Evidence suggests that risk factors for Alzheimer’s disease and related dementias (ADRD) are at least partially modifiable, and that lifestyle risk accumulates as we age. However, the prevalence and impact of lifestyle-related risk factors in young adulthood (i.e., 18–39 years) remain poorly understood, with some risk factors that are developed in early adulthood being difficult to remove and reverse at midlife. The Next Generation (NextGen) Brain Health Survey is the first of its kind to be designed specifically for young adults, with the aim of exploring attitudes, understanding and exposure to ADRD risk and protective factors in this life stage. The NextGen survey is an international, cross-sectional survey of young adults aged 18–39 years. The survey was developed in three phases with ongoing input from public advisors (i.e., young adults from Europe, North America, and Africa). First, we adapted items from existing literature for the target population. Second, we conducted focus groups with young adults to review the items and explore new themes. Third, we piloted the survey in an international network, including brain health researchers, clinicians, and advocacy groups. Feedback was integrated to create the finalized survey. The NextGen survey is conducted online and made available to individuals aged 18–39 years internationally. Results will contribute new knowledge about young adults and ADRD risk exposure before mid-life, including much-needed evidence in populations that are traditionally under-represented in research. Findings will help identify mediators and modifiers of associations between knowledge, attitudes, and risk exposure, and provide the basis for comparison with middle-aged and older populations.

ImportanceTraumatic brain injuries (TBI) represent an important, potentially modifiable risk factor for dementia. Despite frequently observed vascular imaging changes in individuals with TBI, the relationships between TBI-associated changes in brain imaging and clinical outcomes have largely been overlooked in community cases of TBI.ObjectiveTo assess whether TBI are associated with and interact with midlife changes in neuroimaging and clinical features in otherwise healthy individuals.Design, Setting, and ParticipantsThis cross-sectional analysis used baseline data from the PREVENT Dementia program collected across 5 sites in the UK and Ireland between 2014 and 2020. Eligible participants were cognitively healthy midlife adults aged between 40 and 59 years. Data were analyzed between January 2023 and April 2024.ExposureLifetime TBI history was assessed using the Brain Injury Screening Questionnaire.Main Outcomes and MeasuresCerebral microbleeds and other markers of cerebral small vessel disease (white matter hyperintensities [WMH], lacunes, perivascular spaces) were assessed on 3T magnetic resonance imaging. Clinical measures were cognition, sleep, depression, gait, and cardiovascular disease (CVD) risk, assessed using Computerized Assessment of Information Processing (COGNITO), Pittsburgh Sleep Quality Index, Center for Epidemiologic Studies Depression Scale, clinical interviews, and the Framingham Risk Score, respectively.ResultsOf 617 participants (median [IQR] age, 52 [47-56] years; 380 female [61.6%]), 223 (36.1%) had a history of TBI. TBI was associated with higher microbleed count (β = 0.10; 95% CI, 0.01-0.18; P = .03), with a dose-response association observed with increasing number of TBI events (β = 0.05; 95% CI, 0.01-0.09; P = .03). Conversely, TBI was not associated with other measures of small vessel disease, including WMH. Furthermore, TBI moderated microbleed associations with vascular risk factors and clinical outcomes, such that associations were present only in the absence of TBI. Importantly, observations held when analyses were restricted to individuals reporting only mild TBI.Conclusions and RelevanceIn this cross-sectional study of healthy middle-aged adults, detectable changes in brain imaging and clinical features were associated with remote, even mild, TBI in the general population. The potential contribution of vascular injury to TBI-related neurodegeneration presents promising avenues to identify potential targets, with findings highlighting the need to reduce TBI through early intervention and prevention in both clinical care and policymaking.

