bluuebunny/crossref_metadata_2025_split huggingface dataset:
Smartphone‐based long‐term delayed memory performance is associated with the Preclinical Alzheimer’s Cognitive Composite and CSF levels of β‐amyloid
Authors: Öhman Fredrik , Berron David , Skoog Johan , Bodin Timothy Hadarsson , Kern Silke , Zettergren Anna , Papp Kathryn V. , Zetterberg Henrik , Blennow Kaj , Skoog Ingmar , Schöll Michael 
Published: December 2022

AbstractBackgroundRemote and unsupervised cognitive testing using smartphones may improve sensitivity to detect preclinical Alzheimer’s disease (AD). In particular, cognitive testing at‐home enables the evaluation of the potentially more sensitive long‐term delayed memory retrieval, which is commonly not feasible in a clinical setting.MethodHere, we investigated the association between remote and unsupervised smartphone‐based cognitive assessments and in‐clinic cognitive measurement in older participants (CDR = 0, MMSE = 29.2, age = 77). The sample (non‐demented at age 70) was derived from the Swedish population‐based Gothenburg H70 Birth Cohort Studies. In a subsample of participants, the retrospective correlation with cerebrospinal fluid (CSF) biomarkers analyzed at age 70 was further explored. To this point, 177 H70‐participants have consented and were enrolled into the smartphone sub‐study. They completed an “Object‐in‐Room Recall Test“ (ORR) remotely and unsupervised using own mobile devices, and the recall session was initiated 24 hours after the initial learning phase. Available previously assessed CSF measures included the Aβ42/Aβ40‐ratio, t‐tau, p‐tau, neurofilament light (NFL), and neurogranin, available in‐clinic cognitive tests included the Rey Auditory Verbal Learning Test (RAVLT), Semantic Fluency, Digit‐Symbol‐Coding, and Mini Mental State Examination. The above‐mentioned cognitive tests were used to derive the Preclinical Alzheimer’s Cognitive Composite (PACC5), a composite designed to be sensitive to cognitive change in preclinical AD. All associations were examined using Pearson correlation coefficient.ResultPreliminary analyses in a subset of participants yielded relatively strong positive correlations between PACC5 (R = .50, p<.001) and the ORR Long‐term Delayed Retrieval. The strongest correlation for an individual test was observed between the RAVLT Delayed Retrieval and the ORR Long‐term Delayed Retrieval (R = .52, p<.001). Regarding the CSF biomarkers, Aβ42/Aβ40‐ratio at age 70 was positively correlated with the ORR Long‐term Delayed Retrieval at age 77 (R = .43, p<.01), while measures of t‐tau, p‐tau, NFL, and neurogranin at age 70 were not.ConclusionOur findings demonstrate the potential of smartphone‐based cognitive assessment to detect features of preclinical AD in a population‐based sample of older adults. Future analyses will address the relationship between these novel cognitive measures in relation to longitudinal CSF‐ and neuroimaging‐based biomarkers and clinical progression.
Actigraphy and sleep‐monitoring devices to help differentiate dementia with Lewy bodies from Alzheimer’s disease
Authors: Brown Karl , Shutes‐David Andrew , Payne Sarah , Jankowski Adrienne , Seto Edmund , Wilson Katie , Tsuang Debby W 
Published: December 2022

