Publications by authors named "Rachel A Whitmer"

108 Publications

Stroke Belt Birth State and Late-life Cognition in The Study of Healthy Aging in African Americans (STAR).

Ann Epidemiol 2021 Sep 9. Epub 2021 Sep 9.

Department of Neurology, University of California Davis School of Medicine, 4860 Y St, Suite 3700, Sacramento, CA, USA 95817; Department of Public Health Sciences, University of California Davis School of Medicine, Medical Science 1-C, One Shields Ave, Davis, CA, USA 95616.

Purpose: We examined the association of Stroke Belt birth state with late-life cognition in The Study of Healthy Aging in African Americans (STAR).

Methods: STAR enrolled 764 Black Americans ages 50+ who were long-term Kaiser Permanente Northern California members. Participants completed Multiphasic Health Check-ups (MHC;1964-1985) where early-life overweight/obesity, hypertension, diabetes, and hyperlipidemia were measured. At STAR (2018), birth state, self-reported early-life socioeconomic status (SES), and executive function, verbal episodic memory, and semantic memory scores were collected. We used linear regression to examine the association between Stroke Belt birth and late-life cognition adjusting for birth year, gender, and parental education. We evaluated early-life SES and cardiovascular risk factors (CVRF) as potential mechanisms.

Results: Twenty-seven percent of participants were born in the Stroke Belt with a mean age of 69(SD=9) at STAR. Stroke Belt birth was associated with worse late-life executive function (β(95% CI):-0.18(-0.33,-0.02)) and semantic memory (-0.37(-0.53, -0.21)), but not verbal episodic memory (-0.04(-0.20, 0.12)). Adjustment for SES and CVRF attenuated associations of Stroke Belt birth with cognition (executive function (-0.05(-0.25, 0.14)); semantic memory (-0.28(-0.49, -0.07))).

Conclusion: Black Americans born in the Stroke Belt had worse late-life cognition than those born elsewhere, underscoring the importance of early-life exposures on brain health.
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http://dx.doi.org/10.1016/j.annepidem.2021.09.001DOI Listing
September 2021

Prevalence of Instrumental Activities of Daily Living (IADL) Difficulties and Associated Cognitive Predictors Across Racial/Ethnic Groups: Findings from the KHANDLE Study.

J Gerontol B Psychol Sci Soc Sci 2021 Sep 6. Epub 2021 Sep 6.

University of California, Davis, Department of Neurology.

Objective: Cognitive functioning is associated with instrumental activities of daily living (IADL) performance among older adults. The present study examines potential differences in the prevalence of IADL difficulty and association with cognition across diverse groups.

Methods: Participants included 455 non-Hispanic Whites, 395 Blacks, 370 Asians, and 296 Latinos age ≥65 without a current dementia diagnosis from the Kaiser Healthy Aging and Diverse Life Experience cohort. Participants self-reported IADL functioning and cognition was measured across episodic memory and executive functioning.

Results: Older age, male gender, and being Black were associated with more IADL difficulties. Executive functioning showed a stronger association with IADL than memory, and it was independent of health status whereas memory was not. In joint models including both cognitive domains, executive functioning remained a significant predictor of IADL difficulty, but memory did not. Results for both cognitive domains were attenuated with self-rated health added to the joint model. These relationships did not significantly differ across racial/ethnic groups.

Conclusions: Our study supports previous work suggesting that Black older adults are at increased risk for IADL disability. This is the first study we are aware of that examined the association between specific cognitive domains and IADL performance across multiple racial/ethnic groups. Findings indicate that cognitive functioning has similar associations with self-reported IADL disability across diverse groups, and that executive functioning plays a particularly important role in IADL disability among older adults without dementia; however, health status largely attenuates the relationship between IADL difficulty and cognition.
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http://dx.doi.org/10.1093/geronb/gbab163DOI Listing
September 2021

Identifying Potential Intervention Points for Acute Hypoglycemic Events in Patients With Type 2 Diabetes Using Retrospective Clinical Data.

Clin Diabetes 2021 Jul;39(3):304-312

University of California, San Francisco, San Francisco, CA.

This retrospective study examined changes in medication orders as a risk factor for future acute hypoglycemic events. The investigators identified factors associated with acute hypoglycemic events resulting in emergency department visits or inpatient admissions. Non-Hispanic Black race, chronic kidney disease, insulin at baseline, and nonprivate insurance were associated with higher risk of an acute hypoglycemic event, whereas age, sex, and A1C were not. After adjustment for other risk factors, changes in insulin orders after A1C measurement were associated with a 1.5 times higher risk of an acute hypoglycemia (adjusted hazard ratio 1.48, 95% CI 1.08-2.03). These results further understanding of risk factors and clinical processes relevant to predicting and preventing acute hypoglycemia.
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http://dx.doi.org/10.2337/cd20-0057DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8329018PMC
July 2021

Impact of Cardiovascular Risk Factors in Adolescence, Young Adulthood, and Midlife on Late-Life Cognition: Study of Healthy Aging in African Americans.

J Gerontol A Biol Sci Med Sci 2021 Aug;76(9):1692-1698

Department of Neurology, University of California Davis School of Medicine, Sacramento, USA.

Background: Midlife cardiovascular risk factors (CVRFs) increase risk of dementia. Black Americans experience an elevated prevalence of CVRFs and dementia. However, little is known of how CVRFs prior to midlife affect late-life cognition. We examined CVRFs in adolescence, young adulthood, and midlife with late-life cognition in the Study of Healthy Aging in African Americans (STAR).

Method: STAR assesses cognitive aging among 764 Black Americans aged ≥50 (mean age = 69; SD = 9; range = 53-95). Participants' body mass index, blood pressure, glucose, and total cholesterol were collected during Multiphasic Health Checkups (MHC; 1964-1985). At STAR baseline (2018-2019), executive function, verbal episodic memory, and semantic memory were measured using the Spanish and English Neuropsychological Assessment Scales. Linear regression models examined associations between CVRFs and cognition adjusting for demographics and years since MHC.

Results: At MHC, 36% of participants had 1 CVRF and 26% had ≥2. Twenty-two percent of participants were adolescents (age 12-20), 62% young adults (age 21-34), and 16% midlife adults (age 35-56). Overweight/obesity was not associated with cognition. Hypertension was associated with worse executive function (β [95% CI]: -0.14 [-0.28, -0.0003]) and verbal episodic memory (β [95% CI]: -0.22 [-0.37, -0.07]) compared to normotension. Diabetes was associated with worse executive function (β [95% CI]: -0.43 [-0.83, -0.03]). Having ≥2 CVRFs (vs 0) was associated with worse executive function (β [95% CI]: -0.19 [-0.34, -0.03]) and verbal episodic memory (β [95% CI]: -0.25 [-0.41, -0.08]). Adolescents with hypertension had lower late-life executive function compared to normotensive adolescents (β [95% CI]: -0.39 [-0.67, -0.11]). Young adulthood hypertension (β [95% CI]: -0.29 [-0.49, -0.09]) and midlife hyperlipidemia (β [95% CI]: -0.386 [-0.70, -0.02]) were associated with lower verbal episodic memory.

