bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synaptic density is associated with cognitive performance in Alzheimer’s disease: A PET imaging study with [11C]UCB‐J
Authors: van Dyck Christopher H. , Sharp Emily , O'Dell Ryan S. , Banks Emmie R. , Bartlett Hugh H. , Chen Ming‐Kai , Naganawa Mika , Toyonaga Takuya , Harris Joanna E. , Ni Gessica S. , Zhao Wenzhen , Nabulsi Nabeel B. , Wyk Brent C. Vander , Huang Yiyun , Arnsten Amy F. T. , Carson Richard E. , Mecca Adam P. 
Published: February 2022

AbstractBackgroundFor 30 years synapse loss has been referred to as the major pathological correlate of cognitive impairment in Alzheimer’s disease (AD). However, this statement is based on remarkably few patients studied by autopsy or biopsy in limited brain regions, largely at the moderate to severe stages of disease. With the recent advent of synaptic positron emission tomography (PET) imaging, we have begun to evaluate synaptic alterations in vivo. In this study we examined the relationship between synaptic density and cognitive performance in early AD using [11C]UCB‐J PET and an extensive neuropsychological test battery.MethodUsing [11C]UCB‐J binding to SV2A, synaptic density was measured in 45 amyloid positive participants with AD (17 amnestic mild cognitive impairment and 28 mild dementia) and 20 amyloid negative cognitively normal (CN) participants aged 50‐85 years. Synaptic density was calculated as the distribution volume ratio (DVR) in a composite region of interest (ROI) of AD‐affected regions (prefrontal, lateral temporal, medial temporal, lateral parietal, anterior cingulate, posterior cingulate, precuneus, and lateral occipital) using cerebellum as reference region. A neuropsychological test battery assessed performance in five cognitive domains. Domain scores were generated for each AD participant by averaging z‐scores within the domain, and global cognitive scores averaged the domain scores.ResultIn a multiple linear regression model controlling for age, sex, and education, synaptic density ([11C]UCB‐J DVR) was a significant predictor of global cognitive performance in participants with AD (β=3.21, η2=0.29, P=0.0001; Figure 1A), as well as Verbal Memory (P=0.022; Figure 1B), Language (P=0.001; Figure 1C), Executive Function (P=0.001; Figure 1D), Processing Speed (P=0.001; Figure 1E), and Visuospatial Ability (P=0.001; Figure 1F). The association between synaptic density and global cognition survived partial volume correction (PVC; β=2.16, η2=0.23, P=0.001), and synaptic density was a stronger predictor of cognitive performance than gray matter volume. Figure 2 shows correlation maps of global cognitive performance with regional synaptic density (DVR; without and with PVC) and gray matter volume.ConclusionThese results confirm neuropathologic studies, demonstrating a significant association between synaptic density and cognitive performance, and suggest that this correlation extends to the early stages of AD.
Peak alpha frequency and N200 latency as predictors of neuropsychological performance in a memory disorders clinic
Authors: Marin Anna , Lahdo Naheer C. , Schiloski Kylie A. , Hajos Gabor P. , DeCaro Renee , Vives‐Rodriguez Ana , Budson Andrew , Turk Katherine W. 
Published: February 2022

AbstractBackgroundElectrophysiological measures including alpha peak power and frequency, and N200 latency are potential biomarkers of Alzheimer’s Disease (AD) pathology. It is still unclear how these measures can be used in clinical settings to better diagnose AD and differentiate it from other cognitive neurodegenerative disorders. As an initial step towards better understanding clinical utility of electrophysiological measures within a dementia population, this study aims to determine how alpha and gN200 measures can help predict neuropsychological status among an heterogenous sample of patients from memory disorders clinic.MethodData was collected using a seven electrodes COGNISION™ rig. Older veterans with memory complaints aged 50‐100 were recruited from a memory disorders clinic at the VA Boston Healthcare system (N= 185) with a MMSE score of 13 and above. EEG/ERP data was recorded while participants completed a three‐tone auditory oddball task. Participants who failed an audiometry screening test and those with a BPA below 35% were excluded. All subjects were administered a neuropsychological battery to assess degree of cognitive impairment. Amyloid PET results were also available for a small subset of subjects (N=49).ResultLinear regressions were computed for all cognitive measures that correlated with alpha peak frequency and N200 latency. Alpha peak frequency is a significant predictor of encoding (p=0.048) and delayed recall (p=0.014) in the CERAD list learning task, and of verbal category fluency (p=0.033). N200 target latency is a significant predictor of number of intrusions (p=0.0379) of the CERAD recognition task, and of Trails Making Test A (p=0.006) and B (p=0.048) time. Alpha peak frequency is also associated with amyloid PET status (p=0.040) using logistic regression.ConclusionAlpha peak frequency and N200 latency are useful predictors of cognitive status, especially of memory and executive function, among a memory disorders population. Alpha peak frequency is also an important factor in the prediction of amyloid PET status. Overall, alpha peak frequency and N200 latency represent a novel tool to better assess memory disorders patients, and characterize the cognitive profile of their underlying pathology in an heterogenous clinical setting.
Despite heightened risk of cognitive decline, no evidence of local atrophy in people with subjective cognitive decline compared to normal controls in ADNI
Authors: Morrison Cassandra , Dadar Mahsa , Shafiee Neda , Collins Louis 
Published: February 2022

