bluuebunny/crossref_metadata_2025_split huggingface dataset:
Associations between peripheral hearing ability at age 70, brain atrophy and cognitive decline in adults born in the same week of 1946
Authors: Parker Thomas D , Keuss Sarah E , Coath William , Cash David M , Nicholas Jennifer M , Lu Kirsty , Lane Christopher A , Keshavan Ashvini , Buchanan Sarah M , James Sarah‐Naomi , Wagen Aaron Z , Harris Matthew J , Street Rebecca E , Storey Mathew , Barnes Jo , Malone Ian B , Sudre Carole H , Thomas David L , Dickson John , Murray‐Smith Heidi , Freiberger Tamar , Wong Andrew , Bamiou Doris‐Eva , Warren Jason D , Crutch Sebastian J , Richards Marcus , Fox Nick C , Schott Jonathan M 
Published: June 2023

AbstractBackgroundPeripheral hearing impairment has been proposed as a risk factor for dementia. However, the relationship between hearing ability, neurodegeneration and cognitive decline, and the extent to which pathological processes associated with increased risk of specific causes of dementia, such as β‐amyloid and small vessel disease, influence these relationships, is unclear.MethodData were analysed from 287 cognitively normal adults born in the same week of 1946 who underwent pure tone audiometry testing at baseline (mean age = 70.6 years), with cognitive assessment and brain imaging at baseline and at follow‐up on average 2.4 years later. Peripheral hearing impairment was defined as a pure tone average of greater than 25 decibels in the best hearing ear. Rates of change for whole brain, hippocampal and ventricle volume were estimated from structural MRI using the Boundary Shift Integral. Cognition was assessed using the Pre‐clinical Alzheimer’s Cognitive Composite. Regression models were performed to evaluate how baseline hearing impairment associated with subsequent brain atrophy and cognitive decline after adjustment for a range of variables including baseline β‐amyloid deposition (assessed using florbetapir‐PET) and baseline small vessel disease burden (estimated using white matter hyperintensity volume).Results111 out of 287 participants were defined as having peripheral hearing impairment. Hearing impaired individuals demonstrated faster rates of whole brain atrophy (p = 0.031 – figure/table 1) compared with those with normal hearing. Peripheral hearing impairment did not predict change in PACC performance, but there was evidence of an interaction between hearing impairment and whole brain atrophy rates in terms of effect on change in PACC performance. Specifically, faster rates of whole brain atrophy predicted greater cognitive decline in participants with hearing impairment (p = 0.004), whilst there was no evidence of an association between cognitive change and atrophy in participants with preserved hearing (figure/table 2). There was no evidence that β‐amyloid deposition or white matter hyperintensity volume modified these relationships.ConclusionWe present evidence of associations between peripheral hearing ability at age 70, brain atrophy and cognitive decline independent of β‐amyloid and small vessel disease, suggesting hearing may associate with brain health via mechanisms distinct from those typically implicated in pre‐clinical Alzheimer’s disease and vascular cognitive impairment.
Excitability and glymphatic function in an animal model of Alzheimer’s disease
Authors: Müller Luisa , Kirschstein Timo , Köhling Rüdiger , Deike‐Hoffmann Katerina , Radbruch Alexander , Kuhla Angela , Teipel Stefan 
Published: June 2023