Conclusions: Among Black Americans, life-course CVRFs were associated with poorer executive function and verbal episodic memory emphasizing the importance of cardiovascular health on the aging brain.
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http://dx.doi.org/10.1093/gerona/glab143DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8361347PMC
August 2021

Neighborhood racial/ethnic segregation and cognitive decline in older adults.

Soc Sci Med 2021 09 12;284:114226. Epub 2021 Jul 12.

University of California Davis, Davis, CA, United States.

Social determinants of health, including neighborhood factors, play a key role in the health of diverse older adults. However, few longitudinal studies have examined the role of neighborhood racial/ethnic segregation on cognitive decline in diverse samples. We examined older non-Hispanic White (NHW), Black, and Latino participants evaluated at an Alzheimer's Disease Research Center. Neighborhood racial/ethnic segregation was measured using the Getis-Ord G* statistic, a spatial measure of clustering that was created for Latino and Black clustering separately. Cognitive outcomes included episodic memory, semantic memory, and executive function. We used mixed effects multivariable regression models to evaluate associations between segregation and cognitive function and decline. We had 452 individuals: 46% NHW, 26% Black, and 21% Latino in 309 census tracts with an average of 5.2 years of follow-up data (range 0.6-15.0). In analyses that adjusted for a variety of covariates (including neighborhood SES), individuals in neighborhoods with a higher clustering of Latino residents (higher Gi* statistic) had slower declines over time on semantic memory and those in neighborhoods with a higher clustering of Black residents had slower declines over time on episodic memory. In race/ethnicity-stratified adjusted analyses: for Black participants, the association between clustering and cognition was present for episodic memory and executive function, showing lower baseline scores in highly clustered Black and Latino neighborhoods, respectively. There was no association with cognitive change. Among Latino participants, highly clustered Latino neighborhoods were associated with lower baseline scores in semantic memory, but slower declines in episodic memory; Latinos living in neighborhoods with a greater clustering of Black residents also had slower declines in episodic memory. Among NHWs, residing in neighborhoods with a higher clustering of Latino residents was associated with slower declines over time on semantic memory. Segregated neighborhoods may be differentially associated with cognitive outcomes depending on individual race/ethnicity.
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http://dx.doi.org/10.1016/j.socscimed.2021.114226DOI Listing
September 2021

Operationalizing Social Environments in Cognitive Aging and Dementia Research: A Scoping Review.

Int J Environ Res Public Health 2021 07 4;18(13). Epub 2021 Jul 4.

Department of Neurology, University of California Davis, Sacramento, CA 95817, USA.

Background: Social environments are a contributing determinant of health and disparities. This scoping review details how social environments have been operationalized in observational studies of cognitive aging and dementia.

Methods: A systematic search in PubMed and Web of Science identified studies of social environment exposures and late-life cognition/dementia outcomes. Data were extracted on (1) study design; (2) population; (3) social environment(s); (4) cognitive outcome(s); (5) analytic approach; and (6) theorized causal pathways. Studies were organized using a 3-tiered social ecological model at interpersonal, community, or policy levels.

Results: Of 7802 non-duplicated articles, 123 studies met inclusion criteria. Eighty-four studies were longitudinal (range 1-28 years) and 16 examined time-varying social environments. When sorted into social ecological levels, 91 studies examined the interpersonal level; 37 examined the community/neighborhood level; 3 examined policy level social environments; and 7 studies examined more than one level.

Conclusions: Most studies of social environments and cognitive aging and dementia examined interpersonal factors measured at a single point in time. Few assessed time-varying social environmental factors or considered multiple social ecological levels. Future studies can help clarify opportunities for intervention by delineating if, when, and how social environments shape late-life cognitive aging and dementia outcomes.
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http://dx.doi.org/10.3390/ijerph18137166DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8296955PMC
July 2021

Impact of dementia: Health disparities, population trends, care interventions, and economic costs.

J Am Geriatr Soc 2021 Jul;69(7):1774-1783

John Hopkins University, Baltimore, Maryland, USA.

Introduction: The dementia experience is not a monolithic phenomenon-and while core elements of dementia are considered universal-people living with dementia experience the disorder differently. Understanding the patterning of Alzheimer's disease and related dementias (ADRD) in the population with regards to incidence, risk factors, impacts on dementia care, and economic costs associated with ADRD can provide clues to target risk and protective factors for all populations as well as addressing health disparities.

Methods: We discuss information presented at the 2020 National Research Summit on Care, Services, and Supports for Persons with Dementia and Their Caregivers, Theme 1: Impact of Dementia. In this article, we describe select population trends, care interventions, and economic impacts, health disparities and implications for future research from the perspective of our diverse panel comprised of academic stakeholders, and persons living with dementia, and care partners.

Results: Dementia incidence is decreasing yet the advances in population health are uneven. Studies examining the educational, geographic and race/ethnic distribution of ADRD have identified clear disparities. Disparities in health and healthcare may be amplified by significant gaps in the evidence base for pharmacological and non-pharmacological interventions. The economic costs for persons living with dementia and the value of family care partners' time are high, and may persist into future generations.

Conclusions: Significant research gaps remain. Ensuring that ADRD healthcare services and long-term care services and supports are accessible, affordable, and effective for all segments of our population is essential for health equity. Policy-level interventions are in short supply to redress broad unmet needs and systemic sources of disparities. Whole of society challenges demand research producing whole of society solutions. The urgency, complexity, and scale merit a "whole of government" approach involving collaboration across numerous federal agencies.
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http://dx.doi.org/10.1111/jgs.17345DOI Listing
July 2021

Amyloid-PET imaging offers small improvements in predictions of future cognitive trajectories.

Neuroimage Clin 2021 8;31:102713. Epub 2021 Jun 8.

Department of Epidemiology and Biostatistics, University of California San Francisco, United States. Electronic address:

Background: Amyloid β (Aβ) is thought to initiate a cascade of pathology culminating in Alzheimer's disease-related cognitive decline. Aβ accumulation in brain tissues may begin one to two decades prior to clinical diagnosis of Alzheimer's disease. Prior studies have demonstrated that Aβ detected in vivo with positron emission tomography with amyloid ligands (amyloid-PET) predicts contemporaneously measured cognition and future cognitive trajectories. Prior studies have not evaluated the added value of Aβ measures in predicting future cognition when repeated past cognitive measures are available. We evaluated the extent to which amyloid-PET improves prediction of future cognitive changes over and above predictions based only on sociodemographics and past cognitive measures.

