bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterizing Caregiver Outcomes in a Culturally Diverse Sample
Authors: Meyer Oanh L. , Alto Raquel , Harvey Danielle J. , Tran Duyen , Luu San , Nguyen Rachel , Hinton Ladson 
Published: December 2022

AbstractBackgroundCaring for a family member with cognitive impairment is accompanied by challenges that place caregivers at risk for significant health problems. Yet the study of racially/ethnically diverse caregivers across the spectrum of Alzheimer’s disease and related dementias (from mild cognitive impairment: MCI to dementia) is understudied. In this study, we characterize caregiver stress and burden and examine their role on caregiver self‐rated health and depressive symptoms.MethodsWe enrolled 158 adults (non‐Hispanic White (NHW): 66%; Latino: 16%; Black: 9%; Asian: 8%) caring for a family member with MCI (35%) or dementia (65%). Approximately 37% were recruited from an Alzheimer’s Disease Research Center (ADRC) and 63% from the community. Caregivers completed demographic and psychosocial questionnaires online or by paper in English or Spanish. Linear regression models were used to assess associations between perceived stress and burden and caregiver outcomes (depressive symptoms and self‐rated health), controlling for caregiver demographics.ResultsBlack caregivers reported less burden (mean = 23.7) than NHW caregivers (mean = 35.4), p = .007. There was no difference in perceived stress by race/ethnicity (p = .2). Burden was higher (p = .001) for caregivers of individuals with dementia (mean = 35.9) than those with MCI (mean = 27.6), as was perceived stress (dementia caregivers: mean = 16.0; MCI caregivers: mean = 13.6), p = .03.Higher caregiver burden (p<.001) and perceived stress (p<.001) were positively associated with depressive symptoms. Caregiver burden was not associated with self‐rated health (p = .1); but higher perceived stress was associated with poorer self‐rated health (p<.001).ConclusionsCaregivers of persons with cognitive impairment suffer a substantial burden emotionally and physically. Our results indicate that dementia caregivers may have greater challenges in caring for their family member compared to those caring for someone in the early or milder stages of illness. The racial/ethnic difference may be due to the fact that NHW caregivers actually experience more burden in caregiving; an alternative explanation is that burden may not be felt or manifested in the same way in Black caregivers. Lastly, perceived stress is an important determinant of caregiver health and mental health outcomes. More research is needed to understand the variety of factors associated with caregiver outcomes and how they may differ across racial/ethnic groups.
Pathological consequences of microglial derived exosome (MDEs) cargo in vivo
Authors: Winston Charisse N. , Rissman Robert A. , Mante Michael N , Florio Jazmin N , Guzman Estefani N , Salehi Sahar N 
Published: December 2022

AbstractBackgroundExosome cargo proteins may serve as useful biomarkers for AD however very few studies have characterized the pathological consequences of exosome cargo in vivo. We determined that neuronally‐derived exosomes isolated from autopsy‐confirmed demented AD patients induced AD‐like neuropathology in the WT mouse CNS. Here, we extended our previous studies to investigate the neuropathological and behavioral consequences of plasma cargo proteins derived from microglia cells in vivo.MethodPlasma exosomes derived from autopsy‐confirmed, cognitively normal controls and demented AD patients were extracted, precipitated, and enriched against a microglial source (TMEM119, MDE) using magnetic immunocapture. MDEs were characterized by Nanosight and exosome marker profiling. MDEs were injected unilaterally into the brains of normal mouse CNS. Brains from MDE injected mice were probed for AD‐related proteins to confirm cargo transfer to recipient cells at 3 and 6 months post injection (mpi). Deficits in spatial learning and memory, gait stability and anxiety were assessed at 6 mpi.ResultPlasma MDEs demonstrate similar size distributions and shape to previously reported exosome preparations. MDEs were positive for exosome marker Flotilin‐1; microglial markers CD68 and IBA1 and negative for astrocyte marker, GLAST. At 3mpi, pathological forms of tau, as measured by PHF1 and MC1, and amyloid beta (Ab) as measured by 6E10, were observed the cortex and hippocampus of MDE injected mouse. At 6 mpi, we will determine the neuropathological behavioral consequence of MDE cargo in vivo.ConclusionMDEs can transfer AD‐related proteins to normal mouse CNS. The behavioral consequence of MDE cargo in vivo is currently being investigated.
Using a smart audio device, Tochie to deliver family messages in long‐term care
Authors: Hung Lillian , Yang Sophie , Lin Margaret , Chen Irene 
Published: December 2022

