bluuebunny/crossref_metadata_2025_split huggingface dataset:
The relationship between homocysteine, oxidative stress, and cognition in mild cognitive impairment
Authors: Wang RuoDing , Bawa Kritleen , Feng Vivian , Herrmann Nathan , Gallagher Damien , Black Sandra E. , Ramirez Joel , Graham Simon J , Oh Paul I. , Andreazza Ana C. , Kiss Alex , Swardfager Walter , Lanctôt Krista L. ,   Neuropsychopharmacology
Published: December 2021

AbstractBackgroundHomocysteine (Hcy) generates reactive oxygen species and has been associated with cardiovascular disease and impaired cognition. While the relationship between Hcy and cognition has been extensively studied in other disorders, it has not been well characterized in mild vascular cognitive impairment (mVCI). Due to Hcy’s effect on vasculature and increased oxidative stress burden, individuals with elevated Hcy may be at greater risk of developing vascular dementia (VaD). This study investigated the relationship between Hcy, oxidative stress, and cognition.MethodParticipants were mVCI patients enrolled in a cardiac rehabilitation program. Cognition was assessed via National Institute of Neurological Disorders and Stroke and the Canadian Stroke Network (NINDS‐CSN) recommended battery, and blood was analyzed for Hcy and glutathione S‐transferase (GST), which modulates reactive oxygen species. Statistical analyses were performed using linear regression models in SPSS 26.ResultThere are 26 participants (73% male, 69% Caucasian, mean (SD) age=68.1 (7.2), years of education=15.7 (3.3)) with cardiovascular risk factors (62% hypertensive, 65% dyslipidemia, 31% diabetic, BMI=29.8 (5.1)) enrolled in the study to date. Mean plasma Hcy concentration was 13.4 μmol/L, with 9 participants classified as elevated (≥15 μmol/L). In preliminary analyses, plasma Hcy (stand. β=0.09, p=0.65) did not significantly predict executive function (F(2,23)=0.77, p=0.47) or verbal memory (F(2,23) =1.62, p=0.22). Hcy (stand. β = 0.684, p=0.013) significantly predicted GST activity (F(2,11) = 4.542, p=0.013, adj. R2 = 0.353), with a medium effect size.ConclusionFindings suggest that increased Hcy may be associated with compensatory increased GST activity in mVCI. A larger sample size will allow further analysis of cognition with additional covariates in this at‐risk population with increased oxidative stress.
Type and frequency of social contacts associated with low mood before and during the COVID‐19 pandemic in older adults: I‐CONECT project
Authors: Wu Chao‐Yi , Mattek Nora , Fleming Nicole , Scavone Colton , Wild Katherine , Kaye Jeffrey A , Dodge Hiroko H 
Published: December 2021

AbstractBackgroundSocial isolation is a risk factor for dementia, but the underlying mechanism is not well understood. It is possible that lack of social contacts negatively affects emotional well‐being, which leads to cognitive decline. To shed light on this potential mediation mechanism, we examined changes in type and frequency of social contacts and their effects on mood using data collected before and during the COVID‐19 pandemic among socially isolated older adults aged 75 and older.MethodThe data come from an ongoing randomized controlled trial, the Internet‐Based Conversational Engagement Clinical Trial (I‐CONECT, ClinicalTirals.gov: NCT02871921). One hundred forty‐six participants (age=81.0±4.5, 71.9% women) who were in the trial both before and during the pandemic and whose data were available as of November of 2020 were included in the current analysis. Weekly health questionnaires administered on all participants regardless of treatment assignments were collected before and during the COVID‐19 pandemic. Low mood (“Blueness”) was self‐reported as feeling downhearted or blue for three or more days in the past week (YES/NO). Social contacts were self‐reported by amount of time they had interacted, with whom (family; friends; others), and via which modalities (in‐person; phone/video call; text/email).ResultA total of 4,774 weeks of survey data were analyzed (3,047 before COVID 19). The weekly average time spent in‐person, on phone/video call, and via text/email were 282, 113, and 44 minutes, respectively. During the COVID‐19 pandemic, participants on average spent 82 minutes less in total social contact per week (in‐person: reduced 123 minutes, video/call: increased 28 minutes, text/email: increased 13 minutes per week). Generalized estimating equation model revealed that in‐person family contact was associated with less blueness regardless of the pandemic (OR=0.91, p=0.04). There was a COVID*text/email time with friends interaction (OR=0.68, p=0.03), suggesting that during the COVID‐19 pandemic, an increase of 1 hour of texting/emailing with friends per week was associated with 32% decrease in experiencing blueness three or more days per week.ConclusionIn‐person family time is beneficial for mental health. While in‐person contacts become less frequent during the COVID‐19 pandemic, increased text/email time with friends becomes an alternative to maintain mental health for socially isolated older adults.