Methods: We used data from participants in the University of California Davis Alzheimer's Disease Research cohort who were cognitively normal at baseline, participated in amyloid-PET imaging, and completed at least three cognitive assessments prior to amyloid-PET imaging (N = 132 for memory andN = 135 for executive function). We used sociodemographic and cognitive measures taken prior to amyloid-PET imaging to predict cognitive trajectory after amyloid-PET imaging and assessed whether measures of amyloid burden improved predictions of subsequent cognitive change. Improvements in prediction were characterized as percent reduction in the mean squared error (MSE) in predicted cognition post amyloid-PET and increase in percent variance explained.

Results: The base model using only sociodemographics and past cognitive performance explained the majority of variance in both predicted memory measures (55.6%) and executive function measures (74.5%) following amyloid-PET. Adding amyloid positivity to the model reduced the MSE for memory by 0.2%, 95% CI: (0%, 2.6%), p = 0.48 and for executive function by 3.4%, 95% CI: (0.6%, 10.2%), p = 0.002. This corresponded to an increase in the percent variance explained of 0.1%, 95% CI: (0%, 1.2%) for memory and 0.9%, 95% CI: (0.1%, 2.8%) for executive function. Similar results were obtained using a continuous measure of amyloid burden.

Conclusion: In this cohort, the addition of amyloid burden slightly improved predictions of executive function compared to models based only on past cognitive assessments and sociodemographics. When repeated cognitive assessments are available, the additional utility of amyloid-PET in predicting future cognitive impairment may be limited.
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http://dx.doi.org/10.1016/j.nicl.2021.102713DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8233225PMC
September 2021

Participant education, spousal education and dementia risk in a diverse cohort of members of an integrated health care delivery system in Northern California.

BMJ Open 2021 06 18;11(6):e040233. Epub 2021 Jun 18.

Behavioral Health and Aging, Kaiser Permanente Division of Research, Oakland, California, USA.

Objective: The role of spousal education on dementia risk and how it may differ by gender or race/ethnicity is unknown. This study examines the association between one's own education separate from and in conjunction with spousal education and risk of dementia.

Design: Cohort.

Setting: Kaiser Permanente Northern California (KPNC), an integrated health care delivery system.

Participants: 8835 members of KPNC who were aged 40-55, married and reported own and spousal education in 1964-1973.

Primary Outcome Measure: Dementia cases were identified through medical records from 1 January 1996 to 30 September 2017.

Methods: Own and spousal education was self-reported in 1964-1973 and each was classified as four indicator variables (≤high school, trade school/some college, college degree and postgraduate) and as ≥college degree versus
Results: The cohort was 37% non-white, 46% men and 30% were diagnosed with dementia during follow-up from 1996 to 2017 (mean follow-up=12.7 years). Greater participant education was associated with lower dementia risk independent of spousal education, demographics and health indicators. Greater spousal education was associated with lower dementia adjusting for demographics but became non-significant after further adjustment for participant education. The same pattern was seen for spousal education ≥college degree (not adjusting for participant education HR=0.83 (95% CI: 0.76 to 0.90); adjusting for participant education HR=0.92 (95% CI: 0.83 to 1.01)). These associations did not vary by gender or race/ethnicity.

Conclusion: In a large diverse cohort, we found that higher levels of participant's own education were associated with lower dementia risk regardless of spousal education. An inverse association between spousal education and dementia risk was also present, however, the effects became non-significant after adjusting for participant education.
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http://dx.doi.org/10.1136/bmjopen-2020-040233DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8215232PMC
June 2021

Perceived Discrimination, Nativity, and Cognitive Performance in a Multi-ethnic Study of Older Adults: Findings from the Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE) Study.

J Gerontol A Biol Sci Med Sci 2021 Jun 14. Epub 2021 Jun 14.

Department of Public Health Sciences, University of California, Davis, Davis, CA.

Background: Despite growing research on the association between discrimination and disparities in cognitive aging, an evidence gap remains on how the association varies by racial/ethnic group. This study evaluates the associations of experiences of discrimination with cognitive function and whether these associations varied by race/ethnicity and nativity.

Methods: Using the Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE) cohort (N=1,712) with approximately equal groups of Black, White, Latino, and Asian community-dwelling older adults aged 65 years and older, we evaluated the associations between self-reported experiences of everyday and major lifetime discrimination with overall cognitive performance and domain-specific cognition (verbal episodic memory, semantic memory and executive functioning) across race/ethnicity and nativity. Linear regression models examined the cross-sectional association between self-reported experiences of everyday and major lifetime discrimination with z-standardized coefficients for cognition. We tested for effect modification by race and nativity. All models controlled for age, sex and education.

Results: Among KHANDLE participants (mean age: 76 years; standard deviation: 6.8), everyday discrimination was not associated with cognitive scores. Major lifetime discrimination was associated with better average cognitive scores among Black participants but not among other racial/ethnic groups. Major lifetime discrimination was associated with better average cognitive scores among US-born but not among non-US born individuals.

Conclusion: Our findings do not imply that discrimination improves cognition, but rather suggest that future research should include more detailed measures on discrimination and unfair treatment that could help disentangle the extent to which relationships are causal or reflect some other underlying factor.
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http://dx.doi.org/10.1093/gerona/glab170DOI Listing
June 2021

Association of Type 1 Diabetes and Hypoglycemic and Hyperglycemic Events and Risk of Dementia.

Neurology 2021 Jun 2. Epub 2021 Jun 2.

Division of Research, Kaiser Permanente Oakland, CA, USA.

Objective: To determine whether severe hypoglycemic and hyperglycemic events are associated with longitudinal dementia risk in older adults with type 1 diabetes.

Methods: A longitudinal cohort study followed 2,821 members of an integrated healthcare delivery system with type 1 diabetes from 1997-2015. Hypoglycemic and hyperglycemic events requiring emergency room or hospitalization were abstracted from medical records beginning 1/1/1996 through cohort entry. Participants were followed for dementia diagnosis through 9/30/2015. Dementia risk was examined using Cox proportional hazard models adjusted for age (as timescale), sex, race/ethnicity, HbA1c, depression, stroke, and nephropathy.

Results: Among 2,821 older adults (mean age 56) with type 1 diabetes, 398 (14%) had a history of severe hypoglycemia, 335 (12%) severe hyperglycemia and 87 (3%) both. Over a mean 6.9 years of follow-up, 153 individuals (5.4%) developed dementia. In fully adjusted models, individuals with hypoglycemic events had 66% greater risk of dementia than those without a hypoglycemic event (HR=1.66; 95% CI: 1.09, 2.53), while those with hyperglycemic events had >2 times the risk (HR=2.11; 95% CI: 1.24, 3.59) than those without a hyperglycemic event. There was a 6-fold greater risk of dementia in individuals with both severe hypoglycemia and hyperglycemia versus those with neither (HR=6.20; 95% CI: 3.02, 12.70).

