bluuebunny/crossref_metadata_2025 huggingface dataset:
Posttraumatic Stress Disorder and Risk For Dementia
Authors: Neylan Thomas C.
Published: December 2022

Background

Accumulating evidence demonstrates that PTSD is associated with higher risk for neurodegenerative disorders. However, the mechanism which drives this relationship and the question of whether the increased risk pertains to the full spectrum of all neurodegenerative disorders is not known. Given that neurodegeneration, as with most illnesses, is caused by complex gene by environment factors, PTSD may be an important disorder to study given that trauma exposure is a large impact environmental exposure.

Method

This presentation will start with a brief review of prospective epidemiologic studies that examine the potential bidirectional relationship between PTSD and dementia disorders. Next, data from the Department of Defense Alzheimer’s Disease Neuroimaging Initiative (DoD ADNI) on amyloid and tau PET imaging in older Vietnam veterans will be presented.

Result

Data from multiple prospective studies show that having a diagnosis of PTSD is associated with higher risk of subsequent dementia. Further, evidence suggests that PTSD is associated with elevated risk for all types of neurodegenerative disorders including Parkinson’s Disease, though there may be a stronger link to Frontotemporal and Vascular Dementias. Results from a sample 289 non‐demented veterans with PTSD and/or TBI and controls in the DoD ADNI cohort did not show evidence of higher cortical amyloid or tau burden. PTSD was associated with higher prevalence of mild cognitive impairment but in the absence of elevated biomarkers of Alzheimer’s Disease.

Conclusion

There are many important questions that need to be resolved to understand what mechanistic pathways for neurodegeneration are facilitated by PTSD. If results from the DoD ADNI study generalize, then future work should focus on whether PTSD increases risk for non‐AD tauopathies or synucleinopathies. Further, the strong association of PTSD with chronic sleep disturbance and elevated pro‐inflammatory cytokines also suggest that need to focus on these candidate mechanisms for accounting for the link between traumatic stress exposure and the development of neurodegenerative disorders.
Sex differences in dementia risk and gray matter volume associated with hearing impairment
Authors: Fitzhugh Megan C , Pa Judy
Published: December 2022

Background

Hearing impairment is highly prevalent in older adults and was recently recognized as a modifiable risk factor for dementia. However, it is unknown if risk differs by sex and whether other issues associated with hearing, like social engagement or depression, impact these associations.

Method

UK Biobank data was used to identify 165,471 participants (57±8 years, 55% female) without dementia who had a hearing assessment at baseline. Hearing was assessed using a speech reception threshold task, with scores grouped into good, insufficient, and poor severity levels based on previously derived cut‐offs (Dawes et al., 2014). Cox proportional‐hazard models were used to investigate sex differences in the association between hearing impairment and dementia risk. Sensitivity analyses were conducted to determine if social engagement or depressive symptoms mediated these associations. In a subset of participants with MRI data (n=2,322, 62±7 years, 52% female), linear mixed models stratified by sex were conducted to examine if development of impaired hearing from baseline was associated with gray matter atrophy in auditory and limbic regions.

Result

Insufficient and poor hearing were associated with increased risk for dementia compared to good hearing (HR=1.76, 95%CI 1.43‐2.18 and HR=2.13, 95%CI 1.46‐3.11, respectively), but differed by sex. Women with insufficient (HR=1.73, 95% CI 1.25‐2.40) and poor (HR=3.08, 95%CI 1.80‐5.28) hearing had the greatest risk of dementia, whereas only men with insufficient hearing had increased risk (HR=1.78, 95%CI 1.34‐2.35; poor HR=1.60 95%CI 0.94‐2.73). These relationships were not mediated by social engagement or depression. In the MRI subset, women who developed or maintained impaired hearing had greater atrophy over 2.29 years in auditory pathway (e.g., primary auditory cortex, thalamus) and limbic (e.g., hippocampus, parahippocampus, amygdala) regions compared to women with good hearing. Men who developed impairment exhibited decreases over 2.30 years in a secondary auditory region only.

Conclusion

Women with impaired hearing have greater risk of dementia compared to men. These sex differences are not mediated by social engagement or depression. Women with impaired hearing exhibit greater atrophy in auditory and limbic regions, while men do not. Sex differences in gray matter atrophy may explain why women with impaired hearing are at greater risk of dementia.
Tracing the metabolic rewiring of glycolytically compromised neurons
Authors: Sei Yoshitaka J , Bennet Neal , Yang Joyce , Li Huihui , Nakamura Ken
Published: December 2022

Background

While a reduction in cerebral glucose uptake is a diagnostic trait of Alzheimer’s Disease, the neuronal requirement for the uptake and metabolism of glucose is not well understood. To dissect how neurons metabolize glucose, we tracked [U‐13C]glucose metabolism in human iPSC‐derived neurons.

Method

Human WTC‐11 iPSCs expressing the CRISPR inhibition machinery dCas9‐KRAB were differentiated into neurons using a doxycycline‐inducible NGN2. After a 2 week maturation period, neurons were incubated with [U‐13C]glucose at either a physiologically relevant 1.5 mM or a glucose‐scarce 0.15 mM concentration for 24 hours prior to metabolite extraction. To determine the importance of glucose uptake to neurons, a guide for the neuronal glucose transporter GLUT3 was added to the CRISPR machinery to limit the neuronal uptake of glucose (GLUT3 KD). These GLUT3 KD neurons were compared to neurons with uninhibited glucose uptake (non‐target). Student t‐tests or two‐way ANOVAs with Bonferonni correction were used to compare metabolite levels between neuronal groups and the concentration of extracellular [U‐13C]glucose.

