bluuebunny/crossref_metadata_2025 huggingface dataset:
Dorsal hippocampal surface reduction as a biomarker of neurodegeneration in subjects with subjective cognitive decline and MCI converters to dementia
Authors: Verdejo Juan , Cuesta Pablo , Torres Lucia , Fernández Ricardo Bruña , Maestú Fernando
Published: February 2022

Background

Hippocampal atrophy has been proposed as the main neurodegeneration marker in the Alzheimer’s disease (AD) continuum. However, scarce research has found differences on that measure at early stages, i.e. subjective cognitive decline (SCD), and between mild cognitive impairment (MCI) patients that convert or not to AD. Here, we explored whether group differences emerged when other brain characteristics, as the white matter microstructure or the hippocampal surface shape, are used.

Method

The sample was composed by 393 older adults (aged from 57 to 87) recruited from the “Hospital Universitario San Carlos” and the Center for elders at the Chamartín District, all located in Madrid, Spain. They were classified in three groups according to their cognitive and functional status and following the NIA‐AA criteria: 162 were catalogued as MCI, 99 with SCD and normal cognitive performance, and 132 healthy controls without cognitive concerns. 93 of the MCI participants were followed and classified according to their clinical outcome: 31 classified as progressive MCI (p‐MCI) and 62 as stable MCI (s‐MCI). All participants underwent a MRI scan session where structural and diffusion weighted images were collected. None of the participants exhibited a history of psychiatric or neurological disorders (other than MCI). We performed tract‐based spatial statistics analysis on DTI data and vertex‐wise statistics on the structural images to explore groups differences in white matter microstructure, and hippocampal volume and surface shape.

Result

MCI patients exhibited reduced FA, increased MD, and reduced volume and surface of the hippocampus compared to both SCD and control groups. Differences between SCD and control groups emerged in the association between FA values and global hippocampal volume, and also in the surface shape analysis. Finally, when comparing MCI subgroups, the p‐MCI patients showed a reduced hippocampal volume and a bilateral dorsal reduction on the surface of both hippocampi compared to s‐MCI.

Conclusion

These results provide evidence of the progressive subcortical degeneration that occurs at different stages of healthy and pathological aging. Furthermore, they highlight the potential advantage of the use of the shape analysis of the hippocampal surface and the association between different brain measures as predictive biomarkers.
Prediction of cognitive performance from IQ biomarkers and MR volumetrics in the ATN framework depends on diagnosis
Authors: Whittington Alex , Gunn Roger N.
Published: February 2022

Background

The A/T/N classification system has emphasised the importance of considering multi‐channel biomarker readouts in AD research. Further, it is important to establish the relationship of these signals to cognitive performance and their relevance to enable optimum inclusion criteria for clinical trials. The IQ analytics platform provides powerful outcome measures for both Amyloid and Tau PET. In this work, we also consider hippocampal volume and investigate the relationship of these A/T/N biomarkers with cognitive performance at different stages of the disease process.

Method

AmyloidIQ, TauIQ and MR Volumetric analytics were performed on cross‐sectional data from 605 subjects (CN=376, MCI=173, Dementia=56) downloaded from ADNI where each subject had [18F]Florbetapir, [18F]Flortaucipir and a T1 MRI scan. AmyloidIQ determines the overall amyloid burden as an Amyloid Load percentage (Figure 1 and 2) whilst the TauIQ algorithm deconstructs the more complex Tau signal into global signal and local signal (Figure 3 and Figure 4). The hippocampal volumes for each subject were derived in SPM. We performed a multiple regression analysis with ADAS‐COG as the outcome variable and Global Tau Load, Local Tau Load, Amyloid Load and Hippocampal Volume as predictors. All possible linear models (including interaction terms) were evaluated on each diagnosis group separately and the optimum model was selected at in each case by choosing the model with the lowest BIC.

Result

The hippocampal volume was a statistically significant variable in the optimum model in all diagnosis groups but the statistically significant IQ analytics outcome measures were dependent on the diagnosis (Table 1); in the CN group the key parameter was Amyloid Load, in the MCI group, interestingly, both Local Tau Load and Amyloid Load were statistically significant, finally in the Dementia subjects only the Global Tau Load was found to be statistically significant. When evaluated on all subjects simultaneously, the optimum model explained 49% of the variance in ADAS‐Cog scores.

Conclusion

The IQ analytics biomarkers provide orthogonal information that are related to cognitive function in different ways across the disease spectrum. Our results imply that the novel Local Tau Load outcome measure is an important biomarker for stratifying and following MCI subjects.
Characterizing brain structure among middle‐age and older Hispanics/Latinos in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) and SOL‐Investigation of Neurocognitive Aging (SOL‐INCA): Preliminary findings
Authors: Stickel Ariana M. , Tarraf Wassim , Gonzalez Kevin A. , Paredes Alejandra Morlett , Zeng Donglin , Cai Jianwen , Isasi Carmen R. , Kaplan Robert , Lipton Richard B. , Daviglus Martha L. , Testai Fenando D. , Lamar Melissa , Gallo Linda C. , Talavera Gregory A. , Gellman Marc D. , Ramos Alberto R. , Gonzalez Hector M. , DeCarli Charles S.
Published: February 2022

Background

The older Hispanic/Latino population in the U.S. is projected to grow faster than any racial/ethnic group in the country. Little is known about brain aging in this population, and we remain poorly equipped to detect and track brain changes in this population. We characterized brain aging in a sample of Hispanics/Latinos from diverse backgrounds and investigated differences by sex.