AbstractBackgroundAPPswe/PS1dE9 mice reproduce features of amyloid β (Aβ) pathology and neuronal dysfunction as reflected in electrophysiological recordings of neuronal hyperexcitability. This leads to changes in sleep‐wake‐rhythm, downstream affecting brain clearance functionality. Our objective is to investigate the effect of circadian rhythm and Aβ pathology on clearance efficacy in APPswe/PS1dE9 mice.MethodFirst, we examined the brain wide distribution of an intrahippocampal injected fluorescent dye. Dye was injected at 6 am (post wake period) or 6 pm (post sleep period) and sampled 1 or 3 h post injection for histological analysis (Figure 1A) in n = 3 transgenic mice and n = 3 non‐transgenic mice per group. Secondly, in an in vivo approach we analyzed the brain wide distribution of a gadolinium based contrast agent using a T2‐RARE sequence in a 7 Tesla small animal MRI scanner (Bruker BioSpin GmbH, Germany) (Figure 1B) in n = 4 transgenic mice and n = 4 non‐transgenic mice. We measured values for brightness in manually defined regions of interest with PMOD software (version 3.7; PMOD Technologies LLC, Switzerland).ResultIn the first experiment, we were able to observe dye distribution in the brain parenchyma as surrogate for interstitial clearance net flux. Preliminary results point to an effect of circadian rhythm, as a trend of better dye distribution shortly after the sleep period was observed. Furthermore, a possible detrimental effect of the Aβ phenotype on clearance was observed in transgenic mice. In comparison to non‐transgenic mice they showed a trend of lesser dye distribution independent of day‐time. With the second approach, we were able to observe influx and efflux of applied contrast agent into cerebrospinal fluid. Preliminary data point to a trend of an increased slope of the influx as well as decreased slope of the efflux in transgenic mice.ConclusionHistological analysis of a stereotactic injected dye is a feasible method for investigation of dye distribution outlining a possible effect of daytime and amyloid pathology. However, MR‐imaging is a promising tool as we will be able to observe the disease progression in mice longitudinally. Further experiments will be needed to ensure these preliminary results and maybe also point to underlying mechanistic basis.
Homocysteine altered gyrification related to self‐awareness of everyday cognition
Authors: Wang Ziqi , Dong LI , Cai Qingyan , Jian Wei , Yao Dezhong 
Published: June 2023

AbstractBackgroundPrevious studies on homocysteine have verified higher homocysteine may adversely influence cognition performance in individuals with subjective cognitive decline (SCD), whereas the potential mechanisms for this relationship are still unclear.MethodWe analyzed data from 23 individuals with SCD enrolled in the 500 nm light therapy cohort who filled the 12 items Everyday Cognition scale (ECog‐12) and had plasma homocysteine levels assessed at the time of their baseline 3T MRI scans. Gyrification and cortical thickness were obtained by using whole brain region of interest (ROI)‐based approach with the CAT12 toolbox (in SPM12). Statistical analyses used one‐sample t‐test including age and sex as covariates. Regions of significant group effects were used as regions of interest for cognitive performance analyses.ResultAt corrected thresholds (p < 0.05, Holm‐Bonferroni‐corrected), there were significant negative correlations between homocysteine and gyrification in the left temporal pole (p = 0.012000) and right inferior temporal sulcus (p = 0.012268). For cortical thickness, we found a significant positive correlation of homocysteine and cortical thickness in the right inferior temporal sulcus (p = 0.032744). In addition, a significant positive correlation was found between the self‐report ECog‐12 scores and gyrification of the left temporal pole.ConclusionHomocysteine alters local surface shape in temporal lobule in SCD patients and localized low gyrification may imply impaired self‐awareness of everyday cognition.
Centiloid scale measure of amyloid PET by CT‐guided anatomic standardization
Authors: Matsuda Hiroshi , Hanyu Haruo , Kaneko Chikako 
Published: June 2023

AbstractBackgroundCentiloid (CL) scaling has become a standardized quantitative measure in amyloid PET because it facilitates the direct comparison of results across institutions, even when different analytical methods or tracers are used. Standard volumes of interest must be used to calculate the CL scale after the anatomic standardization of amyloid PET images using coregistered MRI; if the MRI is unavailable, the CL scale cannot be accurately calculated. This study sought to determine the substitutability of CT, which is used to correct PET attenuation in PET/CT equipment, by evaluating the measurement accuracy when CT is used as an alternative to MRI in the calculation of the CL scale.MethodAmyloid PET images obtained using 11C‐PiB from 19 patients with possible or probable Alzheimer’s disease were processed to calculate the CL scale using 3D T1‐weighted MRI (Optima MR450w, 1.5T, GE healthcare) and CT of PET/CT (uMI780, United Imaging Healthcare). CLMRI and CLCT were respectively defined as the use of MRI and CT for anatomic standardization and compared. We followed the method advocated by the Global Alzheimer’s Association Interactive Network for the calculation of the CL scale. The whole cerebellum was chosen as a reference area for the CL calculation.ResultA Bland–Altman plot showed that CLCT did not significantly differ from CLMRI (mean ± standard deviation, −0.1 ± 1.5; p = 0.734). The 95% limits of agreement ranged from −0.8 to 0.6. Pearson correlation analysis showed a highly significant correlation of r = 0.999 between CLCT and CLMRI (p < 0.001). The linear regression equation was CLCT = 0.992 × CLMRI + 0.144. In a Bland–Altman plot, Spearman correlation analysis did not identify a significant association between the difference in CLMRI versus CLCT and CL load (ρ = −0.045, p = 0.853).ConclusionCL scales based on CT show a highly significant positive correlation with those based on MRI, regardless of the degree of amyloid accumulation in possible and probable AD patients. A key advantage of the use of CT is the simultaneous acquisition of PET and CT. This method would be applicable to subjects who are unable to undergo MRI.
Apolipoprotein E4 impairs iron efflux in human induced pluripotent stem cell (iPSC)‐derived cortical neurons by reducing ferroportin on cell surface
Authors: Xu He , Gao Huiling 
Published: June 2023