AbstractBackgroundLong‐term care (LTC) residents are more likely to experience loneliness, social isolation and have dementia (Garner et al., 2018; Hou & Ngo, 2021). The effects of isolation have been exacerbated by the COVID‐19 pandemic. While assistive technology has been a popular topic in gerontological health research, there have been limited findings on the experience of technology adoption in complex care environments such as LTC, and on family member and staff perspectives. “Tochie” is a smart audio device that allows family and significant others to remotely record and schedule messages, such as daily reminders or comforting audio recordings, to send to their loved ones in care settings. Our research explores the experiences of residents, families, and staff using the Tochie device in LTC.MethodWe applied qualitative descriptive design with interview and focus group methods. 10 residents, 9 family members, and 6 care staff from two long‐term care homes in British Columbia, Canada, participated in the study. Each resident was given a device to use with their family member for a four‐week intervention period. The research team checked in with family members and staff weekly via telephone and email to provide support and gather feedback. Pre‐ and post‐intervention focus groups and interviews were held via Zoom and phone correspondence to learn about participants’ experiences using Tochie. Thematic analysis was performed to identify themes.ResultFour common themes were identified to describe the experience of using Tochie in LTC: (a) Tochie as a means to facilitate emotional connection (b) Using Tochie in creative, personalized ways (c) Challenges and contextual considerations in LTC (d) Ideas for future developmentsConclusionThe COVID‐19 pandemic has provided us an opportunity to redefine and reconstruct what it means to “keep in touch” with loved ones in care settings. In our study, residents, families and staff highlighted the ways in which Tochie has enabled this connection and provided feedback on their challenges and device recommendations. This study explores the valuable perspectives of residents, their loved ones, and care staff in the use of assistive audio devices to inform product development and adoption into LTC.
Midlife engagement in cognitive activities and cognitive function in middle aged individuals at high risk for AD
Authors: Ravona‐Springer Ramit , Heymann Anthony , Moshier Erin , Yore Iska , Shamir Tamar , Soleimani Laili , Beeri Michal Schnaider 
Published: December 2022

AbstractBackgroundWe examined the cross‐sectional relationship of engagement in cognitive activities with cognitive function in cognitively normal middle‐aged (40‐65y) individuals enriched for high risk for Alzheimer’s disease (AD) due to a parental family history (FH+), and matched controls (FH‐), participants of the Israel Registry for Alzheimer’s Prevention (IRAP) study.MethodEngagement in cognitive activities by type and intensity was evaluated via the Florida Cognitive Activities Scale (FCAS) (score range 0–100), resulting in three scores: 1) FCAS‐Total, 2) FCAS‐Higher Cognitive (HC), capturing activities more cognitively demanding (e.g. playing chess) and 3) FCAS‐Frequent Activity (FA), capturing frequent activities (e.g. watching TV). A comprehensive neuropsychological battery yielded scores for four cognitive domains; executive functions, language, working memory and episodic memory. Global cognition was the mean of the four cognitive domains. Regression analysis adjusting for age, sex and education examined the relationship of each one‐point increase in the FCAS scores on cognitive function for the total sample.ResultThe study included 473 participants (FH+ = 374; FH‐ = 99) (Table 1). Participants' mean age was 54.9 (SD = 6.7) years (64.4% women) with 16.5 (SD = 3.1) years of education. The groups did not differ in sociodemographic, cognitive or FCAS characteristics. The FCAS‐Total score was associated with better global cognition (slope = 0.0150; p = 0.001), executive functions (slope = 0.0147; p = 0.005), language (slope = 0.0095; p = 0.0052) and working memory (slope = 0.0117; p = 0.0142). Higher FCAS‐HC score was associated with better global cognition (slope = 0.0221; p = 0.010), executive functions (slope = 0.0315; p = 0.001), language (slope = 0.0214; p = 0.0008) and working memory (slope = 0.0244; p = 0.006). FCAS‐FA was not associated with function in any of the cognitive domains. There were no associations between total cognitive activity nor its sub‐types with episodic memory.ConclusionHigher engagement in cognitive activities, specifically those requiring higher cognitive effort, is associated with better cognitive function already in midlife. This relationship was not detected for episodic memory, which is the domain most typically affected in the first stages of AD. The longitudinal phase of the IRAP study will reveal the underlying mechanisms and whether reduced engagement in cognitive activity is a risk factor or a very early indicator of incipient cognitive decline high AD risk adults.
Baseline and Longitudinal Ioflupane SPECT Findings in DLB and MCI‐LB
Authors: Boeve Bradley F. , Miyagawa Toji , Przybelski Scott A. , Min Paul H , Jordan Lennon , Lesnick Tim , Savica Rodolfo , Graff‐Radford Jonathan , Jones David T. , Botha Hugo , Ramanan Vijay K , Knopman David S. , Petersen Ronald C. , Graff‐Radford Neill R. , Day Gregory S , Fields Julie A. , Machulda Mary M. , Ferman Tanis J , Forsberg Leah K. , Diaz‐Galvan Patricia , Li Wentao , Christine Cliatt Brown J , Jack Clifford R. , Jain Manoj K. , Kantarci Kejal , Lowe Val J. 
Published: December 2022

