bluuebunny/crossref_metadata_2025_split huggingface dataset:
Monthly computerized at‐home assessments to detect cognitive change in preclinical Alzheimer’s disease
Authors: Jutten Roos J. , Amariglio Rebecca E. , Properzi Michael J , Buckley Rachel F. , Maruff Paul T , Stark Craig E. , Yassa Michael A. , Johnson Keith A. , Sperling Reisa A. , Rentz Dorene M. , Papp Kate V. 
Published: December 2021

AbstractBackgroundAlongside the increased focus on detecting Alzheimer’s disease (AD) pathology in the preclinical stage, there is a need to more rapidly track AD‐related cognitive changes that may emerge during this stage. Computerized cognitive testing has the potential to achieve this by enabling more frequent, remote, unsupervised assessments. Here, we aimed to investigate whether monthly at‐home assessments of a modified version of the Behavioural Pattern Separation Task‐Object Version (BPSO) could detect cognitive change in cognitively unimpaired (CU) individuals with and without abnormal AD biomarkers.MethodN=110 CU participants (age=77.1±4.9, 61% female, MMSE 29±1.3) from the Harvard Aging Brain Study completed the BPSO monthly at‐home on an iPad as part of the Cogstate C3 battery for up to one year (6.3±3.9 months follow‐up). All participants underwent PIB‐PET imaging (1.25±1.05 years before at‐home baseline) and a subset (n=82) underwent Flortaucipir PET (0.56±0.4 years before at‐home baseline). Primary outcome of the BPSO is a metric reflecting the ability to correctly discriminate between stimuli that are similar but not identical to previously learned targets (score range 0‐1, higher scores reflecting better performance). Linear mixed models were used to characterize BPSO performance over months (including both linear and quadratic time terms to investigate nonlinear change), and to examine associations with amyloid (dichotomous) and medial‐temporal tau deposition (continuous) while adjusting for age, sex, education and their interactions with time.ResultOverall, individuals’ BPSO performance improved over months, as shown by a significant quadratic effect of time (β=‐.002,p<.001) with a plateauing learning curve (Figure 1). On average, amyloid‐positive individuals (n=29) showed slightly worse BPSO performance (β=‐.06,p=.03) than amyloid‐negative individuals, but similar trajectories over time. However, the baseline amyloid effect was attenuated when limiting the sample to those with both amyloid and tau imaging. Less improvement over the year was associated with greater tau burden in the entorhinal cortex (Time*tau β=‐0.02,p=.019) (Figure 2).ConclusionWe show that subtle alterations in pattern separation performance over repeated exposure in CU individuals are associated with tau deposition in the medial‐temporal lobe. This implies that unsupervised computerized testing using monthly learning paradigms may be an efficient way to early detect cognitive change associated with preclinical AD.
Cortical microinfarcts along the Alzheimer's disease continuum in adults with Down syndrome
Authors: Aranha Mateus Rozalem , Bejanin Alexandre , Montal Victor , Pegueroles Jordi , Carmona‐Iragui Maria , Videla Laura , Benejam Bessy , Valldeneu Sílvia , Barroeta Isabel , Altuna Miren , Fernandez Susana , Garzón Diana , Padilla Concepción , Iulita M. Florencia , Alcolea Daniel , González‐Ortiz Sofía , Blesa Rafael , Lleó Alberto , Fortea Juan 
Published: December 2021

