bluuebunny/crossref_metadata_2025_split huggingface dataset:
STRUCTURAL BRAIN CHANGES IN LATE ONSET DEPRESSION
Authors: Ribeiz Salma Rose Imanari , Duran Fabio L.S. , da Costa Daniele Lima , Alves Tania Correa de Toledo Ferraz , Filho Geraldo Busatto 
Published: December 2023

AbstractBackgroundStructural brain changes in grey matter in late‐life depression (LLD) remains an intriguing area of research. Furthermore, late‐onset depression (LOD) has been frequently associated with general medical comorbidities, cognitive deficits and structural abnormalities of the brain. This magnetic resonance imaging (MRI) study compares the grey matter volume of elderly people with and without major depression (DSM‐IV‐TR criteria), as well LOD, early onset depression (EOD) and controls.MethodThe sample consisted of elders with and without depression from community. Brain MRI scans were processed using statistical parametric mapping and voxel‐based morphometry.ResultSixty three elders with depression and 24 controls were enrolled. Demographic characteristics were analyzed and sex showed a statistically significant difference (p = 0.001) between the groups, with males representing 17.5% of the patient sample and 54.2% of the control sample. Furthermore, MMSE and CAMCOG showed a statistically significant difference between groups (p<0.0001 for both tests), with the control group performing better. Although we excluded cases of patients with below‐expected performance according to the neuropsychological assessment, it is likely that this cognitive impairment presented by the patient group is secondary to major depressive disorder. We did not find a significant volumetric difference between depressed and control group (CG). We used the age of onset of depression as another way of classifying the patient sample and compared it with the control group regarding key demographic and clinical characteristics. Gender was statistically significant different between groups, however there were only 2 male subjects in the EOD group, making it not possible to control the analysis by gender. Compared to the CG (n = 24), the LOD group (n = 32) showed a statistically significant volumetric reduction with correction for multiple comparisons in the right thalamus (464 voxels; peak xyz coordinates = 14 ‐10 16; Z = 4, 62; p‐FWEcorr = 0.052) when using the whole brain for multiple comparisons.ConclusionOur findings support the use of regional brain atrophy as a tool to better understand LOD.
The Association Between Street Network Accessibility and Cognitive Impairment
Authors: Zied Eman , Wu Yu‐Tzu , Matthews Fiona E 
Published: December 2023

AbstractBackgroundAccess to different amenities has been hypothesised to reduce the risk of cognitive impairment in older adults. Literature in urban planning shows that a well‐connected street network enables access to amenities, however, the role of street network accessibility has not been studied extensively in relation to cognitive function. The aim of this study is to investigate the cross‐sectional relationship between street network accessibility and cognitive impairment in older people in England, UK.MethodThe baseline data from the Cognitive Function and Ageing Study (CFAS) II (2008‐2011), a cohort study of people aged 65+ across three areas in England, was used (N = 7485) excluding 144 housebound participants. Cognitive impairment was defined by the Mini Mental State Exam (MMSE) score: mild‐severe (MMSE<26) and moderate‐severe (MMSE<21). Using Geographical Information System (GIS) data, proximity to a main road was represented by betweenness centrality (shortest routes corresponding to high potential of through movement) of the street network, using normalised angular choice (NACH ‐ range of 0‐1.5, with 0.9+ meaning a main road). Mean NACH was calculated within 300m walk of participants’ postcode centroid and categorised into tertiles (low = NACH<0.8, medium = NACH 0.8‐0.9, high = NACH>0.9). Logistic regression was used to investigate the relationship between proximity to a main road, the risk of mild‐severe and moderate‐severe cognitive impairment adjusting for age, sex, education, and area deprivation.ResultThe prevalence was 24% for mild‐severe cognitive impairment and 7.3% for moderate‐severe cognitive impairment. Compared to those living at low proximity from a main road, those who lived at medium (OR 0.817 95% CI [0.716, 0.932]) and high proximity (OR 0.756 95% CI [0.662, 0.863]) had lower risk of mild‐severe cognitive impairment. The adjusted associations remained similar (OR 0.771 95% CI [0.671, 0.886] for medium proximity, OR 0.755 95% CI [0.656, 0.869] for high proximity). Proximity to a main road was not associated with moderate‐severe cognitive impairment.ConclusionThe results suggest evidence for the role of proximity to a main road in reducing the risk of mild‐severe cognitive impairment in non‐housebound individuals, but not moderate‐severe cognitive impairment. More research is needed on other aspects of street network accessibility.
Characterizing PRN Use of Psychotropic Medications for Acute Agitation in Canadian LTC Residents With Dementia Before and During COVID‐19
Authors: Wang Janet Hui Jue , Kusumo Raphael , Kiss Alex , Tennen Gayla Beth , Marotta Giovanni , Viaje Shirley , Lanctôt Krista L. 
Published: December 2023