Result

Under physiologically relevant glucose conditions, GLUT3 KD neurons had decreased levels of labeled glucose. Despite the difference in internalized glucose, GLUT3 KD did not affect the amount of [U‐13C]glucose‐derived citrate that feeds the TCA cycle. The labeled level of a critical pentose phosphate pathway (PPP) metabolite, R5P, was decreased in GLUT3 KD neurons. When measuring the total levels, both labeled and unlabeled, of R5P and citrate, we found there to be no significant effect of GLUT3 KD. This trend was also observed in a 0.15 mM [U‐13C]glucose condition. With the change in R5P levels exclusively in the amount derived from [U‐13C]glucose, we found that neurons prioritize the usage of glucose to feed the TCA cycle over the PPP.

Conclusion

Neurons rewire their metabolism in response to glucose shortages, demonstrating their sensitivity to and reliance on the availability of glucose. During limited access to glucose, glucose utilization was pulled away from the PPP and shunted to the TCA cycle. In the context of AD, the connection between glucose shortages in neurons and their bioenergetic dysfunction is a critical point of discussion centered on understanding the mechanistic initiation of neurodegeneration.
Overlap of genetic risk for Lewy body and Alzheimer’s disease pathology
Authors: Talyansky Seth D. , Guen Yann Le , Pham Kaitlyn , Belloy Michael E , Kasireddy Nandita , Greicius Michael D
Published: December 2022

Background

Lewy body (LB) pathology is relatively understudied compared to Alzheimer’s disease (AD) pathology, and the genetic risk overlap between the two remains unclear. Chia et al. (2021) identified five genomic loci significantly associated with LB pathology in a genome‐wide association study (GWAS) of LB dementia cases and controls (N = 6,618), where 69% of cases and 15% of controls were pathologically confirmed. Here we gathered a largely distinct set of individuals (5.1% overlap) with genetic data and postmortem assessment for both AD and LB pathology (N = 6,002) to estimate the odds ratio (OR) for risk of sole AD pathology (AD+LB−), sole LB pathology (AD−LB+), and dual AD‐LB pathology (AD+LB+) for the five variants reported by Chia et al. We compared our results for APOE to ORs reported by Tsuang et al. (2013).

Method

Our initial study population comprised 4,579 subjects from the National Alzheimer’s Coordinating Center and 1,423 from the Rush University Medical Center assessed for AD and LB pathology. We separately used criteria from Tsuang et al. and from Kaivola et al. (2021) to classify subjects as AD+LB+, AD+LB−, AD−LB+, or AD−LB−. We performed a GWAS for three phenotypic contrasts: each of AD+LB−, AD−LB+, and AD+LB+ against AD−LB−. We estimated ORs for the variants of interest.

Result

We found that rs769449 (APOE locus) was associated with AD+LB+ and AD+LB− at the genome‐wide significance level and nominally associated with AD−LB+, though with OR estimates lower than those reported by Tsuang et al. We obtained qualitatively similar results for rs6733839 (BIN1). The lead variants reported at the GBA, TMEM175, and SNCA‐AS1 loci (or proxies in high linkage disequilibrium) were not associated with a pathological phenotype, although an independent intronic variant of GBA was nominally associated with AD+LB+ and AD−LB+.

Conclusion

Our results suggest that APOE and BIN1 are associated with both AD and LB pathology, while GBA is associated with LB but not AD pathology. The ORs reported by Tsuang et al. for APOE‐associated risk for single and dual AD‐LB pathology may overestimate the true population values. Overall, AD and LB pathology share APOE and BIN1 as risk factors.
Weights analysis for CNN models in MRI classification
Authors: Khagi Bijen , Kwon Goo‐Rak
Published: December 2022

Background

In deep neural network learnable parameters like weights and bias of convolution kernel, normalization layer or fully connected layers (FCLs) are the one responsible for giving prediction score. Though one parameter or parameters in a layer has not decisive role, however when whole network prediction is to be done, each one has role to generate prediction value. Hence, they are important for the network performance.

Method

We modeled a CNN for classification and trained it using 50% of total MRI scans for 3 classes. After training the network for 50 epochs, the network reaches convergences with 100% training accuracy and around 70% validation accuracy. Then, the trained models’ parameters i.e., weights and bias of FCL layers were analyzed class wise for any correlation with its parent class.

Result

The weights of final FCL are plotted as in Figure 1. The correlation matrix for weights on sample MRIs with trained weights are shown in Tables 1 and 2. Here, two activation functions were used for final test results were ReLU and Leaky ReLU with final test accuracy around 67.3% and 70.9% respectively.

Conclusion

We attempted to study the weights pattern in FCL layer for a trained CNN model along with its correlation value for each class.