AbstractBackgroundIron homeostasis disturbance has been implicated in Alzheimer’s disease (AD), and excess iron exacerbates oxidative damage and cognitive defects. Ferroportin (Fpn) is the only known iron exporter and the expression of Fpn is decreased in the brains of AD patients. Apolipoprotein E (APOE) gene is the most important genetic risk factor for late‐onset AD. The three common proteins encoded by the gene are ApoE2, ApoE3, and ApoE4. They bind to iron with different affinities, which mediates the isoform‐specific antioxidant activity. However, whether ApoE takes part in neuronal iron homeostasis remains unclear.MethodCortical neurons were generated from human iPSCs (All from non‐demented APOE3/E3 carriers). The intracellular iron content was measured using inductively coupled plasma mass spectrometry (ICP‐MS) after co‐treatment of iron and ApoE. Western blot analysis was performed to examine the alterations of various iron storage and transport proteins. Cell surface Fpn expression levels were measured by fluorescence‐activated cell sorting (FACS).ResultIntracellular iron level in ApoE4‐treated neurons was higher than that in ApoE2‐ or ApoE3‐treated neurons. Furthermore, Fpn level on cell surface was reduced by ApoE4 treatment.ConclusionOur study demonstrates that ApoE4 impairs iron efflux and exacerbate iron accumulation via regulating surface Fpn level.
Aquaporin 4 is associated with cerebral amyloid‐beta and tau deposits in mouse models
Authors: Kecheliev Vasil , Maschio Cinzia , Konetiko Uwe , Nitsch Roger M. , Klohs Jan , Ni Ruiqing 
Published: June 2023

AbstractBackgroundEmerging evidence indicates that the glymphatic system plays an important role in Alzheimer’s disease. Aquaporin 4 (AQP4) constitutes a critical part of the glymphatic system in the clearance of accumulated amyloid‐beta and tau from the brain. Here, we aimed to establish the association between AQP4 and tau as well as amyloid‐beta (Aβ).MethodPerfusion and susceptibility weighted imaging (SWI) magnetic resonance imaging (MRI, at 7 or 9.4 T) were performed in arcAβ mouse model of amyloidosis (aged 16‐18 months), P301L mouse model of 4‐repeat tau (pR5 line) and respective nontransgenic littermates (aged 10‐12 months). Immunofluorescence staining was performed using antibodies against AQP4, CD31, astrogliosis (GFAP, s100β), microgliosis (Iba1, CD68), Aβ (6E10), and tau (AT‐8 and AT‐100) in brain tissue slices from transgenic arcAβ mice and wild‐type littermates.ResultCerebral microbleeds were detected in the cortex and subcortical regions in arcAβ mice. Cerebral blood flow was reduced in the cortex and hippocampus of arcAβ compared to nontransgenic mice but preserved in P301L mice. Increased AQP4 levels were observed surrounding tau deposits in the forebrain of P301L mice and parenchymal amyloid plaques/cerebral amyloid angiopathy in the cortex and hippocampus of arcAβ mice. Depolarization of AQP4 was detected in both arcAβ and P301L mice compared to their respective nontransgenic littermates. Increased s100b‐GFAP and CD68‐Iba1 fluorescence intensities indicative of atrogliosis and microgliosis were detected around tau deposits in P301L mice and amyloid plaques in arcAβ mice.ConclusionWe observed impaired perfusion in arcAβ mice but not in P301L mice, and a spatial association of AQP4 with both tau and Aβ in the brain.
Ophthalmic pathology in patients with primary neurodegenerative diseases
Authors: Makhnovich Ekaterina Vladimirovna , Bogolepova Anna Nicolaevna , Andreevna Kovalenko Ekaterina , Alekseevna Osinovskaya Nina 
Published: June 2023

