bluuebunny/crossref_metadata_2025_split huggingface dataset:
Social network characteristics moderate associations between cortical thickness and cognitive functioning in older adults
Authors: Sharifian Neika , Zaheed Afsara B , Morris Emily P , Sol Ketlyne , Manly Jennifer J , Schupf Nicole , Mayeux Richard , Brickman Adam M , Zahodne Laura B 
Published: February 2022

AbstractBackgroundAlthough prior research suggests that brain health is associated with cognitive functioning in later life, the strength of brain‐cognition associations varies. Lifestyle factors may alter these associations by either increasing or decreasing the probability of exhibiting cognitive symptoms at any given level of brain pathology. One lifestyle factor that prior clinicopathologic research has found to influence the association between greater Alzheimer’s disease pathology and lower cognitive performance is an individual’s total social network size. However, little is known about distinct social relationship types (i.e., family vs. friends).MethodThe current cross‐sectional study used data from the Washington Heights‐Inwood Columbia Aging Project (WHICAP; n = 654, 63‐96 years old, 62.40% Female) to examine whether distinct social network characteristics moderate associations between cortical thickness in regions implicated in Alzheimer’s disease and cognitive performance. Initial linear regression models examined the effects of total social network size, cortical thickness and their interaction on global cognitive functioning and individual cognitive domains (memory, language, speed/executive functioning, visuospatial function). Subsequent models tested the effects of distinct social relationship types (i.e., spouse/partner, number of children, other relatives, friends).ResultAlthough there were no main effects of cortical thickness or individual social network components on cognition, there was an interaction between cortical thickness and the size of friend networks. Specifically, lower cortical thickness was associated with lower global cognition among individuals with smaller friend networks, but not individuals with larger friend networks. When broken down by individual cognitive domains, this pattern of results was most prominent for language and speed/executive functioning. Total social network size and family networks (spouse/partner, number of children or relatives) did not moderate associations between cortical thickness and cognition.ConclusionResults are consistent with a growing body of literature suggesting that maintaining more friendships may promote cognitive reserve in older adulthood. Longitudinal, intervention, and functional neuroimaging studies are needed to determine whether interacting with friends strengthens neural networks that can support cognitive performance in the context of poorer brain health.
New insights into the genetics of subcortical volumes across the adult lifespan
Authors: Grand Quentin Le , Satizabal Claudia L. , Seshadri Sudha , Tzourio Christophe , Mazoyer Bernard , Debette Stéphanie 
Published: February 2022

AbstractBackgroundSubcortical brain structures play a key role in pathological processes of many age‐related neurodegenerative disorders. Mounting evidence suggests that factors already present at an early age play a crucial role in the development of common late‐life neurological diseases, including genetic factors that can influence both brain maturation and neurodegeneration.Using large population‐based brain imaging datasets across the adult lifespan, we aimed to identify whether genetic loci associated with subcortical brain structures in older persons also show significant association with the same structures in early adulthood and explore underlying genes using transcriptome‐wide association studies (TWAS).MethodWe first tested variants, previously identified in genome‐wide association study (GWAS) of subcortical volumes in older adults, in young adults (i‐Share cohort, 18‐35y) individually and aggregated in genetic risk scores (GRS). We conducted a TWAS using the summary statistics from the GWAS of subcortical volumes. For the significant signals, we generated gene expression scores in i‐Share and tested them in association with subcortical volumes.ResultWe observed that GRS for smaller caudate nucleus and putamen volume in older adults were associated with smaller volumes of the same structures in young adults. Individually, ten independent loci associated with subcortical volumes in older adults also showed associations with the corresponding volume in young adults, with the strongest association between a variant near KTN1 and putamen volume. In TWAS, expression of several genes in brain tissues was significantly associated with caudate nucleus, putamen and pallidum volumes both in older and young adults, pointing to biological pathways underlying structural brain changes across the adult lifespan, with particularly strong evidence for a causal implication of MYLK2 and TUFM, in relation with caudate nucleus and putamen volume. We observed an association of genetically predicted Alzheimer’s disease with smaller volumes of most subcortical structures in older adults, but not in young adults.ConclusionOur findings provide novel insight into the genetic determinants of changes in subcortical brain structures across the adult lifespan. Further research is needed to decipher the underlying biological mechanisms and inform prevention strategies for common late life neurological diseases.
Alpha power is associated with hippocampal volume in Alzheimer’s disease: A combined MEG and MRI study
Authors: Pitt Jemma , Quinn Andrew J. , Kocagoncu Ece , Karadag‐Assem Melek , Lanskey Juliette , Klimovich‐Gray Anastasia , Cheng Yun‐Ju , Raymont Vanessa , Rowe James B. , Nobre Anna Christina , Woolrich Mark W. 
Published: February 2022

