Publications by authors named "Kristine Yaffe"

582 Publications

The Health & Aging Brain among Latino Elders (HABLE) study methods and participant characteristics.

Alzheimers Dement (Amst) 2021 21;13(1):e12202. Epub 2021 Jun 21.

Department of Psychiatry, Neurology, and Epidemiology and Biostatistics University of California San Francisco California USA.

Introduction: Mexican Americans remain severely underrepresented in Alzheimer's disease (AD) research. The Health & Aging Brain among Latino Elders (HABLE) study was created to fill important gaps in the existing literature.

Methods: Community-dwelling Mexican Americans and non-Hispanic White adults and elders (age 50 and above) were recruited. All participants underwent comprehensive assessments including an interview, functional exam, clinical labs, informant interview, neuropsychological testing, and 3T magnetic resonance imaging (MRI) of the brain. Amyloid and tau positron emission tomography (PET) scans were added at visit 2. Blood samples were stored in the Biorepository.

Results: Data was examined from n = 1705 participants. Significant group differences were found in medical, demographic, and sociocultural factors. Cerebral amyloid and neurodegeneration imaging markers were significantly different between Mexican Americans and non-Hispanic Whites.

Discussion: The current data provide strong support for continued investigations that examine the risk factors for and biomarkers of AD among diverse populations.
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http://dx.doi.org/10.1002/dad2.12202DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8215806PMC
June 2021

Safety and efficacy of pioglitazone for the delay of cognitive impairment in people at risk of Alzheimer's disease (TOMMORROW): a prognostic biomarker study and a phase 3, randomised, double-blind, placebo-controlled trial.

Lancet Neurol 2021 07;20(7):537-547

Takeda Development Center Americas, Cambridge, MA, USA.

Background: The identification of people at risk of cognitive impairment is essential for improving recruitment in secondary prevention trials of Alzheimer's disease. We aimed to test and qualify a biomarker risk assignment algorithm (BRAA) to identify participants at risk of developing mild cognitive impairment due to Alzheimer's disease within 5 years, and to evaluate the safety and efficacy of low-dose pioglitazone to delay onset of mild cognitive impairment in these at-risk participants.

Methods: In this phase 3, multicentre, randomised, double-blind, placebo-controlled, parallel-group study, we enrolled cognitively healthy, community living participants aged 65-83 years from 57 academic affiliated and private research clinics in Australia, Germany, Switzerland, the UK, and the USA. By use of the BRAA, participants were grouped as high risk or low risk. Participants at high risk were randomly assigned 1:1 to receive oral pioglitazone (0·8 mg/day sustained release) or placebo, and all low-risk participants received placebo. Study investigators, site staff, sponsor personnel, and study participants were masked to genotype, risk assignment, and treatment assignment. The planned study duration was the time to accumulate 202 events of mild cognitive impairment due to Alzheimer's disease in White participants who were at high risk (the population on whom the genetic analyses that informed the BRAA development was done). Primary endpoints were time-to-event comparisons between participants at high risk and low risk given placebo (for the BRAA objective), and between participants at high risk given pioglitazone or placebo (for the efficacy objective). The primary analysis included all participants who were randomly assigned, received at least one dose of study drug, and had at least one valid post-baseline visit, with significance set at p=0·01. The safety analysis included all participants who were randomly assigned and received at least one dose of study medication. An efficacy futility analysis was planned for when approximately 33% of the anticipated events occurred in the high-risk, White, non-Hispanic or Latino group. This trial is registered with ClinicalTrials.gov, NCT01931566.

Findings: Between Aug 28, 2013, and Dec 21, 2015, we enrolled 3494 participants (3061 at high risk and 433 at low risk). Of those participants, 1545 were randomly assigned to pioglitazone and 1516 to placebo. 1104 participants discontinued treatment (464 assigned to the pioglitazone group, 501 in the placebo high risk group, and 139 in the placebo low risk group). 3399 participants had at least one dose of study drug or placebo and at least one post-baseline follow-up visit, and were included in the efficacy analysis. 3465 participants were included in the safety analysis (1531 assigned to the pioglitazone group, 1507 in the placebo high risk group, and 427 in the placebo low risk group). In the full analysis set, 46 (3·3%) of 1406 participants at high risk given placebo had mild cognitive impairment due to Alzheimer's disease, versus four (1·0%) of 402 participants at low risk given placebo (hazard ratio 3·26, 99% CI 0·85-12·45; p=0·023). 39 (2·7%) of 1430 participants at high risk given pioglitazone had mild cognitive impairment, versus 46 (3·3%) of 1406 participants at high risk given placebo (hazard ratio 0·80, 99% CI 0·45-1·40; p=0·307). In the safety analysis set, seven (0·5%) of 1531 participants at high risk given pioglitazone died versus 21 (1·4%) of 1507 participants at high risk given placebo. There were no other notable differences in adverse events between groups. The study was terminated in January, 2018, after failing to meet the non-futility threshold.

Interpretation: Pioglitazone did not delay the onset of mild cognitive impairment. The biomarker algorithm demonstrated a 3 times enrichment of events in the high risk placebo group compared with the low risk placebo group, but did not reach the pre-specified significance threshold. Because we did not complete the study as planned, findings can only be considered exploratory. The conduct of this study could prove useful to future clinical development strategies for Alzheimer's disease prevention studies.

Funding: Takeda and Zinfandel.
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http://dx.doi.org/10.1016/S1474-4422(21)00043-0DOI Listing
July 2021

Defining brain health: A concept analysis.

Int J Geriatr Psychiatry 2021 Apr 30. Epub 2021 Apr 30.

Global Brain Health Institute, Trinity College Dublin, Dublin, Ireland.

Objectives: Brain health is an important focus for coming decades due to population ageing. Although the term 'brain health' is increasingly used in lay and professional settings, a clear definition of the term is lacking. We conducted an analysis of the concept of brain health to inform policy, practice, and research.

Methods: We applied a hybrid concept analysis method involving three stages: (1) a review of the extant literature for definitions of brain health; (2) field work, involving an international survey of 'brain health' researchers and practitioners; and (3) a final analysis, integrating the findings into a working definition and model.

Results: Our review of the literature identified 13 articles defining brain health, six of which proposed their own definition. Our survey revealed that the term 'brain health' was used in diverse ways based on different theoretical frameworks. From the review and survey, we extracted attributes, antecedents, and consequences of brain health. These were synthesized into a definition of brain health as a life-long, multidimensional, dynamic state consisting of cognitive, emotional and motor domains underpinned by physiological processes and can be objectively measured and subjectively experienced. It is influenced by eco-biopsychosocial determinants.

