models. RESULTS: Among 21 450 KPNC members who participated in the optional survey, individuals born before availability of educational quality records (n = 87) and missing educational attainment (n = 585) were excluded. The final analytic sample was 20 778 individuals (56.5% women, 43.5% men; mean [SD] age, 74.7 [6.5] years; 18.8% Black; 81.2% White; 41.0% with less than high school education). Among Black individuals, 76.2% to 86.1% (vs 20.8%-23.3% of White individuals) attended schools in states in the lowest educational quality tertiles. Highest (vs lowest) educational quality tertiles were associated with lower dementia risk (student-teacher ratio: hazard ratio [HR], 0.88 [95% CI, 0.83-0.94]; attendance rates: HR, 0.80 [95% CI, 0.73-0.88]; term length: HR, 0.79 [95% CI, 0.73-0.86]). Effect estimates did not differ by race and were not attenuated by adjustment for educational attainment. CONCLUSIONS AND RELEVANCE: In this cohort study, lower state-average educational quality was more common among Black individuals and associated with higher dementia risk. Differential investment in high-quality education due to structural racism may contribute to dementia disparities.

IMPORTANCE: Neuroimaging studies have documented racial and ethnic disparities in brain health in old age. It remains unclear whether these disparities are apparent in midlife. OBJECTIVE: To assess racial and ethnic disparities in magnetic resonance imaging (MRI) markers of cerebrovascular disease and neurodegeneration in midlife and late life. DESIGN, SETTING, AND PARTICIPANTS: Data from 2 community-based cohort studies, Washington Heights–Inwood Columbia Aging Project (WHICAP) and the Offspring Study of Racial and Ethnic Disparities in Alzheimer Disease (Offspring), were used. Enrollment took place from March 2011 and June 2017, in WHICAP and Offspring, respectively, to January 2021. Of the 822 Offspring and 1254 WHICAP participants approached for MRI scanning, 285 and 176 refused participation in MRI scanning, 36 and 76 were excluded for contraindications/ineligibility, and 4 and 32 were excluded for missing key variables, respectively. MAIN OUTCOMES AND MEASURES: Cortical thickness in Alzheimer disease–related regions, white matter hyperintensity (WMH) volume. RESULTS: The final sample included 1467 participants. Offspring participants (497 [33.9%]) had a mean (SD) age of 55 (10.7) years, had a mean (SD) of 13 (3.5) years of education, and included 117 Black individuals (23.5%), 348 Latinx individuals (70%), 32 White individuals (6.4%), and 324 women (65.2%). WHICAP participants (970 [66.1%]) had a mean (SD) age of 75 (6.5) years, had a mean (SD) of 12 (4.7) years of education, and included 338 Black individuals (34.8%), 389 Latinx individuals (40.1%), 243 White individuals (25.1%), and 589 women (65.2%). Racial and ethnic disparities in cerebrovascular disease were observed in both midlife (Black-White: B = 0.357; 95% CI, 0.708-0.007; P = .046) and late life (Black-Latinx: B = 0.149, 95% CI, 0.068-0.231; P < .001; Black-White: B = 0.166; 95% CI, 0.254-0.077; P < .001), while disparities in cortical thickness were evident in late life only (Black-Latinx: B = −0.037; 95% CI, −0.055 to −0.019; P < .001; Black-White: B = −0.064; 95% CI −0.044 to −0.084; P < .001). Overall, Black-White disparities were larger than Latinx-White disparities for cortical thickness and WMH volume. Brain aging, or the association of age with MRI measures, was greater in late life compared with midlife for Latinx (cortical thickness: B = 0.006; 95% CI, 0.004-0.008; P < .001; WMH volume: B = −0.010; 95% CI, −0.018 to −0.001; P = .03) and White (cortical thickness: B = 0.005; 95% CI, 0.002-0.008; P = .001; WMH volume: B = −0.021; 95% CI −0.043 to 0.002; P = .07) participants but not Black participants (cortical thickness: B = 0.001; 95% CI, −0.002 to 0.004; P =.64; WMH volume: B = 0.003; 95% CI, −0.010 to 0.017; P = .61), who evidenced a similarly strong association between age and MRI measures in midlife and late life. CONCLUSIONS AND RELEVANCE: In this study, racial and ethnic disparities in small vessel cerebrovascular disease were apparent in midlife. In Latinx and White adults, brain aging was more pronounced in late life than midlife, whereas Black adults showed accelerated pattern of brain aging beginning in midlife.

IMPORTANCE: Nationally representative data are critical for understanding the causes, costs, and outcomes associated with dementia and mild cognitive impairment (MCI) in the US and can inform policies aimed at reducing the impact of these conditions on patients, families, and public programs. The nationally representative Health and Retirement Study (HRS) is an essential resource for such data, but the HRS substudy providing dementia diagnostic information was fielded more than 20 years ago and more recent data are needed. OBJECTIVE: The Harmonized Cognitive Assessment Protocol (HCAP) was developed to update national estimates of the prevalence of MCI and dementia in the US and examine differences by age, race, ethnicity, and sex. DESIGN, SETTING, AND PARTICIPANTS: HRS is an ongoing longitudinal nationally representative study of people 51 years and older with staggered entry dates from 1992 to 2022 and follow-up ranging from 4 to 30 years. HCAP is a cross-sectional random sample of individuals in HRS who were 65 years or older in 2016. Of 9972 age-eligible HRS participants, 4425 were randomly selected for HCAP, and 3496 completed a comprehensive neuropsychological test battery and informant interview, none of whom were excluded. Dementia and MCI were classified using an algorithm based on standard diagnostic criteria and comparing test performance to a robust normative sample. EXPOSURES: Groups were stratified by age, sex, education, race, and ethnicity. MAIN OUTCOMES AND MEASURES: National prevalence estimates using population weights. RESULTS: The mean (SD) age of the study population sample (N = 3496) was 76.4 (7.6) years, and 2095 participants (60%) were female. There were 551 participants who self-identified as Black and not Hispanic (16%), 382 who self-identified as Hispanic regardless of race (16%), 2483 who self-identified as White and not Hispanic (71%), and 80 who self-identified as another race (2%), including American Indian or Alaska Native, Asian, Native Hawaiian or Pacific Islander, or another self-described race. A total of 393 individuals (10%; 95% CI, 9-11) were classified as having dementia and 804 (22%; 95% CI, 20-24) as having MCI. Every 5-year increase in age was associated with higher risk of dementia (weighted odds ratio [OR], 1.95 per 5-year age difference; 95%, CI, 1.77-2.14) and MCI (OR, 1.17 per 5-year age difference, 95% CI, 1.09-1.26). Each additional year of education was associated with a decrease in risk of dementia (OR, 0.93 per year of school, 95% CI, 0.89-0.97) and MCI (OR, 0.94, 95% CI, 0.91-0.97). Dementia was more common among non-Hispanic Black individuals (OR, 1.81; 95% CI, 1.20-2.75) and MCI in Hispanic individuals (OR, 1.42; 95% CI, 1.03-1.96) compared with non-Hispanic White individuals. Other group comparisons by race and ethnicity were not possible owing to small numbers. No differences in prevalence were found between female individuals and male individuals. CONCLUSIONS AND RELEVANCE: Using a comprehensive neuropsychological test battery and large sample, the national prevalence of dementia and MCI in 2016 found in this cross-sectional study was similar to that of other US-based studies, indicating a disproportionate burden of dementia and MCI among older Black and Hispanic adults and those with lower education.