AbstractBackground
New Therapeutics in Alzheimer’s Disease (NTAD) is a multi‐centre, longitudinal study to develop reliable and sensitive biomarkers for patients in the early stage of Mild Cognitive Impairment (MCI) and Alzheimer’s Disease (AD). The hallmark of E/MEG abnormalities in AD patients is changes to the power and frequency of the alpha rhythm. Here, we explore spontaneous alpha oscillations in the NTAD cohort and how they relate to diagnostic condition (patient vs control), resting task (eyes open vs eyes closed) and hippocampal atrophy.MethodAt present, there has been MRI and E/MEG data collected on neurologically healthy controls (N=15; MMSE M=29.4±0.74) and amyloid positive MCI and AD patients (N=46; MMSE M=24.8±3.37). Resting‐state E/MEG recordings were obtained for two 5‐minute sessions; eyes opened and eyes closed. Average power and peak frequency were computed for each participant. A T1‐weighted MR scan was used to calculate hippocampal volume, whilst accounting for individual brain volume. Firstly, we compared the average power and peak frequency for patients and controls in both the eyes opened and eyes closed conditions. Secondly, we explored how alpha varies across these conditions and diagnoses and how these differences relate to hippocampal volume.ResultWe found that patients had lower peak frequency and power compared to controls. Specifically, there was a decreased power in eyes closed, and decreased frequency in eyes opened. These differences were also present in hippocampal volume as patients had significantly smaller hippocampi than controls, and this was correlated with decreased alpha peak frequency specifically in the eyes opened session (R2 = 0.172). These individual differences were further associated with MMSE scores.ConclusionThere are individual differences between alpha frequency and power between patients and controls. Alpha decreases with increasing cognitive impairment and is related to hippocampal volume. Whilst this is specific to eyes opened or eyes closed, results suggest that progressive atrophy of the hippocampus is associated with decreased alpha frequency. This confirms the clinical benefit of E/MEG measurements in dementia research and improve our understanding of the integration between structural and electrophysiological measures of synaptic dysfunction. Ongoing data analysis will be conducted to standardise these measures for future clinical trials.
Exploring the experiences of living at risk of familial frontotemporal dementia
Authors: Greaves Caroline V , Stott Joshua , Rohrer Jonathan D 
Published: February 2022

AbstractBackgroundFrontotemporal dementia is the second most common form of dementia in those under 65 years of age and is found to be genetic in around a third of cases. Familial FTD has an autosomal dominant pattern of inheritance meaning that the offspring of a mutation carrier has a 50% chance of carrying the mutation themselves. For those at risk of FTD, there are a number of issues that can cause distress including the high penetrance of the most common FTD‐causing genes, heterogeneity of symptoms and unpredictable age of symptom onset. Despite this, there have been no studies looking at the experiences of this group, particularly those who do not pursue predictive testing.MethodSixteen qualitative interviews were analysed using an inductive approach to thematic analysis. Participants were asked about their experience finding out about their risk, how they felt throughout different parts of their journey, their experience of genetic testing if this was performed, as well as the support they had or feel they would have benefited from.ResultKey themes identified included: 1) Depression, uncertainty and survivor guilt – the ups and downs of living at‐risk, 2) Worries about the wider family, 3) Lack of support ‐ “You need people who really understand”, 4) Coping mechanisms ‐ Living like a gene carrier and 5) Seeing at risk status as a positive thing. Almost all participants expressed a need for tailored psychological support facilitated by “someone who understands” the unique issues they face.ConclusionLiving at risk of familial FTD is a psychologically challenging experience, independent of the challenges presented by predictive testing. Those who choose not to undergo predictive testing may also, at times, require specific support. Future research should explore tailored support strategies to assist people in coping with these challenges.
Longitudinal changes in neuropsychiatric symptoms: Impact of discrepancy in everyday preferences between people with cognitive impairment and their care partners
Authors: Wilkins James M 
Published: February 2022