Conclusions: For older individuals with type 1 diabetes, severe hypoglycemic and hyperglycemic events are associated with increased future risk of dementia.
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http://dx.doi.org/10.1212/WNL.0000000000012243DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8302147PMC
June 2021

Racial/Ethnic Disparities in Young Adulthood and Midlife Cardiovascular Risk Factors and Late-life Cognitive Domains: The Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE) Study.

Alzheimer Dis Assoc Disord 2021 Apr-Jun 01;35(2):99-105

University of California Davis School of Medicine, Davis.

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 [β=-0.33; 95% confidence interval (CI)=-0.45, -0.21], executive function (β=-0.26; 95% CI=-0.39, -0.13), verbal episodic memory (β=-0.34; 95% CI=-0.48, -0.20), and semantic memory (β=-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.
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http://dx.doi.org/10.1097/WAD.0000000000000436DOI Listing
October 2020

Impact of Cardiovascular Risk Factors in Adolescence, Young Adulthood, and Midlife on Late-life Cognition: Study of Healthy Aging in African Americans (STAR).

J Gerontol A Biol Sci Med Sci 2021 May 18. Epub 2021 May 18.

Department of Neurology, University of California Davis School of Medicine, Sacramento, CA, USA.

Background: Midlife cardiovascular risk factors (CVRF) increase risk of dementia. Black Americans experience an elevated prevalence of CVRF and dementia. However, little is known of how CVRF prior to midlife affect late-life cognition. We examined CVRF in adolescence, young adulthood, and midlife with late-life cognition in The Study of Healthy Aging in African Americans (STAR).

Methods: STAR assesses cognitive aging among 764 Black Americans ages ≥50 (mean age=69;SD=9;range 53-95). Participants' body mass index, blood pressure, glucose, and total cholesterol were collected during Multiphasic Health Check-ups (MHC;1964-1985). At STAR baseline (2018-2019), executive function, verbal episodic memory, and semantic memory were measured using the Spanish and English Neuropsychological Assessment Scales. Linear regression models examined associations between CVRF and cognition adjusting for demographics and years since MHC.

Results: At MHC, 36% of participants had 1 CVRF and 26% had ≥2. Twenty-two percent of participants were adolescents (ages:12-20), 62% young adults (ages:21-34), and 16% midlife adults (ages:35-56). Overweight/obesity was not associated with cognition. Hypertension was associated with worse executive function [β(95%CI):-0.14(-0.28,-0.0003)] and verbal episodic memory [β(95%CI):-0.22(-0.37,-0.07)] compared to normotension. Diabetes was associated with worse executive function [β(95%CI):-0.43(-0.83,-0.03)]. Having ≥2 CVRF (versus 0) was associated with worse executive function [β(95%CI):-0.19(-0.34,-0.03)] and verbal episodic memory [β(95%CI):-0.25(-0.41,-0.08)]. Adolescents with hypertension had lower late-life executive function compared to normotensive adolescents [β(95%CI):-0.39(-0.67,-0.11)]. Young adulthood hypertension [β(95%CI):-0.29(-0.49,-0.09)] and midlife hyperlipidemia [β(95%CI):-0.386(-0.70,-0.02)] were associated with lower verbal episodic memory.

Conclusions: Among Black Americans, lifecourse CVRF were associated with poorer executive function and verbal episodic memory emphasizing the importance of cardiovascular health on the aging brain.
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http://dx.doi.org/10.1093/gerona/glab143DOI Listing
May 2021

Lifecourse socioeconomic changes and late-life cognition in a cohort of U.S.-born and U.S. immigrants: findings from the KHANDLE study.

BMC Public Health 2021 05 13;21(1):920. Epub 2021 May 13.

Biomedical Sciences 1C, University of California Davis School of Medicine, One Shields Ave., Davis, CA, 95616, USA.

Background: Low socioeconomic status (SES) in early and late life has been associated with lower late-life cognition. Less is known about how changes in SES from childhood to late life are associated with late-life cognition, especially among diverse populations of older adults.

Methods: In a multi-ethnic sample (n = 1353) of older adults, we used linear regression to test associations of change in comprehensive measures of SES (financial, cultural, and social domains) from childhood to late life with semantic memory, episodic memory, and executive function. We tested whether the association between SES trajectory and late-life cognition differed by populations who resided in the U.S. during childhood or immigrated to the U.S. as adults.

Results: Participants with low childhood/high late-life financial capital had better semantic memory (β = 0.18; 95% CI: 0.04, 0.32) versus those with low financial capital in both childhood and late life, regardless of childhood residence. We observed a significant interaction in the association of verbal episodic memory and cultural capital by childhood residence (p = 0.08). Participants with a foreign childhood residence had higher verbal episodic memory if they had low childhood/high late-life cultural capital (β = 0.32; 95% CI: 0.01, 0.63), but lower verbal episodic memory if they had high childhood/low late-life cultural capital (β = - 0.40; 95% CI: - 0.94, 0.13). Having high lifecourse social capital was associated with better verbal episodic memory scores among those with a U.S. childhood (β = 0.34; 95% CI: 0.14, 0.55), but lower verbal episodic memory among those with a foreign childhood (β = - 0.10; 95% CI: - 0.51, 0.31).

Conclusions: High financial and cultural capital in late life is associated with better cognition, regardless of early childhood SES or childhood residence.
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http://dx.doi.org/10.1186/s12889-021-10976-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120825PMC
May 2021

Extension of Mendelian Randomization to Identify Earliest Manifestations of Alzheimer's Disease: Genetic Risk Score for Alzheimer's Disease Reduces BMI by Age 50.

Am J Epidemiol 2021 Apr 12. Epub 2021 Apr 12.

Department of Epidemiology & Biostatistics, University of California, San Francisco, CA.