Conclusion: This working definition of brain health is a foundation for developing policy, practice, research and advocacy. The definition needs to be operationalised through further development of empirical referents, including cross-cultural understanding, adaptation and validation.
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http://dx.doi.org/10.1002/gps.5564DOI Listing
April 2021

Polypharmacy among older adults with dementia compared with those without dementia in the United States.

J Am Geriatr Soc 2021 Jun 8. Epub 2021 Jun 8.

Division of Geriatrics, University of California, San Francisco, California, USA.

Background/objectives: In older persons with dementia (PWD), extensive medication use is often unnecessary, discordant with goals of care, and possibly harmful. The objective of this study was to determine the prevalence and medication constituents of polypharmacy among older PWD attending outpatient visits in the United States.

Design: Cross-sectional analysis.

Setting And Participants: PWD and persons without dementia (PWOD) aged ≥65 years attending outpatient visits recorded in the nationally representative National Ambulatory Medical Care Survey (NAMCS), 2014-2016.

Measurements: PWD were identified as those with a diagnosis of dementia on the NAMCS encounter form and/or those receiving an anti-dementia medication. Visits with PWD and PWOD were compared in terms of sociodemographic, practice/physician factors, comorbidities, and prescribing outcomes. Regression analyses examined the effect of dementia diagnosis on contributions by clinically relevant medication categories to polypharmacy (defined as being prescribed ≥5 prescription and/or nonprescription medications).

Results: The unweighted sample involved 918 visits for PWD and 26,543 visits for PWOD, representing 29.0 and 780 million outpatient visits. PWD had a median age of 81 and on average had 2.8 comorbidities other than dementia; 63% were female. The median number of medications in PWD was eight compared with three in PWOD (p < 0.001). After adjustment, PWD had significantly higher odds of being prescribed ≥5 medications (AOR 3.0; 95% CI: 2.1-4.3) or ≥10 medications (AOR 2.8; 95% CI: 2.0-4.2) compared with PWOD. The largest sources of medications among PWD were cardiovascular and central nervous system medications; usage from other categories was generally elevated in PWD compared with PWOD. PWD had higher odds of receiving at least one highly sedating or anticholinergic medication (AOR 2.5; 95% CI: 1.6-3.9).

Conclusion: In a representative sample of outpatient visits, polypharmacy was extremely common among PWD, driven by a wide array of medication categories. Addressing polypharmacy in PWD will require cross-cutting and multidisciplinary approaches.
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http://dx.doi.org/10.1111/jgs.17291DOI Listing
June 2021

A blood screening tool for detecting mild cognitive impairment and Alzheimer's disease among community-dwelling Mexican Americans and non-Hispanic Whites: A method for increasing representation of diverse populations in clinical research.

Alzheimers Dement 2021 May 31. Epub 2021 May 31.

Institute for Translational Research, University of North Texas Health Science Center, Fort Worth, Texas, USA.

Introduction: Representation of Mexican Americans in Alzheimer's disease (AD) clinical research has been extremely poor.

Methods: Data were examined from the ongoing community-based, multi-ethnic Health & Aging Brain among Latino Elders (HABLE) study. Participants underwent functional exams, clinical labs, neuropsychological testing, and 3T magnetic resonance imaging of the brain. Fasting proteomic markers were examined for predicting mild cognitive impairment (MCI) and AD using support vector machine models.

Results: Data were examined from n = 1649 participants (Mexican American n = 866; non-Hispanic White n = 783). Proteomic profiles were highly accurate in detecting MCI (area under the curve [AUC] = 0.91) and dementia (AUC = 0.95). The proteomic profiles varied significantly between ethnic groups and disease state. Negative predictive value was excellent for ruling out MCI and dementia across ethnic groups.

Discussion: A blood-based screening tool can serve as a method for increasing access to state-of-the-art AD clinical research by bridging between community-based and clinic-based settings.
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http://dx.doi.org/10.1002/alz.12382DOI Listing
May 2021

Sleep Timing and Risk of Dementia Among the Chinese Elderly in an Urban Community: The Shanghai Aging Study.

Front Neurol 2021 29;12:629507. Epub 2021 Apr 29.

Department of Neurology, Memory and Aging Center, Global Brain Health Institute, University of California, San Francisco, San Francisco, CA, United States.

Growing evidence has suggested a link between poor sleep quality and increased risk of dementia. However, little is known about the association between sleep timing, an important behavior marker of circadian rhythms, and dementia risk in older adults, and whether this is independent of sleep duration or quality. We included data from 1,051 community-dwelling older men and women (aged≥ 60y) without dementia from the Shanghai Aging Study. At baseline, participants reported sleep timing, duration, and quality using the Chinese version of the Pittsburgh Sleep Quality Index (CPSQI). Dementia diagnosis over the following 7.3 years was determined by neurologists using DSM-IV criteria. We used Cox proportional hazards models to examine the association between bedtime (before 9 p.m., after 11 p.m. vs. 9-11 p.m.), rise time (before 6 a.m., after 8 a.m. vs. 6-8 a.m.), and risk of dementia. A total of 238 (22.8%), 675 (64.5%), and 133 (12.7%) participants reported going to bed before 9 p.m., between 9 and 11 p.m., and after 11 p.m., respectively, while 272 (26%), 626 (59.9%), and 148 (14.2%) reported getting up before 6 a.m., between 6 and 8 a.m., and after 8 a.m., respectively. Participants who reported going to bed earlier had a lower education level, were less likely to be smokers, more likely to have hypertension or diabetes, and had longer sleep duration but poorer sleep quality compared to those who reported a later bedtime. We found 47 incidents of dementia among 584 participants followed up over an average of 7.3 years. After adjustment for demographics, education, income, body mass index, depressive symptoms, smoking, alcohol use, physical activity, comorbidities, APOE4 genotype, and baseline MMSE, those with a bedtime of before 9 p.m. were two times more likely to develop dementia [hazard ratio (HR)=2.16 (95%CI: 1.06-4.40)], compared to those going to bed between 9 and 11 p.m. Later bedtime (i.e., after 11 p.m.) showed the opposite but had a non-significant association with dementia risk (HR=0.15, 95%CI: 0.02-1.29). We did not find an association for rise time and risk of dementia. Earlier sleep timing in older adults without dementia was associated with an increased risk of dementia. Future studies should examine the underlying mechanisms of this association and explore the usefulness of sleep timing as a preclinical marker for dementia.
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http://dx.doi.org/10.3389/fneur.2021.629507DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8116668PMC
April 2021

Body mass index in early adulthood and dementia in late life: Findings from a pooled cohort.

