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1.
Alzheimer Dis Assoc Disord ; 35(2): 99-105, 2021.
Article in English | MEDLINE | ID: mdl-34006727

ABSTRACT

BACKGROUND: Midlife cardiovascular risk factors (CVRF) increase dementia risk. Less is known about whether CVRF identified before midlife impact late-life cognition in diverse populations. METHODS: Linear regression models examined hypertension, hyperlipidemia, and overweight/obesity at ages 30 to 59 with late-life executive function, semantic memory, verbal episodic memory, and global cognition in a cohort of Asians, blacks, Latinos, and whites (n=1127; mean age=75.8, range=65 to 98). Models adjusted for age at CVRF, age at cognitive assessment, sex, race/ethnicity, participant education, and parental education. RESULTS: Overall, 34% had 1 CVRF at ages 30 to 59; 19% had 2+. Blacks (26%) and Latinos (23%) were more likely to have 2+ CVRF than Asians (14%) or whites (13%). Having 2+ CVRF was associated with lower global cognition [ß=-0.33; 95% confidence interval (CI)=-0.45, -0.21], executive function (ß=-0.26; 95% CI=-0.39, -0.13), verbal episodic memory (ß=-0.34; 95% CI=-0.48, -0.20), and semantic memory (ß=-0.20; 95% CI=-0.33, -0.07). Interaction by age (P=0.06) indicated overweight/obesity was negatively associated with executive function at ages 30 to 39 but not at ages 40 to 59. Race/ethnic-specific effects showed disparities in CVRF prevalence impact population disparities in late-life cognition. CONCLUSION: Being overweight/obese in early adulthood and having 2+ CVRF in early adulthood/midlife are modifiable targets to redress racial/ethnic disparities in cognitive impairment and dementia.


Subject(s)
Aging/physiology , Cognition/physiology , Ethnicity/statistics & numerical data , Heart Disease Risk Factors , Racial Groups/statistics & numerical data , Adult , Aged , California , Cohort Studies , Female , Humans , Hyperlipidemias , Hypertension , Male , Middle Aged , Obesity
2.
Stroke ; 52(5): 1702-1711, 2021 05.
Article in English | MEDLINE | ID: mdl-33722061

ABSTRACT

BACKGROUND AND PURPOSE: Findings from the Framingham Heart Study suggest that declines in dementia incidence rates over recent decades are partially due to decreases in stroke incidence and mortality; however, whether trends of declining dementia rates extend to survivors of incident stroke remains unclear. We investigated evidence for temporal trends in memory change related to incident stroke in a nationally representative cohort. METHODS: Adults age 50+ in the HRS (Health and Retirement Study) were followed across three successive 6-year epochs (epoch 1: 1998-2004, n=16 781; epoch 2: 2004-2010, n=15 345; and epoch 3: 2010-2016; n=15 949). Participants were included in an epoch if they were stroke-free at the start of that epoch. Annual rates of change in a composite z-standardized memory score were compared using demographic-adjusted linear regression models for stroke-free participants, those who survived after stroke, and those who died after stroke, considering memory change before stroke, at the time of stroke, and for years following stroke. RESULTS: Crude stroke incidence rates decreased from 8.5 per 1000 person-years in epoch 1 to 6.8 per 1000 person-years in epoch 3. Rates of memory change before and following stroke onset were similar across epochs. Memory decrement immediately after stroke onset attenuated from -0.37 points (95% CI, -0.44 to -0.29) in epoch 1 to -0.26 (95% CI, -0.33 to -0.18) points in epoch 2 and -0.25 (95% CI, -0.33 to -0.17) points in epoch 3 (P value for linear trend=0.02). CONCLUSIONS: Decreases in stroke-related dementia in recent years may be partially attributable to smaller memory decrements immediately after stroke onset. Findings suggest reductions in stroke incidence and improvements in stroke care may also reduce population burden of dementia. Further investigations into whether temporal trends are attributable to improvements in stroke care are needed.


Subject(s)
Dementia , Memory Disorders , Stroke , Aged , Dementia/epidemiology , Dementia/etiology , Female , Humans , Incidence , Male , Memory Disorders/epidemiology , Memory Disorders/etiology , Middle Aged , Retrospective Studies , Stroke/complications , Stroke/epidemiology , United States/epidemiology
3.
Alzheimer Dis Assoc Disord ; 35(2): 106-113, 2021.
Article in English | MEDLINE | ID: mdl-33044303

ABSTRACT

INTRODUCTION: Educational attainment is associated with late-life cognitive performance and dementia; few studies have examined diverse racial/ethnic groups to assess whether the association differs by race/ethnicity. METHODS: We investigated whether the association between educational attainment and cognition differed between White, Black, Asian, and Latino participants in the Kaiser Healthy Aging and Diverse Life Experiences study (n=1348). Covariate-adjusted multivariable linear regression models examined domains of verbal episodic memory, semantic memory, and executive functioning. RESULTS: We observed significant effect heterogeneity by race/ethnicity only for verbal episodic memory (P=0.0198), for which any schooling between high school and college was beneficial for White, Asian, and Black participants, but not Latino participants. We found no evidence of heterogeneity for semantic memory or executive function. DISCUSSION: With the exception of Latino performance on verbal episodic memory, more education consistently predicted better cognitive scores to a similar extent across racial/ethnic groups, despite likely heterogenous educational and social experiences.


