bluuebunny/crossref_metadata_2025_split huggingface dataset:
Macular vessel density in the superficial plexus is not associated to cerebrovascular damage in non‐demented individuals: data from the NORFACE cohort
Authors: Marquié Marta , García‐Sánchez Ainhoa , Sotolongo‐Grau Oscar , Tartari Juan Pablo , Sanabria Angela , Esteban‐De Antonio Ester , Pérez Alba , Castilla‐Martí Miguel , Castilla‐Martí Luis , Martínez Joan , Alarcón‐Martín Emilio , Alegret Montserrat , Aguilera Núria , Vivas Assumpta , M Gómez‐Chiari , Escudero José Miguel , Tejero Miguel Angel , Tárraga Lluís , Ruiz Agustin , Boada Mercè 
Published: December 2023

AbstractBackgroundOptical Coherence Tomography angiography (OCT‐A) is a novel tool that allows the detection of retinal vascular changes. The comparison of OCT‐A measures with brain vascular burden is essential to validate the former as a surrogate of cerebrovascular damage and biomarker of cognitive decline. We aimed to investigate the association of macular vessel density (VD) in the superficial plexus assessed by OCT‐A with measures of cerebrovascular pathology quantified by brain magnetic resonance imaging (MRI) in a cohort of non‐demented individuals.MethodClinical, demographical, APOE ε4 status, amyloid status, OCT‐A and brain MRI data from non‐demented participants of the FACEHBI and BIOFACE studies were included. We analyzed the association of macular VD in four quadrants (superior, nasal, inferior and temporal) with brain vascular burden using the Fazekas scale scores (dichotomized in two categories, 0‐1 vs 2‐3), assessed in a logistic regression analysis, and the volume of white matter hyperintensities (WMH) quantified by Freesurfer assessed in a multiple regression analysis. We additionally explored the associations of macular VD with hippocampal volume, ventricles volume and Alzheimer Disease cortical signature (ADCS) thickness assessed in a multiple regression analysis. All analyses were adjusted for age and dyslipidemia.ResultThe study cohort comprised 188 participants: 89 with subjective cognitive decline (SCD) and 99 with mild cognitive impairment (MCI). Logistic regression analysis showed no significant differences of regional macular VD between the two Fazekas groups (all, p>0.05). Multiple regression analysis showed no significant association of regional macular VD with the volume of WMH (all, p>0.05). Macular VD in the nasal and inferior quadrants were positively associated with hippocampal volume (p = 0.009 and p = 0.021, respectively), but no association was detected with ventricles volume or ADCS thickness (both p>0.05).ConclusionOur study showed that retinal vascular measures (regional macular VD in the superficial vascular plexus) assessed by OCT‐A were not associated with brain vascular damage quantified by the Fazekas scale and the WMH burden n in a cohort of non‐demented research participants with SCD and MCI.
Longitudinal factors associated with living well in people with mild‐to‐moderate dementia: initial findings from the IDEAL and IDEAL‐2 cohorts over 6 years
Authors: Matthews Fiona E , Gamble Laura D , Clare Linda 
Published: December 2023

AbstractBackgroundUnderstanding the factors associated with quality of life can help us become more effective in optimizing the potential for people with mild‐to‐moderate dementia to ‘live well’ with the condition. Identifying individuals at risk of declining could help to target support more appropriately.MethodsWe used longitudinal data from 1749 individuals with mild‐to‐moderate dementia participating in the IDEAL and IDEAL‐2 studies. Assessments took place on entry and followed up at 12, 24, 48, 72 and 96 months. Using mixed effects modelling we examined change in quality of life since time of diagnosis, and looked at time‐invariant and time‐varying measures and their association with decline in quality of life.ResultsThere was no change in mean quality of life in the years following diagnosis. However, we were able to identify some individuals whose quality of life declined by varying amounts and found that a larger decline was associated with being male and older, and that those with a decline in quality of life had worsening cognitive function and increasing depression in the years following diagnosis.ConclusionsQuality of life does not decline for the majority of people following a diagnosis of dementia. However, for those that did decline we were able to identify some factors associated with this decline. This model allows us to investigate further factors that may influence living well in people with dementia, helping to identify potential factors for intervention.
Dementia subtypes and quality of life in people with mild‐to‐moderate dementia: longitudinal findings from the IDEAL and IDEAL‐2 cohorts over 6 years
Authors: Clare Linda , Gamble Laura D , Martyr Anthony , Matthews Fiona E 
Published: December 2023