Alzheimers Dement 2021 May 13. Epub 2021 May 13.

Departments of Psychiatry, Neurology, and Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California, USA.

Introduction: To examine the independent association of body mass index (BMI) in early adulthood with dementia incidence among men and women.

Methods: We studied 5104 older adults from the Cardiovascular Health Study (CHS) and the Health, Aging, and Body Composition (Health ABC) study. We imputed early adulthood and midlife BMI using a pooled parent cohort with complete adult lifespan coverage and previously established methods. Dementia was ascertained using criteria such as neuropsychological test battery, medical records, and dementia-related drug use. Pooled logistic regression (PLR) models were used.

Results: Compared to women with normal BMI in early adulthood, the odds of dementia were higher among both overweight (odds ratio [OR] = 1.8; 95% confidence interval [CI] = 1.31 to 2.54) and obese (OR = 2.45; 95% CI = 1.47 to 4.06) women, independent of mid- and late-life BMI. Similar relationship was observed in men.

Conclusions: With the growing obesity epidemic among US adults, efforts aimed at reducing dementia may need to begin obesity prevention and treatment early in the life course.
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http://dx.doi.org/10.1002/alz.12367DOI Listing
May 2021

Predicting incident dementia and mild cognitive impairment in older women with nonparametric analysis of circadian activity rhythms in the Study of Osteoporotic Fractures.

Sleep 2021 May 8. Epub 2021 May 8.

Research Institute, California Pacific Medical Center, San Francisco, CA.

Study Objectives: Disrupted daily rhythms are associated with mild cognitive impairment (MCI) and dementia. The specific nature of how rhythms and cognition are related, however, is unknown. We hypothesized characteristics from a nonparametric estimate of circadian rest-activity rhythm patterns would be associated to the development of MCI or dementia.

Methods: Wrist actigraphy from 1232 cognitively healthy, community-dwelling women (mean age 82.6 years) from the Study of Osteoporotic Fractures was used to estimate rest-activity patterns, including intradaily variability (IV), interdaily stability (IS), most active 10-hour period (M10), least active 5-hour period (L5), and relative amplitude (RA). Logistic regression examined associations of these predictors with 5-year incidence of MCI or dementia. Models were adjusted for potential confounders.

Results: Women with earlier sleep/wake times had higher risk of dementia, but not MCI, (early vs. average L5 midpoint: OR, 1.66; 95% CI, 1.08-2.55) as did women with smaller day/night activity differentials (low vs. high RA: OR, 1.96; 95% CI, 1.14-3.35). IV, IS, and M10 were not associated with MCI or dementia.

Conclusion: The timing and difference in day/night amplitude, but not variability of activity, may be useful as predictors of dementia.
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http://dx.doi.org/10.1093/sleep/zsab119DOI Listing
May 2021

Epidemiology of Chronic Effects of Traumatic Brain Injury.

J Neurotrauma 2021 May 5. Epub 2021 May 5.

UCSF and San Francisco VA Medical Center, Neurology, Psychiatry, and Epidemiology, San Francisco, California, United States;

Although many patients diagnosed with traumatic brain injury (TBI), particularly mild TBI, recover from their symptoms within a few weeks, a small but meaningful subset experience symptoms that persist for months or years after injury and significantly impact quality of life for the individual and their family. The factors associated with an increased likelihood of negative TBI outcomes include not only characteristics of the injury and injury mechanism, but also the individual's age, pre-injury status, comorbid conditions, environment, and propensity for resilience. In this article, as part of the Brain Trauma Blueprint: TBI State of the Science framework, we examine the epidemiology of long-term outcomes of TBI, including incidence, prevalence, and risk factors. We identify the need for increased longitudinal, global, standardized, and validated assessments on incidence, recovery, and treatments, as well as standardized assessments of the influence of genetics, race, ethnicity, gender, and environment on TBI outcomes. By identifying how epidemiological factors contribute to TBI outcomes in different groups of people and potentially impact differential disease progression, we can guide investigators and clinicians towards more precise patient diagnosis along with tailored management and improve clinical trial designs, data evaluation and patient selection criteria.
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http://dx.doi.org/10.1089/neu.2021.0062DOI Listing
May 2021

Phenotyping the Spectrum of Traumatic Brain Injury: A Review and Pathway to Standardization.

J Neurotrauma 2021 Jun 10. Epub 2021 Jun 10.

Department of Emergency Medicine, Stanford University School of Medicine, Stanford, California, USA.

It is widely appreciated that the spectrum of traumatic brain injury (TBI), mild through severe, contains distinct clinical presentations, variably referred to as subtypes, phenotypes, and/or clinical profiles. As part of the Brain Trauma Blueprint TBI State of the Science, we review the current literature on TBI phenotyping with an emphasis on unsupervised methodological approaches, and describe five phenotypes that appear similar across reports. However, we also find the literature contains divergent analysis strategies, inclusion criteria, findings, and use of terms. Further, whereas some studies delineate phenotypes within a specific severity of TBI, others derive phenotypes across the full spectrum of severity. Together, these facts confound direct synthesis of the findings. To overcome this, we introduce PhenoBench, a freely available code repository for the standardization and evaluation of raw phenotyping data. With this review and toolset, we provide a pathway toward robust, data-driven phenotypes that can capture the heterogeneity of TBI, enabling reproducible insights and targeted care.
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http://dx.doi.org/10.1089/neu.2021.0059DOI Listing
June 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

Associations between 20-year lipid variability throughout young adulthood and midlife cognitive function and brain integrity.

J Gerontol A Biol Sci Med Sci 2021 Apr 11. Epub 2021 Apr 11.

Departments of Psychiatry, Neurology, and Epidemiology and Biostatistics, University of California San Francisco, CA.

Background: Little is known about long-term lipid variability in young adulthood in relation to cognitive function and brain integrity in midlife.

Methods: We studied 3,328 adults from the Coronary Artery Risk Development in Young Adults. We defined low- and high- density lipoprotein (LDL, HDL) variability as the intra-individual standard deviation of lipid measurements over 20 years of young adulthood (1985-2005). Cognitive tests were administered in 2010. Brain scans were performed in 2010 on 714 participants. To facilitate comparison, cognitive tests and brain metrics were z-scored.