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Objective: This study aimed to investigate the association between dietary prebiotic intake and risk for Alzheimers disease (AD). Methods: This longitudinal study includes 1,837 elderly (≥65 years) participants of a multi-ethnic community-based cohort study who were dementia-free at baseline and had provided dietary information from food frequency questionnaires. Total daily intake of fructan, one of the best-known prebiotics, was calculated based on consumption frequency and fructan content per serving of 8 food items. The associations of daily fructan intake with AD risk were examined using a Cox proportional hazards model, adjusted for cohort recruitment wave, age, gender, race/ethnicity, education, daily caloric intake, and APOE genotype. Effect modification by race/ethnicity, APOE genotype, and gender was tested by including an interaction term into the Cox models, as well as by stratified analyses. Results: Among 1,837 participants (1,263 women [69%]; mean [SD] age = 76 [6.3] years), there were 391 incident AD cases during a mean follow-up of 7.5 years (13736 person-years). Each additional gram of fructan intake was associated with 24% lower risk for AD ((95% CI)=0.60-0.97; P =0.03). Additional adjusting for smoking, alcohol consumption, and comorbidity index did not change results materially. The associations were not modified by race/ethnicity, gender, and APOE genotype, although stratified analyses showed that fructan intake was significantly associated with reduced AD risk in Hispanics but not in non-Hispanic Blacks or Whites. Conclusion: Higher dietary fructan intake is associated with a reduced risk of clinical Alzheimers disease among older adults.

IMPORTANCE: Compared with non-Hispanic White individuals, African American individuals from the same community are approximately twice as likely to develop Alzheimer disease. Despite this disparity, the largest Alzheimer disease genome-wide association studies to date have been conducted in non-Hispanic White individuals. In the largest association analyses of Alzheimer disease in African American individuals, ABCA7, TREM2, and an intergenic locus at 5q35 were previously implicated. OBJECTIVE: To identify additional risk loci in African American individuals by increasing the sample size and using the African Genome Resource panel. DESIGN, SETTING, AND PARTICIPANTS: This genome-wide association meta-analysis used case-control and family-based data sets from the Alzheimer Disease Genetics Consortium. There were multiple recruitment sites throughout the United States that included individuals with Alzheimer disease and controls of African American ancestry. Analysis began October 2018 and ended September 2019. MAIN OUTCOMES AND MEASURES: Diagnosis of Alzheimer disease. RESULTS: A total of 2784 individuals with Alzheimer disease (1944 female [69.8%]) and 5222 controls (3743 female [71.7%]) were analyzed (mean [SD] age at last evaluation, 74.2 [13.6] years). Associations with 4 novel common loci centered near the intracellular glycoprotein trafficking gene EDEM1 (3p26; P = 8.9 × 10−7), near the immune response gene ALCAM (3q13; P = 9.3 × 10−7), within GPC6 (13q31; P = 4.1 × 10−7), a gene critical for recruitment of glutamatergic receptors to the neuronal membrane, and within VRK3 (19q13.33; P = 3.5 × 10−7), a gene involved in glutamate neurotoxicity, were identified. In addition, several loci associated with rare variants, including a genome-wide significant intergenic locus near IGF1R at 15q26 (P = 1.7 × 10−9) and 6 additional loci with suggestive significance (P ≤ 5 × 10−7) such as API5 at 11p12 (P = 8.8 × 10−8) and RBFOX1 at 16p13 (P = 5.4 × 10−7) were identified. Gene expression data from brain tissue demonstrate association of ALCAM, ARAP1, GPC6, and RBFOX1 with brain β-amyloid load. Of 25 known loci associated with Alzheimer disease in non-Hispanic White individuals, only APOE, ABCA7, TREM2, BIN1, CD2AP, FERMT2, and WWOX were implicated at a nominal significance level or stronger in African American individuals. Pathway analyses strongly support the notion that immunity, lipid processing, and intracellular trafficking pathways underlying Alzheimer disease in African American individuals overlap with those observed in non-Hispanic White individuals. A new pathway emerging from these analyses is the kidney system, suggesting a novel mechanism for Alzheimer disease that needs further exploration. CONCLUSIONS AND RELEVANCE: While the major pathways involved in Alzheimer disease etiology in African American individuals are similar to those in non-Hispanic White individuals, the disease-associated loci within these pathways differ.

IMPORTANCE: Black individuals are more likely than white individuals to develop dementia. Whether higher blood pressure (BP) levels in black individuals explain differences between black and white individuals in dementia risk is uncertain. OBJECTIVE: To determine whether cumulative BP levels explain racial differences in cognitive decline. DESIGN, SETTING, AND PARTICIPANTS: Individual participant data from 5 cohorts (January 1971 to December 2017) were pooled from the Atherosclerosis Risk in Communities Study, Coronary Artery Risk Development in Young Adults Study, Cardiovascular Health Study, Framingham Offspring Study, and Northern Manhattan Study. Outcomes were standardized as t scores (mean [SD], 50 [10]); a 1-point difference represented a 0.1-SD difference in cognition. The median (interquartile range) follow-up was 12.4 (5.9-21.0) years. Analysis began September 2018. MAIN OUTCOMES AND MEASURES: The primary outcome was change in global cognition, and secondary outcomes were change in memory and executive function. EXPOSURES: Race (black vs white). RESULTS: Among 34 349 participants, 19 378 individuals who were free of stroke and dementia and had longitudinal BP, cognitive, and covariate data were included in the analysis. The mean (SD) age at first cognitive assessment was 59.8 (10.4) years and ranged from 5 to 95 years. Of 19 378 individuals, 10 724 (55.3%) were female and 15 526 (80.1%) were white. Compared with white individuals, black individuals had significantly faster declines in global cognition (−0.03 points per year faster [95% CI, −0.05 to −0.01]; P = .004) and memory (−0.08 points per year faster [95% CI, −0.11 to −0.06]; P < .001) but significantly slower declines in executive function (0.09 points per year slower [95% CI, 0.08-0.10]; P < .001). Time-dependent cumulative mean systolic BP level was associated with significantly faster declines in global cognition (−0.018 points per year faster per each 10–mm Hg increase [95% CI, −0.023 to −0.014]; P < .001), memory (−0.028 points per year faster per each 10–mm Hg increase [95% CI, −0.035 to −0.021]; P < .001), and executive function (−0.01 points per year faster per each 10–mm Hg increase [95% CI, −0.014 to −0.007]; P < .001). After adjusting for cumulative mean systolic BP, differences between black and white individuals in cognitive slopes were attenuated for global cognition (−0.01 points per year [95% CI, −0.03 to 0.01]; P = .56) and memory (−0.06 points per year [95% CI, −0.08 to −0.03]; P < .001) but not executive function (0.10 points per year [95% CI, 0.09-0.11]; P < .001). CONCLUSIONS AND RELEVANCE: These results suggest that black individuals’ higher cumulative BP levels may contribute to racial differences in later-life cognitive decline.