BackgroundAutistic adults have high risk of mental ill-health and some available interventions have been associated with increased psychiatric diagnoses. Understanding prevalence of psychiatric diagnoses is important to inform the development of individualised treatment and support for autistic adults which have been identified as a research priority by the autistic community. Interventions require to be evaluated both in terms of effectiveness and regarding their acceptability to the autistic community. ObjectiveThis rapid review identified the prevalence of psychiatric disorders in autistic adults, then systematic reviews of interventions aimed at supporting autistic adults were examined. A rapid review of prevalence studies was completed concurrently with an umbrella review of interventions. Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines were followed, including protocol registration (PROSPERO#CRD42021283570). Data sourcesMEDLINE, CINAHL, PsycINFO, and Cochrane Database of Systematic Reviews. Study eligibility criteriaEnglish language; published 2011-2022; primary studies describing prevalence of psychiatric conditions in autistic adults; or systematic reviews evaluating interventions for autistic adults. Appraisal and synthesisBias was assessed using the Prevalence Critical Appraisal Instrument and AMSTAR2. Prevalence was grouped according to psychiatric diagnosis. Interventions were grouped into pharmacological, employment, psychological or mixed therapies. Strength of evidence for interventions was assessed using GRADE (Grading of Recommendations, Assessment, Development and Evaluation). Autistic researchers within the team supported interpretation. ResultsTwenty prevalence studies were identified. Many included small sample sizes or failed to compare their sample group with the general population reducing validity. Prevalence of psychiatric diagnoses was variable with prevalence of any psychiatric diagnosis ranging from 15.4% to 79%. Heterogeneity was associated with age, diagnosis method, sampling methods, and country. Thirty-two systematic reviews of interventions were identified. Four reviews were high quality, four were moderate, five were low and nineteen critically low, indicating bias. Following synthesis, no intervention was rated as 'evidence based.' Acceptability of interventions to autistic adults and priorities of autistic adults were often not considered. ConclusionsThere is some understanding of the scope of mental ill-health in autism, but interventions are not tailored to the needs of autistic adults, not evidence based, and may focus on promoting neurotypical behaviours rather than the priorities of autistic people.

Background: Evidence suggests that risk factors for Alzheimer’s disease and related dementias (ADRD) are at least partially modifiable, and that lifestyle risk accumulates as we age. However, the prevalence and impact of lifestyle-related risk factors in young adulthood (i.e., 18-39 years) remain poorly understood, with some risk factors that are developed in early adulthood being difficult to remove and reverse at midlife. The Next Generation (NextGen) brain health survey is the first of its kind to be designed specifically for young adults, with the aim of exploring attitudes, understanding and exposure to ADRD risk and protective factors in this life stage.Methods: The NextGen survey is an international, cross-sectional survey of young adults aged 18-39 years. The survey was developed in three phases with ongoing input from public advisors (i.e., young adults from Europe, North America, and Africa). First, we adapted items from existing literature for the target population. Second, we conducted focus groups with young adults to review the items and explore new themes. Third, we piloted the survey in an international network, including brain health researchers, clinicians, and advocacy groups. Feedback was integrated to create the finalized survey.Discussion: The NextGen survey will be conducted online and made available to individuals aged 18-39 years internationally. Results will contribute new knowledge about young adults and ADRD risk exposure before mid-life, including much-needed evidence in populations that are traditionally under-represented in research. Findings will also help to identify mediators and modifiers of associations between knowledge, attitudes, and risk exposure, and provide the basis for comparison with middle-aged and older populations.

Introduction Digital cognitive assessments are gathering importance for the decentralized remote clinical trials of the future. Before including such assessments in clinical trials, they must be tested to confirm feasibility and acceptability with the intended participant group. This study presents usability and acceptability data from the Speech on the Phone Assessment (SPeAk) study. Methods Participants ( N = 68, mean age 70.43 years, 52.9% male) provided demographic data and completed baseline and 3-month follow-up phone based assessments. The baseline visit was administered by a trained researcher and included a spontaneous speech assessment and a brief cognitive battery (immediate and delayed recall, digit span, and verbal fluency). The follow-up visit repeated the cognitive battery which was administered by an automatic phone bot. Participants were randomized to receive their cognitive test results acer the final or acer each study visit. Participants completed acceptability questionnaires electronically acer each study visit. Results There was excellent retention (98.5%), few technical issues ( n = 5), and good interrater reliability. Participants rated the assessment as acceptable, confirming the ease of use of the technology and their comfort in completing cognitive tasks on the phone. Participants generally reported feeling happy to receive the results of their cognitive tests, and this disclosure did not cause participants to feel worried. Discussion The results from this usability and acceptability analysis suggest that completing this brief battery of cognitive tests via a telephone call is both acceptable and feasible in a midlife-to-older adult population in the United Kingdom, living at risk for Alzheimer's disease.

