bluuebunny/crossref_metadata_2025_split huggingface dataset:
The unique contribution of tau pathology in the amygdala to depressive symptoms in cognitively normal older adults
Authors: Markova Teodora Z. , Fonseca Corrina S. , Ciampa Claire J. , Murphy Alice , Landau Susan M. , Harrison Theresa M. , Jagust William J. , Berry Anne S. 
Published: January 2025

AbstractBackgroundAlthough most PET imaging studies have focused on entorhinal cortex as an early site of medial temporal lobe tau accumulation, the amygdala displays substantial tau deposition in cognitively normal individuals. We examined amygdala tau in relation to changes in affective health that often precede Alzheimer’s disease (AD).MethodsWe ran parallel analyses in non‐depressed, cognitively normal older adults from ADNI (60‐91 years) and the Berkeley Aging Cohort Study (BACS, 60‐96 years). Participants in both cohorts had cross‐sectional and longitudinal tau PET scans, Aβ status, APOE ε4 status, longitudinal Geriatric Depression Scale (GDS) scores, longitudinal memory performance, and longitudinal non‐memory cognition composites. Longitudinal slopes reflecting changes over time were calculated using linear mixed effects models. Group‐level differences in amygdala tau were established using ANCOVAs (adjusting for age), and multiple linear regressions tested direct and interactive effects between tau and Aβ/APOE/sex.ResultsCompared to non‐carriers, APOE ε4 carriers had higher levels of amygdala tau in ADNI (F(1,371)=18.81, p<.001) and BACS (F(1,124)=3.70, p=.057, marginal), as did Aβ positive individuals compared to negative (ADNI F(1,404)=34.25, p<.001, BACS F(1,128)=8.14, p=.005). APOE ε4 carriers also had greater longitudinal increases in amygdala tau in ADNI (ADNI F(1,155)=10.26, p=.002, BACS F(1,71)=2.48, p=.120), as did Aβ positive individuals in both samples (ADNI F(1,157)=11.53, p<.001, BACS F(1,72)=5.85, p=.018, Figure 1). There were no direct relationships between amygdala tau and longitudinal GDS in ADNI (cross‐sectional t(344)=0.65, p=.520, longitudinal t(152)=‐0.87, p=.384) or BACS (cross‐sectional t(127)=0.44, p=.661, longitudinal t(71)=0.44, p=.661). In APOE ε4 carriers, higher baseline amygdala tau predicted worsening GDS in ADNI (t(320) = 2.43, p = .016), while longitudinal amygdala tau predicted worsening GDS in BACS (t(64) = 2.34, p = .022, Figure 2). Results remained significant with adjustments for entorhinal tau or entorhinal tau slopes, respectively. Neither Ab status nor sex predicted GDS change, and amygdala tau did not predict memory or non‐memory change in either sample.ConclusionsThese results demonstrate relationships between amygdala tau pathology and depressive symptoms that are related to APOE genotype, but are independent of the effects of entorhinal tau alone. Given the nuanced effects observed, future research in understanding amygdala tau accumulation is critical.
Validation of Remote Neuropsychological Testing with the California Cognitive Assessment Battery (CCAB)
Authors: Baldo Juliana , Lwi Sandy J. , Herron Timothy J , Chok Jas M. , Curran Brian , Spinelli Maria G , Santavicca Isabella , Thomas Lexie , Schendel Krista , Hall Kathleen , Geraci Kristin , Blank Michael , Pebler Peter , Woods David L. 
