@article {7544, title = {Late-Life Depressive Symptoms as Partial Mediators in the Associations between Subclinical Cardiovascular Disease with Onset of Mild Cognitive Impairment and Dementia.}, journal = {Am J Geriatr Psychiatry}, year = {2017}, month = {2017 Nov 20}, abstract = {

OBJECTIVE: To study whether depression contributes to the association between subclinical cardiovascular disease (CVD) and dementia, and identify the contribution{\textquoteright}s magnitude.

METHODS: Among participants from the Cardiovascular Health Study Cognition Study who did not have baseline CVD-related events (N = 2,450), causal mediation methodology was implemented to examine whether late-life depressive symptoms, defined as 10-item Center for Epidemiologic Studies-Depression (mCES-D) Scale scores >=8 from 2 to 3 years after baseline, partially mediated the association of baseline subclinical CVD (CAC, carotid intimal medial thickness, stenosis, and ankle brachial index) with mild cognitive impairment (MCI)/dementia onset occurring between 5 and 10 years from baseline. The total effect was decomposed into direct and indirect effects (via late-life depressive symptoms), obtained from an accelerated failure time model with weights derived from multivariable logistic regression of late-life depressive symptoms on subclinical CVD. Analyses were adjusted by baseline covariates: age, race, sex, poverty status, marital status, body mass index, smoking status, ApoE4 status, and mCES-D.

RESULTS: Participants contributed 20,994 person-years of follow-up with a median follow-up time of 9.4 years. Subclinical CVD was associated with 12\% faster time to MCI/dementia (time ratio [TR]: 0.88; 95\% CI: 0.83, 0.93). The total effect of subclinical CVD on MCI/dementia onset was decomposed into a direct effect (TR: 0.95, 95\% CI: 0.92, 0.98) and indirect effect (TR: 0.92, 95\% CI: 0.88, 0.97); 64.5\% of the total effect was mediated by late-life depressive symptoms.

CONCLUSIONS: These data suggest late-life depressive symptoms partially mediate the association of subclinical CVD with MCI/dementia onset.

}, issn = {1545-7214}, doi = {10.1016/j.jagp.2017.11.004}, author = {Armstrong, Nicole M and Carlson, Michelle C and Schrack, Jennifer and Xue, Qian-Li and Carnethon, Mercedes R and Rosano, Caterina and Chaves, Paulo H M and Gross, Alden L} } @article {7545, title = {Role of Late-Life Depression in the Association of Subclinical Cardiovascular Disease With All-Cause Mortality: Cardiovascular Health Study.}, journal = {J Aging Health}, year = {2017}, month = {2017 Nov 01}, pages = {898264317744921}, abstract = {

OBJECTIVES: To evaluate whether late-life depression mediates the association of subclinical cardiovascular disease (CVD) with all-cause mortality.

METHOD: Using data from 3,473 Cardiovascular Health Study participants, the Cox proportional hazards model was used to examine the direct and indirect (via late-life depression) effects of the association between baseline subclinical CVD and all-cause mortality with weights derived from multivariable logistic regression of late-life depression on subclinical CVD.

RESULTS: Subclinical CVD led to a higher risk of all-cause mortality (hazard ratio [HR] = 1.51, 95\% confidence interval, [CI] = [1.42, 1.94]). Total effect of subclinical CVD on all-cause mortality was decomposed into direct (HR = 1.41, 95\% CI = [1.37, 1.58]) and indirect (HR = 1.07, 95\% CI = [1.01, 1.23]) effects; 16.3\% of the total effect of subclinical CVD on all-cause mortality was mediated by late-life depression.

DISCUSSION: Late-life depression accounts for little, if any, of the association between subclinical CVD, a risk factor of all-cause mortality, and all-cause mortality.

}, issn = {1552-6887}, doi = {10.1177/0898264317744921}, author = {Armstrong, Nicole M and Carlson, Michelle C and Xue, Qian-Li and Schrack, Jennifer and Carnethon, Mercedes R and Chaves, Paulo H M and Gross, Alden L} } @article {8398, title = {Association Between Blood Pressure and Later-Life Cognition Among Black and White Individuals.}, journal = {JAMA Neurol}, year = {2020}, month = {2020 Apr 13}, abstract = {

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{\textquoteright} higher cumulative BP levels may contribute to racial differences in later-life cognitive decline.