AbstractBackgroundCortical microinfarcts (CMI) are emerging biomarkers of vascular damage that are visually detectable with 3T‐MRI, associated with cognitive decline, and more frequent in AD patients. However, no study assessed CMI in Down syndrome (DS), a genetically determined form of AD. Therefore, we aimed to quantify CMI in a population‐based cohort of adults with DS and assess the relationship with age, sex, clinical status, and APOE genotype.MethodCross‐sectional, proof‐of‐principle study. We selected 31 adults with DS from the Down Alzheimer Barcelona Neuroimaging Initiative (DABNI) cohort with available 3T‐MR (8 asymptomatic, 11 prodromal AD, and 12 AD dementia individuals; target sample size: 200 DABNI subjects). An expert neuroradiologist blind to clinical diagnosis, age, and APOE status visually analyzed the 3T‐MRI images following previously validated protocol (Figure 1) to detect and manually segment CMI. First, we compared the presence and volume of CMI in the different clinical groups along the AD continuum, in APOEε4 carriers vs. non‐carriers, and in males vs. females using Chi‐square, Mann‐Whitney, or Kruskal‐Wallis tests when appropriate. Then, we assessed the association between the volume of CMI and age using Spearman's correlation test.ResultCMI were detected in 68% of adults with DS. The frequency of CMI was nominally higher in the prodromal and demented (73% and 75%, respectively) compared to the asymptomatic group (50%, p=0.46) and in males (70%) than females (64%, p=0.72), and significantly higher in APOEε4 carriers (100%) than non‐carriers (58%, p=0.05). The volume of CMI was nominally higher in prodromal and AD dementia patients (16.7 and 12.3mm3, respectively) than in asymptomatic subjects (2.6mm3, p=0.46), in males (12.3 mm3) than in females (7.9mm3, p=0.32), and in APOEε4 carriers (14.9mm3) compared to non‐carriers (7.9mm3, p=0.11) (Tables 1, 2 and 3). No correlations between age and CMI were observed (p=0.37, rSpearman= ‐0.17) (Figure 2).ConclusionCMI are detectable using 3T‐MRI in adults with DS and are more frequent than in the general population (6% in non‐demented elderly and 32% in AD dementia patients). They are more prevalent in APOEε4 carriers and might increase along the AD continuum and be more frequent in males.
Ethnicity influences risk of dementia in the UK Biobank
Authors: Bonnechère Bruno , Liu Jun , Thomson Alexander , Amin Najaf , Van Duijn Cornelia M 
Published: December 2021

AbstractBackgroundThe number of people with dementia is increasing globally and it is expected that low and mid‐income and minorities in high‐income countries will be more severely affected in the next decades. Yet most of the research of dementia has focused on patients of European descent. Findings of US based studies suggest differences in risk across ethnic groups but data are largely lacking with Europe. The aim of this study is to compare the risk and risk factors of dementia across ethnicities in UK.MethodWe analyzed the results of the UK Biobanks (UKB), with participants aged more than 55 year to assess prospectively the risk of dementia according to the ethnicities. The data of all‐cause dementia was obtained from the hospital inpatiant records available. All the previously identified genetic, medical, lifestyle and environmental risk factors were studied using Cox‐regression, adjusting for age, sex and other putative confounders. 278,376 participants were included in the final analysis, among whom the vast majority are identified as White (97.79%) by UKB, followed by Asian (1.36%), and Black (0.84%). The mean duration of the follow‐up was 11.2 years with 3,111,197 person‐years in total.Result5,029 participants developed dementia during the follow‐up: the incidence of dementia is 160 cases/100,000 person‐years in White, 178 cases/100,000 person‐years in Asian, and 274/100,000 person‐years in Black. After adjusting for risk factors, participants identified as Black in the UKB are at increased risk of developing dementia (HR = 1.63 [1.22 – 2.19], p < .002), but not (HR = 1.14 [0.85 – 1.54], p = .205). This increased risk may be due to the higher proportion of APOE44 carriers in UKB Blacks (5.4%) compared to Whites (2.3%) and Asians (1.1%) but also more frequent comorbidity including head trauma and hypertension. Despite the higher prevalence of diabetes and related factors in those of Asian descent, the risk of dementia was not significantly increased.ConclusionIn contrast to earlier US based findings, our study shows an increased risk of dementia in those of African descent living in the UK, which is partly explained by genetic risk factors and comorbidity.
A high‐performance biomarker panel for Alzheimer’s disease screening and staging identified by large‐scale plasma proteomic profiling
Authors: Jiang Yuanbing , Zhou Xiaopu , Ip Fanny C.F. , Chan Philip , Chen Yu , Lai Nicole Chit Hang , Cheung Kit , Lo Ronnie M.N. , Tong Estella Pui‐Sze , Wong Bonnie W.Y. , Chan Andrew L.T. , Mok Vincent C.T. , Kwok Timothy C.Y. , Mok Kin Y. , Hardy John , Zetterberg Henrik , Fu Amy K.Y. , Ip Nancy Y. 
Published: December 2021