Subject(s)
Aging/physiology , Cognition , Educational Status , Ethnicity/statistics & numerical data , Racial Groups/statistics & numerical data , Aged , Female , Humans , Male , Neuropsychological Tests/statistics & numerical data
4.
Alzheimer Dis Assoc Disord ; 35(3): 271-274, 2021.
Article in English | MEDLINE | ID: mdl-32568784

ABSTRACT

Cancer diagnoses are associated with better long-term memory in older adults, possibly reflecting a range of social confounders that increase cancer risk but improve memory. We used spouse's memory as a negative control outcome to evaluate this possible confounding, since spouses share social characteristics and environments, and individuals' cancers are unlikely to cause better memory among their spouses. We estimated the association of an individual's incident cancer diagnosis (exposure) with their own (primary outcome) and their spouse's (negative control outcome) memory decline in 3601 couples from 1998 to 2014 in the Health and Retirement Study, using linear mixed-effects models. Incident cancer predicted better long-term memory for the diagnosed individual. We observed no association between an individual's cancer diagnosis and rate of spousal memory decline. This negative control study suggests that the inverse association between incident cancer and rate of memory decline is unlikely to be attributable to social/behavioral factors shared between spouses.


Subject(s)
Memory/physiology , Neoplasms/diagnosis , Spouses/statistics & numerical data , Aged , Female , Humans , Male , Middle Aged , Surveys and Questionnaires
5.
Alzheimer Dis Assoc Disord ; 34(3): 198-205, 2020.
Article in English | MEDLINE | ID: mdl-32427599

ABSTRACT

BACKGROUND: Subjective cognitive decline (SCD) may represent a low-burden indicator of dementia risk. The value of SCD as a proxy marker, however, depends on the consistency of associations between subjective and objective cognitive measures across sociodemographic and psychological factors. METHODS: We evaluated baseline data from the Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE) study (n=1615). SCD was measured using the 12-item Everyday Cognition (ECog) scale. Using linear regression models with interaction terms, we evaluated 6 potential modifiers (age, sex, race/ethnicity, educational attainment, family history of dementia, and depressive symptoms) of the association between cognitive performance (episodic memory, executive function) and SCD. RESULTS: Lower episodic memory and executive function scores were associated with higher log(ECog scores) (more SCD). Older age and elevated depressive symptoms were associated with higher log(ECog scores). Age (interaction P=0.002) and education (interaction P=0.01) modified the association between executive function and log(ECog scores). Specifically, associations between executive function and log(ECog scores) were stronger among participants with more education and less pronounced among older participants. CONCLUSIONS: The association between cognitive performance and log(ECog scores) differed little across sociodemographic and psychological factors. SCD as measured by the ECog may be a valuable proxy for cognitive performance in diverse older adults.


Subject(s)
Cognitive Dysfunction , Ethnicity/statistics & numerical data , Neuropsychological Tests/statistics & numerical data , Age Factors , Aged , Aged, 80 and over , California , Cognitive Dysfunction/ethnology , Cognitive Dysfunction/psychology , Cohort Studies , Female , Humans , Independent Living , Male , Sex Factors
6.
Am J Epidemiol ; 189(10): 1124-1133, 2020 10 01.
Article in English | MEDLINE | ID: mdl-32383448

ABSTRACT

Low physical activity (PA) among older adults increases the risk of cardiovascular disease (CVD) and mortality through metabolic disorders such as type 2 diabetes. We aimed to elucidate the extent to which diabetes mediates the effect of nonoccupational PA levels on CVD and mortality among older Mexican Americans. This study included 1,676 adults from the Sacramento Area Latino Study on Aging (1998-2007). We employed Cox proportional hazards regression models to investigate associations of PA level with all-cause mortality, fatal CVD, and nonfatal CVD events. Utilizing causal mediation analysis within a counterfactual framework, we decomposed the total effect of PA into natural indirect and direct effects. Over a median of 8 years of follow-up, low PA (<25th percentile) was associated with increased risks of all-cause mortality (hazard ratio (HR) = 1.36, 95% confidence interval (CI): 1.06, 1.75), fatal CVD (HR = 2.05, 95% CI: 1.42, 2.97), and nonfatal CVD events (HR = 1.67, 95% CI: 1.18, 2.37) in comparison with high PA (>75th percentile). Diabetes mediated 11.0%, 7.4%, and 5.2% of the total effect of PA on all-cause mortality, fatal CVD, and nonfatal CVD events, respectively. Our findings indicate that public health interventions targeting diabetes prevention and management would be a worthwhile strategy for preventing CVD and mortality among older Mexican Americans with insufficient PA levels.