Weight loss or lower Body Mass Index (BMI) may be an early symptom of Alzheimer's disease (AD) but when this begins to emerge is difficult to estimate with traditional observational data. In an extension of Mendelian randomization, we used genetic risk for late-onset AD risk to estimate the causal effect of AD on BMI and the earliest ages at which AD-related weight loss (or lower BMI as a proxy) occurs. 407,386 UK Biobank participants enrolled 2007-2010 without dementia, aged 39-73, with Caucasian genetic ancestry, with BMI (kg/m2), and an AD genetic risk score (AD-GRS) based on 23 genetic variants. Using linear regressions, we tested the association of AD-GRS with BMI stratified by decade and calculated the age of divergence in BMI-trends between low and high AD-GRS. AD-GRS was not associated with BMI in 39-49 year-olds (β:0.00;95%CI:-0.03,0.03). AD-GRS was associated with lower BMI in 50-59 year-olds (β:-0.03; 95%CI:-0.06,-0.01) and 60-73 year-olds (β:-0.09;95%CI:-0.12,-0.07). Model-based BMI age-curves for high versus low AD-GRS began to diverge after age 47. Sensitivity analyses found no evidence for pleiotropy or survival bias. Longitudinal replication is needed; however, our findings suggest that AD genes may begin to reduce BMI decades prior to dementia diagnosis.
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http://dx.doi.org/10.1093/aje/kwab103DOI Listing
April 2021

Measuring cognitive health in ethnically diverse older adults.

J Gerontol B Psychol Sci Soc Sci 2021 Apr 12. Epub 2021 Apr 12.

University of California Davis, Department of Neurology.

Objective: Understanding racial/ethnic disparities in late-life cognitive health is a public health imperative. We used baseline data from the Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE) study to examine how age, education, gender, and clinical diagnosis, a proxy for brain health, are associated with cross-sectional measures of cognition in diverse racial/ethnic groups.

Method: Comprehensive measures of cognition were obtained using the Spanish and English Neuropsychological Assessment Scales and the NIH Toolbox Cognitive Health Battery in a sample of 1695 KHANDLE participants (Asians 24%, Blacks 26%, Latinos 20%, Whites 29%). A 25% random subsample was clinically evaluated and diagnosed with normal cognition, mild cognitive impairment (MCI), or dementia. Cognitive test scores were regressed on core demographic variables and diagnosis in the combined sample and in multiple group analyses stratified by racial/ethnic group.

Results: Race/ethnicity and education were variably associated with test scores with strongest associations with tests of vocabulary and semantic memory. Older age was associated with poorer performance on all measures, and gender differences varied across cognitive tests. Clinical diagnosis of MCI or dementia was associated with average decrements in test scores that ranged from -0.41 to -0.84 SD, with largest differences on tests of executive function and episodic memory. With few exceptions, associations of demographic variables and clinical diagnosis did not differ across racial/ethnic groups.

Discussion: The robust associations of cognitive test results with clinical diagnosis independent of core demographic variables and race/ethnicity supports the validity of cognitive tests as indicators for brain health in diverse older adults.
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http://dx.doi.org/10.1093/geronb/gbab062DOI Listing
April 2021

Diversity and Disparities in Dementia Diagnosis and Care: A Challenge for All of Us.

JAMA Neurol 2021 Jun;78(6):650-652

Alzheimer's Disease Research Center, Department of Public Health Sciences, University of California, Davis.

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http://dx.doi.org/10.1001/jamaneurol.2021.0285DOI Listing
June 2021

Temporal Trends in Stroke-Related Memory Change: Results From a US National Cohort 1998-2016.

Stroke 2021 May 16;52(5):1702-1711. Epub 2021 Mar 16.

Department of Epidemiology and Biostatistics (C.W.E., M.M.G.), University of California San Francisco.

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 ( 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.
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http://dx.doi.org/10.1161/STROKEAHA.120.031063DOI Listing
May 2021

Cardiovascular risk and midlife cognitive decline in the Study of Women's Health Across the Nation.

Alzheimers Dement 2021 08 12;17(8):1342-1352. Epub 2021 Mar 12.

Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

Introduction: Cardiovascular risk factors in midlife have been linked to late life risk for Alzheimer's disease and related dementias (ADRD). The relation of vascular risk factors on cognitive decline within midlife has been less studied.

Methods: Using data from the Study of Women's Health Across the Nation, we examined associations of midlife hypertension, elevated lipid levels, diabetes, fasting glucose, central adiposity, and Framingham heart age with rates of cognitive decline in women who completed multiple cognitive assessments of processing speed, and working and verbal memory during midlife.

Results: Diabetes, elevated fasting glucose, central obesity, and heart age greater than chronological age were associated with rate of decline in processing speed during midlife. Vascular risk factors were not related to rate of decline in working or verbal memory.

Discussion: Midlife may be a critical period for intervening on cardiovascular risk factors to prevent or delay later life cognitive impairment and ADRD.
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http://dx.doi.org/10.1002/alz.12300DOI Listing
August 2021

Evaluation of Selective Survival and Sex/Gender Differences in Dementia Incidence Using a Simulation Model.

JAMA Netw Open 2021 03 1;4(3):e211001. Epub 2021 Mar 1.

Fielding School of Public Health, Department of Epidemiology, University of California, Los Angeles.

Importance: Dementia research is susceptible to bias arising from selective survival, a process that results in individuals with certain characteristics disproportionately surviving to old age. Spurious associations between risk factors and dementia may be induced when factors associated with longer survival also influence dementia incidence.

Objective: To assess the role of selective survival in explaining reported sex/gender differences in dementia incidence.

Design, Setting, And Participants: This decision analytical model used a simulated cohort of US participants aged 50 years and without dementia at baseline followed up for incident dementia through age 95 years. Selective survival was induced by a selection characteristic (eg, childhood social disadvantage or Alzheimer genetic risk) that influenced both mortality and dementia incidence at varying magnitudes. Data analysis was performed from April 2018 to May 2020.

Exposure: Sex/gender, conceptualized as the combination of biological sex and social consequences of gender.

Main Outcomes And Measures: Dementia incidence rate ratios (IRRs) for women compared with men. In all simulations, it was assumed that there would be no true effect of sex/gender on dementia incidence; all observed sex/gender differences were due to selective survival.

Results: At baseline, the simulation included 100 000 participants aged 50 years (51 000 [51%] women, mirroring the 1919-1921 US birth cohort of non-Latino White individuals at age 50 years); distributions of the selection characteristic were standard normal (mean [SD], 0.0 [1.0]). Observed sex/gender differences in dementia incidence in individuals aged 85 years or older ranged from insignificant (IRR, 1.00; 95% CI, 0.91-1.11) to consistent with sex/gender differences (20% higher risk for women [IRR, 1.20; 95% CI, 1.08-1.32]) reported in an extant study. Simulations in which bias was large enough to explain prior findings required moderate to large differential effects of selective survival (eg, hazard ratio for selection characteristic on mortality at least 2.0 among men, no effect among women).

Conclusions And Relevance: These results suggest that selective survival may contribute to observed sex/gender differences in dementia incidence but do not preclude potential contributions of sex/gender-specific mechanisms. Further research on plausibility of selection characteristics with outcomes of the magnitude required for selective survival to explain sex/gender differences in dementia incidence and sex/gender-specific mechanisms represent an opportunity to understand prevention and treatment of dementia.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.1001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7944377PMC
March 2021

Physical Performance and Cognition in a Diverse Cohort: Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE) Study.

