Brenda L. Plassman

Low educational attainment is recognized as a modifiable risk factor for dementia. Despite the commonly accepted notion that greater educational attainment confers lower dementia risk, few family-based studies have investigated the causal bases for the association. Using data from seven twin samples from Sweden, Denmark, Australia, and the US participating in the IGEMS (Interplay of Genes and Environment in Multiple Studies) consortium ( N = 60,027, 10.92% with dementia), we tested whether twins who achieve higher education than their co-twins have lower risk of dementia. The primary analysis applied a multilevel between-within regression framework, supported by descriptive statistics of within-pair differences. Results confirmed an overall association between educational attainment and dementia risk, such that individuals with higher educational attainment had less likelihood of developing dementia (phenotypic regression coefficient = -0.68, p <.0001). Within twin pairs, however, twins who achieved greater education than their co-twins did not uniformly show lower dementia risk (within-family regression coefficient = -0.07, p =.0983, while between-family regression coefficient = -0.98, p <.0001). Taken together, the pattern of results shows that the effect of educational attainment on dementia risk is largely attributable to genetic influences in common to educational attainment and dementia, although there are also contributions from environmental influences shared between members of the same family. Results were similar in men and women. These findings add to the literature by using a co-twin control design to address possible reasons that low educational attainment is associated with greater dementia risk.

Background: Silicone wristbands can detect exposure to multiple chemicals. In the last decade, health studies have used them to assess environmental exposures, but few have included aging men, particularly those actively working with pesticides. Objective: To explore the feasibility, acceptability, and/or receptiveness of older adults to wear a wristband for multiple days while collecting other biomarkers (serum and urine). Additionally, we aimed to assess exposure differences among actively farming pesticide applicators versus non-farming older adults and examine correlations between pesticides and organophosphate ester flame retardants [OPEFR] detected in the wristbands with target serum/urine metabolites. Methods: Fifteen males age 70-plus in North Carolina; 10 farmers, pesticide applicators and 5 non-farmers with no reported pesticide use. Participants wore wristbands for 5 consecutive days 24/hours a day, provided a serum sample on day one and end-of-day urine samples on days 1, 3, and 5. Six pesticides and four OPEFR were measured in wristbands. Results: All participants were receptive to wristbands and wore them for the required time, were compliant in study procedures, and did not report any adverse reactions to the wristbands. In wristbands, atrazine (Geometric means (GM) of specific gravity-corrected levels=14.5 ng/g) and malathion (GM=21.8 ng/g) were detected only in farmers. wristbands GMs were higher in farmers than non-farmers for chlorpyrifos GM difference=408.8 ng/g, and trans-permethrin GM difference=569.2 ng/g. However, wristbands DDT GM was 1.8 ng/g higher in non-farmers than farmers. OPEFRs TCEP and TDCIPP GMs were higher among farmers while TCIPP and TPHP were higher among non-farmers. wristbands pesticide levels and urinary metabolite correlations were weak-to-moderate. A moderate correlation was observed between DDE in wristbands and DDE in serum (r _s =.44; p =0.20). Conclusion: Despite the short test time, wristbands detected multiple chemical exposures regardless of farming status. More research is required to understand the utility of wristbands in assessing pesticide exposures in older populations. Impact Statement: Silicone wristbands are inexpensive, easy to wear passive sampling devices able to capture multiple chemicals providing a snapshot of environmental exposures. Recent research supports wristbands as promising tools to capture flame retardant exposures, but more studies are needed to determine the efficacy of the wristbands for pesticide exposures in older occupational cohorts.

Background: Diverse racial/ethnic representation in scientific studies is crucial for generalizability of results and development of potentially effective treatments. Racially diverse registries with research ready individuals have the potential to fill this gap. However, despite having signed up as part of a research registry and being invited to participate in clinical trials, many do not participate. To better understand research participation, the NC Registry for Brain Health surveyed its members to identify the characteristics of those likely to participate in research studies, their views on research, expectations when joining the group, and impediments to participation.Method: The NC Registry for Brain Health has been state‐funded since 2018 with goals of increasing access for all to information and research opportunities in brain health. Focused recruitment to under‐served and under‐represented groups across the State occurs through community outreach events sponsored by a five member university network. An email survey was sent to the 5,946 Registry members enrolled as of October 15, 2021.Result: Approximately 10% (n = 576) responded to this anonymized survey. Most were older women with high levels of formal education (Table 1). Despite the Registry’s demographics of 28% African American enrollees, only 8% of the survey respondents self‐identified as African Americans. Most individuals joined the Registry for the joint purpose of getting involved in research and receiving information about brain health (75%). When asked to describe what “brain health research” means, most reported studies involving dementia risk factors and memory testing. All participants had been approached to get involved in studies, but only 60% recalled getting an email invitation. The biggest impediment noted for participating in studies was inconvenient appointment times. The participants also wanted more available studies and more information about the opportunities.Conclusion: This study suggests that most participants in the Registry are seeking to be informed about brain health and have access to research opportunities at times convenient with their schedules. There was an observed gap between African Americans enrolled in the research registry and those who participated in the survey. Addressing gaps in research involvement of under‐represented groups in research is necessary to achieve inclusive representative science.