Distinct cognitive and neuropsychiatric features of amnestic dementia with comorbid Alzheimer’s and TDP‐43 proteinopathies
Authors: Kochheiser Makayla L , Kawles Allegra , Minogue Grace , Keszycki Rachel M. , Riley Michaela , Mao Qinwen , Flanagan Margaret E , Mesulam Marsel , Geula Changiz , Weintraub Sandra , Gefen Tamar 
Published: December 2021

AbstractBackgroundInclusions containing phosphorylated transactive response DNA‐binding protein 43 (TDP‐43) aggregates have been shown to coexist in ∼60% of cases with postmortem Alzheimer’s disease (AD) pathology, typically confined to mediotemporal brain regions. Together, these comorbid proteinopathies (TDP/AD) can lead to an amnestic dementia syndrome. The goal of this study was to identify, at early symptom onset, the shared versus distinct clinical, neuropsychological, and psychiatric features of cases with amnestic dementia and comorbid TDP/AD compared to those with AD as the primary neuropathologic diagnosis.MethodTwenty‐six individuals with amnestic impairment (Memory CDR=0.5 or 1) were identified from the Northwestern Alzheimer’s Disease Research Center and stratified by the presence of either postmortem AD pathology (N=13) or comorbid TDP/AD (N=13). Neuropsychological scores from tests of attention, language, executive functioning, visuoconstructional abilities, and mood/neuropsychiatric symptoms were analyzed from the NIA’s Uniform Data Set, version 2.0 or 3.0. Verbal (narrative and list‐learning) encoding and recall, and visual recall were included in memory assessment. In a subset of cases, a “visual‐to‐verbal” recall score was computed to determine the relative strength of visual memory compared to verbal. Student t‐tests with Welch’s correction were used to determine differences between groups.ResultThere were no differences in age at onset or death, frequency of APOE‐4 allele, or years of education between clinical groups. Preliminary findings showed no differences in attentional, executive, language, or visuoconstructional abilities. However, at disease onset, the TDP/AD group showed substantially higher frequency and severity of neuropsychiatric symptoms, including depression (p<0.005). Memory testing showed no group differences at the levels of learning/encoding verbal information; however, the TDP/AD group performed significantly worse in long‐term recall for narrative information (p<0.05). Qualitatively, the TDP/AD group showed stronger visual recall abilities (relative to verbal), whereas the AD group showed comparable performances in recall of material‐specific information.ConclusionPreliminary findings suggest that comorbid TDP/AD underlying amnestic impairments demonstrate a distinct cognitive and neuropsychiatric phenotype at disease onset. These findings help lay the groundwork for future in‐depth clinicopathologic studies and can help guide proper diagnosis of multiple etiology amnestic dementia.