AbstractBackgroundPeople with subjective cognitive decline (SCD) are at increased risk for developing Alzheimer’s disease (AD). SCD may thus be a very early clinical manifestations of AD. However, identifying which individuals with SCD will develop AD is difficult with current biomarker techniques. To predict whether someone with SCD will progress to AD, it is necessary to determine whether people with SCD display neurodegeneration in brain regions associated with AD.MethodWe included 1769 baseline and follow‐up MRI scans for 447 participants (177 normal controls, NC; 100 SCD; and 170 early mild cognitive impairment, eMCI) from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). All scans were pre‐processed through a previously validated pipeline. Deformation‐based morphometry (DBM) was performed to examine the pattern of volumetric change over time. An atlas‐based approach was also used to examine mean volume differences for regions of interest (ROIs; lateral ventricles, entorhinal cortex, and amygdala from CerebrA atlas (Manera et al., 2020)) estimated by integrating the Jacobian of the deformation field within the ROI. A previously validated MRI analysis method (SNIPE) was used to determine volume and grading of the hippocampus (Coupe et al., 2012). We applied a linear mixed effects model for all analysis (volume ∼Diagnostic Group +Age +Sex +Amyloid Positivity +APOE e4 +Education +1|ID).ResultLongitudinal volume analysis showed slight atrophy in eMCI compared to NC and SCD. ROI analysis revealed that eMCI had smaller volumes than SCD and NC in the amygdala (NC & SCD: p<.001) and entorhinal cortex (NC: p<.001; SCD: p=.01), and larger lateral ventricles (NC & SCD: p=.01). SNIPE volume and grading analysis revealed that eMCI hippocampal volume differed from both NC and SCD (p<.001). SCD and NC did not differ in any of the analyses. With respect to demographics, people with SCD had 2 years more education (p<0.001) than eMCI and NC.ConclusionThe structural differences observed in eMCI may act as an early biomarker for AD. Although SCD participants’ brain volumes significantly differed from eMCI, they did not differ from NC. However, lack of SCD:NC differences may be due to confounds (e.g., greater education in SCD) within the sample.
The role of the hippocampus in mediating cognitive impairment in cerebral amyloid angiopathy
Authors: Perosa Valentina , Zotin Maria Clara Zanon , Schoemaker Dorothee , Sveikata Lukas , Etherton Mark , Charidimou Andreas , Greenberg Steven M. , Viswanathan Anand 
Published: February 2022

AbstractBackgroundThe interplay between cerebrovascular and Alzheimer’s pathology has an important role in the development of cognitive impairment1. Vascular risk factors and neuroimaging markers of cerebral small vessel disease (CSVD), have well been characterized in patients with Alzheimer’s disease (AD) in the past years2,3. Conversely, few studies asked how hippocampal neurodegeneration, a benchmark of AD, relates to cognition in CSVD patients4.MethodWe set out to investigate the relation between hippocampal neurodegeneration and cognition in a memory clinic cohort of 101 (75.8 ± 6.7 y, 58 F) patients with possible and probable cerebral amyloid angiopathy (CAA), a common CSVD form with defined diagnostic criteria. Linear regression models were used to assess the associations between the volume of hippocampal subfields and cognitive measures. Neuroimaging markers of CSVD were subsequently included in the analyses, to evaluate how they mediate the relation between cognition and hippocampal neurodegeneration.ResultWe found a significant positive association between CA1 volume and cognitive domains (memory: b=0.14, p=0.008; processing speed: b=0.15, p=0.03; language: b=0.14, p=0.03; executive function: b=0.20, p=0.01). CA1 volume was significantly related to memory and executive function, even when accounting for neuroimaging markers of CSVD. Furthermore, presence of cortical superficial siderosis and peak width of skeletonized mean diffusivity (PSMD), a measure of white matter (WM) integrity, were negatively associated with hippocampal and subfields’ volumes.ConclusionThese results suggest that neurodegeneration of CA1 is related to cognitive impairment in CAA patients, and may further support established links between vascular pathology and loss of CA1 integrity and/or overlap of AD pathology in these patients5‐7. Moreover, further studies exploring the relationship between WM and hippocampal integrity may be warranted.
Comparison of neuronal activity profiles in Alzheimer’s disease and frontotemporal dementia measured by resting‐state fMRI
Authors: Haddad Seyyed Mohammad Hassan , Scott Christopher J.M. , Arnott Stephen R. , Ozzoude Miracle , Strother Stephen C. , Black Sandra E. , Borrie Michael , Finger Elizabeth , Trataglia Maria Carmela , Kwan Donna , Beaton Derek , Symons Sean , Soddu Andrea , Menon Ravi S. , Montero‐Odasso Manuel , Bartha Robert 
Published: February 2022

