04157nas a2200409 4500008004100000022001400041245009900055210006900154260001600223520291000239100002303149700002003172700002303192700002103215700002403236700002703260700002303287700002303310700002303333700002003356700002603376700002303402700002103425700002003446700002603466700002203492700001903514700002303533700002003556700002003576700002003596700002303616700002403639700002403663700002403687856003603711 2020 eng d a2168-615700aAssociation Between Blood Pressure and Later-Life Cognition Among Black and White Individuals.0 aAssociation Between Blood Pressure and LaterLife Cognition Among c2020 Apr 133 a

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.

1 aLevine, Deborah, A1 aGross, Alden, L1 aBriceño, Emily, M1 aTilton, Nicholas1 aKabeto, Mohammed, U1 aHingtgen, Stephanie, M1 aGiordani, Bruno, J1 aSussman, Jeremy, B1 aHayward, Rodney, A1 aBurke, James, F1 aElkind, Mitchell, S V1 aManly, Jennifer, J1 aMoran, Andrew, E1 aKulick, Erin, R1 aGottesman, Rebecca, F1 aWalker, Keenan, A1 aYano, Yuichiro1 aGaskin, Darrell, J1 aSidney, Stephen1 aYaffe, Kristine1 aSacco, Ralph, L1 aWright, Clinton, B1 aRoger, Veronique, L1 aAllen, Norrina, Bai1 aGalecki, Andrzej, T uhttps://chs-nhlbi.org/node/839802795nas a2200313 4500008004100000022001400041245013700055210006900192260000900261300001400270490000700284520181400291100002302105700002002128700002302148700002302171700002602194700002602220700002002246700002402266700002002290700002302310700002502333700002202358700002202380700002002402700002302422856003602445 2021 eng d a1875-890800aPre-Statistical Considerations for Harmonization of Cognitive Instruments: Harmonization of ARIC, CARDIA, CHS, FHS, MESA, and NOMAS.0 aPreStatistical Considerations for Harmonization of Cognitive Ins c2021 a1803-18130 v833 a

BACKGROUND: Meta-analyses of individuals' cognitive data are increasing to investigate the biomedical, lifestyle, and sociocultural factors that influence cognitive decline and dementia risk. Pre-statistical harmonization of cognitive instruments is a critical methodological step for accurate cognitive data harmonization, yet specific approaches for this process are unclear.

OBJECTIVE: To describe pre-statistical harmonization of cognitive instruments for an individual-level meta-analysis in the blood pressure and cognition (BP COG) study.

METHODS: We identified cognitive instruments from six cohorts (the Atherosclerosis Risk in Communities Study, Cardiovascular Health Study, Coronary Artery Risk Development in Young Adults study, Framingham Offspring Study, Multi-Ethnic Study of Atherosclerosis, and Northern Manhattan Study) and conducted an extensive review of each item's administration and scoring procedures, and score distributions.

RESULTS: We included 153 cognitive instrument items from 34 instruments across the six cohorts. Of these items, 42%were common across ≥2 cohorts. 86%of common items showed differences across cohorts. We found administration, scoring, and coding differences for seemingly equivalent items. These differences corresponded to variability across cohorts in score distributions and ranges. We performed data augmentation to adjust for differences.

CONCLUSION: Cross-cohort administration, scoring, and procedural differences for cognitive instruments are frequent and need to be assessed to address potential impact on meta-analyses and cognitive data interpretation. Detecting and accounting for these differences is critical for accurate attributions of cognitive health across cohort studies.

1 aBriceño, Emily, M1 aGross, Alden, L1 aGiordani, Bruno, J1 aManly, Jennifer, J1 aGottesman, Rebecca, F1 aElkind, Mitchell, S V1 aSidney, Stephen1 aHingtgen, Stephanie1 aSacco, Ralph, L1 aWright, Clinton, B1 aFitzpatrick, Annette1 aFohner, Alison, E1 aMosley, Thomas, H1 aYaffe, Kristine1 aLevine, Deborah, A uhttps://chs-nhlbi.org/node/891903920nas a2200505 4500008004100000022001400041245005800055210005700113260001500170300001200185490000600197520255500203653000902758653002602767653002202793653001902815653002302834653001102857653001102868653001602879653000902895653001602904653001702920653001802937100002302955700002002978700002302998700002103021700002303042700002303065700002303088700002003111700002403131700002603155700002303181700002603204700002303230700002003253700002003273700001803293700002303311700002003334700002403354856003603378 2021 eng d a2574-380500aSex Differences in Cognitive Decline Among US Adults.0 aSex Differences in Cognitive Decline Among US Adults c2021 02 01 ae2101690 v43 a

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 < .001), executive function (2.13 points higher; 95% CI, 1.98 to 2.29 points; P < .001), and memory (1.89 points higher; 95% CI, 1.72 to 2.06 points; P < .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 < .001) and executive function (-0.06 points/y faster; 95% CI, -0.07 to -0.05 points/y; P < .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.