Alzheimer Dis Assoc Disord 2021 Jan-Mar 01;35(1):23-29

Departments of Public Health Sciences.

Background: The authors assessed the cross-sectional association of physical function measures with cognition in the Kaiser Healthy Aging and Diverse Life Experiences Cohort.

Methods: Analyses included 1369 participants (24% Asian, 26% Black, 18% Latino, 32% White). Grip strength was measured using a hand-held dynamometer (kilograms) and gait speed was measured over a 4-m walk (seconds/meter). The Spanish and English Neuropsychological Assessment Scales was used to evaluate cognitive domains of executive function, semantic memory, and verbal episodic memory. Physical function measures (per SD) were associated with cognitive test z-scores in linear regression models adjusted for demographic, behavioral, and clinical factors. Racial/ethnic differences were tested using interaction terms and stratification.

Results: Stronger grip was associated with better executive function [β=0.10 (95% confidence interval, 0.05-0.15)], semantic memory [β=0.13 (0.09-0.18)] and verbal episodic memory [β=0.07 (0.02-0.13)] with no racial/ethnic differences. Faster gait was associated with better executive function [β=0.29 (0.22-0.36)], semantic memory [β=0.23 (0.16-0.30)], and verbal episodic memory [β=0.20 (0.13-0.27)]; however, the association between gait speed and executive function varied by race/ethnicity with the strongest associations in Asians and Whites.

Conclusion: Across race/ethnicity, grip strength and gait speed were associated with cognition with racial/ethnic differences in the association of gait speed and executive function.
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http://dx.doi.org/10.1097/WAD.0000000000000428DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7904590PMC
May 2020

Are adverse childhood experiences associated with late-life cognitive performance across racial/ethnic groups: results from the Kaiser Healthy Aging and Diverse Life Experiences study baseline.

BMJ Open 2021 02 5;11(2):e042125. Epub 2021 Feb 5.

Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California, USA

Objectives: Evidence on adverse childhood experiences (ACEs) and late-life cognitive outcomes is inconsistent, with little research among diverse racial/ethnic groups. We investigated whether ACE exposures were associated with worse late-life cognition for all racial/ethnic groups and at different ages of exposure.

Design: Covariate-adjusted mixed-effects linear regression models estimated associations of: (1) total number of ACEs experienced, (2) earliest age when ACE occurred and (3) type of ACE with overall cognition.

Setting: Kaiser Permanente Northern California members aged 65 years and older, living in Northern California.

Participants: Kaiser Healthy Aging and Diverse Life Experiences study baseline participants, aged 65 years and older (n=1661; including 403 Asian-American, 338 Latino, 427 Black and 493 white participants).

Results: Most respondents (69%) reported one or more ACE, most frequently family illness (36%), domestic violence (23%) and parental divorce (22%). ACE count was not adversely associated with cognition overall (β=0.01; 95% CI -0.01 to 0.03), in any racial/ethnic group or for any age category of exposure. Pooling across all race/ethnicities, parent's remarriage (β=-0.11; 95% CI -0.20 to -0.03), mother's death (β=-0.18; 95% CI -0.30 to -0.07) and father's death (β=-0.11; 95% CI -0.20 to -0.01) were associated with worse cognition.

Conclusion: Adverse childhood exposures overall were not associated with worse cognition in older adults in a diverse sample, although three ACEs were associated with worse cognitive outcomes.
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http://dx.doi.org/10.1136/bmjopen-2020-042125DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7925876PMC
February 2021

Sex, diabetes status and cognition: findings from the study of longevity in diabetes.

BMJ Open Diabetes Res Care 2021 01;9(1)

Department of Epidemiology, University of Kentucky, Lexington, Kentucky, USA.

Introduction: Women comprise two-thirds of people with dementia, making female sex a significant dementia risk factor. Both type 1 diabetes (T1D) and type 2 diabetes (T2D) are known dementia risk factors with an increasing global incidence. Understanding whether subtle sex differences persist in cognitive function prior to dementia in the context of diabetes may help elucidate the magnitude of sex effects on dementia risk.

Research Design And Methods: We examined cross-sectional data from the Study of Longevity in Diabetes (SOLID), a prospective cohort study of members of Kaiser Permanente Northern California aged 60 years and older with T1D (n=758), T2D (n=232) and without either T1D or T2D (n=247). We used factor analysis to generate summary scores of cognitive domains and used regression analyses to examine the associations between sex and cognition adjusting for sociodemographic and cardiovascular confounders.

Results: We included 1237 participants (630 women and 607 men) with mean age 68 years. By design, the distribution of men and women in T1D, T2D and no diabetes was similar. Women had better cognitive performance than men in global cognition (β=0.21, 95% CI 0.16 to 0.26), language (β=0.08, 95% CI 0.004 to 0.15), executive function (β=0.13, 95% CI 0.05 to 0.20), episodic verbal memory (β=0.68, 95% CI 0.59 to 0.77) and attention (β=0.20, 95% CI 0.11 to 0.28) but not in episodic visual memory (β=0.006, 95% CI -0.07 to 0.09) adjusting for age and education independent of diabetes status. We did not find an interaction between sex and diabetes status for any of the cognitive outcomes.

Conclusions: Women in late mid-life have better cognitive performance than men in many cognitive domains independent of the presence of T1D or T2D. Further work is required to understand whether these differences change over time or in older cohorts and to understand their relationship to subsequent dementia.
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http://dx.doi.org/10.1136/bmjdrc-2020-001646DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7845709PMC
January 2021

Generation and age of immigration on later life cognitive performance in KHANDLE.

Int Psychogeriatr 2020 Dec 23:1-12. Epub 2020 Dec 23.

Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA.

Objectives: We examined the association of generational status and age at immigration with later life cognitive outcomes in a diverse sample of Latinos and Asian Americans.

Design: Baseline data were obtained from the Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE) study, and a prospective cohort is initiated in 2017.

Setting: Older adults in Northern California.

Participants: Our cohort consisted of Asians (n = 411) and Latinos (n = 340) who were on average 76 years old (SD = 6.8).

Measurements: We used multivariable linear regression models to estimate associations between generational status and age at immigration (collapsed into one five-level variable) with measures of verbal episodic memory, semantic memory, and executive function, adjusting for age, gender, race and ethnicity, and own- and parental education.