AbstractBackgroundNeuropsychiatric symptoms (NPS) of major neurocognitive disorders are common and debilitating facets of the illness process. Yet, little is known about the impact on NPS of discrepancy in the importance of everyday preferences between persons with cognitive impairment (CI) and proxy ratings by their care partners.MethodThe sample included 48 dyads of persons with CI (Clinical Dementia Rating Scale score ≥ 0.5) and their care partners. NPS of the person with CI were measured using the Neuropsychiatric Inventory brief Questionnaire (NPI‐Q) and 15‐item Geriatric Depression Scale (GDS‐15) at baseline and follow‐up (mean 486 days). The Preferences for Everyday Living Inventory was used to assess importance of preferences for persons with CI at baseline; care partners separately completed concurrent proxy assessments at baseline. Mixed random and fixed effects longitudinal models were used to evaluate the impact of baseline discrepancy in everyday preferences assessment between persons with CI and their car partners on changes in NPS across time.ResultHigher levels of underestimation of the importance of “social engagement” preferences in the proxy ratings of care partners relative to the self‐ratings of persons with CI were associated with a higher degree of neuropsychiatric symptoms across time as a whole as measured by the NPI‐Q but not the GDS‐15.ConclusionThis study yields new insights into the relationship between discrepant importance ratings of “social engagement” preferences and neuropsychiatric manifestations of neurocognitive disorders, suggesting that a baseline level of discrepancy is associated with changes in neuropsychiatric symptoms over time. Resolving such discrepancies may then offer a therapeutic avenue to lessen NPS over time for persons with CI.
Dyadic interactions, physical environment, and social environment in dementia mealtime care: A systematic review of psychometric properties of instruments
Authors: Liu Wen 
Published: February 2022

AbstractBackgroundIt is critical to use validated instruments to assess dyadic interactions, social environment, and/or physical environment during mealtime care of persons living with dementia to evaluate the process and efficacy of mealtime assistance and environmental interventions. However, the quantity and psychometric quality of such instruments are unknown. This systematic review aimed to synthesize the quantity and quality of instruments that assess dyadic interactions, physical environment, and/or social environment during mealtime care for persons living with dementia.MethodsWe searched Pubmed, CINAHL, AgeLine, PsychINFO, and Cochrane Library for records published between 1980 and 2020. Records were eligible if they included any instrument that measures concepts of interest (i.e., mealtime dyadic interactions, physical and/or social dining environment). From eligible records, eligible instruments originally developed or later modified to measure concepts of interest were identified. From eligible records, eight characteristics of eligible instruments were extracted: 1) development process, 2) concept/construct being operationalized, 3) sample and setting, 4) administration method, 5) description of items, 6) scoring format/interpretation, 7) reliability, and 8) validity. A newly developed psychometric quality assessment tool was used to evaluate the psychometric quality of eligible instruments.ResultsIn total, 26 eligible instruments were identified. Seventeen instruments assessed dyadic interactions, 1 assessed only physical environment, and 8 assessed physical and social environment. All instruments were observational tools and scored as having low psychometric quality. Reasons for low psychometric quality included use of small sample size compared to the number of items, limited psychometric testing, and inadequate estimates.ConclusionsA number of instruments were developed and/or used to assess dyadic interactions, physical and/or social environment in dementia mealtime care. All instruments warrant further testing to accumulate psychometric evidence in larger diverse samples in different care settings for use in research and practice.
MIND MAPS: Molecular imaging of the mitochondrial‐endoplasmic reticulum‐synaptic axis in patients with Alzheimer's spectrum disorders
Authors: Rabiner Eugenii A. 
Published: February 2022

