bluuebunny/crossref_metadata_2025_split huggingface dataset:
Altered patterns of brain activity during a fMRI memory task in cognitively normal adults carrying the APOE ε4 allele
Authors: Corbo Daniele , Quattrini Giulia , Saglia Silvia , Agnelli Giancarlo , Mega Anna , Marizzoni Moira , D'Aprile Ilari , Cattaneo Annamaria , Bortoletto Marta , Gasparotti Roberto , Pievani Michela 
Published: December 2023

AbstractBackgroundThe e4 allele of the Apolipoprotein E gene (APOE) is a well‐established risk factor for Alzheimer’s disease (AD), e4 carriers showing earlier onset and more severe memory impairment than non‐carriers. Neuroimaging evidence suggests that APOEe4 may modulate neural activity in AD since early stages. The purpose of this study was to determine whether APOEe4 influences brain activity in the memory circuit in older cognitively unimpaired individuals.MethodThirty cognitively unimpaired participants (n = 10 APOEe4 heterozygous carriers, age = 65± 5 years, 50% females, MMSE score = 29±1; n = 20 APOEe4 non‐carriers, age = 68±5 years, 35% females, MMSE score = 30±1) were recruited and underwent multidomain (i.e., memory, visuospatial abilities, language, attention) neuropsychological exams and functional MRI scan during an associative memory task, which consisted of two phases: (i) encoding of face‐name associations; (ii) recognition of the name associated to each face. Image preprocessing and voxel‐wise comparisons were conducted using the Statistical Parametric Mapping (SPM, v12). Clusters were considered significant at an uncorrected threshold of p<0.001.ResultParticipants were comparable for demographic and cognitive features (p>0.10) and performed similarly on the in‐scanner face‐name association memory task (p>0.10). Compared to e4 non‐carriers, carriers showed (i) greater activation during the encoding task in the left temporo‐occipital cortex/fusiform gyrus, (ii) greater activation during the recognition task in the middle temporal gyrus/temporo‐occipital cortex bilaterally and in the right cerebellum, and (iii) lower activation during the recognition task in the medial supplementary motor area.ConclusionThese preliminary results confirm that the APOE e4 allele is associated with a different pattern of brain functional activity during an associative memory task in cognitively unimpaired older. Given the similar cognitive performance between groups, higher activation in temporo‐occipital regions might reflect a compensatory process in regions vulnerable to AD pathology.
White matter hyperintensity shape in relation to long‐term small vessel disease progression in community‐dwelling older adults
Authors: Keller Jasmin Annica , Sigurdsson Sigurdur , van Buchem Mark A. , Launer Lenore J J. , Van Osch Matthias J.P. , Gudnason Vilmundur , de Bresser Jeroen H.J.M. 
Published: December 2023

AbstractBackgroundWhite matter hyperintensity (WMH) shape was recently introduced as a novel small vessel disease (SVD) marker that may provide a more detailed characterization of WMH than volume alone. We aimed to investigate the association between baseline WMH shape and cerebrovascular disease progression over 5 years in community‐dwelling individuals.MethodData from the Age, Gene/Environment Susceptibility‐Reykjavik (AGES) study (n = 2297) was used in the current study. FLAIR and T1‐weighted brain MRI scans were acquired at baseline from 2002 to 2006 on a 1.5 Tesla Signa Twinspeed system (General Electric Medical Systems, Waukesha, Wisconsin). Five years later, follow‐up MRI scans were acquired from 2007 to 2011 with the same protocol. Baseline WMH shape was assessed using an in‐house developed pipeline (see figure 1).ResultA more irregular shape of periventricular/confluent (solidity, convexity, concavity index, fractal dimension) and deep WMH (eccentricity, fractal dimension) at baseline were associated with increased progression of WMH volume over 5 years (see figure 2). A more irregular shape of periventricular/confluent WMH (solidity, convexity, concavity index, fractal dimension) was associated with new subcortical infarcts and new microbleeds at the 5 year follow‐up (see figure 3).ConclusionOur findings indicate that a more irregular WMH shape is associated with SVD progression and may aid prediction of disease progression.
Stability of Magnetoencephalography and Electroencephalography Spectral Features in Mild Cognitive Impairment
Authors: Kinnunen Antti S , Kulashekhar Shrikanth , Saarinen Timo , Mäntynen Ville , Hotta Jaakko , Koivisto Anne M , Liljeström Mia , Renvall Hanna 
Published: December 2023