Subject(s)
Cardiovascular Diseases/epidemiology , Diabetes Mellitus, Type 2/complications , Exercise , Mexican Americans/statistics & numerical data , Mortality , Aged , California/epidemiology , Diabetes Mellitus, Type 2/epidemiology , Female , Humans , Male , Middle Aged
7.
JAMA Netw Open ; 2(6): e196160, 2019 06 05.
Article in English | MEDLINE | ID: mdl-31225893

ABSTRACT

Importance: Patients with a history of cancer, even nonfatal cancers, have lower subsequent Alzheimer disease incidence. An inverse biological link between carcinogenesis and neurodegeneration has been hypothesized, although survival and detection biases are possible explanations. Objective: To compare long-term memory trajectories before and after incident cancer with memory trajectories of similarly aged individuals not diagnosed with cancer. Design, Setting, and Participants: This population-based cohort study included 14 583 US adults born before 1949 with no cancer history from the Health and Retirement Study. Biennial assessments were performed for up to 16 years from 1998 to 2014. Data analysis was performed from January 8 to October 5, 2018. Exposures: Self-reported physician diagnosis of any cancer (excluding nonmelanoma skin cancer) during follow-up. Main Outcomes and Measures: A composite memory score standardized to a mean (SD) of 0 (1) at baseline was based on immediate and delayed word-list recall and proxy assessments. The rate of memory change among people diagnosed with cancer during follow-up before and after diagnosis was compared with rate of memory change in individuals who remained cancer free during follow-up using linear mixed-effect models with random intercepts and slopes. Results: A total of 14 583 participants were included in the sample (mean [SD] age, 66.4 [10.4] years; 8453 [58.0%] female). The mean (SD) follow-up was 11.5 (5.1) years; 2250 had a cancer diagnosis during follow-up, and 12 333 had no cancer diagnosis during follow-up. The rate of memory decline in the decade before a cancer diagnosis was 10.5% (95% CI, 6.2%-14.9%), which was slower than memory decline in similarly aged cancer-free individuals. For individuals diagnosed at 75 years of age, mean memory function immediately before diagnosis was 0.096 SD units (95% CI, 0.060-0.133 SD units) higher compared with that among similarly aged cancer-free individuals. A new cancer diagnosis was associated with a short-term decline in memory of -0.058 (95% CI, -0.084 to -0.032) SD units compared with memory before diagnosis. After diagnosis, the rate of memory decline was 3.9% (95% CI, 0.9%-6.9%) slower in individuals with cancer than in those without a cancer diagnosis. Conclusions and Relevance: In this study, older individuals who developed cancer had better memory and slower memory decline than did similarly aged individuals who remained cancer free. These findings support the possibility of a common pathologic process working in opposite directions in cancer and Alzheimer disease.


Subject(s)
Memory Disorders/etiology , Neoplasms/psychology , Aged , Aged, 80 and over , Cohort Studies , Female , Humans , Male , Memory/physiology , Memory Disorders/epidemiology , Middle Aged , Neoplasms/epidemiology , United States/epidemiology
8.
Circulation ; 139(7): 850-859, 2019 02 12.
Article in English | MEDLINE | ID: mdl-30612448

ABSTRACT

BACKGROUND: Income volatility is on the rise and presents a growing public health problem. Because in many epidemiological studies income is measured at a single point in time, the association of long-term income volatility with incident cardiovascular disease (CVD) and mortality has not been adequately explored. The goal of this study was to examine associations of income volatility from 1990 to 2005 with incident CVD and all-cause mortality in the subsequent 10 years. METHODS: The Coronary Artery Risk Development in Young Adults Study is an ongoing prospective cohort study conducted within urban field centers in Birmingham, AL; Chicago, IL; Minneapolis, MN; and Oakland, CA. We studied 3937 black and white participants 23 to 35 years of age in 1990 (our study baseline). Income volatility was defined as the intraindividual SD of the percent change in income across 5 assessments from 1990 to 2005. An income drop was defined as a decrease of ≥25% from the previous visit and less than the participant's average income from 1990 to 2005. CVD events (fatal and nonfatal) and all-cause mortality between 2005 and 2015 were adjudicated with the use of medical records and death certificates. CVD included primarily acute events related to heart disease and stroke. RESULTS: A total of 106 CVD events and 164 deaths occurred between 2005 and 2015 (incident rate, 2.76 and 3.66 per 1000 person-years, respectively). From Cox models adjusted for sociodemographic, behavioral, and CVD risk factors, higher income volatility and more income drops were associated with greater CVD risk (high versus low volatility: hazard ratio, 2.07; 95% CI, 1.10-3.90; ≥2 versus 0 income drops: hazard ratio, 2.54; 95% CI, 1.24-5.19) and all-cause mortality (high versus low volatility: hazard ratio, 1.78; 95% CI,1.03-3.09; ≥2 versus 0 income drops: hazard ratio, 1.92; 95% CI, 1.07-3.44). CONCLUSIONS: In a cohort of relatively young adults, income volatility and drops during a 15-year period of formative earning years were independently associated with a nearly 2-fold risk of CVD and all-cause mortality.