Results: Generational status and age at immigration were associated with cognitive outcomes in a graded manner. Compared to third-generation or higher immigrants, first-generation immigration in adulthood was associated with lower semantic memory (β = -0.96; 95% CI: -1.12, -0.81) than immigration in adolescence (β = -0.68; 95% CI: -0.96, -0.41) or childhood (β = -0.28; 95% CI: -0.49, -0.06). Moreover, immigration in adulthood was associated with lower executive function (β = -0.63; 95% CI: -0.78, -0.48) than immigration in adolescence (β = -0.49; 95% CI: -0.75, -0.23). Similarly, compared to third-generation individuals, first-generation immigrants had lower executive functioning scores.

Conclusions: Our study supports the notion that sociocontextual influences in early life impact later life cognitive scores. Longitudinal studies are needed to further clarify how immigration characteristics affect cognitive decline.
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http://dx.doi.org/10.1017/S1041610220003774DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8219806PMC
December 2020

Association Between Ambient Air Pollution and Amyloid Positron Emission Tomography Positivity in Older Adults With Cognitive Impairment.

JAMA Neurol 2021 Feb;78(2):197-207

Memory and Aging Center, Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco.

Importance: Amyloid-β (Aβ) deposition is a feature of Alzheimer disease (AD) and may be promoted by exogenous factors, such as ambient air quality.

Objective: To examine the association between the likelihood of amyloid positron emission tomography (PET) scan positivity and ambient air quality in individuals with cognitive impairment.

Design, Setting, And Participants: This cross-sectional study used data from the Imaging Dementia-Evidence for Amyloid Scanning Study, which included more than 18 000 US participants with cognitive impairment who received an amyloid PET scan with 1 of 3 Aβ tracers (fluorine 18 [18F]-labeled florbetapir, 18F-labeled florbetaben, or 18F-labeled flutemetamol) between February 16, 2016, and January 10, 2018. A sample of older adults with mild cognitive impairment (MCI) or dementia was selected.

Exposures: Air pollution was estimated at the patient residence using predicted fine particulate matter (PM2.5) and ground-level ozone (O3) concentrations from the Environmental Protection Agency Downscaler model. Air quality was estimated at 2002 to 2003 (early, or approximately 14 [range, 13-15] years before amyloid PET scan) and 2015 to 2016 (late, or approximately 1 [range, 0-2] years before amyloid PET scan).

Main Outcomes And Measures: Primary outcome measure was the association between air pollution and the likelihood of amyloid PET scan positivity, which was measured as odds ratios (ORs) and marginal effects, adjusting for demographic, lifestyle, and socioeconomic factors and medical comorbidities, including respiratory, cardiovascular, cerebrovascular, psychiatric, and neurological conditions.

Results: The data set included 18 178 patients, of which 10 991 (60.5%) had MCI and 7187 (39.5%) had dementia (mean [SD] age, 75.8 [6.3] years; 9333 women [51.3%]). Living in areas with higher estimated biennial PM2.5 concentrations in 2002 to 2003 was associated with a higher likelihood of amyloid PET scan positivity (adjusted OR, 1.10; 95% CI, 1.05-1.15; z score = 3.93; false discovery rate [FDR]-corrected P < .001; per 4-μg/m3 increments). Results were similar for 2015 to 2016 data (OR, 1.15; 95% CI, 1.05-1.26, z score = 3.14; FDR-corrected P = .003). An average marginal effect (AME) of +0.5% (SE = 0.1%; z score, 3.93; 95% CI, 0.3%-0.7%; FDR-corrected P < .001) probability of amyloid PET scan positivity for each 1-μg/m3 increase in PM2.5 was observed for 2002 to 2003, whereas an AME of +0.8% (SE = 0.2%; z score = 3.15; 95% CI, 0.3%-1.2%; FDR-corrected P = .002) probability was observed for 2015 to 2016. Post hoc analyses showed no effect modification by sex (2002-2003: interaction term β = 1.01 [95% CI, 0.99-1.04; z score = 1.13; FDR-corrected P = .56]; 2015-2016: β = 1.02 [95% CI, 0.98-1.07; z score = 0.91; FDR-corrected P = .56]) or clinical stage (2002-2003: interaction term β = 1.01 [95% CI, 0.99-1.03; z score = 0.77; FDR-corrected P = .58]; 2015-2016: β = 1.03; 95% CI, 0.99-1.08; z score = 1.46; FDR-corrected P = .47]). Exposure to higher O3 concentrations was not associated with amyloid PET scan positivity in both time windows.

Conclusions And Relevance: This study found that higher PM2.5 concentrations appeared to be associated with brain Aβ plaques. These findings suggest the need to consider airborne toxic pollutants associated with Aβ pathology in public health policy decisions and to inform individual lifetime risk of developing AD and dementia.
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http://dx.doi.org/10.1001/jamaneurol.2020.3962DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7879238PMC
February 2021

Dyadic Group Exercises for Persons with Memory Deficits and Care Partners: Mixed-Method Findings from the Paired Preventing Loss of Independence through Exercise (PLIÉ) Randomized Trial.

J Alzheimers Dis 2020 ;78(4):1689-1706

San Francisco Veterans Affairs Health Care System, San Francisco, CA, USA.

Background: Non-pharmacological therapies for persons with dementia (PWD) are needed.

Objective: To develop and test the Paired Preventing Loss of Independence through Exercise (PLIÉ) program, an integrative group movement program for PWD and care partners (CPs).

Methods: Participants were randomized to immediate or delayed start to Paired PLIÉ in community-based classes (1 hour, 2 days/week, 12 weeks, 3 home visits). Co-primary outcomes included standard measures of cognition, physical function,and quality of life (PWD) and caregiver burden (CPs) assessed by blinded assessors, analyzed using linear mixed models to calculate effect sizes for outcome changes during Paired PLIÉ, controlling for randomization group. Anonymous satisfaction surveys included satisfaction ratings and thematic analysis of open-ended responses.

Results: Thirty dyads enrolled, 24 (80%) completed. PWD (mean age 80; 55% female) experienced significant improvement in self-rated quality of life (Effect Size+0.23; p = 0.016) when participating in Paired PLIÉ, while CPs experienced a non-significant increase in burden (-0.23, p = 0.079). Changes in physical and cognitive function in PWD were not significant. All CPs returning the satisfaction survey (n = 20) reported being moderately-to-highly satisfied with the program. Thematic analyses identified physical (e.g., sit-to-stand, more energy), emotional (enjoyment), and social benefits (peer-to-peer interaction) for PWD and CPs; challenges were primarily related to getting to the in-person classes.

Conclusion: Paired PLIÉ is a promising integrative group movement program that warrants further study. It is feasible and may improve self-rated quality of life in PWD. Although CPs may experience increased burden due to logistical challenges, most reported high satisfaction and physical, emotional, and social benefits.
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http://dx.doi.org/10.3233/JAD-200713DOI Listing
January 2020

Do the Benefits of Educational Attainment for Late-life Cognition Differ by Racial/Ethnic Group?: Evidence for Heterogenous Treatment Effects in the Kaiser Healthy Aging and Diverse Life Experience (KHANDLE) Study.