[Acknowledgement]

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (No. NRF‐2021R1I1A3050703). And this research was supported by the BrainKorea21Four Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (4299990114316).
Mild behavioral impairment symptom severity predicts tau hyperphosphorylation assessed by plasma p‐tau181 across the Alzheimer’s disease spectrum
Authors: Lussier Firoza Z , Therriault Joseph , Tissot Cécile , Servaes Stijn , Benedet Andréa Lessa , Ashton Nicholas J. , Karikari Thomas K , Chamoun Mira , Stevenson Jenna , Rahmouni Nesrine , Zetterberg Henrik , Blennow Kaj , Ismail Zahinoor , Pascoal Tharick A , Rosa‐Neto Pedro
Published: December 2022

Background

Mild behavioral impairment (MBI) is a neurobehavioral syndrome characterized by the emergence of persistent non‐cognitive neuropsychiatric symptoms (NPS) in older adults, representing an at‐risk state for dementia and a potential marker of Alzheimer’s disease (AD). However, few studies have investigated associations between MBI and plasma biomarkers of AD pathophysiology, specifically tau hyperphosphorylation.

Method

Individuals across the AD spectrum (cognitively unimpaired (CU) and impaired (CI)) were selected from the Translational Biomarkers of Aging and Dementia (TRIAD) cohort. MBI was assessed using the MBI‐Checklist (MBI‐C), which assesses NPS severity in five subdomains: decreased motivation (apathy), emotional dysregulation (mood/anxiety symptoms), impulse dyscontrol (agitation, impulsivity, abnormal reward salience), social inappropriateness (impaired social cognition), and abnormal thoughts/perception (psychosis). Plasma levels of p‐tau181 were quantified in all individual, and log‐transformed due to right skew. Spearman correlation analysis investigated cross‐sectional associations between plasma p‐tau181 and MBI‐C scores, and between baseline plasma p‐tau181 and annual change in MBI‐C. Multivariable linear regression analyses assessed the ability of cross‐sectional and longitudinal MBI‐C scores to predict plasma p‐tau181, adjusting for age, sex, education, and diagnostic group (CU/CI, Aβ +/‐).

Result

Cross‐sectional MBI data were available for 211 individuals, with longitudinal data available for 128 individuals (). Significant correlations were found between plasma p‐tau181 and MBI‐C total and apathy scores in the cross‐sectional sample (Figure A). Further, significant correlations were found with plasma p‐tau181 and the annual change in MBI‐C total and apathy scores (Figure B). These associations were corroborated by significant standardized and adjusted regression coefficients from multivariate regression models, which showed that baseline and longitudinal MBI‐C total and apathy score predicted plasma level of p‐tau181 (Figure C).

Conclusion

Our study provides novel findings on the association between MBI and tau hyperphosphorylation assessed using plasma biomarkers in an AD cohort. These results add to the existing evidence for MBI as a clinical manifestation of AD pathology and support the use of the MBI‐C as an enrichment tool for clinical trial enrollment and therapeutic intervention.
Association between mid‐ and late‐ life cardiometabolic multimorbidity and dementia risk: a nationwide twin study
Authors: Dove Abigail , Guo Jie , Fastbom Johan , Marseglia Anna , Vetrano Davide Liborio , Pedersen Nancy L. , Xu Weili
Published: December 2022

Background

Cardiometabolic diseases (CMDs) have been linked to increased dementia risk, but their combined impact on dementia and its major subtypes remains unknown. We aimed to examine the association between mid‐ and late‐ life onset cardiometabolic multimorbidity with risk of dementia, Alzheimer’s disease (AD), and vascular dementia (VaD), and to explore whether genetic background contributes to this association.

Method

Within the Swedish Twin Registry, 17,387 dementia‐free individuals aged ≥60 were followed for up to 18 years to detect incident dementia. Dementia (including AD and VaD) was identified based medical records from the National Patient Registry (NPR) and the Swedish Cause of Death Register. CMDs (including type 2 diabetes, heart disease, and stroke) and age at onset (mid‐life [<60 years] vs. late life [≥60 years]) were ascertained from NPR records. CMD multimorbidity was defined as the presence of ≥2 co‐morbid CMDs. Data were analyzed using two strategies: 1) unmatched analysis using Cox models conducted among all twin individuals (to assess the CMD‐dementia association); and 2) co‐twin matched analysis using Cox models stratified by zygosity in dementia‐discordant pairs (to assess the role of genetics in this association).

Result

Of all participants, 3,176 (18.3%) had a single CMD and 789 (4.5%) had CMD multimorbidity at baseline. During the follow‐up, 2,494 participants developed dementia (including 817 AD and 515 VaD cases). The hazards ratios (HRs, 95% CIs [confidence intervals]) of dementia were 1.36 (1.23‐1.51) (1.23, 1.03‐1.49 for AD and 1.53, 1.23‐1.89 for VaD) for a single CMD, and 1.82 (1.48‐2.23) (1.39, 0.93‐2.09 for AD and 2.41, 1.64‐3.55 for VaD) for CMD multimorbidity. In stratified analysis, the HRs of the associations between mid‐ and late‐ life onset CMD multimorbidity and dementia were 2.47 (1.43‐4.28) and 1.72 (1.39‐2.14), respectively. In co‐twin matched analysis, the CMD‐dementia association remained significant in dizygotic twins (n = 544; HR 1.68, 95% CI 1.26‐2.39), but was greatly attenuated among monozygotic twins (n = 102; 0.84, 0.42‐1.65) (p = 0.045 for interaction).

