bluuebunny/crossref_metadata_2025 huggingface dataset:
Epidemiological profile of early‐onset Alzheimer’s mortality in Brazil from 2010 to 2019
Authors: Toscan Luiza , De Mattos Ana Carolina Squeff
Published: June 2023

Background

Early‐onset Alzheimer disease (EOAD) is not just late‐onset AD (LOAD) at a younger age; there are substantial differences between these 2 categories of AD (Mendez, 2017). Therefore, the first step is to understand its population context. In this way, we sought in this study to determine the socio‐epidemiological aspects of Early‐onset Alzheimer disease (EOAD) mortality in Brazil. This is the first study that analyzes the epidemiology of EOAD in Brazilian territory.

Method

Data from the Ministry of Health’s Mortality Information System (SIM) were analyzed for the epidemiological characterization of deaths from Alzheimer’s (ICD‐10 code G30.0) between 2010 and 2019, considering the variables available on the death certificates. EOAD mortality was considered as death from Alzheimer’s in patients younger than 60 years of age. The sociodemographic variables chosen were sex, race/color, marital status, education and region of the country.

Result

Between 2010 and 2019, SIM recorded 804 cases of EOAD. Of these, 50.62% were male and 49.37% were female. As for race, 63.6% were white, 26.6% brown, 4.97% black, 0.62% yellow, and in 4.10% this information was ignored on the death certificate. It was found that 45% were married, 25% single, 10.9% widowed, 8.2% divorced, 2.2% other and 8.45% were ignored. The level of education was 1 to 3 years in 21.3%, 21% for 4 to 7 years, 15.9% for 8 to 11 years, 7.8% for more than 12 years, 12.4% none and in 21.39% we did not obtain this data. It was also observed 48.8% cases in the Southeast, 21.2% in the South, 20.1% in the Northeast, 6.84% in the Midwest and 2.8% in the North.

Conclusion

The prevalence of early Alzheimer’s mortality was higher in male, white, married patients, from the Southeast region, with 1 to 3 years of schooling. The epidemiological profile is a fundamental part for the elaboration of programs of preventive actions and health promotion. Strengths of this study include the production of information on mortality from early Alzheimer’s disease in Brazil, in a context of lack of research of this type in the country.
The analysis of fMRI complexity as a biomarker of cognitive decline compared to tau‐PET
Authors: Park Gilsoon , Kim Hosung , Jann Kay
Published: June 2023

Background

Tau‐PET detects the neurofibrillary tangle pathology and is considered a biomarker of neuronal injury and cognitive decline. However, PET imaging has radiation exposure risks and is costly. Recently, brain entropy mapping based on rs‐fMRI has emerged as a brain functionality biomarker that indicates the complexity of BOLD signals. Various studies have implied that reduced brain entropy values correlate significantly with cognitive decline in Alzheimer’s disease. This study analyzes the effect of fMRI complexity as a biomarker of cognitive decline in AD compared to tau‐PET.

Method

We obtained the dataset for this study from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). The dataset consisted of 147 subjects (age = 72.5±7.5, M/F = 60/87, CN/MCI/AD = 95/45/7) with a tau‐PET (tracer: 18F‐AV1451) and two fMRI scans. FMRI images underwent standard processing to generate Multi‐Scale Entropy (MSE) maps. We calculated parametric SUVR values based on cerebellar reference regions from tau‐PET images. To determine the ability of MSE and PET images as a risk factor of cognitive decline in AD, convolutional neural networks were used to classify individuals into CN or MCI/AD groups. Each classifier was trained separately with fMRI complexity images or SUVR images. These two models had the same network structures and hyperparameters. We performed a 5‐fold cross‐validation to evaluate each model.

Result

The classifier using fMRI‐MSE achieved an accuracy equivalent to that using tau‐PET (0.7823 vs. 0.7687). We also calculated the Area Under the ROC curve (AUC) to evaluate sensitivity and specificity and observed that the model using fMRI‐MSE achieved AUC of 0.7022, and that using tau‐PET resulted in AUC of 0.6889.

Conclusion

The classification performance showed that use of fMRI‐MSE could potentially be an AD biomarker alternative to tau‐PET. Further studies with multisite, larger datasets are required to validate our preliminary results and provide more conclusive evidence.
A call for utilizing various screening tools in dementia diagnosis: A systematic review
Authors: Dahab Lubaba , Elsayed Sarah , Abdelsamad Alaa Alaa , Sumi Dey , Patel Krupa , Bakhtiarpuri Avinash , Obeid Tamadur , Yousif Samah , Choudhry Varda , Elomeiri Leina , Ibrahim Mohammed B. , Ahmed Samah , Alatta Lina , Ahmed Hilali
Published: June 2023

Background

Dementia is a disorder distinguished by progressive and irreversible global cognitive impairment. About 45 million live with dementia globally, with an estimated increase to 75 million by 2030. Early recognition and diagnosis of dementia could enhance the efficiency of health care and quality of life. Hence, Medicare implemented a covered visit for assessing cognitive function for eligible patients as of January 2021. Previous studies described many tests and screening tools that clinicians can use to diagnose dementia. However, choosing a suitable test is solely left for clinicians to decide. We conducted a systematic review to provide an evidence‐based screening tool guide to facilitate dementia diagnosis.