10aAged10aCognitive Dysfunction10aCognitive Reserve10aCohort Studies10aExecutive Function10aHumans10aMemory10aMiddle Aged10aRisk10aSex Factors10aTime Factors10aUnited States1 aLevine, Deborah, A1 aGross, Alden, L1 aBriceño, Emily, M1 aTilton, Nicholas1 aGiordani, Bruno, J1 aSussman, Jeremy, B1 aHayward, Rodney, A1 aBurke, James, F1 aHingtgen, Stephanie1 aElkind, Mitchell, S V1 aManly, Jennifer, J1 aGottesman, Rebecca, F1 aGaskin, Darrell, J1 aSidney, Stephen1 aSacco, Ralph, L1 aTom, Sarah, E1 aWright, Clinton, B1 aYaffe, Kristine1 aGalecki, Andrzej, T uhttps://chs-nhlbi.org/node/870904341nas a2200385 4500008004100000022001400041245006700055210006600122260001600188520323500204100002603439700001203465700001703477700002603494700001503520700002103535700002303556700002303579700001903602700002603621700002303647700002003670700001903690700002203709700002003731700002003751700002003771700002003791700002103811700002003832700002303852700002103875700002303896856003603919 2023 eng d a2168-615700aAssociation Between Acute Myocardial Infarction and Cognition.0 aAssociation Between Acute Myocardial Infarction and Cognition c2023 May 303 a

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.

1 aJohansen, Michelle, C1 aYe, Wen1 aGross, Alden1 aGottesman, Rebecca, F1 aHan, Dehua1 aWhitney, Rachael1 aBriceño, Emily, M1 aGiordani, Bruno, J1 aShore, Supriya1 aElkind, Mitchell, S V1 aManly, Jennifer, J1 aSacco, Ralph, L1 aFohner, Alison1 aGriswold, Michael1 aPsaty, Bruce, M1 aSidney, Stephen1 aSussman, Jeremy1 aYaffe, Kristine1 aMoran, Andrew, E1 aHeckbert, Susan1 aHughes, Timothy, M1 aGalecki, Andrzej1 aLevine, Deborah, A uhttps://chs-nhlbi.org/node/937703752nas a2200493 4500008004100000022001400041245008000055210006900135260001600204300001400220490000800234520239900242653000902641653003002650653001402680653002602694653001102720653001102731653000902742653001602751653001202767653001702779653001802796653001002814100002002824700002402844700002102868700002102889700002302910700002602933700002802959700002602987700002203013700002003035700002303055700002303078700002003101700002003121700002003141700001803161700002003179700002303199856003603222 2023 eng d a1526-632X00aAssociation of Obesity With Cognitive Decline in Black and White Americans.0 aAssociation of Obesity With Cognitive Decline in Black and White c2023 Jan 10 ae220-e2310 v1003 a

BACKGROUND AND OBJECTIVES: There are disparities in the prevalence of obesity by race, and the relationship between obesity and cognitive decline is unclear. The objective of this study was to determine whether obesity is independently associated with cognitive decline and whether the association between obesity and cognitive decline differs in Black and White adults. We hypothesized that obesity is associated with greater cognitive decline compared with normal weight and that the effect of obesity on cognitive decline is more pronounced in Black adults compared with their White counterparts.

METHODS: We pooled data from 28,867 participants free of stroke and dementia (mean, SD: age 61 [10.7] years at the first cognitive assessment, 55% female, 24% Black, and 29% obese) from 6 cohorts. The primary outcome was the annual change in global cognition. We performed linear mixed-effects models with and without time-varying cumulative mean systolic blood pressure (SBP) and fasting plasma glucose (FPG). Global cognition was set to a t-score metric (mean 50, SD 10) at a participant's first cognitive assessment; a 1-point difference represents a 0.1 SD difference in global cognition across the 6 cohorts. The median follow-up was 6.5 years (25th percentile, 75th percentile: 5.03, 20.15).

RESULTS: Obese participants had lower baseline global cognition than normal-weight participants (difference in intercepts, -0.36 [95% CI, -0.46 to -0.17]; < 0.001). This difference in baseline global cognition was attenuated but was borderline significant after accounting for SBP and FPG (adjusted differences in intercepts, -0.19 [95% CI, -0.39 to 0.002]; = 0.05). There was no difference in the rate of decline in global cognition between obese and normal-weight participants (difference in slope, 0.009 points/year [95% CI, -0.009 to 0.03]; = 0.32). After accounting for SBP and FPG, obese participants had a slower decline in global cognition (adjusted difference in slope, 0.03 points/year slower [95% CI, 0.01 to 0.05]; < 0.001). There was no evidence that race modified the association between body mass index and global cognitive decline ( = 0.34).

DISCUSSION: These results suggest that obesity is associated with lower initial cognitive scores and may potentially attenuate declines in cognition after accounting for BP and FPG.