Subject(s)
Cardiovascular Diseases/mortality , Employment/trends , Income/trends , Social Determinants of Health/trends , Adult , Age Factors , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/economics , Cardiovascular Diseases/ethnology , Cause of Death/trends , Employment/economics , Female , Humans , Incidence , Longitudinal Studies , Male , Prospective Studies , Risk Assessment , Risk Factors , Sex Factors , Social Class , Social Determinants of Health/ethnology , Time Factors , United States/epidemiology
9.
Am J Prev Med ; 54(3): 430-439, 2018 03.
Article in English | MEDLINE | ID: mdl-29241724

ABSTRACT

INTRODUCTION: Although infrequently recorded in electronic health records (EHRs), measures of SES are essential to describe health inequalities and account for confounding in epidemiologic research. Medical Assistance (i.e., Medicaid) is often used as a surrogate for SES, but correspondence between conventional SES and Medical Assistance has been insufficiently studied. METHODS: Geisinger Clinic EHR data from 2001 to 2014 and a 2014 questionnaire were used to create six SES measures: EHR-derived Medical Assistance and proportion of time under observation on Medical Assistance; educational attainment, income, and marital status; and area-level poverty. Analyzed in 2016-2017, associations of SES measures with obesity, hypertension, type 2 diabetes, chronic rhinosinusitis, fatigue, and migraine headache were assessed using weighted age- and sex-adjusted logistic regression. RESULTS: Among 5,550 participants (interquartile range, 39.6-57.5 years, 65.9% female), 83% never used Medical Assistance. All SES measures were correlated (Spearman's p≤0.4). Medical Assistance was significantly associated with all six health outcomes in adjusted models. For example, the OR for prevalent type 2 diabetes associated with Medical Assistance was 1.7 (95% CI=1.3, 2.2); the OR for high school versus college graduates was 1.7 (95% CI=1.2, 2.5). Medical Assistance was an imperfect proxy for SES: associations between conventional SES measures and health were attenuated <20% after adjustment for Medical Assistance. CONCLUSIONS: Because systematically collected SES measures are rarely available in EHRs and are unlikely to appear soon, researchers can use EHR-based Medical Assistance to describe inequalities. As SES has many domains, researchers who use Medical Assistance to evaluate the association of SES with health should expect substantial unmeasured confounding.


Subject(s)
Electronic Health Records/statistics & numerical data , Epidemiologic Research Design , Health Status Disparities , Medical Assistance/statistics & numerical data , Social Class , Adult , Female , Humans , Logistic Models , Male , Middle Aged , Risk Factors , Surveys and Questionnaires/statistics & numerical data
10.
Alzheimer Dis Assoc Disord ; 31(3): 181-186, 2017.
Article in English | MEDLINE | ID: mdl-28406845

ABSTRACT

BACKGROUND: Asian Americans are a rapidly growing and diverse population. Prior research on dementia among Asian Americans focused on Japanese Americans or Asian Americans overall, although marked differences in cardiometabolic conditions between subgroups have been documented. MATERIALS AND METHODS: We compared dementia incidence among 4 Asian American subgroups (n=8384 Chinese; n=4478 Japanese; n=6210 Filipino; n=197 South Asian) and whites (n=206,490) who were Kaiser Permanente Northern California members aged 64 years and above with no dementia diagnoses as of January 1, 2000. Dementia diagnoses were collected from medical records January 1, 2000 to December 31, 2013. Baseline medical utilization and comorbidities (diabetes, depression, hypertension, stroke, cardiovascular disease) were abstracted from medical records January 1, 1996 to December 31, 1999. We calculated age-standardized dementia incidence rates and Cox models adjusted for age, sex, medical utilization, and comorbidities. RESULTS: Mean baseline age was 71.7 years; mean follow-up was 9.6 years. Age-standardized dementia incidence rates were higher among whites than "All Asian-Americans" or any subgroup. Compared with Chinese (13.7/1000 person-years), dementia incidence was slightly higher among Japanese [14.8/1000 person-years; covariate-adjusted hazard ratio (adjusted-HR)=1.08; 95% confidence interval (CI), 0.99-1.18] and Filipinos (17.3/1000 person-years; adjusted-HR=1.20; 95% CI, 1.11-1.31), and lower among South Asians (12.1/1000 person-years; adjusted-HR=0.81; 95% CI, 0.53-1.25). CONCLUSIONS: Future studies are needed to understand how immigration history, social, environmental, and genetic factors contribute to dementia risk in the growing and diverse Asian American population.