Method

A systematic review of studies published between 2010 and 2020 in English that targeted older patients. The search included multiple global databases; Cambridge Core, Cochrane Library, Google Scholar, PubMed, and Wiley online library. Keywords: “Dementia” “Screening” “Older people” “General Hospital” and “Inpatient''. Seven independent reviewers checked the studies to avoid bias.

Result

32 articles met the review criteria. More than ten dementia screening tools and tests were identified in the various clinical settings. However, the Mini‐Mental State Examination (MMSE) is the leading test with three times usage compared to other tests, followed by Montreal Cognitive Assessment (MoCA).

Conclusion

The Mini‐Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) are the commonly used tools in diagnosing dementia. The review revealed other tests with a higher potential for early detection of dementia in various clinical settings. Thus, this is a call for clinicians to benefit and diversify the tools in diagnosing dementia and enrich the evidence‐based research with more confirmatory studies.
Large‐scale pQTL analysis of over 3,000 CSF samples
Authors: Western Daniel , Wang Ciyang , Timsina Jigyasha , Wang Lihua , Ruiz Agustin , Marquié Marta , Boada Mercè , de Rojas Itziar , Alvarez Ignacio , Aguilar Miquel , Pastor Pau , Sung Yun Ju , Cruchaga Carlos
Published: June 2023

Background

Expression quantitative trait locus (eQTL) studies have been influential in identifying gene targets for many complex diseases. However, levels of mRNA often correlate poorly with levels of the protein that they encode, due to rates of degradation, translation, or alternative splicing, among other reasons. By correlating protein levels to genetic variation, pQTLs can elucidate a more accurate genetic architecture that underlies disease. While few large‐scale studies have considered cerebrospinal fluid (CSF) protein levels, CSF biomarker levels are one of the primary diagnostic tools in Alzheimer’s disease (AD), highlighting CSF’s relevance to brain aging and AD pathology. Here, we present CSF pQTL analysis of over 3,000 individuals.

Method

We generated CSF levels of 7,584 analytes for 3,065 samples using the aptamer‐based SOMAscan 7k platform. CSF levels of 4,884 analytes for additional 1,158 samples were also included. After stringent quality control, 3,107 unrelated European samples were selected for analysis. We performed pQTL analysis using a linear model with protein levels as the outcome variable, using a three‐stage study design: discovery, replication, and meta‐analysis. We performed colocalization of our pQTLs with eQTLs and GWAS loci, and compared our results to pQTLs from plasma studies to identify CSF‐specific pQTLs. We used Mendelian Randomization (MR) to identify proteins potentially causative for AD and other traits.

Result

This study represents the first use of the SOMAscan 7k platform in CSF, as well as the largest pQTL analysis of CSF to date. Of 3818 analytes currently tested in our discovery set, 1480 have at least one SNP associated with analyte level at p < 5×10−8. Analyses are ongoing.

Conclusion

We previously performed pQTL analysis of CSF using the SOMAscan 1.3k platform, where 425 pQTLs were identified and 3 proteins (PTP1B, Siglec‐3, and SLAF5) were found through MR to be involved in AD risk, as well as 48 additional protein associations for other neurodegenerative diseases. This study expands on those findings by including 6,000 more proteins and much larger samples, allowing for greater power. This study will be vital for identifying novel proteins involved in AD and elucidate novel drug targets for AD and other neurodegenerative disorders.
Transient global amnesia recurrence: prevalence and risk factor meta‐analysis
Authors: Hernández Micaela A , Arena Julieta , Alessandro Lucas , Allegri Ricardo Francisco , Calandri Ismael Luis
Published: June 2023

Background

TGA is an acute amnestic disorder with unclear pathophysiology. Although considered a benign phenomenon, the possibility of a recurrence is a major concern for the patient and their relatives. Our aim is: to identify the prevalence of transient global amnesia (TGA) recurrence and risk factors for it, to help clinicians counsel patients about it.

Method

According to PRISMA guidance, we screened 1658 studies from MEDLINE, Lilacs and Embase databases, published from 1985 to April 2021, in English or Spanish. We included 36 observational case‐control and cohort studies that included patients with TGA according to Caplan’s or Hodges and Warlow’s diagnostic criteria. We performed a meta‐analysis with a random effect model for proportions and calculation of odds ratio for identified risk factors. Methodological quality was assessed according to the Newcastle‐Ottawa Scale.

Result

We identified 4514 TGA and 544 recurrence events (12.73%). Follow‐up had no impact on its variance. We identified a significant association between recurrence and sexual activity as a trigger, personal history of migraine and depression (OR 1,481 95%CI [1,0341; 2,1222] p = 0,04; OR = 2,0795 IC95% [1,3892; 3,1128] p = 0,003; and OR = 4,487195%CI[1,890; 10,651] p = 0,0288, respectively).

Conclusions

The analysis showed that about 1 out of 8 subjects may have recurrence, with an increased risk in case of history of migraine, depression or sexual intercourse prior to the event. Personal history of migraine and depression are associated with two and four times risk, with cortical spreading depression as a possible pathophysiological mechanism.
Graph deep neural network for discovery of multi‐omic subnetworks related to Alzheimer’s Disease
Authors: Raj Yash , Xie Linhui , Varathan Pradeep , Naidu Divya Sagar Vella , He Bing , Nho Kwangsik , Risacher Shannon L. , Saykin Andrew J. , Salama Paul , Yan Jingwen
Published: June 2023

Background

The recent multi‐omics analysis explores the integration of multiple biological data types, which can suggest a more comprehensive view of biological processes underlying complex diseases, such as Alzheimer’s disease (AD). Various biological networks have been leveraged as prior knowledge with attempt to discovery of more interpretable multi‐omics markers [1]. We applied a new graph neural network to take advantage of this rich prior knowledge together with multi‐omics data for identification of system‐level AD markers.