Method

Nunweighted=1,389 Hispanics/Latinos (ages 39‐85 years; 66% female) from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) underwent brain magnetic resonance imaging (MRI) as part of the Study of Latinos ‐ Investigation of Neurocognitive Aging MRI (SOL‐INCA MRI) ancillary study. MRI outcomes of interest included global (gray matter, total brain) and regional (lobar cortices, hippocampus) brain volumes, lateral ventricle volume, and total white matter hyperintensity (WMH) volume. All MRI measures were residualized for total cranial volume prior to calculating brain aging trajectories using linear regressions that included sex, height, and Hispanic/Latino background as terms in the model. We also tested for effect modification by sex.

Result

Mean age was 60.8± 10.3 years. Age was associated with decrements in total (β
total
=‐0.66; p<0.001) and hippocampal volumes (β
hippocampus
=‐0.20; p<0.001) as well as incremental enlargements in lateral ventricle and WMH volumes (β
log_lateralvent
=0.48; p<0.001; β
log_WMH
=0.54; p<0.001). Age was also inversely linked to total brain gray matter as well as all lobar cortical gray matter volumes. Age‐related decrements in total and regional brain volumes, but not lateral ventricle or WMH, were exacerbated in men relative to women (all p<0.05). Adjusting for height and background, women had larger total brain (standardized beta β
total
=0.27; p<0.001), frontal (β
frontal
=0.27; p<0.001), and parietal (β
parietal
=0.17; p=0.025) volumes, smaller hippocampal and lateral ventricle volumes, and larger gray matter volumes, but did not differ in WMH as compared to men.

Conclusion

These findings suggest that increasing age is associated with smaller regional MRI brain measures in Hispanic/Latino individuals. Aging patterns in gray matter volumes appeared to be exacerbated among men compared to women whereas age‐related differences in lateral ventricular volume and white matter hyperintensities were consistent between sexes. Our findings help establish the trajectories of brain aging among middle‐aged and older Hispanics/Latinos.
Differential cognitive correlates of tau and neurofilament light chain in cerebrospinal fluid of frontotemporal lobar degeneration patients with and without Alzheimer’s markers
Authors: Vasilevskaya Anna , Taghdiri Foad , Multani Namita , Salvo Cristina , Anor Cassandra Jessica , Misquitta Karen , Burke Charles , Tang‐Wai David F. , Lang Anthony E. , Fox Susan , Slow Elizabeth , Tartaglia Maria Carmela
Published: February 2022

Background

Frontotemporal lobar degeneration (FTLD) phenotypes can be associated with Alzheimer’s disease (AD). It is unknown whether differences exist in relationship between markers of degeneration such as tau and neurofilament light chain (NFL) and cognition between FTLD with and without AD.

Method

40 FTLD patients were included in this study: (A) 31 FTLD without AD [5 behavioral variant FTD, 11 corticobasal syndrome (CBS), 1 non‐fluent variant primary progressive aphasia (nfvPPA), 12 progressive supranuclear palsy (PSP), 2 semantic variant PPA (svPPA); age (67.74±10.28); sex (20M:11F)]; and (B) 9 FTLD positive for AD [6 CBS‐AD, 1 nfvPPA‐AD, 1 PSP‐AD, 1 svPPA‐AD; age (66±8.46); sex (5M:4F)]. CSF levels of Aβ42, phosphorylated tau (p‐tau) & total tau (t‐tau) were measured using sandwich ELISA and AD pathology was deemed present if p‐tau > 68 pg/mL and Aβ42 to t‐tau index < 0.8. CSF NFL was measured using SIMOA. Full neuropsychological battery was completed, controlled for age/education.

Result

In the FTLD cohort, significant relationships were observed between CSF t‐tau and CDR sum of boxes (r=0.599, p=.001) and MOCA (r=‐0.530, p=.004). In FTLD group, digit span backwards (DSB) was significantly associated with CSF t‐tau (r=‐0.492, p=.009) & NFL (r=‐0.427, p=.02); while verbal fluency, Trail Making Test part A & digit span forward (DSF) were only related to NFL (r=‐0.410, p=.03; r=0.463, p=.02; r=‐0.374, p=.05, respectively). In the FTLD‐AD cohort, MOCA was significantly associated with CSF p‐tau (r=‐1.00, p<.0001) & t‐tau (r=‐0.887, p=.02); memory and executive function tests including California verbal learning test 30s recall, DSB & DSF were significantly associated with CSF t‐tau (r=‐0.788, p=.04; r=‐0.836, p=.04; r=‐0.760, p=.07, respectively); while verbal fluency & category fluency were significantly associated with CSF markers of NFL (r=‐0.841, p=.04; r=‐1.00, p<.0001), p‐tau (r=‐0.981, p<.001; r=‐1.00, p<.0001), & t‐tau (r=‐0.984, p<.001; r=‐0.977, p=.004).