Subject(s)
Asian/psychology , Dementia/diagnosis , Dementia/psychology , Aged , Aged, 80 and over , California/epidemiology , Cohort Studies , Dementia/epidemiology , Electronic Health Records/trends , Female , Follow-Up Studies , Humans , Incidence , Male , White People/psychology
11.
Alzheimer Dis Assoc Disord ; 31(1): 48-54, 2017.
Article in English | MEDLINE | ID: mdl-28225507

ABSTRACT

BACKGROUND: Type 2 diabetes (T2D) is an established risk factor for dementia, but evidence for T2D and memory decline is less consistent. Understanding how T2D and blood glucose relate to memory decline is crucial to elucidating the mechanisms linking T2D and dementia. MATERIALS AND METHODS: For 8888 Health and Retirement Study participants aged 50+, glycosylated hemoglobin (HbA1c) was measured in either 2006 or 2008 and physician's diagnosis of diabetes was self-reported in the same year. Composite memory (z scored) was assessed biennially through 2012 using immediate and delayed word list recall or the Informant Questionnaire for Cognitive Decline. Marginal mean regression models for repeated outcomes were specified to predict memory decline as a function of diabetes or HbA1c, using age as the timescale and adjusting for health and social confounders. RESULTS: Diabetes was associated with a 10% faster rate of memory decline [ß=-0.04 per decade; 95% confidence interval (CI), -0.06 to -0.01). A 1 U increase in HbA1c corresponded with a 0.05 SD decrease in memory score per decade (95% CI, -0.08 to -0.03). Even among individuals with HbA1c<6.5% (threshold for diabetes), higher HbA1c was associated with memory decline (ß=-0.05 per decade; 95% CI, -0.08 to -0.03). DISCUSSION: Diabetes accelerated memory loss and higher HbA1c predicted memory decline even in nondiabetics.


Subject(s)
Cognition Disorders/complications , Diabetes Mellitus, Type 2/complications , Glycated Hemoglobin/analysis , Memory Disorders , Aged , Biomarkers/blood , Cognition Disorders/blood , Dementia , Diabetes Mellitus, Type 2/blood , Female , Humans , Male , Middle Aged , Models, Statistical , Risk Factors , Surveys and Questionnaires
12.
Alzheimers Dement ; 13(7): 761-769, 2017 Jul.
Article in English | MEDLINE | ID: mdl-28174069

ABSTRACT

INTRODUCTION: Information on anticipated survival time after dementia diagnosis among racially/ethnically diverse patients is needed to plan for care and evaluate disparities. METHODS: Dementia-free health care members aged ≥64 years were followed (1/1/2000-12/31/2013) for dementia diagnosis and subsequent survival (n = 23,032 Asian American; n = 18,778 African American; n = 21,000 Latino; n = 4543 American Indian/Alaska Native; n = 206,490 white). Kaplan-Meier curves were estimated for survival after dementia diagnosis by race/ethnicity. We contrasted mortality patterns among people with versus without dementia using Cox proportional hazards models. RESULTS: After dementia diagnosis (n = 59,494), whites had shortest median survival (3.1 years), followed by American Indian/Alaska Natives (3.4 years), African Americans (3.7 years), Latinos (4.1 years), and Asian Americans (4.4 years). Longer postdiagnosis survival among racial/ethnic minorities compared with whites persisted after adjustment for comorbidities. Racial/ethnic mortality inequalities among dementia patients mostly paralleled mortality inequalities among people without dementia. DISCUSSION: Survival after dementia diagnosis differs by race/ethnicity, with shortest survival among whites and longest among Asian Americans.