Method

We used GWAS genotype, RNA‐Seq gene expression, and protein expression data from the ROS/MAP Project. In total, 133 subjects with full set of ‐omics features were included in the study (Table. 1). There are 1,751 functionally connected ‐omics features in the prior biological network, including 186 peptides, 743 unique genes, and 822 single‐nucleotide polymorphisms (SNPs). Multi‐omic network of functional connections between SNPs, genes and proteins were created based on the REACTOME database, SNP‐gene mapping relationship and the SNP2TFBS database [2]. This network was applied to guide the architecture design of the neural network. The input layer consists of all ‐omics features. A biological drop‐connect layer of Varmole was set as for transparent layer that duplicate of protein and gene nodes in the input layer [3]. Links between input layer and transparent layer were added based on the prior multi‐omic network. In addition, we also added self‐connection links for all genes and proteins.

Result

Our proposed integrated multi‐omic DNN largely outperforms other state‐of‐the‐art models (Table. 2). With cut‐off at 0.00001, 538 features were identified as discriminative. Three largest connected components were observed with more than 30 nodes (Fig. 1), among which 28 SNPs, 309 genes and 31 proteins form the largest connected component. Top hub nodes are proteins PIK3R1, GRB2, FYN. Shown in Fig. 2 is the list of top REACTOME pathways enriched by genes and proteins in the largest connected component [4].

Conclusion

Integrated multi‐omic DNN identified multi‐mic subnetworks with great predictive power, providing critical functional connections contributing to AD. [1] Xie, et al., BIB, 2021. [2] Fabregat et al., NAR, 2018. [3] Nguyen, et al., Bioinformatics, 2021. [4] Kanehisa, et al., NAR, 2000.
The correction of health misconceptions in older adults with cognitive impairment
Authors: DeCaro Renee , Marin Anna , Schiloski Kylie A , Hajos Gabor P , Turk Katherine W , Domenico Alberto Di , Palumbo Rocco , Budson Andrew E
Published: June 2023

Background

The use of a refutational technique (e.g., “myths” versus “facts”) to correct health‐related misconceptions is ubiquitous, yet little work has addressed whether older adults’ cognitive status influences misconception correction. We examined belief in COVID‐19 misconceptions in older individuals with and without cognitive impairment, and whether a simple refutational technique would be effective at reducing misconception belief in these populations.

Method

Older adults (N = 62, 36 Males) took a pretest of 10 COVID misconceptions (from the CDC) over the telephone. Participants received immediate corrective feedback (i.e., the correct answer and an explanation of the correct answer). Individuals took a surprise retest after 25 minutes and again one week later. Cognitive status was assessed with a telephone‐administered neuropsychological battery and Montreal Cognitive Assessment‐Blind (MoCA‐Blind). Cognitive status groups were compared on misconception belief and corrections. Exploratory analysis correlated corrections with performance on the neuropsychological battery and demographics.

Results

Older adults (M = 75.26 years, SD = 6.61) were split into a cognitively impaired group (N = 28) and an unimpaired group (N = 34) based on recommended cutoffs for the MoCA‐Blind; these groups did not differ in terms of age or education. Impaired older adults endorsed more misconceptions on the pretest than unimpaired older adults, t(60) = 3.61, p < .001, d = .92. Importantly, both groups made equivalent corrections from the pretest to the first retest (p = .439, d = .21) and maintained those corrections across the one week delay (p = .907, d = .03). Only memory errors on the recognition portion of the neuropsychological battery were associated with performance gains (r = ‐ .33, p < .01). Individuals who made more false alarms (i.e., incorrectly recognizing a word as having been presented) were less likely to correct misconceptions.

Conclusion

A refutational technique can be effectively used to correct health‐related misconceptions in even older adults who are cognitively impaired. Moreover, this easily‐implementable technique was effective for older adults of all ages and education levels. Rather, recognition memory errors alone were important in the correction of misconceptions.
Deformation‐based morphometry analysis shows early degeneration in Nucleus basalis of Meynert in Alzheimer’s disease
Authors: Shafiee Neda , Fonov Vladimir S , Dadar Mahsa , Spreng R. Nathan , Collins D Louis
Published: June 2023

Background

Nucleus basalis of Meynert (NbM) is the main source of cholinergic projection to the cerebral cortex, including entorhinal cortex (EC). Both cholinergic cells of NbM and their receptive targets in EC show degeneration during early stages of Alzheimer’s disease (AD). While precise delineation of NbM region on T1w scans is difficult due to limited spatial resolution and contrast, we sought to quantify the degeneration of NbM along the disease trajectory and confirm recent studies suggesting that NbM degeneration happens before degeneration in the EC using deformation‐based morphometry (DBM).

Method

Data included MRI scans of 1473 subjects from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) dataset. Resolution was increased to 0.5 mm isotropic voxel‐size before non‐linear registration to an ADNI‐based unbiased symmetric template. The resulting deformation fields were used to compute the Jacobian determinant map for each subject as a proxy for local volume. NbM and EC masks were mapped to our high‐resolution template and mean determinant values inside these masks were calculated for groups with different baseline diagnosis, and sex‐ and age‐corrected z‐scores were calculated. Two‐sample t‐tests were then used to compare the scores between different groups.