Evidence suggests that the early detection and management of modifiable risk factors can reduce, or partially prevent, incidence of neurodegenerative diseases. While there is consensus that risk factors should be addressed as early as possible, research has largely focused on childhood or mid- and later-life. As a result, there is a significant gap in our understanding of risk (and protective) factors in younger adulthood, as well as attitudes towards brain health in this group. The PREVENT Next Generation (PNG) study builds on the PREVENT Dementia project to investigate risk and protective factors in 18-40 year olds. The first phase of the PNG study will establish a foundational understanding of knowledge and attitudes towards brain health and risk reduction among adults aged 18-40 years. We will conduct focus groups with adults aged 18-40 years with and without a family history of neurodegenerative disease (n = 10 per group). Participants will be recruited via links with volunteer and community centre enterprises in the UK. To ensure inclusion of equitable perspectives, we will emphasise recruitment of diverse populations, including racialized and neurodiverse communities, and those with lower socioeconomic status. Focus groups will be recorded and transcribed. Data will be analysed using thematic analyses. Themes identified will be used to inform the next phase of the PNG study, which is to develop and distribute an online survey about brain health to an international sample of adults aged 18-40 years. Survey findings will inform the development of a large cohort study aimed at identifying biological, psychological and lifestyle factors that influence brain health in adults up to mid-life.

There is growing interest in the development of speech markers as novel, non-invasive biomarkers of early Alzheimer’s disease (AD). Before including such speech assessments in clinical trials, the technology must be tested to confirm feasibility of administration and acceptability with the target population to ensure future engagement. This study aimed to assess feasibility and acceptability in an at-risk population receiving automated administration of cognitive tasks over the telephone during the Speech on the Phone Assessment (SPeAk) study [35]. A second goal of the study was to assess participant acceptability of receiving cognitive test results - an important consideration for psychological safety. Participants (n = 68, mean age 70.43 years, 52.9% male) completed a baseline – administered by a trained researcher - and three month follow up visit – administered by an automated phonebot. Tasks included a spontaneous speech assessment and cognitive battery (immediate and delayed recall, digit span and verbal fluency). Participants were randomized to receive their cognitive test results after the final or after each study visit. Participants completed acceptability questionnaires electronically after each study visit. Retention was high (98.5%), with few technical issues (n = 6.7%), there was good inter rater reliability, and test scores were similar when administered by phonebot compared to human administrator in most subtests. A significant lower mean score in digit span was noted at follow up. These findings indicate general feasibility of the assessment. Participants preferred a human tester but rated the automated assessments as acceptable and would be happy to complete a phonebot assessment again, confirming the ease of use of the technology and comfort of completing cognitive tasks on the phone. Participants generally reported feeling happy to receive their cognitive tests results, and this disclosure did not cause participants to feel worried. The results from this usability and acceptability analysis suggests that completing this brief battery of cognitive tests via a telephone call is both acceptable and feasible in a midlife-to-older adult population in the UK, living at risk for AD.

Background Age-related changes in frailty have been documented in the literature. However, the evidence regarding changes in frailty prior to death is scarce. Understanding patterns of frailty progression as individuals approach death could inform care and potentially lead to interventions to improve individual’s well-being at the end of life. In this paper, we estimate the progression of frailty in the years prior to death. Methods Using data from 8,317 deceased participants of the Survey of Health, Ageing, and Retirement in Europe, we derived a 56-item Frailty Index. In a coordinated analysis of repeated measures of the frailty index in 14 countries, we fitted growth curve models to estimate trajectories of frailty as a function of distance to death controlling both the level and rate of frailty progression for age, sex, years to death and dementia diagnosis. Results Across all countries, frailty before death progressed linearly. In 12 of the 14 countries included in our analyses, women had higher levels of frailty close to the time of death, although they progressed at a slower rate than men (e.g. Switzerland (-0.008, SE = 0.003) and Spain (-0.004, SE = 0.002)). Older age at the time of death and incident dementia were associated with higher levels and increased rate of change in frailty, whilst higher education was associated with lower levels of frailty in the year preceding death (e.g. Denmark (0.000, SE = 0.001)). Conclusion The progression of frailty before death was linear. Our results suggest that interventions aimed at slowing frailty progression may need to be different for men and women. Further longitudinal research on individual patterns and changes of frailty is warranted to support the development of personalized care pathways at the end of life.

