bluuebunny/crossref_metadata_2025_split huggingface dataset:
Retinal microvasculature and neurodegenerative changes in males vs females with Alzheimer’s disease: A case‐control study
Authors: Mirzania Delaram , Thompson Atalie C. , Robbins Cason B. , Soundararajan Srinath , Liu Andy , Johnson Kim , Grewal Dilraj S. , Fekrat Sharon 
Published: February 2022

AbstractBackgroundWomen comprise two‐thirds of people living with AD, regardless of age and ethnicity. Retinal imaging is being increasingly investigated as a potential non‐invasive method to understand neuropathological and microvascular changes in AD. The purpose of this study was to evaluate differences among males and females in the superficial capillary plexus (SCP) of the retinal microvasculature in patients with Alzheimer’s disease (AD) compared to age‐matched cognitively healthy controls.MethodProspective cross‐sectional study of participants ³50 years of age with a diagnosis of AD compared to cognitively healthy controls who underwent optical coherence tomography OCT angiography (OCTA). The foveal avascular zone area (FAZ) and vessel density (VD) and perfusion density (PD) in the 3 and 6‐mm circle and ring using EDTRS overlay were calculated.ResultTwo hundred and two eyes (101 cases, 101 controls) were included. No significant sex differences were found in the AD or control cohorts in regard to VD or PD. Central subfield thickness (CST) and FAZ area were not different between male and female AD. Among controls, males had a thicker CST (p < 0.001) and smaller FAZ area (P=0.003). Retinal nerve fiber layer (p > 0.05) and ganglion cell layer (p=0.054) thicknesses were similar among male AD, female AD, and controls.ConclusionThere may be a loss of the physiologic sex‐related differences in retinal structure and microvasculature in AD compared to controls. Further studies are needed to elucidate the pathophysiological basis for these findings.
Amyloid and tau PET in a middle‐aged, racially and ethnically diverse, community‐based cohort
Authors: Lao Patrick J. , Berroa Joncarlos , Benavides Andrea , Tejeda Emely , Shouel Heather , Igwe Kay , Maas Benjamin , Schupf Nicole , Mayeux Richard , Manly Jennifer J. , Brickman Adam M. 
Published: February 2022

AbstractBackgroundAlzheimer’s disease (AD) pathophysiology (i.e., amyloid and tau) develops first and then leads to subsequent neurodegeneration and cognitive impairment. Anti‐amyloid or anti‐tau interventions would be most effective in the earliest stages of disease, prior to irreversible neuronal death, i.e., during midlife. Our objective was to characterize the patterns of distribution for amyloid and tau PET in a middle‐aged, racially and ethnically diverse sample.MethodIn an ongoing study, participants (63±6 years old, 73% women, 19±5 years of education, 8 Non‐Hispanic White/21 Non‐Hispanic Black/47 Latinx) underwent amyloid PET imaging with Florbetaben (n=76; weighted average SUVR in Thaal phase regions) and tau PET imaging with MK‐6240 (n=59; average SUVR in Braak stages I‐VI) in the Offspring Study of Racial and Ethnic Disparities in Alzheimer’s Disease. Amyloid positivity was considered at >1.25 global SUVR, while tau positivity was considered at >2SD above the mean in Braak stage I in an independent healthy sample. A series of general linear models on the region of interest and voxel level were performed to determine the associations among age, amyloid, and tau PET.ResultRegional patterns of amyloid and tau burden were similar across race/ethnicity groups (Figure 1). In our middle‐aged sample, 13% were amyloid positive, while 7% were tau positive in Braak stage I. Amyloid positivity was observed as early as 60 years old and tau positivity was observed as early as 62 years old. Older age was associated with increased global amyloid (r=0.36, p=0.001), but was not associated with tau burden in any Braak stage. Using amyloid continuously, increased global amyloid was associated with increased tau in Braak stage I (r=0.25, p=0.06), but not with tau in Braak stages II‐VI after adjusting for age. Using amyloid dichotomously, tau burden was higher in amyloid positive compared with amyloid negative individuals in Braak stages I‐V after adjusting for age (p<0.04; voxelwise results in Figure 2).ConclusionPreliminary data suggest a range of AD pathophysiology during midlife in a racially and ethnically diverse sample. Amyloid increased in an age‐dependent manner, while tau increased in an amyloid‐dependent manner suggesting that the amyloid cascade begins in midlife.
Translating magnetic resonance imaging research in clinical practice for dementia: The Oxford Brain Health Centre
Authors: Griffanti Ludovica , Clare O'Donoghue M. , Blane Jasmine , Mitchell Robert , Aikin Nicola , Lindsay Karen , Campbell Jon , Semple Juliet , Nobis Lisa , Raymont Vanessa , Martos Lola , Mackay Clare 
Published: February 2022