Result

Figure 1 shows the mean DBM score of both NbM and EC regions for Normal Controls (CN), subjects with early‐ and late‐stage mild cognitive impairment (EMCI and LMCI) and subjects with probable AD dementia. Results corrected for multiple comparisons showed a significant difference between CN and both EMCI and LMCI for left and right NbM. A significant difference was also observed between EMCI and LMCI in left NbM (p‐value = 0.0024). Z‐scored EC volumes did not show a significant difference between CN and EMCI groups; However, results from EMCI and LMCI differ significantly in both hemispheres. We also observed the expected differences between each group with AD in both NbM and EC (P<0.001).

Conclusion

Our results show that while macroscopic changes in EC emerge as MCI subjects advance toward the later stages, NbM degeneration starts sooner, as early as preliminary stages of MCI. This points to MRI‐based measurements of NbM as potential biomarkers for early detection of AD and as a marker of disease burden.
Subjective cognitive decline and unmet care needs highest among transgender women: A comparison of subjective cognitive decline and related limitations among transgender communities in the U.S.
Authors: Cicero Ethan C. , Goodman Michael , Barnes Lisa L. , Tangpricha Vin , Flatt Jason D.
Published: June 2023

Background

The transgender population is composed of subgroups that are diverse in gender identity (e.g., transgender women [TW], transgender men [TM], nonbinary [NB] individuals). Research investigating Alzheimer’s disease and related dementias (ADRD) among transgender adults is limited and no study has delineated the factors associated with the brain health of TW, TM, or NB adults. Compared to their cisgender peers, transgender adults are more likely to report subjective cognitive decline (SCD), which may be one of the first clinical manifestations of ADRD. It remains unclear if SCD prevalence and related limitations vary by transgender subgroups.

Method

2015‐2020 Behavioral Risk Factor Surveillance System data, representing 39 U.S. states that assessed SCD (confusion/memory loss happening more often/getting work over previous 12 months) and self‐reported gender identity were used to examine differences in SCD prevalence and SCD‐related limitations (activities of daily/independent living) by transgender subgroups, TW (n = 442), TM (n = 298), and NB (n = 183). Age‐adjusted odds ratios (OR) along with 95% confidence intervals (CI) were calculated to investigate group differences in prevalence of SCD. Separate analyses compared SCD‐associated limitations, demographics, and health characteristics across study groups among participants reporting SCD.

Result

SCD prevalence was highest among NB (21.3%), followed by TW (16.3%) and TM (14.1%). After accounting for age, subgroup differences remained; the odds of SCD were 1.6 times higher among TW compared to TM (95% CI: 1.1‐2.4, p = 0.012). Among those with SCD, TW were less likely to receive help they needed with day‐to‐day activities when compared to TM (OR = 7.9; 95% CI: 0.1–0.2, p<0.001) and NB (OR = 5.0; 95% CI: 0.1–0.4, p = 0.001); and TW were more likely to be deaf (OR = 4.2; 95% CI: 1.7‐10.1, p = 0.002) and have asthma (OR = 2.8; 95% CI: 1.4‐5.7, p = 0.005) when compared to NB adults. No other SCD‐related limitation, demographic, or health differences were found.

Conclusion

Health and social inequities are not uniformly experienced across transgender subgroups, and it is important to understand how these factors uniquely impact the brain health of TW, TM, and NB adults. There is an urgent need for ADRD and cognitive aging studies in this population.
Increased apparent blood flow and volume of the choroid plexus in the Alzheimer’s Disease patients
Authors: Lu Peilin , Li Jiaxin , Zhao Li
Published: June 2023

Background

Recent works suggested the association between the dysfunctional glymphatic system and Alzheimer's Disease, which shows as alternated cerebrospinal fluid production. It is believed that the choroid plexus is the major site of CSF production conventionally and the choroid plexus blood flow is related to the production rate directly. Therefore, we investigated the choroid plexus perfusion in AD patients using arterial spin labeling (ASL) and MRI retrospectively.

Method

21 AD patients (15 males, 76.1±5.7 years), 36 MCI patients (20 males, 72.6±7.9 years), and 88 healthy controls (40 males, 74.8±8.0 years) from the ADNI3 were included in this study. The lateral choroid plexus regions were segmented automatically based on a 3D U‐net deep learning method, which has been demonstrated with higher accuracy compared to the Freesurfer. In addition, the gray matter mask was segmented from the T1 weighted images using SPM12, and it was used to transfer the ASL and M0 images to the T1 weighted image space. Relative cerebral blood flow was quantified by first dividing the ASL image with its smoothed M0 image (a Gaussian filter with the sigma of 4 pixels), and then normalizing the mean signal of the choroid plexus region with the mean of the gray matter region. The gray matter mask was chosen as the region with a probability higher than 0.5.

Result

In the nonparametric Mann‐Whitney U test, the choroid plexus volume of the AD patients (1.58±0.40ml) was significantly larger (p = 0.036) than that of the healthy controls (1.41±0.39). In addition, the AD patients (0.85±0.30) showed significantly higher (p = 0.017) relative perfusion of the choroid plexus regions than the healthy controls (0.70±0.20).

