bluuebunny/crossref_metadata_2025_split huggingface dataset:
Continuous associations between remote self‐administered cognitive measures and amyloid and tau PET biomarkers of Alzheimer’s disease
Authors: Boots Elizabeth A. , Frank Ryan D. , Fan Winnie Z. , Christianson Teresa J. , Karstens Aimee J. , Kremers Walter K. , Stricker John L. , Machulda Mary M. , Fields Julie A. , Hassenstab Jason J. , Graff‐Radford Jonathan , Vemuri Prashanthi , Jack Clifford R. , Knopman David S. , Mielke Michelle M. , Petersen Ronald C. , Stricker Nikki H. 
Published: December 2023

AbstractBackgroundEasily accessible and self‐administered cognitive assessments that can aide early identification of individuals at risk for Alzheimer’s disease (AD) dementia are critical for timely intervention. Mayo Test Drive (MTD) is a remote, self‐administered, multi‐device compatible, web‐based cognitive assessment (Stricker et al., 2022). We investigated continuous associations between MTD and amyloid and tau PET biomarkers and compared the strength of association to PET biomarkers and in‐person cognitive measures.Method556 adults from the Mayo Clinic Study of Aging participated (mean age = 70.6; mean education = 16.0 years; 50.7% female; 97.5% white). Participants were predominantly cognitively unimpaired (95.3%; 4.7% had a consensus diagnosis of mild cognitive impairment). Participants completed (1) brain amyloid and tau PET scans, (2) in‐person neuropsychological assessment including Mayo Preclinical Alzheimer’s disease Cognitive Composite (Mayo‐PACC) and Global‐z, and (3) remote MTD comprised of the Stricker Learning Span (SLS) and the Symbols test, which are combined into an MTD composite. Multiple regressions adjusted for age, sex, and education queried associations between imaging biomarkers [amyloid meta‐region of interest (ROI), tau meta‐ROI, and tau entorhinal cortex (EC)‐ROI)] and composite and subtest scores from remote and in‐person measures. Davidson‐Mackinnon J‐test compared R‐squared values of models with remote versus in‐person composites.ResultLower performances on MTD composite and Mayo‐PACC were associated with higher amyloid meta‐ROI (p’s<.05; Table 1). MTD composite was also negatively associated with tau meta‐ROI and EC‐ROI (p’s<.05). For memory measures, SLS sum of trials was negatively associated with tau meta‐ROI (p = .01) and EC‐ROI (p<.001) with no associations between AVLT sum of trials and PET (p’s≥.06; Table 2). Among processing speed/executive function measures, worse Trails B performance was associated with higher amyloid meta‐ROI (p<.001). Symbols and Digit Symbol Coding were not associated with PET (p’s≥.29). A multivariable model with MTD explained significantly less variance (p = .04) for amyloid meta‐ROI (adjusted R‐squared = 0.165) than a multivariable model with Mayo‐PACC (adjusted R‐squared = 0.176); remote and in‐person composite measures were comparable for other associations (p’s>.05).ConclusionMTD is associated with continuous measures of amyloid and tau PET biomarkers of AD, demonstrating criterion validity for MTD. Several associations were comparable to relationships between gold‐standard in‐person neuropsychological tests and imaging biomarkers.
Low circulating choline levels correlate with Alzheimer’s disease pathology severity and cognitive impairment
Authors: Judd Jessica M , Winslow Wendy , Jasbi Paniz , Klein‐Seetharaman Judith , Velazquez Ramon 
Published: December 2023