Published: January 2025

AbstractBackgroundPaper‐and‐pencil neuropsychological tests have traditionally been considered the “gold standard” for clinical testing in AD/ADRD, but they have significant limitations: They are time‐consuming, costly to administer, vulnerable to examiner bias and error, and unavailable to some patients due to location, transportation challenges, and cost. Manual tests also fail to comprehensively analyze many aspects of test performance. Computerized neuropsychological test batteries have been developed to address these shortcomings. However, most computerized tests cannot score verbal responses and correlate poorly with gold standard manual tests. In the current study, we evaluated the validity and reliability of a new computerized battery, the California Cognitive Assessment Battery (CCAB), which includes 15 non‐verbal and 17 verbal cognitive tests. The CCAB utilizes speech‐to‐text technology for automatic recording and scoring of patients’ verbal responses.Method85 healthy adults were tested remotely on the CCAB at home and were also assessed with traditional in‐person neuropsychological testing, in counterbalanced order. The in‐person neuropsychological battery included standardized, paper‐and‐pencil versions of the most widely used equivalent manual tests (e.g., CVLT, digit span, etc.). The CCAB was re‐administered to evaluate test‐retest reliability. Sessions lasted approximately 1.5 hours.ResultsStrong correlations were observed between the CCAB and traditional in‐person tests of episodic memory for word lists and face‐name recall (.60‐.73), working memory (.61‐.66), processing speed (.69), executive functioning (.63‐.71), and vocabulary (.82). Test‐retest reliability on the CCAB was also high across measures (.65‐.80).ConclusionThe CCAB is a valid and reliable means of assessing cognitive functioning in remote settings: Correlations with traditional paper‐and‐pencil tests were strong and test‐retest reliability was robust. The CCAB provides comprehensive assessment with sensitive measures and state‐of‐the‐art technology, and it overcomes limitations of other computerized tools and also that of traditional testing by allowing for efficient, reliable, remote assessment of neuropsychological functioning that can address the critical need for longitudinal monitoring of individuals with AD/ADRD. Early diagnosis of dementia risk with accessible remote testing provides patients the best opportunity to take advantage of new treatment interventions that slow cognitive decline in AD/ADRD, which can prolong quality of life for patients and their families.
Comparing plasma Aβ42/40 and pTau217 to predict Amyloid‐β status across the Alzheimer’s disease continuum
Authors: Doecke James D. , Chenna Ahmed , Lo Mintzu , Badal Youssouf , Yee Brandon , Martone Robert L. , Petropoulos Christos , Fowler Christopher J , Laws Simon M. , Smith Stephanie Rainey , Martins Ralph N , Rowe Christopher C. , Masters Colin L , Winslow John W 
Published: January 2025

AbstractBackgroundRecent advances in immunoassays have enabled sensitive detection of Aβ42/40 and pTau217 in plasma, components of Alzheimer’s disease (AD) neuropathological markers. Further characterization of increased diagnostic accuracy with PET Amyloid‐β (Aβ) across the AD continuum is needed for clinical application.MethodParticipants from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study of ageing (N=197) representing a cross‐sectional population of four clinical and PET‐Aβ subgroups: cognitive unimpaired (CU) Aβ‐ (n=75), CU Aβ+ (n=48), mild cognitive impairment (MCI) Aβ+ (n=26), and AD Aβ+ (n=48). EDTA plasma was analyzed with Aβ42/40 (Quanterix Simoa & Fujirebio Lumipulse) and pTau217 (ALZpath Simoa & Lumipulse). Data were investigated using Cohen’s D for effect size, Receiver Operating Characteristic (ROC) analyses to define AUC values for PET‐Aβ positivity and Spearman’s Rho for correlation between biomarkers and Centiloid.ResultLower Lumipulse and Simoa plasma Aβ42/40 ratios were observed in Aβ+ vs Aβ‐ groups (p<0.0001; with effect size Cohen’s D indices = 1.39 and 1.07, respectively). Aβ42/40 ratios initially decreased with increasing amyloid PET Centiloid levels through the positivity threshold (25CL), levelling off with increasing Centiloid values across the disease continuum (Figure 1A). Highest effects sizes were seen for pTau217 when comparing Aβ+ vs Aβ‐ groups (p<0.0001; Cohen’s D: 1.54 [Simoa] and 1.49 [Lumipulse]), with stepwise increases per Centiloid group (Figure 1B). Biomarker AUC values to predict PET‐Aβ were highest for pTau217 in the complete sample compared with the CU sample (Simoa AUC: 0.947/0.906, Lumipulse AUC: 0.941/0.906). For the Aβ42/40 ratio, AUC values were higher in the CU group as compared with the complete sample (Lumipulse AUC: 0.896/0.889, Simoa AUC: 0.885/0.849 (Figure 1C). Adding in age, gender, and APOE ε4 allele status improved prediction of PET‐Aβ, with AUC values reaching 0.97 for pTau217 (Figure 1C). Correlations between biomarker and Centiloid were higher for pTau217 (Simoa: r=0.744 (Figure 1D), Lumipulse r=0.732) as compared with the Aβ42/40 ratio (Lumipulse r=‐0.509, Simoa r=‐0.462).ConclusionSensitive assays for the Aβ42/40 ratio may be more appropriate to detect Aβ burden in CU participants while p‐Tau217 appears to be more accurate and has the highest effect size and AUC values to predict Aβ‐PET across the AD continuum.
