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Early identification of deficits in our ability to perceive odors is important as many normal (i.e., aging) and pathological (i.e., sinusitis, viral, neurodegeneration) processes can result in diminished olfactory function. To realistically enable population-level measurements of olfaction, validated olfaction tests must be capable of being administered outside the research laboratory and clinical setting. The purpose of this study was to determine the feasibility of remotely testing olfactory performance using a test that was developed with funding from the National Institutes of Health as part of a ready-to-use, non-proprietary set of measurements useful for epidemiologic studies (NIH Toolbox Odor ID Test). Eligible participants older than 39 years and active (within 6 months) in the Brain Health Registry (BHR), an online cognitive assessment platform which connects participants with researchers, were recruited for this study. Interested participants were mailed the NIH Toolbox Odor ID Test along with instructions on accessing a website to record their responses. Data obtained from subjects who performed the test at home was compared to the normative data collected when the NIH Toolbox Odor ID Test was administered by a tester in a research setting and validated against the Smell Identification Test. The age-range and composition of the population ensured we had the ability to observe both age-related decline and gender-related deficits in olfactory ability, as shown in the experimental setting. We observed that age-associated olfactory decline and gender-associated performance was comparable to performance on the administered test. Self-administration of this test showed the age-related loss in olfactory acuity, F(4, 1156)=14.564, p<.0001 as well as higher accuracy for women compared to men after controlling for participants' age, F(1, 1160) = 22.953, p <.0001. The effect size calculated as Hedge's g, was 0.41. These results indicate that the NIH Toolbox Odor ID Test is an appropriate instrument for self-administered assessment of olfactory performance. The ability to self-administer an inexpensive olfactory test increases its utility for inclusion in longitudinal epidemiological studies and when in-person testing is not feasible.

The reference standard for amyloid-PET quantification requires structural MRI (sMRI) for preprocessing in both multi-site research studies and clinical trials. Here we describe rPOP (robust PET-Only Processing), a MATLAB-based MRI-free pipeline implementing non-linear warping and differential smoothing of amyloid-PET scans performed with any of the FDA-approved radiotracers (18F-florbetapir/FBP, 18F-florbetaben/FBB or 18F-flutemetamol/FLUTE). Each image undergoes spatial normalization based on weighted PET templates and data-driven differential smoothing, then allowing users to perform their quantification of choice. Prior to normalization, users can choose whether to automatically reset the origin of the image to the center of mass or proceed with the pipeline with the image as it is. We validate rPOP with n = 740 (514 FBP, 182 FBB, 44 FLUTE) amyloid-PET scans from the Imaging Dementia—Evidence for Amyloid Scanning – Brain Health Registry sub-study (IDEAS-BHR) and n = 1,518 scans from the Alzheimer's Disease Neuroimaging Initiative (n = 1,249 FBP, n = 269 FBB), including heterogeneous acquisition and reconstruction protocols. After running rPOP, a standard quantification to extract Standardized Uptake Value ratios and the respective Centiloids conversion was performed. rPOP-based amyloid status (using an independent pathology-based threshold of ≥24.4 Centiloid units) was compared with either local visual reads (IDEAS-BHR, n = 663 with complete valid data and reads available) or with amyloid status derived from an MRI-based PET processing pipeline (ADNI, thresholds of >20/>18 Centiloids for FBP/FBB). Finally, within the ADNI dataset, we tested the linear associations between rPOP- and MRI-based Centiloid values. rPOP achieved accurate warping for N = 2,233/2,258 (98.9%) in the first pass. Of the N = 25 warping failures, 24 were rescued with manual reorientation and origin reset prior to warping. We observed high concordance between rPOP-based amyloid status and both visual reads (IDEAS-BHR, Cohen's k = 0.72 [0.7–0.74], ∼86% concordance) or MRI-pipeline based amyloid status (ADNI, k = 0.88 [0.87–0.89], ∼94% concordance). rPOP- and MRI-pipeline based Centiloids were strongly linearly related (R2:0.95, p<0.001), with this association being significantly modulated by estimated PET resolution (β= -0.016, p<0.001). rPOP provides reliable MRI-free amyloid-PET warping and quantification, leveraging widely available software and only requiring an attenuation-corrected amyloid-PET image as input. The rPOP pipeline enables the comparison and merging of heterogeneous datasets and is publicly available at https://github.com/leoiacca/rPOP.

