bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluating the co‐design of a program to supporting living well with dementia
Authors: Bechard Lauren Elizabeth , Wei Cindy , Tupling Olivia , Keller Heather , McAiney Carrie A , Middleton Laura E 
Published: February 2022

AbstractBackgroundEngaged research involves stakeholders as active partners in the research process, not just as research participants. Engaged dementia research can improve the relevance and quality of research, empower persons living dementia (PLWD) and family care partners, and acknowledge their expertise gained through lived experience. Conducting engaged research is challenging during COVID‐19 when in‐person interactions are difficult or impossible. The Dementia Lifestyle Intervention for Getting Health Together (DELIGHT) project used an online, engaged research approach to co‐design the DELIGHT program, a 12‐week program to support the health and well‐being goals of PLWD and care partners. Here, we used mixed‐methods to evaluate the DELIGHT co‐design process, its alignment with an Authentic Partnership approach, and experiences, satisfaction, and suggestions for future online co‐design processes.MethodThe DELIGHT project engaged 29 people in the co‐design process during Summer 2020, including PLWD, care partners, service/program providers, healthcare providers, and researchers. The co‐design team met over six, 1.5‐hour online meetings (via Zoom) to develop the program. Although the co‐design process is on‐going, evaluation focused on this first phase of the co‐design process. A 17‐item survey assessed alignment with an Authentic Partnerships approach. Focus groups and interviews used a semi‐structured guide to assess experiences, satisfaction, and suggestions for future on‐line co‐design.ResultSurveys were completed by 11 co‐design members, and 11 co‐design members participated in interviews or focus groups (not all completed both). Initial analysis of survey results indicates co‐design members felt respected and safe in the co‐design process, felt their perspectives and opinions were valued, and valued the contributions of other members (100% agreed or strongly agreed). All survey respondents felt they gained knowledge and strategies for living well with dementia during the co‐design process. All survey respondents also strongly agreed that the DELIGHT program, when implemented, will have a positive impact on PLWD and care partners. Analysis of interviews/focus groups is ongoing and will be available in Spring 2021.ConclusionCo‐design members expressed high satisfaction with the process and felt their experiences were valued and heard. All members expressed a strong belief that the program developed will benefit PLWD and care partners.
Preliminary findings in a platform‐based MCI trial designed to promote adaptive behaviors
Authors: Gibson Allison , Kelly Parsons R , Oaks Dawn C , Pope Caitlin N , Rhodus Elizabeth K , Bardach Shoshana H , Johnson Julia , Barber Justin M , Jicha Gregory A 
Published: February 2022

AbstractBackgroundReceiving a diagnosis of mild cognitive impairment (MCI) may lead to experiences of emotional turmoil stemming from a perceived lack of clarity around diagnosis and prognosis. Previous research has identified several maladaptive behaviors resulting from the diagnosis of MCI that may be targeted for intervention in order to help those with a new diagnosis of MCI best adapt behaviors to maintain functional abilities.MethodA platform‐based MCI trial cohort of individuals, newly diagnosed with MCI from a U.S. Alzheimer’s Disease Research Center, was used to pilot a multicomponent interdisciplinary intervention targeting adaptive behavioral responses to the diagnosis of MCI. Thematic analysis was employed with fifteen focus groups across three study groups of 14 participants. After engaging with each of the platform‐based MCI trial components, participants’ and their study partner’s perceptions of each intervention’s acceptability, satisfaction, and compliance across the multicomponent interdisciplinary intervention were assessed.ResultsThemes that emerged from the data included a preference towards education, learning new information, and skill development. Both persons with MCI and study partners favored intervention components that were novel to them. They also reported higher satisfaction with activities facilitated by a professional (e.g., social worker, physical therapist, or pharmacist) as opposed to intervention activities that were self‐directed. Participants with MCI and their study partners reported those with impairment’s challenges utilizing technology independently, requiring assistance in setting up online medical portals, using wearable exercise trackers and automated pillboxes that represented technology‐dependent components of the intervention.ConclusionThese data suggest that persons, newly diagnosed with MCI, are interested in adaptive, biopsychosocial interventions for persons with MCI. Acceptability, satisfaction, and compliance may be increased when individuals are engaging in learning novel information and skills that are led and supported by professionals. Assistance with and or training in the use of technology‐based interventions may be needed to maximize the impact of such approaches. Further studies exploring the impact on the cognitive and functional decline that may be mediated by adaptive behavioral interventions in persons newly diagnosed with MCI are warranted.
The interaction of APOE genotype and amyloid‐β PET predicts PET but not CSF measures of tauopathy in regions of high APOE mRNA expression
Authors: Dincer Aylin , Chen Charles D. , McKay Nicole S. , McCullough Austin A. , Flores Shaney E. , Keefe Sarah J. , Schultz Stephanie A. , Feldman Rebecca L. , Hornbeck Russ C. , Cruchaga Carlos , Holtzman David M. , Morris John C. , Benzinger Tammie L.S. , Gordon Brian A. 
Published: February 2022