AbstractBackgroundDementia with Lewy bodies (DLB) is difficult to differentiate from Alzheimer’s disease (AD) in clinical settings. Actigraphy and sleep‐monitoring devices have the potential to generate data in between clinic visits to help improve the identification of DLB.ObjectiveWe will assess the feasibility of measuring activity and sleep, including day/night reversal, in participants with DLB (n=5) and AD (n=4).MethodParticipants were asked to wear actigraphy devices on their wrists for 2 weeks and sleep‐monitoring EEG devices on their foreheads for 2 nights. Actigraphy recording errors were detected by logging instances in which the majority of acceleration values approached the maximum; reliability was evaluated by logging 15‐minute actigraphy and 1‐hour sleep‐monitoring periods with at least some valid data. Actigraphy tolerability was evaluated by examining non‐wear times. Ten variables were selected to evaluate day/night reversal.ResultAveraged across all individuals, only 0.02% of the 15‐minute actigraphy recording periods had a recording error, 100% of the 15‐minute periods had at least some valid data, and only 0.15% of the periods reflected non‐wear times. For the sleep‐monitoring device, an average of 78% of each nightly recording were considered valid. Of the ten day/night reversal variables, two sleep‐monitor variables showed the strongest differences between DLB and AD: sleep efficiency (mean [SD] = 0.56 [0.19] for DLB; mean [SD] = 0.74 [0.11] for AD; see Fig. 1) and percent sleep in REM (mean [SD] = 6.83 [9.16] for DLB; mean [SD] = 18.3 [4.13] for AD; see Fig. 2). The ratio of nighttime to daytime activity as measured by actigraphy (mean [SD] = 0.37 [0.18] for DLB; mean [SD] = 0.38 [0.08] for AD) showed strong differences in the variability of measurements between AD and DLB (see Fig. 3).ConclusionThese findings suggest that actigraphy and sleep‐monitoring devices are tolerable for participants with dementia and that the devices can reliably collect valid activity and sleep data in between clinic visits. Sleep efficiency and percentage REM sleep were lower in participants with DLB than in participants with AD. Larger studies should further explore the promise of actigraphy and sleep‐monitoring devices for differentiating DLB and AD.
Assessing the relationship between relational memory and segregation of intrinsic functional brain networks vulnerable to Alzheimer’s Disease during periadolescent development: preliminary findings from the PRANK study
Authors: Phipps Connor J , Sexton Jennifer N , Behm Lillian , DeCesare Thomas A , Heller Abi M , Maerlender Arthur C. , Phatak Vaishali S , Cramer Justin A. , Blair James , Murman Daniel L , Warren David E 
Published: December 2022

AbstractBackgroundAlzheimer’s disease (AD) is an insidious disease process that is frequently diagnosed following complaints of memory loss. The AD‐related decline in memory abilities has been attributed to functional and pathological changes in the hippocampus and distributed functional networks supporting hippocampal‐dependent memory. Although AD manifests in late life, lifelong risk factors for AD may be influenced by childhood brain development. The default mode network (DMN) is one functional network associated with the hippocampus and has been well‐characterized in adulthood. However, there is a gap in the literature regarding the connection between DMN network properties and relational memory abilities in childhood. Here we report preliminary findings from our ongoing study (Polygenic Risk of Alzheimer’s disease in Nebraska Kids, PRANK). The PRANK study collects functional MRI, cognitive measures, and AD polygenic risk scores from periadolescent children in Nebraska (age 8‐13 years). Here, we report the current findings measuring the relationship between brain network measures and cognitive outcomes from the PRANK study.MethodTo assess the relationship between intrinsic functional networks of the brain and hippocampal‐dependent memory, we applied brain and cognitive measures from a preliminary sample of periadolescent children (N=90) from the PRANK study. Cognitive assessments measured hippocampal‐dependent memory and other cognitive domains. Brain measures included both structural and resting‐state functional MRI data. Two properties of brain networks were measured, modularity and participation coefficient. These measures were derived from resting‐state MRI data with help of the Human Connectome Project’s Connectome Workbench tool. For comparison, brain and cognitive measures were also collected from a separate dataset of healthy young adults.ResultOur analysis observed differences between the PRANK and young adult datasets. The observed between‐group differences included graph theoretic measures of network architecture, particularly modularity. The relationship between relational memory performance and the network properties PRANK participants was also assessed.ConclusionThe ongoing PRANK study seeks to determine the association of brain measures and cognitive performance. Here, our preliminary analysis measured the relationship between brain and cognitive measures in periadolescent children with a focus on brain network properties and relational memory.
Ancestral Analysis of the Presenilin‐1 G206A Variant Reveals it as a Founder Event on an African Haplotype in the Puerto Rican Population
Authors: Hamilton‐Nelson Kara L. , Griswold Anthony J. , Rajabli Farid , Whitehead Patrice L. , Contreras Maricarmen , Tejada Sergio , Sanchez Jose Javier , Mena Pedro Ramon , Adams Larry D. , Starks Takiyah D. , Silva‐Vergara Concepcion , Cuccaro Michael L. , Vance Jeffery M. , Byrd Goldie S. , Haines Jonathan L. , Beecham Gary W. , Feliciano‐Astacio Briseida E. , Pericak‐Vance Margaret A. , Celis Katrina 
Published: December 2022