Depressive symptoms in cognitively unimpaired older adults are associated with decreased structural and functional integrity in the limbic network
Authors: Touron Edelweiss , Moulinet Inès , Kuhn Elizabeth , Sherif Siya , Ourry Valentin , Landeau Brigitte , Mézenge Florence , Vivien Denis , Klimecki Olga M , Poisnel Géraldine , Marchant Natalie L , Chetelat Gaël ,   the Alzheimer’s Disease Neuroimaging Initiative,   the Medit‐Ageing Research Group
Published: December 2021

AbstractBackgroundSubclinical depressive symptoms are prevalent in older adults. They are associated with increased risk for both clinical depression and Alzheimer’s disease (AD), and may at least partly reflect early AD manifestations. However, the brain mechanisms underlying the relationship between depressive symptoms and AD remain to be elucidated. The aim of this study was to provide a comprehensive overview of the brain substrates of subclinical depressive symptoms in cognitively unimpaired older adults using complementary multimodal neuroimaging data in two independent cohorts.MethodWe selected 135 cognitively unimpaired older adults from the baseline data of the primary cohort Age‐Well, and 252 from the replication cohort ADNI. In both cohorts, subclinical depressive symptoms were assessed using the 15‐item version of the Geriatric Depression Scale (GDS); based on this scale, participants were classified as having depressive symptoms (DepS; GDS > 0) or not (NoDepS; GDS = 0). Voxelwise between‐group comparisons were performed to highlight differences in gray matter volume and amyloid deposition (both cohorts), as well as white matter integrity, brain perfusion (Age‐Well) and glucose metabolism (ADNI). Analyses were corrected for age, sex and education (and anxiety when available i.e. in Age‐Well) and thresholded at p<0.005.ResultOlder adults with subclinical depressive symptoms had significantly lower gray matter volume, perfusion and glucose metabolism in the hippocampus compared to participants without symptoms (Fig. 1). Glucose hypometabolism extended to the amygdala, precuneus/posterior cingulate and medial prefrontal cortex, insula, and temporoparietal cortex. Older adults with subclinical depressive symptoms also showed lower white matter integrity in the fornix and the posterior parts of the cingulum and corpus callosum. Brain amyloid deposition was not associated with the presence of subclinical depressive symptoms in either cohort.ConclusionThe presence of subclinical depressive symptoms in cognitively unimpaired older adults are associated with brain structural and functional changes in regions of the limbic network known to be particularly vulnerable to AD. Structural and functional changes overlapped in the hippocampus, indicating that deterioration in this region could underlie the relationship between depressive symptoms and AD while amyloid deposition does not appear to be involved at this stage.
Caspase activation and inflammation observed in the olfactory bulb of APOE4 transgenic mice
Authors: AlOtaibi Majed , Lessard‐Beaudoin Mélissa , Gonzales Laura M. , Chouinard‐Watkins Raphaël , Plourde Melanie , Calon Frederic , Graham Rona 
Published: December 2021

AbstractBackgroundAlzheimer disease (AD) is a chronic neurodegenerative disorder that affects millions of individuals worldwide. Olfactory dysfunction is a common symptom of several neurological disorders including AD. Studying the mechanisms underlying the olfactory dysfunction may lead to the discovery of biomarkers and/or treatments for neurodegenerative diseases. Objectives: To characterize the olfactory system in a murine model expressing a genetic risk factor for AD. We investigated olfactory brain region atrophy as well as caspase expression and tissue inflammation in the APOE4 mouse model of AD.MethodWe assessed the olfactory system in 12 month old wild type (WT) and APOE4 olfactory bulb (OB) for atrophy, caspase activation, markers of neurogenesis and inflammation. We used Western blotting, RT‐PCR and immunohistochemistry.ResultThere was a significant decrease in OB bulb weight in APOE4 mice compared to WT (p<0.01). There was a significant increase in the full length (p<0.05) form