AbstractBackgroundThe apolipoprotein E (APOE) ε4 allele is the most well‐established genetic risk factor for late‐onset Alzheimer disease (AD). The ε4 allele is strongly linked with cerebral β‐amyloidosis whereas its relationship with tauopathy is less established. Here we investigate the relationship between APOE ε4 carrier status, regional amyloid‐β‐ (Aβ) and tau‐ positron emission topography (PET), APOE mRNA expression patterns, and cerebrospinal fluid phosphorylated tau (CSF ptau).Method350 participants from the Knight Alzheimer Disease Research Center (mean age = 69.7) underwent tau‐PET ([18F]‐flortaucipir) and Aβ‐PET ([18F]‐florbetapir) imaging. Tau‐ and Aβ‐ PET data were converted to standardized uptake value ratios (SUVRs). APOE ε4 carrier status was defined by the presence of at least one ε4 allele. CSF ptau data was available for 270 of the participants. Linear regression models were used to predict regional Aβ‐ and tau‐PET levels from APOE ε4 carrier status. Additional models were used to predict regional tau‐PET and CSF ptau from the interaction of APOE genotype and global Aβ‐PET. Age and sex were included as covariates in all models. Regional APOE mRNA expression was derived from the Allen Human Brain Atlas (Fig. 3G).ResultStrong associations were found between elevated regional tau‐ and Aβ‐ PET levels and APOE ε4 carrier status (Fig. 1A, B). There was a significant interaction between APOE genotype and global Aβ‐PET predicting tau‐PET levels specifically in the entorhinal, amygdala, and superior temporal regions (Fig 1C), but not CSF ptau (Fig. 2). The spatial pattern of APOE mRNA expression was significantly associated to the spatial pattern of APOE ε4 genotype exerted on regional tau‐PET, but less so for regional Aβ‐PET (Fig. 3).Conclusion
APOE ε4 genotype exerts influence on tauopathy above its effect on Aβ. These effects occur in regions of the brain that have high APOE mRNA expression, suggesting potential local tissue vulnerability to tauopathy. The lack of an interaction in CSF ptau may be due to different roles soluble and aggregated forms of the tau protein play in AD pathophysiology.
Sex differences in brain aging among adults with APOE4 genetic risk and family history of Alzheimer’s disease
Authors: Subramaniapillai Sivaniya , Rajagopal Sricharana , Snytte Jamie , Otto Ross , Einstein Gillian , Rajah Natasha ,   the PREVENT‐AD Research Group
Published: February 2022

AbstractBackgroundDetermining the effect of AD risk factors on brain aging in healthy middle‐aged and older women, compared to men, is critical for understanding whether there are sex differences in the pathways towards AD in cognitively intact, at risk adults. The goal of this study was to use an elastic net regression model to predict the effect of family history of AD [+FH] and the APOE‐e4 [+APOE4] genotype on brain age gap (BAG) in cognitively normal women and men.MethodThis cross‐sectional study used T1‐weighted structural MRIs from the Dallas Lifespan Brain Study (DLBS), South Asian Lifespan Dataset (SALD), Montreal Memory and Aging Lifespan Study (MMALS), and Pre‐symptomatic Evaluation of Experimental or Novel Treatments for Alzheimer’s Disease (PREVENT‐AD) cohorts. Data were collected from multiple sites: Dallas, USA (DLBS); Chonqing, China (SALD); Montreal, Canada (MMALS and PREVENT‐AD). 1067 cognitively normal adults (18‐89 years; 697 [65%] women) were randomly split into train and test sets. In the train set: 596 unknown FH (uFH) participants (mean [SD] age = 47.39 [18.46] years, 63% women); in the test set: 251 uFH (47.50 [19.15] years, 64% women) and 220 +FH participants (61.53 [6.04] years, 72% women). BAG, was measured as the difference between Predicted Age, estimated by the elastic net model, and Chronological Age.ResultThe age prediction model applied to the test set revealed greater BAG deviations in the +FH cohort compared to the uFH cohort (31% vs. 74% of the age variance, respectively; MAE = 8.22 years). A significant interaction was observed between FH status and Sex: +FH women had more advanced brain aging compared to +FH men. APOE genotype interacted with Sex in the +FH group: +APOE4 women had more positive BAG than +APOE4 men. In a sub‐cohort of individuals with AD risk factors, we observed sex differences in the role of modifiable factors of Body Mass Index and physical activity in preserving brain aging.ConclusionAD risk factors have more negative consequences to brain aging in cognitively normal women with family history than men with family history, but that modifiable factors can interact with genetic factors to potentially protect against brain aging.
A global resilience score captures associations with AD pathology and predicts cognitive decline in cognitively healthy older adults
Authors: Dobyns Lindsey , Zhuang Kailin , Baker Suzanne L. , Jagust William J. , Harrison Theresa M. 
Published: February 2022