AbstractBackgroundVariants in the presenilin‐1 gene (PSEN1) are known to be pathogenic for Alzheimer disease (AD). The change of glycine at amino acid 206 to alanine (G206A) in PSEN1 has been identified in AD Caribbean Hispanic families from Puerto Rico with variable ages of onset and incomplete segregation (Athan et.al., 2001). Here we set out to confirm the role of G206A in the genetic etiology of AD in Puerto Rico while investigating its ancestral history and founding haplotype.MethodWe performed genotyping and whole genome sequencing (WGS) of 43 AD families (N = 182: 87 AD, 41 MCI, and 44 cognitively unimpaired) and 272 AD, 145 MCI, and 297 cognitively unimpaired unrelated individuals of Puerto Rican background and identified carriers of G206A. Genotyping data were phased using SHAPEIT to identify local ancestry of the PSEN1 haplotype followed by RFMix to estimate the genetic ancestral background (African, European, or Amerindian). Haplotype modeling was performed using MERLIN software.ResultWe identified 19 carriers of G206A among individuals with sequencing data in eight of the 43 families (14 AD, two MCI, one neuropsychiatric disorder, and two cognitively unimpaired individuals under 65 years old). G206A did not completely explain AD in these eight families as six other AD cases in the families did not carry the variant. In the unrelated cohort, we identified 13 carriers (nine AD, one MCI, one Pick’s disease, and two cognitively unimpaired under 65 years old). Local ancestry indicated that the mutation arose on an African ancestral haplotype. However, in screening WGS of individuals of primarily African ancestry from Ibadan, Nigeria (63 AD and 648 controls) and African Americans part of the Alzheimer Disease Sequencing Project (1347 AD, 2290 controls) no other carriers were identified.ConclusionOur results support that G206A contributes to AD in the Puerto Rican population, but in AD families does not completely explain the genetic risk. We also show that this variant occurs on a common haplotype across carriers representing a founder event on an African haplotype background in Puerto Rico.
Adapting to reality: Effect of Online Assessments as Compared to In‐Person Assessments
Authors: Pallen Vanessa , Rahmouni Nesrine , Tissot Cécile , Stevenson Jenna , Stevenson Alyssa , Poltronetti Nina Margherita , Bezgin Gleb , Lussier Firoza Z , Therriault Joseph , Kunach Peter , Pascoal Tharick , Servaes Stijn , Savard Melissa , Wang Yi‐Ting , Arias Jaime Fernandez , Chamoun Mira , Mathotaarachchi Sulantha , Vitali Paolo , Gauthier Serge , Rosa‐Neto Pedro ,   McGill University Research Centre for Studies in Aging
Published: December 2022

AbstractBackgroundNeuropsychological evaluations are normally assessed in‐person by a trained psychometrician using a variety of tests representing several domains. The COVID‐19 pandemic has obliged medicine and research to switch to online assessment. However, minimal research has tested the reliability of conducting cognitive evaluations online versus in‐person. This study aims to explore the clinical utility of virtually assisted neuropsychological evaluations in a comparative analysis following the effects of the COVID‐19 pandemic.Method62 cognitively unimpaired (CU) individuals from the TRIAD cohort underwent baseline and follow‐up neuropsychological assessments which included the Boston Naming Test (Short Form), BORB‐Object Recognition Task, WASI‐II Matrix Reasoning, WAIS‐III Digit Span, D‐KEFS Category Fluency Tests, Rey Auditory Verbal Learning Test (RAVLT), and Free & Cued Selective Reminding Test (FCSRT). Participants were considered CU when they obtained a CDR score of 0, MMSE ≥ 26, with negative amyloid‐β and tau statuses (global amyloid‐β [18F]AZD4694 <1.55 SUVR and temporal meta‐ROI [18F]MK6240 <1.24 SUVR). Participants were divided into two equally represented groups, both of which completed an in‐person baseline evaluation. 30 participants completed their follow‐up evaluation in‐person and 32 completed their evaluation virtually. A mixed linear regression model was used to assess the difference in the rate of change in scores between cohorts using age, sex, and years of education as covariates.ResultFollow‐up at‐home neuropsychological test results did not significantly differ from in‐person scores across all domains. Participant demographics are shown in table 1. The Boston Naming Test (Short Form), BORB‐Object Recognition Task, WASI‐II Matrix Reasoning, WAIS‐III Digit Span, D‐KEFS Category Fluency Tests, Rey Auditory Verbal Learning Test (RAVLT), and Free & Cued Selective Reminding Test (FCSRT) yielded p values of 0.47, 0.74, 0.17, 0.28, 0.13, 0.53, and 0.77, respectively.ConclusionScores from our battery were selected to represent the different cognitive domains. Based on our findings, there was no difference when individuals conducted in‐person versus online assessments. These results will allow for the geriatric community to receive the medical assistance they require without having to impose any inconveniences or unnecessary health risks. Additionally, virtual assessments will assist to increase contact for prospective participants which would otherwise not be possible in‐person.
Hypomorphic PERK promotes a maladaptive phenotype in response to pathologic tau
Authors: Lessard Christian B , Tolton Samantha G , Abisambra Jose F. F 
Published: December 2022