Cerebral microbleeds (CMB) are predictive of increased risk of dementia and stroke. Although commonly regarded as vascular markers, CMB can also stem from non-vascular aetiologies like head injuries or traumatic brain injury (TBI), although these are often overlooked. Therefore, this study examines CMB in relation to TBI, and their differential causes (i.e., risk factors) and consequences (i.e., clinical outcomes). In 605 healthy middle-aged adults (aged 40-59), CMB were rated on 3T susceptibility weighted imaging (SWI) MRI. TBI was assessed using the Brain Injury Screening Questionnaire (BISQ). TBI+ was defined as at least one blow to the head resulting in loss of consciousness (36.0%; n = 217). Memory was assessed using the COGNITO battery. Interaction analyses examined TBI*CMB interactions on hypertension, gait, and memory. Dominance analysis examined the relative contribution of TBI and vascular risk factors on predicting gait disturbances and memory. All models adjusted for sex, age, education, and study site. TBI was related to higher CMB count (t = 2.06, p = .039), and were more common in males (48.3%) than females (28.0%) (Χ2 = 28.91, p<.001). Number of TBI events related to poorer memory (t = -2.62, p = .009) and gait disturbances (t = 3.54, p<.001). Interaction analyses demonstrated that hypertension (t = -2.26, p = .024), memory (t = 2.70, p = .007) and gait (t = -2.29, p = .023) were less closely related to CMB in individuals with greater number of TBI events, relative to those with fewer TBIs. Regionally, these interactions were significant for lobar CMB, but not deep subcortical CMB. Within the TBI+ group, dominance analysis demonstrated that number of TBI events outperformed vascular risk factors in predicting gait disturbances (Contribution to R2: TBI = 52.9%, vascular risk = 32.6%) and memory (TBI = 28.7%, vascular risk = 1.2%). CMB appeared to differ aetiologically and clinically in those with and without TBI. In individuals with TBI, TBI itself was the dominant driver of clinical deficits. When compared to CMB of presumed vascular origins cross-sectionally, TBI-related CMB may appear to be less detrimental. However, longitudinal analysis is required to determine how TBI-related CMB differ in clinical trajectory and downstream pathologies. This study highlights the importance of differentiating between CMB of vascular origins vs. TBI in both research and clinically to aid prognosis and treatment decisions.

Introduction:Women are significantly more likely to develop Alzheimer's disease and related dementias (ADRD) than men. Suggestions to explain the sex differences in dementia incidence have included the influence of sex hormones with little attention paid to date as to the effect of hormonal contraception on brain health. The aim of this scoping review is to evaluate the current evidence base for associations between hormonal contraceptive use by women and non-binary people in early adulthood and brain health outcomes. Methods:A literature search was conducted using EMBASE, Medline and Google Scholar, using the keywords "hormonal contraception" OR "contraception" OR "contraceptive" AND "Alzheimer*" OR "Brain Health" OR "Dementia". Results:Eleven papers were identified for inclusion in the narrative synthesis. Studies recruited participants from the UK, USA, China, South Korea and Indonesia. Studies included data from women who were post-menopausal with retrospective data collection, with only one study contemporaneously collecting data from participants during the period of hormonal contraceptive use. Studies reported associations between hormonal contraceptive use and a lower risk of ADRD, particularly Alzheimer's disease (AD), better cognition and larger grey matter volume. Some studies reported stronger associations with longer duration of hormonal contraceptive use, however, results were inconsistent. Four studies reported no significant associations between hormonal contraceptive use and measures of brain health, including brain age on MRI scans and risk of AD diagnosis. Discussion:Further research is needed on young adults taking hormonal contraceptives, on different types of hormonal contraceptives (other than oral) and to explore intersections between sex, gender, race and ethnicity. Systematic Review Registration:https://doi.org/10.17605/OSF.IO/MVX63, identifier: OSF.io: 10.17605/OSF.IO/MVX63.