AbstractBackgroundIn mild cognitive impairment (MCI), the first neurodegenerative changes may occur years before they can be effectively detected with current clinical tools. Early pathology has been linked to synaptic dysfunction causing brain network disturbances that may be observed with electroencephalography (EEG) and magnetoencephalography (MEG). These methods are still not widely utilized in dementia risk assessment, and the stability of suggested EEG and MEG features and their correlation has not been thoroughly addressed in this patient group.MethodIn a 5‐year EU Horizon2020 project ‘AI‐Mind’, we collect EEG and simultaneous MEG data from MCI subjects, to be compiled with cognitive, genetic and plasma biomarker measures and techniques based on artificial intelligence (AI) for predicting the overall dementia risk. Here, we analyzed a subset of 31 Finnish MCI participants (20 females, age 68 ± 5; mean ± SD) from the AI‐Mind dataset to assess the stability of prominent signal features from resting‐state EEG and MEG recordings. We determined within‐session test‐retest reliability for spectral peak frequencies and relative peak power over occipital brain regions in the 8‐13 Hz range, by utilizing intraclass correlation (ICC) for subsequent 5‐min runs of EEG and MEG data in both eyes‐closed (EC) and eyes‐open (EO) conditions. In addition, we determined the consistency of the features across methods (EEG/MEG).ResultThe results indicate good (ICC>0.6) test‐retest reliability across runs for EEG (peak frequency: 0.72 (EC); relative power: 0.86 (EC) and 0.66 (EO); p<0.001) and excellent test‐retest reliability (ICC>0.75) for MEG (peak frequency: 0.83 (EC); relative power: 0.96 (EC) and 0.85 (EO); p<0.001). Consistency across EEG and MEG was excellent (peak frequency: 0.86 (EC); relative power 0.89 (EC) and 0.84 (EO); p<0.001).ConclusionElectrophysiological recordings of brain networks are emerging as a diagnostic tool for early detection of dementia. Good stability of the measured signal features is a prerequisite for a clinically feasible tool. Here, we demonstrate good or excellent stability for prominent spectral features both within and across EEG and MEG recordings.
Comparing approaches based on the global functional organization of the brain versus local connectivity to predict tau‐PET across the Alzheimer’s disease phenotypic spectrum
Authors: Corriveau‐Lecavalier Nick , Botha Hugo , Schumacher Julia , Dicks Ellen , Barnard Leland R , Lee Jeyeon , Sintini Irene , Gunter Jeffrey L. , Kamykowski Michael G. , Graff‐Radford Jonathan , Ramanan Vijay K , Fields Julie A. , Machulda Mary M. , Boeve Brad F. , Lowe Val J. , Kantarci Kejal , Knopman David S. , Whitwell Jennifer L , Josephs Keith A , Petersen Ronald C. , Jack Clifford R. , Jones David T. 
Published: December 2023

AbstractBackgroundPredictive models of tau‐PET accumulation have largely relied on the functional connectome to estimate its spatial patterns in Alzheimer’s disease (AD). Patterns of global functional organization represent a promising avenue as they encapsulate many biological properties relevant to neurodevelopment, cognition and degeneration. We compared approaches based on local connectivity (from task‐free fMRI) and global organization (from FDG‐PET) to predict regional tau‐PET across AD phenotypes.MethodWe included 430 cognitively unimpaired (CU) individuals (214 A+T‐, 216 A+T+) and 62 amnestic mild cognitive impairment (aMCI), 64 amnestic AD, 21 dysexecutive AD (dAD), 41 logopenic progressive aphasia (LPA) and 49 posterior cortical atrophy (PCA) patients (all A+T+) from the Alzheimer’s Disease Research Center, Mayo Clinic Study of Aging, and Neurodegenerative Research Groups (referred to as “Mayo cohort”). The connectivity approach consisted of assessing the relationship between a region’s tau level and its functional connectivity to the region of highest tau (epicenter). The global organization approach consisted of 1) performing a principal component analysis on 3000 FDG‐PET images that did not overlap with the Mayo cohort, 2) projecting FDG‐PET images of the Mayo cohort onto the low‐dimensional space generated in Step 1 and extracting corresponding weighted values across the first 100 components, 3) using these weighted values as predictors of regional tau‐PET in a linear model and determining optimal parameters based on predicted R2 values, and 4) using the parameters from the model built in Step 3 to predict tau‐PET in the ADNI cohort (n = 86) (Fig.2).ResultThe connectivity‐based approach yielded adjusted R2 values ranging from 0.19‐0.45 across diagnostic groups (Fig.1). The global organization approach yielded averaged adjusted R2 and predicted R2 values of 0.71 and 0.63, respectively, in the Mayo cohort. Out‐of‐sample median R2 in the ADNI cohort was 0.41 (range 0.10‐0.60) (Fig.3).ConclusionAn unbiased approach based on the global functional organization of the brain and using an imaging modality widely used in clinical settings outperformed a connectome‐based one to predict regional tau‐PET across the AD phenotypic spectrum. Patterns of tau accumulation may better relate to the large‐scale physiology of the brain underlying specific mental functions rather than local connectivity factors.
Cognitive decline and longitudinal atrophy in successful and typical aging
Authors: Pezzoli Stefania , Giorgio Joseph , Chen Xi , Harrison Theresa M. , Jagust William J. 
Published: December 2023