AbstractBackgroundNeurodegeneration is a pathognomonic feature of a variety of CNS disorders, including ALzhemimer's diosease. A dysfucntion of the mitochondrial‐endoplasmic reticulum‐synaptic axis is found in a variety of neurodegenerative disorders and has been linked to other pathological features such as misfolded protein accumulation, neuroinflammation, dysfunction of neurotransmitter release and neuronal loss.MethodWe examined a 12 patients with Alzheimer's spectrum disorder (ASD, MMSE range 16‐29) at baseline and 12‐18 months later with three PET radioligands; [18f]BCPP‐EF, [11C]SA4503 and [11C]UCB‐J, highly specific molecular markers of the mitochondrial complex 1 (MC1), the sigma 1 receptor (s1R) and the synaptic vesicular glycoprotein 2A (SV2A). The baseline data from the patient group was compared to a group of 16 age matched healthy volunteers.ResultWe found significant differences between the patient group and healthy volunteers for all three molecular markers in multiple brain regions. In addition, changes in mitochondrial markers were seen in the cortical areas of patients over the period of 12‐18 month.ConclusionMarkers of disruption of the mitochondrial‐endoplasmic reticulum‐synaptic axis can be detected in ASD patients in vivo, and can be demonstrated to change over a period of 12 ‐18 months. The imaging of multiple molecular markers enhances the evaluation of neurodegeneration pathology. Ashwin V. Venkataraman, Gaia Rizzo, and the MIND MAPS Consortium
Centiloid scale evaluation for β‐amyloid PET of cognitively normal elderly and SuperAgers
Authors: de Souza Giordana Salvi , Andrade Michele Alberton , Borelli Wyllians Vendramini , de Araújo Adriel Silva , De Almeida Mantovani Dimitri Brigide , Schilling Lucas Porcello , Matushita Cristina Sebastião , da Costa Jaderson Costa , Portuguez Mirna Wetters , da Silva Ana Maria Marques 
Published: February 2022

AbstractBackgroundThe Centiloid scale (CL) represents an attempt to standardize amyloid imaging to create a measure of global cortical β‐amyloid deposition using positron emission tomography (PET). The CL approach transforms standard uptake value ratio (SUVR) into values ranging from 0 to 100. This study aims to investigate the brain amyloid load in SuperAgers (SA), healthy age‐matched controls (ACs), and healthy middle‐aged controls (MCs).MethodThirty cognitively healthy individuals were evaluated with a cognitive screening and the Rey Auditory‐Verbal Learning Test (A7 list). They underwent an amyloid PET image with PIB were acquired in 3D mode from 40 to 60 minutes after injection using a PET/CT scanner (Discovery 600, GE Healthcare). Image analysis was performed using the PMOD software ‐ PNEURO tool (PMOD Technologies). SUVR was transformed to CTX (Global Cortical Target region) using the whole cerebellum (WC) as reference. The equation used to convert SUVR to CL is CL=100 (SUVR‐0.987)/1.019 and fits the parameters described previously.ResultTotal sample included 10 MCs (58.7±5.52 years‐old; A7 = 10.7±3.4), 10 ACs (83.5±4.2 years‐old; A7 = 6.9±1.7) and 10 SA (83.3±2.63 years‐old; A7 = 11.4±2.01). No significant difference was observed in the group analysis between amyloid SUVR between MC, SA, and AC groups (p=0.084). However, the mean CL values were for MCs: 0.65±6.5 CL; ACs: 31.20±34.5 CL; SA: 21.2±33.7 CL. The SuperAgers group exhibited a similar amyloid‐β burden compared with AC, even though A7‐RAVLT test results were significantly different (p=0.001).ConclusionThe CL approach was successfully implemented in various cognitive aging trajectories using the [11C]PiB PET. SuperAgers exhibited a similar amyloid‐β load to that of age‐matched healthy controls in both SUVR and CL analyses. Tau studies could help to find a better relationship between biomarker load and cognitive behavior.
Impact of polygenic risk score on normative models of hippocampal volumes
Authors: Janahi Mohammed , Aksman Leon M. , Schott Jonathan M. , Altmann Andre 
Published: February 2022