AbstractBackgroundThe heterogeneity of symptoms across dementia subtypes may influence the capability of people with dementia to ‘live well’. We investigated how quality of life varies across dementia subtypes and over time.MethodWe assessed 1749 individuals with mild‐to‐moderate dementia on entry to the IDEAL or IDEAL‐2 studies and followed them up at 12, 24, 48, 72 and 96 months. We used mixed effects models to examine whether quality of life varied by dementia subtype at the time of diagnosis and how quality of life trajectories changed over time.Result52.4% of participants had a diagnosis of Alzheimer’s disease, 10.2% vascular dementia, and 19.8% mixed Alzheimer’s and vascular dementia. Of the rarer subtypes, 5.7% had frontotemporal dementia, 4.2% had Parkinson’s disease dementia and 5.3% had dementia with Lewy bodies, with 2.4% having other/mixed dementias. The strongest associations between dementia subtype and quality of life were seen at the time of diagnosis. Compared to individuals with Alzheimer’s disease, people with Parkinson’s disease dementia (‐4.89, 95% CI ‐6.60 ‐ ‐3.17) and dementia with Lewy bodies (‐4.90, 95% CI ‐6.38 ‐ ‐3.42) had relatively poor quality of life. People with vascular dementia (‐2.45, 95% CI ‐3.55 ‐ ‐1.35) and mixed Alzheimer’s and vascular dementia (‐1.70, 95% CI ‐2.47 ‐ ‐0.92) had somewhat poorer quality of life, but the difference was less marked. There was no difference between people with Alzheimer’s disease and people with frontotemporal dementia (‐0.39, 95% CI ‐1.73 – 0.95). There was little change in quality of life over time and we found no differences in quality of life trajectories according to dementia subtype.ConclusionAt the time of diagnosis, quality of life already differs according to dementia subtype, and this pattern is maintained over time. People with Parkinsonian dementias in particular may need extra support with the challenges they face.
Masupirdine (SUVN‐502) for the Potential Treatment of Agitation in Patients with Dementia of the Alzheimer’s Type: Preliminary Efficacy and Phase‐3 Study Design
Authors: Nirogi Ramakrishna , Abraham Renny , Ravula Jyothsna , Jetta Satish , Benade Vijay , Shinde Anil K , Rasheed Mohammed Abdul , Badange Rajesh Kumar , Goyal Vinod Kumar , Palacharla Veera Raghava Chowdary , Subramanian Ramkumar , Jayarajan Pradeep 
Published: December 2023

AbstractBackgroundAlzheimer’s disease (AD) is a progressive neurodegenerative disorder with manifestations in cognitive, functional and neuropsychiatric symptoms (NPS). Agitation is one of the most prevalent and challenging NPS to manage. Antipsychotics are widely used for the pharmacological management of agitation. However, they offer modest efficacy, and the side effects are substantial.Serotonin‐6 receptor (5‐HT6) blockade may have therapeutic utility in the management of disorders associated with mood and behavior. Masupirdine is a potent and selective 5‐HT6 receptor antagonist.MethodMasupirdine has been evaluated in a phase‐2, 26‐week proof‐of‐concept clinical study (NCT02580305). Subgroup analyses of study results based on the neuropsychiatric inventory scale was carried out. Masupirdine was also evaluated in animal models to assess its effect on behavior and brain neurotransmitters modulations.A double‐blind, randomized, placebo‐controlled, parallel group, adequately powered global phase‐3 study is in progress to evaluate the efficacy, safety, tolerability, and pharmacokinetics of masupirdine for the treatment of agitation in participants with dementia of the Alzheimer’s type (NCT05397639). A total of 375 patients are planned to be enrolled in the study who will be randomly assigned to receive either 50 mg masupirdine or 100 mg masupirdine or placebo. Patients will be treated for 12 weeks. The primary efficacy endpoint of this study is the Cohen‐Mansfield Agitation Inventory items score aligning to the international psychogeriatric association agitation criteria domains (physical aggression, excessive motor activity, and verbal aggression) and the key secondary endpoint is improvement in modified Alzheimer’s Disease Cooperative Study‐Clinical Global Impression of Change score as related to agitation.ResultThe observations from the post hoc analysis of phase‐2 clinical study in AD patients and animal models support the potential beneficial effects of masupirdine on agitation.The phase‐3 study has been initiated in USA and Europe, and the subject enrolment is expected to be completed by Q3 2024.ConclusionThe need for new treatments for the management of agitation is significant and unmet. The Phase‐3 study results will inform the utility of masupirdine for the potential treatment of agitation in patients with dementia of Alzheimer’s type. Phase‐3 study data readout is anticipated in Q1/Q2 2025.
Longitudinal patterns of behavioral and psychological symptoms of dementia in community‐dwelling older people
Authors: Arai Asuna , Katsumata Yuriko 
Published: December 2023