AbstractBackgroundGreater hippocampal volume (HV) and thicker mid‐cingulate cortex (MCC) are features of successful agers (SA), defined as exceptional cognitive performers, compared to typical agers (TA). This study aimed at examining whether SA experience different longitudinal change in cognition and atrophy from TA, and how baseline ß‐amyloid (Aß) affects these relationships.Method190 cognitively normal older adults (70+ years old) underwent 11C‐Pittsburgh compound B (PiB)‐PET to derive baseline Aß positivity, and longitudinal structural MRI and cognitive testing. A machine learning cognitive‐age model was used to predict participants’ cognitive‐age from cognitive testing. Cognitive‐age gap (CAG = cognitive‐age – chronological age) was computed to represent individual variability in cognitive aging, wherein negative values indicate better cognitive performance than expected for age; SA were below the 20th percentile (n = 39). Linear mixed‐effects models were used to investigate the relationship between longitudinal changes in 1) Preclinical Alzheimer’s Cognitive Composite (PACC), 2) HV, and 3) MCC, with baseline CAG or SA‐status, as well as Aß‐status as predictors.ResultWe found a significant main effect on PACC for CAG (p<0.001), but not Aß‐status (p = 0.9), and significant CAG x time (p = 0.002) and Aß‐status x time (p = 0.02) interactions (Figure 1). Results were similar when participants were dichotomized into SA and TA. In addition, baseline CAG showed significant main effects on 1) HV (p<0.001) and 2) MCC (p = 0.02), but the CAG x time interactions were not significant (HV: p = 0.6; MCC: p = 0.7) (Figure 2). Finally, when CAG, Aß‐status, and HV were included in the same model to predict PACC change, we found a significant main effect for CAG (p<0.001), significant CAG x time (p = 0.01) and Aß‐status x time (p = 0.02) interactions, and a marginally significant HV x time interaction (p = 0.06) (Figure 3).ConclusionLower baseline CAG scores, indicating younger cognitive‐age, were related to greater HV and thicker MCC cross‐sectionally, but not longitudinal atrophy differences, suggesting that better cortical integrity in SA may reflect longstanding differences from TA. Lower baseline CAG and Aß negativity were independently associated with slower cognitive decline. These findings suggest that factors underlying SA include separate contributions of both brain maintenance and reserve.
Voxel‐by‐Voxel regression analysis identifies association between postmortem TDP‐43 and antemortem fractional anisotropy within white matter fibers connected to the hippocampus
Authors: Heywood Ashley , Stocks Jane K , Schneider Julie A , Bennett David A. A , Arfanakis Konstantinos , Beg Mirza Faisal , Wang Lei 
Published: December 2023