AbstractBackgroundThe concepts of resilience and reserve were developed to help explain the variability in the relationship between pathology and cognition in older adults. We created a global resilience score that considers cognitive reserve, brain reserve, and cognitive resilience. We examined the relationship between global resilience and cross‐sectional PET measures of amyloid (PiB) and tau (FTP) and longitudinal change in cognition.Method130 cognitively normal older adults over the age of 60 (76.13±6.13 years, 76% F, 55% PiB+) were included in the analysis. Confirmatory factor analysis was used to create composite scores for episodic memory (EM) and executive function (EF). A partial least squares path model was used to derive a global resilience factor, a second‐order latent variable, from three first‐order latent variables estimating cognitive resilience, brain reserve, and cognitive reserve (Fig 1). PET data were coregistered to the structural MRIs and extracted from FreeSurfer‐segmented regions. A global PiB DVR and partial volume corrected FTP SUVR regional values were calculated. Longitudinal change in cognition was calculated as the slope of the linear fit over time for EM and EF.ResultThere were no significant relationships between global resilience and global PiB DVR (Fig 2A). Greater global resilience score was associated with lower entorhinal (ERC) FTP SUVR across the whole sample (R2 = 0.079, p = 0.001) and in PIB‐ (R2 = 0.062, p = 0.032) and PIB+ individuals (R2 = 0.088, p = 0.029) separately (Fig 2B). In PiB+ individuals, lower global resilience scores predicted greater decline in EM (R2 = 0.144, p = 0.008) and in EF (R2 = 0.098, p = 0.030) with PiB‐ individuals showing no significant relationships (Fig 3).ConclusionGlobal resilience score is associated with ERC tau and predicts cognitive change in amyloid+ individuals for both EM and EF. Our model reflects the proposed sequence of biomarker change in AD as global resilience is unassociated with PiB DVR but significantly correlated with ERC tau and cognitive change. These results indicate that a computed global resilience variable derived from measures of cognitive reserve, brain reserve and cognitive resilience is related to AD pathology and cognitive trajectory.
Plasma extracellular vesicle biomarkers for cognitive impairment in Parkinson’s disease
Authors: Blommer Joseph M. , Pitcher Toni , Mustapic Maja , Meissner Wassilios , Anderson Tim , Kapogiannis Dimitrios 
Published: February 2022