IMPORTANCE: Genetic causes of late-onset Alzheimer disease (LOAD) are not completely explained by known genetic loci. Whole-exome and whole-genome sequencing can improve the understanding of the causes of LOAD and provide initial steps required to identify potential therapeutic targets. OBJECTIVE: To identify the genetic loci for LOAD across different ethnic groups. DESIGN, SETTING, AND PARTICIPANTS: This multicenter cohort study was designed to analyze whole-exome sequencing data from a multiethnic cohort using a transethnic gene-kernel association test meta-analysis, adjusted for sex, age, and principal components, to identify genetic variants associated with LOAD. A meta-analysis was conducted on the results of 2 independent studies of whole-exome and whole-genome sequence data from individuals of European ancestry. This group of European American, African American, and Caribbean Hispanic individuals participating in an urban population-based study were the discovery cohort; the additional cohorts included affected individuals and control participants from 2 publicly available data sets. Replication was achieved using independent data sets from Caribbean Hispanic families with multiple family members affected by LOAD and the International Genetics of Alzheimer Project. MAIN OUTCOMES AND MEASURES: Late-onset Alzheimer disease. RESULTS: The discovery cohort included 3595 affected individuals, while the additional cohorts included 5931 individuals with LOAD and 5504 control participants. Of 3916 individuals in the discovery cohort, we included 3595 individuals (1397 with LOAD and 2198 cognitively healthy controls; 2451 [68.2%] women; mean [SD] age, 80.3 [6.83] years). Another 321 individuals (8.2%) were excluded because of non-LOAD diagnosis, age younger than 60 years, missing covariates, duplicate data, or genetic outlier status. Gene-based tests that compared affected individuals (n = 7328) and control participants (n = 7702) and included only rare and uncommon variants annotated as having moderate-high functional effect supported PINX1 (8p23.1) as a locus with gene-wide significance (P = 2.81 × 10−6) after meta-analysis across the 3 studies. The PINX1 finding was replicated using data from the family-based study and the International Genetics of Alzheimer Project. Full meta-analysis of discovery and replication cohorts reached a P value of 6.16 × 10−7 for PINX1 (in 7620 affected individuals vs 7768 control participants). We also identified TREM2 in an annotation model that prioritized highly deleterious variants with a combined annotation dependent depletion greater than 20 (P= 1.0 × 10−7). CONCLUSIONS AND RELEVANCE: This gene-based, transethnic approach identified PINX1, a gene involved in telomere integrity, and TREM2, a gene with a product of an immune receptor found in microglia, as associated with LOAD. Both genes have well-established roles in aging and neurodegeneration.

Background: Accumulating evidence suggests that dietary factors are associated with Alzheimer's disease, cognition, and brain health in older adults. It is however unclear whether inflammation explains this association. Objective: To examine whether an inflammation-related nutrient pattern (INP) was associated with neuroimaging and cognitive measures of brain health. Method: The current cross-sectional study included 330 non-demented elderly (mean age 79 years at MRI scan) participants in a multi-ethnic, community-based cohort study who had information on nutritional intake (estimated from food frequency questionnaire), circulating C-reactive protein and interleukin- 6 (measured by ELISA), MRI scans, and cognition. Diet and blood samples were collected approximately 5.3 years prior to the MRI and cognitive test visit. We used a reduced rank regression model to derive an INP based on 24 nutrients' relationship with CRP and interleukin-6. We examined the association of the INP with brain and cognitive measures using regression models adjusted for age, sex, race/ethnicity, education, caloric intake, APOE genotype, body mass index, and vascular burden, as well as intracranial volume for the brain MRI measures. Results: The INP was characterized by low intake (effect loading <-0.15) of calcium, vitamins (D, E, A, B1, B2, B3, B5, B6), folate, Ω-3 poly-unsaturated fatty acids, and high intake (>0.15) of cholesterol. As designed, this INP was positively correlated with CRP (Pearson's r=0.25 p=0.005) and interleukin-6 (r=0.30, p<0.0001). Each unit increase in INP was associated with 36.8 cm3 (p=0.023) smaller total brain volume and 0.21 (p=0.038) lower visuospatial z-score. Mediation analysis showed that TGMV (b=0.002, p=0.003) was associated with visuospatial cognitive function, and there was a significant mediation effect by TGMV (indirect effect: -0.049, 95% CI: -0.1121 ~ -0.0131) for the association between INP and visuospatial cognitive score. Conclusions: Among older adults, a diet with high inflammatory potential is associated with less favorable brain and cognitive health.

Goal 1 of the National Plan to Address Alzheimer’s Disease is to prevent and effectively treat Alzheimer disease and Alzheimer disease–related dementias by 2025. To help inform the research agenda toward achieving this goal, the NIH hosts periodic summits that set and refine relevant research priorities for the subsequent 5 to 10 years. This proceedings article summarizes the 2016 Alzheimer's Disease–Related Dementias Summit, including discussion of scientific progress, challenges, and opportunities in major areas of dementia research, including mixed-etiology dementias, Lewy body dementia, frontotemporal degeneration, vascular contributions to cognitive impairment and dementia, dementia disparities, and dementia nomenclature.

Introduction:Long-term neurological consequences (eg, stroke, impaired cognition) have been linked to SARS-CoV-2 infection and severity. There are limited data from studies with racial, ethnic, socioeconomic, and geographic diversity. C4R is a prospective study of adults from 14 cohorts that aims to link pre-COVID phenotyping, including cognition (8 studies), to COVID related illness and sequelae. We aimed to conduct pre-statistical harmonization of cognitive tests administered in English and Spanish from 8 cohorts: ARIC, CARDIA, FHS, HCHS/SOL-INCA, MESA, NOMAS, REGARDS, and SHS (Table).Methods:We conducted extensive item-level review of administration, scoring, and coding procedures and score distributions for 84 tests administered in English (all studies) and Spanish (NOMAS, MESA, HCHS/SOL-INCA).Results:Orientation to time and 3-word registration and recall spanned all studies and both languages. Word list recall and verbal fluency (animal; letter) spanned 7 studies (Table). There was variability in the structure, content, administration, scoring, and data coding procedures for items across cohorts and between Spanish and English. Word lists varied by number of words (9-16) and learning trials (3-5). Animal naming varied by time (30 vs. 60 seconds), animal type (4-legged vs. any animal), and scoring (allowing mythical/imaginary animals). Letter fluency varied by whether both Spanish and English words were permitted. Other tests differed by version, study-specific adaptations, prompts/cues, and specificity of scoring rules across cohorts.Conclusions:Cognitive test harmonization requires detailed review of administration, scoring, coding, translation, and procedural differences. Accounting for this variability is essential to cognitive data interpretation. Our pre-statistical harmonization will inform data augmentation and formal harmonization to yield harmonized measures of cognition to clarify population-level differences in cognitive outcomes linked to SARS-CoV-2 infection.

