bluuebunny/crossref_metadata_2025_split huggingface dataset:
MINDER Smart home test bed site – embedding dementia research into primary health and social care. Wingfield, D. Daniels, S. Norman, C. Lai, H. Hassim, N. Nilforooshan, R. Barnarghi, P. Sharp, D
Authors: Wingfield David 
Published: June 2023

AbstractBackgroundDigitally enabled healthcare is becoming mainstream NHS (1) and adoption has been accelerated in response to the COVID‐19 pandemic (2) The UK Dementia Research Institute Care Research & Technology Centre, established in 2019, explores the value of using technology in people’s homes to improve care and has developed a system (MINDER) using IOT/smart home technology and medical devices, integrating activity and health data for research purposes and generating health alerts to the mainstream provider via a clinical monitoring team. Initially launched in Surrey and Borders Partnership NHS Trust (n = 40); in April 2021, an additional research site was established within primary care in North West London.MethodWe collated data from both sites and describe an integrated delivery model for research within primary health and social care. Cohort description and case studies illustrate the challenges and benefits of conducting this research across urban and sub‐urban settings.ResultsOver 55 participants are currently enrolled on the study. 15 of these from primary care/general practice in the London Borough of Hammersmith and Fulham. Opportunities arising from this setting include leveraging the patient – provider (nurse/doctor/allied health professional/social care) relationship to introduce the study and recruit, and rapid escalation of any problems arising in a research context to the clinical/care teams responsible to delivering care (for example; potential urinary tract infections). Challenges to recruitment have included lack of specialist confirmation of dementia diagnosis in primary care records, lack of consistent engagement/availability of the required MINDER study partner as well as the impact of the COVID 19 pandemic limited face to face contact.ConclusionEarly data suggests that a complex dementia study can be embedded successfully in General Practice and leads to strengthening of relations with care giving bodies. This offers the opportunity for development and translation of new technologies within front line primary and social care, that can be fully evaluated within the real world context of service delivery.References 1)The NHS Long Term Plan (2019) gov.uk 2) Baird B, Maguire D. Understanding factors that enabled digital service change in general practice during the Covid‐19 pandemic. London: The King’s Fund. 2021 Feb.
Effects of long‐term oral treatment with a novel estrogen receptor beta agonist on memory, vasomotor, and anxiety outcomes in an EFAD mouse model of Alzheimer’s disease
Authors: Fleischer Aaron W , Schwabe Miranda R , Kuehn Rachel K , Chaudury Subhabrata , York Jason , Ladu Mary Jo , Sem Daniel S , Donaldson William A , Frick Karyn M 
Published: June 2023

AbstractBackgroundThe prevalence and severity of Alzheimer’s disease (AD) are increased by female sex, apolipoprotein E (APOE) genotype, and age, such that postmenopausal female carriers of the Apoe4 allele are at greater risk of developing AD than age‐matched males. Although estrogen therapy shows promise in preventing and reducing menopause‐ and AD‐related symptoms, activation of estrogen receptor alpha (ERa) is associated with increased risk for health concerns, such as breast cancer. Therefore, treatments more selective for estrogen receptor beta (ERb) may provide estrogen‐related health benefits without the risks of activating ERa. Long‐term or acute treatment of wild‐type mice with the novel ERb agonist, EGX358, improves memory and reduces drug‐induced vasomotor alterations. However, efficacy of this compound in an AD model is unknown.MethodFemale APOE‐TR+/+/5xFAD+/− (EFAD) mice expressed five familial AD and were homozygous for human APOE3 (E3FAD) or heterozygous for APOE3 and APOE4 (E3/4FAD). Mice were ovariectomized at 5 months of age and then treated orally with vehicle (1% DMSO) or EGX358 (10 mg/kg/day) via hydrogel for 8 weeks. Mice were weighed weekly and tested for spatial and object memory in the object placement (OP) and object recognition (OR) tasks, respectively. Anxiety‐like behaviors were also tested in the open field and elevated plus maze, and vasomotor symptoms were assessed via tail temperature following injection of the tachykinin receptor 3 agonist, senktide.ResultEGX358 significantly enhanced OR memory in both E3FAD and E3/4FAD mice. However, treatment did not affect OP memory or anxiety in the open field or elevated plus maze. Interestingly, there were significant genotype differences in open field, vasomotor response, and body weight such that E3/4FADs spent more time in the center of open field, had a greater increase in tail temperature following senktide injection, and gained more weight compared to E3FADs.ConclusionOur findings indicate a potential for ERβ‐specific estrogen treatment to improve memory for the identity of objects. Unexpected genotype differences indicate the need to further study how APOE genotype affects anxiety and metabolic outcomes in AD.
Prevalence and pathological correlates of unawareness of memory impairment in non‐demented individuals with autosomal dominant Alzheimer’s disease: an item‐level investigation of the Memory Complaints Scale
Authors: Vannini Patrizia , Gagliardi Geoffroy Pierre , Gatchel Jennifer R , Hanseeuw Bernard J , Vila‐Castelar Clara , Langella Stephanie , Munera Diana , Martinez Jairo E. , Baena Ana Y. , Johnson Keith A. , Sperling Reisa A. , Lopera Francisco , Quiroz Yakeel T. 
Published: June 2023