AbstractBackgroundAgitation is a prevalent and disabling neuropsychiatric symptom of dementia that comprises a constellation of behaviours involving excessive motor activity, physical aggression, and verbal aggression. Pro re nata (PRN) injections of antipsychotics and benzodiazepines can be administered for severe acute agitation, but best practices surrounding their use remain poorly characterized. The aim of this study was to compare the frequency of use of injectable PRN haloperidol, olanzapine, and lorazepam for acute agitation in Canadian long‐term care (LTC) residents with dementia before and during the COVID‐19 pandemic.MethodsA retrospective chart review was conducted for patients from two Canadian LTC facilities who had orders for PRN haloperidol, olanzapine, or lorazepam between January 1, 2018–May 1, 2019 (i.e. pre‐COVID‐19) and January 1, 2020–May 1, 2021 (i.e. COVID‐19). We reviewed electronic medical records to document PRN administrations of these psychotropic medications and collect data on age, sex, dementia diagnosis, days of observation, care type, medical history, and concomitant medications. Descriptive statistics and multivariate logistic and Poisson regression models were used to analyze the data.ResultsOf the 250 residents with dementia included, 45 of 103 (44%) people in the pre‐COVID‐19 period and 85 of 147 (58%) people in the COVID‐19 period with standing orders for injectable PRN haloperidol, olanzapine, or lorazepam received ≥1 injections of their prescribed medication. Haloperidol was the most frequently used agent (74% pre‐COVID‐19 and 81% during COVID‐19) and excessive motor activity (85% and 80%) was the most common indication for use in both time periods. Residents in the COVID‐19 period were two times more likely to receive PRN injections compared with those in the pre‐COVID‐19 period (OR = 1.96; 95% CI = 1.15‐3.34; p = 0.01). Count of injections per patient was not significantly different between the two time periods (IRR = 1.35; 95% CI = 0.78‐2.33; p = 0.3).ConclusionOur results contribute to the mounting evidence that agitation worsened in LTC residents with dementia during the pandemic and add to the limited existing literature on actual use of PRN psychotropic medications for acute agitation. The increased need for PRN rescue medications may be an indirect consequence of COVID‐19 restrictions, particularly the restrictions on socialization.
A longitudinal analysis of the frontotemporal dementia rating scale as a sensitive measure of disease trajectory
Authors: Ferry‐Bolder Eve , Bouzigues Arabella , Foster Phoebe H , Peakman Georgia , Greaves Caroline V , Convery Rhian S , van Swieten John C. , Jiskoot Lize C. , Seelaar Harro , Moreno Fermin , Sanchez‐Valle Raquel , Laforce Robert , Graff Caroline , Masellis Mario , Tartaglia Carmela , Rowe James B. , Borroni Barbara , Finger Elizabeth , Synofzik Matthis , Galimberti Daniela , Vandenberghe Rik , de Mendonça Alexandre , Butler Christopher , Gerhard Alexander , Ducharme Simon , Ber Isabelle Le , Tiraboschi Pietro , Santana Isabel , Pasquier Florence , Levin Johannes , Otto Markus , Sorbi Sandro , Rohrer Jonathan D. , Russell Lucy L. ,   Genetic FTD Initiative (GENFI)
Published: December 2023