Background:A history of pregnancy-induced hypertension (PIH) is associated with higher risk of developing cerebrovascular disease. Data are lacking on the relationship between PIH, chronic hypertension, and MRI markers of cerebral small vessel disease (CSVD) in older people.Methods:We recruited parous individuals without dementia from the Northern Manhattan Study and the Washington Heights-Inwood Washington Heights-Hamilton Heights-Inwood Columbia Aging Project, two long-running prospective cohort studies in New York City. Detailed obstetric and medical histories were obtained by interview. We defined history of PIH as self-report of at least one pregnancy complicated by gestational hypertension, preeclampsia or eclampsia. We categorized participants as having no hypertension, current hypertension without history of PIH, or current hypertension with history of PIH. Number and location of infarcts and white matter hyperintensity (WMH) volume was assessed by MRI. We used generalized linear models to compare imaging outcomes between groups, adjusting for demographics and cardiovascular risk factors. To account for the effects of early onset hypertension, we performed a sensitivity analysis in NOMAS participants only, adjusting for hypertension as a time varying covariate.Results:A total of 221 participants were interviewed (mean age 69 years [SD 7.5]; 22% white, 28% non-Hispanic Black, 48% Hispanic) of whom 128 (58%) had current hypertension without history of PIH, and 16 (7%) had current hypertension with history of PIH. Adjusting for covariates, hypertensive participants with a history of PIH had higher WMH volume, but no difference in deep silent brain infarcts (Table).Conclusions:In a multiethnic cohort of older parous individuals, those with hypertension and a history of PIH had the highest volume of WMH, suggesting a higher burden of CSVD.

To examine the association between markers of sleep-disordered breathing (SDB) and white matter hyperintensity (WMH) volume in an elderly, multiethnic, community-dwelling cohort.

Recent studies of bilingualism as a protective factor in cognitive aging have reported conflicting findings, and researchers have begun to explore the methodological complications that may explain differences across studies. This article details the current research landscape and addresses several methodological issues relevant to the study of bilingualism and late-life cognitive function: study design, establishing causal relationships, confounding factors, operationalizing bilingualism, predicting cognitive level versus cognitive change, and incorporating brain structural variables to interrogate cognitive reserve.

IMPORTANCE: Mutations in known causal Alzheimer disease (AD) genes account for only 1% to 3% of patients and almost all are dominantly inherited. Recessive inheritance of complex phenotypes can be linked to long (>1-megabase [Mb]) runs of homozygosity (ROHs) detectable by single-nucleotide polymorphism (SNP) arrays. OBJECTIVE: To evaluate the association between ROHs and AD in an African American population known to have a risk for AD up to 3 times higher than white individuals. DESIGN, SETTING, AND PARTICIPANTS: Case-control study of a large African American data set previously genotyped on different genome-wide SNP arrays conducted from December 2013 to January 2015. Global and locus-based ROH measurements were analyzed using raw or imputed genotype data. We studied the raw genotypes from 2 case-control subsets grouped based on SNP array: Alzheimer’s Disease Genetics Consortium data set (871 cases and 1620 control individuals) and Chicago Health and Aging Project–Indianapolis Ibadan Dementia Study data set (279 cases and 1367 control individuals). We then examined the entire data set using imputed genotypes from 1917 cases and 3858 control individuals. MAIN OUTCOMES AND MEASURES: The ROHs larger than 1 Mb, 2 Mb, or 3 Mb were investigated separately for global burden evaluation, consensus regions, and gene-based analyses. RESULTS: The African American cohort had a low degree of inbreeding (F ~ 0.006). In the Alzheimer’s Disease Genetics Consortium data set, we detected a significantly higher proportion of cases with ROHs greater than 2 Mb (P = .004) or greater than 3 Mb (P = .02), as well as a significant 114-kilobase consensus region on chr4q31.3 (empirical P value 2 = .04; ROHs >2 Mb). In the Chicago Health and Aging Project–Indianapolis Ibadan Dementia Study data set, we identified a significant 202-kilobase consensus region on Chr15q24.1 (empirical P value 2 = .02; ROHs >1 Mb) and a cluster of 13 significant genes on Chr3p21.31 (empirical P value 2 = .03; ROHs >3 Mb). A total of 43 of 49 nominally significant genes common for both data sets also mapped to Chr3p21.31. Analyses of imputed SNP data from the entire data set confirmed the association of AD with global ROH measurements (12.38 ROHs >1 Mb in cases vs 12.11 in controls; 2.986 Mb average size of ROHs >2 Mb in cases vs 2.889 Mb in controls; and 22% of cases with ROHs >3 Mb vs 19% of controls) and a gene-cluster on Chr3p21.31 (empirical P value 2 = .006-.04; ROHs >3 Mb). Also, we detected a significant association between AD and CLDN17 (empirical P value 2 = .01; ROHs >1 Mb), encoding a protein from the Claudin family, members of which were previously suggested as AD biomarkers. CONCLUSIONS AND RELEVANCE: To our knowledge, we discovered the first evidence of increased burden of ROHs among patients with AD from an outbred African American population, which could reflect either the cumulative effect of multiple ROHs to AD or the contribution of specific loci harboring recessive mutations and risk haplotypes in a subset of patients. Sequencing is required to uncover AD variants in these individuals.

The National Alzheimer's Project Act, signed into law in 2011, mandates a National Plan to Address Alzheimer's Disease that is updated annually. In the Plan, the term Alzheimer diseaseincludes not only Alzheimer disease (AD) proper, but also several specified related dementias, namely, frontotemporal, Lewy body, vascular, and mixed dementia. In response to a specific action item in the 2012 National Plan, the National Institute of Neurological Disorders and Stroke, in collaboration with the National Institute on Aging, convened panels of experts and conducted a 2-day public conference to develop research priorities and timelines for addressing Alzheimer disease–related dementias (ADRD) in 5 topic areas: multiple etiology dementias, health disparities, Lewy body dementias including dementia with Lewy bodies and Parkinson disease dementia, frontotemporal dementia and related tauopathies, and vascular contributions to ADRD. By design, the product was up to 8 prioritized research recommendations in each topic area including estimated timelines from when work on a recommendation is started to completion or to full implementation of an ongoing activity, and recognition of shared research themes across recommendations. These included increased education and training of both researchers and health care professionals, addressing health disparities, fundamental neurobiology research, advanced diagnostics, collaborative biosample repositories, and a focus on developing effective interventions to prevent or treat ADRD by the year 2025 as targeted by the National Plan.