AbstractBackgroundThe Oxford Brain Health Centre (BHC) is a pioneering psychiatry‐led joint clinical‐research service launched in 2020. It provides NHS patients with existing memory problems access to high‐quality assessments not routinely available in clinical practice, including MRI rather than CT. This abstract describes the MRI protocol of the BHC, designed to translate dementia research advances into clinical practice, and shows preliminary data from the BHC pilot.MethodThe BHC MRI protocol (details in Table 1) is structured to include core clinical sequences (high‐resolution T1, FLAIR, SWI and 3D DWI) and optional research sequences (TOF, ASL, DWI, resting state fMRI). Patients can consent to use of clinical scans for research, additional research sequences, and recontact about future research. Sequences were matched as much as possible to the UK Biobank (UKB) imaging protocol (Miller et al., 2016 Nat Neurosci.) to take advantage of its high‐quality data, clinically feasible acquisition time, and availability of big population data. Additional scans on healthy controls are planned to improve generalizability of UKB and enrich the age range of interest.ResultThirty‐three patients attended the BHC between August and December 2020 (average age 77.5 years, age range 66‐90 years, 58% female). 94% of patients completed the clinical scans and consented use for research, 64% consented to additional research sequences and 42% completed the research scan. Table 1 details the number of currently available scans for each modality. An adapted version of the UK Biobank pipeline (Alfaro‐Almagro et al., 2018 Neuroimage) is being developed to extract quantitative measures from the scans (imaging derived phenotypes, IDPs). For example, Figure 1 shows how hippocampal volumes for 11 BHC patients compare with UKB data: most of them fall in the lower percentiles, suggesting potentially pathological deviations from the norm.ConclusionThe data acquired in the first months of the BHC pilot phase demonstrate that the MRI protocol is well tolerated and provides good quality data both for research and clinical purposes. Future work aims to integrate quantitative measures in the radiology reports of the BHC and evaluate their impact in the clinical practice.
The effect of memantine on cortical network function in frontotemporal lobar degeneration is conditional on baseline GABA physiology
Authors: Perry Alistair , Adams Natalie E. , Hughes Laura , Kocagoncu Ece , Rouse Matthew A. , Murley Alexander G. , Bevan‐Jones W. Richard , Passamonti Luca , Street Duncan , Naessens Michelle , Holland Negin , Nesbitt David , Cope Thomas E. , Rowe James B. 
Published: February 2022