AbstractBackgroundThe priority problem of modern healthcare is irreversible dementia due to the steady increase in morbidity. Among irreversible dementias, Alzheimer’s disease takes the first place. Most often, only with sufficiently pronounced cognitive disorders, the doctor can diagnose Alzheimer’s disease, although it is obvious that the neurodegenerative process begins even before the clinical manifestations of the disease. Due to the common origin of the eye and the brain, we can say that the eye is a “window to the brain”. Many scientists note the similarities between gerontophthalmological diseases and Alzheimer’s disease.MethodThe study examined 60 patients who were divided into 2 groups: the first group included patients with Alzheimer’s disease, the second group included patients with vascular dementia. Each group included 9 men and 21 women, with an average age of 65.5 years. All patients underwent a comprehensive neuropsychological examination, using the short Mental Status Assessment Scale (MMSE), the Montreal Cognitive Function Assessment Scale (MoCA), the battery of tests for assessing frontal dysfunction (FAB), the clock drawing test. Also, all patients underwent ophthalmological examination of the visometry, measurement of intraocular pressure, examination of the anterior segment of the eye and fundus, and spectral optical coherence tomography.ResultIn the course of the study, significant ophthalmic pathology was detected in the group with neurodegenerative changes ‐ age‐related macular degeneration was found in 16.7%, pseudoexfoliative syndrome‐20%, primary open‐angle glaucoma‐46.7%.ConclusionThis means that the risk of developing gerontophthalmological diseases increases in patients with neurodegenerative disorders. Therefore, we can assume that the retina is a mirror of neurodegenerative changes in the brain, which will allow to diagnose the disease at early stages and with the help of drug therapy to delay further development of the disease, resulting in reduced disability for patients and socio‐economic costs of society.The results obtained are promising for the early diagnosis of primary neurodegenerative diseases and indicate the need for further research on this topic.
Using Academic Detailing to enhance the knowledge, skills and attitudes of clinicians caring for patients with behavioral and psychological symptoms of dementia: 18‐month follow‐up
Authors: Walaszek Art , Schroeder Molly , Albrecht Tammi , LeCaire Tamara J. , Carlsson Cynthia M. 
Published: June 2023

AbstractBackgroundApproximately 90% of persons with dementia experience behavioral and psychological symptoms of dementia (BPSD) over the course of their illness. Primary care clinicians often provide care because specialty geriatric psychiatry consultation may be difficult to obtain. Academic detailing (AD) is an evidence‐based approach for engaging and persuading healthcare professionals to make changes in their practice. We sought to enhance the knowledge, skills and attitudes of primary care providers’ care of patients with BPSD using the AD model.MethodsWe implemented AD in an urban clinic serving a largely Black community and a rural clinic serving a largely White community. Each AD visit included didactic content, case discussion, and consultation regarding patients. Eleven visits over 18 months were planned for each site. Outcome measures included a 10‐item multiple‐choice knowledge assessment and an adaptation of the General Practitioners Attitude and Confidence Scale for Dementia at baseline, 6 and 18 months, and Likert‐scale measurement of acceptability at 6 and 18 months, all self‐report. Differences in knowledge and attitude scores were determined for those providing complete responses at baseline and follow‐up. Thematic analysis of qualitative feedback collected 18 months will be completed.ResultsFive urban and 14 rural providers completed baseline assessments. Providers were mostly White (95%) and Non‐Hispanic (100%); 47% were female (Table 1). Seventeen (89%) participated in one or more AD visits and 13 (68%) participated in the 6‐month survey. Knowledge, attitudes and confidence regarding BPSD and dementia care increased (Table 2). Assessments at 18‐months and qualitative analysis of case discussions are forthcoming and will be presented.ConclusionsAcademic detailing (AD) is a feasible way of increasing self‐reported knowledge and skills and improving self‐reported attitudes of primary care providers responsible for the care of patients with BPSD. Knowledge and confidence in BPSD and dementia care increased after 6 months’ participation in AD. During the pandemic we successfully adapted the AD model to a virtual platform, which has implications for portability of this model to other settings. The pilot data collected in this study will inform the design of a larger study to measure the impact of AD on patient outcomes.
Amyloid PET ordering practices in a memory disorders clinic
Authors: Turk Katherine W , Vives‐Rodriguez Ana , Schiloski Kylie A , Marin Anna , Wang Ryan , Singh Prabhjyot , Hajos Gabor P , Powsner Rachel , DeCaro Renee , Budson Andrew E 
Published: June 2023