Traumatic brain injury (TBI) is an established risk factor for dementia. However, the magnitude of risk is highly variable across studies. Identification of sub-populations at highest risk, with careful consideration of potential sources of bias, is urgently needed to guide public health policy and research into mechanisms and treatments. We conducted a systematic review and meta-analysis of risk of all-cause dementia after all-severity TBI. We assessed for effect of participant age and sex, veteran status, research methods, and region. The search window covered January 1990 to January 2019. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines. Thirty-two studies met inclusion criteria. Data were pooled using random effects models. Population attributable risk (PAR) of dementia due to TBI in the U.S. was calculated by sex and veteran status. Pooled risk ratio (RR) for dementia after TBI was 1.66 (95% confidence interval 1.42-1.93). Younger age, male sex, and studies from Asia were associated with significantly higher risk; veteran status was not. Risk of dementia associated with “head injury/trauma” was not significantly different from that associated with “TBI” diagnosis specifically. PAR of dementia due to TBI among U.S. veterans was twice that of the general U.S. population, largely due to the high prevalence of TBI exposure in the majority male veteran population. This meta-analysis found that TBI is associated with nearly 70% increased risk of dementia. Risk may be highest among younger adults, men, and cohorts in Asia. Efforts to prevent TBI and also to prevent post-TBI dementia are of high importance. Additionally, improved methods for diagnosing and tracking TBI on a public health level, such as national registries, may improve the quality and generalizability of future epidemiological studies investigating the association between TBI and dementia.

Introduction: Evidence from clinical samples and geographically limited population studies suggests that vascular health, diabetes and apolipoprotein ε4 (APOE) are associated with dementia. Methods: A population-based sample of 856 individuals aged 71 years or older from all contiguous regions of the United States received an extensive in-home clinical and neuropsychological assessment in 2001-2003. The relation of hypertension, diabetes, heart disease, stroke, medication usage, and APOE ε4 to dementia was modelled using adjusted multivariable logistic regression. Results: Treated stroke (odds ratio [OR] 3.8, 95% confidence interval [CI] 2.0, 7.2), untreated stroke (OR 3.5, 95% CI 1.7, 7.3), and APOE ε4 (OR 2.8, 95% CI 1.7, 4.5) all increased the odds of dementia. Treated hypertension was associated with lower odds of dementia (OR 0.5, 95% CI 0.3, 1.0). Diabetes and heart disease were not significantly associated with dementia. A significant interaction was observed between APOE ε4 and stroke (P = 0.001). Conclusions: Data from the first dementia study that is representative of the United States population suggest that stroke, the APOE ε4 allele and their interaction are strongly associated with dementia.

Aim: Little is known about the concordance rate in twins for dementia with Lewy bodies (DLB). The rate of agreement between clinical and pathological diagnoses for DLB is typically low, necessitating confirmation of the diagnosis neuropathologically. Methods: Participants were 17 twin pairs enrolled in the Duke Twins Study of Memory in Aging in which at least one member of the pair had an autopsy confirmed diagnosis of DLB, Alzheimer’s disease (AD) with Lewy bodies or frontotemporal dementia with Lewy bodies. The characteristics of those with dementia were assessed and rates of concordance for pathological confirmed dementia were examined. Results: Four monozygotic twin pairs had a proband with neuropathologically confirmed pure DLB; all remained discordant for dementia for periods up to 16 years or more. Five of 13 pairs in which the proband had AD plus DLB were concordant for dementia but only one pair was concordant for AD plus DLB, while the co-twins in the other four pairs had other types of dementia. Conclusions: The present study indicates that even among twins, a diagnosis of DLB in one twin does not predict the same diagnosis in the other twin. Neuropathological discordance in type of dementia among monozygotic pairs hints at environmental or epigenetic factors playing a role in Lewy body pathology.