AbstractBackgroundFrontotemporal lobar degeneration (FTLD) is associated with deficits to GABA and glutamatergic neurotransmitters, particularly in the frontal cortex. While targeting GABAergic systems has shown to restore frontotemporal deficits in FTLD, little is known whether pharmacological probes of glutamatergic functioning have similar effects in these circuits.MethodTwenty participants with a FTLD‐associated syndrome (11 with PSP, 9 with bvFTD) and 20 healthy‐controls undertook two magnetoencephalography (MEG) sessions with a roving auditory oddball paradigm assessing frontotemporal change detection: (1) session on placebo and (2) after 10mg of oral memantine, which aims to blocks glutamatergic ecotoxicity. The mean amplitude of MEG “mismatch negativity” responses (MMN; standard‐deviants, 125‐175ms) was calculated across gradiometer sensors and for bilateral frontotemporal sources. Glutamate and GABA levels were measured using 7T proton magnetic resonance spectroscopy of the right inferior frontal gyrus (IFG). Frequentist and Bayesian ANOVAs assessed the differential mean MMN responses between controls and patients across placebo and drug conditions. Evoked difference waveforms (standard‐deviants) across the peristimulus time‐window were analysed using random field theory (RFT) (crit p=0.05, FWER) for the interaction effects of interest (i.e. drug session x group and drug x MRS levels).ResultPatients and controls did not demonstrate differential mean MMN amplitudes on placebo at the average‐sensor (p=0.95) or source‐level (p>0.27) (BF10=0.3‐0.5). Across sensors, only controls exhibited a differential drug‐dependent MMN, reflected by a steeper rebound of difference waveforms between 206‐288ms on memantine (Fig 1A; pFWER=0.026, cluster‐level). However, no interaction was found for mean MMNs (p>0.053). Notably, RFT (Fig 1B) and linear mixed models (Fig 1C) identified that greater GABA levels in patients are significantly associated with stronger MMN responses in right‐hemisphere areas under memantine. Glutamate levels did not moderate the mean MMN response to memantine (p>0.065).ConclusionOverall, we show that targeting glutamatergic systems may not lead to a restoration of frontotemporal physiology across patients. However, the effects of memantine are conditional on patient's baseline GABA, suggesting a critical balance between glutamatergic and GABA physiology that may underlie the large‐scale neural deficits in FTLD.
Improving mealtime care for people with dementia: A training intervention for care home staff
Authors: Faraday James , Abley Clare , Exley Catherine , Patterson Joanne 
Published: February 2022

AbstractBackgroundMore and more people with dementia are living in care homes. Often they depend on care home staff for help with eating and drinking. It is essential that care home staff are able to provide good care at mealtimes. The aim of this intervention development study was to produce a staff training intervention to improve mealtimes for people with dementia.MethodThere were three phases to the study. The first phase was an evidence synthesis of relevant peer‐reviewed and grey literature, using robust systematic review methods. Data were interrogated to identify thematic categories of carer‐resident interaction in mealtime care. The second phase was an ethnography conducted in UK care homes, to explore current practice in mealtime care, and identify good practice. This included over twenty‐five hours of mealtime observations, and twenty‐two semi‐structured interviews with care home staff, family carers, and visiting health and social care professionals. The third phase was a series of co‐development workshops, in which key stakeholders worked together to create a prototype training intervention, informed by evidence from phases one and two.ResultThe training intervention content was selected to promote key components of mealtime care, including empowerment, independence, and social interaction. The delivery methods were designed to employ collaborative learning techniques and interactive activities. Issues of implementation, evaluation and context were considered. This will inform the design of a feasibility study, which will aim to ensure that the intervention is scalable, transferable and sustainable.ConclusionTraining interventions which are developed using relevant evidence and in collaboration with key stakeholders are more likely to be successful. This intervention development study seeks to demonstrate the value of such an approach. The feasibility study will test the intervention’s acceptability to recipients, and potential to impact practice.
Feasibility and acceptability of a virtual adaptation of mentalizing imagery therapy for Spanish language family dementia caregivers
Authors: Ramirez‐Gomez Liliana A , Johnson Julene K , Stewart Anita L , Meyer Ashley K , Tan Emily R , Mischoulon David , Trina Chang E , Jain Felipe A 
Published: February 2022