Conclusion

In both FTLD with and without AD, overall severity was related to CSF t‐tau but executive function in FTLD without AD was related to CSF NFL while in FTLD‐AD it was related to p‐tau and t‐tau. The presence of AD in FTLD phenotypes alters relationship to NFL, which may be indicative of differences in extent of degeneration.
PS1 mutation position influences regional PiB‐uptake and white matter lesion volume
Authors: Joseph‐Mathurin Nelly , Feldman Rebecca L. , Toomer Carmen , McKay Nicole S. , Strain Jeremy F. , Kilgore Collin B. , Gordon Brian A. , McCullough Austin A. , Chen Charles D. , Schultz Stephanie A. , Cruchaga Carlos , Xiong Chengjie , Morris John C. , Bateman Randall J. , Chhatwal Jasmeer P. , Benzinger Tammie L.S. ,   Dominantly Inherited Alzheimer Network
Published: February 2022

Background

Mutations in the Presenilin‐1 (PS1) gene account for 80% of dominantly inherited Alzheimer disease (DIAD). Previous findings suggest PS1 mutation position relative to codon 200 may impact the distribution and amount of cerebral β‐amyloid pathology (Mann et al., 2001; Ryan et al., 2015). We investigated the effect of mutation position on imaging markers of β‐amyloidosis and small vessel disease with a focus on regional variability and disease progression.

Method

Individuals with PS1 mutations before (Pre‐200MC, n=76) or after codon‐200 (Post‐200MC, n=126) and non‐carriers of these mutations (n=129) from the same families were assessed with the Clinical Dementia Rating (CDR) scale and underwent neuroimaging including PiB‐PET to assess β‐amyloid burden and T2‐FLAIR MRI to assess white matter lesions. A subset (52 non‐carriers, 63 Pre‐200MC, 73 Post‐200MC) had longitudinal data available. Accounting for estimated year to symptom onset (EYO) and APOE‐ɛ4 status, cross‐sectional and longitudinal linear mixed‐effects models evaluated the effect of mutation positions on PiB‐uptake (SUVR) in 40 FreeSurfer regions, white matter hyperintensity (WMH) volumes in periventricular and deep areas, and their associations with dementia.

Result

Pre‐200MC had earlier age of symptom onset versus Post‐200MC (43.34±8.97 versus 46.81±7.55 years, p<0.0001). Pre‐200MC presented with higher amyloid burden (mean cortical SUVR of 2.28±1.27 versus 1.91±1.0, p<0.02). Differences were observed mostly in frontal, temporal, and subcortical regions. Stronger associations between PiB‐uptake and EYO were observed in Pre‐200MC versus Post‐200MC in nearly all regions (precuneus: F(1,192)=9.37, p<0.01; caudate: F(1,192)=17.65, p<0.001; Figure 1A). In contrast, Post‐200MC presented with stronger associations of periventricular WMH with EYO (F(1,25)=5.02, p<0.05) and deep WMH with dementia as measured by CDR‐SB (F(1,25)=14.01, p=0.01). Longitudinal analyses showed higher rates of change in PiB uptake in Pre‐200MC versus Post‐200MC in several frontal, temporal, and striatal regions (inferior temporal: F(1,171)=13.71, p<0.0005; caudate: F(1,171)=8.22, p<0.005; Figure 1B). Mutation position did not influence rates of change in WMH volumes nor cognitive decline.

Conclusion

These findings confirm that mutation position within the PS1 gene influences disease presentation in DIAD. Improved characterization of heterogeneity in disease progression may inform further clinical trials in this population. Further investigation into biological mechanisms responsible for these differences is necessary. Funding: AARFD‐20‐681815;U19AG032438.
Piloting of a compensatory memory digital health intervention in a group of individuals with subject cognitive complaints
Authors: Weakley Alyssa , Schmitter‐Edgecombe Maureen , Namboodiri Sudev , Randhawa Jagnoor , Farias Sarah Tomaszewski
Published: February 2022

Background

Traditional paper‐based calendars and to‐do lists have limitations related to difficulty retrieving information and no automated way to prompt completion of activities. Such limitations may be overcome using a digital format through organized files, search functions, and alarms. This pilot project trained older adults at risk for cognitive decline to use the Digital Memory Notebook (DMN), a tablet‐based application, to support everyday memory. The primary goal was to obtain preliminary information regarding a 6‐week, group‐based DMN training intervention in terms of acceptability and satisfaction.

Method

Ten participants with subject cognitive complaints (SCC), a risk factor for Alzheimer’s disease, enrolled in the study. Participants met 2‐hours per week for 6‐weeks. A manualized curriculum covered specific DMN functions and weekly homework/goal‐setting targets. Following the intervention, participants continued to use the DMN for 4‐weeks and then provided feedback, which was audio recorded and transcribed.

Results

Three participants left the study after the initial consenting session and one participant discontinued after the second session, all specifying that they were already efficiently using similar electronic systems. The remaining six participants had an average attendance rate of 89%, which was above our initial target rate of 80%. Overall, participants reported that they enjoyed the group intervention and believe the DMN is a useful everyday memory aid. Participants endorsed seeing benefit of having multiple functions (e.g., calendar, to‐do list, notes, journal) in a single, senior‐friendly application. Participants particularly enjoyed the journal and note taking functions, emphasizing the organization and search functions to be the most beneficial. Three participants chose to download the DMN onto their personal tablet device for continued use and one participant downloaded a notes/journal specific application to their phone.

Conclusions

Initial feedback for the DMN group intervention is promising and suggests that individuals find value in using the DMN as a compensatory tool. That said, participants may lack initial buy‐in if they are already using a similar electronic system. Information gleaned from this pilot study will help improve the group intervention and digital health tool.
Dementia grief reconceptualized: Systemic review of psychotherapeutic approaches for BPSD and NPS during COVID‐19
Authors: Ione Adrienne
Published: February 2022

Background

The biopsychosocial effects of COVID‐19 experienced by people ages 65 and greater are unprecedented. The gravity of losses will not be realized for decades. Physical, personal, economic and social constraints remain in place, generating feelings of stress and anger. Even graver of a situation is a subset of this population ‐ people who have been diagnosed with dementia and those who are more vulnerable to stress effects on the aging brain ‐ where mental health ramifications of stress are magnified. Traumatic experiences hold the possibility of reactivating previous losses that have not been fully integrated into the gut‐brain axis. At the same time, traumatic events present possibilities in releasing emancipating power when losses are modulated by access to grief‐based psychotherapies. With access to psychotherapy remaining severely limited for the most vulnerable among us, the vastness of mental health disparities remains undocumented.