AbstractBackgroundParkinson’s Disease (PD) pathogenesis involves intraneuronal a‐synuclein accumulation, but also insulin resistance, characterized by decreased Tyr and increased Ser insulin receptor substrate‐1 (IRS‐1) phosphorylations. Besides motor symptoms, some PD patients develop mild cognitive impairment (PD‐MCI) or dementia (PD‐D), partly due to overlapping Alzheimer’s disease (AD) pathology. For PD prognosis, there is a need for biomarkers distinguishing PD with normal cognition (PD‐N) from PD‐MCI/D. Neuronal‐origin extracellular vesicles (NEVs) contain signaling and pathogenic proteins that may serve as biomarkers.MethodFrom 104 PD‐N, 83 PD‐MCI, 39 PD‐D patients and 48 age/sex‐matched Controls, we immunocaptured plasma NEVs using anti‐L1CAM antibody. We measured biomarkers by immunoassays for: 1) PD and AD pathogenic proteins (a‐synuclein, Aβ42, total tau and p181‐tau) 2) insulin signaling mediators (pTyr20 and pSer312 IRS‐1). Particle concentration was measured by Nanoparticle Tracking Analysis and immunoblots were used to characterize NEV preparations.Resulta‐synuclein was lower in PD compared to Controls (p = 0.005) and stepwise lower in PD‐MCI (p = 0.007) and PD‐D (p < 0.001) compared to PD‐N; it tended to decrease with increasing motor symptom severity by MDS‐UPDRS III (p = 0.06). Aβ42 trended towards being higher in PD‐MCI compared to PD‐N (p = 0.06). pTau181 was higher in PD patients compared to Controls (p = 0.003) and in PD‐MCI compared to PD‐N (p = 0.02). Total Tau was not different between groups. pTyr20‐IRS‐1 was lower in PD compared to Controls (p = 0.03) and in PD‐MCI compared to PD‐N (p = 0.01) and decreased with increasing motor symptom severity by MDS‐UPDRS III (p = 0.008). The ratio pSer312/pTyr20 IRS‐1 (indicating insulin resistance) was higher in PD patients compared to Controls (p = 0.02) and in PD‐MCI and PD‐D compared to PD‐N (p = 0.01).ConclusionPD patients with cognitive impairment exhibited lower NEV levels of a‐synuclein and pTyr20‐IRS‐1 and higher levels of pTau181 than cognitively intact PD patients. Additionally, a‐synuclein and IRS‐1pTyr20 were associated with PD motor symptom severity. Plasma NEVs offer novel biomarkers for PD and indicate Alzheimer's pathology and insulin resistance partially underly cognitive impairment in the disease.
Sparse canonical correlation analysis reveals relationships between TDP‐43 within the entorhinal cortex and fractional anisotropy across widespread white matter tracts
Authors: Heywood Ashley , Schneider Julie A. , Bennett David A. , Arfanakis Konstantinos , Beg Mirza Faisal , Wang Lei 
Published: February 2022

AbstractBackgroundWhile research has focused on gray matter alterations in neurodegeneration, investigating the relationship between white matter and neuropathology allows for additional insight into disease effects on broad brain networks. TAR DNA‐binding protein 43 (TDP‐43), which has shown to be involved in various neurodegenerative disorders involving axonal damage including ALS, FTLD, and LATE, is associated with lower WM integrity. We used sparse canonical correlation analysis (SCCA) to explore the relationships between ante‐mortem WM integrity and post‐mortem TDP‐43.MethodDiffusion weighted images were gathered on a 1.5T scanner and processed using TORTOISE in order to calculate fractional anisotropy (FA) in a sample of 70 older adults from two longitudinal cohort studies, the Religious Orders Study and Rush Memory and Aging Project. We registered the white matter ROIs from the John’s Hopkins University (JHU) DTI atlas to the study‐specific template using ANTS. Average FA was computed for each ROI and was included in the SCCA. A semi‐quantitative rating of TDP‐43 severity was assessed in 5 regions. Disease burden in each region and average FA within 48 ROIs were inputs for the SCCA. A fused lasso penalty based on permutation testing was employed to promote sparsity.ResultThe 70 subjects were 91.10 (SD=6.08) years old at death with a median interval from MRI to death of 3.11 years (SD=1.45). Sixty‐four percent were female, and 36% had dementia at their last study visit prior to death. TDP pathology was present in 47% of individuals. SCCA produced one canonical variable (Cor=0.36) which identified one regional pathology variable (TDP‐43 within the entorhinal cortex; Feature weight =‐1.0) and six FA ROIs: pontine crossing tract (0.597), splenium of corpus callosum (0.531), right anterior limb of internal capsule (0.001), superior corona radiata (0.411), and bilateral anterior corona radiata (Right: 0.115 and Left: 0.422).ConclusionIdentified WM ROIs within the brainstem align with previous research within TDP‐43 related disorders, including those with motor neuron involvement such as FTLD‐U. Further, findings within bundles connecting parietal and temporal areas indicate the importance of TDP‐43 in broad brain networks which could relate to the deficits seen in memory and executive functions within FTLD and related disorders.
Unmet needs and health‐related quality of life for Alzheimer’s disease and related dementia caregivers during transition to long‐term care placement: A scoping review
Authors: Lee Kyungmi , Pickering Carolyn E 
Published: February 2022