Subject(s)
Dementia/diagnosis , Dementia/ethnology , Racial Groups , Survival Analysis , Aged, 80 and over , Female , Humans , Male , Mortality , Socioeconomic Factors
13.
Am J Epidemiol ; 183(4): 302-14, 2016 Feb 15.
Article in English | MEDLINE | ID: mdl-26825924

ABSTRACT

Improvements in cognitive test scores upon repeated assessment due to practice effects (PEs) are well documented, but there is no empirical evidence on whether alternative specifications of PEs result in different estimated associations between exposure and rate of cognitive change. If alternative PE specifications produce different estimates of association between an exposure and rate of cognitive change, this would be a challenge for nearly all longitudinal research on determinants of cognitive aging. Using data from 3 cohort studies-the Three-City Study-Dijon (Dijon, France, 1999-2010), the Normative Aging Study (Greater Boston, Massachusetts, 1993-2007), and the Washington Heights-Inwood Community Aging Project (New York, New York, 1999-2012)-for 2 exposures (diabetes and depression) and 3 cognitive outcomes, we compared results from longitudinal models using alternative PE specifications: no PEs; use of an indicator for the first cognitive visit; number of prior testing occasions; and square root of the number of prior testing occasions. Alternative specifications led to large differences in the estimated rates of cognitive change but minimal differences in estimated associations of exposure with cognitive level or change. Based on model fit, using an indicator for the first visit was often (but not always) the preferred model. PE specification can lead to substantial differences in estimated rates of cognitive change, but in these diverse examples and study samples it did not substantively affect estimated associations of risk factors with change.


Subject(s)
Aging/psychology , Cognition , Epidemiologic Studies , Models, Statistical , Practice, Psychological
14.
Alzheimer Dis Assoc Disord ; 30(3): 195-202, 2016.
Article in English | MEDLINE | ID: mdl-26756387

ABSTRACT

Evidence on whether genetic predictors of Alzheimer disease (AD) also predict memory decline is inconsistent, and limited data are available for African ancestry populations. For 8253 non-Hispanic white (NHW) and non-Hispanic black (NHB) Health and Retirement Study participants with memory scores measured 1 to 8 times between 1998 and 2012 (average baseline age=62), we calculated weighted polygenic risk scores [AD Genetic Risk Score (AD-GRS)] using the top 22 AD-associated loci, and an alternative score excluding apolipoprotein E (APOE) (AD-GRSexAPOE). We used generalized linear models with AD-GRS-by-age and AD-GRS-by-age interactions (age centered at 70) to predict memory decline. Average NHB decline was 26% faster than NHW decline (P<0.001). Among NHW, 10% higher AD-GRS predicted faster memory decline (linear ß=-0.058 unit decrease over 10 y; 95% confidence interval,-0.074 to -0.043). AD-GRSexAPOE also predicted faster decline for NHW, although less strongly. Among NHB, AD-GRS predicted faster memory decline (linear ß=-0.050; 95% confidence interval, -0.106 to 0.006), but AD-GRSexAPOE did not. Our nonsignificant estimate among NHB may reflect insufficient statistical power or a misspecified AD-GRS among NHB as an overwhelming majority of genome-wide association studies are conducted in NHW. A polygenic score based on previously identified AD loci predicts memory loss in US blacks and whites.


Subject(s)
Alzheimer Disease/genetics , Black or African American/genetics , Genome-Wide Association Study/methods , Memory Disorders/genetics , White People/genetics , Ethnicity , Female , Follow-Up Studies , Humans , Male , Middle Aged , Risk Factors , United States
15.
Alzheimer Dis Assoc Disord ; 30(1): 15-20, 2016.
Article in English | MEDLINE | ID: mdl-26650880

ABSTRACT

BACKGROUND: Mendelian Randomization (MR) studies have reported that type 2 diabetes (T2D) was not associated with Alzheimer disease (AD). We adopted a modified, mechanism-specific MR design to explore this surprising result. METHODS: Using inverse-variance weighted MR analysis, we evaluated the association between T2D and AD using data from 39 single nucleotide polymorphisms (SNPs) significantly associated with T2D in DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) and the corresponding associations of each SNP with AD risk obtained from the International Genomics of Alzheimer's Project (IGAP, n=17,008 AD cases and n=37,154 controls). We evaluated mechanism-specific genetic subscores, including ß-cell function, insulin sensitivity, and adiposity, and repeated analyses in 8501 Health and Retirement Study participants for replication and model validation. RESULTS: In IGAP, the overall T2D polygenic score did not predict AD [odds ratio (OR) for the T2D polygenic score=1.01; 95% confidence interval (CI), 0.96, 1.06] but the insulin sensitivity polygenic score predicted higher AD risk (OR=1.17; 95% CI, 1.02, 1.34). In the Health and Retirement Study, polygenic scores were associated with T2D risk; the associations between insulin sensitivity genetic polygenic score and cognitive phenotypes were not statistically significant. CONCLUSIONS: Evidence from polygenic scores suggests that insulin sensitivity specifically may affect AD risk, more than T2D overall.