Methods

Critically review psychological intervention studies investigating the biopsychosocial effects of COVID‐19 among people with dementia and assess the evidence for incorporation of grief‐based psychotherapy and presence of strengths‐based language. A systematic review of Web of Science databases was carried out by using keywords dementia and COVID‐19, employing Boolean operating word AND, with search results limited to 2020‐2021.

Results

From a total of 229 initial search results, 156 did not meet study criteria and were omitted. Of the 73 studies that met criteria, six thematic therapeutic approaches emerged: neuroscience, management of BPSD, pharmacological, lifestyle, social work, and technological interventions. Secondarily, studies were assigned to one of three categories on viewing COVID‐19 as an event that is: limiting or constraining, growth opportunity, or something else.

Conclusion

Current evidence suggests that the biopsychosocial effects of COVID‐19 and dementia present a complex, dynamic and evolving relationship. Prolonged and sustained exposure to stress and trauma develops a deepening cognitive divide, where people transition from mild cognitive impairment to meeting diagnostic criteria of dementia. These times demand increasing access to grief‐informed psychological services, such as Active Capabilities Therapy, in an attempt to diminish the gut‐brain axis harms of BPSD and NPS as experienced by the individual.
Exploring the basis of phenotypic diversity in Alzheimer’s disease
Authors: Wan Yutong
Published: February 2022

Background

Alzheimer’s Disease (AD) is the most common type of dementia and affects more than 50 million people around the world. Although there is no effective treatment for the disease at the moment, early detection is still critical to start an early management plan and try out various interventions. Besides the stereotypical Amnestic Syndrome, many atypical pehnotypes exist which make accurate early diagnosis challenging.

Method

Examined Corticobasal Syndrome (CBS), behavioural variant of Frontotemporal Dementia (bvFTD), Posterior Cortical Atrophy (PCA), and Primary Progressive Aphasia (PPA) cases correlating with AD's onset. As such, this literature review investigated the reasons underpinning the selective regional vulnerability leading to clinical diversity in AD.

Result

The majority of AD is sporadic, caused by phosphorylated‐tau aggregates and amyloid‐β depositions in neurons or extracellular space. Increasing age is the dominant risk factor for AD development and the major genetic risk factor for sporadic AD is ApoE4. A small proportion of AD is familial, due to mutations in APP, PSEN1, and PSEN2 genes. The available research findings suggest that diverse clinical presentations correlated with selective degeneration and pathology development in different brain regions. The different regions with originally pathological alternations of each phenotype may help explain the conundrum of polytropic presentations, that primary motor cortex is significantly affected in CBS, basal ganglia in bvFTD, posterior part of the brain in PCA, and temporoparietal areas in PPA. Research indicates that the presence of ApoE4 is significant for the development of all AD phenotypes. In addition, while some studies reported several famial cases, these are not typically thought to be representative and thus more studies are needed.

Conclusion

The diverse clinical phenotypes of AD, including AS, CBS, bvFTD, PCA, and PPA, share similar pathogenesis and genetic factors, but each phenotype has divergent patterns of regional distribution of the pathology.
Effects of the culturally sensitive DEmentia Competence Education for Nursing home Taskforce (DECENT) programme in mainland China: A quasi‐experimental study
Authors: Zhao Yayi , DING Yaping , Liu Li , Chan Helen YL
Published: February 2022

Background

A number of dementia care educational programmes are developed to build nursing‐home staff’s care competence in the Western culture. However, their applicability and cultural relevancy to Chinese population are questionable. This study aimed to develop and evaluate a Culturally Specific DEmentia Competence Education for Nursing home Taskforce (DECENT) programme in mainland China.

Method

A multi‐centre two‐arm repeated‐measures quasi‐experimental study was conducted with 217 care staff from 10 nursing homes. Nursing homes were pair‐matched and allocated into intervention (n = 5) and control group (n = 5). Participants were allocated into intervention group (n=101) who received the DECENT programme or control group (n = 116) who received the printed educational materials according to the settings they worked. The DECENT programme comprised eight topics and was delivered through multiple pedagogical strategies by a qualified educator once per week for 60‐90 minutes over eight weeks. The study outcomes were the sense of competence in dementia care, dementia knowledge, attitudes towards people with dementia, person‐centred care in nursing homes and the severity of behavioural and psychological symptoms of dementia (BPSD) of residents with dementia and staff‐perceived disturbance. They were measured at baseline (T0), immediately post‐intervention (T1) and 3‐month after intervention (T2). Generalised estimating equation models were performed to analyse the effect.

Result

The intervention group improved more significantly than the control group in sense of competence in dementia care both at T1 (B = 5.24, p < .001) and T2 (B = 4.43, p = .013). In terms of dementia knowledge and person‐centred care in nursing homes, the intervention group only showed significant improvement at T1 (B = 3.18, p = .001; B = 5.75, p = .018, respectively), but not at T2 (p = .089 and .104, respectively), when compared to control group. Attitudes towards people with dementia and severity of BPSD and staff‐perceived disturbance were not significant both at T1 and T2 relative to control group.