Conclusion

The enlarged volume and increased blood flow of the choroid plexus may suggest the over‐compensation of CSF production in AD patients. However, further investigation is required to separate the blood flow and CSF signal in ASL at the choroid plexus region.
Remote cognitive evaluation in aging adults: A new software implementation during COVID‐19
Authors: Johnson David K , Adesida Praise , Montenegro Esteban , Woods David
Published: June 2023

Background

Remote cognitive testing is a convenient and efficient method to evaluate older adults especially because of the sanitary restrictions due to COVID 19. Our aim was to test the psychometric properties of newly developed versions of two visuospatial attention subtests, Hidden Patterns and Identical Pictures, administered by remote cognitive evaluation platform developed by Neurobehavioral Systems, Inc. We conducted testing and analysis in a sample of healthy aging adults.

Methods

Participants were recruited in East‐Bay, California; 184 aging adults completed the computerized hidden patterns test, and 160 older adults answered the identical picture test. The mean age was 70.11 years old with a range of 60 to 85 years old. Most of the participants were female (59.60%), and dementia symptoms were not reported. Participants were evaluated twice in one year at home, the software created by Neurobehavioral Systems, Inc allowed a synchronous interaction with the remote evaluator, which helped to monitor and answer any question before, during or after the evaluation.

Result

Difficulty and discrimination analysis (classical test theory) was performed in R (version 4.1.0),. We estimated a Bayesian 1PL Item Response Model (IRT) for each test along with DIF testing by gender. The IRT models were calculated with the package rstan (Stan Development Team, 2020)

Conclusion

The IRT models showed group differences at the items’ difficulty. The estimated reliability showed to be adequate (α > .75), and test – retest correlations were medium to high (r > .50). Correlations with age ranged from r = ‐.33 to r = .25.
Genetic architecture of plasma Alzheimer’s disease biomarkers
Authors: Bradley Joseph , Gorijala Priyanka , Schindler Suzanne E. , Sung Yun Ju , Mafimoghaddam Samira , Wang Fengxian , Cruchaga Carlos
Published: June 2023

Background

Case‐control genome‐wide association studies (GWAS) have identified loci associated with risk for Alzheimer disease (AD), but they require very large sample sizes and identify variants with small effect sizes. GWAS of informative endophenotypes for disease have more power to identify novel variants and provide information about biological mechanisms. By analyzing data from 1,269 individuals, we previously identified risk variants for AD that were associated with CSF levels of tau and p‐tau, including a novel variant associated with AD risk. Recent technological developments have led to new assays in plasma for Aβ, p‐tau and NFL with high predictive power. However, no GWAS have been performed using these plasma biomarkers as quantitative trait.

Method

Plasma Aβ and NFL were obtained from 882 individuals from the Knight‐ADRC, plasma Aß from 160 individuals from the Human Connectome Project, and plasma Aß, NFL, tau and p‐tau from 1,694 individuals from ADNI. GWAS and sequencing data is also available from these samples. We performed linear regression to determine single nucleotide polymorphisms (SNPs) associated with these plasma AD biomarkers. SKAT‐O was used to perform gene‐based analyses including rare non‐synonymous variants. GCTA and LDSC was used to determine the proportion of biomarker variability explained by genetic variants. We used colocalization to determine if the loci associated with plasma biomarker levels are also associated with AD risk, onset or progression. Mendelian randomization and LDSC was used to determine the overlap in the genetic architecture of plasma AD biomarkers with other traits, including cardiovascular and inflammation‐related traits.

Result

This represents the largest GWAS for plasma AD biomarkers measured with the novel and more powerful assays. We found several genome‐wide significant hits, including APOE. Additional analyses are ongoing.

Conclusion

Previous studies using CSF biomarker levels as quantitative traits identified novel genes implicated in AD risk, onset and progression. This current study using plasma biomarker levels as quantitative traits can be critical to identification of novel genes that impact AD and more accurate interpretation of plasma biomarker levels.
Direct‐care workforce training in best care practices for persons with Alzheimer’s disease or related dementias utilizing long‐term services and supports
Authors: Dassel Kara B , Savage Kirstie , Telonidis Jacqueline , Edelman Linda S.
Published: June 2023

Background

Approximately 34,000 adults over the age of 65 were diagnosed with Alzheimer’s disease (AD) in Utah in 2020; by 2025, this number is expected to increase 23.5%, to 42,000 (Alzheimer’s Association, 2021). As a result, the use of long‐term services and supports (LTSS) is increasing and the capacity and competencies of the workforce, families, and caregivers will need to be expanded to provide value‐based, person‐centered care (Poo & Kalipeni, 2017). The LTSS workforce is unstable due to a myriad of issues including workforce shortages and inadequate training and education, particularly in the area of dementia care (Stone, 2017).

Method

To fill this gap, an interdisciplinary team developed an online training program to increase knowledge about AD best care practices. The three hour asynchronous training program has four modules: 1) Dementia: Causes, Symptoms, and Trajectory, 2) Treatment Options for Challenging Behaviors; 3) Effective Interprofessional Care Teams, and 4) Dementia‐Focused Communication Techniques. Segments of a video case study of “Mrs. Jones”, demonstrating the skills and techniques taught in each module are interwoven. Pre‐ and post‐evaluation include demographics, Alzheimer’s Disease Knowledge Scale (ADKS) (Carpenter et al., 2009) and training satisfaction.