AbstractBackgroundBehavioral and psychological symptoms of dementia (BPSD) exhibit fluctuate by symptoms. This can cause difficulty for caregivers in addressing symptoms and a greater care burden. Few studies have analyzed the longitudinal course of multiple BPSD together. We aimed to identify the trajectory groups of 12 BPSD symptoms and assess the predictors of trajectory group membership.MethodData were drawn from the National Alzheimer’s Coordinating Center Uniform Data Set comprising participants who were followed up approximately annually in the United States. We examined home‐dwelling participants who were followed‐up for at least 1 year from 2015 to 2020. Individuals with cognitive decline (Clinical Dementia Rating of more than 0.5 and diagnosis of mild cognitive impairment or dementia) were included (n = 1,585). Twelve symptoms of BPSD were measured using the Neuropsychiatric Inventory. We used group‐based multi‐trajectory models to identify latent trajectory groups. Multinomial logistic regression analysis was conducted to assess participants’ characteristics at baseline associated with trajectory groups.ResultAmong participants, mean age was 75.7 years, median annual number of visits was 3 (interquartile range: 2‐5 visits), 44% were female, 74% lived with their spouse/partner, and 38% were able to live independently. Four trajectory groups were identified. One group showed relatively higher levels of all symptoms across years. In two groups, moderate levels of agitation, irritability, and depression, and moderate levels of apathy, appetite disturbances, and hallucinations were observed. The fourth group exhibited lower levels of all symptoms. Multinomial logistic regression models revealed that, compared with the lower‐level group, older age was associated with lower odds of other group membership. The level of dependence and cognitive decline were associated with higher odds of other group membership, although their interaction indicated lower odds. Male was a predictor of higher‐level group. Living with someone was a predictor for a group with moderate levels of apathy, appetite disturbances, and hallucinations.ConclusionWe identified at least four trajectories in 12 BPSD symptoms over 5 years, and their common and specific predictors among community‐dwelling people with dementia. Inferring individual group membership using these predictors may be helpful for determining appropriate measures for addressing expected BPSD.
Digital Endpoints for Assessing Instrumental Activities of Daily Living in Mild Cognitive Impairment: A Systematic Review
Authors: Lawson Lauren , Ardle Ríona Mc , Wilson Sarah , Beswick Emily , Karimi Radin , Slight Sarah 
Published: December 2023

AbstractBackgroundImpairments in instrumental activities of daily living (IADLs) can be subtle indicators of cognitive decline. By measuring declining IADLs in individuals with Mild Cognitive Impairment (MCI), we may be able to identify those who are at risk of progression to dementia and aid early intervention strategies. Digital technologies (e.g., wearables/ambient sensors) can continuously and objectively assess IADL‐related behaviours. However, it is unclear in the literature what digital methods and metrics have been used to assess IADL‐related behaviours in MCI, and what differences have been observed between MCI and normal ageing. We conducted a systematic review to address this knowledge gap.MethodEight databases (CINAHL/Embase/Medline/ProQuest/PsycInfo/PubMed/Web of Science/Scopus) were searched using key terms. Studies published between 2004‐2022 that used continuous, remote, digital technology to assess IADL‐related behaviours in people with MCI were included. Exclusion criteria included populations with diagnoses of other conditions that may have impacted cognition or function, research conducted in aged‐care facilities, or that had used scripted tasks. IADL‐related behaviours were taken from existing assessments and sorted into relevant domains (e.g., Activities Outside of the Home; Everyday Technology Use). This review was registered with PROSPERO (CRD42022326861) and followed the PRISMA guidelines.ResultFifteen articles were included from 16,099 identified titles. Eleven different technologies were used to assess IADL‐related behaviours, with motion sensors the most common. Ambient technology was used by 93% (n = 14) of studies. Only two studies measured user acceptability of technologies, with >80% of participants providing positive feedback. Seventy‐nine digital metrics were reported; computer use time and time out‐of‐home were the most commonly used. Two studies reported significant decreases in IADLs in the Activities Outside of Home domain for people with MCI compared to normal ageing. Two studies reported significant decreases in Everyday Technology Use, and one study reported a significant decrease in IADLs related to Orientation for people with MCI compared to normal ageing.ConclusionFindings from this review will inform the selection of tools to digitally assess IADL‐related behaviours in populations with MCI. We recommend standardisation and increased validation of digital methods and metrics used to continuously and remotely assess IADLs.
UK Biobank imaging in a memory clinic population: associations between imaging‐derived phenotypes and cognition in the Oxford Brain Health Clinic
Authors: Gillis Grace , Bhalerao Gaurav V , O'Donoghue M Clare , Blane Jasmine , Mitchell Robert , Martos Lola , Raymont Vanessa , Mackay Clare , Griffanti Ludovica 
Published: December 2023