AbstractBackgroundA major challenge in the field of tauopathies, such as progressive supranuclear palsy (PSP) is identification of effective therapeutic targets. PKR‐like endoplasmic reticulum (ER) kinase haplotype A (PERK‐A) adapts cells undergoing ER stress. PERK haplotype B (PERK‐B) does not resolve ER stress effectively and increases the risk for PSP. The mechanism by which PERK‐A and ‐B confer distinct outcomes remains unknown. The overall hypothesis is that PERK‐B promotes maladaptive response that increases tauopathy outcomes.MethodsWe developed new inducible cell lines, unfolded protein response sensors, and PERK plasmids (‐A, ‐B, and an inactive variant, ‐K). We performed molecular biology approaches in vitro including co‐expression, co‐immunoprecipitation assays, and RNAseq.ResultsWe found that unlike PERK‐A, PERK‐B was not an effective modulator of pathological tau species. The transcriptome and translatome of PERK‐A and ‐B are distinct. Surprisingly, the PERK‐A translatome has pro‐survival factors.ConclusionPERK‐A confers benefits in tauopathy. The PERK‐A translatome is replete with novel therapeutic targets. PERK‐B data offer novel insights into the pathogenesis and progression of PSP, which may be linked to other tauopathies.
Plasma amyloid‐β profiles and the correlation with neuropsychological performance in patients with cognitive decline
Authors: Lee Jin San , Kim Hyun‐Ho , Park Key‐Chung , Rhee Hak Young , Hwang Kyo Seon 
Published: December 2022

AbstractBackgroundThis study aimed to investigate the relationship between the level of plasma amyloid‐β (Aβ) and neuropsychological performance in patients with cognitive decline, classified according to amyloid PET positivity using a highly sensitive nano‐biosensing platform.MethodA total of 44 patients with cognitive decline who underwent plasma Aβ analysis, amyloid PET scanning, and detailed neuropsychological tests were recruited in this study. The participants comprised 20 patients with subjective cognitive decline, 7 with amnestic mild cognitive impairment, and 17 with probable AD dementia. Patients were classified into a normal control (NC, N = 25) or Alzheimer’s disease (AD, N = 19) group based on amyloid PET positivity. Multiple linear regression was performed to determine whether plasma Aβ (Aβ40, Aβ42, and Aβ42/40) levels were associated with neuropsychological test results.ResultThe plasma levels of Aβ42/40 were significantly different between the NC and AD groups and were the best predictor of amyloid positivity by receiver operating characteristic curve analysis. There were significant differences in the neuropsychological performance of cognitive domains (language, visuospatial, verbal/visual memory, and frontal/executive functions) between the NC and AD groups. However, in multivariate regression analysis, upon inclusion of age, education, vascular risk factors, and apolipoprotein E ε4 status, higher levels of plasma Aβ42/40 showed significant negative correlations with verbal and visual memory performance, including immediate recall, delayed recall, and recognition tests.ConclusionWe suggest that our study might have clinical significance because plasma Aβ analysis using a highly sensitive nano‐biosensing platform could not only be a useful non‐invasive method for diagnosing AD, but also showed a significant association with memory performance in patients with cognitive decline. Further investigations with a larger sample size are necessary to clarify the possible relevance of plasma Aβ as a blood‐based biomarker for precise AD diagnosis.
Smartphone‐based long‐term delayed memory performance is associated with the Preclinical Alzheimer's Cognitive Composite and CSF levels of β‐amyloid
Authors: Öhman Fredrik , Berron David , Skoog Johan , Bodin Timothy Hadarsson , Kern Silke , Zettergren Anna , Papp Kathryn V. , Zetterberg Henrik , Blennow Kaj , Skoog Ingmar , Schöll Michael 
Published: December 2022