OBJECTIVE To evaluate the association of late-life depression with mild cognitive impairment (MCI) and dementia in a multiethnic community cohort. DESIGN AND SETTING A cohort study was conducted in Northern Manhattan, New York, New York. PARTICIPANTS A total of 2160 community-dwelling Medicare recipients aged 65 years or older were included in the study. METHODS Depression was assessed using the 10-item version of the Center for Epidemiological Studies Depression scale (CES-D) and defined by a CES-D score of 4 or more. We used logistic regression for cross-sectional association analyses and proportional hazards regression for longitudinal analyses. MAIN OUTCOME MEASURES Mild cognitive impairment dementia, and progression from MCI to dementia were the main outcome measures. We also used subcategories of MCI (amnestic and nonamnestic), and dementia (probable Alzheimer disease and vascular dementia, including possible Alzheimer disease with stroke). RESULTS Baseline depression was associated with prevalent MCI (odds ratio, 1.4; 95% CI, 1.1-1.9) and dementia (2.2; 1.6-3.1). Baseline depression was associated with an increased risk of incident dementia (hazard ratio [HR], 1.7; 95% CI, 1.2-2.3) but not with incident MCI (0.9; 0.7-1.2). Persons with MCI and coexisting depression at baseline had a higher risk of progression to dementia (HR, 2.0; 95% CI, 1.2-3.4), especially vascular dementia (4.3; 1.1-17.0), but not Alzheimer disease (1.9; 1.0-3.6). CONCLUSION The association of depression with prevalent MCI and with progression from MCI to dementia, but not with incident MCI, suggests that depression accompanies cognitive impairment but does not precede it.

BACKGROUND New-onset Alzheimer disease (AD) is often attributed to degenerative changes in the hippocampus. However, the contribution of regionally distributed small vessel cerebrovascular disease, visualized as white matter hyperintensities (WMHs) on magnetic resonance imaging, remains unclear. OBJECTIVE To determine whether regional WMHs and hippocampal volume predict incident AD in an epidemiological study. DESIGN A longitudinal community-based epidemiological study of older adults from northern Manhattan, New York. SETTING The Washington Heights/Inwood Columbia Aging Project. PARTICIPANTS Between 2005 and 2007, 717 participants without dementia received magnetic resonance imaging scans. A mean (SD) of 40.28 (9.77) months later, 503 returned for follow-up clinical examination and 46 met criteria for incident dementia (45 with AD). Regional WMHs and relative hippocampal volumes were derived. Three Cox proportional hazards models were run to predict incident dementia, controlling for relevant variables. The first included all WMH measurements; the second included relative hippocampal volume; and the third combined the 2 measurements. MAIN OUTCOME MEASURE Incident AD. RESULTS White matter hyperintensity volume in the parietal lobe predicted time to incident dementia (hazard ratio [HR] = 1.194; P = .03). Relative hippocampal volume did not predict incident dementia when considered alone (HR = 0.419; P = .77) or with the WMH measures included in the model (HR = 0.302; P = .70). Including hippocampal volume in the model did not notably alter the predictive utility of parietal lobe WMHs (HR = 1.197; P = .049). CONCLUSIONS The findings highlight the regional specificity of the association of WMHs with AD. It is not clear whether parietal WMHs solely represent a marker for cerebrovascular burden or point to distinct injury compared with other regions. Future work should elucidate pathogenic mechanisms linking WMHs and AD pathology.

BACKGROUND Telephone-based interviews can be used for screening and to obtain key study outcomes when participants in longitudinal studies die or cannot be seen in person, but must be validated among ethnically and educationally diverse people. OBJECTIVE To determine the accuracy of a telephone interview in classifying (1) demented from nondemented participants, (2) cognitively impaired participants from cognitively normal participants, and (3) participants with mild cognitive impairment (MCI) from those with normal cognition or (4) MCI from dementia among an ethnically and educationally diverse community-based sample. METHOD The sample consisted of 377 (30.5% non-Hispanic white, 34.7% non-Hispanic black, and 33.7% Caribbean Hispanic) older adults. The validation standard was diagnosis of dementia and MCI based on in-person evaluation. The Telephone Interview for Cognitive Status (TICS) and the Dementia Questionnaire (DQ) were administered within the same assessment wave. RESULTS The sample included 256 people (67.9%) with normal cognition, 68 (18.0%) with MCI, and 53 (14.1%) with dementia. Validity of the TICS was comparable among non-Hispanic whites, non-Hispanic blacks, and Hispanics. Among non-Hispanic whites, the DQ had better discrimination of those with dementia from those without dementia and from those with MCI than among other racial/ethnic groups. Telephone measures discriminated best when used to differentiate demented from nondemented participants (88% sensitivity and 87% specificity for the TICS; 66% sensitivity and 89% specificity for DQ) and when used to differentiate cognitively normal participants from those with cognitive impairment (ie, MCI and dementia combined; 73% sensitivity and 77% specificity for the TICS; 49% sensitivity and 82% specificity for DQ). When demographics and prior memory test performance were used to calculate pretest probability, consideration of the telephone measures significantly improved diagnostic validity. CONCLUSIONS The TICS has high diagnostic validity for identification of dementia among ethnically diverse older adults, especially when supported by the DQ and prior visit data. However, telephone interview data were unable to reliably distinguish MCI from normal cognition.Arch Neurol. 2011;68(5):607-614--

OBJECTIVE To reexamine the association of lipid levels with Alzheimer disease (AD) using Cox proportional hazards models. DESIGN Prospective cohort study. SETTING Northern Manhattan, New York. PARTICIPANTS One thousand one hundred thirty elderly individuals free of cognitive impairment at baseline. MAIN OUTCOME MEASURE High-density lipoprotein cholesterol (HDL-C) levels. RESULTS Higher levels of HDL-C (>55 mg/dL) were associated with a decreased risk of both probable and possible AD and probable AD compared with lower HDL-C levels (hazard ratio, 0.4; 95% confidence interval, 0.2-0.9; P = .03 and hazard ratio, 0.4; 95% confidence interval, 0.2-0.9; P = .03). In addition, higher levels of total and non–HDL-C were associated with a decreased risk of AD in analyses adjusting for age, sex, education, ethnic group, and APOE e4 genotype. CONCLUSION High HDL-C levels in elderly individuals may be associated with a decreased risk of AD.Arch Neurol. 2010;67(12):1491-1497--