Conclusion

Cardiometabolic multimorbidity, particularly in mid‐life, is associated with an increased risk of dementia, AD, and VaD after age 60. Genetic background appears to underpin the CMD‐dementia association.
Tau PET shows both direct and atrophy‐mediated effects on cognition: 4‐way decomposition of the effects of tau PET and atrophy on cognitive performance
Authors: Higgins Cesar , Aslanyan Vahan , Cody Karly Alex , Ward Tyler J. , Choi Seo‐Eun , Wei Jingkai , Amofa Priscilla A , Crane Paul K. , Harrison Theresa M.
Published: December 2022

Background

Evidence suggests that tau pathology predicts subsequent neurodegeneration and that atrophy is associated with cognitive impairment. However, in vivo studies have shown that structural measures only partially mediate tau‐cognition relationships, with direct effects of tau on cognition remaining. The objective of current study is to decompose the overall effect of tau on domain‐specific cognitive performance, in the presence of atrophy as a mediator with which tau may interact.

Method

705 participants with flortaucipir (FTP)‐PET were selected from Alzheimer’s Disease Neuroimaging Initiative—3 (Table 1). MRI scans closest to FTP were used to measure cortical thickness and volume in a priori regions (Desikan atlas, FreeSurfer v7.1) associated with memory, executive function, language, and visuospatial cognitive domains. Using a causal mediation framework, tau accumulation measured with FTP‐PET in a temporal meta‐region was the primary exposure, cognitive domain scores were the primary outcomes and regional structural measures were the hypothesized mediators. Statistical models incorporating exposure—mediator interactions (4‐way decomposition) were used to identify natural direct and indirect effects.

Result

Across the entire cohort (age 74.26 (7.82), 58% cognitively unimpaired, 30.8% MCI, 11.2% Demented), regional morphometry in medial temporal lobe (MTL) subregions selected a priori for their relationship with memory function mediated the effect of tau on all cognitive domains (Table 2). Hippocampal volume had the largest total indirect effect (mediating the effect of tau) across all domains (37% (95% confidence intervals (CI): 28%, 47%) for memory, 28% (CI: 18%, 38%) for executive function, 37% (CI: 24%, 50%) for language, and 29% (CI: 10%, 49%) for the visuospatial domain). Similar mediating effects were observed for entorhinal cortical thickness and to a lesser extent parahippocampal cortical thickness. In contrast, the morphology of regions selected a priori based on functional neuroanatomical associations with executive function, language or visuospatial domains did not mediate tau‐cognition relationships.

Conclusion

Our results suggest that the effect of MTL atrophy on tau‐cognition associations may extend beyond memory function and be an important mechanism by which tau accumulation affects multiple cognitive domains. Follow‐up longitudinal studies will help to characterize the temporal dynamics of atrophy‐mediated associations between tau and cognition.
Symptomatic Concussions, Depression, and Impulsivity in Fighters with a Family History of Dementia
Authors: Esagoff Aaron I. , Bray Michael J.C. , Shan Guogen , Narapareddy Laren , Bernick Charles B. , Peters Matthew E. , Narapareddy Bharat R.
Published: December 2022

Background

Professional boxers and Mixed Martial Arts (MMA) fighters regularly sustain blunt force trauma to the head leading to Traumatic Brain Injury (TBI) and concussion; therefore, fighters are at high risk for chronic traumatic encephalopathy and neurodegenerative disease. Family history of dementia (fhD) may significantly modulate fighter response to TBI. Genetic polymorphisms associated with dementia have been reported to modulate an individual’s response to brain injury and to influence emotionality, risk‐taking, and cognition. A recent study in male college athletes found that fhD predisposed athletes to poorer recovery after concussion and to decrements in impulse control following injury. Furthermore, in a population‐based cohort study from the Netherlands, researchers found that parental history of dementia led to increased rates of depression in mid‐life. The present study aims to investigate how fhD in fighters may relate to history of symptomatic concussions, depression, and impulsivity.

Methods

Using data from the Professional Fighters Brain Health Study (longitudinal cohort study of fighters), we included active, professional boxers and MMA fighters (n = 198) for cross‐sectional analyses. The latest study visits with available data were utilized to generate multivariate regression analyses examining the number of self‐reported symptomatic concussions in a fighter’s career, Patient Health Questionnaire (PHQ)‐9 scores, and Barratt Impulsiveness Scale Version 11 (BIS‐11) scores, adjusting for age, sex, education, and number of professional fights.

Results

FhD was significantly associated with more symptomatic concussions during one’s career (p<0.05), higher PHQ‐9 scores (p<0.01), and higher BIS‐11 scores (p<0.01).