AbstractBackgroundBlood proteins are emerging candidate biomarkers for Alzheimer’s disease (AD). A comprehensive investigation of the AD blood proteome will help identify additional biomarkers to delineate the disease’s pathways and define specific AD stages.MethodWe quantified 1,160 plasma proteins in a Hong Kong Chinese cohort (n = 106 AD patients, n = 74 healthy controls) by high‐throughput proximity extension assay to identify AD‐associated plasma proteins.ResultPlasma proteins involved in diverse biological processes were found to be dysregulated in AD. A subset of plasma proteins was selected to represent the AD plasma protein profile, which formed the basis of a scoring system that can accurately classify AD and associated endophenotypes. In addition, we showed that certain plasma proteins and biological processes exhibit stage‐specific dysregulation in AD, thus adding biological annotations to AD stages.ConclusionThis study comprehensively profiled the AD plasma proteome and serves as a foundation for a high‐performance, blood‐based test for clinical AD screening and staging.
Neural signatures of meaning in life dimensions and its contribution to self‐perceived cognition in middle‐aged individuals
Authors: Abellaneda‐Pérez Kilian , Cattaneo Gabriele , Cabello‐Toscano María R , Vaqué‐Alcázar Lídia , Solana Javier , Mulet‐Pons Lídia , Bargalló Núria , Tormos‐Muñoz Josep M , Pascual‐Leone Alvaro , Bartrés‐Faz David 
Published: December 2021

AbstractBackgroundMeaning in life (MiL) encompasses purpose in life (PiL), engagement with life (EwL), and sense of coherence (SoC) dimensions. MiL estimates have been associated with self‐reported cognitive status amongst middle‐aged individuals (Bartrés‐Faz et al., Alzheimers Res Ther. 2018;10(1):47). Later in life, MiL factors have been related to reduced cognitive decline and delayed onset of dementia in Alzheimer’s disease (AD; Boyle et al., Arch Gen Psychiatry. 2010;67(3):304‐310). However, how MiL dimensions are associated with brain networks’ expression and if these functional systems could mediate the influence of MiL on self‐perceived cognition remains unknown.MethodsDemographic, cognitive, and neuroimaging data was obtained from 585 middle‐aged adults (mean age 54.26 ± 7.1; 289 women) from the Barcelona Brain Health Initiative cohort (https://bbhi.cat/en/). Linear regression analyses were used to investigate the associations between MiL and its three dimensions [motivational (PiL), emotional (EwL), and cognitive (SoC)] and the strength of functional connectivity within the main brain resting‐state networks (RSNs; Shirer et al. Cereb Cortex. 2012;22(1):158‐165). Further analyses were computed to explore to which extent RSNs mediate the effect of MiL and its dimensions on self‐reported cognition, derived from the PROMIS® Cognitive Abilities and Concerns scale. Data was adjusted for age, personality, cognitive reserve, and affective status. Correction for multiple comparisons was applied.ResultsMiL estimates and its SoC factor, but not EwL and PiL, were correlated with RSNs. Specifically, significant associations for SoC emerged for those RSNs linked to higher‐order cognitive processing, such as the default‐mode, the salience and the left and right executive‐control networks. However, associations with sensorimotor systems were not significant. The links between SoC and self‐perceived cognitive function were mediated by the salience and the left executive‐control circuits (Fig. 1).ConclusionThe observed associations between SoC and the functional systems subtending cognitive processing, but not sensorimotor functions, may be related to previous observations indicating that MiL‐related factors are associated to greater than expected cognitive function for a given level of AD pathological load (Boyle et al., Arch Gen Psychiatry. 2012;69(5):499‐505), therefore promoting brain resilience in advanced age.
Is depression associated with cognitive decline in a diverse cohort of the oldest‐old? Findings from the LifeAfter90 Study
Authors: Whitmer Rachel A. , Gilsanz Paola , Mungas Dan M. , George Kristen M. , DeCarli Charles S. , Kawas Claudia H. , Vieira Katharine E. , Glymour M. Maria , Corrada Maria M. 
Published: December 2021