AbstractBackgroundAwareness of memory was previously found to be reduced in the pre‐dementia stages, reaching unawareness/anosognosia 6‐years before dementia onset in individuals who carry the PSEN1 E280A mutation for autosomal dominant Alzheimer’s disease (Vannini et al.,2021). Whether there are potential differences in awareness for specific types of situations involving memory as well as their association with molecular markers of AD disease progression in preclinical AD is unknown. Here, we investigated memory awareness on an item‐level basis as well as its relationship to neocortical amyloid and regional tau levels in non‐demented mutation carriers and non‐carrier family members.MethodA total of 119 Colombian kindred members, 56 carriers (7 mildly impaired) and 63 non‐carriers were included (Table.1). Awareness indexes were calculated using participant and study‐partner discrepancy scores for each of the 15 questions of the Memory Complaint Scale (Spanish version). A score of ≥0 indicates that the participant is aware and <0 unaware. A subset of 67 kindred members (N = 31 carriers, 1 impaired) underwent amyloid (PiB) and tau (FTP) scans. For each question, odds ratio and Fisher’s exact test were used to evaluate prevalence of awareness/unawareness in carriers and non‐carriers. Pearson correlations, corrected for multiple comparisons, were used to assess the associations between awareness and pathology in the mutation carriers.ResultMutation carriers had significantly decreased overall awareness (p = 0.03), increased mean cortical amyloid (p<0.001) and inferior temporal tau (p = 0.001), compared to non‐carriers. Two questions (items 10 and 15), showed significantly lower awareness in the carriers than non‐carriers (both p = 0.002, Table.2). These results remained significant after removing impaired carriers. In carriers, decreased awareness was related to increased tau for 5/15 (33%) questions (Table.3 and Figure.1). No significant associations were found between awareness and amyloid.ConclusionOur results support previous findings that awareness is decreased in pre‐dementia stages of AD and related to tau, and not to amyloid pathology (Gagliardi et al.,2021). Importantly, we found that loss of awareness of specific memory items could differentiate carriers from non‐carriers. These findings support the usefulness of study‐partner‐reported cognitive decline. Individuals who become unaware of cognitive changes may represent a specific risk group to harbor pathology and develop AD dementia.
Single walled carbon nanotube optical reporter for amyloid beta detection
Authors: Antman‐Passig Merav , Heller Daniel A , Wong Eitan , Frost Georgia , Cupo Christian , Shah Janki , Agustinus Albert , Chen Ziyu , Mancinelli Chiara , Kamel Maikel , Li Thomas , Jones Lauren A , Li Yueming 
Published: June 2023