AbstractBackgroundPrevious research in genetic frontotemporal dementia (FTD) has suggested that the FTD Rating Scale (FRS) may be a more sensitive measure of disease severity than the Clinical Dementia Rating scale plus National Alzheimer’s Coordinating Centre Frontotemporal Lobar Degeneration score (CDR+NACC FTLD). This study aims to assess the potential of longitudinal measurement of the FRS to track disease trajectory, using data from the Genetic FTD Initiative (GENFI).Method119 mutation negative controls and 270 mutation carriers (52 MAPT, 107 GRN, 111 C9orf72) from the GENFI cohort completed the FRS at their baseline and follow‐up visits. Participants were grouped by disease severity according to their CDR+NACC FTLD global score at the baseline visit, which generated five mutation groups: asymptomatic (0), prodromal (0.5), mild (1), moderate (2), and severe (3), plus the control group. Annualised FRS change scores were generated for each participant (mean interval between visits = 1.3 years, standard deviation = 0.6). For each of the genetic groups, correlations with annualised change score for the MMSE and the CDR+NACC FTLD SOB were performed.ResultAs disease becomes more severe, the annualised change in FRS was larger, peaking at the moderate stage: asymptomatic 0.6 (8.0), prodromal ‐5.1, (23.2), mild ‐7.2 (24.8), moderate ‐7.8 (11.6), severe ‐1.8 (8.2). The moderate group was significantly different from controls (p = 0.018) and the asymptomatic group (p = 0.030). The annualised change in FRS negatively correlated with the annualised change in CDR+NACC FTLD Sum of Boxes (Rho = ‐0.4, p<0.001) and positively correlated with the annualised change in MMSE (Rho = 0.3, p = 0.001) in GRN MCs but not in MAPT or C9orf72.ConclusionThe FRS shows promise as a sensitive clinical outcome measure, but only at certain stages of the disease. More sophisticated modelling utilising the wider GENFI cohort will help to establish the real potential for use in clinical settings.
The relationship between telomere length and neuropsychological test performance in a diverse sample of Wisconsin Alzheimer’s Disease Research Center participants
Authors: McLester‐Davis Lauren W. Y. , James Taryn T. , Norton Derek L. , Salazar Hector , Papale Ligia A , Alisch Reid S , Hogan Kirk J. , Jeffers Beckie , Gooding Diane C. , Lewis Jordan P. , Roy Trevor R , Drury Stacy S , Gleason Carey E. , Zuelsdorff Megan 
Published: December 2023

AbstractBackgroundAge is the most significant predictor of Alzheimer’s disease and related dementias (ADRD). Biological age, in contrast to chronological age, is modifiable – shaped by environmental and social factors which contribute to the functional declines observed in aging. Accelerated biological aging has been observed in historically underrepresented populations in ADRD research who are at highest risk for developing ADRD. Telomere length (TL) is a marker of biological age and empirically associated with cognitive aging. However, this association has not been investigated in historically underrepresented populations such as American Indians / Alaska Natives (AI/AN). This study reports on the utility of TL to predict cognitive performance in a sample of middle‐aged and older adults from Wisconsin communities historically underrepresented in ADRD research.MethodThe Wisconsin Alzheimer’s Disease Research Center’s (WADRC) Inclusion of Underrepresented Groups Core engages AI/AN, Blacks / African Americans (B/AA), and participants of multi‐race and ethnicity identities through community based participatory research practices. A sample (n = 188) identifying their race as AI/AN or B/AA were included if they provided whole blood and completed the Rey Auditory Verbal Learning Test (RAVLT, Trials 1‐5) and the Trails Making Test (TMT, A and B times) for verbal learning and executive functioning, respectively. DNA was extracted from whole blood and analyzed with monochrome multiplex quantitative polymerase chain reaction for TL. Multivariable linear regression analyses tested relationships between TL and cognitive test performance.ResultThe participants (mean age = 60.88 ±9.06) were majority female, with 79.26% B/AA and 12.77% AI/AN (Table 1). In bivariate analyses, TL significantly correlated with all outcomes: longer telomeres correlated with better verbal learning and executive functioning performance (Figure 1A‐C). In multivariable regression models, TL significantly predicted cognitive performance for all outcomes independent of participant sex, race, age, and cognitive status (Table 2).ConclusionThese findings suggest that TL is a strong predictor of cognitive performance for historically underrepresented populations, offering potential opportunities for screening of accelerated biological aging and interventions. The community‐led research at the WADRC makes this analysis the first of its kind to include AI/AN participants. Future ADRD research should consider behavioral and socioeconomic interventions shown to modify biological aging.
Comparison of Anthropometry Measures between Urban and Rural Aging Cohort in India
Authors: M Amitha C , L Abhishek M , Stezin Albert , Hameed Shafeeq K Shahul , Malo Palash Kumar , M Divya N , Partha Ajith , Menon Meenakshi , Narayanasamy Rajitha , R Meghana , Velavarajan Goutham , Diwakar Latha , Kommaddi Reddy Peera , Singh Sadhana , Arvind Prathima , HS Sunitha , Sundarakumar Jonas S. , Issac Thomas Gregor 
Published: December 2023