Traumatic brain injury (TBI) disrupts normal brain function and can lead to chronic symptoms of sleep disturbance, pain, irritability, and depression. Sleep disorders occur in 30-70% of individuals who have experienced TBI. Disturbed sleep impairs the recovery process and may exacerbate other issues that arise because of brain injury (e.g., headaches, depression). Noticeable benefits have been reported when sleep problems due to TBI are addressed and treated; for instance, treating post-TBI insomnia reduces the expression of inflammatory genes, potentially reducing ongoing neurological damage. In this review, we discuss twenty-four randomised clinical trials (RCT) published to date (August 2021), exploring interventions for sleep disturbances resulting from TBI. Treatment effects were observed for insomnia, circadian rhythm disorders, hypersomnia, and general sleep disturbance. However, the evidence remains limited and significant methodological issues are discussed with a recommendation for further research.

BACKGROUND AND OBJECTIVES:There is an urgent need to better understand frailty and its predisposing factors. Although numerous cross-sectional studies have identified various risk and protective factors of frailty, there is a limited understanding of longitudinal frailty progression. Furthermore, discrepancies in the methodologies of these studies hamper comparability of results. Here, we use a coordinated analytical approach in 5 independent cohorts to evaluate longitudinal trajectories of frailty and the effect of 3 previously identified critical risk factors: sex, age, and education. RESEARCH DESIGN AND METHODS:We derived a frailty index (FI) for 5 cohorts based on the accumulation of deficits approach. Four linear and quadratic growth curve models were fit in each cohort independently. Models were adjusted for sex/gender, age, years of education, and a sex/gender-by-age interaction term. RESULTS:Models describing linear progression of frailty best fit the data. Annual increases in FI ranged from 0.002 in the Invecchiare in Chianti cohort to 0.009 in the Longitudinal Aging Study Amsterdam (LASA). Women had consistently higher levels of frailty than men in all cohorts, ranging from an increase in the mean FI in women from 0.014 in the Health and Retirement Study cohort to 0.046 in the LASA cohort. However, the associations between sex/gender and rate of frailty progression were mixed. There was significant heterogeneity in within-person trajectories of frailty about the mean curves. DISCUSSION AND IMPLICATIONS:Our findings of linear longitudinal increases in frailty highlight important avenues for future research. Specifically, we encourage further research to identify potential effect modifiers or groups that would benefit from targeted or personalized interventions.

Background Macrostructural brain alterations in the form of brain atrophy or cortical thinning typically occur during the prodromal Alzheimer’s disease stage. Mixed findings largely dependent on the age of the examined cohorts have been reported during the preclinical, asymptomatic disease stage. In the present study, our aim was to examine the association of midlife dementia risk with brain macrostructural alterations. Methods Structural 3T MRI scans were acquired for 647 cognitively normal middle-aged (40–59 years old) participants in the PREVENT-Dementia study. Cortical thickness, volumes of subcortical structures, the hippocampus and hippocampal subfields were quantified using Freesurfer version 7.1. The clarity of the hippocampal molecular layer was evaluated based on T2-weighted hippocampal scans. Associations of structural measures with apolipoprotein ε4 (APOE4) genotype and dementia family history (FHD), were investigated using linear regression. Correlations between the CAIDE dementia risk score (incorporating information about blood pressure, cholesterol, physical activity, body mass index, education, age and sex) and structural measures were further investigated. Results A higher CAIDE score was associated with thinner cortex and a larger hippocampal fissure. APOE4 genotype was associated with reduced molecular layer clarity. Conclusions Our findings suggest that a higher CAIDE score is associated with widespread cortical thinning. Conversely, APOE4 carriers and participants with FHD do not demonstrate prominent macrostructural alterations at this age range. These findings indicate that cardiovascular and not inherited risk factors for dementia are associated with macrostructural brain alterations at midlife.