AbstractBackgroundModifiable environmental risk factors may help reduce Alzheimer’s disease (AD) incidence. Choline plays key roles in healthy body and brain function (Blusztajn, 1998) and supplementation above the adequate daily intake (ADI) reduces AD pathology (Velazquez et al., 2019). Choline deficiency increases AD risk and pathology (Dave et al., 2023; Yuan et al., 2022). Notably, recent reports estimate that ∼90% of Americans do not reach the ADI for dietary choline (Zeisel, 2017), making it imperative to better understand the link between choline and AD risk.MethodWe obtained serum samples from severe AD (AD‐Sev; Braak stage VI), moderate AD (AD‐Mod; Braak stage IV), and healthy control (CON; < Braak stage III) subjects (n = 12/group; balanced for sex) from the Banner Sun Health Research Institute’s Brain and Body Donation Program. Cognitive test scores (Mini‐Mental State Examination (MMSE)), plaque burden, and Braak stage was characterized by Banner Sun Health. We assessed free choline, acetylcholine (ACh), and TNFα levels. Gas‐chromatography‐mass spectrometry was used to profile aqueous metabolites and short‐chain fatty acids.ResultThere were no significant group differences for post‐mortem interval (M = 3.79). We found disease associated differences, where AD‐Sev and AD‐Mod patients had lower levels of free choline and ACh, and higher levels of pro‐inflammatory cytokine TNFα, than CON. AD‐Mod showed a significant difference in all these measurements compared to AD‐Sev. Free choline and ACh were positively correlated to MMSE scores, whereas free choline and ACh levels were negatively correlated with total plaque and Braak Stage. Free choline and ACh were negatively correlated with TNFα. Metabolomics analysis revealed significant differences (p < 0.05) in the metabolisms of beta‐alanine, linoleic acid, and of taurine and hypotaurine.ConclusionCollectively, as free choline and ACh levels decreased, AD pathology increased. Free choline was also associated with MMSE score. Increased TNFα was observed in cases with lower choline, illustrating increased inflammation. Together, this data expands on our recent (Dave et al., 2023) and others (Yuan et al., 2022) publications, highlighting links between low choline and AD risk.
Regional dementia diagnostic intensity and healthcare use among older U.S. adults living with Alzheimer’s disease and other related dementias
Authors: Davis Matthew A. 
Published: December 2023

AbstractBackgroundRecent studies have demonstrated that the diagnosis of Alzheimer’s disease and other related dementias (ADRD) varies across the U.S. Residing in an area of high ADRD identification may be associated with better care; yet, healthcare use according to regional ADRD diagnosis intensity has not be examined.MethodWe conducted a cross‐sectional study using a 20% sample of 2018 Fee‐For‐Service Medicare older Americans (age≥65). Diagnosis codes were to identify those who received a new ADRD diagnosis (incident cohort) and those who died with an ADRD diagnosis (decedent cohort). An established measure of ADRD diagnostic intensity across the 306 U.S. Hospital Referral Regions was used and collapsed into terciles. We constructed measures of healthcare use (e.g., outpatient visits, inpatient use) in the first year following diagnosis and the last six months of life. Measures of preventable hospitalizations among those newly diagnosed and measures on life‐prolonging treatment among ADRD decedents were also constructed. Mixed models were used to adjust for sociodemographic characteristics and comorbidity and account for clustering within region of residence.ResultWe identified 158,908 older Americans who received a new ADRD diagnosis and 97,431 ADRD decedents in 2018. The mean age of the incident ADRD cohort was 82.8 (SD = 8.0) and 85.9 (SD = 7.8) among the decedent cohort. Across both cohorts, approximately 61% were female and 83% were While older adults. In adjusted analyses among the incident cohort, the only two differences across tercile of ADRD diagnostic intensity were mean No. of home health days (from 26.4 in T1 (lowest) to 40.3 in T3 (highest), p‐value<0.001) and mean No. of inpatient days, p‐value = 0.01 (Table 1). After adjusting for differences, outpatient, inpatient, and life‐prolonging treatment did not vary across tercile of ADRD diagnostic intensity among ADRD decedents – except for mean No. of home health days, p‐value< 0.001, hospice use in the last year of life, p‐value = 0.03, and ‘other inpatient’ as a place of death, p‐value = 0.02 (Table 2 and Figure 1).ConclusionAcross the disease course of ADRD, regional ADRD diagnostic intensity is not associated with worse healthcare (e.g., ED use, preventable hospitalization) but is associated with home healthcare and higher hospice use.
Education protects against the detrimental effect of hippocampal atrophy on episodic memory decline
Authors: LaPlume Annalise , Mellah Samira , Rajah Natasha , Belleville Sylvie 
Published: December 2023