AbstractBackgroundDepression impacts 50% of the elderly population and is a risk factor for dementia but its prevalence and role in cognitive decline in Non‐Whites and the oldest‐old is unclear.MethodLifeAfter90 is a racially/ethnically diverse cohort of individuals aged 90+ that launched in 2018 with the aim of characterizing cognitive and brain aging after the 9th decade of life. Participants are members of an integrated healthcare delivery system without a dementia diagnosis in their medical record at recruitment. Depression at baseline was evaluated with the Global Depression Scale (GDS) and defined as GDS>4. Cognitive testing every 6 months uses the Spanish and English Neuropsychological Assessment Scales (SENAS), to assess cognitive domains of episodic memory, semantic memory, and executive function. Linear mixed models with random intercepts, evaluated the baseline and longitudinal association of depression with each SENAS domain. The models used years since baseline as the time variable, and adjusted for baseline age, sex, race/ethnicity, education, and practice effects. An interaction term (depression*time) tested for differences in decline in cognitive domains by baseline depression status.ResultOf 655 participants 32% are White, 22% Asian, 22% Black, 15% Latino, and 8% Other/Multiracial. 35% had <high school education, 38% were male, and mean age was 93 years. At baseline, 32% were classified as having depression with the highest prevalence among Latinos and those with <high school education (Table 1). The average follow‐up was 0.9 years (range: 0‐1.9). Depression was associated with poorer semantic memory (ß=‐0.17) and executive function (ß=‐0.18) but not with episodic memory (Table 2). Semantic memory (ß=‐0.28) and executive function (ß=‐0.11) decreased over time, however episodic memory did not. The semantic memory and executive function decline did not differ by depression (Figure 1 & Table 2).ConclusionDepression impacts one third of this ethnically diverse cohort of oldest‐old individuals and ais more prevalent in Latino participants. While depression is associated with poorer baseline semantic memory and executive function; it is not associated with episodic memory, nor is it associated with greater cognitive decline. These results suggest that while depression may impact cognitive performance it may not impact cognitive change in those aged 90+.
Towards optimizing the measurement of self‐perceived cognitive functioning: Examination of harmonized subjective cognitive items
Authors: Rabin Laura , Tommet Douglas , Jones Richard N , Crane Paul K. , Sikkes Sietske A.M. ,   SCD‐I Working Group, SCD‐PIA
Published: December 2021

AbstractBackgroundFor the item analysis project of the Subjective Cognitive Decline Initiative (SCD‐I) Working Group, we have pooled item level data from North American, European, and Australian cognitive aging studies. As a step toward developing a questionnaire that can be used across settings and studies, we examined similarly worded groups of items and compared their psychometric quality.MethodItem‐level subjective cognitive data were combined from 21 studies (>18,000 participants). Unidimensional models consistent with item response theory captured a general subjective cognition factor using ADNI as the reference sample. Other studies were calibrated by using parameter constraints on common items. We characterized the measurement properties of 648 items from 35 measures utilized in the contributing studies. Next, we identified 20 groups of items (median items per group=6) with overlapping content from our previous study (Rabin et al., 2015), and plotted their item information curves, reflecting the items’ ability to discriminate between trait scores at different levels of the subjective cognition factor score. We then considered items with the highest peak information across groupings and identified commonalities in key features such as terminology of item stems, temporal referents, and response options.ResultWe present instrument characteristics (Table 1) and item information curves for 6 groupings (Figure 1). For items with the greatest information, we observed trends for the following features: clarity and directness of language of stem, utilization of current as opposed to other time referents, assessment of ability/level of difficulty rather than change over time or frequency of problem (Table 2).ConclusionWe identified key linguistic/structural features of subjective cognitive functioning items with the greatest contributions to measurement precision. We next plan to analyze all item groupings in our test bank to facilitate construction of a measure with high quality items from cognitive domains of interest (e.g., memory, language, executive functioning). Ultimately, we hope to derive a subjective cognitive screening tool that enables reliable identification of subtle cognitive changes in clinically normal individuals.
A remote smartphone cognitive testing battery for frontotemporal dementia: Completion rate, reliability, and validity
Authors: Staffaroni Adam M. , Taylor Jack C , Clark Annie L , Heuer Hilary W. , Forsberg Leah K. , Bahl Riley , Manoochehri Masood , Vento Stephanie , Bajorek Lynn P. , Ong Elise , You Michelle , Boeve Bradley F. , Kramer Joel H , Rosen Howard J. , Boxer Adam L. 
Published: December 2021