AbstractBackgroundRemote and unsupervised cognitive testing using smartphones may improve sensitivity to detect preclinical Alzheimer’s disease (AD). In particular, cognitive testing at‐home enables the evaluation of the potentially more sensitive long‐term delayed memory retrieval, which is commonly not feasible in a clinical setting.MethodHere, we investigated the association between remote and unsupervised smartphone‐based cognitive assessments and in‐clinic cognitive measurement in older participants (CDR = 0, MMSE = 29.2, age = 77). The sample (non‐demented at age 70) was derived from the Swedish population‐based Gothenburg H70 Birth Cohort Studies. In a subsample of participants, the retrospective correlation with cerebrospinal fluid (CSF) biomarkers analyzed at age 70 was further explored. To this point, 177 H70‐participants have consented and were enrolled into the smartphone sub‐study. They completed an “Object‐in‐Room Recall Test“ (ORR) remotely and unsupervised using own mobile devices, and the recall session was initiated 24 hours after the initial learning phase. Available previously assessed CSF measures included the Aβ42/Aβ40‐ratio, t‐tau, p‐tau, neurofilament light (NFL), and neurogranin, available in‐clinic cognitive tests included the Rey Auditory Verbal Learning Test (RAVLT), Semantic Fluency, Digit‐Symbol‐Coding, and Mini Mental State Examination. The above‐mentioned cognitive tests were used to derive the Preclinical Alzheimer's Cognitive Composite (PACC5), a composite designed to be sensitive to cognitive change in preclinical AD. All associations were examined using Pearson correlation coefficient.ResultPreliminary analyses in a subset of participants yielded relatively strong positive correlations between PACC5 (R = .50, p<.001) and the ORR Long‐term Delayed Retrieval. The strongest correlation for an individual test was observed between the RAVLT Delayed Retrieval and the ORR Long‐term Delayed Retrieval (R = .52, p<.001). Regarding the CSF biomarkers, Aβ42/Aβ40‐ratio at age 70 was positively correlated with the ORR Long‐term Delayed Retrieval at age 77 (R = .43, p<.01), while measures of t‐tau, p‐tau, NFL, and neurogranin at age 70 were not.ConclusionOur findings demonstrate the potential of smartphone‐based cognitive assessment to detect features of preclinical AD in a population‐based sample of older adults. Future analyses will address the relationship between these novel cognitive measures in relation to longitudinal CSF‐ and neuroimaging‐based biomarkers and clinical progression.
Differential item functioning of the CSI’D in the MexCog
Authors: Cantu Phillip A , Garcia Joshua M 
Published: December 2022

AbstractDifferential item functioning of the CSI’D in the MexCogBackgroundPrevious research shows that Spouse and Child informants in the MexCog report higher levels of cognitive impairment than other family and non‐family informants, even when controlling for direct cognitive assessments. The question remains, are the higher levels of cognitive impairment reported by spouses and children because they are informants for the most impaired older adults or because they respond to the questions differently? Additionally, direct cognitive assessments of low education populations may downwardly bias results. Individuals who are illiterate or who have had no formal schooling may score worse on cognitive assessments due inability to answer questions that require reading and writing or unfamiliarity with testing in general. The extent to which informant assessments of cognition can be used to better capture cognitive impairment for low educated population has not been studied.MethodsUsing item response theory (IRT) we examine the extent to which there is differential item functioning (DIF) between different types of informants and other associated with lower direct assessment for the Community Screening Interview for Dementia (CSI’D).ResultsThe anticipated results of this study will allow us to compare the observed CSI’D Score to an IRT weighted CSI’D score, controlling for DIF. The difference in observed and IRT weighted CSI’D score will show to what extent the differences in CSI’D score are due to differences in measurement.ConclusionThe item level bias, or lack of, will shed light on the importance of informants in measurement of cognitive impairment. Knowing how different informants answer informant questionnaires could have important implications for population‐based studies of cognitive decline.