AbstractBackgroundTAR DNA‐binding protein 43 (TDP‐43), has been shown to be involved in various neurodegenerative disorders involving axonal damage including ALS, FTLD, and LATE. Studying the relationships between postmortem TDP‐43 and antemortem white matter (WM) structural integrity can allow for a better understanding of the disease, rather than exploring clinical presentations alone.MethodIn‐vivo diffusion‐weighted images were gathered on a 1.5T scanner from subjects from the Religious Orders Study and the Rush Memory and Aging Project. Images were processed using TORTOISE to calculate fractional anisotropy (FA). We utilized the IIT probabilistic WM atlas to identify voxels containing fibers that originate or terminate in the hippocampus. A semi‐quantitative rating of TDP‐43 severity was assessed in 5 brain regions. We utilized regression models to relate postmortem disease and antemortem FA within each voxel. Coexisting disease including ß‐amyloid plaques, tau tangles, and cerebrovascular disease were used as covariates, along with demographic variables.ResultThe 58 subjects were 91.10 (SD = 6.37) years old at death with a median interval from MRI to death of 2.8 years (SD = 1.19). Results revealed a significant negative relationship (p<0.05) between postmortem TDP‐43 and FA within fibers connecting the hippocampus to the parahippocampal and entorhinal cortices, fornix, and lingual gyrus. Preliminary results did not survive multiple comparisons correction.ConclusionOur findings indicate that greater TDP‐43 disease burden is associated with lower white matter integrity within regions of the limbic system. These findings suggest the TDP‐43 disease process may contribute to reduced structural connectivity between the hippocampus and related regions, which may impact larger brain networks.
Biological sex and vessel specific relationships between cerebral pulsatility and white matter hyperintensities: a 4D flow MRI study
Authors: Moir M. Erin , Fico Brandon G. , Loggie Nicole A. , Gaynor‐Metzinger Sarean H.A. , Norby Alexander M. , Howery Anna J. , Rivera‐Rivera Leonardo A. , Eisenmenger Laura B. , Wieben Oliver , Johnson Sterling C , Barnes Jill N. 
Published: December 2023

AbstractBackgroundBrain vascular dysfunction is a contributing factor to the increased risk of Alzheimer’s disease with advancing age. Cerebral pulsatility represents a marker of vascular function that quantifies fluctuations in blood flow within each cardiac cycle in the cerebral arteries. Increases in cerebral pulsatility may contribute to structural damage in the brain such as white matter hyperintensities (WMH). Additionally, biological sex differences are apparent in brain vascular function and Alzheimer’s disease risk. As such, this research aimed to determine associations between cerebral pulsatility and WMH and evaluate the influence of sex. This research tested the hypothesis that elevated cerebral pulsatility is associated with higher WMH, and that the associations are sex‐specific.Method407 cognitively healthy middle‐aged and older adults (45‐87 years of age; 271 females) completed magnetic resonance imaging (MRI) performed on a 3T MRI scanner. WMH volumes were evaluated from T2 fluid‐attenuated inversion retention (FLAIR) images, while cerebral pulsatility index (PI) was evaluated in multiple intracranial arteries from 4D flow MRI. WMH fraction was calculated as the cubic root of WMH volume relative to intracranial volume.ResultPI in the vertebral arteries (VA) and basilar artery was positively associated with WMH fraction in females only (all female P = 0.01, all male P = 0.20). In contrast, PI in the internal carotid arteries (ICA) and middle cerebral arteries (MCA) was positively associated with WMH fraction in both sexes (all P = 0.01). However, the relationship between WMH fraction and PI in the MCA differed by sex such that the slope of the relationship was stronger in males than females (all P = 0.03). For example, higher right MCA PI was associated with greater WMH fraction in males (ß = 0.39±0.09 a.u., R2 = 0.13) compared with females (ß = 0.18±0.05 a.u., R2 = 0.05).ConclusionThese data suggest that, among cognitively healthy middle‐aged and older adults, elevated cerebral pulsatility is linked to greater WMH. However, the associations are sex‐ and vessel‐specific which may contribute to sex‐specific trajectories in Alzheimer’s disease with advancing age. The present results support the idea that elevated cerebral pulsatility contributes to structural alterations in the brain and thus reducing cerebral pulsatility may represent a promising target for mitigating cognitive decline.
Association between lifestyle at different life periods and brain integrity in older adults
Authors: TURPIN Anne‐Laure , Felisatti Francesca , Ourry Valentin , Mézenge Florence , Landeau Brigitte , Vivien Denis , la Sayette Vincent De , Chetelat Gael , Gonneaud Julie 
Published: December 2023