AbstractBackgroundSpanish speaking family dementia caregivers have limited supportive resources in Spanish, and there are few scientifically validated, culturally acceptable approaches for alleviating their distress. We investigated the feasibility of a Spanish language adaptation of Mentalizing Imagery Therapy (MIT), which provides guided imagery and mindfulness training to reduce depression, increase interpersonal understanding, and promote well‐being.Methods12 female Spanish‐speaking dementia caregivers enrolled in a 4‐week virtual MIT program consisting of weekly videoconference group meetings and home practice using audiovisual recordings. Caregivers were 52±8 (mean±SD) years of age [range 38‐61] and had been caregivers for 6±3 years. 60% had no more than a high school education, and MMSE was 27.7±2.0 [range 25‐30]. Validated Spanish‐language questionnaires were administered before and after MIT (at 5 weeks), assessing hedonic well‐being, perceived cognitive function, dispositional mindfulness, and interpersonal support. Depressive symptoms were assessed before each group session and at follow‐up, and satisfaction with MIT components was assessed after MIT. Depressive symptoms were analyzed with a mixed linear model with time as the fixed effect and a random factor for participant. Pre to post questionnaires were analyzed with one‐sided paired t‐tests, hypothesizing pre‐post improvement. Effect sizes pre to post MIT were calculated using Cohen’s d.ResultsParticipation in the four weekly group meetings was 100%. Caregivers completed home practice of 4±1 meditation session per week. Satisfaction with MIT reached 19±2 of a possible 20 points. Reduction in depression from baseline was observed by week 3 (d=.7, p=.01) and maintained through follow‐up at 5 weeks (d=.6, p<.005). There were significant pre to post increases in perceived cognitive function (d=.6, p<.05), hedonic well‐being (d=.5, p=.05), dispositional mindfulness (d=.6, p<.05), and interpersonal support (d=.7, p<.05).ConclusionsMentalizing Imagery Therapy (MIT) was successfully adapted and culturally tailored for Spanish language family dementia caregivers within a virtual group environment. MIT is feasible and acceptable and may help reduce depressive symptoms and improve subjective well‐being. Larger, randomized controlled trials should determine duration of effects and validate specific efficacy of MIT.
Mid‐life physical activity and late‐life cognitive performance among American Indians in the Strong Heart Study
Authors: Carty Cara L , Noonan Carolyn , Muller Clemma , Suchy‐Dicey Astrid M , Fretts Amanda M , Verney Steven P , Howard Barbara , Buchwald Dedra 
Published: February 2022

AbstractBackgroundResearch on factors associated with late‐life cognitive performance in diverse racial/ethnic groups is increasingly important due to the growing size and racial diversity of the elder population. American Indian elders suffer disproportionately from health conditions and behaviors that increase the risk of cognitive impairment, such as hypertension, diabetes, smoking, physical inactivity, and obesity. To inform prevention efforts in the growing at‐risk population, a better understanding of the relationships between modifiable cognitive risk factors and cognitive impairment is critical.MethodUsing data on 816 American Indians from the Strong Heart Study, we measured associations between mid‐life physical activity (PA), assessed by questionnaire, and performance on 4 cognitive tests administered ∼21 years later. Cognitive tests assessed general cognitive function, phonemic fluency, verbal learning and memory and processing speed domains. To estimate associations, we used regression models with and without inverse probability weights that accounted for potential attrition bias due to drop out between the PA and cognitive assessments. A subset of participants (n=165) had pedometer PA measured ∼12 years after the questionnaire PA assessment. In separate models, we also estimated associations between average daily steps and cognitive test scores.ResultParticipants had mean ages of 52 years at the questionnaire‐based PA assessment and 73 years at cognitive testing. The pedometer subset was mostly sedentary at the time of measurement with 66% completing <5000 steps/day, on average. Nevertheless, both questionnaire and pedometer measures of PA were positively associated with cognitive performance in later life. Participants in the top quartile of questionnaire‐based PA had Modified Mini‐Mental State examination scores 3.2 (95%CI: 1.5‐4.9) points higher than participants in the lowest quartile. Phonemic fluency scores also trended higher for participants in the top compared to bottom quantiles for both PA measures. We observed no associations between PA and tests assessing verbal learning and memory, or processing speed. Weighted model results were similar to unweighted results, but less precise.ConclusionIn this cohort of American Indians with relatively low levels of PA, positive associations between mid‐life PA and late‐life cognitive performance were domain‐specific and of modest clinical significance.
Links between acculturation and level and change in cognition among middle‐aged and older Hispanics/Latinos: Findings from the HCHS/SOL and SOL‐INCA
Authors: Stickel Ariana M , Tarraf Wassim , Gonzalez Kevin A , Breton Jordana , Keamy Alexandra J , Morlett Alejandra , Gallo Linda C , Medina Luis D , Cai Jianwen , Pirzada Amber , Daviglus Martha L , Isasi Carmen R , Kaplan Robert , Wassertheil‐Smoller Sylvia , Lamar Melissa , Gonzalez Hector M 
Published: February 2022