AbstractBackgroundReduced striatal uptake on ioflupane SPECT is considered an indicative biomarker for Dementia with Lewy Bodies (DLB), and has been proposed as an indicative biomarker for Mild Cognitive Impairment with Lewy Bodies (MCI‐LB). Little data exists on the profile of uptake on key striatal regions of interest (ROIs) in DLB or MCI‐LB.MethodParticipants with DLB or MCI‐LB at baseline based on the presence of ≥2 core clinical DLB features, and ≥2 ioflupane SPECT scans performed approximately annually, were identified from the Mayo ADRC database. Minimum brain laterality z‐score values for the putamen (whole, anterior and posterior), caudate and striatum were determined using DaTQUANT 2 software. Baseline clinical and scan data was used for all analyses, and the annualized minimum putamen z‐change was determined on serial scans. The scan was considered abnormal if the minimum putamen z‐score was <‐0.98 based on clinicopathologic data.Result27 participants were included (21 DLB and 6 MCI‐LB, 96% male). Compared to MCI‐LB, DLB had a lower mean MoCA score and a trend toward a higher UPDRS score compared to MCI‐LB; there were no statistically significant differences in age, sex, onset age or duration of cognitive decline, or presence of other core DLB features. The majority (89%) had an abnormal scan at baseline. All ROI z‐scores showed the expected general trend of DLB<MCI‐LB, and the annualized z‐change was more negative in DLB, but none of the findings reached statistical significance.ConclusionThese findings suggest in MCI‐LB and DLB that 1) an abnormal ioflupane SPECT scan is frequently present at diagnosis, 2) z‐scores become more negative over time, and 3) the annualized z‐change is similar. Similar findings in larger cohorts would support the use of ioflupane SPECT as a biomarker in both MCI‐LB and DLB clinical trials.
NOVEL VIRTUAL REALITY‐ BASED METHOD FOR OBJECTIVE MEASUREMENT OF EMOTIONAL REACTIVITY IN PATIENTS WITH ALZHEIMER'S DISEASE
Authors: Ravona‐Springer Ramit , Wilf Meytal , Koren Or , Rosenblum Uri , Galor Noam , Lapid Michal , Plotnik Meir 
Published: December 2022