Conclusion

The DECENT programme is effective in improving nursing‐home staff’s perceived dementia‐care competence. Nevertheless, continual learning and support at organisational level is needed for cultivating changes in practice and residents’ outcomes.
Insights on FTD: An externally led patient‐focused drug development meeting
Authors: Niehoff Debra , Dodge Shana G , Graham Elizabeth , Barker Megan S , Cosentino Stephanie , Wheaton Dianna KH , Denny Sharon S , Dacks Penny A , Dickinson Susan
Published: February 2022

Background

Understanding the lived experience of those affected by a disorder should be central to the development and evaluation of therapeutics. Disease‐specific Externally Led Patient‐Focused Drug Development (EL‐PFDD) meetings were established by the FDA to hear directly from those living with a condition about experiences, symptoms, treatments, and hopes for new therapies. Such insights are particularly important for frontotemporal degeneration (FTD), a genetically and clinically heterogenous condition that includes behavioral variant FTD (bvFTD), primary progressive aphasias, progressive supranuclear palsy, corticobasal syndrome, and ALS with FTD.

Method

On March 5, 2021, AFTD hosted an EL‐PFDD for FTD; 382 caregivers, family members, and persons with FTD participated, plus 171 professionals. In preparation, AFTD and the FTD Disorders Registry conducted the FTD Insights Survey, gathering information on clinical and genetic characteristics of respondents; the earliest, current, and most concerning symptoms; and perspectives on treatments and clinical trials. 1,237 persons with FTD, care partners/caregivers, and family members in the US, Canada and UK had completed the survey by October 31, 2020.

Result

People living with all FTD syndromes described challenges in activities of daily life, including preparing meals, managing finances, driving, and conversing. Symptoms vary within and across disorders, encompassing language, motor function, thinking/decision‐making, interpersonal/emotional functioning, among others. Many people diagnosed have limited awareness of their symptoms (65% bvFTD; 37% other FTD disorders). In genetic FTD, the path to diagnosis can be simpler, yet a lifetime of perceived or known risk can dramatically influence life decisions. The lack of effective, approved therapies – disease‐modifying or symptomatic – was a universal concern. Non‐prescription and off‐label prescription therapies may stabilize symptoms temporarily while prescribed acetylcholinesterase inhibitors can exacerbate symptoms. Many people are willing to participate in clinical research depending on illness stage and burden imposed by trial design.

Conclusion

The community of those affected by FTD offers insights into this condition as partners in research. Central themes of the EL‐PFDD meeting for FTD will be summarized by AFTD in a Voice of the Patient reported submitted to the FDA. Results of the FTD Insights Survey are available to researchers through the FTD Disorders Registry.
Differential impact of sub‐threshold amyloid‐beta deposition on intra‐ and inter‐network functional connectivity for cognitively normal older adults according to APOE genotype
Authors: Kang Dong Woo , Lim Hyun Kook , Wang Sheng‐Min , Um Yoo Hyun
Published: February 2022

Background

Previous research has demonstrated that sub‐threshold amyloid‐beta retention is related to cognitive performance, functional brain change, and further amyloid‐beta /tau accumulation. However, few previous studies have examined an effect of APOE genotype on the association between functional connectivity (FC) and memory performance in the earliest stage of Alzheimer’s disease (AD). We aimed to evaluate the difference in intra‐ and inter‐regional FC between cognitive older adults with and without APOE ε4‐allele and examined an impact of intra‐ and inter‐regional FC on memory performance in cognitively intact older adults, according to APOE ε4‐allele status.

Method

Cognitively normal older adults with and without APOE ε4 allele (carrier, n=32; non‐carrier, n=80) underwent neuropsychological battery, resting‐state functional magnetic resonance imaging (MRI) scans, and positron emission tomography (PET) scans with [18F] flutemetamol. We employed a priori defined regions of interest to investigate the intra‐ and inter‐network FC profiles of default mode network (DMN), central executive network (CEN), and salience network (SN). We evaluated difference in intra‐ and inter‐regional FC via analysis of covariance and examined the intra‐ and inter‐regional FC‐by‐APOE genotype interaction for memory performance by multiple linear regression analysis, adjusting for age, sex, and education years.

Result

There was no significant difference in intra‐ and inter‐regional FC for cognitively intact older adults without amyloid‐beta retention between APOE ε4 non‐carrier and carrier. The inter‐regional FC between DMN and CEN displayed a significant interaction with APOE genotype for word list memory, total memory, and total scores (uncorrected p < 0.001; uncorrected p < 0.005; uncorrected p < 0.05). Cognitively normal older adults with APOE ε4 allele exhibited steeper slope for a positive relationship between the inter‐regional FC and memory performances than those without APOE ε4 allele.

Conclusion

The inter‐regional FC between DMN and CEN has a differential impact on memory performances according to the representative AD risk factor, APOE ε4 allele in the earliest phase of AD. These results could contribute to the deeper understanding of the initial pathogenesis of AD.
Differential impact of sub‐threshold amyloid‐beta deposition on regional homogeneity for cognitively normal older adults according to APOE genotype: Whole brain voxel‐wise analysis
Authors: Kang Dong Woo , Lim Hyun Kook , Wang Sheng‐Min , Um Yoo Hyun
Published: February 2022

Background

Previous research has demonstrated that sub‐threshold amyloid‐beta retention is related to cognitive performance, functional brain change, and further amyloid‐beta /tau accumulation. However, little research has investigated an effect of APOE genotype on the association between sub‐threshold amyloid‐beta deposition and intra‐regional brain activity in the earliest stage of Alzheimer’s disease (AD). This study set out to evaluate the impact of sub‐threshold global and regional amyloid‐beta retention on intra‐regional brain activity, measured by regional homogeneity (ReHo), in cognitively normal older adults, according to APOE ε4‐allele status.