AbstractBackgroundAnthropometric characteristics of individuals and populations are simple and strong predictors of nutrition, future ill health, functional impairment and mortality (WHO‐TRS 854). Our objective was to observe differences in various anthropometric measurements between urban and rural aging participants in India. The Tata Longitudinal Study of Aging (TLSA) and Srinivaspura Aging Neurosenescence and COGnition (SANSCOG) study are ongoing, large‐scale, prospective, population‐based cohort studies in urban and rural India respectively (Sundarakumar J et.al 2020).MethodA cross‐sectional comparative study that included 1089 urban and 4913 rural participants of both the genders aged 45 years and above were selected from ongoing TLSA and SANSCOG studies. Anthropometric measurements such as Height, Weight, Waist circumference, Hip circumference, Waist‐Hip ratio, Waist‐Height ratio, Body fat and Visceral fat of both the groups were obtained through a structured clinical protocol by trained physicians and nurses and Tanita body composition analyzer. Chi‐square and Mann Whitney U tests were used to analyze the results as the data was not normally distributed.ResultUrban participants were older and had more years of education. The proportion of males and females did not differ between both cohorts as shown in Table 1. Mann‐Whitney U test was conducted to determine whether there was a difference in various anthropometric measures between Urban and Rural cohorts. The results indicate significant difference between the groups as shown in Table 2.ConclusionUrban participants were observed to have comparatively high range of anthropometric measurements compared to rural participants. This difference may be because mean age of rural cohort was less where they mostly engage in more physically demanding occupation such as farming while their urban counterparts were elder and may engage in sedentary occupation.
Investigating how telephone‐based mindfulness training impacts family conflict and communication for rural African American dementia caregivers
Authors: Shafer Jennifer Suzanne , Harr Elondra , Roth Isabel , Faurot Kim 
Published: December 2023

AbstractBackgroundOlder African Americans (AA) are disproportionately affected by Alzheimer’s disease and related dementias (ADRD). In turn, AA ADRD caregivers are more likely to provide in‐home care while being less likely to use respite services as compared to White caregivers. Caregiving for people with ADRD is associated with considerable physical, financial, and emotional strain (Alzheimer’s Association, 2022). Mindfulness‐based interventions (MBI) can be effective at addressing these issues for ADRD caregivers and have been found to be culturally acceptable for AA caregivers (Woods‐Giscombé et al., 2014). However, few studies have tested targeted MBI on rural AA caregivers. As part of a broader study, we investigated the effects of a telephone‐delivered MBI on AA ADRD caregiver burden and relevant secondary outcomes for both caregiving team members. The purpose of this study is to explore how mindfulness training impacts family conflict within the informal caregiving team.MethodPrimary caregivers and care partners of people with dementia participated in an eight‐week MBSR training program consisting of eight telephone‐delivered, instructor‐led classes and one virtual retreat. Post‐participation interviews with study participants (n = 51) were analyzed using Atlas.ti to assign descriptive meaning to sections of the data. After all codes were finalized, a detailed codebook was created, which included each code, its definition, and an example quote, along with any comments.ResultOur analysis revealed four key themes illustrating how the mindfulness intervention served to positively impact family conflict and communication among participating caregivers. Mindfulness training: 1) is helpful in resolving present family conflict; 2) provides tools for future conflict resolution; 3) helps the caregiver feel more present/in control despite family conflict; and 4) enriches already positive family connections.ConclusionNearly all caregivers described the intervention as being helpful in resolving current family conflict, and those caregivers who did not endorse present family conflict stated that the mindfulness training provided tools for alleviating future conflict should it occur. Most caregivers reported that the intervention helped them to feel more present and better able to work through conflict when family miscommunication did occur. Similarly, caregivers confirmed that mindfulness training acted to reinforce already positive family connections.
The Alzheimer multifactorial therapeutic agent E2F4DN prevents long‐term potentiation and cognitive loss and improves neuronal survival in homozygous 5xFAD mice
Authors: Sanchez‐Puelles Crisitna , Fraj Alberto , Cano‐Daganzo Vanesa , Garrido‐García Alberto , Perea Gertrudis , Frade Jose María 
Published: December 2023