AbstractBackgroundIn preparation for treatment trials in frontotemporal dementia (FTD), sensitive assessments to detect early clinical deficits and track longitudinal changes are needed. Remote digital data collection using smartphones may improve sensitivity to detect and follow abnormalities by allowing novel methods of data capture and more frequent assessments. Furthermore, remote evaluations can reduce patient and staff burden. Despite these benefits, little is known about the reliability and validity of self‐administered cognitive testing completed on smartphones.MethodWe investigated self‐administered smartphone cognitive tests from the ALLFTD Mobile App in a mixed sample of 45 participants, including 10 functionally intact older adults, 24 participants from families harboring pathogenic FTD mutations (asymptomatic n=14; mildly symptomatic n=10;), and 11 symptomatic FTD‐spectrum participants. A subset (n=15) was missing CDR®+NACC‐FTLD data but consensus diagnoses were available. Participants were asked to complete five tests that were repeated three times over eight days. Tests included versions of N‐back, Stroop, Flanker, and Go/No‐Go paradigms, and an adaptive spatial working memory test. Reliability was assessed using split‐half reliability (first testing session, 100 simulations) and intraclass correlations (ICC) across the three testing sessions. Linear models were fitted to evaluate the association of test performance with age and disease severity (CDR®+NACC‐FTLD Global and Box Scores), covarying for sex and education level. Models evaluating age associations excluded symptomatic participants.ResultParticipants completed 72.4% of available instruments. Split‐half reliability (range: 0.76 to 0.97) and ICCs (0.70 to 0.92) suggested adequate‐to‐excellent internal consistency and test‐retest reliability. Across the five tests, negative associations were observed with CDR®+NACC‐FTLD Box Scores (ßs = ‐0.24 to ‐0.77), and in clinically asymptomatic individuals, negative associations were observed with age (ßs = ‐0.43 to ‐0.88). Performance on all measures was worse in symptomatic participants compared to asymptomatic (p‐values<.05). Mildly symptomatic cases (CDR®+NACC‐FTLD=0.5) performed worse on Stroop, Flanker, and spatial working memory than asymptomatic participants (p‐values<.03). Flanker and Stroop tasks consistently showed the strongest reliability and validity findings.ConclusionSmartphone adaptations of common neuropsychological tests produced promising preliminary results. Strong associations with disease severity and age suggest these metrics may be valid for detecting clinically relevant cognitive changes, even in mildly symptomatic FTD.
Association of air quality improvement with slower decline of cognitive function in older women
Authors: Younan Diana , Wang Xinhui , Millstein Joshua , Petkus Andrew J , Beavers Daniel P , Espeland Mark A , Chui Helena C , Resnick Susan M , Gatz Margaret , Kaufman Joel D , Wellenius Gregory , Whitsel Eric A , Manson JoAnn E , Rapp Stephen R , Chen Jiu‐Chiuan 
Published: December 2021

AbstractBackgroundLate‐life exposure to ambient air pollution is a modifiable risk factor for dementia, but epidemiological studies have shown inconsistent evidence for cognitive decline. Improved air quality (AQ) is associated with decreased mortality and improved respiratory health, but no studies have examined the association with cognitive function.MethodsParticipants included 2,232 U.S. community‐dwelling older women (aged 74‐92) from the Women’s Health Initiative Memory Study‐Epidemiology of Cognitive Health Outcomes (WHIMS‐ECHO) without dementia at enrollment. Measures of annual (2008‐18) cognitive function included general cognitive status (assessed by the Telephone Interview for Cognitive Status‐modified, TICSm) and episodic memory (assessed by the telephone‐based California Verbal Learning Test, CVLT). Regionalized universal kriging models were used to estimate annual exposures (1996‐2012) to fine particulate matter (PM2.5) and nitrogen dioxide (NO2) at residential locations, which were averaged over the 3‐year periods immediately preceding (recent exposure) and 10 years prior to (remote exposure) WHIMS‐ECHO enrollment. Individual‐level improvements in AQ were calculated as the reduction from remote to recent exposures. We used linear mixed effect models to examine the associations between improved AQ and the rates of cognitive decline in TICSm and CVLT trajectories, adjusting for sociodemographic, lifestyle, and clinical characteristics.ResultsAQ improved significantly for both PM2.5 and NO2 over the 10 years before enrollment. During a median of 6.2 (inter‐quartile‐range [IQR]=5.0) years of follow‐up, general cognitive status (βTICSm=‐0.42/year, 95% CI: ‐0.44, ‐0.40) and episodic memory (βCVLT=‐0.59/year, 95% CI: ‐0.64, ‐0.54) significantly declined. Greater AQ improvement was associated with slower decline in TICSm (βPM2.5=0.026/year per IQR=1.79 µg/m3, 95% CI: 0.001, 0.05; βNO2=0.034/year per IQR=3.92 ppb, 95% CI: 0.01, 0.06) and CVLT (βPM2.5=0.070/year per IQR=1.79 µg/m3, 95% CI: 0.02, 0.12; βNO2=0.060/year per IQR=3.97 ppb, 95% CI: 0.005, 0.12). The respective associations with TICSm and CVLT were equivalent to the slower declines found in women 0.9‐1.2 and 1.4‐1.6 years younger, and did not significantly differ by age, region, education, ApoE e4 genotypes, or cardiovascular risk factors. The benefits were attenuated after excluding incident dementia cases but remained after excluding prevalent or incident stroke cases.ConclusionsLong‐term improvement in AQ in late‐life was associated with slower cognitive declines in older women.