Conclusions

Our findings suggest that professional boxers and MMA fighters with fhD may be more likely to experience symptomatic concussions, depression, and impulsivity during their active fighting career. We postulate that fhD may predispose fighters to experience a higher burden of neuropsychiatric symptoms after sustaining a TBI, potentially due to differences in the brain’s response to injury. These findings may be used to advise those with fhD to minimize possible exposures to TBI and to educate fighters with fhD regarding risks of chronic neurotrauma exposure. Future research should evaluate potential genetic and/or molecular mechanisms behind these trends and behavioral outcomes associated with the sequelae of TBI in those with fhD.
Gabapentin utilization among older adults with different cognitive status: Results from the National Alzheimer’s Coordinating Center database (2006‐2019)
Authors: Oh GYeon , Moga Daniela C , Abner Erin L
Published: December 2022

Background

Although gabapentin use has been increasing among older adults, its safety is understudied. We aimed to examine gabapentin utilization trends among older adults with different cognitive status and investigate potentially inappropriate concurrent medication use with gabapentin.

Methods

Data were extracted from National Alzheimer’s Coordinating Center Uniform Data Set (2006‐2019). We included participants (age 65+) with any medications reported at the time of visit. Within each study year, we estimated the prevalence of gabapentin use among the participants at each visit, both overall and within subgroups defined by cognitive status [normal, mild cognitive impairment, and dementia] and demographics [age and sex]. Additionally, we assessed prevalence of concurrent use of gabapentin with Central Nervous System (CNS) depressants, including opioid, combined opioid and benzodiazepine, antidepressant, and antipsychotic.

Results

Overall, participant‐reported gabapentin use nearly tripled (2.2 to 6.1%) from 2006 to 2019. Further, prevalence increased over this period in every participant subgroup. Among gabapentin users, the concurrent use of antidepressants or antipsychotics was more common in participants with a dementia diagnosis than those with normal cognition. Over half of gabapentin users with dementia also reported use of antidepressants. The concurrent use of gabapentin with opioids ranged from 10 to 30%, and the concurrent use of gabapentin, benzodiazepine, and opioids was below 8% throughout the study period.

Conclusions

Given increasing use among older adults, including those with cognitive impairment and dementia, rigorous studies are needed to examine the safety of gabapentin in this population, especially when using gabapentin with other CNS medications concurrently.
Why Bayesian analysis of clinical trials may be a good idea– a worked example of the aducanumab studies
Authors: Teipel Stefan , Ly Alexander , van Doorn Jonny , Wagenmakers Eric‐Jan , Tang Yi , Lutz Michael W. , Temp Anna G.M.
Published: December 2022

Background

The FDA decision to approve Aducanumab has sparked controversy. Here, we argue that some of these controversies are rooted in the conclusions facilitated by classical frequentist analysis. We suggest that a Bayesian analysis would answer some of the burning questions the aducanumab trials have posed to the field.

Method

We applied Bayesian analysis of model plausibility and effect sizes based on simulated data (the original data are not publicly available) of the two phase 3 trials (trials 301 and 302) of aducanumab in prodromal and mild dementia stages of Alzheimer’s disease.

Result

Excluding the rapid progressors from our simulated data did not produce decisive evidence supporting aducanumab’s treatment effect. The Bayesian analysis suggested that the study indicator (study 301 or study 302) was irrelevant as a predictor of treatment effect (Bayes Factor (BF)exc = 42.16). Our simulated data further offered overwhelming evidence against Biogen’s assumption that rapid progressors affected any treatment arm of either study disproportionately (i.e., BFexc = 9910.74). We also found anecdotal evidence against the treatment arms (i.e., BFexc = 2.65) as a predictor of CDR‐SB change (Figure 1). The prior and posterior plots show that if the effect existed, it would be very small, likely ranging from Kendall’s tau 0.007 to 0.052, with a median of 0.029 (Figure 2).

Conclusion

Bayesian analysis can quantify evidence in favor of the presence or absence of an effect, as well as assess the strength of the effect. In the case of our simulated data, Bayesian analysis quantified evidence that studies 301 and 302 do not provide diverging evidence, and that the treatment arm‐specific rapid progressor effect was absent. The Bayesian analysis thus provides more informative and nuanced conclusions than the reported frequentist tests, which leave many questions unanswered.
CenTauRz: A standardized quantification of tau PET scans
Authors: Dore Vincent , Bullich Santiago , Bohorquez Sandra Sanabria , Leuzy Antoine , Shimada Hitoshi , Rowe Christopher , Bourgeat Pierrick , Lopresti Brian J , Huang Kun , Krishnadas Natasha , Fripp Jurgen , Takado Yuhei , Stephens Andrew W , Weimer Robby , Higuchi Makoto , Hansson Oskar , Villemagne Victor L
Published: December 2022

Background

Over the past decade, several PET tracers were developed to visualise and quantify tau pathology in vivo. However, all these tracers have distinct off‐target binding, different dynamic ranges and likely different levels of non‐specific binding resulting in large variability in semiquantification. We propose to standardise the sampling and the quantification across all available tau tracers.

Method

549 participants underwent tau scans with either 18F‐FTP (Cognitively Unimpaired (CU)=54/AD=14), 18F‐MK6240 (CU=186/AD=89), 18F‐PI2620 (CU=17/AD=21), 18F‐PM‐PBB3 (CU=30/AD=28), 18F‐GTP1 (CU=7/AD=38) or 18F‐RO948 (CU=35/AD=30). All CU individuals were Aβ‐ and all AD were Aβ+. The tau scans were spatially normalized using CapAIBL and the cerebellar cortex was used as reference region. We constructed a “universal” tau mask from the intersection of all the specific tau tracer masks, after subtracting AD from CU. All tau PET studies were sampled with a Mesial Temporal (MTL) and a Meta Temporal (MetaT) composites constrained by the universal mask. For each tracer and in composite, the mean and standard deviation of the Aβ‐ CU SUVR for each tau tracer were used to generate z‐scores (CenTauRz).