Results: Mean age at baseline was 25.4 years. Higher 20-year LDL variability was associated with worse verbal memory in midlife (β=-0.25, 95% CI [-0.42, -0.08]), adjusted for important covariates. Higher 20-year HDL variability was associated with worse processing speed in midlife (β=-0.80, 95% CI [-1.18, -0.41]) and brain integrity, e.g. smaller total brain volume (β=-0.58, 95% CI [-0.82, -0.34]) and worse total brain fractional anisotropy (β=-1.13, 95% CI [-1.87, -0.39]).

Conclusions: Higher long-term lipid variability in adulthood was associated with worse cognition and brain integrity in midlife, in a relatively young cohort.
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http://dx.doi.org/10.1093/gerona/glab108DOI Listing
April 2021

Associations between 20-year lipid variability throughout young adulthood and midlife cognitive function and brain integrity.

J Gerontol A Biol Sci Med Sci 2021 Apr 11. Epub 2021 Apr 11.

Departments of Psychiatry, Neurology, and Epidemiology and Biostatistics, University of California San Francisco, CA.

Background: Little is known about long-term lipid variability in young adulthood in relation to cognitive function and brain integrity in midlife.

Methods: We studied 3,328 adults from the Coronary Artery Risk Development in Young Adults. We defined low- and high- density lipoprotein (LDL, HDL) variability as the intra-individual standard deviation of lipid measurements over 20 years of young adulthood (1985-2005). Cognitive tests were administered in 2010. Brain scans were performed in 2010 on 714 participants. To facilitate comparison, cognitive tests and brain metrics were z-scored.

Results: Mean age at baseline was 25.4 years. Higher 20-year LDL variability was associated with worse verbal memory in midlife (β=-0.25, 95% CI [-0.42, -0.08]), adjusted for important covariates. Higher 20-year HDL variability was associated with worse processing speed in midlife (β=-0.80, 95% CI [-1.18, -0.41]) and brain integrity, e.g. smaller total brain volume (β=-0.58, 95% CI [-0.82, -0.34]) and worse total brain fractional anisotropy (β=-1.13, 95% CI [-1.87, -0.39]).

Conclusions: Higher long-term lipid variability in adulthood was associated with worse cognition and brain integrity in midlife, in a relatively young cohort.
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http://dx.doi.org/10.1093/gerona/glab108DOI Listing
April 2021

The presence of emphysema on chest imaging and mid-life cognition.

ERJ Open Res 2021 Jan 15;7(1). Epub 2021 Mar 15.

Minneapolis Veterans Affairs Health Care System, Minneapolis, MN, USA.

Background: Airflow obstruction is associated with cognitive dysfunction but studies have not assessed how emphysema, a structural phenotype of lung disease, might be associated with cognitive function independent from pulmonary function measured by spirometry. We aimed to determine the relationship between the presence of visually detectable emphysema on chest computed tomography (CT) imaging and cognitive function.

Methods: We examined 2491 participants, mean age of 50 years, from the Coronary Artery Risk Development in Young Adults study who were assessed for the presence of emphysema on chest CT imaging and had cognitive function measured 5 years later with a battery of six cognitive tests.

Results: Of those assessed, 172 (7%) had emphysema. After adjusting for age, sex, height, study centre, race, body mass index, education and smoking, visual emphysema was significantly associated with worse performance on most cognitive tests. Compared to those without emphysema, participants with emphysema performed worse on cognitive testing: 0.39 sd units lower (95% CI -0.53- -0.25) on the Montreal Cognitive Assessment, 0.27 sd units lower (95% CI -0.42- -0.12) on the Rey Auditory Verbal Learning Test, 0.29 sd units lower (95% CI -0.43- -0.14) on the Digit Symbol Substitution Test and 0.25 sd units lower (95% CI -0.42- -0.09) on letter fluency. Further adjustment for forced expiratory volume in 1 s (FEV), peak FEV and annualised FEV decline did not attenuate these associations.

Conclusions: The presence of emphysema on chest CT is associated with worse cognitive function, independent of airflow obstruction. These data suggest that emphysema may be a novel risk factor for cognitive impairment.
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http://dx.doi.org/10.1183/23120541.00048-2021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957295PMC
January 2021

Atrial Fibrillation and Longitudinal Change in Cognitive Function in CKD.

Kidney Int Rep 2021 Mar 5;6(3):669-674. Epub 2021 Jan 5.

Department of Medicine, University of Illinois at Chicago, Chicago, Illinois, USA.

Background: Studies in the general population suggest that atrial fibrillation (AF) is an independent risk factor for decline in cognitive function, but this relationship has not been examined in adults with chronic kidney disease (CKD). We investigated the association between incident AF and changes in cognitive function over time in this population.

Methods And Results: We studied a subgroup of 3254 adults participating in the Chronic Renal Insufficiency Cohort Study. Incident AF was ascertained by 12-lead electrocardiogram (ECG) obtained at a study visit and/or identification of a hospitalization with AF during follow-up. Cognitive function was assessed biennially using the Modified Mini-Mental State Exam. Linear mixed effects regression was used to evaluate the association between incident AF and longitudinal change in cognitive function. Compared with individuals without incident AF ( = 3158), those with incident AF ( = 96) were older, had a higher prevalence of cardiovascular disease and hypertension, and lower estimated glomerular filtration rate. After median follow-up of 6.8 years, we observed no significant multivariable association between incident AF and change in cognitive function test score.

Conclusion: In this cohort of adults with CKD, incident AF was not associated with a decline in cognitive function.
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http://dx.doi.org/10.1016/j.ekir.2020.12.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7938064PMC
March 2021

Cardiovascular Risk Factors Across the Life Course and Cognitive Decline: A Pooled Cohort Study.

Neurology 2021 04 17;96(17):e2212-e2219. Epub 2021 Mar 17.

From the Departments of Psychiatry and Neurology (K.Y.) and Epidemiology & Biostatistics (K.Y., E.V.), University of California San Francisco; San Francisco Veterans Affairs Medical Center (K.Y.); Northern California Institute Research for Research and Education (T.H.), San Francisco; Department of Psychiatry (K.M.), University of Pittsburgh, PA; Department of Medicine (S.H.G.), Johns Hopkins University School of Medicine; Department of Epidemiology (S.H.G.), Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD; and Department of Epidemiology (A.Z.A.H.), Mailman School of Public Health, Columbia University, New York, NY.