AbstractBackgroundHippocampal volume loss and episodic memory decline are early signs of Alzheimer’s disease (AD). Cognitive reserve refers to individual differences that enable people to perform cognitive tasks at a higher level than expected based on their current level of neurodegeneration (Stern et al., 2020).In the current study we test the hypothesis that education, a sociobehavioural proxy of reserve, moderates the association between hippocampal atrophy and memory function in persons at preclinical stages of AD.MethodData from the Quebec Consortium for the early identification of Alzheimer’s disease were used (CIMAQ; Belleville et al., 2019). Sixty two older adults (38 females, 24 males; mean age = 74 years old, SD = 5.4, range = 65‐88; mean education = 15 years, SD = 3.3, range = 7‐22) were diagnosed with subjective cognitive decline (SCD) or mild cognitive impairment (MCI). Anatomical 3D‐T1‐w MRIs were collected at baseline and used to calculate hippocampal volume with FreeSurfer 5.3 (Belleville et al., 2021). A Face‐Name associative memory test was conducted at three time points: baseline, two years later, and four years later. Memory change was measured as the average individual slope (over three time points) of associative memory accuracy (correctly recognizing face‐name pairs). Analyses were conducted with using R (R Core Team, 2020).ResultYears of education significantly moderated the effect of hippocampal volume on memory over time, β = ‐1.97 (SE = 0.93; 95% CI = ‐3.83, ‐0.11), p = .04. Hippocampal volume had a significant negative correlation with memory over time in people with lower education levels (1 SD below the mean), but not for mean levels or higher education levels (1 SD above the mean; Figure 1). A Johnson‐Neyman plot revealed that people with over 14 years of education showed resilience to the negative association of hippocampal volume loss and memory over time, while those with 14 years or below did not (Figure 2).ConclusionEducational attainment contributes to cognitive reserve by buffering against the detrimental effect of hippocampal atrophy on declining associative memory in preclinical AD. The current findings offer practical relevance by showing that 14 years is a threshold amount of education that confers a protective influence against memory decline.
The relationship of neuroticism to amyloid and tau pathologies in cognitively normal older adults
Authors: Bacci Julia R. , Hennessee Joseph P. , Smith Evan T. , Monier Sarah A. , Park Denise C. 
Published: December 2023

AbstractBackgroundPrior work has shown that individuals with higher levels of neuroticism are at an increased risk of developing Alzheimer’s Disease (AD). Increasing evidence has indicated an association of increased neuroticism to increased amyloid‐beta (Aβ) and tau burdens, suggesting that this personality trait is a risk factor for increased pathological accumulations. However, the cross‐sectional nature of these studies do not offer the ability to infer causality. Here, we replicate and extend upon previous work, assessing the relationship of neuroticism to AD pathologies in 60 older adults across three time‐points.MethodThis study included 60 cognitively normal participants from the Dallas LifeSpan Brain Study, aged 50+, that completed three time‐points of cortical Aβ scanning and a baseline personality assessment. Linear regressions were used to model the relationship of neuroticism to cortical Aβ burden (n = 60) and cortical tau burden (n = 48). Utilizing linear mixed effects models, neuroticism was used to predict cortical Aβ accumulation over 7‐10 years.ResultWe found that the effects of neuroticism on AD pathologies differs by brain regions and facets of neuroticism. Most notably, increased neuroticism predicted increased global Aβ burden (p = .042) beyond the effects of baseline age, sex, education, and depressive symptoms. When we further investigated this relationship using the facets comprising the neuroticism score, only the anger‐hostility facet of neuroticism predicted increased global Aβ burden (p = .003). Regional investigations demonstrated a significant effect of neuroticism on Aβ burden in the anterior cingulate cortex (p = .028), lateral parietal cortex (p = .035), and the posterior cingulate cortex (p = .021) and a trending effect in the dorsolateral prefrontal cortex (DLPFC) (p = .054). Contrary to our hypotheses, we did not find a significant effect of neuroticism on global or regional Aβ accumulation. Tau analyses detected an effect of neuroticism on tau burden in the DLPFC (p = .03), a predetermined region of interest. Additionally, only the anger‐hostility facet of neuroticism significantly predicted global tau burden (p = .036).ConclusionThis work demonstrates that certain regions of the brain may be at an increased risk for AD pathologies in individuals with higher neuroticism. Specific facets of neuroticism, such as anger‐hostility, may also confer additional risk for these augmented accumulations.
Cerebral amyloid angiopathy is associated with higher gray matter regional R2 relaxation rate: An ex‐vivo MRI and pathology study
Authors: Yasar Md Tahmid , Evia Arnold M , Bennett David A. A , Schneider Julie A , Arfanakis Konstantinos 
Published: December 2023