AbstractBackgroundNormative Models are widely used across clinical applications from infant growth charts to brain volume charts. For Alzheimer’s disease (AD), reduction in hippocampal volume (HV) is an early and often presymptomatic feature. Thus, precisely measuring deviation of HV from healthy aging facilitates earlier diagnosis. Brain volumes have been reported with heritability of 40‐90%, thus, implying that normative ranges of HV are heavily influenced by genetics. Here we investigate whether genetic information can improve HV nomograms for AD.MethodWe used Gaussian Process Regression (GPR) to generate nomograms of HV from 40,000 participants in UKBB aged 45‐82. These nomograms were contrasted to a previously reported Sliding Window method (SWM; PMID: 31254939). Next, we computed a Polygenic Risk Score (PRS) for HV using a large independent GWAS (N=33,536; PMID: 28098162). Participants were stratified into high and low PRS for HV; nomograms were built for each strata separately. Next, we used subjects from the ADNI dataset labelled cognitively normal (CN) or AD (N=226 and N=122) to examine the difference between using stratified versus non‐stratified nomograms.ResultNomograms generated using GPR matched those generated with the SWM with an average of difference of 17 mm3 (about 0.4%). Compared to the SWM, GPR extended the age range of the nomograms by ten years in either direction (from 56‐73 y/o to 47‐83 y/o: Figure 1). Nomograms stratified by PRS showed an average shift of 28 mm3 upward/downward for high/low PRS scoring samples (Figure 1). In ADNI, using non‐stratified nomograms led to a difference of 13% in median HV percentiles between high‐PRS and low‐PRS CN participants, which was reduced to 3.3% using stratified nomograms (Figure 2); this effect was not observed for the AD group.ConclusionGPR‐based nomograms were similar to the SWM‐nomograms while extending the range into areas critical for the analysis of aging diseases. Including genetics through a PRS for HV shifted HV nomograms in the expected direction. The small shift in nomograms of HV did not affect the sensitivity of AD diagnosis. However, it led to better adjusted estimates within CN subjects. Thus, genetics‐adjusted HV estimates may improve biomarker‐based AD‐risk predictions (PMID: 31526625).
Longitudinal PET imaging identifies earliest stages of Aβ accumulation in Down syndrome
Authors: Zammit Matthew D. , Tudorascu Dana L. , Laymon Charles M. , Cohen Ann D. , Zaman Shahid , Ances Beau M. , Hartley Sigan L. , Johnson Sterling C. , Stone Charles K. , Mathis Chester A. , Klunk William E. , Handen Benjamin L. , Christian Bradley T. 
Published: February 2022

AbstractBackgroundAdults with Down syndrome (DS) are genetically predisposed to Alzheimer’s disease (AD) and accumulate beta‐amyloid plaques (Aβ) early in life. Our previous work in this population comparing centiloids and amyloid load (AβL) identified an amyloid‐positive cutoff of 20 AβL. The aim of this study was to evaluate longitudinal AβL change across DS groups based on Aβ status.Method175 adults with DS (age=39.8 (8.64) years) were recruited through the Alzheimer’s Biomarker Consortium ‐ Down Syndrome study. Of the 175 adults, N=79 underwent up to four longitudinal [C‐11]PiB scans (2.64 (0.71) years apart). Longitudinal Aβ change was calculated for each individual using AβL. Cluster analysis identified a group of A‐ individuals with significant Aβ increase at subthreshold detection levels, and was used to inform a subthreshold A+ cutoff. Rates of AβL change were compared across groups of A‐ (AβL < 13.3), subthreshold A+ (13.3 < AβL < 20) and A+ (AβL > 20) DS. Average SUVr images were then generated across all participants for each group and SUVrs were extracted to evaluate regional Aβ burden.ResultThe A‐ group showed longitudinal change of 0.32 (0.66) AβL/year, while the subthreshold A+ and A+ groups showed change of 2.60 (1.11) and 3.22 (1.26) AβL/year, respectively (Figure 1). AβL change was statistically different across all groups (ANCOVA F = 76.7, p < .0001) while adjusting for imaging site. Post hoc Student’s t‐tests revealed that the subthreshold A+ and A+ groups had significantly greater AβL change compared to the A‐ group (Bonferroni‐adjusted p < .0001). No significant difference in AβL change was observed between the subthreshold A+ and A+ groups. Figure 2 displays the average SUVr images for each Aβ group. Relative to the A‐ group, the subthreshold A+ group showed greater regional Aβ burden (Table 1).ConclusionDS adults with a subthreshold A+ classification showed indistinguishable rates of Aβ change compared to those who are conventionally A+, suggesting that longitudinal PET imaging can identify significant Aβ change early during AD progression. These longitudinal findings can inform sample size estimates for AD clinical trials aimed at early intervention in this population.