AbstractBackgroundSince August 2020, the Oxford Brain Health Clinic (BHC) has seen over 200 NHS memory clinic patients (O’Donoghue et al., 2022). In addition to high‐quality cognitive and lifestyle assessments and opportunities for research participation, patients receive a clinical MRI scan (T1‐weighted, T2‐FLAIR, and SWI) and can consent to additional research scans (diffusion MRI – dMRI, resting‐state functional MRI – rfMRI, and arterial spin labelling ‐ ASL) aligned to the UK Biobank (Griffanti et al., 2022). In this project, we aimed to automatically extract imaging‐derived phenotypes (IDPs) from the different imaging modalities acquired at the BHC and perform unimodal group‐level analyses to explore associations with cognition and diagnoses in this real‐world memory clinic population.MethodAs of January 2023, scans were analysed from 176 BHC patients, 101 of whom completed the additional research MRI scans. Cognitive scores (ACE‐III total score, N = 166) were available from the BHC appointment, and subsequent diagnoses (N = 118) were extracted from electronic healthcare records. Scans were processed using the UK Biobank pipeline (Alfaro‐Almagro et al., 2018), adapted to include previously described modifications (Griffanti et al., 2022). All IDPs were deconfounded for age, sex, and head size. We calculated Spearman correlations with ACE‐III cognitive scores and group comparisons (Kruskal‐Wallis tests) between 3 diagnostic groups: dementia, MCI, and no dementia‐related diagnosis. Results were corrected for multiple comparisons (false discovery rate with Benjamini‐Hochberg procedure; FDR‐adjusted p = 0.000016).Result11 IDPs significantly correlated with ACE‐III (Figure 1). Four voxel‐based morphometry temporal lobe measures, 3 FreeSurfer temporal lobe measures, FIRST left hippocampal volume, and SIENAX peripheral grey matter volume positively correlated with ACE‐III, in line with known dementia‐related atrophy patterns (Figure 2). dMRI mean diffusivity in the bilateral parahippocampal part of the cingulum negatively correlated with ACE‐III, highlighting white matter disruption (Figure 3). No FDR‐corrected differences were found between diagnostic groups.ConclusionUsing an unselected patient population, all of whom have a degree of memory problems, this work provides real‐world validation of associations that are well‐established in the research context. This represents a key step towards integrating research‐quality imaging in the memory clinic. Imaging and clinical variables are planned to be available through DPUK.
SUVN‐I6107: A True Positive Allosteric Modulator (PAM) at Muscarinic M1 Receptors for the Treatment of Cognitive Disorders
Authors: Palacharla Veera Raghava Chowdary , Guduru Naga Sai Soma Chandra Sekhar , Medapati Rajesh Babu , Srirangavaram Maheshwari , Grandhi Venkata Ramalingayya , Ganuga Narender , Badange Rajesh Kumar , Nakka Harish , Subramanian Ramkumar , Nirogi Ramakrishna 
Published: December 2023