BackgroundAlzheimer's Disease, the leading cause of dementia, is over-represented in females. The apolipoprotein E (APOE) ε4 allele is the strongest genetic risk factor for late-onset AD and is associated with aberrant cerebrospinal fluid levels (CSF) of total tau (t-tau), phosphorylated tau (p-tau), and amyloid-β (Aβ). There is some evidence that sex may mediate the relationship between APOE status and CSF tau, however, evidence is mixed.MethodsWe aimed to examine the interaction between sex, APOE ε4 status, CSF Aβ on t-tau and p-tau in 1599 mid-to-late life individuals without a diagnosis of dementia in the European Prevention of Alzheimer's Dementia (EPAD) longitudinal cohort study.FindingsWe found a significant interaction between APOE status, sex, and CSF Aβ on CSF p-tau levels (β = 0·18, p = 0·04). Specifically, there was a stronger association between APOE status and CSF Aβ42 on CSF p-tau in males compared to females. Further, in females with high Aβ levels (reflecting less cortical deposition), ε4 carriers had significantly elevated p-tau levels relative to non-carriers (W = 39663, p = 0·01). However, there were no significant differences in p-tau between male ε4 carriers and non-carriers with high Aβ (W = 23523, p = 0·64).InterpretationAn interaction between sex and cerebrospinal fluid Aβ may mediate the relationship between APOE status and CSF p-tau. These data suggest tau accumulation may be independent of Aβ in females, but not males.FundingInnovative Medicines Initiative, Swedish Research Council, Alzheimer Drug Discovery Foundation, Swedish Alzheimer Foundation, the Swedish state under the agreement between the Swedish government and the County Councils: the ALF-agreement, and the Alzheimer's Association 2021 Zenith Award.

Background: Telephone and videoconference administration of cognitive tests introduce additional sources of variance compared to in-person testing. Reviews of test-retest reliability have included mixed neurocognitive and psychiatric populations with limited consideration of methodological and statistical contributions. Objective: We reviewed reliability estimates from comparison studies of older adults with and without dementia, considering test-retest analyses and study methods. Methods: Medline, Embase, PsycINFO, andWeb of Science were systematically searched from 1 January 2000 to 9 June 2020 for original articles comparing telephone or videoconference administered cognitive instruments to in-person administration in older adults with and without dementia or mild cognitive impairment. Results: Of 4,125 articles, 23 were included: 11 telephone (N = 2 dementia cohorts) and 12 videoconference (N = 4 dementia cohorts). Telephone administered subtest scores trended in the same direction as in-person with comparable means. Person-level data were scarce. Data on dementia was only available for MMSE, with resulting subtle modality bias. MMSE, SMMSE, Letter Fluency, and HVLT-R in healthy to mild-moderate Alzheimer's disease were particularly reliable for videoconference administration. Other tests show promise but require more observations and comprehensive analyses. Most studies used high-speed stable videoconferencing hardware resulting in a lack of ecological validity for home administration. Conclusion: Remote administration is often consistent with in-person administration but variable and limited at the person/test level. Improved statistical design and inclusion of dementia related cohorts in telephone studies is recommended. Reliability evidence is stronger for videoconferencing but with limited applicability to home administration and severe dementia. Improved reporting of administrative procedures is recommended.

Background and Objectives Frailty describes an increased vulnerability to adverse events such as disease or injury. Combating this state remains a major challenge for geriatric research. By exploring how and why frailty changes throughout later life we will be better positioned to improve ways of identifying and treating those at high risk. Research Design and Methods We systematically reviewed publications that captured rate of frailty progression over time and established any associated risk or protective factors that affected this progression. We included longitudinal observational studies which quantified frailty trajectories in adults aged 50+ using any validated continuous frailty measurement tool. Results After screening 8,318 publications, 25 met our criteria. Findings show that despite a great degree of heterogeneity in the literature, progression of frailty is unquestionably affected by numerous risk and protective factors, with particular influence exhibited by social demographics, brain pathology, and physical comorbidities. Discussion and Implications Findings that the gradient of frailty progression is affected by various influencing factors are valuable to clinicians and policymakers as they will help identify those at highest frailty risk and inform prevention strategies. However, the heterogeneous methodological approaches of the publications included in this review highlight the need for consensus within the field to promote more coordinated research. Improved consistency of methods will enable further data synthesis and facilitate a greater understanding of the shape of frailty over time and the influencing factors contributing to change, the results of which could have crucial implications for frailty risk reduction.