}, issn = {2168-6157}, doi = {10.1001/jamaneurol.2020.0568}, author = {Levine, Deborah A and Gross, Alden L and Brice{\~n}o, Emily M and Tilton, Nicholas and Kabeto, Mohammed U and Hingtgen, Stephanie M and Giordani, Bruno J and Sussman, Jeremy B and Hayward, Rodney A and Burke, James F and Elkind, Mitchell S V and Manly, Jennifer J and Moran, Andrew E and Kulick, Erin R and Gottesman, Rebecca F and Walker, Keenan A and Yano, Yuichiro and Gaskin, Darrell J and Sidney, Stephen and Yaffe, Kristine and Sacco, Ralph L and Wright, Clinton B and Roger, Veronique L and Allen, Norrina Bai and Galecki, Andrzej T} } @article {8919, title = {Pre-Statistical Considerations for Harmonization of Cognitive Instruments: Harmonization of ARIC, CARDIA, CHS, FHS, MESA, and NOMAS.}, journal = {J Alzheimers Dis}, volume = {83}, year = {2021}, month = {2021}, pages = {1803-1813}, abstract = {

BACKGROUND: Meta-analyses of individuals{\textquoteright} 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{\textquoteright}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.

}, issn = {1875-8908}, doi = {10.3233/JAD-210459}, author = {Brice{\~n}o, Emily M and Gross, Alden L and Giordani, Bruno J and Manly, Jennifer J and Gottesman, Rebecca F and Elkind, Mitchell S V and Sidney, Stephen and Hingtgen, Stephanie and Sacco, Ralph L and Wright, Clinton B and Fitzpatrick, Annette and Fohner, Alison E and Mosley, Thomas H and Yaffe, Kristine and Levine, Deborah A} } @article {8709, title = {Sex Differences in Cognitive Decline Among US Adults.}, journal = {JAMA Netw Open}, volume = {4}, year = {2021}, month = {2021 02 01}, pages = {e210169}, abstract = {

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.

}, keywords = {Aged, Cognitive Dysfunction, Cognitive Reserve, Cohort Studies, Executive Function, Humans, Memory, Middle Aged, Risk, Sex Factors, Time Factors, United States}, issn = {2574-3805}, doi = {10.1001/jamanetworkopen.2021.0169}, author = {Levine, Deborah A and Gross, Alden L and Brice{\~n}o, Emily M and Tilton, Nicholas and Giordani, Bruno J and Sussman, Jeremy B and Hayward, Rodney A and Burke, James F and Hingtgen, Stephanie and Elkind, Mitchell S V and Manly, Jennifer J and Gottesman, Rebecca F and Gaskin, Darrell J and Sidney, Stephen and Sacco, Ralph L and Tom, Sarah E and Wright, Clinton B and Yaffe, Kristine and Galecki, Andrzej T} } @article {9291, title = {Association of Obesity With Cognitive Decline in Black and White Americans.}, journal = {Neurology}, volume = {100}, year = {2023}, month = {2023 Jan 10}, pages = {e220-e231}, abstract = {

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{\textquoteright}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.

}, keywords = {Aged, Black or African American, Cognition, Cognitive Dysfunction, Female, Humans, Male, Middle Aged, Obesity, Risk Factors, United States, White}, issn = {1526-632X}, doi = {10.1212/WNL.0000000000201367}, author = {Quaye, Emmanuel and Galecki, Andrzej T and Tilton, Nicholas and Whitney, Rachael and Brice{\~n}o, Emily M and Elkind, Mitchell S V and Fitzpatrick, Annette L and Gottesman, Rebecca F and Griswold, Michael and Gross, Alden L and Heckbert, Susan R and Hughes, Timothy M and Longstreth, W T and Sacco, Ralph L and Sidney, Stephen and Windham, B Gwen and Yaffe, Kristine and Levine, Deborah A} } @article {9616, title = {Trajectory of Cognitive Function After Incident Heart Failure.}, journal = {medRxiv}, year = {2024}, month = {2024 Feb 11}, abstract = {

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.

}, doi = {10.1101/2024.02.09.24302608}, author = {Shore, Supriya and Li, Hanyu and Zhang, Min and Whitney, Rachael and Gross, Alden L and Bhatt, Ankeet S and Nallamothu, Brahmajee K and Giordani, Bruno and Brice{\~n}o, Emily M and Sussman, Jeremy B and Gutierrez, Jose and Yaffe, Kristine and Griswold, Michael and Johansen, Michelle C and Lopez, Oscar L and Gottesman, Rebecca F and Sidney, Stephen and Heckbert, Susan R and Rundek, Tatjana and Hughes, Timothy M and Longstreth, William T and Levine, Deborah A} }