AbstractBackgroundThe objective of the current study was to assess amyloid PET scan ordering practices in a Veterans Affairs memory disorders clinic, where such scans are readily available, and the extent to which amyloid PET ordering may occur in memory disorders clinics if covered by insurance in the future.MethodsUsing retrospective chart review over a three‐year period, we compared patient demographic, clinical, and MRI structural features that were predictive of ordering an amyloid PET scan in a memory disorders clinic to those of patients who did not have one ordered. The percentage of patients who met previously published appropriate use criteria were evaluated.ResultOverall 34.9% of patients received an amyloid PET scan as part of their diagnostic workup and 97.9% of these ordered scans were consistent with appropriate use criteria. Patients who received an amyloid PET were younger on average and more likely to have an initial diagnosis of suspected AD. Overall, 64.4% of patients without an amyloid PET scan ordered would have met appropriate use criteria for amyloid PET. Thus, fewer patients received an amyloid PET scan than were eligible according to current appropriate use criteria.ConclusionA little more than a third of veterans in a memory disorders clinic received an amyloid PET scan as part of their diagnostic work up when ordering was freely available to cognitive behavioral neurologists and not constrained by third‐party reimbursement. The vast majority of amyloid PET scans ordered were consistent with current appropriate use criteria. Future versions of the appropriate use criteria for amyloid PET could address ordering in patients with subjective cognitive decline with behavioral/functional impairments as well as patients under consideration for possible anti‐amyloid therapy treatment with Aducanumab and other medications in this class.
Risks and mitigating factors in psychosocial adjustment of spousal caregivers of people with dementia
Authors: Ho‐yin Lai Frank 
Published: June 2023

AbstractBackgroundWe are living in an era when the world’s aging population is rapidly expanding. The importance of family caregivers has been receiving increasing attention since last decade. With longer lifespans and limited caregiving resources from the affected ones’ own children, some of whom are even childless, caregiving for older adults has become the main responsibility of their spouses. Caring for older adults with dementia has always been a family endeavor and spousal caregivers play a crucial role in caring for people affected by dementia in the communityMethodBy applying the Stress Process Model to examine the characteristics of people with dementia and their spousal caregivers, this study aims to identify the potential risk and mitigating factors of psychosocial adjustment among the spousal caregivers. We recruited 80 care recipient‐caregiver couples in Hong Kong and examined the relationships of socio‐economic, care recipient’s, and caregiver’s factors with spousal caregivers’ psychosocial adjustment through the use of questionnaire survey.ResultIt was found that care recipients’ cognitive functions were associated with caregivers’ reported frequencies of their behavioral and psychological symptoms of dementia (BPSD) (r = .30, p = .008), and caregivers’ perceived burden of caregiving (r = ‐.54, p = .008). Caregivers’ quality of life was associated with their perceived caregiving burden (r = ‐.82, p = .001) and self‐efficacy (r = .32, p = .001). Upon further examining the caregiving model with these parameters, a significant multivariate general linear model was found with (F (1, 12) = 13.06, p = .001, partial eta square = .70, observed power = .99). Moreover, female caregivers reported higher sense of caregiving stress and poorer quality of life than male caregivers.ConclusionThis study found that the cognitive functions and BPSD of care recipients with dementia and perceived level of caregiving burden are strongly associated with degrees of psychosocial adjustment among their spousal caregivers. The self‐perceived caregiving role in a family is also a possible confounding factor contributing to the perceived caregiving burden. To support in‐home caregiving of people with dementia, strategies to empower spousal caregivers to execute their caregiving roles are recommended.