Scalable tools to efficiently identify individuals likely to have cognitive impairment (CI) are critical in the Alzheimer disease and related dementias field. The Everyday Cognition scale (ECog) and its short form (ECog12) assess subjective cognitive and functional changes and are useful in predicting CI. Recent advances in online technology have enabled the use of web-based cognitive tests and questionnaires to identify CI with greater convenience and scalability. While the effectiveness of the ECog has been demonstrated in clinical settings, its potential to detect CI in remote, unsupervised formats remains underexplored. This study aimed to compare the ability of the web-based ECog and the in-clinic ECog in distinguishing between individuals with CI and those who are cognitively unimpaired (CU), and to evaluate the effectiveness of the ECog12-the short version of the ECog-compared to the full-length ECog in a web-based setting. Participants were recruited from the Brain Health Registry (BHR; web-based) and Alzheimer's Disease Neuroimaging Initiative (ADNI; in-clinic) settings with available clinical diagnoses. The ability of the self-reported ECog (Self-ECog), study partner-reported ECog (SP-ECog), Self-ECog12, and SP-ECog12 to discriminate individuals with CI from CU was assessed using receiver operating characteristic (ROC) curves. Area under the ROC curves (AUCs) between BHR and ADNI were compared using the DeLong test, as were AUCs between ECog12 and ECog in BHR. Web-based Self-ECog and SP-ECog scores effectively discriminated CI from CU with AUCs of 0.722 and 0.818, respectively. Similarly, the abbreviated web-based versions, Self-ECog12 and SP-ECog12, also demonstrated discriminative ability (AUC=0.709 and 0.777, respectively). When compared to in-clinic ECog scores, there were no significant differences in the ability to distinguish CI from CU between web-based and in-clinic versions (BHR Self-ECog AUC=0.722 vs ADNI Self-ECog AUC=0.769, DeLong P=.06; BHR SP-ECog AUC=0.818 vs ADNI SP-ECog AUC=0.840, DeLong P=.50). Additionally, the comparison between web-based ECog and ECog12 showed no significant difference in AUCs (BHR Self-ECog AUC=0.722 vs BHR Self-ECog12 AUC=0.709, DeLong P=.18). Web-based ECog scores, both the full-length and short-form, were as valid as in-clinic ECog scores for identifying clinically diagnosed CI. In addition, Self-ECog12 was as effective as full-length Self-ECog to identify CI in a web-based setting, offering a cost-effective and accessible screening tool for large-scale studies. These results highlight the value of the web-based ECog as a valid tool for identifying older adults with CI in a remote clinical study, facilitating early detection and referral for comprehensive evaluations for identifying potential candidates for disease-modifying therapy.

Inefficient chromium (III)–collagen cross-linking during leather tanning generates solid waste and effluents containing residual chromium, raising environmental and health concerns. Biological strategies are increasingly popular for tannery waste treatment, but the microbial communities involved in leather degradation remain poorly understood. This study did not seek to evaluate leather disintegration according to standardised compostability criteria, but to establish a thermophilic composting system suitable for characterising leather-associated microbial communities, biofilm formation on leather and isolating cultivable strains. Composting assays were carried out at two scales, in which wet blue leather was mixed with organic compost under self-heating thermophilic conditions. Temperature was monitored, and mass loss and changes in leather structure were determined by gravimetry and scanning electron microscopy. Bacterial and fungal communities in compost with and without leather were analysed using high-throughput amplicon sequencing. Thermophilic consortia dominated by Firmicutes, Actinobacteria and Ascomycota were established, and several bacterial isolates and a filamentous fungus were recovered. Together, these results provide a first basis for understanding the communities and strains associated with chromium-tanned leather during thermophilic composting, supporting future searches for microorganisms and enzymes of interest for biological strategies to manage chromium-tanned leather waste.

The Sm protein superfamily includes Sm, like-Sm (Lsm), and Hfq found in the Eukarya, Archaea, and Bacteria domains. Archaeal Lsm proteins have been shown to bind sRNAs and are probably involved in various cellular processes, suggesting a similar function in regulating sRNAs by Hfq in bacteria. Moreover, archaeal Lsm proteins probably represent the ancestral Lsm domain from which eukaryotic Sm proteins have evolved. In this work, Haloferax mediterranei was used as a model organism because it has been widely used to investigate the nitrogen cycle and its regulation in Haloarchaea. Predicting this protein’s secondary and tertiary structures has resulted in a three-dimensional model like the solved Lsm protein structure of Archaeoglobus fulgidus. To obtain information on the oligomerization state of the protein, homologous overexpression and purification by means of molecular exclusion chromatography have been performed. The results show that this protein can form hexameric complexes, which can aggregate into 6 or 12 hexameric rings depending on the NaCl concentration and without RNA. In addition, the study of transcriptional expression via microarrays has allowed us to obtain the target genes regulated by the Lsm protein under nutritional stress conditions: nitrogen or carbon starvation. Microarray analysis has shown the first universal stress proteins (USP) in this microorganism that mediate survival in situations of nitrogen deficiency.