Evaluation and Modification of the 10‐Item Short Form Communicative Participation Item Bank for Persons with Primary Progressive Aphasia and their Communication Partners
Authors: Fegter Ollie , Shaunfield Sara , Bona Matthew , Roberts Angela C , Rogalski Emily J 
Published: January 2025

AbstractBackgroundPrimary progressive aphasia (PPA) is a dementia syndrome characterized by language and communication impairments, with relative sparing of other cognitive domains. As a relatively rare dementia syndrome, there are few measures developed and validated for individuals with PPA. Development of outcome measures tailored to the communication experiences of persons with PPA (PwPPA) is critical for the accurate assessment of interventions success. The 10‐item Communicative Participation Item Bank (CPIB) has been used as a measure for communication participation in PPA. However, the CPIB was validated as a disorder‐agnostic measure and its content validity for PPA has not been evaluated. This study aims to evaluate the face and content validity of the 10‐item CPIB for PwPPA and their communication partners (CP).MethodCognitive interviews were conducted with participants (N = 12) who had previously completed the CPIB during the Communication Bridge 2 randomized controlled trial (NCT03371706) and with four participants unfamiliar with the CPIB. PwPPAs and CPs completed the CPIB during a semi‐structured interview assessing measure format, instructions, response options, item comprehension, and item relevance. To evaluate content validity, participants were asked open‐ended questions to elicit relevant communication participation experiences missing from the questionnaire. Closed‐ended responses (e.g., clarity, relevance) were tabulated, and open‐ended responses (e.g., item comprehension, missing content) were thematically analyzed. Summaries of measure format, instructions, and response options were generated, as well as item‐level findings regarding comprehension, relevance, and missing content.ResultBoth PwPPAs and CPs: a) considered the instructions to be clear (n = 16, 100%); b) recommended adding a fifth response option (e.g., “Somewhat; n = 11) to better represent the range of communication situations; c) reported all items except one (“persuade…to see a different point of view”) were relevant (n≥13; ≥81%, for 9 items); and d) talking on the phone was the most reported missing communicative participation situation (n = 12; 75%). Further, 3 participants reported talking over videochat, and 4 participants reported email/texting as missing. Results were similar between CPIB‐experienced and CPIB‐naïve participants.ConclusionFindings indicate that modifications to the 10‐item CPIB short form may be needed for use with PwPPA and their CPs to more fulsomely capture communication participation in PPA.
Association of frailty and neuropathology of neurodegenerative and brain vascular diseases
Authors: Soares Felipe Bozi , Leite Renata Elaine Paraizo , Grinberg Lea T. , Paes Vitor Ribeiro , Rodriguez Roberta Diehl , Pasqualucci Carlos Augusto , Jacob‐Filho Wilson , Suemoto Claudia Kimie 
Published: January 2025

AbstractBackgroundFrailty, characterized by increased physical vulnerability, is associated with a higher incidence and severity of cognitive impairment and also a higher burden of neurodegenerative and cerebrovascular diseases. This study investigates the association between frailty and neurodegenerative and cerebrovascular pathologies.MethodCross‐sectional analysis using clinical and neuropathological data from individuals aged 60 or older, enrolled in the Biobank for Aging Studies between 2004 and 2023. A 42‐item frailty index was constructed. Cognitive impairment was defined as a clinical dementia rating score (CDR) of 0.5 or over and participants were stratified according to cognitive status. Linear regression models, adjusting for age, sex, education and race, explored the association between frailty and neuropathology, including Alzheimer´s disease (AD), argyrophilic grain disease (AGD), Lewy‐type pathology (LBP), hippocampal sclerosis, cerebral amyloid angiopathy (CAA), lacunar infarcts, hyaline arteriosclerosis, TDP‐43 pathology and a neuropathological comorbidity score (NPC).ResultsWe examined data from 1.343 subjects. The group with cognitive impairment was older, predominantly female, had lower education, a higher frailty index, and no race differences (Table 1). This group also exhibited a higher prevalence of all neuropathologies previously described (Table 2). In adjusted analyses, frailty was associated with AD Braak staging (β = 0.022, 95% CI=0.017; 0.028, p<0.001 ), CERAD score (β = 0.021, CI 95% = 0.013; 0.029 p<0.001), CAA (β = 0.065, 95% CI = 0.039; 0.092 p<0.001), LBD (β = 0.051, 95% CI = 0.027; 0.075 p<0.001), hippocampal sclerosis (β= 0.053, CI 95% = 0.008; 0.100 p=0.022), lacunar infarcts (β=0.071, CI 95%= 0.046; 0.097 p<0.001), siderocalcinosis (β=0.033, CI 95%= 0.015; 0.051 p<0.001), hyaline arteriosclerosis (β=0.065, CI 95%= 0.050‐0.081 p<0.001) and NPC score (Table 3) (β=0.032, CI 95%= 0.024; 0.040 p<0.001). Frailty was not associated with AGD and TDP‐43.ConclusionFrailty was associated with several neuropathological markers of neurodegenerative and cerebrovascular diseases. More studies are warranted to investigate how this association relates to relevant outcomes such as cognitive impairment.