of caspase‐8 and in the p30 fragment (p<0.05) in the APOE4 OB. Moreover, a trend increase in caspase‐8 mRNA (p=0.08) and significant increase in caspase‐9 mRNA in the APOE4 OB vs. WT. Furthermore, there was a decrease in the expression of the mature neuronal marker NeuN in the OB of the APOE4 mice compared to WT. This was with both the 46kDa (p<0.05) and 48kDa (p<0.05) isoforms of NeuN. As atrophy was observed in the APOE4 OB we then assessed for inflammation. Using the IBA‐1 marker for microglia demonstrated that there was a significant increase in IBA‐1 expression (p<0.01) and a trend increased in IBA‐1 positive cells (p=0.054) in the APOE4 OB compared to WTConclusionThese data suggest that there are alterations in neurogenesis in the OB of human APOE4 transgenic mice in addition to inflammation. This corresponds well with what has been observed in human AD brain tissue. Caspase activities detected may play a role in the inflammation observed. Studying the olfactory system in the aging population may help to discover biomarkers in the early stages of AD
Person‐centered care for family caregivers of people living with dementia: Co‐designing an education program for the healthcare workforce
Authors: Parmar Jasneet , Anderson Sharon Dorothy , Pollard Cheryl , Duggleby Wendy , Charles Lesley , Poole Lisa , Leslie Myles , McGhan Gwen , Huhn Arlene , Sereda Sandy , Marion Cecelia , Tarnowski Glenda , Mah Jennifer , Melenberg Denise , Weir Carolyn , Pooler Charlotte , Maclaughlin Nora , Brémault‐Phillips Suzette 
Published: December 2021

AbstractBackgroundRecent research recommends the healthcare workforce receive competency‐based education to identify, assess, support and partner with family‐caregivers [FCGs} across the care trajectory.[1 2] Although the risk of FCG anxiety, burden, and loneliness to FCG’s wellbeing is widely documented, typically education has been targeted towards FCG’s to increase their care skills rather to educate healthcare providers to support FCG’s caregiving and wellbeing.[3]
ObjectivesWe will present the co‐design process used to create a competency‐based education program for the healthcare workforce that ensures a person‐centered focus on FCGs and introduce our Health Workforce Caregiver‐Centered Care Education focused on dementia. Co‐design is the act of creating with stakeholders to ensure the results meet their needs and are usable.Project DescriptionWe began by coining the concept “caregiver‐centered care,” defining it as: a collaborative working relationship between families and healthcare providers aimed at supporting FCGs in their caregiving role, decisions about services, care management, and advocacy [4 5]. From this definition, and working with multi‐level interdisciplinary stakeholders we designed[6] and validated[7] a Caregiver‐Centered Care Competency Framework in a Modified Delphi Process. Stakeholders (n= 101) including FCGs, health providers, policy makers, community organizations, research team, script writer, and educational designers then used effective practices for dementia education for the health workforce [8‐11] to co‐design the first or ‘foundational’ level of a Caregiver Centered Care education program.ResultsTeaching and learning resources include six competency‐aligned educational modules with videos and interactive exercises that encourage reflection. With the COVID‐19 pandemic, we moved the education online (caregivercare.ca). In the first two months online, November 9, 2020‐January 9, 2021, 352 healthcare providers completed the education. To date, learners’ qualitative evaluations have been positive, “Very good information for professionals working with caregivers; especially relevant to homecare, geriatricians, allied health, and others working within the Seniors’ Health realm. Engaging format that really evokes empathy for caregivers.”DiscussionWe continue to use mixed methods to evaluate the Caregiver‐Centered Care Education, for acceptability and effectiveness, in five care contexts (primary, acute, home, supportive living, long‐term care).ConclusionWe expect that our education will support caregiver‐centered care in all settings providing dementia‐related care.