Objective: Cardiovascular risk factors (CVRFs) are associated with increased risk of cognitive decline, but little is known about how early adult CVRFs and those across the life course might influence late-life cognition. To test the hypothesis that CVRFs across the adult life course are associated with late-life cognitive changes, we pooled data from 4 prospective cohorts (n = 15,001, ages 18-95).

Methods: We imputed trajectories of body mass index (BMI), fasting glucose (FG), systolic blood pressure (SBP), and total cholesterol (TC) for older adults. We used linear mixed models to determine the association of early adult, midlife, and late-life CVRFs with late-life decline on global cognition (Modified Mini-Mental State Examination [3MS]) and processing speed (Digit Symbol Substitution Test [DSST]), adjusting for demographics, education, and cohort.

Results: Elevated BMI, FG, and SBP (but not TC) at each time period were associated with greater late-life decline. Early life CVRFs were associated with the greatest change, an approximate doubling of mean 10-year decline (an additional 3-4 points for 3MS or DSST). Late-life CVRFs were associated with declines in early late life (<80 years) but with gains in very late life (≥80 years). After adjusting for CVRF exposures at all time periods, the associations for early adult and late-life CVRFs persisted.

Conclusions: We found that imputed CVRFs across the life course, especially in early adulthood, were associated with greater late-life cognitive decline. Our results suggest that CVRF treatment in early adulthood could benefit late-life cognition, but that treatment in very late life may not be as helpful for these outcomes.
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http://dx.doi.org/10.1212/WNL.0000000000011747DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8166431PMC
April 2021

Atrial Fibrillation is Associated With Greater Risk of Dementia in Older Veterans.

Am J Geriatr Psychiatry 2021 Feb 9. Epub 2021 Feb 9.

Departments of Psychiatry, Neurology, and Epidemiology (KY), University of California, San Francisco VA Medical Center, San Francisco, CA.

Objectives: To examine the association of atrial fibrillation (AF) with incident dementia in older veterans and the effect of anticoagulation on that association.

Methods: Around 407,871 veterans aged ≥55 years receiving care from US Veterans Health Administration between August 2003 and September 2015 were included in our retrospective study. AF and incident dementia were determined according to ICD-9-CM codes. Logistic regressions with veterans grouped into high-dimensional propensity scores deciles were used, and a mediation analysis was employed to examine the extent of cardio/cerebrovascular diseases that may also account for that association.

Results: AF was associated with greater dementia risk (odds ratio = 1.14; 95% confidence interval 1.07-1.22), partially mediated by cardio/cerebrovascular disease. Among veterans with AF taking anticoagulants, the risk of dementia was 44% higher (odds ratio =1.44; 95% CI 1.27-1.63) compared to those without anticoagulants, likely related to AF severity.

Conclusion: Our findings underscore the importance of considering cognitive function in the management of AF patients.
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http://dx.doi.org/10.1016/j.jagp.2021.02.038DOI Listing
February 2021

Traumatic Brain Injury and Incidence Risk of Sleep Disorders in Nearly 200,000 US Veterans.

Neurology 2021 03 3;96(13):e1792-e1799. Epub 2021 Mar 3.

From the Department of Psychiatry (Y. Leng, A.L.B., D.E.B., K.Y.), Department of Epidemiology and Biostatistics (A.L.B., D.E.B., K.Y.), and Department of Neurology (K.Y.), University of California, San Francisco; and San Francisco Veterans Affairs Health Care System (A.L.B., D.E.B., C.B.P., Y. Li., K.Y.), CA.

Objective: To test the hypothesis that veterans with traumatic brain injury (TBI) have an increased subsequent risk of sleep disorders, we studied the longitudinal association between TBI and incident sleep disorders in nearly 200,000 veterans.

Methods: We performed a cohort study of all patients diagnosed with a TBI in the Veterans Health Administration system from October 1, 2001, to September 30, 2015, who were age-matched 1:1 to veterans without TBI. Veterans with prevalent sleep disorders at baseline were excluded. Development of sleep disorders was defined as any inpatient or outpatient diagnosis of sleep apnea, hypersomnia, insomnia, or sleep-related movement disorders based on ICD-9 codes after the first TBI diagnosis or the random selection date for those without TBI. We restricted the analysis to those with at least 1 year of follow-up. We used Cox proportional hazards models to examine the association between TBI and subsequent risk of sleep disorders.

Results: The study included 98,709 veterans with TBI and 98,709 age-matched veterans without TBI (age 49 ± 20 years). After an average follow-up of 5 (1-14) years, 23,127 (19.6%) veterans developed sleep disorders. After adjustment for demographics, education, income, and medical and psychiatric conditions, those who had TBI compared to those without TBI were 41% more likely to develop any sleep disorders (hazard ratio 1.41 [95% confidence interval 1.37-1.44]), including sleep apnea (1.28 [1.24-1.32]), insomnia (1.50 [1.45-1.55]), hypersomnia (1.50 [1.39-1.61]), and sleep-related movement disorders (1.33 [1.16-1.52]). The association was stronger for mild TBIs, did not differ appreciably by presence of posttraumatic stress disorder, and remained after a 2-year time lag.

Conclusion: In 197,418 veterans without sleep disorders, those with diagnosed TBI had an increased risk of incident sleep disorders over 14 years. Improved prevention and long-term management strategies for sleep are needed for veterans with TBI.
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http://dx.doi.org/10.1212/WNL.0000000000011656DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8055309PMC
March 2021

Non-alcoholic fatty liver disease and cognitive function in middle-aged adults: the CARDIA study.

BMC Gastroenterol 2021 Mar 2;21(1):96. Epub 2021 Mar 2.

Kaiser Permanente Northern California, Oakland, CA, USA.

Background: Non-alcoholic fatty liver disease (NAFLD) is associated with cardiovascular disease (CVD) risk factors that have been linked to cognitive decline. Whether NAFLD is associated with cognitive performance in midlife remains uncertain.

Methods: Coronary Artery Risk Development in Young Adults study participants with CT examination and cognitive assessment at Y25 (2010-2011; n = 2809) were included. Cognitive function was reassessed at Y30. NAFLD was defined according to liver attenuation and treated both continuously and categorically (using ≤ 40 and ≤ 51 Hounsfield units to define severity) after exclusion for other causes of liver fat. Cognitive tests including the Digit Symbol Substitution (processing speed), Rey Auditory Verbal Learning (verbal memory), and Stroop (executive function) were analyzed with standardized z-scores. Linear models were constructed to (a) examine the cross-sectional associations of NAFLD with cognitive scores and (b) evaluate its predictive role in 5-year change in cognitive performance.