Result

Using a threshold of 2 CenTauRz in the MetaT regions, all tracers highly discriminated Aβ+ AD from Aβ‐ CU (ACC=[0.94‐1], sens=[0.84‐1], spec=[0.96‐1]) with mean CenTauRz for the different AD cohorts ranging from 8 to 14. Lower accuracy was observed in the MTL (ACC=[0.78‐1]) due to lower sensitivity in some cohorts [0.65‐1] however, the specificity was similar to that in the MetaT composite (spec=[0.94,1]).

Conclusion

All tracers exhibited comparably high discriminative power to separate Aβ+ AD from Aβ‐ CU, where AD Aβ+ displayed a consistent range of CenTauRz across tracers. However, there were some differences between cohorts. For example, different PET scanners, with different sensitivities were used. For some cohorts, scans were selected as extreme representative cases, while for others the scans were more representative of clinical settings, with AD patients at early stages (with low or negative tau scans) or with suspected hippocampal sparing subtype that likely explains the lower accuracy in the MTL for some cohorts. Further studies with larger cohorts to validate the universal mask and CenTauRz scale are ongoing.
The Greek Dementia Helpline: experience and impact
Authors: Blekou Patra , Sakka Paraskevi , Leonti Antigoni Athina , Megagianni Sotiria , Zoi Panagiota
Published: December 2022

During the Covid‐19 pandemic in Greece, quality and quantity of support for people with dementia and their family carers varies widely and depends on the availability of resourses in different areas. The pandemic forced an urgent transition from face‐to‐face to telehealth services.

The Greek Dementia Helpline 1102 was launched on February 2021, as a telephone service staffed by psychologists, neurologists and social workers with expertise in dementia care and is provided by Athens Alzheimer Association. The aim of the helpline is to offer counseling about dementia, to support and guide family carers and link them with community support services and programs. Between February 2021 and October 2021, more than 8000 people have called Helpline 1102 and more than 2500 people have contacted the line via email or live webchat (68% women and 32% men). The beneficiaries of the helpline were family carers (75%), health professionals (15%) and lay people requesting information on dementia prevention, care and treatment. Especially, carers were interested in availability of dementia services in different areas of Greece, disability allowances, legal issues, and how to choose residential homes or paid caregivers.

After using the Dementia Helpline, carers have reported increased sensitivity to the challenges faced by their loved ones with dementia, and more able to make the needed adjustments to their care‐giving task.

Dementia Helpline 1102 provides dementia carers with a reliable a framework through the implementation of appropriate counseling by trustworthy healthcare professionals. Athens Alzheimer Association offers this service free of charge.
A social robot to support people with dementia at mealtimes: Design, implementation and preliminary evaluation
Authors: Astorga Misael , Favela Jesus , Cruz‐Sandoval Dagoberto , Riek Laurel D
Published: December 2022

Background

People with dementia often experience difficulties eating at mealtimes, which is a common cause of concern to informal caregivers. These difficulties include becoming agitated or angry at mealtimes, taking food from someone else’s plate, or refusing to eat the food being offered. These behaviors manifest differently in each individual, are context‐dependent, and vary overtime.

Method

We engaged in a user‐centered design process to create a social robot that can serve as an eating companion for people with dementia (PwD). Interviews with caregivers (n=6) helped identify common problematic behaviors during mealtimes, and strategies to address them. Additionally, we conducted iterative, interaction co‐design sessions to define the robot's behaviors. The EVA robotic platform was used to implement the PwD‐robot interaction and to create videos of short interactions to show how the social robot can help to deal with these problematic behaviors. These videos were shown to informal caregivers (n=14) who were asked to assess user adoption using the Almere model (Heerink et al. 2010). A machine learning model was trained to detect disruptive eating behaviors from images captured by the social robot and to trigger appropriate responses.

Result

Caregivers found the scenarios to be realistic and perceived the robot to be enjoyable and easy to use. A 92% precision was obtained from the trained Machine Learning model in detecting that an individual is eating (83% sensitivity and 96% specificity), using a capture rate of one frame per second.

Conclusion

The results provide evidence of the technical feasibility of implementing a social robot to act as an eating companion for people with dementia and the positive perception of caregivers regarding its potential adoption.
Intricate connections between aging and Alzheimer’s diseases molecular trajectories revealed by plasma proteomics
Authors: kosti idit , Nanasi Tibor , Ruiz Agustin , Boada Mercè , Marquié Marta , Cano Amanda , Braithwaite Steven P , Lehallier Benoit
Published: December 2022

Background

Aging is the greatest non‐genetic risk factor for many diseases including Alzheimer’s Disease (AD) and its mechanisms are thus increasingly recognized as potential therapeutic targets.

Since the molecular relationships between normal aging and AD are still largely unknown, we took advantage of recent methodological developments to measure more than 7k proteins in plasma to identify common but also different molecular mechanisms involved in aging and AD.