Person‐centered care for family caregivers of people living with dementia: Evaluating an education program for the healthcare workforce
Authors: Parmar Jasneet 
Published: December 2021

AbstractBackgroundWhile family caregivers[FCGs] provide over 90% of care for people with dementia[1 2] most members of the healthcare workforce do not meaningfully involve FCGs as partners in care[3 4] or support FCGs in maintaining their own wellbeing. Recent research recommends the healthcare workforce receive competency‐based education to identify, assess, support and partner with FCGs across the care trajectory.[5 6] A multi‐level interdisciplinary team (n=101) co‐designed competency‐based person‐centered education for the health workforce. It is offered free online (caregivercare.ca)ObjectivesReport on a mixed methods evaluation of a person‐centered competency‐based education program for the healthcare workforce.Project descriptionTo create the program we began by coining the concept “caregiver‐centered care,” defining it as: a collaborative working relationship between families and healthcare providers aimed at supporting FCGs in their caregiving role, decisions about services, care management, and advocacy [7 8]. From this definition, multi‐level, interdisciplinary stakeholders including FCGs (n=101) co‐designed a first or ‘foundational’ level of a Caregiver‐Centered Care education program. Teaching and learning resources include six competency‐aligned educational modules with videos and interactive exercises that encourage reflection.MethodsThe Kirkpatrick Barr[9 10] health workforce training evaluation framework underpinned our mixed methods evaluation design. We used the Student Satisfaction with Education Scale to measure participant’s reaction to the education (Level 1) and the Caregiver‐Centered Care Knowledge Assessment Test [CKAT] to assess changes in learner’s knowledge and confidence to work with FCGs (Level 2).ResultsIn the first two months 352 healthcare providers completed the education through caregivercare.ca. Learners were satisfied with the overall quality of education (Mean 4.69 (SD=.6) Median 5). Student’s paired samples T‐test indicates pre‐post education changes in knowledge and confidence to work with FCGs were significant. Pre (M=37.8, Sd=7.6) to post (M=47.2, SD=3.5) t (125) = ‐14.39, p<.0005 (two‐tailed). Qualitative results derived from open responses mirrored the quantitative results.DiscussionEducating the health workforce is a population health approach to address known gaps in supporting and working with FCGs across the care trajectory[2 3 11].ConclusionThe Care‐Giver Centered Care education provides a foundation for educating healthcare providers working with FCGs to provide person‐centered care to FCGs.
Another side of the coin: Primary progressive aphasia in Chinese language
Authors: Tee Boon Lead , Tempini Maria Luisa Gorno , Chen Ta‐Fu , Lo Raymond Y. , Wang Pei‐Ning , Chan Andrew LT , Chen Lorinda Li‐Ying Kwan , Wong Adrian , Yan Connie TY , Tsoh Joshua , Lu Chien Jung 
Published: December 2021

AbstractBackgroundPrimary Progressive Aphasia (PPA) is a neurodegenerative syndrome that presents with speech and language impairments and is generally classified into three variants: semantic (svPPA), nonfluent/ agrammatic (nfvPPA), and logopenic variants (lvPPA). Current understanding of PPA has been mostly derived from English language patients. Expanding PPA research into non‐English languages encourages language‐specific linguistic‐adapted assessments and enriches our knowledge in linguistic features distinct from English language. This presentation focuses on three Chinese linguistic features that differ from English language: lexical tones, classifier, and logographic script. Chinese is a tonal and classifier language in which tones are lexically contrastive, and classifiers are obligatory to quantify nouns numerally. It also adopts logographic script that has complex visuospatial configurations and weak grapheme‐phoneme correspondence.MethodThe CLAP (Chinese LanguageAssessment for PPA) battery is designed to characterize the neurolinguistics features of Chinese speaking PPA individuals. In CLAP classifier task, participants are asked to spontaneously produce classifiers specific to numerous nouns and presented with multiple choices when failed. To evaluate Chinese writing skills, participants are tasked with dictating 60 Chinese characters of varying lexicality, character frequency, and stroke number. The motor speech function is assessed by multiple repetitions of Chinese characters that differ in articulation places, manners, and tones.ResultsThe CLAP project enrolled 20 controls and 33 PPA individuals (7 nfvPPA, 10 svPPA, and 16 lvPPA). In classifier task, svPPA and lvPPA scored lower (p<0.01), though lvPPA were more responsive to choices than svPPA (p<0.001). The classifier score significantly correlated with volumetric changes over the left middle, inferior temporal, and fusiform gyri, brain regions typically associated with semantic functions. For orthographic dictation task, all three PPA variants performed worse than controls (p<0.001), and distinctive dysgraphia phenotypes were noted in each variant (svPPA: phonological plausible and perseveration errors; nfvPPA: motoric, radical and morphemic errors; lvPPA: visual and stroke errors, P<0.001). In motor speech task, nfvPPA showed lower performance when tasked with repeating characters that vary in articulation places and tones (p=0.018, p<0.001) but not in articulation manners (p=0.076).ConclusionThe clinical features and assessment strategies for PPA syndrome may vary across languages and should ideally be tailored linguistically.