Result

Thus far, 526 participants have completed the entire training and post‐evaluation survey. Data demonstrate that the modules are used by a variety of professionals: Certified Nursing Assistants (18.15%), Nurses (40.26%), family caregivers (2.27%), Social Workers (1.70%), and “other” (52.74%; e.g., students, administrators). Completers “Strongly agreed” or “agreed” that the training met educational needs (89.98%), was engaging (77.69%), will improve care (89.60%), provided useful examples (89.98%), and met the stated goals (91.87%). There was a significant (t = 11.818; p<0.001) increase in ADKS scores between pre‐evaluation (mean = 12.96; S.D. = 1.71) and post‐training evaluation (mean = 13.85; S.D. = 1.41).

Conclusion

Evaluation results demonstrate that the online ADRD best practice in LTSS training provides useful information, improves participant’s knowledge about AD, and is well‐received by participants. Additional research is needed to evaluate the impact of AD training on resident/client outcomes in LTSS. To increase direct workforce participation in free trainings, employers should consider incentivizing staff to complete additional AD‐specific trainings.
SING, SING IAB PROJECT ‐ Family caregivers online support group of Instituto Alzheimer Brasil
Authors: Novais Ticyana Moralez da Silva , Piovezan Elizabeth S , Piovezan Mauro Roberto , Silva e Moreira Raissa Carla Paulino , Stein Angelica Miki , de Santana Beatriz Raz Franco
Published: June 2023

The Instituto Alzheimer Brasil (IAB) is a non‐governmental organization that promotes information about Alzheimer’s disease to the community, offering support for people with dementia, caregivers, and familiars. During the covid pandemic, it was implemented an online support group via messaging app using music as an instrument for relaxation and exchange of positive experiences among family caregivers. The present study aimed to describe the SING SING IAB PROJECT and its benefits to participants.

The group was created in November 2020 and the invitation was made to family caregivers who participated in our monthly online support meetings. To participate in the group, the family caregiver must rehearse a song that has some relation to their personal history, or that of their family member with Alzheimer’s, record a personal video and post it in the group (messaging application) for other participants to enjoy. These videos can be only of the caregiver, the family, or with the family member who has Alzheimer’s disease and can be recorded only with singing, accompanied by musical instruments, or karaoke. The rule to remain in the group is the confidentiality of the images, which are restricted to the group only, and the posting only of videos with musical recordings or positive comments to the videos posted. So far, we have had the participation of 62 caregivers and family members with Alzheimer’s Disease. The project has continued since November 2020, so far we have had the participation of 62 caregivers and family members with AD. 357 videos were published up to January 2022. We are collecting reports of the benefits of the group of caregivers and patients with AD. The objective was to use music as a therapeutic intervention in mental health and improve the quality of life of caregivers and family members with AD.

Participants' reports refer to several benefits such as not feeling alone in caring, a welcoming and friendly environment amid so many difficulties, beneficially interfering with the quality of life of the caregiver and their family members with AD.
Incidence of cognitive, depressive and anxiety disorders in COVID‐19 patients
Authors: Kovalenko Ekaterina Аndreevna , Makhnovich Ekaterina Vladimirovna , Bogolepova Anna Nicolaevna , Alekseevna Osinovskaya Nina
Published: June 2023

Background

The COVID‐19 pandemic has become a serious global problem that has affected almost all aspects of modern society, especially public health. Among the significant health problems one can single out ‐ an increase in the number of people with cognitive, depressive and anxiety disorders in COVID‐19 patients. These disoders may be due to the severity of the patient’s condition during the period of COVID‐19 disease, the presence of significant events after suffering COVID‐19 or premorbid cognitive (vascular pathology or Alzheimer’s disease) and emotional status.

Method

We examined 60 patients after COVID‐19, 33 (55%) were men, at 7.34 ± 0.14 months follow‐up after hospital treatment. Mean age ‐ 59.93±1.32. Participants were completed the Montreal Cognitive Assessment (MoCA) and The Frontal Assessment Battery (FAB). Depression and anxiety were identified using the Hospital Anxiety and Depression Scale (HADS).

Result

According to the measured MoCA, 30 (50%) of the examined patients had mild cognitive impairments, no severe cognitive impairments were detected. According to the FAB scale, 25 (41.7%) patients had moderate frontal dysfunction, no severe frontal dysfunction were detected. According to the HADS scale: anxiety was detected in 10 (16.6%) patients; depression — in 3 (5%) patients. The study found evidence that cognitive impairment was more common in patients with a low level of education, atherosclerosis of the brachiocephalic arteries, and chronic heart failure (p<0.05). Cognitive impairment and anxiety disorders were significantly more frequently recorded in older patients (p<0.05).

Conclusion

COVID‐19 survivors showed a considerable prevalence of cognitive impairment. Considering the alarming impact of COVID‐19 infection on mental health, we recommend to assess cognitive and emotional status of COVID‐19 survivors for early diagnosis and treatment of cognitive and emotional disorders.
Myelin‐weighted MR Imaging in Patients with Alzheimer’s Disease
Authors: Lim Seung‐Hyun , Lee Jiyoon , Jung Sumin , Rhee Hak Young , Park Soonchan , Cho Ah Rang , Ryu Chang‐Woo , Jahng Geon‐Ho
Published: June 2023

Background

Developing an imaging technique to map myelin changes in the brain within a short scan time is needed due to the inability of Alzheimer’s disease (AD) patients to remain motionless during MRI scanning.