OBJECTIVE To develop a simple summary risk score for the prediction of Alzheimer disease in elderly persons based on their vascular risk profiles. DESIGN A longitudinal, community-based study. SETTING New York, New York. PATIENTS One thousand fifty-one Medicare recipients aged 65 years or older and residing in New York who were free of dementia or cognitive impairment at baseline. MAIN OUTCOME MEASURES We separately explored the associations of several vascular risk factors with late-onset Alzheimer disease (LOAD) using Cox proportional hazards models to identify factors that would contribute to the risk score. Then we estimated the score values of each factor based on their β coefficients and created the LOAD vascular risk score by summing these individual scores. RESULTS Risk factors contributing to the risk score were age, sex, education, ethnicity, APOE ε4 genotype, history of diabetes, hypertension or smoking, high-density lipoprotein levels, and waist to hip ratio. The resulting risk score predicted dementia well. According to the vascular risk score quintiles, the risk to develop probable LOAD was 1.0 for persons with a score of 0 to 14 and increased 3.7-fold for persons with a score of 15 to 18, 3.6-fold for persons with a score of 19 to 22, 12.6-fold for persons with a score of 23 to 28, and 20.5-fold for persons with a score higher than 28. CONCLUSIONS While additional studies in other populations are needed to validate and further develop the score, our study suggests that this vascular risk score could be a valuable tool to identify elderly individuals who might be at risk of LOAD. This risk score could be used to identify persons at risk of LOAD, but can also be used to adjust for confounders in epidemiologic studies.Arch Neurol. 2010;67(7):835-841--

BACKGROUND The importance of subclinical cerebrovascular disease in the elderly is increasingly recognized, but its determinants have not been fully explicated. Elevated blood pressure (BP) and fluctuation in BP may lead to cerebrovascular disease through ischemic changes and compromised cerebral autoregulation. OBJECTIVE To determine the association of BP and long-term fluctuation in BP with cerebrovascular disease. DESIGN A community-based epidemiological study of older adults from northern Manhattan. SETTING The Washington Heights–Inwood Columbia Aging Project. PARTICIPANTS A total of 686 nondemented older adults who had BP measurements during 3 study visits at 24-month intervals and underwent structural magnetic resonance imaging (corresponding temporally with the third assessment). We derived the mean (SD) of the mean BP for each participant during the 3 intervals and divided the participants into 4 groups defined as below or above the group median (≤96.48 or >96.48 mm Hg) and further subdivided them as below or above the median SD (≤7.21 or >7.21 mm Hg). This scheme yielded 4 groups representing the full range of BPs and fluctuations in BP. MAIN OUTCOME MEASURES Differences in white matter hyperintensity (WMH) volume and presence of brain infarctions across groups. RESULTS White matter hyperintensity volume increased across the 4 groups in a linear manner, with the lowest WMH volume in the lowest mean/lowest SD group and the highest WMH volume in the highest mean/highest SD group (F3,610 = 3.52, P = .02). Frequency of infarction also increased monotonically across groups (from 22% to 41%, P for trend = .004). CONCLUSIONS Compared with individuals with low BP and low fluctuations in BP, the risk of cerebrovascular disease increased with higher BP and BP fluctuations. Given that cerebrovascular disease is associated with disability, these findings suggest that interventions should focus on long-term fluctuating BP and elevated BP.Arch Neurol. 2010;67(5):564-569--

BACKGROUND High-sensitivity C-reactive protein (hsCRP) is a biomarker of cardiovascular risk that is suggested to be a biomarker for cognitive impairment. OBJECTIVE To explore the association between hsCRP and cognitive impairment. DESIGN Cross-sectional analysis of a population-based community aging study. SETTING Northern Manhattan, New York, New York. OTHER PARTICIPANTS One thousand three hundred thirty-one participants from a longitudinal study of aging without dementia and with available hsCRP and neuropsychological testing data at baseline. MAIN OUTCOME MEASURES Four cognitive scores (memory, visuospatial, executive, and language impairment) derived from a neuropsychological battery. Cognitive impairment was defined by scores below 1.5 SDs of demographically corrected means. RESULTS Participants in the highest hsCRP tertile had higher adjusted odds of impaired memory (odds ratio [OR], 1.5; 95% confidence interval [CI], 1.0-2.1; P = .03) than participants in the lowest tertile. Subjects in the highest hsCRP tertile also had greater odds of visuospatial impairment (OR, 1.6; 95% CI, 1.0-2.3; P = .03). Higher hsCRP was not associated with executive or language impairment. Persons with at least 1 APOE ε4 allele and hsCRP in the highest tertile had the greatest odds of impaired memory (OR, 2.7; 95% CI, 1.6-4.4). CONCLUSIONS High hsCRP may be a marker of memory and visuospatial impairment in the elderly. The role of APOE ε4 requires further exploration.Arch Neurol. 2010;67(1):87-92--

BACKGROUND Higher adherence to the Mediterranean diet (MeDi) may protect from Alzheimer disease (AD), but its association with mild cognitive impairment (MCI) has not been explored. OBJECTIVE To investigate the association between the MeDi and MCI. DESIGN, SETTING, AND PATIENTS In a multiethnic community study in New York, we used Cox proportional hazards to investigate the association between adherence to the MeDi (0-9 scale; higher scores indicate higher adherence) and (1) the incidence of MCI and (2) the progression from MCI to AD. All of the models were adjusted for cohort, age, sex, ethnicity, education, APOE genotype, caloric intake, body mass index, and duration between baseline dietary assessment and baseline diagnosis. MAIN OUTCOME MEASURES Incidence of MCI and progression from MCI to AD. RESULTS There were 1393 cognitively normal participants, 275 of whom developed MCI during a mean (SD) follow-up of 4.5 (2.7) years (range, 0.9-16.4 years). Compared with subjects in the lowest MeDi adherence tertile, subjects in the middle tertile had 17% less risk (hazard ratio [HR] = 0.83; 95% confidence interval [CI], 0.62-1.12; P = .24) of developing MCI and those in the highest tertile had 28% less risk (HR = 0.72; 95% CI, 0.52-1.00; P = .05) of developing MCI (trend HR = 0.85; 95% CI, 0.72-1.00; P for trend = .05). There were 482 subjects with MCI, 106 of whom developed AD during a mean (SD) follow-up of 4.3 (2.7) years (range, 1.0-13.8 years). Compared with subjects in the lowest MeDi adherence tertile, subjects in the middle tertile had 45% less risk (HR = 0.55; 95% CI, 0.34-0.90; P = .01) of developing AD and those in the highest tertile had 48% less risk (HR = 0.52; 95% CI, 0.30-0.91; P = .02) of developing AD (trend HR = 0.71; 95% CI, 0.53-0.95; P for trend = .02). CONCLUSIONS Higher adherence to the MeDi is associated with a trend for reduced risk of developing MCI and with reduced risk of MCI conversion to AD.Arch Neurol. 2009;66(2):216-225--