AbstractBackgroundAmyloid beta (Aß) extracellular deposits are one of the pathohistological hallmarks of Alzheimer’s Disease (AD). In recent years intracellular accumulation of Aß has been linked with early pathogenic mechanisms. Recent reports now associate intracellular Aβ accumulation, and lysosomal disfunction as an early event in the disease, preceding extracellular amyloid‐deposits. Today methods to visualize intracellular Aβ accumulation rely on antibody staining or pre‐labeled Aβ. There is an outstanding need for live‐imaging tools capable of monitoring Aβ dynamics at the cellular level.MethodWe have developed an optical sensor that can monitor Aß in live cells transiently. Single wall carbon nanotubes (SWCNT) present advantages as optical sensors owing to their near‐infrared emission, as well as photostability and high‐sensitivity. SWCNT emission spectra (wavelength ranges of 1100‐1150nm) is within the biological transparency window (1000‐1700nm) allowing for optimal imaging in live samples. SWCNT were non‐covalently biofunctionalized; by which we confer selectivity to Aβ.To obtain intracellular detection we used two cell lines: monocytes (THP‐1) and differentiated SH‐SY5Y. Cells were incubated with functionalized nanotubes. We utilized near‐infrared spectroscopy and hyper‐spectral microscopy to obtain spectral response from live‐cells.ResultWe developed and characterized a new class of bio‐functionalized intrinsically photoluminescent SWCNT sensor that can detect Aß via shifting of their intrinsic near‐infrared emission wavelength. Our biofunctionalized sensors specifically recognize Aβ in the solution phase, showing a monochromatic center wavelength decrease in a dose‐dependent fashion. The reporters show high specificity compared to competing analytes and in serum samples. In cell models, nanosensors accumulate intracellularly and probe Aβ introduced to the cells specifically. Finally, initial through‐skull near‐IR imaging in‐vivo in an AD model (5XFAD), following intracranial injection, show significant decrease in central wavelength in AD mice compared to wild type.ConclusionThe SWCNT sensor provide a framework for dynamically investigating Aβ in live samples. We believe utilizing the nanosensors can enhance the study of Aβ ‐pathogenic mechanism, structure and molecular function and consequently improve and accelerate effective amyloid‐targeted therapies.
Increased cerebral blood flow is associated with higher baseline amyloid burden in a cognitively unimpaired population
Authors: Padrela Beatriz E. , Lorenzini Luigi , Collij Lyduine E. , Tomassen Jori , Bader Ilse , Shekari Mahnaz , van Berckel Bart N.M. , Visser Pieter Jelle , Barkhof Frederik , Petr Jan , Mutsaerts Henk‐Jan 
Published: June 2023

AbstractBackgroundAs cerebrovascular and Alzheimer’s proteinopathy have previously shown to affect cerebral blood flow (CBF) as well as cognition, CBF could be a potential early hemodynamic biomarker of cognitive decline. Here, we investigated to what extent cardiovascular risk factors and amyloid burden affect CBF in an elderly cognitively unimpaired (CU) population.MethodWe included 153 CU participants (minimal MMSE = 28) from the EMIF‐AD PreclinAD Twin60++ cohort (Table 1), who underwent [18F]flutemetamol PET and arterial spin labeling (ASL) MRI. Amyloid‐PET scans were visually assessed as negative or positive, upon which participants were grouped based on their longitudinal changes in amyloid positivity (visual read groups). Cortical amyloid burden was quantified with the Centiloid method globally and for 4 early amyloid accumulation regions of interest (ROIs). ASL scans were processed and quantified with ExploreASL for total gray matter (GM), and for vascular territories overlapping with the amyloid ROIs (Figure 1). Longitudinal analysis including baseline Centiloid values and yearly CBF change rates (Delta CBF) was performed for 98 participants with longitudinal imaging data available (4.23 years ± 0.43 follow‐up time). Associations between CBF and amyloid — with and without the interaction of vascular risk factors (i.e., Framingham score) — were assessed using generalized estimating equations (GEEs), both for baseline and rates of change measurements. Models were adjusted for age, sex, and twin dependency.ResultWhile no association between amyloid burden and CBF was observed across the cohort, in participants with a high Framingham vascular risk score, higher amyloid was associated with increased CBF, for most ROIs (Table 2, Figure 2). Additionally, precuneus amyloid burden was predictive of CBF change in the corresponding vascular territory (Figure 3). Visual reading shows that subjects with high amyloid burden at baseline had a higher increase of CBF at follow‐up (Stable AB+, Figure 4).ConclusionWe found that the combination of cardiovascular risk and amyloid burden in AD signature regions was associated with increased CBF in CU individuals, which may reflect a vascular or inflammatory compensatory response to early Alzheimer pathology. Future studies may help understanding how these mechanisms affect cognition.
Mobile memory gas station: A valid phone screen for cognitive impairment
Authors: Huang Yu‐Yuan , Yu Jin‐Tai 
Published: June 2023