Purpose

To investigate myelin loss in both AD and mild cognitive impairment (MCI) patients with a new myelin water mapping technique within reasonable scan time and evaluate the clinical relevance of the apparent myelin water fraction (MWF) values by assessing the relationship between decreases in myelin water and the degree of memory decline or aging.

Method

In this prospective study from March 2019 to October 2021, the participants were allocated as follows: 29 individuals were assigned to the cognitively normal (CN) elderly group (mean ± SD, 73 ± 5 years, 16 females), 32 participants were assigned to the MCI group (74 ± 5 years, 21 females), and 31 patients were assigned to the AD group (74 ± 6 years, 26 females). A 3D visualization of the short transverse relaxation time component (ViSTa)‐gradient and spin‐echo (GraSE) sequence was developed to map apparent MWF. Then, the MWF values were compared between the three participant groups, and was evaluated the relationship with the degree of memory loss.

Result

A total of 92 participants were evaluated. The AD group showed a reduced apparent MWF compared to the CN and MCI groups. Moreover, the MWF was decreased with age and positively correlated with Mini‐Mental State Examination scores. The largest AUC value (0.799) was in the corpus callosum and used to classify the CN and AD groups using the apparent MWF.

Conclusion

The ViSTa‐GraSE sequence can be a useful tool to map the MWF in a reasonable scan time. Combining the MWF in the corpus callosum with the detection of atrophy in the hippocampus can be valuable for group classification.

Funding

The research was supported by the National Research Foundation of Korea (NRF) grant funded by Ministry of Science and ICT (No. 2020R1A2C1004749, GHJ), Republic of Korea.
Establishment of Cerebral Organoid‐like Structures from Dental Pulp Stem Cells (DPSCs) to Model Neurodegenerative Diseases.
Authors: Gutierrez‐Malacara Andres‐Ivan , Silva‐Lucero Maria del Carmen , Lopez‐Toledo Gustavo , Gomez‐Virgilio Laura , Cardenas‐Aguayo Maria del Carmen
Published: June 2023

Background

3D‐cell cultures are closer to in vivo conditions than the monolayers. There are different 3D‐cell culture models, the most relevant is the Cerebral Organoids (CO) model (Lancaster et al. 2014), it can show complex processes and proved to show molecular and structural changes when modeling Alzheimer´s disease (AD), and other diseases. One of the main limitations of using this model is the requirement for Induced Pluripotent Stem Cells (iPSC) or Human Embryonic Stem Cells (hESC) for the CO generation; because iPSC could undergo epigenetic changes during the process of reprogramming; moreover, hESC are controversial because of their ethical implications. We proposed to use DPSCs instead of iPSC or hESC to generate organoid‐like structures due to their capability to differentiate into the neuronal lineage, lack of pluripotency, and its easy access.

Method

The DPSCs were obtained by dissociating the dental pulp of a healthy 46 years old female with a colagenase‐dispase mix at 37°C, isolated and cultured. The cells phenotype was characterized by Western‐Blot, RT‐PCR and immunofluorescence. We cultured the DPSC into low‐adherence wells for 6 days in a DMEM/F12 medium + thiazovivin 50 mM, bFGF 4ng/mL, BFS 20%, Glutamax® 200x, MEM‐NEAA 1:100, 2‐mercaptoethanol 100 µm and murine LIF 10 µg/mL until cell aggregation into embryoid‐like structures. After that, neural induction was carried out.

Result

We successfully characterized DPSC phenotype by detecting pluripotential markers OCT4, Actin, NanoG, mesenchymal markers CD105, CD73, and the neuronal marker β‐III Tubulin which is always present in the DPSCs lineage, as well as the lack of hematopoietic markers CD14, CD34, and CD45. We obtained Cerebral Organoids‐like structures from de DPSCs after 35 days of the differentiation protocol and detected NeuN, MAP2, β‐III Tubulin, and tau, all neural markers that claim a neuronal phenotype.

Conclusion

Our results suggest a potential use of this approach to the CO generation using DPSCs instead of iPSC or hESC with the benefits of a shorter time and a less expensive protocol likewise, DPSCs could resemble the molecular aging changes. Further studies are needed to validate the use of this CO to model neurodegenerative diseases such as AD.
Microvascular Morphology MR Imaging Using Relaxation Rate Change with Gadolinium‐Based Contrast Agent in Patients with Alzheimer’s Disease
Authors: Guo Xiao‐Yi , Kwon HyeokJung , Rhee Hak Young , Park Soonchan , Cho Ah Rang , Ryu Chang‐Woo , Jahng Geon‐Ho
Published: June 2023

Background

Conventional MRI techniques cannot demonstrate microvascular alterations in mild and moderate Alzheimer’s disease (AD). Thus, the diagnosis of microvascular pathology commonly relies on postmortem. The purpose of this study was to evaluate alterations of microvascular structures in patients with AD using a 3T clinical MRI system with a commercially available contrast agent.

Method

Eleven patients with AD and 11 non‐AD controls were included in this cross‐sectional prospective study. R2 and R2* relaxation rate changes (∆R2 and ∆R2*) before and after a Gd‐based contrast agent injection were calculated from images obtained with a multi‐echo turbo spin‐echo sequence and multi‐echo gradient‐echo sequence to obtain microvascular index maps of blood volume fraction (BVf), mean vessel diameter (mVD), vessel size index (VSI), mean vessel density (Q), and microvessel‐weighted imaging (MvWI). Two‐sample t‐test was used to compare those values between the two groups. Correlation analysis was performed to evaluate the relationship between those values and the mini‐mental state examination (MMSE) score.