Background Recruitment is often a bottleneck in secondary prevention trials in Alzheimer disease (AD). Furthermore, screen-failure rates in these trials are typically high due to relatively low prevalence of AD pathology in individuals without dementia, especially among cognitively unimpaired. Prescreening on AD risk factors may facilitate recruitment, but the efficiency will depend on how these factors link to participation rates and AD pathology. We investigated whether common AD-related factors predict trial-ready cohort participation and amyloid status across different prescreen settings. Methods We monitored the prescreening in four cohorts linked to the European Prevention of Alzheimer Dementia (EPAD) Registry ( n = 16,877; mean ± SD age = 64 ± 8 years). These included a clinical cohort, a research in-person cohort, a research online cohort, and a population-based cohort. Individuals were asked to participate in the EPAD longitudinal cohort study (EPAD-LCS), which serves as a trial-ready cohort for secondary prevention trials. Amyloid positivity was measured in cerebrospinal fluid as part of the EPAD-LCS assessment. We calculated participation rates and numbers needed to prescreen (NNPS) per participant that was amyloid-positive. We tested if age, sex, education level, APOE status, family history for dementia, memory complaints or memory scores, previously collected in these cohorts, could predict participation and amyloid status. Results A total of 2595 participants were contacted for participation in the EPAD-LCS. Participation rates varied by setting between 3 and 59%. The NNPS were 6.9 (clinical cohort), 7.5 (research in-person cohort), 8.4 (research online cohort), and 88.5 (population-based cohort). Participation in the EPAD-LCS ( n = 413 (16%)) was associated with lower age (odds ratio (OR) age = 0.97 [0.95–0.99]), high education (OR = 1.64 [1.23–2.17]), male sex (OR = 1.56 [1.19–2.04]), and positive family history of dementia (OR = 1.66 [1.19–2.31]). Among participants in the EPAD-LCS, amyloid positivity (33%) was associated with higher age (OR = 1.06 [1.02–1.10]) and APOE ɛ4 allele carriership (OR = 2.99 [1.81–4.94]). These results were similar across prescreen settings. Conclusions Numbers needed to prescreen varied greatly between settings. Understanding how common AD risk factors link to study participation and amyloid positivity is informative for recruitment strategy of studies on secondary prevention of AD.

Background: Substantial research is dedicated to understanding the aging-related dynamics among individual differences in level, change, and variation across physical and cognitive abilities. Evaluating replicability and synthesizing findings has been limited by differences in measurements, samples, study design, and statistical analyses that confound between-person differences with within-person changes. Here, we systematically reviewed longitudinal results on the aging-related dynamics linking pulmonary function and cognitive performance. Methods: Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines were used to systematically review longitudinal studies of pulmonary function and cognition. Results: Only four studies thoroughly investigating cognitive and pulmonary longitudinal associations (three or more measurement occasions) were identified. Expanded review criteria identified three studies reporting two measurement occasions, and seven studies reporting one measurement of pulmonary function or cognition and two or more measurements of the other. We identified numerous methodological quality and risk for bias issues across studies. Conclusions: Despite documented correlational associations between pulmonary function and cognition, these results show there is very limited research thoroughly investigating their longitudinal associations. This highlights the need for longitudinal data, rigorous methodological design including key covariates, and clear communication of methods and analyses to facilitate replication across an array of samples. We recommend systematic study of outcome measures and covariates, inclusion of multiple measures (e.g., peak expiratory flow, forced expiratory volume in 1 s, and forced vital capacity), as well as application of the same analytic approach across multiple datasets.