AbstractBackgroundIncreasing evidence suggests that lifestyle factors are related to cerebral markers of aging and Alzheimer’s disease (AD) in older individuals. However, most studies addressed the association between current lifestyle and neuroimaging, providing little information on the relative effect of lifestyle at different life periods on older adults’ brain integrity. We proposed to determine the life period(s) at which lifestyle factors have the greatest influence on older adults’ brain health.MethodWe included baseline data of 135 cognitively unimpaired older adults (aged>65) from the Age‐Well study (NCT02977819). They underwent multimodal neuroimaging providing measures of Gray Matter volume (GMv), glucose metabolism, perfusion (early‐Florbetapir‐PET) and beta‐amyloid burden. The Lifestyle Experiences Questionnaires (LEQ) was used to assess complex mental activities during early‐ (13‐30y), mid‐ (30‐65y) and late‐life (>65y). To evidence the effect of activities at each life period controlling for the others, multiple regressions were conducted including the three LEQ sub‐scores to predict each neuroimaging modality, both 1) focusing on AD‐signature regions and 2) voxel‐wise. In the presence of significant associations, complementary analyses were realized to directly compare the effect of life periods between them. All analyses were controlled for age and sex.ResultLEQ scores were not associated with AD‐signature regions. Voxel‐wise analyses revealed that higher LEQ score at midlife were positively associated with GMv, including the anterior cingulate cortex (Fig.1a), and negatively associated with amyloid burden, notably in the precuneus (Fig.1b). When compared with the other periods, these associations were statistically stronger for midlife. On the other hand, late‐life activities were positively associated with perfusion (Fig.2a) and glucose metabolism (Fig.2b), mainly in medial frontal regions, and these associations were stronger for late‐life than for any other life period.ConclusionOur study suggests that complex mental activities at midlife are more strongly associated with structural and molecular markers of brain integrity in older adults, while late‐life (i.e. current) activities are more strongly correlated with brain function. Interestingly, these associations were not found on AD‐signature regions but in brain regions relevant to reserve and aging. Lifestyle at different life periods might have an influence on distinct markers of brain health in late‐life.
Examining a telecognitive assessment‐derived Preclinical Alzheimer’s Cognitive Composite, the tPACC, for cognitive migration over one year in community‐dwelling older adults
Authors: Duran Tugce , Bateman James R. , Gaussoin Sarah A. , Rundle Melissa M. , Okonmah‐Obazee Stephanie E. , Espeland Mark A. , Williams Benjamin J. , Hughes Tim M. , Craft Suzanne , Lockhart Samuel N. , Sachs Bonnie C. 
Published: December 2023

AbstractBackgroundADRD clinical trials often target preclinical disease, where hope of averting the pathologic cascade and eventual cognitive decline remains highest. The preclinical Alzheimer’s cognitive composite (PACC5) was developed for in‐person administration to capture subtle cognitive decline. Early cognitive fluctuations may inform multidirectional disease progression, defined as cognitive migration. It is desirable to have a harmonized composite measurement derived from in‐person and remote assessments for detecting cognitive migration.MethodWe examined in‐person data from 417 adults (70.6±8.0y) from the Wake Forest ADRC Clinical Core, who received MRI, clinical evaluation and cognitive testing. The primary outcome was cognitive migration status determined by global CDR (0 and 0.5) increase/decrease between baseline (BL) and follow‐up (mean difference = 13.9 months): CDR‐0 Stable (51% maintained CDR‐0), CDR‐0.5 Stable (27% maintained CDR‐0.5), Reverter+ (13% migrated from CDR‐0.5 to CDR‐0) and Migrant‐ (9% migrated from CDR‐0 to CDR‐0.5). In‐person PACC5 was calculated (RAVLT Delayed Recall, Digit Symbol Coding [DSC], semantic fluency, Craft Story Delayed Verbatim, total MMSE) using BL participants with global CDR = 0 as reference. tPACC used measurements available at both in‐person and remote visits with minor modifications from PACC5: Montreal Cognitive Assessment (MoCA) replaced MMSE and DSC not included. We performed intraclass correlation coefficient (ICC) analysis and generated Bland‐Altman plots for BL tPACC and PACC5. We also evaluated associations between tPACC and neuroimaging.ResultParticipant characteristics and group differences in MRI markers are in Table 1. Bland‐Altman plots show differences and mean of tPACC and PACC5 (dashed line: ±1.96 SD, solid line: mean difference/bias). 92% of values lie within limit of agreement, indicating good agreement (overall ICC = .960, 95%CI = [.952, .967]), between tPACC and PACC5 in each group (Figure 1). At BL, there was a significant absolute agreement between in‐person tPACC and PACC5 in all groups (Figure 1). tPACC showed significant associations (Table 2) with Temporal Meta ROI thickness, hippocampal volume as % head size (ICV) and white matter hyperintensities (logWMH controlled for ICV) overall and in some cognitive migration groups.ConclusionThere is generally good agreement between BL tPACC and PACC5 across cognitive migration groups. BL tPACC may predict BL neuroimaging based on cognitive migration status. Longitudinal tPACC examination is warranted.