AbstractBackgroundNeuronal activity (NA) and metabolism are impaired in the early stages of Alzheimer’s Disease (AD) and Frontotemporal Dementia (FTD) leading to specific patterns of cognitive decline. Detailed disease models elucidating how and where in brain these NA disturbances commence and how they gradually progress remain incomplete. Recently, we introduced several NA metrics quantified based on fluctuations of the resting‐state fMRI (rs‐fMRI) signal. NA was significantly lower in AD and mild cognitive impairment compared to normal elderly controls (NEC). Here we extend this work using the most sensitive metric to examine NA profile differences between people with AD and FTD.Method3T MRI rs‐fMRI data (TR=∼2.4 Sec, 250 volumes) were obtained from the Ontario Neurodegenerative Disease Research Initiative (AD group: N=40, aged 71.8 ± 8.1, 42% female; and FTD group: N=50, aged 67.8 ± 7.3, 36% female), and Gait and Brain Study (NEC group: N=46, aged 71.0 ± 5.5, 33% female). The rs‐fMRI signal was pre‐processed and decomposed into independent components (ICs) using IC analysis. The ICs were classified into neuronal and non‐neuronal sources using a support vector machine classifier. Voxelwise NA was quantified based on the magnitude of neuronal ICs in the rs‐fMRI signal composition. This metric was utilized to create resting‐state NA maps in each subject, which were compared between groups voxel by voxel using a multiple comparisons permutation test (MCPT) with 1000 permutations.ResultGroup average NA maps are provided in Fig. 1. Average NA was lower in FTD (24%) and AD (40%) compared to NEC. There was a significant difference (adjusted p‐values from MCPT) between NEC and FTD (p<0.001), NEC and AD (p<0.001), and FTD and AD (p<0.05). Difference NA maps comparing the groups and associated significance maps are shown in Fig. 2. The FTD group had significantly higher NA compared to AD in ∼53% of brain voxels (Fig. 2).ConclusionSignificantly lower NA was detected in AD and FTD compared to NEC. Localized significant NA differences between AD and FTD were detected emerging mostly as clusters in occipital and subcortical areas that are known to be less affected by FTD.
Differences in emotional health across cognitively normal adults and with mild cognitive impairment and Alzheimer’s disease: Results from the Advancing Reliable Measurement in Alzheimer’s Disease and Cognitive Aging (ARMADA) study
Authors: Zhang Manrui , Ho Emily , Nowinski Cindy , Fox Rina , Novack Miriam , Dodge Hiroko H , Weintraub Sandra , Gershon Richard 
Published: February 2022