Results: Participants' mean age (Y25) was 50.1 (SD 3.6) years (57% female; 48% black), with 392 (14%) having mild NAFLD and 281 (10%) having severe NAFLD. NAFLD was positively associated with CVD risk factors and inversely associated with cognitive scores. However, after adjustment for CVD risk factors, no associations were shown between NAFLD and cognitive scores (all βs ≈ 0). Similarly, no associations were observed with 5-year cognitive decline. CVD history, hypertension, smoking, diabetes and hypertriglyceridemia showed stronger associations with baseline cognitive scores and were predictive of subsequent cognitive decline (all P ≤ .05).

Conclusion: Among middle-aged adults, inverse associations between NAFLD and cognitive scores were attenuated after adjustment for CVD risk factors, with the latter predictive of poorer cognitive performance both at baseline and follow-up.
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http://dx.doi.org/10.1186/s12876-021-01681-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7927393PMC
March 2021

COllaborative Neuropathology NEtwork Characterizing ouTcomes of TBI (CONNECT-TBI).

Acta Neuropathol Commun 2021 03 1;9(1):32. Epub 2021 Mar 1.

Institute of Neuroscience and Psychology, University of Glasgow, Queen Elizabeth University Hospital, Glasgow, UK.

Efforts to characterize the late effects of traumatic brain injury (TBI) have been in progress for some time. In recent years much of this activity has been directed towards reporting of chronic traumatic encephalopathy (CTE) in former contact sports athletes and others exposed to repetitive head impacts. However, the association between TBI and dementia risk has long been acknowledged outside of contact sports. Further, growing experience suggests a complex of neurodegenerative pathologies in those surviving TBI, which extends beyond CTE. Nevertheless, despite extensive research, we have scant knowledge of the mechanisms underlying TBI-related neurodegeneration (TReND) and its link to dementia. In part, this is due to the limited number of human brain samples linked to robust demographic and clinical information available for research. Here we detail a National Institutes for Neurological Disease and Stroke Center Without Walls project, the COllaborative Neuropathology NEtwork Characterizing ouTcomes of TBI (CONNECT-TBI), designed to address current limitations in tissue and research access and to advance understanding of the neuropathologies of TReND. As an international, multidisciplinary collaboration CONNECT-TBI brings together multiple experts across 13 institutions. In so doing, CONNECT-TBI unites the existing, comprehensive clinical and neuropathological datasets of multiple established research brain archives in TBI, with survivals ranging minutes to many decades and spanning diverse injury exposures. These existing tissue specimens will be supplemented by prospective brain banking and contribute to a centralized route of access to human tissue for research for investigators. Importantly, each new case will be subject to consensus neuropathology review by the CONNECT-TBI Expert Pathology Group. Herein we set out the CONNECT-TBI program structure and aims and, by way of an illustrative case, the approach to consensus evaluation of new case donations.
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http://dx.doi.org/10.1186/s40478-021-01122-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7919306PMC
March 2021

Sex Differences in Cognitive Decline Among US Adults.

JAMA Netw Open 2021 02 1;4(2):e210169. Epub 2021 Feb 1.

Cognitive Health Services Research Program, Department of Internal Medicine, University of Michigan, Ann Arbor.

Importance: Sex differences in dementia risk are unclear, but some studies have found greater risk for women.

Objective: To determine associations between sex and cognitive decline in order to better understand sex differences in dementia risk.

Design, Setting, And Participants: This cohort study used pooled analysis of individual participant data from 5 cohort studies for years 1971 to 2017: Atherosclerosis Risk in Communities Study, Coronary Artery Risk Development in Young Adults Study, Cardiovascular Health Study, Framingham Offspring Study, and Northern Manhattan Study. Linear mixed-effects models were used to estimate changes in each continuous cognitive outcome over time by sex. Data analysis was completed from March 2019 to October 2020.

Exposure: Sex.

Main Outcomes And Measures: The primary outcome was change in global cognition. Secondary outcomes were change in memory and executive function. Outcomes were standardized as t scores (mean [SD], 50 [10]); a 1-point difference represents a 0.1-SD difference in cognition.

Results: Among 34 349 participants, 26 088 who self-reported Black or White race, were free of stroke and dementia, and had covariate data at or before the first cognitive assessment were included for analysis. Median (interquartile range) follow-up was 7.9 (5.3-20.5) years. There were 11 775 (44.7%) men (median [interquartile range] age, 58 [51-66] years at first cognitive assessment; 2229 [18.9%] Black) and 14 313 women (median [interquartile range] age, 58 [51-67] years at first cognitive assessment; 3636 [25.4%] Black). Women had significantly higher baseline performance than men in global cognition (2.20 points higher; 95% CI, 2.04 to 2.35 points; P < .001), executive function (2.13 points higher; 95% CI, 1.98 to 2.29 points; P < .001), and memory (1.89 points higher; 95% CI, 1.72 to 2.06 points; P < .001). Compared with men, women had significantly faster declines in global cognition (-0.07 points/y faster; 95% CI, -0.08 to -0.05 points/y; P < .001) and executive function (-0.06 points/y faster; 95% CI, -0.07 to -0.05 points/y; P < .001). Men and women had similar declines in memory (-0.004 points/y faster; 95% CI, -0.023 to 0.014; P = .61).

Conclusions And Relevance: The results of this cohort study suggest that women may have greater cognitive reserve but faster cognitive decline than men, which could contribute to sex differences in late-life dementia.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.0169DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7907956PMC
February 2021

Early to Midlife Smoking Trajectories and Cognitive Function in Middle-Aged US Adults: the CARDIA Study.

J Gen Intern Med 2021 Jan 26. Epub 2021 Jan 26.

Department of Psychiatry, University of California, San Francisco, Veterans Affairs Medical Center, San Francisco, CA, USA.

Background: Smoking starts in early adulthood and persists throughout the life course, but the association between these trajectories and midlife cognition remains unclear.

Objective: Determine the association between early to midlife smoking trajectories and midlife cognition.

Design: Prospective cohort study.

Participants: Participants were 3364 adults (mean age = 50.1 ± 3.6, 56% female, 46% Black) from the Coronary Artery Risk Development in Young Adults (CARDIA) study: 1638 ever smokers and 1726 never smokers.