AbstractBackgroundDespite many decades of work, we still lack effective therapies against Alzheimer’s disease (AD), likely due to its complex etiology, which requires a multifactorial therapeutic approach. Among the variety of proposed etiological factors, synaptic failure has proof to be an early hallmarks of AD (Nat. Neurosci. 2016;19:443‐453), which precedes neuronal‐death (J. Neurosci. 2006;26:10129‐10140). We have recently shown, using both transgenic mice and gene therapy, that E2F4 is a multifactorial therapeutic target against AD (Neurotherapeutics 2021;18:2484‐2503, Mol. Neurobiol. 2022;59:3016‐3039), likely due to its homeostatic function (Int. J. Mol. Sci. 2022;23:12093). The phosphorylation of two conserved Thr residues of E2F4 is necessary to induce cognitive loss in AD (Neurotherapeutics 2021;18:2484‐2503). Therefore, we have developed a novel therapy consisting in neuronal expression of a dominant negative form of E2F4 (E2F4DN), which cannot be phosphorylated in the conserved Thr residues (Neurotherapeutics 2021;18:2484‐2503, Mol. Neurobiol. 2022;59:3016‐3039). In this work we wanted to verify whether the expression of E2F4DN could correct AD‐associated synaptic dysfunction and neuronal loss in 5xFAD mice, a known mouse model of AD.MethodWe expressed E2F4DN (intravenous administration of AAV‐E2F4DN) in 6 weeks old control and homozygous 5xFAD mice, and stereological, electrophysiological and behavioral studies were performed at 6 months. Cell counting was achieved by unbiased stereology in the CA1 hippocampal region. Cognition was analyzed through novel‐object location and contextual fear conditioning test. Synaptic function (basal synaptic transmission, presynaptic function and long‐term potentiation (LTP)) were measured by electrophysiological recordings of field excitatory postsynaptic potentials in hippocampal CA3‐CA1 synapses. Afterwards, the mechanism underlying memory recovery was evaluated analyzing protein levels of different subunits of the synaptic receptors AMPA and NMDA.ResultE2F4DN expression in neurons prevents neuronal death in the hippocampus (CA1) of homozygous 5xFAD mice, reaching similar values of cell number and CA1 volume to those observed in control mice. Moreover, E2F4DN prevents LTP loss leading to cognitive improvement, as 5xFAD mice treated with our therapy present a noticeable improvement hippocampal‐dependent memory. This effect correlates with the increase of key LTP regulators.ConclusionE2F4‐Based Gene Therapy improves neuronal survival, LTP and cognition, being a safe multifactorial approach for AD treatment.
Acoustic stimulation during sleep predicts long‐lasting increases in memory performance and beneficial amyloid response in older adults
Authors: Wunderlin Marina , Zeller Céline J. , Teunissen Charlotte E. , Nissen Christoph , Klöppel Stefan , Züst Marc Alain 
Published: December 2023

AbstractBackgroundPhase‐locked acoustic stimulation (PLAS) during slow wave sleep (SWS) is able to boost SWS and – as a downstream effect – improve sleep‐dependent memory consolidation. Due to an assumed bi‐directional link between SWS disturbances and memory decline in aging, older adults might benefit most from interventions targeting SWS improvements.MethodHere, 32 healthy older adults (mean age: 68.9) were allocated to an intervention or control group and completed a three‐night protocol with either real‐PLAS (intervention group) or sham‐PLAS (control group), preceded by a baseline night with sham‐PLAS and an adaptation night. Memory was assessed across the intervention and at a one‐week and three‐months follow up.ResultPLAS consistently induced an entrainment of slow oscillations (SOs) with stimulation‐locked increases in spectral‐power bands associated with sleep (SO, delta, and spindle power) as well as a global increase of 24% in the number of SO‐coupled spindles, a proposed mechanism for memory consolidation. The individual magnitude of the PLAS‐induced increases in spectral‐power bands and SO/spindle coupling strength predicted memory performance across the intervention and up to three months post intervention in a dose‐dependent manner. PLAS‐induced increases in memory performance were further associated with a direct beneficial change in plasma amyloid levels. Importantly, all results were exclusive to the intervention group.ConclusionWe demonstrate for the first time that PLAS is associated with both long‐lasting benefits in memory and metabolite clearance in older adults, rendering PLAS a promising tool for the treatment of cognitive decline.