AbstractBackgroundChanges in emotional health are common both as part of typical aging and for individuals with mild cognitive impairment (MCI) and Alzheimer's disease (AD). Thus, there is a critical need to identify differences in emotional functioning between adults with and without cognitive impairment. In the current study, we explore whether the NIH‐Toolbox Emotional Battery (NIHTB‐EB), a set of validated, reliable, and efficient measures of emotional functioning, can be used to potentially detect differences in emotional functioning across older adults with varying levels of cognitive impairment.MethodData were drawn from a longitudinal, multi‐site study ‐ the Advancing Reliable Measurement in Alzheimer’s Disease and Cognitive Aging (ARMADA). Participants were recruited from 11 existing cohorts nationwide, and included 1) cognitively normal (NC) adults (N=276), 2) individuals with MCI (N=103), and 3) individuals with AD (N=69); Mage= 78 (SD = 8.25); 53.2% were female. Baseline emotional health was assessed from 2019 to 2020 using NIHTB‐EB. Univariate and ANCOVA analyses tested differences in a variety of emotion dimensions across three groups, adjusting for important covariates, and post‐hoc Tukey pairwise comparisons were performed.ResultControlling for age, gender, marital status, and education, a significant main effect of clinical group was found on measures of sadness, fear‐affect, anger‐physical aggression, loneliness, self‐efficacy, and the negative affect composite score [all ps<0.05; see Figure 1]. Tukey post‐hoc pairwise comparison showed MCI and NC differed in negative affect (diff=4.18), sadness (diff=3.08), and anger‐physical aggression (diff=3.08); and AD and NC differed in negative affect (diff=3.65), anger‐physical aggression (diff=4.60), loneliness (diff=3.95), sadness (diff=4.60), and self‐efficacy (diff=‐3.18) [all ps < 0.05; Figure 1].ConclusionIndividuals with MCI and AD reported higher levels of negative emotions and a lower level of self‐efficacy than normal controls. Based on a comprehensive set of emotional functioning measures, these findings extended our understanding of how older adults with and without cognitive impairment differ on aspects emotional functioning essential to quality of life. Importantly, we found that the NIHTB‐EB is a useful tool to assess and differentiate emotional health outcomes among cognitively normal adults as well as those with MCI and AD diagnoses.
Relationships among socioeconomic factors, quality of life, family stigma and psychological outcomes in family caregivers of patients with early onset Alzheimer disease due to E280A‐PSEN1 mutation and frontotemporal dementia in Antioquia‐Colombia
Authors: Velilla Lina M , Acosta‐Baena Natalia , Calle Andres , Allen Isabel Elaine , Lopera Francisco , Kramer Joel H 
Published: February 2022

AbstractBackgroundCaregiving itself does not lead to adverse psychological outcomes, burden, stigma, and/or quality of life reduction but socioeconomic factors have been hypothesized as risk factors among dementia caregivers. We aimed to analyze the associations between socioeconomic factors and type of dementia as potential predictors of family stigma, Quality of life (QoL.), depressive symptoms, anxiety, and caregiver burdenMethodWe assessed 151 family caregivers distributed as early‐onset Alzheimer disease group (EOAD), frontotemporal dementia (FTD), and late‐onset dementia group (LOAD) for comparative means. Participants underwent questionnaires about family stigma, caregiver burden, depression, anxiety, QoL., and a questionnaire to explore socioeconomic factors. We performed a multivariable regression model with socioeconomic factors and the group as predictors. We included age, education, patient’s clinical‐stage, and behavioral changes as covariates.ResultBeing a caregiver of an FTD patient reduced physical functioning (β=‐13,5 p=0,018), working part‐time increased physical functioning (β=22,1 p=0,032) while working from home increased general health (β=22,4 p=0,028). The perception of living in a safe neighborhood reduced role limitation due to emotional problems (β=46,2 p=0,013). The perception of financial problems related to patients' care or disease cost increased the role limitation due to emotional problems (β=‐29,8 p=0,007). The caregiver burden increased together with the perception of financial problems related to patient's care or disease cost (β=13,9 p<0,001) and was mediated by patient’s behavioral changes (β=0,47 p<0,001). Family stigma is increased by the perception of financial problems related to patient's care or disease cost (β=0,31 p=0,013) and was mediated by the caregiver’s education (β=0,04 p=0,026) and patient’s behavioral changes (β=0,10 p=0,001). Depression increased by the perception of financial problems related to patient's care or disease cost (β=2,01 p=0,033) and the mediation of patient’s behavioral changes (β=0,06 p=0,015).ConclusionSocioeconomic factors can predict disturbances in QoL. among dementia caregivers. Education, being an FTD caregiver, and patient’s behavioral changes mediated among socioeconomic factors and negative psychological outcomes. When a caregiver may have low education and is caring for a patient with FTD and/or behavioral problems the risk of negative outcomes and family stigma increases significantly.
Determinants of enlarged perivascular spaces (ePVS) on MRI: The Florida Vascular Imaging Phenotypes (FL‐VIP) Study of AD risk
Authors: Rundek Tatjana , Brutto Victor Del , Goryawala Mohammed , Saporta Anita Seixas Dias , Merritt Stacy S. , Camargo Christian , Agudelo Christian , Ariko Taylor , Dong Chuanhui , Loewenstein David , Duara Ranjan , Haq Ihtsham U. 
Published: February 2022