AbstractBackgroundCerebral amyloid angiopathy (CAA) is characterized by accumulation of amyloid‐β (Aβ) protein in the walls of cortical and meningeal small vessels. CAA is common in older adults. It has been linked to intracerebral hemorrhage and cognitive decline. In this study, the association of CAA with the transverse relaxation rate R2 values was investigated in gray matter regions from a large number of community‐based older adults.MethodCerebral hemispheres from 802 older adults participating in four cohort studies of aging, the Rush Memory and Aging Project, the Minority Aging Research Study, the Religious Orders Study, and the Clinical Core of the Rush Alzheimer’s Disease Research Center (Fig. 1a) were included in this work. All hemispheres were imaged ex‐vivo using 3T MRI scanners. R2 maps were generated from multi‐echo spin‐echo images. Gray matter was segmented into 34 cortical and 8 subcortical regions. Median R2 values were obtained from each region.Following ex‐vivo MRI, all hemispheres underwent detailed neuropathologic assessment (Fig. 1b). Evaluated neuropathologies included: CAA, Aβ plaques, neurofibrillary tangles, gross infarcts, microinfarcts, TDP‐43 pathology, hippocampal sclerosis, Lewy bodies, atherosclerosis, and arteriolosclerosis.Multiple linear regression was conducted in each segmented gray matter region separately to test the association of the corresponding median R2 value with the global CAA score, controlling for all other neuropathologies, age at death, sex, education, postmortem interval to fixation and to imaging, and scanners. False discovery rate (FDR) was used to correct for multiple comparisons. Statistical significance was set at p<0.05.ResultA significant positive association of median R2 with CAA pathology was found in several cortical regions of the temporal and frontal lobes as well as in subcortical structures (Fig. 2,3). No gray matter region showed lower median R2 for higher CAA score. Furthermore, we obtained similar findings when also controlling in the linear regression models for normalized regional volume and for clinical variables such as history of hypertension, diabetes, smoking, blood pressure levels, and the presence of the APOE‐ε4 allele.ConclusionThis investigation showed that CAA is independently associated with elongated R2 in cortical regions of the temporal and frontal lobes as well as in subcortical structures.
Sharing History through Active Reminiscence and Photo‐imagery: Effect of Walking Reminiscence Therapy on Mental Health Among Older Black Adults in Gentrifying Neighborhoods
Authors: Fennell Charles T , Fuller Patrice , Aron Sophia , Wachana Ann , Kaye Jeffrey A , Croff Raina 
Published: December 2023

AbstractBackgroundOlder Black adults facing gentrification may engage less in neighborhood walking and social opportunities because of gentrification’s effect on mental health. Reminiscence therapy promotes coping which mediates negative feelings, improves mood and emotional well‐being, and improves depressive symptoms.MethodThe Sharing History Through Active Reminiscence and Photo‐Imagery (SHARP) Study integrated reminiscence with neighborhood walking. In two pilots (n = 19 healthy; n = 21 including 8 with MCI) Black adults aged >55 engaged in image‐prompted conversations about local history while walking 1‐mile 3x/week for 6 months in Portland, Oregon’s historically Black neighborhoods. At months 1, 3, and 6, surveys assessed past‐month mental health and mood. Focus groups assessed participant satisfaction with the intervention.ResultSeventy‐five percent of participants completed all pilot measures, including all 8 with MCI. Pre/post rankings of “all,” “most,” or “a good bit” of the time (vs. “some,” “little,” or “none of the time”) in the past 4 weeks feeling downhearted/blue was maintained in Pilot 1 at 8%, but in Pilot 2 increased 0% to 10% (healthy) and decreased 13% to 0% (MCI). Feeling calm or peaceful increased in Pilot 1 67% to 83%, and in Pilot 2 60% to 80% (healthy) and 50% to 75% (MCI). Having lots of energy decreased in Pilot 1 92% to 83%, and increased in Pilot 2 70% to 80% (healthy) and 14% to 88% (MCI). In pilots combined, 93% ranked their mood “better” right after group walks and 90% ranked their mood “better” since walks began. In discussions, participants described reminiscing while walking as “joyful,” “very important,” and “something to look forward to.” Conversational reminiscence helped them “become more engaged,” “go through all their feelings” and “respond to changes in a healthy manner."ConclusionReminiscence therapy, particularly when paired with walking, may be critical for developing positive coping to mediate the trauma of gentrification and improve mood among older Black adults. Group reminiscence therapy may help healthy and impaired older Black adults cope with neighborhood changes and maintain good mental health, critical for supporting other healthy behaviors like physical and social activity that may prevent cognitive decline and onset of dementia symptoms.
The impact of female reproductive period length, parity, and hormonal replacement therapy on cognitive performance
Authors: Keinert Ana A M , Bertola Laiss , Lima‐Costa Maria Fernanda , Ferri Cleusa P , Barbosa Matheus Ghossain 
Published: December 2023

