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Background: Past research suggests that ethnoracialized groups differ in their willingness to engage in preclinical Alzheimer's disease (AD) research overall. Studies indicated that participation willingness was affected by attitudes toward research and perceived invasiveness of biomarker collection techniques. However, comparative quantitative studies are few, and minoritized groups are under-included. Objective: In a cross-sectional online survey, we sought to explore community-based adults' willingness to engage in preclinical AD biomarker testing, comparing their attitudes about research and different types of biomarker procedures. Methods: We conducted an online survey with a diverse group of participants. African American (AA), American Indian/Alaska Native (AI/AN), Latinx (LTX), and Non-Hispanic White (NHW) adults aged 26–90 were asked about their research attitudes, biomarkers, and willingness to participate in specific biomarker test procedures (i.e., brain imaging via PET scanning, blood draws, and cerebrospinal fluid collection by lumbar puncture). We also assessed participants' perceived safety, burden, and distress for each of the three biomarker collection methods. To understand the association between research willingness and ethnoracial identity, we ran linear regression models for each procedure, adjusting for age, gender, educational attainment, and attitudes toward research. Results: The AA group expressed greater willingness to engage in biomarker testing involving blood draws than the NHW group. The AI/AN group was significantly less willing to undergo lumbar puncture than the NHW group; this difference remained after adjusting for various sociodemographic factors and research attitudes. Conclusions: Respondents' willingness to engage in preclinical AD biomarker research was affected by their perceptions about the testing collection procedure. [ABSTRACT FROM AUTHOR]

Previous research assessing consequences of interpregnancy intervals (IPIs) on child development is mixed. Utilizing a population-based US sample (n = 5339), we first estimate the associations between background characteristics (e.g. sociodemographic and maternal characteristics) and short ([less than or equal to]1 year) and long (>3 years) IPI. Then, we estimate associations between IPI and birth outcomes, infant temperament, cognitive ability, and externalizing symptoms. Several background characteristics, such as maternal age at childbearing and previous pregnancy loss, were associated with IPI, indicating research on the putative effects of IPI must account for background characteristics. After covariate adjustment, short IPI was associated with poorer foetal growth and long IPI was associated with lower infant activity level; however, associations between short and long IPI and the other outcomes were neither large nor statistically significant. These findings indicate that rather than intervening to modify IPI, at-risk families may benefit from interventions aimed at other modifiable risk factors.

Background: Each year, millions of Americans experience mild traumatic brain injury (mTBI). Current research on the long‐term effects of mTBI vary considerably. Several mechanisms linking mTBI to dementia have been proposed including amyloid plaque formation and cerebrovascular injury following mTBI. Veterans have higher rates of mTBI than non‐Veterans. As efforts to increase Veteran enrollment in clinical trials and studies related to Alzheimer disease expand, it is critical to understand the potential impact of mTBI on cognitive ability and factors related to risk for AD. This study leveraged two cohorts to examine the association between history of mTBI and white matter hyperintensity lesion volume (WMLV), CSF pTau181, total tau, and Aβ42, and cognitive ability. Method: The sample comprises, N = 131 VA eligible Veterans without memory impairment enrolled in the Brain Amyloid and Vascular Effects of Eicosapentaenoic Acid (BRAVE) clinical trial (NCT02719327) and N = 320 participants in the Wisconsin ADRC clinical core, including n = 36 identified as Veterans. BRAVE participants reported if they had experienced symptoms of mTBI (e.g. loss of consciousness, dizziness, headache). ADRC participants indicated if they had a recent or remote mTBI; participants with a recent mTBI were excluded (n = 6). CSF samples were assayed using elecsys® beta‐Amyloid(1_42) CSF II, phopho‐Tau (181P), and Total tau assays (Roche Diagnostics International, Switzerland) and log‐transfomed prior to analyses. WMHLV adjusted for TIV was binarized to WMH presence or absence. Separate Preclinical Alzheimer's Cognitive Composite scores were created for BRAVE and were analyzed separately. Regression models included gender, age at study visit, clinical status and education level (PACC only) as covariates. Result: Demographics and study outcomes stratified by cohort and Veteran status are shown in Table 1 and 2. Veterans had higher rates of mTBI than non‐Veterans. History of mild TBI status was unrelated to study outcomes (see Figure 1; WMH presence: p =.06; CSF biomarkers: ps =.50 to.88; BRAVE‐PACC: p =.15, ADRC‐PACC, p =.48). Conclusion: History of mild TBI had no long‐term impact on cerebrovascular dysfunction, AD biomarkers or baseline cognitive performance. Further analyses will explore severity of TBI (with or without loss of consciousness) on study outcomes as well asexamine the impact of mTBIon change in cognitive performance and biomarkers of neuroinflammation. [ABSTRACT FROM AUTHOR]