Method

Cognitively normal older adults with and without APOE ε4 allele (carrier, n=32; non‐carrier, n=80) underwent functional magnetic resonance imaging (MRI) scans and positron emission tomography (PET) scans with [18F] flutemetamol. Whole‐brain voxel wise analysis was conducted for evaluating the sub‐threshold Ab deposition‐by‐ APOE genotype interaction for ReHo, adjusting for age, sex, and education years.

Result

Sub‐threshold amyloid‐beta deposition in temporal lobe showed a significant interaction with APOE genotype for ReHo of left calcarine fissure and surrounding cortex, cerebellum 7, and cerebellum 6 (FDR‐adjusted p < 0.05, cluster size > 100 voxels). Cognitively normal older adults with APOE ε4 allele exhibited a positive relationship between sub‐threshold amyloid‐beta retention in temporal lobe and ReHo, while those without APOE ε4 allele showing an opposing association.

Conclusion

Thus, even sub‐threshold amyloid‐beta deposition has a differential impact on ReHo according to the representative AD risk factor, APOE ε4 allele in the earliest phase of AD. These results could contribute to the deeper understanding of the initial pathogenesis of AD.
Adjustments in the range of activities offered in long‐term care facilities during the COVID‐19 visitor ban: Lessons learned
Authors: van der Roest Henriëtte G , Kroezen Marieke , Hartstra Egbert , Van der Velden Claudia , Prins Marleen
Published: February 2022

Background

Residents of long term care facilities (LTCFs) are one of the most vulnerable groups worldwide to the coronavirus. During the COVID‐19 outbreak in the Netherlands, as well as in many other countries, a national visitor‐ban for LTCFs was in place (starting 20 March and (partly) ending on 15 June 2020). Organized (group) activities, offering a meaningful and pleasant day structure for both residents, were scaled down or completely stopped. So far, it remains unclear which particular types of activities were cancelled, whether ‘replacement’ activities were introduced that may acquire a structural character in the future, and how this affected care workers.

Method

Online questionnaire research into the consequences of the COVID‐19 outbreak and restrictive measures in long term care facilities in the Netherlands was conducted at two points in time; six weeks after the COVID‐19 visitor‐ban was implemented (T1) and one week after the ban was (partly) lifted (T2). Residents, family members and care professionals were recruited independently for each measurement. This study only uses care professionals’ data. Descriptive statistics, frequencies and independent t‐tests were performed.

Result

During T1, 811 professionals completed the questionnaire, during T2 324. Care workers reported a decrease in regular group activities during the visitor‐ban. For example, exercise activities, creative activities and music activities were undertaken less frequently. Domestic activities such as eating together and watching television were also scaled down as compared to before the visitor‐ban. However, activities that could be easily done on the unit with sufficient social distance, such as music activities, conversations and playing games in the living room, were undertaken more frequently during the visitor‐ban. The impact of the up‐ and downscaling of activities on care professional burden, and the perceived ability to provide adequate care, will be presented.

Conclusion

Activities are an important means for residents of long term care facilities for obtaining pleasure and giving a meaningful structure to the day. Future lessons can be learned from the adjustments that had to be made in the range of activities offered during the COVID‐19 visitor‐ban.
Increased intra‐network functional connectivity in MCI patients progressing towards dementia compared to stable MCI
Authors: Malotaux Vincent , Dricot Laurence , Quenon Lisa , Ivanoiu Adrian , Lhommel Renaud , Hanseeuw Bernard J.
Published: February 2022

Background

Few resting‐state functional magnetic resonance imaging (rs‐fMRI) studies were carried out in patients with mild cognitive impairment (MCI). Most were cross‐sectional and brought conflicting results with both decrease and increase of rs‐fMRI connectivity reported. We used a recently developed atlas of resting‐state networks specific for late adulthood to investigate longitudinal changes in rs‐fMRI in MCI patients, both within and between networks.

Method

Sixty older adults underwent rs‐fMRI using the Atlas55+[1] to assess intra and inter‐network functional connectivity and a baseline [18F]‐Flutemetamol‐PET to estimate their Amyloid‐β (Aβ) load. Sixteen stable Aβ‐negative clinically normal volunteers performed a baseline rs‐fMRI scan while 44 MCI patients performed 2 to 4 acquisitions with an average follow‐up duration of 14,5 months. Aβ was expressed in Centiloids and a threshold of 27 was used to define Aβ positivity based on previous work[2]. Intra and inter‐network functional connectivity analyses were performed using both progression to dementia and Aβ status as grouping variables. Demographics and follow‐up durations are provided in Table 1. Linear mixed‐models with random intercept and slope predicted changes in rs‐fMRI over time, adjusting for age, sex, education and e4 status.

Result

We observed that MCI patients who progressed to dementia during follow‐up had increased intra‐network connectivity over time, compared to stable MCI. Specifically, the time‐by‐outcome (progression vs stable) interaction for the intra‐network functional connectivity in the default‐mode, the executive control and the visual networks were significant (Fig. 1‐3). Similar results were found when limiting analyses to Aβ positive MCI and adjusting for volume effects, except for the visual network. Baseline intra‐network functional connectivity did not differ between groups (all p‐values>0,05). Inter‐network functional connectivity did not change between groups over time (all p>0,05).