Method

Recently, we developed new data‐driven bioinformatics approaches that uncovered marked non‐linear alterations in the human plasma proteome with age (Lehallier et al. Nature Medicine 2019). We applied these machine learning approaches to 271 patients at different stages of AD (61 subjects with Subjective Cognitive Decline: SCD, 106 with Mild Cognitive Impairment: MCI and 104 with AD) and compared these changes to those observed in a healthy aging cohort (370 subjects, 18‐69 years).

Result

The analysis of proteomics trajectories confirmed marked non‐linear alterations in the human plasma proteome with aging and uncovered the complex molecular choreography of AD. By analyzing trajectories of groups of proteins, we identified multiple clusters of proteins that are differentially affected during aging and AD. These clusters were enriched for various biological processes relevant for AD progression such as the complement and coagulation cascades, axon guidance and angiogenesis (q<0.05)

Conclusion

Altogether, our results reveal the intricate connections between aging and AD at the molecular level. The integrated proteomics trajectories analysis performed in this study allows the identification of new targets possibly playing a key role in AD but also pinpoints when these proteins are deviating from their normal trajectories and thus when they should be targeted by new therapies.
Prediction of Progression Along the Transition Points within the Continuum of Cognitive Impairment from Subjective Cognitive Complaints to Dementia Using Dyadic Patterns of Subjective Reporting
Authors: Pérez‐Blanco Lucía , Felpete Alba , Mallo Sabela C. , Campos‐Magdaleno Maria , Nieto‐Vieites Ana , Lojo‐Seoane Cristina , Juncos‐Rabadán Onésimo , Pereiro Arturo X
Published: December 2022

Background

The validity of Subjective Cognitive Complaints (SCCs) from dyadic patterns to predict progression to dementia is not yet clear. Some studies suggest that the validity of informant report in predicting dementia increases as cognitive function and awareness of symptoms decline. Our aim was to compare validity of informant and participant reports, and its agreement, to predict progression to MCI and conversion to dementia.

Method

A total of 226 participants from the CompAS study were longitudinally assessed (intervals 18–24 months). The sample consisted of SCD (198) and MCI (28) participants. SCCs from participants and informants were assessed at baseline, 1st and 2nd follow‐ups using the QAM questionnaire. Informant‐participant total score agreement (disagreement, over‐ and under‐estimation, were identically considered) were calculated. Logistic regressions were separately performed to distinguish SCD stables and participants progressing either from SCD to MCI/dementia or from MCI to dementia using SCCs reports from participants, informants and agreement as predictive variables.

Results

Informant report at baseline significantly predicted conversion to dementia from baseline to the 3rd follow‐up (β = .173; SE = .048; p<.001; OR = 1.189, CI = 1.082‐1.306), similarly to that observed for informant reports at 1st follow‐up to predict conversion from 1st to the 3rd follow‐up (β = .225; SE = .050; p = .001; OR = 1.252; CI = 1.135‐1.381), and at 2nd follow‐up to predict conversion from 2nd to the 3rd follow‐up (β = .271; SE = .083; p<.001; OR = 1.313; CI = 1.110–1.552) (see Table 1).

Informant report at baseline also successfully predicted the progression to MCI from baseline to the 3rd follow‐up (β = .139; SE = .057; p = .017; OR = 1.49; CI = 1.025‐1.288), similarly to that observed for informant reports at 1st (β = .124; SE = .056; p = .026; OR = 1.132; CI = 1.015‐1.264), and the 2nd follow‐ups (β = .195; SE = .073; p = .008; OR = 1.216; CI = 1.053‐1.404) (see Table 2).

Conversion to dementia (β = .113; SE = .048; p = .018; OR = 1.119; CI = 1.020‐1.229) and progression to MCI (β = .138; SE = .054; p = .011; OR = 1.148; CI = 1.032‐1.277) using Self‐report were only significantly predicted using 1st follow‐up reports.

Agreement did not significantly predict the progression to MCI or dementia at any of measurement points.

Conclusions

Informant report successfully predicted progression and conversion at any transition point. Self‐reports were only predictive at 1st follow‐up. Agreement did not significantly predict progression and conversion.
Otiom ‐ Developing a Dementia tracking solution in collaboration with people living with dementia and their family caregivers
Authors: Thoft Diana Schack
Published: December 2022

Background

The study focused on developing a dementia tracking solution for people with dementia and their family caregivers that were user‐friendly and had a high user‐acceptability. Thus, high reliability, precision and low battery use. The study was a public private innovation project involving users, municipalities, universities and private companies.

Method

Three workshops with people with dementia and their family caregivers, were held to ensure their experiences and needs were addressed (two groups of people with dementia and one group of relatives). The workshops focused on: Introduction and brainstorm for developing a new tracking solution, Introduction to possible new and existing tracking solutions and Evaluation and presentation of the developed tracking solution. Each workshop was planned in relation to the wishes and resources of the participants and involved creative and innovative methods.

Result

The workshops made it possible for people with dementia and their caregivers to contribute to the development of the tracking solution. People with dementia found the involvement exciting but also challenging, here peer‐support were experienced positively. The family caregivers wanted to participate as they found the involvement important but often, they had difficulties in finding time due to their caring role.