BACKGROUND Aging is accompanied by a decrease in brain volume and by an increase in cerebrovascular disease. OBJECTIVE To examine the effects of age, sex, race/ethnicity, and vascular disease history on measures of brain morphology, including relative brain volume, ventricular volume, hippocampus and entorhinal cortex volumes, and white matter hyperintensity (WMH) burden, in a large community-based cohort of racially/ethnically diverse older adults without dementia. DESIGN The associations of age, sex, race/ethnicity, and self-reported vascular disease history with brain morphology were examined in a cross-sectional study using multiple linear regression analyses. Sex × race/ethnicity interactions were also considered. SETTING The Washington Heights–Inwood Columbia Aging Project, a community-based epidemiological study of older adults from 3 racial/ethnic groups (white, Hispanic, and African American) from northern Manhattan. PARTICIPANTS Beginning in 2003, high-resolution quantitative magnetic resonance (MR) images were acquired in 769 participants without dementia. MAIN OUTCOME MEASURES Relative brain volume (total brain volume/intracranial volume), ventricular volume, and hippocampus and entorhinal cortex volumes were derived manually on high-resolution MR images. White matter hyperintensities were quantified semiautomatically on fluid-attenuated inversion recovery–T2-weighted MR images. RESULTS Older age was associated with decreased relative brain volume and with increased ventricular and WMH volumes. Hispanic and African American participants had larger relative brain volumes and more severe WMH burden than white participants, but the associations of these variables with age were similar across racial/ethnic groups. Compared with men, women had larger relative brain volumes. Vascular disease was associated with smaller relative brain volume and with higher WMH burden, particularly among African Americans. CONCLUSIONS Older age and vascular disease, particularly among African Americans, are associated with increased brain atrophy and WMH burden. African American and Hispanic subjects have larger relative brain volumes and more WMH than white subjects. Racial/ethnic group differences in WMH severity seem to be partially attributable to differences in vascular disease. Future work will focus on the determinants and cognitive correlates of these differences.Arch Neurol. 2008;65(8):1053-1061--

BACKGROUND Type 2 diabetes mellitus is an important risk factor for Alzheimer disease and is more prevalent in elderly minority persons compared with non-Hispanic white persons. OBJECTIVE To determine whether diabetes is related to a higher risk of mild cognitive impairment (MCI), a transitional stage between normal cognition and Alzheimer disease, in a multiethnic cohort with a high prevalence of diabetes. DESIGN Longitudinal cohort study. SETTING Northern Manhattan in New York, NY. PARTICIPANTS We studied persons without prevalent MCI or dementia at baseline and with at least 1 follow-up interval. Of 1772 participants with a complete neuropsychological evaluation, 339 (19.1%) were excluded because of prevalent dementia, 304 were excluded because of prevalent MCI (17.2%), and 211 were excluded because of loss to follow-up (11.9%), resulting in a final sample of 918 participants for longitudinal analyses. MAIN OUTCOME MEASURES We related diabetes defined by self-report to incident all-cause MCI, amnestic MCI, and nonamnestic MCI. We conducted multivariate analyses with proportional hazards regression adjusting for age, sex, years of education, ethnic group, apolipoprotein E (APOE) ε4 allele, hypertension, low-density lipoprotein level, current smoking, heart disease, and stroke. RESULTS A total of 334 persons had incident MCI, 160 (47.9%) had amnestic MCI, and 174 (52.1%) had nonamnestic MCI. Diabetes was related to a significantly higher risk of all-cause MCI and amnestic MCI after adjustment for all covariates. Diabetes was also related to a higher risk of nonamnestic MCI, but this association was appreciably attenuated after adjustment for socioeconomic variables and vascular risk factors. The risk of MCI attributable to diabetes was 8.8% for the whole sample and was higher for African American persons (8.4%) and Hispanic persons (11.0%) compared with non-Hispanic white persons (4.6%), reflecting the higher prevalence of diabetes in minority populations in the United States. CONCLUSION Diabetes is related to a higher risk of amnestic MCI in a population with a high prevalence of this disorder.Arch Neurol. 2007:64;570-575 --

A crucial issue for health researchers is how to measure health and health-related behaviors across racial/ethnic groups. This commentary outlines an approach that involves the deconstruction of race/ethnicity, which clarifies the independent influences of acculturation, quality of education, socioeconomic class, and racial socialization on outcomes of interest. Research on the influence of these variables on health outcomes in general, and cognitive test performance specifically, is presented. This research indicates that when variables such as quality of education, wealth, and perceived racism are taken into account, the effect of race/ethnicity on health outcomes is greatly reduced. In other words, race/ethnicity serves as a proxy for these more meaningful variables, and explicit measurement of these constructs will improve research of health within majority and minority ethnic groups.

The current study sought to determine if discrepancies in quality of education could explain differences in cognitive test scores between African American and White elders matched on years of education. A comprehensive neuropsychological battery was administered to a sample of African American and non-Hispanic White participants in an epidemiological study of normal aging and dementia in the Northern Manhattan community. All participants were diagnosed as nondemented by a neurologist, and had no history of Parkinson's disease, stroke, mental illness, or head injury. The Reading Recognition subtest from the Wide Range Achievement Test–Version 3 was used as an estimate of quality of education. A MANOVA revealed that African American elders obtained significantly lower scores than Whites on measures of word list learning and memory, figure memory, abstract reasoning, fluency, and visuospatial skill even though the groups were matched on years of education. However, after adjusting the scores for WRAT–3 reading score, the overall effect of race was greatly reduced and racial differences on all tests (except category fluency and a drawing measure) became nonsignificant. These findings suggest that years of education is an inadequate measure of the educational experience among multicultural elders, and that adjusting for quality of education may improve the specificity of certain neuropsychological measures. (JINS, 2002, 8, 341–348.)

Two studies were conducted to examine the relationship of acculturation to neuropsychological test performance among (1) medically healthy, neurologically normal African Americans (N = 170); and (2) HIV positive (HIV+) subgroups of African Americans and Whites (Ns = 20) matched on age, education, sex, and HIV disease stage. Acculturation was measured through self report for all participants, and linguistic behavior (Black English use) was assessed in a subset of medically healthy individuals (N = 25). After controlling for the effects of age, education, and sex, medically healthy African Americans who reported less acculturation obtained lower scores on the WAIS–R Information subtest and the Boston Naming Test than did more acculturated individuals. Black English use was associated with poor performance on Trails B and the WAIS–R Information subtest. HIV+ African Americans scored significantly lower than their HIV+ White counterparts on the Category Test, Trails B, WAIS–R Block Design and Vocabulary subtests, and the learning components of the Story and Figure Memory Tests. However, after accounting for acculturation, ethnic group differences on all measures but Story Learning became nonsignificant. These results suggest that there are cultural differences within ethnic groups that relate to neuropsychological test performance, and that accounting for acculturation may improve the diagnostic accuracy of certain neuropsychological tests. (JINS, 1998, 4, 291–302.)