Conclusion

In Alzheimer's Disease, intra‐network functional connectivity increases during the progression of MCI to dementia compared to stable MCI. References:1. Doucet, Gaelle E et al. Cereb Cortex. 2021;31(3):1719‐1731. doi:10.1093/cercor/bhaa321.

2. Hanseeuw, Bernard J et al. Eur J Nucl Med Mol Imaging. 2021;48(1):302‐310. doi:10.1007/s00259‐020‐04942‐4.
Genetic Creutzfeldt Jakob disease: Can MRI serve as an early diagnostic biomarker?
Authors: Omer Nurit , Silbak Rawan , Trabulus Noa , Gana‐Weisz Mali , Goldstein Orly , Glinka Tal , Orr‐Urterger Avi , Giladi Nir , Droby Amgad , Bregman Noa
Published: February 2022

Background

Genetic CJD (gCJD) is a rare prion disease, with a large cluster in Jews of Libyan origin. The disease is caused by an E200K mutation in the PRNP gene, and is inherited in an autosomal dominant manner with penetrance approaching 100% throughout life. While the mutation is inborn, symptoms usually appear in late adulthood, leading to a rapid neurological deterioration until death. Characterization of a prodromal stage is crucial for understanding the processes leading to disease onset, and eventually for defining the right timing for disease modifying treatment, when available. Objective: To investigate early MRI candidate markers in asymptomatic E200K carriers based on diffusion tensor imaging (DTI).

Method

51 participants (>49 years old) first degree relatives of gCJD patients were enrolled. All participants underwent genetic sequencing and an MRI scan at 3T acquiring DTI datasets. Tract Based Spatial Statistics (TBSS) was performed for DTI.

Result

E200K mutation was detected in 24 participants (55.8+−6.25, F:M 13:11). Based on TBSS, reduced fractional anisotropy was detected in the anterior limb of internal capsule, the superior fronto‐occipital fasciculus, thalamus and anterior thalamic radiation, and ventromedial prefrontal cortex when compared to non‐carriers (p=0.001 uncorrected). However, these between group differences did not survive correction for multiple comparisons (FDR).

Conclusion

Based on the obtained results, only subtle white matter differences can be detected between carriers and non‐carriers of E200K. A longitudinal study design with a larger sample size is warranted in order to characterize the evolution of underlying pathophysiological processes prior to phenoconversion
Reduced zwitterionic graphene oxide sheets decorated with nickel nanoparticles as magnetically and efficient catalyst for A3‐coupling reactions under optimized green experimental conditions
Authors: Chaabane Laroussi , Baouab Mohamed Hassen V. , Beyou Emmanuel
Published: February 2022

A Ni‐based supported reduced zwitterionic graphene oxideN,N‐bis(2‐pyridylmethyl)ethylenediamine 1,3‐propanesultone (GO‐BPED‐PS) material was prepared for the catalysis of A3‐coupling reactions under green experimental conditions. First, the in situ generation of nickel nanoparticles (NiNPs) onto the reduced zwitterionic GO‐BPED‐PS sheets was characterized by various techniques such as Fourier infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), X‐ray diffraction (XRD), scanning electron microscopy (SEM), and vibrating sample magnetometer (VSM) analysis. Moreover, the electron density map of NiNPs onto the reduced zwitterionic GO‐based sheets was produced through the X‐ray crystallographic analysis. Then, the as‐prepared reduced GO‐BPED‐PS NiNPs (rGO‐BPED‐PS@NiNPs) material was used as a heterogeneous catalyst for the three‐component coupling reaction (A3‐coupling reaction) of benzaldehyde, morpholine, and terminal alkynes. The experimental conditions were performed in order to obtain very good green chemistry metrics. In particular, we obtained a high catalytic efficiency when usingγ‐valerolactone as solvent, a reaction time of 3 h and a temperature of 100°C. In addition, it was demonstrated that the rGO‐BPED‐PS@NiNPs catalyst could be recycled for 11 times without a significant decrease in its catalytic activity.
The effects of carbon nanotubes selective location on the structures and properties of polyphenylene sulfide/polyamide 66 fibers
Authors: Su Zexi , Zeng Luxian , Zhang Shengchang , Xu Qibin , Jiang Mengjin , Liu Ju , Wang Chong , Liu Pengqing
Published: February 2022

Carboxyl modified carbon nanotubes (H‐CNTs) are added into 10 wt%‐polyamide 66/90 wt%‐polyphenylene (10‐PA 66/90‐PPS) blending system to improve the compatibility of blends. In order to investigate the effects of H‐CNTs selective location and H‐CNTs addition on the structures, morphologies, and properties of PPS/PA 66 composite fibers, three blending orders among H‐CNTs, PPS, and PA 66 are applied in the blending extrusion of ternary resins. The structures, morphologies, and properties of composite fibers are characterized via scanning electron microscopy, transmission electron microscopy, high‐pressure capillary rheometer, differential scanning calorimeter, tensile test, and dry heat shrinkage test. Experimental results indicate that the migration of H‐CNTs from PPS phase to the interface between PPS and PA 66 results in the increases of the crystallinity of PPS, the tensile strength and the high‐temperature resistance of ternary fibers. When H‐CNTs are blended with PA 66 firstly, the locking effects of H‐CNTs causes a phase‐inversion phenomenon, where major component PPS forms dispersed phase and minor component PA 66 forms continuous phase. Even though this phenomenon weakens the mechanical properties and the high‐temperature resistance of composite fibers, the shrinkage of composite fibers at high temperature is improved.
BMI changes and the risk of lung cancer in male never‐smokers: A prospective cohort study
Authors: Wu Zheng , Xie Shuanghua , Wang Fei , Chen Shuohua , Su Kai , Li Fang , Cui Hong , Cao Wei , Yu Yiwen , Qin Chao , Zheng Yadi , Dong Xuesi , Yang Zhuoyu , Luo Zilin , Zhao Liang , Xu Yongjie , Chen Hongda , Li Jiang , Wang Gang , Wu Shouling , Dai Min , Li Ni , He Jie
Published: February 2022

Background

To investigate the association between the risk of lung cancer and short‐term body mass index (BMI) changes in male never‐smokers of a large population‐based prospective study.