AbstractBackgroundDiminished emotional reactivity in cognitively normal (CN) older adults and in patients with Alzheimer's disease (AD) is associated with higher burden of neuropathology and predicts faster cognitive decline, stressing its potential to serve as a behavioral screening tool for individuals at high AD‐risk and for a more aggressive disease course. Its measurement is currently based on questionnaires which are prone to subjectivity biases. We present preliminary results of a study aimed to examine the feasibility of using autonomic nervous system (ANS) reactivity to emotional stimuli presented in a virtual reality (VR) environment, as an objective measurement tool of emotional reactivity. Specifically, we test the hypothesis that emotional reactivity, as expressed by galvanic skin response (GSR), will be reduced in patients with AD compared to CN individuals.MethodParticipants are patients with mild‐ moderate AD and cognitively normal age matched controls. Cognitive function is assessed via the Montreal Cognitive Assessment (MoCA) battery. Participants are exposed in the VR‐ environment to emotionally‐ laden stimuli (positive, neutral and aversive, 12 repetitions per stimulus type) while measuring GSR. Response weighted mean was calculated for each participant for each stimulus type. Non parametric group comparisons (AD vs. CN) were performed (U‐test) for each stimulus type separately (Bonferroni corrected).ResultSo far, 30 patients with AD and 21 CN individuals have been recruited. Participants' mean age is 75.6 years, 60.8 % females (Table 1). Patients with AD had lower scores on the MoCA (p<0.001), but did not differ from CN in demographic variables. VR‐based evaluation was well accepted by the participants with no adverse events. CN participants showed higher GSR reactivity as compared to AD patients for aversive stimuli (p<0.05) but not for neutral or positive stimuli (Figure 1).ConclusionGSR reactivity to emotional stimuli presented in the VR environment is a feasible method to study emotional reactivity in CN older adults and in participants with AD. GSR reactivity to aversive stimuli is reduced in AD participants compared to CN. These preliminary findings should be further established in larger populations while detecting the optimal type of stimulus required to differentiate between clinically distinguished cohorts.
Earlier Alzheimer's disease onset is associated with a shift of tau pathology towards brain hubs which facilitates tau spreading
Authors: Franzmeier Nicolai , Ewers Michael , Brendel Matthias , Biel Davina , Ossenkoppele Rik , Hager Paul , Steward Anna , Dewenter Anna , Rubinski Anna , Buerger Katharina , Janowitz Daniel , Binette Alexa Pichet , Smith Ruben , Strandberg Olof , Mattsson‐Carlgren Niklas , Dichgans Martin , Frontzkowski Lukas , Hansson Oskar 
Published: December 2022

AbstractBackgroundIn Alzheimer’s disease (AD), younger symptom onset is associated accelerated cognitive decline and tau spreading, yet the drivers of faster disease manifestation in patients with earlier symptom onset are unknown. Earlier symptom onset is associated with stronger tau pathology in fronto‐parietal regions which typically harbor globally connected hubs that are central for cognition. Since tau spreads across connected regions, globally connected hubs may accelerate tau spreading due to their large number of connections to other brain regions. Thus, we hypothesized that a pattern shift of tau pathology towards globally connected brain hubs may facilitate tau spreading and earlier symptom manifestation in AD.MethodWe included two independent samples with longitudinal Flortaucipir tau‐PET covering the AD spectrum (ADNI: n(controls/AD‐preclinical/AD‐symptomatic)=93/60/89, BioFINDER, n(controls/AD‐preclinical/AD‐symptomatic)=16/16/25). In addition, we included resting‐state fMRI from human connectome project participants (n=1000), applying a 200‐ROI brain atlas to obtain a global connectivity map for assessing brain hubs (Fig.1A‐D). Applying the same atlas to tau‐PET we transformed SUVRs to tau positivities using a pre‐established gaussian‐mixture modeling approach (Fig.1E‐F). By mapping tau‐PET positivities to the fMRI‐derived global connectivity map (Fig.1G‐L), we assessed the degree to which subject specific tau‐PET patterns were shifted towards globally connected hubs or non‐hubs, while adjusting for global tau levels. Using linear regression, we then tested whether a stronger shift of tau towards hubs was associated with earlier symptom manifestation and faster longitudinal tau accumulation.ResultIn symptomatic AD patients, younger age was associated with a stronger shift of tau‐PET towards globally connected brain hubs (p[ADNI/BiOFINDER]=0.024/0.018, Fig.2A&B), and with higher global connectivity of epicenters with highest tau pathology (p[ADNI/BiOFINDER]<0.001/0.001, Fig.2C&D). In symptomatic AD, younger age (p[ADNI/BiOFINDER]=0.009/0.001) and a stronger shift of tau‐PET towards hubs predicted faster subsequent tau accumulation (p[ADNI/BiOFINDER]=0.004/0.002), supporting the view that that hubs facilitate tau spreading (Fig.3). Further, a stronger shift of tau‐PET towards globally connected brain hubs mediated the association between younger age and faster tau accumulation in symptomatic AD patients (p[ADNI/BiOFINDER]=0.039/0.046).ConclusionYounger AD symptom onset is associated with stronger tau pathology in globally connected brain hubs, which facilitates faster tau spreading.
Antipsychotic prescriptions and neuropsychiatric symptoms (NPS) in nursing home (NH)residents with dementia: a comparison of pre‐ and during COVID pandemic.
Authors: McDermid Joanne , Khan Zunera , Sweetnam Adrienne , Ballard Clive G 
Published: December 2022

