New articles from Prof. Kristine Yaffe, our Associate Editor

Our staff editors continue to share exciting, interesting, and thought-provoking reading material in the recommended articles series.

This week, we would like to share several latest articles from Prof. Kristine Yaffe, our Associate Editor.

Title: The Health & Aging Brain among Latino Elders (HABLE) study methods and participant characteristics
Authors: Sid E. O’Bryant, Leigh A. Johnson, Robert C. Barber, Meredith N. Braskie, Bradley Christian, James R. Hall, Nalini Hazra, Kevin King, Deydeep Kothapalli, Stephanie Large, David Mason, Elizabeth Matsiyevskiy, Roderick McColl, Rajesh Nandy, Raymond Palmer, Melissa Petersen, Nicole Philips, Robert A. Rissman, Yonggang Shi, Arthur W. Toga, Raul Vintimilla, Rocky Vig, Fan Zhang, Kristine Yaffe, for the HABLE Study Team
Type: Research Article from Alzheimer’s & Dementia
Abstract:
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.
Access this article: https://doi.org/10.1002/dad2.12202

Title: Sex Differences in Cognitive Decline Among US Adults
Authors: Deborah A. Levine, Alden L. Gross, Emily M. Briceño, Nicholas Tilton, Bruno J. Giordani, Jeremy B. Sussman, Rodney A. Hayward, James F. Burke, Stephanie Hingtgen, Mitchell S. V. Elkind, Jennifer J. Manly, Rebecca F. Gottesman, Darrell J. Gaskin, Stephen Sidney, Ralph L. Sacco, Sarah E. Tom, Clinton B. Wright, Kristine Yaffe, Andrzej T. Galecki
Type: Original Investigation of Neurology
Abstract:
Importance
Sex differences in dementia risk are unclear, but some studies have found greater risk for women.
Objective
To determine associations between sex and cognitive decline in order to better understand sex differences in dementia risk.
Design, Setting, and Participants
This cohort study used pooled analysis of individual participant data from 5 cohort studies for years 1971 to 2017: Atherosclerosis Risk in Communities Study, Coronary Artery Risk Development in Young Adults Study, Cardiovascular Health Study, Framingham Offspring Study, and Northern Manhattan Study. Linear mixed-effects models were used to estimate changes in each continuous cognitive outcome over time by sex. Data analysis was completed from March 2019 to October 2020.
Exposure
Sex.
Main Outcomes and Measures
The primary outcome was change in global cognition. Secondary outcomes were change in memory and executive function. Outcomes were standardized as t scores (mean [SD], 50 [10]); a 1-point difference represents a 0.1-SD difference in cognition.
Results
Among 34 349 participants, 26 088 who self-reported Black or White race, were free of stroke and dementia, and had covariate data at or before the first cognitive assessment were included for analysis. Median (interquartile range) follow-up was 7.9 (5.3-20.5) years. There were 11 775 (44.7%) men (median [interquartile range] age, 58 [51-66] years at first cognitive assessment; 2229 [18.9%] Black) and 14 313 women (median [interquartile range] age, 58 [51-67] years at first cognitive assessment; 3636 [25.4%] Black). Women had significantly higher baseline performance than men in global cognition (2.20 points higher; 95% CI, 2.04 to 2.35 points; P < .001), executive function (2.13 points higher; 95% CI, 1.98 to 2.29 points; P < .001), and memory (1.89 points higher; 95% CI, 1.72 to 2.06 points; P < .001). Compared with men, women had significantly faster declines in global cognition (−0.07 points/y faster; 95% CI, −0.08 to −0.05 points/y; P < .001) and executive function (−0.06 points/y faster; 95% CI, −0.07 to −0.05 points/y; P < .001). Men and women had similar declines in memory (−0.004 points/y faster; 95% CI, −0.023 to 0.014; P = .61).
Conclusions and Relevance
The results of this cohort study suggest that women may have greater cognitive reserve but faster cognitive decline than men, which could contribute to sex differences in late-life dementia.
Access this article: https://doi.org/10.1001/jamanetworkopen.2021.0169

Title: Phenotyping the Spectrum of Traumatic Brain Injury: A Review and Pathway to Standardization
Authors: Mary Jo Pugh, Eamonn Kennedy, Eric M. Prager, Jeffrey Humpherys, Kristen Dams-O’Connor, Dallas Hack, Mary Katherine McCafferty, Jessica Wolfe, Kristine Yaffe, Michael McCrea, Adam R. Ferguson, Lee Lancashire, Jamshid Ghajar, Angela Lumba-Brown
Type: Review of Journal of Neurotrauma
Abstract:
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.
Access this article: https://doi.org/10.1089/neu.2021.0059

Title: COllaborative Neuropathology NEtwork Characterizing ouTcomes of TBI (CONNECT-TBI)
Authors: Douglas H. Smith, Jean-Pierre Dollé, Kamar E. Ameen-Ali, Abigail Bretzin, Etty Cortes, John F. Crary, Kristen Dams-O’Connor, Ramon Diaz-Arrastia, Brian L. Edlow, Rebecca Folkerth, Lili-Naz Hazrati, Sidney R. Hinds, Diego Iacono, Victoria E. Johnson, C. Dirk Keene, Julia Kofler, Gabor G. Kovacs, Edward B. Lee, Geoffrey Manley, David Meaney, Thomas Montine, David O. Okonkwo, Daniel P. Perl, John Q. Trojanowski, Douglas J. Wiebe, Kristine Yaffe, Thomas McCabe, William Stewart
Type: Methodology article of Acta Neuropathologica Communications
Abstract:
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.
Access this article: https://doi.org/10.1186/s40478-021-01122-9

Title: Epidemiology of Chronic Effects of Traumatic Brain Injury
Authors: Juliet Haarbauer-Krupa, Mary Jo Pugh, Eric M Prager, Nicole Harmon, Jessica Wolfe, Kristine Yaffe
Type: Review of Journal of Neurotrauma
Abstract:
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 person and their family. Factors associated with an increased likelihood of negative TBI outcomes include not only characteristics of the injury and injury mechanism, but also the person'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, sex, and environment on TBI outcomes. By identifying how epidemiological factors contribute to TBI outcomes in different groups of persons and potentially impact differential disease progression, we can guide investigators and clinicians toward more-precise patient diagnosis, along with tailored management, and improve clinical trial designs, data evaluation, and patient selection criteria.
Access this article: https://doi.org/10.1089/neu.2021.0062

Title: Sleep Timing and Risk of Dementia Among the Chinese Elderly in an Urban Community: The Shanghai Aging Study
Authors: Xiantao Li, Ding Ding, Qianhua Zhao, Wanqing Wu, Zhenxu Xiao, Jianfeng Luo, Kristine Yaffe, Yue Leng
Type: Original Research Article of Front Neurol
Abstract:
Background
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.
Methods
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.
Results
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.
Conclusion
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.
Access this article: https://doi.org/10.3389/fneur.2021.629507

Title: Longitudinal Associations of Midlife Accelerometer Determined Sedentary Behavior and Physical Activity With Cognitive Function: The CARDIA Study
Authors: Kara M. Whitaker, Dong Zhang, Kelley Pettee Gabriel, Monica Ahrens, Barbara Sternfeld, Stephen Sidney, David R. JacobsJr, Priya Palta, Kristine Yaffe
Type: Research Article of Journal of the American Heart Association
Abstract:
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.
Access this article: https://doi.org/10.1161/JAHA.120.018350