AbstractBackgroundConventional neuropsychological assessments for cognitive impairment are burdensome. We developed a novel Wechat applet for detecting cognitive impairment. The Mobile Memory Gas Station is an assessment tool for rapid screening of cognitive functions, covering 7 important cognitive domains (memory, attention, executive function, language, visuospatial skills, social cognition, and computing).Method102 patients were recruited (Normal control: 51; mild cognitive impairment: 32, dementia: 19) to detect the diagnostic ability of this applet.ResultCompared to conventional neuropsychological assessments, Mobile Memory Gas Station results in faster evaluations (10 min) and generates higher accuracy at detecting abnormal cognition. Our Results showed that this applet had good correlation with MMSE (P < 0.01), MoCA (P< 0.01) and moderate agreement for detecting MCI and dementia.ConclusionThis applet demonstrated sufficient psychometric properties to be useful for screening of MCI, especially when clinic visits are not feasible. These findings are instrumental for patient screening, monitoring and management.
Vitamin D’s influence on aging brain function: Literature review
Authors: Elsayed Sarah , Patel Krupa , Dahab Lubaba , Elshaikh Abeer , Ibrahim Mohammed B. , Obeid Tamadur , Alatta Lina , Mohamed Suzan , Joda Malaz , Ahmed Khlood , Abdelrahman Nadir G 
Published: June 2023

AbstractBackgroundVitamin D receptors are located in neurons and glial cells of the brain. Vitamin D protects the nervous system by stimulating the synthesis of neurotrophin and neuromodulators, maintaining intracellular calcium homeostasis, and preventing oxidative brain damage. Vitamin D deficiency/insufficiency affects around 50% of the population, with rates varying according to race and ethnic origin. Vitamin D deficiency/insufficiency is a major public health concern because of its association with cognitive impairment and dementia. We aim to do a follow‐up review of the literature on the association between vitamin D insufficiency and cognitive impairment, including dementia.MethodWe reviewed vitamin D insufficiency and cognitive function studies published between 2010 and 2021. Except for animal models and research on human subjects with dementia, stroke, or brain malignancies, we reviewed clinical trials, case‐control, cohort, cross‐sectional, systematic reviews, and meta‐analyses. Adults worldwide were the target demographic. There were no limits on vitamin D levels or intake. PubMed, Cochrane, Clinicaltrials.gov, and Google Scholar were all accessed databases using keyword combinations such as “Vitamin D AND Alzheimer’s,” “Vitamin D AND cognitive,” “Vitamin D AND Geriatric,” and “Vitamin D AND Dementia”. All team members reviewed and verified the studies.ResultNine studies matched our inclusion criteria, involving 69,643 people with an average age of 53.6 years old. Vitamin D deficiency/insufficiency has been linked to impaired executive function, processing speed, visuoperceptual ability, and dementia in five studies. Two investigations established a direct proportional association between the degree of vitamin D insufficiency and the severity of memory and cognitive impairment. Vitamin D supplementation, according to one study, increases cognitive and memory functions.ConclusionAdults with vitamin D deficiency have reduced cognitive function and an increased risk of dementia. A significant limitation is that Africans, Hispanics, and Asians are underrepresented in the studies. Additionally, larger randomized controlled trials are needed to examine the many effects of vitamin D deficiency/insufficiency, supplementation, and its relationship to cognition in the aging brain.
Depression in Alzheimer’s disease hospitalized patients: A descriptive analysis of a nationwide database
Authors: Brás Bernardo , Ferreira Ana Rita , Gonçalves‐Pinho Manuel , Freitas Alberto , Fernandes Lia 
Published: June 2023