Subject(s)
Alzheimer Disease/genetics , Diabetes Mellitus, Type 2/genetics , Genetic Predisposition to Disease , Phenotype , Alzheimer Disease/etiology , Diabetes Mellitus, Type 2/complications , Humans , Insulin , Mendelian Randomization Analysis/methods , Polymorphism, Single Nucleotide , Risk Factors
16.
Alzheimer Dis Assoc Disord ; 29(3): 206-12, 2015.
Article in English | MEDLINE | ID: mdl-25650694

ABSTRACT

Estimating effects of diabetes on cognitive change among older Mexican Americans is important, yet challenging, because diabetes and cognitive decline both predict mortality, which can induce survival bias. Older Mexican Americans in the Sacramento Area Latino Study on Aging (n=1634) completed Modified Mini-Mental State Exams (3MSE) and diabetes assessments up to 7 times (from 1998 to 2007). We examined baseline and new-onset diabetes and cognitive decline with joint longitudinal-survival models to account for death. At baseline, 32.4% of participants had diabetes and 15.8% developed diabetes during the study. During the study period, 22.8% of participants died. In joint longitudinal-survival models, those with baseline diabetes experienced faster cognitive decline (P=0.003) and higher mortality (hazards ratio=1.88; 95% confidence interval, 1.48-2.38) than those without diabetes. Cognitive decline and mortality were similar for those with new-onset diabetes and those without diabetes. For a typical person, 3MSE scores declined by 2.3 points among those without diabetes and 4.3 points among those with baseline diabetes, during the last 6 years of study. Ignoring the impact of death yielded a 17.0% smaller estimate of the effect of baseline diabetes on cognitive decline. Analyses that overlook the association between cognitive decline and mortality may underestimate the effect of diabetes on cognitive aging.


Subject(s)
Cognition Disorders/complications , Diabetes Mellitus, Type 2/complications , Aged , Aging , Cognition/physiology , Cognition Disorders/ethnology , Cognition Disorders/mortality , Diabetes Mellitus, Type 2/ethnology , Female , Humans , Longitudinal Studies , Male , Mexican Americans , Risk Factors
17.
Neuroepidemiology ; 43(3-4): 220-7, 2014.
Article in English | MEDLINE | ID: mdl-25402639

ABSTRACT

BACKGROUND: Diabetes predicts late-life dementia, but the association with rate of cognitive decline is inconsistent and has rarely been examined in non-white populations, despite the high prevalence of diabetes in African Americans. We evaluated the effect of diabetes on cognitive decline in middle-aged African Americans and whites. METHODS: Atherosclerosis Risk in Communities (ARIC) Brain MRI Study participants (n = 1,886, mean age = 60, 49% African American) underwent assessments of verbal memory, processing speed, and verbal fluency four times over 14 years. Using race-stratified mixed linear effects models, we examined cognitive change for participants with prevalent (baseline) diabetes and incident (diagnosed after baseline) diabetes versus those without diabetes. RESULTS: African Americans had more advanced diabetes, as indicated by fasting blood glucose levels, anti-diabetes medication use, and cardiovascular risk profiles. African Americans with prevalent diabetes experienced 41% greater annual decline in processing speed scores (p = 0.048) and 50% greater annual decline in verbal fluency scores (p = 0.042) than those without diabetes; incident diabetes was not associated with cognitive decline. Among whites, diabetes was not associated with cognitive decline. CONCLUSIONS: Prevalent diabetes was associated with greater cognitive decline in middle-aged African Americans, possibly reflecting adverse effects of longer duration and more advanced diabetes.


Subject(s)
Cognition Disorders/complications , Diabetes Mellitus, Type 2/complications , Black or African American , Aged , Cognition Disorders/ethnology , Diabetes Mellitus, Type 2/ethnology , Diabetes Mellitus, Type 2/psychology , Female , Humans , Incidence , Male , Memory , Middle Aged , Neuropsychological Tests , Prevalence , Risk Factors , White People
18.
Diabetes Care ; 37(4): 1009-15, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24271192