Result

Compared with the non‐AD group, BVf was significantly increased in the AD group at the parahippocampal gyrus (p = 0.033), gray matter area (p = 0.008), and white matter area (p = 0.010). MvWI was also significantly increased in the AD group at the hippocampus (p = 0.010), parahippocampal gyrus (p = 0.010), precuneus (p = 0.045), and globus pallidus (p = 0.008). Both mVD and VSI were only significantly decreased in the AD group at the white matter hyperintensity (WMHI) area (p = 0.045 with mVD; p = 0.033 with VSI). BVf and MvWI were significantly positively correlated with age at some areas. VSI was significantly positively correlated with MMSE at caudate (rho = 0.475/ p = 0.030) and corpus callosum (rho = 0.435/ p = 0.049).

Conclusion

Microvascular index was a useful non‐invasive method to evaluate microvascular morphology alteration. The microvascular morphology of AD was manifested as vessel constriction and increasing blood volume fraction. It was associated with MMSE score.
Centiloid harmonisation across PET cameras without using paired scan
Authors: Li Shenpeng , Bourgeat Pierrick , Lebrat Leo , O'Keefe Graeme , Fripp Jurgen , Villemagne Victor L , Rowe Christopher C. , Dore Vincent
Published: June 2023

Background

The Centiloid (CL) scale allows quantification of amyloid‐b accumulation across multiple PET tracers for the diagnosis of Alzheimer’s disease. The CL quantification on different PET cameras may result in significant quantification bias when merging cohorts acquired from multiple cameras or in the longitudinal studies when change of camera occurs. In this study, we propose a harmonisation method, based on the non‐negative matrix factorisation (NMF), to reduce the quantification bias between different cameras without using paired scans.

Method

Three hundred and forty‐eight 18F‐NAV4694 scans from Australian Imaging Biomarkers and Lifestyle study acquired on three PET cameras (N = 116 each), Siemens Biograph mCT, Philips Allegro and Philips Gemini TF64 were used to train the model. Participants who switched camera between two consecutive timepoints were selected as the validation data. Seventeen participants imaged on the Biograph mCT and Gemini (2.63±0.51 years scan interval), and fifty‐two participants imaged on the Gemini and Allegro (2.73±0.73 years). One hundred participants who have two scans (2.26±0.82 years) on Gemini were used to define a reference rate of change (CL/year). Figure 1 illustrates the harmonisation workflow.

Result

Figure 2 compares the curves of CL change rate against baseline CL for mCT to Gemini compared to the reference. The harmonised fitting is closer to the reference than the one without harmonisation in the low to middle CL range. The fitting in high CL range (CL>80) deviates from the reference probably because of the lack of subjects in this range. Figure 3 compares the results between Phillips Allegro and Gemini TF 64. The harmonised fitting in Figure 3 is nearly parallel to the reference for the entire CL range. In contrast, the fitting on the unharmonized data shows negative rate of change for the very negative subjects and much higher CL change rate for the very positive subjects, which are strongly different compared to the reference.

Conclusion

We propose a practical and economical CL harmonisation for different PET cameras without using paired data. The NMF based method shows promising results for scanner harmonisation, though more validation are needed in future for different PET models.
Relationship between blood pressure and cognitive decline in normal cognitive population: A four‐year follow‐up study in rural Xi'an
Authors: Wang Jin
Published: June 2023

Background

Hypertension is a modifiable risk factor for cognitive impairment, although the relationship between hypertension and cognitive impairment is not fully understood. The objective of to clarify the relationship between blood pressure and cognitive decline in cognitive normal population through a longitudinal follow‐up study.

Method

Cognitively normal population was selected from people who lived in the suburbs of Xi’an, China.The mini‐mental state examination (MMSE) and neuropsychological battery were used to assess cognition. Four years later, MMSE was tested again and cognitive decline was defined as a decrease in MMSE scores ≥2 points.The relationship between blood pressure parameters [systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial blood pressure (MABP),] and cognitive impairment was analyzed by logistic regression models using interaction and stratified analysis. Blood pressure and age were regarded as both continuous and categorical data。

Result

A total of 1024 participants completed the study, among whom 168 subjects (16.41%) presented cognitive decline.Interaction analysis for the total population showed that SBP (when regarded as continuous data) was positively correlated with cognitive impairment (OR = 1.173 [95% CI,1.030‐1.335] per 10mmHg, P = 0.016); however, the age by SBP interaction term was inclined to be negatively correlated with cognitive impairment (OR = 0.850 [95% CI, 0.711–1.016] per10mmHg×year, P = 0.074), indicating that the relationship between SBP and cognitive impairment was age‐dependent. When the blood pressure and age were considered as binary data, the results were similar to those obtained when they were considered as continuous variables.Stratified multivariate analysis revealed that the relationship between SBP (when regarded as continuous data) and cognitive impairment was positive for patients aged 50‐59 years (OR = 1.209 [95% CI:1.025–1.427] per 10mmHg, P = 0.024).However, positive results were not obtained for DBP and MABP.

Conclusion

Elevated blood pressure is positively correlated with cognitive impairment in the middle age(50‐59), but this positive association declines with increasing age.