Background Most Alzheimer's disease (AD) and AD related dementia clinical research studies and trials requires study partner enrollment. The participant is usually the first point of contact. We developed and pilot tested a novel approach in an online research registry, which recruits the study partner first. Method The Brain Health Registry (BHR) is an online research registry (n >106,000), collecting longitudinal self‐reported health and cognitive data. The BHR Study Partner Portal allows BHR participants to enroll a study partner (SP) in BHR. The SP answers questions about the participant's brain health. Since 2016, >10,000 participant‐SP pairs (dyads) have enrolled. In July 2024, BHR launched a novel feature to expand SP data collection. Enrolled BHR participants are presented with a new task, which allows them to enroll as a SP without having been invited by a participant. The SP can either invite an associated participant (AP) to join (if the SP feels the AP is capable of enrolling and has an email address), or the SP can serve as a proxy and complete assessments about the AP on their behalf. Here we assess the preliminary feasibility of this approach in terms of enrollment and task completion. Result Within 7 months, 1,144 participants registered in SP First task. 699 have provided their AP's first name. 553 have indicated that they believed their AP was capable of enrolling, and 508 provided their AP's email address. Out of 473 APs that received an email invitation, 40 APs enrolled, and 17 APs completed all assessments. 380 SPs indicated that their AP either didn’t have an email address and/or was not capable of enrolling. Of those, 103 SPs agreed to serve as a Proxy for their AP, and 52 SPs completed all proxy questionnaires. Conclusion Our findings demonstrate feasibility of the approach, which can be used to engage and assess SPs whose AP drops out of a study or cannot enroll, mitigating the selection bias against older adults who are too impaired or unmotivated to participate. Future efforts will expand this initiative through email invitations to BHR participants and recruitment of the public through social media.

Background Recruitment of older adults for clinical Alzheimer's Disease (AD) and aging observational studies and trials is expensive, time consuming, and causes study delays. Many studies have inadequate recruitment. Internet‐based registries are an efficient, scalable approach to help enroll participants into AD research. The Brain Health Registry (BHR) is an online registry and observational cohort that addresses this critical need by referring participants to AD and aging observational studies and trials. Methods BHR includes an engaging, online platform for registration, consent, and assessment. Participants enroll through the BHR website, sign online informed consent, and complete digital questionnaires and cognitive tests at 6‐month intervals. All assessments are completed remotely, unsupervised, on one's own device. Questionnaires include demographics, determinants of health, subjective cognitive decline, head injury, mood, and medical history. Cognitive tests include the Cambridge Cognition Paired Associates Learning test. BHR participants who opt in to learning about future research opportunities can be referred to additional studies, including collaborator studies and sub‐studies led by BHR investigators. The BHR database is used to identify participants who meet study inclusion and exclusion criteria. Eligible participants receive automated emails inviting them to the study and explaining next steps. BHR demographic, cognitive, and health data is often used to screen and prioritize participants for referral. Collaborators can manage their referrals online through an Investigator Portal within BHR. Results BHR includes >104,000 participants and >10,000 study partners, including >81,000 participants age 55+ (Table 1), and >20,000 from minoritized ethnocultural groups. Over 90% of all BHR participants opt in to learning about future research opportunities. Since 2014, BHR has completed >489,000 invitations to additional studies. From those, >42,000 participants have enrolled in at least one of 35 collaborator studies. This includes in‐clinic observational studies, online studies, and clinical trials. Conclusions The results support use of BHR to facilitate efficient recruitment into AD and aging clinical research studies. Prescreening using BHR data can be used to reduce burden of in‐clinic screening. Planned improvements to the referral process include further automation of participant selection and communications to facilitate recruitment of participants across different demographic strata (e.g., age, education, ethnocultural identity).