Healthy Dietary Intake Diminishes the Effect of Vascular Pathology on Cognitive Performance in Older Adults
Authors: Bauer Christopher E. , Zachariou Valentinos , Pappas Colleen , Maillard Pauline , Caprihan Arvind , Satizabal Claudia L , Gold Brian T 
Published: January 2025

AbstractBackgroundCognitive reserve (CR) in the context of Alzheimer’s’ disease has been widely studied, yet less is known about how CR protects against vascular brain pathologies. Here, we explored whether dietary factors might attenuate the association between magnetic resonance imaging (MRI)‐derived vascular biomarkers and cognition.MethodSeventy‐one older adults (ages 60‐85) were scanned using a 3‐Tesla MRI Siemens Magnetom Prisma at the University of Kentucky. Data from a 3D T1‐weighted sequence, a 3D fluid‐attenuated inversion recovery sequence, and a 126‐direction diffusion MRI sequence were acquired. The vascular biomarkers used [White Matter Hyperintensity Volume (WMHV), Free Water (FW), and Peak Width of Skeletonized Mean Diffusivity (PSMD)] were developed and validated through the MarkVCID consortium (https://markvcid.partners.org). WMHV was computed using a 4‐tissue segmentation model, mean FW in all white matter was calculated using a two‐compartment model, and PSMD was calculated as the difference between the 95th and 5th percentiles in white matter MD values. Grey matter volume (GMV; non‐vascular biomarker) and intracranial volume (ICV) were estimated using FreeSurfer. The “Newly Developed Antioxidant Nutrient Questionnaire” was used to quantify dietary‐intake for the preceding month. Nutrients were grouped into nutrition factors based on previous literature and factor analysis (Factor 1= representing fruits and vegetables; Factor 2= representing nuts, healthy oils, and fish; Factor 3= representing green tea). All participants completed the Montreal Cognitive Assessment (MoCA). Multivariate linear regression models tested whether dietary factors, vascular biomarkers, and/or their interaction (i.e. moderation) were associated with MoCA scores. All models controlled for age, sex, ICV, and education.ResultThere were no significant main effects of WMHV, FW, PSMD, or GMV on MoCA scores. However, Factor 2 (but not other factors) positively moderated all 3 vascular biomarkers [WMHV (β=0.309, p=0.009); FW (β=0.324, p=0.007); PSMD (β=0.354, p=0.008)] such that a negative association between vascular markers and MoCA scores was only present in those with low but not high Factor 2 intake (Figure 1). Factor 2 did not moderate the association between non‐vascular biomarkers (i.e. GMV) and MoCA scores.ConclusionOur results suggest that consuming more nuts, healthy oils, and fish may help protect against vascular contributions to cognitive impairment.