Conclusion

The participants evaluated the involvement positively. Most of them also found the developed solution user‐friendly and ‐acceptable as it was nice, simple to use and had different mounting options. Several were keen to test it. However, some were also critical towards it and expressed a need for more features, another design and the possibility of individualisation.
Quantifying AD‐related brain amyloid with linearised progression models: model‐based vs. data‐based.
Authors: Wink Alle Meije , Shekari Mahnaz , Dicks Ellen , Collij Lyduine E. , Salvadó Gemma , García David Vállez , Gispert Juan Domingo , Tijms Betty M. , Alves Isadora Lopes , Yaqub Maqsood , Barkhof Frederik
Published: December 2022

Background

Brain amyloid‐β (Aβ) is the pathological hallmark of Alzheimer's disease (AD). In logistic disease models, Aβ accumulation is a sigmoid function of time‐since‐disease‐onset (TSDO) (figure 1). Previous positron emission tomography (PET)‐based models vary accumulation onset(t50) and duration(r) globally; capacity(K) and baseline(NS) regionally (Whittington2018). We confirm existing approaches and propose a more powerful ICA‐based approach to quantify disease severity and estimate TSDO.

Method

We used 1071 18F‐florbetapir standard uptake value ratio (SUVR) images from the ADNI‐2 study (adni.loni.usc.edu/data‐samples/data‐types/pet). Images were mapped into MNI space. Averages were extracted using the Harvard‐Oxford brain‐atlas. Whole‐brain tracer‐specific sigmoid parameters (Jack2013) obtained from the literature were used to estimate TSDO.

Of 16 models of regional Aβ accumulation (each of the 4 regional sigmoid parameters varied either regionally or globally), the optimal Bayesian information criterion was found with global t50 and r, and regional NS and K (figure 1) with global values r=6.16y and t50=4.10y.

Linearised maps of NS and K were obtained by regressing the SUVR maps onto the global sigmoid. We also estimated these maps as independent components, using a 2‐component ICA on the SUVR maps. Both outcomes were used to quantify Aβ accumulation from SUVR images as weighting factors of the accumulation map.

We compared the weights from the logistic model and the ICA model in ADNI, using effect size measured with Hedges' g between cognitively normal (CN), subjective memory complaints (SMC), mild cognitive impairment (EMCI/MCI/LMCI) and AD groups. We compared 3 longitudinal visits (N=112) in the OASIS‐3 study (see www.oasis‐brains.org) with both methods, global SUVR and Centiloid (Klunk2015) using 11C‐PiB PET SUVR images.

Result

Maps of accumulation capacity from both models had spatial correlation of 0.86 (figure 2); baseline maps had spatial correlation of 0.95. Hedges' g between ADNI groups was 2.25 for K, and 2.42 for ICA (1.46 for global SUVR). In OASIS‐3, Hedges' g between visits was 1.24 for K, 1.46 for ICA (global SUVR 0.15, Centiloid 0.4).

Conclusion

We demonstrate that linear accumulation models can be used to quantify brain Aβ with PET; maps obtained by ICA yield larger effect sizes than the logistic method for differentiating groups and measuring changes between visits.
Needs Assessment Study in Colombia: Recruitment Phase‐Design of Remote Communication Strategies to Encourage participation in dementia research during COVID‐19 pandemic
Authors: Romero‐VanegasPardo Sara JulietaRodrigo , Moreno‐Angarita Marisol
Published: December 2022

Background

During the pandemic, we face multiple challenges during the research. One of them was recruiting participants in the age of social distancing. As a result, we had to use creative approaches that would allow us to access the study population contemplating all the complexities, difficulties or problems that research during a pandemic demands. For dementia, we design a method to encourage the participation of patients, caregivers, professionals and associations in Colombia. Combining different virtual frameworks, tools and techniques. We embraced biosafety provisions from health policy authorities mitigating the exposition of our high‐risk groups, making up the majority of our target population.

Objective

Design a methodological communication strategy that allows the dissemination of project knowledge and participation of the target populations (patients with mild dementia, formal and informal caregivers and health care professionals).

Method

We summoned caregivers, people with dementia and health care professionals through multiple channels: Social media, e‐mail, caregiver´s databases, press, radio, physician specialists invitation, Dementia Research Groups (Antioquia University and Colombia National University), and voluntary associations (Alzheimer Colombia Family Action Foundation, Grupo Cuídame). We presented remote conferences about the project, panel discussions about the invisible needs of the population with dementia in Colombia. Also, we sought collaborative efforts with radio and television programs to increase the awareness in the population about the dementia challenges.

Result

Over 100 people attended each event. We carried out collaborations with national groups increasing visibility of the project and amplifying citizen participation. Interviews with written, oral, and electronic media contributed to fostering interest in the study population. Remote communication strategies stimulated the involvement of various actors (patient‐family‐caregiver‐professional) from multiple cities and contexts.

Conclusion

Researching pandemic time has tested our creative ability to address the various challenges we face as researchers. Accessing the participants contemplated by the study has led to a little‐explored space, which has directed us towards non‐face‐to‐face alternatives, prompting us to design a methodological communication strategy that allows the dissemination of the project and participation of the dementia population in Colombia without requiring in‐person attendance.