AbstractBackgroundThe COVID‐19 pandemic has put tremendous pressures on nursing homes, but there is limited direct data evaluating the impact on residents or prescribing practicesMethodAs part of our clinical trial programme in nursing homes we have baseline data from 971 residents across 69 nursing homes collected in 2016/17 prior to the pandemic, and from 747 participants across 149 nursing homes from the baseline assessment of our COIVD WHELD RCT collected in 2021/22. In both studies the frequency if antipsychotic prescriptions was recorded and the Neuropsychiatric Inventory Nursing Home version was completed.ResultsThe average age of residents (84.5 v 85.1) and gender balance (71%F v 69% F) was similar in both cohorts. In the current study 64% of participating nursing homes had experienced a COVID‐19 outbreak. There were fewer people with severe dementia in the COVID WHELD Cohort (6.7% v 23%). Antipsychotic usage was 55% higher in the COVID WHELD cohort compared to the original WHELD cohort (28% v 18%), with 25% of nursing homes having prescription rates >40%, but the rates of neuropsychiatric symptoms were similar in the 2 studies. To ensure that the results were not confounded by the lower number of people with severe dementia in the COVID WHELD cohort, a further comparison was undertaken for people with moderate/moderately severe dementia, with very similar results. We undertook an additional analysis comparing nursing homes above and below prescription rates of 20% (the pre‐COVID level of prescribing). Nursing homes with increased antipsychotic prescribing had significantly higher levels of overall neuropsychiatric symptoms on the NPI (p = 0.02), and significantly higher levels of agitation (p = 0.02) compared to nursing homes with lower prescribing rates. There were also 31% more staff sick days in the higher prescribing nursing homes.ConclusionThere is a substantial increase in antipsychotic prescriptions in 50% of nursing homes since the onset of the COVID‐19 pandemic, associated in those nursing homes with an increase in neuropsychiatric symptoms. This will need to be a major focus as we begin to move forward from the pandemic.
Increased pro‐inflammatory plasma markers are associated with a longitudinal decrease in left hippocampal volumes in MCI patients
Authors: Breese James , Nowell Joseph , Crook Harry , Edison Paul 
Published: December 2022

AbstractBackgroundApart from amyloid and tau, neuroinflammation plays a significant role in the Alzheimer’s disease (AD) pathogenesis. However, the role of blood bound pro‐inflammatory cytokines on neurodegeneration is still being debated. It is theorised that the activation of inflammation‐associated microglia in the CNS can oscillate through AD’s course, showing elevations in the early stages of AD progression [1]. This study aimed to establish the relationship between the presence of pro‐inflammatory markers and hippocampal volumes, in individuals with an AD diagnosis, late mild cognitive impairment (LMCI) and a cognitively normal control.Method281 participants were recruited from the AD Neuroimaging Initiative (ADNI; adni.loni.usc.edu) database. For each participant, left and right hippocampal volume values were calculated from the volumetric MRI at baseline and after 12 months follow up. 34 known pro‐inflammatory plasma biomarkers were measured at baseline and 12 months. Principal component analysis (PCA) was conducted on the pro‐inflammatory cytokine change. The change in each participant’s hippocampal volumes was correlated with the independent component‐1 of pro‐inflammatory cytokine change, in the AD, LMCI and control groups.ResultWe demonstrated a negative correlation between changes in left hippocampal volume and changes in the independent component‐1 for pro‐inflammatory cytokines in the LMCI group (r=‐0.245; p=0.011). No correlation was found in the change in left and right hippocampal volumes and the pro‐inflammatory markers in both the AD group, and in the cognitively normal control group.ConclusionThese results indicate that pro‐inflammatory markers can have a deleterious effect on hippocampal volume in individuals with LMCI – and are strongly linked to atrophy in this region. This suggests that peripheral inflammation could be a driving force of neurodegeneration in the early stages of AD’s trajectory. The lack of correlation in the AD patients may imply that once neuronal damage is triggered, a vicious cycle of neurodegeneration occurs, which is independent of peripheral cytokines. These findings suggest that therapeutics which target the pro‐inflammatory response early in AD’s progression trajectory could prevent AD’s progression.