Background: Mild behavioral impairment (MBI) is associated with all‐cause dementia. Little is known about MBI's effects on cognitive function among individuals in earlier disease stages, particularly in racially diverse samples. We examined relationships between MBI and cognitive decline in a richly characterized sample of white and African American (AA) older‐middle aged adults. AA participants were enrolled in African Americans Fighting Alzheimer's in Midlife (AA‐FAIM), an ancillary study of the Wisconsin Disease Research Center's (WADRC) Clinical Core. Method: Analytic sample included participants without dementia, with ≥1 study visits and measures of cognitive/clinical function. A baseline MBI rating (present/absent) was derived using study partners' report of neuropsychiatric symptoms at two consecutive visits, (i.e., two consecutive positive MBI scores = MBI present). Cognitive outcomes included measures of speed, mental flexibility and memory. Result: Table 1 provides characteristics by MBI status for white (N = 450), AA (N = 100), and other underrepresented group (URG) (N = 34) participants. In the full sample, baseline MBI significantly moderated cognitive trajectory on Trails B, though not on any other tasks. Participants with MBI displayed worse trajectory of decline on Trails B relative to those without MBI (Figure 1). Additionally, MBI at baseline significantly predicted progression to cognitive impairment CDR >0 (HR est: 2.84; HR 95% CI: 1.68 — 4.81; p = 0.0001) (Figure 2). Stratified analysis in a smaller AA subgroup showed a similar pattern but was not significant. Conclusion: MBI associated with more adverse cognitive trajectory and predicted incident cognitive decline in older, middle aged participants without dementia. Our findings highlight the importance of identifying MBI as a possible target for intervention in early disease stages. A fifth of our sample (21.5%) identified as Black/URG. Still, ongoing work in inclusive cohorts is needed to better understand MBI in under‐represented groups. [ABSTRACT FROM AUTHOR]

Background: In cognitively unimpaired (CU) older adults, the presence of a subjective cognitive decline (SCD) combined with evidence of abnormal b‐amyloid (Ab) is proposed as stage 2 of Alzheimer's disease (AD) by the NIA‐AA framework (Jack et al., 2018). However, the associations found between SCD and preclinical AD are inconsistent across studies, highlighting the importance of better understanding which specific SCD features are associated with either Ab or tau burden. Methods: The present study includes cross‐sectional data from 9 independent cohorts with a total of 7217 CU older adults (57% female), aged 69.34 (1.20) years, recruited from general and memory‐clinic populations. Ab and tau biomarkers were measured by positron emission tomography (PET) or cerebrospinal fluid (CSF). Using established cut‐offs, 28% of participants were Aβ+, and 12% were Aβ+T+ (approximately one‐third of the sample had available tau data). We examined four SCD‐plus criteria as well as the mean number of SCD criteria met (i.e., mean SCD‐severity) in relation to both biomarker status and levels in logistic/linear regressions adjusted for age and sex for each cohort. Summary statistics were extracted for meta‐analyses. Results: The overall frequency of stage 2 AD varied from 7‐16% [4‐26%] according to each SCD‐plus criterion endorsement. Only 1‐5% [0‐8%] of participants meeting the SCD‐plus criteria also had both high Aβ and tau burden (Fig.1). The presence of self‐reported memory decline (SMD), an associated concern/worry, and a higher mean SCD‐severity were each associated with high Ab (status and continuous). Only the latter was associated with high tau status (Fig.2). Onset of SCD within the last 5 years, and feeling of worse performance than same‐age peers, were not associated with AD biomarkers at a Bonferroni‐corrected threshold. Conclusions: Our results suggest that widespread endorsement of multiple SCD features is more powerful than a single criterion alone in identifying both Aβ and tau in CU older adults. We found that the isolated SCD criterion was particularly sensitive to elevated Aβ, even after adjustment for tau, supporting the power of SCD as a very early behavioral marker of preclinical AD. [ABSTRACT FROM AUTHOR]