Alzheimer Dis Assoc Disord 2021 Apr-Jun 01;35(2):106-113

Division of Research, Kaiser Permanente Northern California, Oakland.

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.
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http://dx.doi.org/10.1097/WAD.0000000000000418DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8176621PMC
April 2020

Association of genetic risk for Alzheimer disease and hearing impairment.

Neurology 2020 10 2;95(16):e2225-e2234. Epub 2020 Sep 2.

From the Department of Psychiatry and Behavioral Sciences (W.D.B., K.Y.), Department of Epidemiology and Biostatistics (K.Y., S.F.A., T.J.H., M.M.G.), Department of Neurology (K.Y.), and Institute for Human Genetics (T.J.H.), University of California, San Francisco; 23andMe (T.J.F.), Mountain View; San Francisco VA Health Care System (K.Y.), CA; Department of Medicine and Public Health (S.W.), Rey Juan Carlos University, Madrid, Spain; Kaiser Permanente Northern California Division of Research (E.J.), Oakland; and Public Health Sciences (R.A.W.), Division of Epidemiology, Alzheimer's Disease Research Center, UC Davis School of Medicine, CA.

Objective: To test the hypothesis that incipient Alzheimer disease (AD) may adversely affect hearing and that hearing loss may adversely affect cognition, we evaluated whether genetic variants that increase AD risk also increase problem hearing and genetic variants that increase hearing impairment risk do not influence cognition.

Methods: UK Biobank participants without dementia ≥56 years of age with Caucasian genetic ancestry completed a Digit Triplets Test of speech-in-noise hearing (n = 80,074), self-reported problem hearing and hearing with background noise (n = 244,915), and completed brief cognitive assessments. A genetic risk score for AD (AD-GRS) was calculated as a weighted sum of 23 previously identified AD-related polymorphisms. A genetic risk score for hearing (hearing-GRS) was calculated using 3 previously identified polymorphisms related to hearing impairment. Using age-, sex-, and genetic ancestry-adjusted logistic and linear regression models, we evaluated whether the AD-GRS predicted poor hearing and whether the hearing-GRS predicted worse cognition.

Results: Poor speech-in-noise hearing (>-5.5-dB speech reception threshold; prevalence 14%) was associated with lower cognitive scores (ß = -1.28; 95% confidence interval [CI] -1.54 to -1.03). Higher AD-GRS was significantly associated with poor speech-in-noise hearing (odds ratio [OR] 1.06; 95% CI 1.01-1.11) and self-reported problems hearing with background noise (OR 1.03; 95% CI 1.00-1.05). Hearing-GRS was not significantly associated with cognitive scores (ß = -0.05; 95% CI -0.17 to 0.07).

Conclusions: Genetic risk for AD also influences speech-in-noise hearing. We failed to find evidence that genetic risk for hearing impairment affects cognition. AD disease processes or a that shared etiology may cause speech-in-noise difficulty before dementia onset.
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http://dx.doi.org/10.1212/WNL.0000000000010709DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7713783PMC
October 2020

Racial/Ethnic Differences in Sleep Quality among Older Adults: Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE) Study.

Ethn Dis 2020 9;30(3):469-478. Epub 2020 Jul 9.

Department of Public Health Sciences, University of California Davis School of Medicine, Davis, CA.

Background: We assessed cross-sectional differences in sleep quality and risk factors among Asian, Black, Latino, and White participants in the Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE) Study.

Methods: KHANDLE enrolled community-dwelling adults aged ≥65 years living in northern California. Participants completed a modified Pittsburgh Sleep Quality Index to measure six sleep components and a global sleep score (scored 0-24). Covariates included age, sex, central adiposity, education, income, alcohol consumption, ever smoking, physical activity, and depression. Ordinal logistic regression was used to model sleep component scores across race/ethnic groups. Linear regression was used to assess racial/ethnic differences in global sleep score and the association between risk factors and global sleep score.

Results: 1,664 participants with a mean age of 76 (SD=7) and mean global sleep score of 6 (SD=4) were analyzed. Using Latinos as reference (highest average sleep score), Blacks had an average .96 (.37, 1.54) unit higher global sleep score (worse sleep) while Asians [: .04 (-.56, .63)] and Whites [: .28 (-.29, .84)] did not significantly differ. Compared with Latinos, Blacks and Asians had greater odds of a worse score on the sleep duration component; Blacks and Whites had greater odds of a worse score on the sleep disturbances component; and, Whites had greater odds of a worse score on the medication component. Risk factors for poor sleep did not differ by race/ethnicity except alcohol consumption (interaction P=.04), which was associated with poor sleep in Blacks only.

Conclusions: In this cohort, racial/ethnic differences in sleep quality were common.
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http://dx.doi.org/10.18865/ed.30.3.469DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7360172PMC
April 2021

Differences in association of leisure time activities and cognition in a racially/ethnically diverse cohort of older adults: Findings from the KHANDLE study.

Alzheimers Dement (N Y) 2020 26;6(1):e12047. Epub 2020 Jun 26.

University of California Davis School of Medicine Davis California USA.

Introduction: Leisure time activity is associated with better cognitive function but has not been well studied in racially/ethnically diverse cohorts, who may have different access to activities.

Methods: Frequency of participation in 10 leisure time activities (eg, reading, attending cultural events) and cognition (executive function, semantic memory, and verbal episodic memory) were assessed at Wave 1 in the Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE) study, a prospective cohort initiated in 2017. Linear regression models adjusted for sociodemographics and depression estimated cross-sectional associations between leisure time activity variety and frequency and cognitive domains overall and by race/ethnicity. Logistic regression models estimated odds of cognitive impairment among those in the lowest quartiles of activity variety and frequency. All models controlled for age, sex, education, income, retirement status, and depression.

Results: Higher leisure time activity variety was significantly associated with better cognition for all, except for verbal episodic memory among Asians (β = 0.05, 95% confidence interval [CI]: -0.004, 0.11) and semantic memory among Latinos (β = 0.04, 95% CI: -0.01, 0.08). Low activity variety was associated with nearly three-fold increased odds of cognitive impairment (adjusted odds ratio [OR] = 2.87, 95% CI: 1.77, 4.64). Activity frequency was associated with higher executive function only among whites (β = 0.10, 95% CI: 0.02, 0.18). Patterns by race/ethnicity were not explained by education.

Discussion: Engaging in a wider variety of leisure time activities may be more important than frequently participating in fewer activities for cognitive aging in racially/ethnically diverse cohorts.
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http://dx.doi.org/10.1002/trc2.12047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7317643PMC
June 2020
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