IMPORTANCE: Sex differences in dementia risk are unclear, but some studies have found greater risk for women. OBJECTIVE: To determine associations between sex and cognitive decline in order to better understand sex differences in dementia risk. DESIGN, SETTING, AND PARTICIPANTS: This cohort study used pooled analysis of individual participant data from 5 cohort studies for years 1971 to 2017: Atherosclerosis Risk in Communities Study, Coronary Artery Risk Development in Young Adults Study, Cardiovascular Health Study, Framingham Offspring Study, and Northern Manhattan Study. Linear mixed-effects models were used to estimate changes in each continuous cognitive outcome over time by sex. Data analysis was completed from March 2019 to October 2020. EXPOSURE: Sex. MAIN OUTCOMES AND MEASURES: The primary outcome was change in global cognition. Secondary outcomes were change in memory and executive function. Outcomes were standardized as t scores (mean [SD], 50 [10]); a 1-point difference represents a 0.1-SD difference in cognition. RESULTS: Among 34?349 participants, 26?088 who self-reported Black or White race, were free of stroke and dementia, and had covariate data at or before the first cognitive assessment were included for analysis. Median (interquartile range) follow-up was 7.9 (5.3-20.5) years. There were 11?775 (44.7%) men (median [interquartile range] age, 58 [51-66] years at first cognitive assessment; 2229 [18.9%] Black) and 14?313 women (median [interquartile range] age, 58 [51-67] years at first cognitive assessment; 3636 [25.4%] Black). Women had significantly higher baseline performance than men in global cognition (2.20 points higher; 95% CI, 2.04 to 2.35 points; P?&lt;?.001), executive function (2.13 points higher; 95% CI, 1.98 to 2.29 points; P?&lt;?.001), and memory (1.89 points higher; 95% CI, 1.72 to 2.06 points; P?&lt;?.001). Compared with men, women had significantly faster declines in global cognition (-0.07 points/y faster; 95% CI, -0.08 to -0.05 points/y; P?&lt;?.001) and executive function (-0.06 points/y faster; 95% CI, -0.07 to -0.05 points/y; P?&lt;?.001). Men and women had similar declines in memory (-0.004 points/y faster; 95% CI, -0.023 to 0.014; P?=?.61). CONCLUSIONS AND RELEVANCE: The results of this cohort study suggest that women may have greater cognitive reserve but faster cognitive decline than men, which could contribute to sex differences in late-life dementia.

ObjectiveTo evaluate trials of drugs that target amyloid to determine whether reductions in amyloid levels are likely to improve cognition.DesignInstrumental variable meta-analysis.Setting14 randomized controlled trials of drugs for the prevention or treatment of Alzheimer’s disease that targeted an amyloid mechanism, identified from ClinicalTrials.gov.PopulationAdults enrolled in randomized controlled trials of amyloid targeting drugs. Inclusion criteria for trials vary, but typically include adults aged 50 years or older with a diagnosis of mild cognitive impairment or Alzheimer’s disease, and amyloid positivity at baseline.Main outcome measuresAnalyses included trials for which information could be obtained on both change in brain amyloid levels measured with amyloid positron emission tomography and change in at least one cognitive test score reported for each randomization arm.ResultsPooled results from the 14 randomized controlled trials were more precise than estimates from any single trial. The pooled estimate for the effect of reducing amyloid levels by 0.1 standardized uptake value ratio units was an improvement in the mini-mental state examination score of 0.03 (95% confidence interval −0.06 to 0.1) points. This study provides a web application that allows for the re-estimation of the results when new data become available and illustrates the magnitude of the new evidence that would be necessary to achieve a pooled estimate supporting the benefit of reducing amyloid levels.ConclusionsPooled evidence from available trials reporting both reduction in amyloid levels and change in cognition suggests that amyloid reduction strategies do not substantially improve cognition.

Objective:To estimate the association of rural vs urban living in the United States (US) with incident cognitive impairment (ICI), and to assess confounding, mediation, and effect heterogeneity by demographic, social, behavioral, and clinical risk factors.Methods:REGARDS is a cohort of 30,239 adults aged 45+ in the 48 contiguous states. We analyzed 20,592 participants who at baseline (2003-2007) were cognitively intact with no history of stroke and had cognition assessed an average of 7.1 years later. We used Rural-Urban Commuting Area (RUCA) codes to classify participants as urban (n = 16,436), large city/town (n = 2,420), or small/isolated rural (n = 1,736) at baseline. We defined ICI as falling ≥1.5 SD below the mean on at least two of three cognitive tests administered during follow-up: word list learning, word list delayed recall, and animal naming. Using urban as the referent, we estimated odds ratios of ICI for rural and for large city/town.Results:ICI occurred in 1,291 participants (6.3%). Rural residents had 49% higher odds of ICI adjusted for confounding by demographics (Model 2 in Table, OR = 1.49 [95% CI: 1.19, 1.85]). After further adjusting for potential mediators (Models 3-6), odds of ICI remained 25% higher for rural vs urban (Model 6, OR = 1.25 [0.99, 1.56]). In assessing effect heterogeneity, we found synergism of rural dwelling with black race, physical inactivity, and low self-rated health (all P < 0.1; see ORs in Table), but not for other ICI risk factors. We found no difference in ICI for large city/town vs urban (demographics-adjusted OR = 1.08 [0.88, 1.33]; fully adjusted OR = 0.95 [0.77, 1.18]), and no effect heterogeneity of ICI risk factors by large city/town (all P > 0.2).Conclusion:Rural living is an important social determinant of cognitive health in the US. ICI was significantly more frequent among rural dwellers than urban dwellers, partly due to confounding or mediation by ICI risk factors. Odds of ICI were highest for rural dwelling combined with black race, physical inactivity, or low self-rated health.

First erratum: The following is a correction for an error that occurred in the Journal of the International Neuropsychological Society, Vol. 8, No. 2. An abstract titled “Parkinson's Disease Affects the Attentional Control of Unpracticed Movements,” by M. Lévesque, S. Lemay, S. Chouinard, P. Blanchet, M.-A. Bédard, and F. Richer, was accidently left out. This abstract was supposed to appear on p. 230 after C. Boulet et al., in the Executive Function subsection of Poster 4, which was a part of the Friday Morning, February 16, group of sessions. Second erratum: The following is a correction for an error that occurred in Journal of the International Neuropsychological Society, 8:2. On page 276, the abstract at the bottom of the left column has a laterality error, and “right” was supposed to appear instead of “left.” Third erratum: The following is a correction for an error that occurred in the Journal of the International Neuropsychological Society, Vol. 8, No. 3. The error occurred in the article titled “Reading level attenuates differences in neuropsychological tests performance between African American and White Elders,” pp. 341–348, by Manly et al. On page 343, under the subheading “Reading Level,” the last line in the paragraph should state the age range as 65–74 and not 70–75 years. Cambridge University Press and the authors regret the inconvenience that these inadvertent errors may have caused.