AbstractBackgroundSome evidence suggests that Alzheimer’s disease and cognitive decline are more prevalent in women and that risk factors specific to the female sex could be involved. The aim of this study is to estimate the association between the length of female reproductive period, parity, hormonal replacement therapy (HRT) and later life cognition in a large cohort of Brazilian older adults.MethodWe analyzed cross‐sectional data from 4,558 women and 3,799 men. Cognitive function was measured through a global cognitive score composed of orientation, verbal fluency, and memory tests. Age at menarche and menopause, parity and use of HRT were self‐reported. Multiple linear regression analyses were performed to identify hormone related factors associated with current cognitive functioning in women, adjusting for relevant covariates. Afterwards, we performed an analysis among men for number of children.ResultHigher parity was associated with worse cognitive functioning (β = ‐0.01, p < 0.001), while lengthier reproductive life (β = 0.00, p = 0.001) and HRT use (β = 0.04, p = 0.023) were associated with better cognitive performance. We performed a sensitivity analysis, after dividing women into parity groups. When compared with 0 births, the group with 1‐5 had better cognition (β = 0.08, p = 0.001), while the other groups displayed no differences. After excluding nulliparous women, compared to women with 1‐5 births, women with 6‐10 (β = ‐0.1, p < 0.001) and 11+ births (β = ‐0.16, p < 0.001) had an increasingly worse cognitive performance. We also analyzed number of children data for men, which had no impact on cognition (β = ‐0.00, p = 0.688).ConclusionResults indicate a protective effect on cognition of longer reproductive life, HRT use and 1‐5 childbirths, when compared to being nulliparous or having 6+ births. Among men, number of children was not associated with cognitive performance. These findings indicate a positive effect of estrogen on the brain, unrelated to current offspring. This effect might be mitigated by frequent pregnancies, but a smaller number of childbirths may not be enough to exert an impact, while bringing positive psychological effects that are protective for cognition.
Design and application of a game‐based WeChat mini‐program for screening cognitive impairments in Chinese older adults
Authors: Wu Jingnan , Chen Nan , Xia Huanhuan , Wang Ziming , Li Yatian 
Published: December 2023

AbstractBackgroundEarly screening for mild cognitive impairment (MCI) is the key method to prevent and delay dementia. Digital screening tools are more efficient than traditional paper‐and‐pencil cognitive assessments, and gamified versions would promote engagement and completion rates. We introduced here the design and development of the Game‐based Cognitive Assessment ‐ 3 Minute Version (G3) WeChat mini‐program for MCI screening in Chinese older adults.MethodG3 is a battery of three one‐minute digital games built within the WeChat platform. Developed based on the cognitive paradigm and classic neuropsychological tests such as Trail Making Test (TMT), the Silhouettes test, the Brief Visuospatial Memory Test‐Revised (BVMT‐R) test, and California Card Sorting Tests (CCST), the G3 mini‐games, “Number Ordering”, “Species Sorting”, and “Gold finding” would measure the computational and executive function, abstractive function and visual perception, memory, and attention, respectively. In each game, the difficulty will be automatically adjusted according to performance. G3 integrates users’ game scores, age, gender, and education levels, to generate a comprehensive assessment of cognitive function with results of the six cognitive domains (Figure 2).ResultAs of August 31, 2022, more than 11 million users have completed G3 tests, 85.38% of them are aged under 40, and 2.05% of them are aged over 60 (Figure 3). Although people in all age groups have desired to know their cognitive function, the number of users decreased as people aged. Among users aged 40‐70, more females than males participated in G3 games, indicating middle‐aged and older women paid more attention to cognitive function. Among users over 45 years old, those of lower education levels (primary school or no education), middle levels (middle or high school), and university degrees accounted for 2.93%, 32.4%, and 59.65% respectively. The completion rate of users aged over 45 is 92.28%, and those over 80 years exceeded 86%.ConclusionThe G3 was a battery of three novel 1‐minute game‐based digital cognitive tests. The process is simple, efficient, and interesting. It is a promising tool for self‐administering, advancing large‐scale community screening, and social education for MCI in Chinese older adults, warranting further clinical trials to validate its feasibility, sensitivity, and diagnostic value.