User evaluation of registry‐supported recruitment: The Collaborative Approach for Asian Americans, Native Hawaiians, and Pacific Islanders (AANHPI) Research and Education (CARE)
Authors: Tzuang Marian , Grill Joshua D , Tsoh Janice Y. , Huang Daren , Nam Bora , Gallagher‐Thompson Dolores , Hinton Ladson , Meyer Oanh L. , Park Van Ta 
Published: January 2025

AbstractBackgroundThe Collaborative Approach for Asian Americans, Native Hawaiians, and Pacific Islanders (AANHPI) Research and Education (CARE) is a recruitment registry that has enrolled over 10,000 AANHPI participants who expressed willingness to participate in Alzheimer’s disease and related dementias (ADRD), aging, caregiving, and other health research. We report survey results from 24 of the 28 study principal investigators (“users”) who utilized CARE between January 2021 and October 2023 to support their study recruitment.MethodUsers answered five questions on a 4‐point Likert scale (0 = Strongly disagree to 3 = Strongly agree) related to (1) user experience, (2) usefulness in accelerating recruitment, (3) improving AANHPI representation, (4) whether they would use the registry again, and (5) whether they would recommend the registry to others. The survey also included open‐ended questions for suggestions to improve the registry and collect information on products (e.g., publications) for each of the CARE‐supported studies.ResultAmong 24 CARE‐supported studies with available user survey data, 14 (58%) were related to ADRD or dementia caregiving, 10 (42%) recruited specific AANHPI sub‐groups (e.g., Chinese, Korean), and 10 (42%) were funded by the National Institutes of Health. Half of users learned about CARE through word of mouth. All users agreed or strongly agreed they would recommend the registry to others and that the referral request process was well‐organized. Also, 83% and 93% agreed or strongly agreed that CARE accelerated their study recruitment and improved the representation of AANHPI participants in their study, respectively. Lastly, 96% of users agreed or strongly agreed they would submit a referral again for future research. Open‐ended responses identified several study‐level characteristics (e.g., in‐person requirement, stringent eligibility criteria) of the referred studies as challenges to successful recruitment from the registry. Collectively, these studies have produced 12 peer‐reviewed publications and 32 abstracts at professional conferences.ConclusionUsers overall reported positive experiences with the referral process and indicated that CARE can aid recruitment and diversify study samples. CARE provides a promising recruitment source to support studies seeking to include AANHPI participants.
Feasibility and acceptability of APOE genotyping in Dutch Brain Research Registry participants
Authors: Waterink Lisa , van der Lee Sven J , Nijland Daphne , Visser Leonie N.C. , Pijnenburg Yolande A.L. , Sikkes Sietske A.M , van der Flier Wiesje M. , Zwan Marissa D. 
Published: January 2025

AbstractBackgroundParticipant recruitment for Alzheimer’s disease (AD) research and clinical trials is challenging. Online registries can be used to identify and pre‐screen eligible participants. Additional APOE genotyping has the potential to better identify individuals at‐risk for AD. Our goal was to assess feasibility and acceptability of APOE genotyping in cognitively‐normal, older registrants of Dutch Brain Research Registry (DBRR).Methods9,511 registrants over the age of 50 with no self‐reported diagnosis of mild cognitive impairment or dementia were invited for APOE genotyping. Registrants were informed that they would not receive their results, yet that results may be used to pre‐screen participants for future studies for which it might be relevant to learn their genetic risk. After providing consent on an elaborate online informed consent procedure including a video, participants were enrolled, and received a buccal swab at home. Feasibility was measured in response rate (%interested/invited), enrolment rate (%enrolled/interested), and completion rate (%returned swabs/enrolled). To assess acceptability, participants answered online questions about our information provision, the project’s aim, and motivation for study participation. APOE genotyping is currently ongoing.Result3,393 registrants were interested (35% response rate), of which 3,158 actually enrolled (93% enrolment rate; 57% female; median age [IQR] = 68 [63, 73]), and 2,602 successfully returned the buccal swab (82% completion rate; Figure 1). 20% of enrolled registrants report having subjective memory complaints, and 45% had a first‐degree relative with dementia. Of 1,065 registrants that declined participation, 344 registrants provided reasons which were mostly time related (n = 104;30%), health‐issues (n = 61;18%), or wanting to receive results of APOE genotyping (n = 59;17%). Only 8% (n = 26) replied not wanting to learn their genetic risk. Among the enrolled registrants 2,093 filled out the survey, of which the vast majority was content with our information provision (87‐97%), and had good comprehension about the project’s aim (91‐98%). Most endorsed reasons to participate was ‘to contribute to scientific research’ (97%) and ‘to participate in future research to learn their genetic risk of dementia’ (34%).ConclusionOur results suggest that APOE genotyping within an online research registry is feasible and well received for pre‐screening to accelerate inclusion for preclinical AD trials.