AbstractBackgroundPVS are fluid filled compartments surrounding small intracerebral vessels. They are conduits for fluid transport, exchange, and waste clearance. Their relationship to cardiovascular markers is unknown. We tested whether ePVS counts are affected by vascular risk factors and comorbidities.MethodWe analyzed nondemented subjects’ brains from the FL‐VIP (comprised of 1Florida ADRC participants with available high quality 3T MRI). ePVS were defined as parenchymal hypo/hyperintensities of <3 mm seen on a single axial T1, T2 or FLAIR section through the basal ganglia (BG) and centrum semiovale (CSO). ePVS were defined as parenchymal hyperintensities <3 mm and graded as 0 (none), 1 (<10), 2 (11‐20), 3 (21‐40), and 4 (>40). The side with highest ePVS count was graded. BG and CSO scores were summed to yield a 0‐8 total. Generalized linear models were used to estimate ePVS score associations with demographics, vascular risk factors, and vascular comorbidities (VASCom score).ResultOf 228 non‐demented participants (mean age 72±8 years; 61% women, 60% Hispanic, mean education 15±4 years, 33% ApoE4 carriers), 59% were hypertensive, 21% diabetic, 66% hypercholesteremic, and 30% obese. Mean VASCom score was 2.3±1.6. ePVS scores ranged from 0‐7 (mean 2.5±1.4), 0‐4 for BG (mean 1.3±0.7) and CSO (mean 1.2 ±0.9). Majority of subjects (73%) had a total ePVS score greater than 1. In unadjusted analysis, BG ePVS were correlated with age (r=0.27, P<0.001), hypertension (r=0.19, p=0.008), MI/CHF/Angina (r=0.14, P=0.03), and coronary bypass (r=0.20, P=0.004). CSO ePVS were correlated with age (r=0.23, P=0.0005), obesity (r=‐0.15, p=0.03), and dyslipidemia (r=‐0.14, P=0.04). In multivariable stepwise regression analyses, BG ePVS were associated with age (β=0.024 per year, p=0.0001), being Hispanic (OR=0.21, P=0.035), coronary bypass (OR=0.70, p=0.025), and hypertension (OR =0.17, p=0.079). CSO PeVS were associated with age (β=0.028 per year, P<0.001) and dyslipidemia (OR=‐0.31, P=0.02).ConclusionePVS were more prevalent with aging, greater vascular risk burden, and Hispanic origin. Hypertension, cardiovascular disease and prior coronary bypass surgery were associated with ePVS in BG, but not in CSO. BG ePVS may be an important marker of small vessel disease linking vascular burden and cognitive impairment.
Genetic and environmental influences on Alzheimer’s disease neuroimaging signatures
Authors: Williams McKenna E. , Gillespie Nathan A. , Dale Anders M. , Elman Jeremy A. , Eyler Lisa T. , Fennema‐Notestine Christine , Hagler Donald J. , McEvoy Linda K. , Neale Michael C. , Panizzon Matthew S. , Sanderson‐Cimino Mark E. , Franz Carol E. , Kremen William S. 
Published: February 2022

AbstractBackgroundComposite scores of MRI‐based brain morphometry, commonly termed ‘Alzheimer’s disease (AD) signatures,’ have demonstrated associations with AD symptom severity and progression to AD. Our group recently showed that two AD signatures, a cortical thickness/volume and mean diffusivity (MD) signature, aid prediction of progression to mild cognitive impairment among cognitively normal adults in their 50s. Genetic and environmental influences on these signatures, and whether the signatures capture unique AD‐related variance, remains unclear.MethodParticipants were from the Vietnam Era Twin Study of Aging (age=56.18, SD=2.61). Our previously published thickness/volume signature, a novel MD signature using the same regions and weights as the thickness/volume signature, and an MRI‐based measure of predicted brain age (ns=310‐502) were used in trivariate twin models to determine the relative influence of genetic and environmental factors on each phenotype. Correlations were examined to determine if the latent genetic and environmental influences overlap among the three phenotypes.ResultHeritability estimates were similar for the signatures and predicted brain age (0.68‐0.71). Phenotypic correlations ranged from ‐0.47 to 0.27. Genetic correlations were: 0.33 [95% CI: 0.19,0.47] (thickness/volume signature and predicted brain age); ‐0.55 [95% CI: ‐0.66,‐0.42] (MD signature and predicted brain age); and ‐0.36 [95% CI: ‐0.51,‐0.20] (thickness/volume and MD signatures).ConclusionBoth AD brain signatures are highly heritable. However, despite very similar heritability estimates among the three phenotypes, genetic correlations demonstrated that the two AD signatures are not redundant with each other or with a measure of predicted brain age. The results suggest that each AD signature captures some unique genetic variance, including genetic influences that are distinct from genetic influences on general brain aging.