AbstractBackgroundLong‐term care placement is a transition in the caregiving trajectory that may have a crucial health‐related quality of life implications for many Alzheimer’s diseases and related dementia family caregivers. The lack of knowledge related to family caregivers’ needs and their health‐related quality of life outcomes surrounding long‐term care placement represents a gap in the field as it limits our ability to support caregiving families with appropriate interventions effectively. The objective of this study is to identify experiences, unmet needs, and health‐related quality of life for caregivers of persons with Alzheimer’s disease and related dementia as the process of transitioning into long‐term care placement.MethodScoping review of published literature. Electronic searches of PubMed, PsycINFO, Scopus, and CINAHL databases were conducted using keywords related to Alzheimer’s disease or related dementia, family caregiver, unmet needs, and health‐related quality of life. The literature search was performed in July 2020, with no specified date limits. The Arksey and O’Malley methodological framework guided the review. Studies were screened independently for inclusion by two persons.Result19 studies were organized around three major categories. First, caregiver experiences of pre and post long‐term care placement (n = 18, 95%): contexts of long‐term care placement (n = 10, 53%), distress and emotional responses (n = 9, 47%), and changes in relationships and responsibilities (n = 9, 47%). Second, caregivers’ unmet needs of surrounding long‐term care placement (n = 7, 37%): emotional concerns and support (n = 4, 21%) and knowledge, and information (n = 5, 26%). Third, caregivers’ health‐related quality of life during transitioning long‐term care placement (n=6, 32%): assistance from professional care (n=2, 11%), and physical and mental health (n=5, 26%).ConclusionFamily caregivers are exposed to risk for adverse health outcomes even after the long‐term care placement of their care‐recipients. Family caregivers considering long‐term care placement need to be informed of what may change following long‐term care placement. We can suggest based on these findings that interventions may be to support caregivers during this transition with teaching skills, care planning, helping with conflict resolution, training in the use of communication strategies, and organizing services.
Development and evaluation of high‐resolution gray matter labels for the MIITRA atlas
Authors: Niaz Mohammad Rakeen , Wu Yingjuan , Ridwan Abdur Raquib , Qi Xiaoxiao , Bennett David A. , Arfanakis Konstantinos 
Published: February 2022

AbstractBackgroundHigh resolution gray matter labels were constructed for the Multichannel Illinois Institute of Technology & Rush university Aging (MIITRA) atlas based on manually edited gray matter labels of the older adults included in the atlas. The performance of the new labels in labeling the gray matter of a separate group of older adults was evaluated.MethodT1w images (400 images, 1mm isotropic) from the older adults included in the MIITRA atlas (50% male; 64.9‐98.9 age‐range; 54% white, 43% black) were processed with Freesurfer’s standard recon‐all pipeline, which segmented subcortical and cortical gray matter into 84 regions according to the Desikan Killiany atlas. The Freesurfer output for all images was manually edited. The ANTs‐derived transformations applied on individual T1w images to build the MIITRA T1w template were used to map the corresponding gray matter labels from raw space to exact physical locations in the final MIITRA space. The label in a 0.5mm isotropic voxel in MIITRA space was calculated using majority voting among all the labels that were mapped to that voxel. The performance of the MIITRA gray matter labels in segmentation of the gray matter of a separate group of 100 older adult individuals was evaluated in terms of label overlap, geometry, and dissimilarity when comparing the MIITRA labels warped to each individual’s space, to the respective manually edited reference labels.ResultExamples of the MIITRA gray matter labels and corresponding confidence maps are shown in Figure 1. The measures of overlap were generally high, with an average Dice coefficient of 0.82±0.10, Jaccard coefficient of 0.70±0.13 (Fig. 2), sensitivity of 0.77±0.13, and specificity of 0.89±0.09 (Fig. 3). There was a high correlation in label geometry both in terms of the average volume (correlation coefficient=0.997, p‐value<10‐10) and in terms of the average surface area (correlation coefficient=0.988, p‐value<10‐10) (Fig. 4). The values of dissimilarity were low, with an average volume error of 0.18±0.18 and an average Hausdorff distance of 8.69±8.78 (Fig. 5).ConclusionThe MIITRA gray matter labels, in combination with the high‐resolution T1w template of the atlas, allow segmentation of the gray matter of older adults that is in good agreement with the manually‐edited Freesurfer‐based segmentation.