Background Early onset dementia (EOD) affects people at the peak of personal and professional responsibilities and economic productivity. Alzheimer's disease (AD) and Frontotemporal Dementia (FTD) are the most common EOD etiologies, but have not been studied in a sample representative of the general US population. Multiple barriers impede research participation for many groups, but community‐engaged research (CER) strategies to enhance recruitment may make research participation more accessible and convenient for all. Method BEYONDD is an NIH‐funded, community‐based study focused on understanding the etiology of EOD, uses CER strategies such as remote assessments and return of research results as tools for enhancing sample representativeness. Participants are recruited using social media and local in‐person CER strategies and screened via an online platform for eligibility (age 40‐64, with concerns about cognitive or behavioral function). Remote completion of online questionnaires, cognitive testing, and an in‐home blood draw for standard labs, Aβ42/40 and p‐tau217 ratios, and plasma NfL comprise the initial visit. Participants are invited for more comprehensive onsite evaluation at one of 7 BEYOND in‐clinic sites, followed by tailored referral to other NIH‐funded research programs. Participants can learn their results remotely or in person. Result Using a novel, CER‐based approach for social media ad deployment, BEYONDD has recruited over 1700 potential participants across the US and Puerto Rico; over half (n = 881) completed the online screening survey. Of the 206 participants enrolled in the online procedures, 80% (n = 165) were women and most were Latino (n = 83; 40%) or Black (n = 68; 33%) and over a quarter (n = 74; 36%) reported less than 16 years of education. We have completed over 95 blood draws across 17 states and invited participants for onsite visits. Results have been shared with 22 participants (10 on‐site, 12 remotely). Preliminary analyses reveal a high Aβ42/40 positivity rate (∼30%) and the most prevalent routine lab abnormalities include: LDL‐Cholesterol (63%), homocysteine (36%), hs‐CRP (35%) and HgbA1C (33%). Abnormal p‐tau217 ratios (n = 4; 5%) and APS2 scores (n = 3; 4%) have also been identified in this community‐based sample. Conclusion Preliminary results suggest feasibility and acceptability of this innovative CER approach in a more representative sample of the US population.

The ability to remotely monitor cognitive skills is increasing with the ubiquity of smartphones. The Mobile Toolbox (MTB) is a new measurement system that includes measures assessing Executive Functioning (EF) and Processing Speed (PS): Arrow Matching, Shape-Color Sorting, and Number-Symbol Match. The purpose of this study was to assess their psychometric properties. MTB measures were developed for smartphone administration based on constructs measured in the NIH Toolbox® (NIHTB). Psychometric properties of the resulting measures were evaluated in three studies with participants ages 18 to 90. In Study 1 ( = 92), participants completed MTB measures in the lab and were administered both equivalent NIH TB measures and other external measures of similar cognitive constructs. In Study 2 ( = 1,021), participants completed the equivalent NIHTB measures in the lab and then took the MTB measures on their own, remotely. In Study 3 ( = 168), participants completed MTB measures twice remotely, two weeks apart. All three measures exhibited very high internal consistency and strong test-retest reliability, as well as moderately high correlations with comparable NIHTB tests and moderate correlations with external measures of similar constructs. Phone operating system (iOS vs. Android) had a significant impact on performance for Arrow Matching and Shape-Color Sorting, but no impact on either validity or reliability. Results support the reliability and convergent validity of MTB EF and PS measures for use across the adult lifespan in remote, self-administered designs.

Early onset dementia (EOD) affects people at the peak of personal and professional responsibilities and economic productivity. Alzheimer's disease (AD) and Frontotemporal Dementia (FTD) are the most common EOD etiologies, but have not been studied in a sample representative of the general US population. Multiple barriers impede research participation for many groups, but community-engaged research (CER) strategies to enhance recruitment may make research participation more accessible and convenient for all. BEYONDD is an NIH-funded, community-based study focused on understanding the etiology of EOD, uses CER strategies such as remote assessments and return of research results as tools for enhancing sample representativeness. Participants are recruited using social media and local in-person CER strategies and screened via an online platform for eligibility (age 40-64, with concerns about cognitive or behavioral function). Remote completion of online questionnaires, cognitive testing, and an in-home blood draw for standard labs, Aβ42/40 and p-tau217 ratios, and plasma NfL comprise the initial visit. Participants are invited for more comprehensive onsite evaluation at one of 7 BEYOND in-clinic sites, followed by tailored referral to other NIH-funded research programs. Participants can learn their results remotely or in person. Using a novel, CER-based approach for social media ad deployment, BEYONDD has recruited over 1700 potential participants across the US and Puerto Rico; over half (n = 881) completed the online screening survey. Of the 206 participants enrolled in the online procedures, 80% (n = 165) were women and most were Latino (n = 83; 40%) or Black (n = 68; 33%) and over a quarter (n = 74; 36%) reported less than 16 years of education. We have completed over 95 blood draws across 17 states and invited participants for onsite visits. Results have been shared with 22 participants (10 on-site, 12 remotely). Preliminary analyses reveal a high Aβ42/40 positivity rate (∼30%) and the most prevalent routine lab abnormalities include: LDL-Cholesterol (63%), homocysteine (36%), hs-CRP (35%) and HgbA1C (33%). Abnormal p-tau217 ratios (n = 4; 5%) and APS2 scores (n = 3; 4%) have also been identified in this community-based sample. Preliminary results suggest feasibility and acceptability of this innovative CER approach in a more representative sample of the US population.