Background: The National Institutes of Health Toolbox for Assessment of Neurological and Behavioral Function (NIHTB) was developed to address the need for a brief yet comprehensive instrument to facilitate more uniform assessment in large‐scale research studies. Here, we investigated whether the cognitive measures of the NIHTB detect cognitive decline in biomarker‐confirmed Alzheimer's disease (AD). Method: We used data from N = 178 participants (age 76.5±8; 53% female) from the Assessing Reliable Measurement in Alzheimer's Disease and Cognitive Aging (ARMADA) study, who were recruited across nine research centers in the United States and had amyloid PET or amyloid‐beta42/tau CSF data available within two years of their baseline NIHTB assessment. Participants' cognitive status (normal (CN) or impaired (CI), based on standardized protocols) and amyloid status (Aβ‐/Aβ+, based on site‐specific cut‐offs) were combined to create three groups: healthy controls (CN Aβ‐, n = 113), asymptomatic AD (CN Aβ+, n = 24), and prodromal‐to‐mild AD (CI Aβ+, n = 34) (Table 1). The NIHTB was assessed at baseline, 12 and 24 months and includes five tasks measuring fluid cognition (attention, executive functions, processing speed, working memory, and episodic memory) and two tasks reflecting crystallized cognition (oral word reading and auditory word comprehension). Linear mixed‐effect models correcting for age, sex, and education were used to examine cross‐sectional and longitudinal NIHTB scores in the three study groups. Result: Compared to healthy controls, the prodromal‐to‐mild AD group had lower baseline scores on most NIHTB fluid tasks (Flanker Inhibitory Control and Attention, Dimensional Change Card Sort, Picture Sequence Memory, List Sort Working Memory) and showed accelerated decline over 12‐24 months on Pattern Comparison Processing Speed, List Sorting Working Memory and Picture Vocabulary (Figure 1). None of the NIHTB tasks detected cross‐sectional or longitudinal differences in the asymptomatic Aβ+ group compared to healthy controls over the course of this study. Conclusion: The NIHTB detects cross‐sectional impairment in episodic memory, attention, executive functions and working memory and longitudinal change in processing speed, working memory and auditory word comprehension in prodromal‐to‐mild AD. These findings further support the use of the NIHTB in AD research, but also imply that the optimal NIHTB composite to detect cognitive decline may differ across AD clinical stages. [ABSTRACT FROM AUTHOR]

Objective: Biomarkers of Alzheimer disease vary between groups of self‐identified Black and White individuals in some studies. This study examined whether the relationships between biomarkers or between biomarkers and cognitive measures varied by racialized groups. Methods: Cerebrospinal fluid (CSF), amyloid positron emission tomography (PET), and magnetic resonance imaging measures were harmonized across four studies of memory and aging. Spearman correlations between biomarkers and between biomarkers and cognitive measures were calculated within each racialized group, then compared between groups by standard normal tests after Fisher's Z‐transformations. Results: The harmonized dataset included at least one biomarker measurement from 495 Black and 2,600 White participants. The mean age was similar between racialized groups. However, Black participants were less likely to have cognitive impairment (28% vs 36%) and had less abnormality of some CSF biomarkers including CSF Aβ42/40, total tau, p‐tau181, and neurofilament light. CSF Aβ42/40 was negatively correlated with total tau and p‐tau181 in both groups, but at a smaller magnitude in Black individuals. CSF Aβ42/40, total tau, and p‐tau181 had weaker correlations with cognitive measures, especially episodic memory, in Black than White participants. Correlations of amyloid measures between CSF (Aβ42/40, Aβ42) and PET imaging were also weaker in Black than White participants. Importantly, no differences based on race were found in correlations between different imaging biomarkers, or in correlations between imaging biomarkers and cognitive measures. Interpretation: Relationships between CSF biomarkers but not imaging biomarkers varied by racialized groups. Imaging biomarkers performed more consistently across racialized groups in associations with cognitive measures. ANN NEUROL 2024;95:495–506 [ABSTRACT FROM AUTHOR]

Background: Prediction of antisocial behavior is important, given its adverse impact on both the individuals engaging in antisocial behavior and society. Additional research identifying early predictors of future antisocial behavior, or antisocial propensity, is needed. The present study tested the hypothesis that both concern for others and active disregard for others in distress in toddlers and young children predict antisocial behavior during middle childhood and adolescence. Methods: A representative sample of same-sex twins ("N" = 956) recruited in Colorado was examined. Mother-rated and researcher-observed concern and disregard for others assessed at age 14-36 months were examined as predictors of parent- (age 4-12), teacher- (age 7-12), and self-reported (age 17) antisocial behavior. Results: Observed disregard for others predicted antisocial behavior assessed by three different informants (parents, teachers, and self), including antisocial behavior assessed 14 years later. It also predicted a higher order antisocial behavior factor (beta = 0.58, p less than 0.01) after controlling for observed concern for others. Mother-rated disregard for others predicted parent-reported antisocial behavior. Contrary to predictions, neither mother-rated nor observed concern for others inversely predicted antisocial behavior. Results of twin analyses suggested that the covariation between observed disregard for others and antisocial behavior was due to shared environmental influences. Conclusions: Disregard for others in toddlerhood/early childhood is a strong predictor of antisocial behavior in middle childhood and adolescence. The results suggest the potential need for early assessment of disregard for others and the development of potential interventions. (Contains 2 figures, 1 table, and 2 footnotes.)