10aAged10aBlack or African American10aCognition10aCognitive Dysfunction10aFemale10aHumans10aMale10aMiddle Aged10aObesity10aRisk Factors10aUnited States10aWhite1 aQuaye, Emmanuel1 aGalecki, Andrzej, T1 aTilton, Nicholas1 aWhitney, Rachael1 aBriceño, Emily, M1 aElkind, Mitchell, S V1 aFitzpatrick, Annette, L1 aGottesman, Rebecca, F1 aGriswold, Michael1 aGross, Alden, L1 aHeckbert, Susan, R1 aHughes, Timothy, M1 aLongstreth, W T1 aSacco, Ralph, L1 aSidney, Stephen1 aWindham, Gwen1 aYaffe, Kristine1 aLevine, Deborah, A uhttps://chs-nhlbi.org/node/929103136nas a2200253 4500008004100000245009000041210006900131260001600200520233000216100002302546700002402569700002002593700002302613700002102636700002002657700002402677700002602701700002302727700002702750700002002777700002602797700002302823856003602846 2023 eng d00aPrediction of Multiple Individual Primary Cardiovascular Events Using Pooled Cohorts.0 aPrediction of Multiple Individual Primary Cardiovascular Events  c2023 Aug 023 a

INTRODUCTION: Most current clinical risk prediction scores for cardiovascular disease prevention use a composite outcome. Risk prediction scores for specific cardiovascular events could identify people who are at higher risk for some events than others informing personalized care and trial recruitment. We sought to predict risk for multiple different events, describe how those risks differ, and examine if these differences could improve treatment priorities.

METHODS: We used participant-level data from five cohort studies. We included participants between 40 and 79 years old who had no history of myocardial infarction (MI), stroke, or heart failure (HF). We made separate models to predict 10-year rates of first atherosclerotic cardiovascular disease (ASCVD), first fatal or nonfatal MI, first fatal or nonfatal stroke, new-onset HF, fatal ASCVD, fatal MI, fatal stroke, and all-cause mortality using established ASCVD risk factors. To limit overfitting, we used elastic net regularization with alpha = 0.75. We assessed the models for calibration, discrimination, and for correlations between predicted risks for different events. We also estimated the potential impact of varying treatment based on patients who are high risk for some ASCVD events, but not others.

RESULTS: Our study included 24,505 people; 55.6% were women, and 20.7% were non-Hispanic Black. Our models had C-statistics between 0.75 for MI and 0.85 for HF, good calibration, and minimal overfitting. The models were least similar for fatal stroke and all MI (0.58). In 1,840 participants whose risk of MI but not stroke or all-cause mortality was in the top quartile, we estimate one blood pressure-lowering medication would have a 2.4% chance of preventing any ASCVD event per 10 years. A moderate-strength statin would have a 2.1% chance. In 1,039 participants who had top quartile risk of stroke but not MI or mortality, a blood pressure-lowering medication would have a 2.5% chance of preventing an event, but a moderate-strength statin, 1.6%.

CONCLUSION: We developed risk scores for eight key clinical events and found that cardiovascular risk varies somewhat for different clinical events. Future work could determine if tailoring decisions by risk of separate events can improve care.

1 aSussman, Jeremy, B1 aWhitney, Rachael, T1 aBurke, James, F1 aHayward, Rodney, A1 aGalecki, Andrzej1 aSidney, Stephen1 aAllen, Norrina, Bai1 aGottesman, Rebecca, F1 aHeckbert, Susan, R1 aLongstreth, William, T1 aPsaty, Bruce, M1 aElkind, Mitchell, S V1 aLevine, Deborah, A uhttps://chs-nhlbi.org/node/943703423nas a2200361 4500008004100000245006700041210006600108260001600174520236000190100001902550700001402569700001502583700002102598700002002619700002102639700002902660700002002689700002302709700002302732700002002755700002002775700002202795700002602817700002002843700002602863700002002889700002302909700002002932700002302952700002702975700002303002856003603025 2024 eng d00aTrajectory of Cognitive Function After Incident Heart Failure.0 aTrajectory of Cognitive Function After Incident Heart Failure c2024 Feb 113 a

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 -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.

1 aShore, Supriya1 aLi, Hanyu1 aZhang, Min1 aWhitney, Rachael1 aGross, Alden, L1 aBhatt, Ankeet, S1 aNallamothu, Brahmajee, K1 aGiordani, Bruno1 aBriceño, Emily, M1 aSussman, Jeremy, B1 aGutierrez, Jose1 aYaffe, Kristine1 aGriswold, Michael1 aJohansen, Michelle, C1 aLopez, Oscar, L1 aGottesman, Rebecca, F1 aSidney, Stephen1 aHeckbert, Susan, R1 aRundek, Tatjana1 aHughes, Timothy, M1 aLongstreth, William, T1 aLevine, Deborah, A uhttps://chs-nhlbi.org/node/9616