AbstractBackgroundAlzheimer’s disease (AD) is the leading cause of dementia worldwide. About 40‐50% of AD patients are also affected by depression, with mounting evidence suggesting its association with worse disease prognosis and negative outcomes, such as lower quality of life, higher mortality, and more hospitalizations, with a prolonged length of stay (LoS) and greater socioeconomic burden. This study aimed to describe the main sociodemographic characteristics and hospitalization outcomes of AD patients with a register of depression.MethodA retrospective observational study was conducted using a Portuguese nationwide hospitalization database from all mainland public hospitals. All episodes of inpatients ≥65 years old with a primary or secondary diagnosis of AD (ICD‐9‐CM code 331.0), with a concomitant register of depression at any diagnostic position (codes 296.2X, 296.3X and 311), discharged between 2008‐2015, were selected. Descriptive statistics were performed using SPSS IBM v26®.ResultA total of 1.637 hospitalizations were analysed. An upward trend has been registered from 65 (2008) to 407 episodes (2015), with most episodes occurring in female patients (73,7%), with a mean age of 80±6 (SD) years. Pneumonia (15,0%), urinary tract infections (8,5%), fracture of neck of femur/hip (6,5%), acute cerebrovascular disease (5,3%), and delirium, dementia, amnestic and other cognitive disorders (4,4%) were the most frequent primary diagnoses. A median LoS of 8 days (Q1‐Q3: 5‐14) was observed and a total of 162 (9,9%) patients died during hospitalization. Each episode had a mean estimated hospitalization charge of 3.219,15€, which represents a sum of 5.269.750,98€ for the total episodes analysed.ConclusionThe increased register of depression can be explained by the improvement in the quality of hospital‐coded data, particularly secondary coding. Moreover, the data raises awareness of depression impact in the number, duration, and cost of hospitalized patients with AD, which could conduce to more diligent healthcare interventions.
Theta‐Gamma Phase‐Amplitude Coupling Deficit in Streptozotocin AD Rat Model
Authors: Sedghizadeh Mohammad Javad , Taei Afsaneh Asgari , Karimani Farnaz , Dargahi Leila , Aghajan Hamid , Dehaqani Mohammad‐Reza Abolghasemi 
Published: June 2023

AbstractBackgroundTheta rhythms are known to encode sensory information and reflect their effect into gamma oscillations through a modulation process known as theta‐gamma phase‐amplitude coupling (PAC) (Amemiya et al., Cell Reports 2018). The role of the PAC as a network‐level indicator of cognitive impairment in disorders such as dementia and Alzheimer’s disease has received much attention recently (Zheng et al. Nature communication 2020).Injection of Streptozotocin (STZ) in animals is reported to cause resistance to insulin uptake in the brain, leading to memory and cognitive impairment (Kamat, Neural Regeneration Research 2015). The current study examines the induced deficit in the PAC as an early indicator of neurodegenerative effects of STZ.Method3 adult male Wistar rats were included in this study (270 – 300 g). Intraventricular injection of STZ was performed at a dose of 3 mg / Kg with a volume of 10 μl. Two stainless steel electrodes were implanted in the hippocampus (CA1) and medial prefrontal cortex (mPFC). The rats were free to move during recording. LFP data were recorded and segmented into windows of 20 s. Preprocessing and noisy trial rejection were employed for artifact removal, and the theta‐gamma PAC was measured using the mean vector length (tf‐MVL) method (Munia et al., Scientific Reports 2019).ResultOne week after STZ injection, the theta‐gamma PAC values did not show a significant change but after two weeks variation was observed. During this period, the power of different frequency bands was also measured and no significant change was observed even after two weeks. Theta‐gamma PAC deficiency was observed in both regions (CA1 and mPFC).ConclusionSTZ’s intracerebro‐ventricular injection is known to produce cognitive deficits along with an increase in Aβ deposition. This study reports that cross‐frequency coupling deficiency is also observed in this AD mouse model. Moreover, the PAC deficit was detected earlier than any change was observed in the spectral analysis of the data, suggesting that it can serve as a diagnosis tool for memory impairment due to neurodegeneration in the STZ mouse model of AD.