Methods

A total of 37,085 male never‐smokers from Kailuan cohort with at least ≥2 BMI measurements were recruited in the present study. The BMI change in the follow‐up was calculated as the annual percent change between BMI at last examination and that at baseline, and categorized into five groups: stable (−0.1 to <0.1 kg/m2/year), minor loss (−1.0 to <0.1 kg/m2/year) or gain (0.1 to <1.0 kg/m2/year), and major loss (<−1.0 kg/m2/year) or gain (≥1.0 kg/m2/year). The hazards ratios (HRs) and its 95% confidence intervals (CI) were estimated using Cox regression models.

Results

During a median follow‐up of 5.16 years, 224 lung cancer cases were identified. We found a U‐shaped association between BMI changes and lung cancer risk. Compared to men with stable BMI, those with major loss had a nearly twofold higher risk of lung cancer (HR = 1.97, 95% CI: 1.12–3.45), as well as those with major gain had more than twofold higher risk of lung cancer (HR = 2.15, 95% CI: 1.15–4.02). The associations existed when the analysis was stratified by BMI, waist circumference and blood lipids, and lipoproteins concentration at baseline examination.

Conclusions

The dramatic changes in BMI, both gain and loss, might increase lung cancer risk. The control of body weight would be a potential way for lung cancer prevention especially for the nonsmokers.
Keep your eye on…
Authors: Knopf Alison
Published: February 2022

The need for telemental health for infants

Recommendations for COVID‐19 vaccinations from AAP

The role of school nurses in teen mental health
Pediatricians call for ‘reproductive justice’ for young patients
Authors: Knopf Alison
Published: February 2022

Declaring that young people need more autonomy in their reproductive decision‐making, pediatricians are calling for “reproductive justice,” which sets the stage for interactions with adolescents' care providers. This discussion goes way beyond the abortion controversy and focuses on the lack of training most pediatricians have in contraception counseling, according to a viewpoint published last year in JAMA Pediatrics describing how the “reproductive justice” movement fits into pediatrics.
IgE and high‐affinity IgE receptor in chronic inducible urticaria, pathogenic, and management relevance
Authors: Giménez‐Arnau Ana M. , Ribas‐Llauradó Clara , Mohammad‐Porras Nasser , Deza Gustavo , Pujol Ramón M. , Gimeno Ramón
Published: February 2022

Background

IgE and high‐affinity IgE receptor (FcεRI) expression on basophils have been scarcely explored in patients with chronic inducible urticaria (CIndU).

Objectives

To investigate baseline serum IgE and FcεRI expression on blood basophils in a large cohort of CIndU patients and its relationship to treatment response.

Methods

Baseline total serum IgE and basophil FcεRI expression measured by flow cytometry in 165 patients with CIndU was studied. The relationship of both parameters with the response to antihistamine and anti‐IgE (omalizumab) treatment was considered in a subsample of CIndU patients. FcεRI expression in basophils was assessed by mean fluorescence intensity (MFI) and basophil FcεRI standardized density (receptors/cell).

Results

The median FcεRI expression standardized per density in blood basophils was found significantly higher in patients with CIndU compared to HCs. A positive correlation was found between IgE serum levels and basophil FcεRI expression. Basal FcεRI expression was not related to antihistamine treatment response. However, it was related to omalizumab, and patients responding to omalizumab showed higher basal basophil expression of FcεRI levels. Non‐responders to the antihistamine showed significantly higher IgE serum levels.

Conclusions

FcεRI receptor overexpression in patients with CIndU shows almost the same pattern than chronic spontaneous urticaria. It seems to be independent of CIndU subtypes. Although additional studies would be welcome, our work highlights the relevance of FcεRI receptor regulation in CIndU supporting autoimmune basophil and mast cell activation and may be a biomarker for response to anti‐IgE therapy.
A smart access control mechanism based on user preference in online social networks
Authors: Shan Fangfang , Li Fuyang , Ji Peiyu
Published: February 2022

Access control can effectively protect users' data and privacy in social networks. Different access control models address different data privacy requirements, and the corresponding implementation technologies and performance are also quite different. The existing access control mechanisms of social networks rarely take into account the individual preferences of users, and cannot provide personalized services for users. Therefore, we have studied an analysis mechanism of user preference to quantify user preferences, and then use user preference values and some key information of users' social resources as decision vectors, and proposed an access control mechanism based on user preference (ACMBUP). ACMBUP turns the problem of access decision‐making into a problem of classification, that is, whether to allow access or not to allow access. At the same time, we add an encryption and decryption mechanism in ACMBUP to prevent data leakage and protect data when users interact with access mechanisms. Experiments show that this mechanism can automatically generate appropriate access control policies to meet the potential privacy needs of different users, so as to better protect the privacy of social networks data.