AbstractBackgroundMuscarinic acetylcholine receptors belong to the family of G‐protein coupled receptors and are expressed widely throughout the body. Muscarinic receptors have been implicated in the pathophysiology of various central nervous system disorders. M1 subtype of muscarinic receptors play a crucial role in cognition, attention, and sensory processing. The discovery and development of selective ligands targeting M1 subtype have been unsuccessful largely due to the highly conservative orthosteric binding site. Thus, ligands that selectively bind to a less conserved allosteric site of M1 receptors and positively modulate the orthosteric site may circumvent the selectivity issues as posed by orthosteric ligands.MethodSUVN‐I6107 is a clinical candidate identified from the M1 positive allosteric modulator (M1‐PAM) program. The effects of SUVN‐I6107 on the allosteric site of the M1 receptor were evaluated using the reporter gene assay. Binding liability towards orthosteric sites across all the muscarinic receptor subtypes was also evaluated. The pharmacokinetic properties of SUVN‐I6107 were studied both in rodent and non‐rodent species. The pro‐cognitive potential of SUVN‐I6107 was evaluated in diverse animal models of learning and memory. The safety of SUVN‐I6107 was assessed using various in vitro and in vivo systems.ResultSUVN‐I6107 was found to be a selective M1‐PAM with no agonistic activity at Muscarinic M1 and selective across other muscarinic receptor subtypes. SUVN‐I6107 showed good oral bioavailability in rat, dog and monkey. It also has excellent brain penetration with adequate protein free fraction. SUVN‐I6107 reversed the delay‐induced memory deficit in object recognition task. It also attenuated scopolamine‐induced memory deficit in the object recognition as well as contextual fear conditioning task. SUVN‐I6107 enhanced cerebral blood flow, potentiated the effects of donepezil and promoted non‐amyloidogenic amyloid precursor protein processing in rats. SUVN‐I6107 is devoid of side effects associated with the stimulation of the cholinergic system. SUVN‐I6107 was found to be safe in the safety pharmacology and phase‐1 enabling animal toxicity studies.ConclusionSUVN‐I6107, a novel, potent and selective M1‐PAM demonstrated efficacy in animal models and devoid of cholinergic side effects
Hospital‐to‐home care transition for dementia patients and family care partners: communication, decision‐making, and support experience of a culturally diverse sample
Authors: Kwak Jung , Kvale Elizabeth A , Mills Sarah , Patel Snehal , Mancuso Claire E , Oppong Kwaku Duah 
Published: December 2023

AbstractBackgroundPersons living with dementia (PLWD) are twice as likely to be hospitalized than non‐dementia peers, and while hospitalized, more likely to suffer from delirium, falls, procedure‐related complications, and death. PLWDs and their care partners (CPs) need support and preparation for hospital‐to‐home transition to avoid unnecessary readmission to hospitals. The current study aims to identify and examine communication, decision‐making, and caregiver support experience of racially and financially diverse PLWDs/CP dyads during hospital‐to‐home care transition in the U.S.MethodWe analyzed preliminary data from an ongoing mixed methods study of care transition experience of hospitalized PLWD/CP dyads. We used survey and hospital case notes data from 22 dyads and in‐depth interviews with 12 CPs recruited from two urban hospitals. We conducted descriptive and content analysis with quantitative and qualitative data.ResultHalf of PLWDs were non‐white (50%), frail with recent history of fall (68%) or hospitalization (50%) in the last three months, lacked advance directives (46%), and received palliative care consult while hospitalized (77%). Majority of CPs were non‐White (68%), PLWD’s adult child/grandchild (64%), and reported knowing a little or not much at all about dementia (82%). Themes on CP communication, decision‐making and caregiving support emerged: CPs find surrogate decision‐making difficult; proactive palliative care prepares CPs for terminal trajectory of dementia; CPs need education and training on hands‐on caregiving tasks to keep PLWDs safe and comfortable at home; and CPs’ social needs need to be addressed to achieve goals of care for PLWDs.ConclusionPLWDs and CPs need education, training, coaching, and individualized support during care transitions in order to develop self‐efficacy and maintain resilience. Palliative care, currently offered in over 80% of U.S. hospitals, provides important education and support for PLWDs and CPs. However, palliative care support ends after discharge for most families. Findings from our study suggest that continuing comprehensive palliative care support after discharge may be needed, when PLWD and CPs may need support the most. Future studies should examine needs of PLWDs and CPs living in communities and the role of palliative care to address informational and support needs.