Main Measures: Smoking trajectories were identified in latent class analysis among 1638 ever smokers using smoking measures every 2-5 years from baseline (age 18-30 in 1985-1986) through year 25 (2010-2011). Poor cognition was based on cognitive domain scores ≥ 1 SD below the mean on tests of processing speed (Digit Symbol Substitution Test), executive function (Stroop), and memory (Rey Auditory Verbal Learning Test) at year 25.

Results: Five smoking trajectories emerged over 25 years: quitters (19%), and minimal stable (40%), moderate stable (20%), heavy stable (15%), and heavy declining smokers (5%). Heavy stable smokers showed poor cognition on all 3 domains compared to never smoking (processing speed AOR = 2.22 95% CI 1.53-3.22; executive function AOR = 1.58 95% CI 1.05-2.36; memory AOR = 1.48 95% CI 1.05-2.10). Compared to never smoking, both heavy declining (AOR = 1.95 95% CI 1.06-3.68) and moderate stable smokers (AOR = 1.56 95% CI 1.11-2.19) exhibited slower processing speed, and heavy declining smokers additionally had poor executive function. For minimal stable smokers (processing speed AOR = 1.12 95% CI 0.85-1.51; executive function AOR = 0.97 95% CI 0.71-1.31; memory AOR = 1.21 95% CI 0.94-1.55) and quitters (processing speed AOR = 0.96 95% CI 0.63-1.48; executive function AOR = 0.98 95% CI 0.63-1.52; memory AOR = 0.97 95% CI 0.67-1.39), no association was observed.

Conclusions: The association between early to midlife smoking trajectories and midlife cognition was dose-dependent. Results underscore the cognitive health risk of moderate and heavy smoking and the potential benefits of quitting on cognition, even in midlife.
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http://dx.doi.org/10.1007/s11606-020-06450-5DOI Listing
January 2021

Agent Orange Exposure and Dementia Diagnosis in US Veterans of the Vietnam Era.

JAMA Neurol 2021 Apr;78(4):473-477

San Francisco Veterans Affairs Health Care System, San Francisco, California.

Importance: Agent Orange is a powerful herbicide that contains dioxin and was used during the Vietnam War. Although prior studies have found that Agent Orange exposure is associated with increased risk of a wide range of conditions, including neurologic disorders (eg, Parkinson disease), metabolic disorders (eg, type 2 diabetes), and systemic amyloidosis, the association between Agent Orange and dementia remains unclear.

Objective: To examine the association between Agent Orange exposure and incident dementia diagnosis in US veterans of the Vietnam era.

Design, Setting, And Participants: This cohort study included Veterans Health Administration data from October 1, 2001, and September 30, 2015, with up to 14 years of follow-up. Analyses were performed from July 2018 to October 2020. A 2% random sample of US veterans of the Vietnam era who received inpatient or outpatient Veterans Health Administration care, excluding those with dementia at baseline, those without follow-up visits, and those with unclear Agent Orange exposure status.

Exposures: Presumed Agent Orange exposure documented in electronic health record.

Main Outcomes And Measures: Fine-Gray competing risk models were used to compare the time to dementia diagnosis (with age as the time scale) for veterans with vs without presumed Agent Orange exposure (as per medical records), adjusting for demographic variables and medical and psychiatric comorbidities.

Results: The total sample was 511 189 individuals; after exclusions, 316 351 were included in analyses. Veterans were mostly male (n = 309 889 [98.0%]) and had a mean (SD) age of 62 (6.6) years; 38 121 (12.1%) had presumed Agent Orange exposure. Prevalence of most conditions, including Parkinson disease, diabetes, and amyloidosis, was similar at baseline among veterans with and without Agent Orange exposure. After adjusting for demographic variables and comorbidities, veterans exposed to Agent Orange were nearly twice as likely as those not exposed to receive a dementia diagnosis over a mean (SD) of 5.5 (3.8) years of follow-up (1918 of 38 121 [5.0%] vs 6886 of 278 230 [2.5%]; adjusted hazard ratio: 1.68 [95% CI, 1.59-1.77]). Veterans with Agent Orange exposure developed dementia at a mean of 1.25 years earlier (at a mean [SD] age of 67.5 [7.0] vs 68.8 [8.0] years).

Conclusions And Relevance: Veterans with Agent Orange exposure were nearly twice as likely to be diagnosed with dementia, even after adjusting for the competing risk of death, demographic variables, and medical and psychiatric comorbidities. Additional studies are needed to examine potential mechanisms underlying the association between Agent Orange exposure and dementia.
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http://dx.doi.org/10.1001/jamaneurol.2020.5011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7835948PMC
April 2021

Longitudinal Associations of Midlife Accelerometer Determined Sedentary Behavior and Physical Activity With Cognitive Function: The CARDIA Study.

J Am Heart Assoc 2021 02 20;10(3):e018350. Epub 2021 Jan 20.

University of California San Francisco CA.

Background To determine if accelerometer measured sedentary behavior (SED), light-intensity physical activity (LPA), and moderate-to-vigorous-intensity physical activity (MVPA) in midlife is prospectively associated with cognitive function. Methods and Results Participants were 1970 adults enrolled in the CARDIA (Coronary Artery Risk Development in Young Adults) study who wore an accelerometer in 2005 to 2006 (ages 38-50 years) and had cognitive function assessments completed 5 and/or 10 years later. SED, LPA, and MVPA were measured by an ActiGraph 7164 accelerometer. Cognitive function tests included the Digit Symbol Substitution Test, Rey Auditory Verbal Learning Test, and Stroop Test. Compositional isotemporal substitution analysis examined associations of SED, LPA, and MVPA with repeated measures of the cognitive function standardized scores. In men, statistical reallocation of 30 minutes of LPA with 30 minutes of MVPA resulted in an estimated difference of SD 0.07 (95% CI, 0.01-0.14), SD 0.09 (95% CI, 0.02-0.17), and SD -0.11 (95% CI, -0.19 to -0.04) in the Digit Symbol Substitution Test, Rey Auditory Verbal Learning Test, and Stroop scores, respectively, indicating better performance. Associations were similar when reallocating time in SED with MVPA, but results were less robust. Reallocation of time in SED with LPA resulted in an estimated difference of SD -0.05 (95% CI, -0.06 to -0.03), SD -0.03 (95% CI, -0.05 to -0.01), and SD 0.05 (95% CI, 0.03- 0.07) in the Digit Symbol Substitution Test, Rey Auditory Verbal Learning Test, and Stroop scores, respectively, indicating worse performance. Associations were largely nonsignificant among women. Conclusions Our findings support the idea that for men, higher-intensity activities (MVPA) may be necessary in midlife to observe beneficial associations with cognition.
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http://dx.doi.org/10.1161/JAHA.120.018350DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7955419PMC
February 2021

Increased risk of dementia in older female US veterans with alcohol use disorder.