ABSTRACT

OBJECTIVE Although patients with type 2 diabetes have double the risk of dementia, potential racial/ethnic differences in dementia risk have not been explored in this population. We evaluated racial/ethnic differences in dementia and potential explanatory factors among older diabetic patients. RESEARCH DESIGN AND METHODS We identified 22,171 diabetic patients without preexisting dementia aged ≥60 years (14,546 non-Hispanic whites, 2,484 African Americans, 2,363 Latinos, 2,262 Asians, 516 Native Americans) from the Kaiser Permanente Northern California Diabetes Registry. We abstracted prevalent medical history (1 January 1996 to 31 December 1997) and dementia incidence (1 January 1998 to 31 December 2007) from medical records and calculated age-adjusted incidence densities. We fit Cox proportional hazards models adjusted for age, sex, education, diabetes duration, and markers of clinical control. RESULTS Dementia was diagnosed in 3,796 (17.1%) patients. Age-adjusted dementia incidence densities were highest among Native Americans (34/1,000 person-years) and African Americans (27/1,000 person-years) and lowest among Asians (19/1,000 person-years). In the fully adjusted model, hazard ratios (95% CIs) (relative to Asians) were 1.64 (1.30-2.06) for Native Americans, 1.44 (1.24-1.67) for African Americans, 1.30 (1.15-1.47) for non-Hispanic whites, and 1.19 (1.02-1.40) for Latinos. Adjustment for diabetes-related complications and neighborhood deprivation index did not change the results. CONCLUSIONS Among type 2 diabetic patients followed for 10 years, African Americans and Native Americans had a 40-60% greater risk of dementia compared with Asians, and risk was intermediate for non-Hispanic whites and Latinos. Adjustment for sociodemographics, diabetes-related complications, and markers of clinical control did not explain observed differences. Future studies should investigate why these differences exist and ways to reduce them.


Subject(s)
Aging , Dementia/ethnology , Diabetes Mellitus, Type 2/ethnology , Aged , Asian People , California/epidemiology , Female , Hispanic or Latino , Humans , Incidence , Indians, North American , Male , Middle Aged , Risk , White People
19.
J Womens Health (Larchmt) ; 23(1): 38-43, 2014 Jan.
Article in English | MEDLINE | ID: mdl-24156617

ABSTRACT

BACKGROUND: Oral contraceptive (OC) use seems to have little effect on weight change in normal weight women. Most previous studies have excluded obese women, so the effect of OC use on weight change in obese women is unknown. METHODS: This analysis evaluates weight and body composition change with OC use among obese (body mass index [BMI] 30.0-39.9) and normal weight (BMI 19.0-24.9) women who were randomly assigned to two OC doses: 20 µg ethinyl estradiol (EE) and 100 µg levonorgestrel (LNG) OCs or 30 µg EE and 150 µg LNG OCs. Follow-up occurred after three to four OC cycles. Weight and body composition were measured at baseline and at follow-up using a bioelectrical impedance analyzer. RESULTS: Among 150 women (54 obese and 96 normal weight) who used OCs for 3 to 4 months, there were no clinically or statistically significant weight or body composition changes in the overall group or by BMI or OC formulation group. CONCLUSIONS: These findings add to evidence that EE/LNG OCs are not associated with short term weight or body composition change for normal weight women and suggest that OCs are also are not associated with short term weight or body composition change in obese women.


Subject(s)
Body Composition , Contraceptives, Oral/administration & dosage , Ethinyl Estradiol/administration & dosage , Levonorgestrel/administration & dosage , Obesity , Weight Gain , Weight Loss , Adult , Body Mass Index , Dose-Response Relationship, Drug , Electric Impedance , Female , Follow-Up Studies , Humans , Outcome Assessment, Health Care , Prospective Studies , Time Factors , Young Adult
20.
Diabetes Care ; 36(9): 2600-6, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23514732

ABSTRACT

OBJECTIVE: Type 2 diabetes has been linked with increased risk of dementia and cognitive impairment among older adults and with premature mortality in young and middle-aged adults. No studies have evaluated the association between diabetes and dementia among Mexican Americans, a population with a high burden of diabetes. We evaluated the association of diabetes with incidence of dementia and cognitive impairment without dementia (CIND) among older Mexican Americans while accounting for competing risk from death. RESEARCH DESIGN AND METHODS: This study included 1,617 participants 60-98 years of age from the Sacramento Area Latino Study on Aging followed up to 10 years from 1998. We evaluated the association between diabetes and dementia/CIND with competing risk regression models. RESULTS: Participants free of dementia/CIND at baseline (n = 1,617) were followed annually up to 10 years. There were 677 (41.9%) participants with diabetes, 159 (9.8%) incident dementia/CIND cases, and 361 (22.3%) deaths. Treated and untreated diabetes (hazard ratio 2.12 [95% CI 1.65-2.73] and 2.15 [1.58-2.95]) and dementia/CIND (2.48 [1.75-3.51]) were associated with an increased risk of death. In models adjusted for competing risk of death, those with treated and untreated diabetes had an increased risk of dementia/CIND (2.05 [1.41-2.97] and 1.55 [0.93-2.58]) compared with those without diabetes. CONCLUSIONS: These findings provide evidence that the association between type 2 diabetes and dementia/CIND among Mexican Americans remains strong after accounting for competing risk of mortality. Treatments that modify risk of death among those with diabetes may change future dementia risk.


Subject(s)
Cognition Disorders/physiopathology , Dementia/physiopathology , Diabetes Mellitus, Type 2/physiopathology , Aged , Diabetes Mellitus, Type 2/complications , Female , Humans , Male , Mexican Americans , Middle Aged
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