AbstractBackgroundHispanics/Latinos in the United States vary widely in their levels of acculturation (adoption of Anglo‐American culture) which may have implications for cognitive functioning in older age. We aimed to characterize the relationships of acculturation with cognition and cognitive change among diverse U.S. Hispanics/Latinos.MethodSelected Hispanics/Latinos (unweighted n=5,901; ages 50+ years) from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) were enrolled in the Study of Latinos ‐ Investigation of Neurocognitive Aging (SOL‐INCA) ancillary study. Three measures of acculturation were collected at baseline (Short Acculturation Scale for Hispanics (SASH) – Social and Language subscales (Marin et al., 1987) and MESA Acculturation score (Kandula et al., 2008). On all measures higher scores reflect greater acculturation. Cognition was measured at two time‐points, on average, 7‐years apart. Global cognition based on a composite measure from learning and memory, executive functioning, and processing speed tests at the second testing was the main outcome of interest in addition to change in global scores. Survey linear regressions were used to separately model the associations between acculturation measures (quartiles) and cognitive outcomes (z‐scores), controlling for baseline age, sex, education, Hispanic/Latino background, field center, income, marital status, and insurance status.ResultAverage age of the target population was 63.3 ± 8.3(SD) years, 55% were female, 39% reported less than high school education, and 43% were currently uninsured. Adjusting for covariates, the least acculturated (lowest quartile) according to the SASH had lower global cognition compared to all other groups (all p‐values<0.01; Social subscale: b=0.10; SE=0.03, b=0.15; SE=0.03, and b=0.13; SE=0.03, for the 2nd, 3rd, and 4th quartiles respectively; Language subscale: b=0.15; SE=0.03, b=0.12; SE=0.03, and b=0.23; SE=0.03). Individuals with the lowest MESA acculturation quartile had lower global cognition relative to those with scores in the highest quartile only (b=0.13; SE=0.04; p<0.01). None of the acculturation indices were associated with global cognitive change. Associations with domain specific cognitive outcomes were largely similar in pattern.ConclusionAcculturation may be indicative of baseline differences in cognition rather than risk for cognitive change. Alternatively, acculturation‐based distinctions in cognition may be related to differences in familiarity with testing environments or approaches to cognitive tasks.
Systematic review of the current psychosocial interventions for people with moderate to severe dementia
Authors: Hui Esther K , Tischler Victoria , Wong Gloria HY , Lau WY Tiffany , Spector Aimee E 
Published: February 2022

AbstractBackgroundDementia, a global epidemic, currently affects 40 to 50 million individuals worldwide. There are currently limited effective treatments for moderate to severe dementia, and most treatments focus on reducing symptoms rather than improving positive factors. It is unclear if improvements are not possible due to disease severity. This review examines the efficacy of the current psychosocial interventions for people with moderate to severe dementia, focusing on improving cognition and quality of life to evaluate what treatments are working and whether improvements are possible.MethodA systematic search was conducted using six key databases to identify psychosocial interventions for people with moderate to severe dementia, measuring cognition or quality of life in randomized controlled trials (RCTs), published between 2000 and 2020.ResultThe search identified 4193 studies, and 74 articles were assessed for full‐text review. Fourteen RCTs were included and appraised with the Physiotherapy Evidence Database Scale. The included RCTs were moderate in quality.ConclusionAromatherapy and reminiscence therapy showed the strongest evidence in improving quality of life. There was some evidence that aerobic exercise enhanced cognition, and a multi‐component study improved quality of life. However, a quality assessment, using pre‐specified criteria, indicated many methodological weaknesses. While we found improvements in cognition and quality of life for moderate to severe dementia, results must be interpreted with caution. Future interventions with rigorous study designs are a pressing need and required before we can recommend specific interventions.