Addiction 2021 Aug 3;116(8):2049-2055. Epub 2021 Feb 3.

Department of Psychiatry, University of California, San Francisco, CA, USA.

Aim: To determine whether alcohol use disorder (AUD) is associated with increased dementia risk among older women veterans.

Design: Cohort study.

Setting: United States.

Participants: Women veterans with AUD aged ≥ 55 years (n = 2207), receiving care from Veterans Health Administration medical centers from October 2004 to September 2015 with one or more follow-up visit and an age-matched sample of women veterans without AUD (n = 2207). Women at baseline with prevalent dementia or AUD in remission were excluded.

Measurements: AUD, substance use disorder (SUD), smoking, psychiatric (depression, anxiety, post-traumatic stress disorder, anxiety) and medical comorbidities (diabetes, hypertension, stroke, chronic obstructive pulmonary disorder, traumatic brain disorder) and dementia determined by the International Classification of Diseases, 9th revision, Clinical Modification codes. Cox proportional hazards models were used to determine the association between AUD and dementia risk during follow-up. Sensitivity analyses were performed by excluding women (n = 349) with comorbid SUD and by excluding women (n = 1568) currently smoking.

Findings: Veteran women had a mean [standard deviation (SD)] age of 65.0 (5.6) years at baseline. During follow-up (median 4 years, interquartile range: 2-6) 3.7% of women (n = 82) with AUD developed dementia compared with 1.1% (n = 24) without AUD (P < 0.001). After adjustment for demographics, medical and psychiatric conditions and accounting for different Veteran's Integrated Service Networks, the adjusted hazard ratio (aHR) for dementia was 3.12 (95% CI = 1.90-5.12) for women with AUD compared with women without AUD. After removing women with SUD (aHR = 3.53, 95% CI = 2.13-5.85) and women currently smoking (aHR = 3.80, 95% CI = 2.11-6.84), results were similar.

Conclusions: Alcohol use disorder among female US veterans aged more than 55 years appears to be associated with a more than threefold increase of dementia.
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http://dx.doi.org/10.1111/add.15416DOI Listing
August 2021

Breast Arterial Calcification Is Not Associated with Mild Cognitive Impairment or Incident All-Cause Dementia Among Postmenopausal Women: The MINERVA Study.

J Womens Health (Larchmt) 2021 Jun 7;30(6):848-856. Epub 2020 Dec 7.

Departments of Psychiatry and Neurology and Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California, USA.

Since vascular risk factors are implicated in cognitive decline, and breast arterial calcification (BAC) is related to vascular risk, we postulated that BAC may be associated with cognitive impairment and dementia. We used a multiethnic cohort of 3,913 asymptomatic women 60-79 years of age recruited after mammography screening at a large health plan in 2012-2015. A BAC mass score (mg) was derived from digital mammograms. Cognitive function was measured at baseline using the Montreal Cognitive Assessment (MoCA) and incident all-cause dementia ( = 49 events; median follow-up = 5.6 years) were ascertained with validated ICD-9 and ICD-10 codes. We used cross-sectional linear regression of MoCA scores on BAC, then multinomial logistic regression predicting mild cognitive impairment not progressing to dementia and incident all-cause dementia and, finally, Cox regression of incident all-cause dementia. No association by linear regression was found between MoCA scores and BAC presence in unadjusted or adjusted analysis. Women with severe (upper tertile) BAC had a MoCA score lower by 0.58 points (standard error [SE] = 0.18) relative to women with no BAC. However, this difference disappeared after multivariate adjustment. No significant associations were found in multinomial logistic regression for either BAC presence or gradation in unadjusted or adjusted analysis. No significant associations were found between BAC presence with incident all-cause dementia (fully adjusted hazard ratio = 0.74; 95% confidence interval: 0.39-1.39). Likewise, no significant association with incident all-cause dementia was noted for BAC gradation. Our results do not support the hypothesis that BAC presence or gradation may contribute to cognitive impairment or development of all-cause dementia.
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http://dx.doi.org/10.1089/jwh.2020.8372DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8217600PMC
June 2021

Vascular health across young adulthood and midlife cerebral autoregulation, gait, and cognition.

Alzheimers Dement 2021 05 7;17(5):745-754. Epub 2020 Dec 7.

Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.

Introduction: To test the association of vascular health (VH) across young adulthood with midlife dynamic cerebral autoregulation (dCA), gait, and cognition; and to test whether dCA is a modifying factor.

Methods: We studied 196 participants from the Coronary Artery Risk Development in Young Adults cohort who were followed over 30 years. VH was assessed at each visit according to American Heart Association recommendations. At year 30, dCA was measured using transcranial Doppler ultrasound and several gait and cognitive domains were assessed.

Results: Worse VH from baseline through year 7, but not at year 30, was associated with less efficient dCA (all P < .05). Worse VH at all visits was associated with slower gait speed, and at year 7 with worse executive and global cognition (all P < .05). The association of baseline VH and midlife gait, but not cognition, was moderated by dCA (interaction P < .05).

Conclusions: VH as early as young adulthood may influence midlife brain health, and dCA may modify this relationship.
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http://dx.doi.org/10.1002/alz.12246DOI Listing
May 2021

The necessity of diplomacy in brain health.

Lancet Neurol 2020 12;19(12):972-974

Global Brain Health Institute, University of California San Francisco, San Francisco, CA 94143, USA; Global Brain Health Institute, Trinity College Dublin, Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin 2, Ireland; Department of Psychiatry, University of Melbourne, Royal Melbourne Hospital, Melbourne, VIC, Australia; Deakin University, IMPACT SRC, School of Medicine, Geelong, VIC, Australia; Brainstorm Laboratory for Mental Health Innovation, Department of Psychiatry, Stanford University School of Medicine, Palo Alto, CA USA; Discipline of Psychiatry, School of Medicine, University of Adelaide, Adelaide, SA, Australia.

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http://dx.doi.org/10.1016/S1474-4422(20)30358-6DOI Listing
December 2020