bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessment of cognition in Chinese older population from a digital game‐based mobile applet: an observational study
Authors: Huang Lin , Li Yatian , Wu Jingnan , Xia Huanhuan , Li Kun , Wang Ziming , Guo Qihao 
Published: December 2023

AbstractBackgroundA rapid and reliable digital instrument is needed to improve the efficiency of dementia screening. We developed a digital game‐based mobile applet, Game‐based Cognitive Assessment – 3‐minute Version (G3), and aimed to summarize the demographic characteristics and cognitive performance of the online users in a large‐scale Chinese population.MethodThe G3 instrument is self‐administered, and includes cognitive tasks designed as interesting games to automatically assess individuals’ performance on six cognitive domains, i.e., calculation, executive function, visual perception, abstraction, memory and attention. We used an observational design to review all participants who registered for G3 assessment between Feb 28, 2020, and Oct 31, 2022. We restricted our analysis to a population of middle aged and older adults aged 45 to 89, as the focus of our study population. We descriptively analyzed the demographics, global cognitive scores, and the six domain scores of G3 users stratified by sex, education and geographic location.ResultA total of 12,113,327 individuals were enrolled in this study, of which 1,273,521 were 45∼89 years old. Among the population aged 45∼89, the mean G3 total score was 61.7±13.1 for women (n = 575490) and 60.1±13.2 for men (n = 698031). There was a tendency for the G3 scores in all cognitive domains to decrease with age and women were observed to achieve significantly higher scores than men in almost all age groups. When classified by education level, the G3 scores tended to decline with age in all groups, whereas those with relative low education level (below primary school) and advanced age (80‐89 years old) were heterogeneous. When classified by geographic locations, significant increases in G3 scores were observed among those aged 65‐69 years old in central China.ConclusionOur findings characterized the demographic characteristics and cognitive performance of Chinese older population via G3 instrument in a large sample and support the application of G3 for cognitive screening in a community‐based population with different ages and education levels in all regions of China. However, interpretation should be cautious in a population with low education and advanced age.
Association of kidney function with dementia and structural brain differences: a large population‐based cohort study
Authors: Wang Shuqi , Wang Jiao , Dove Abigail , Guo Jie , Miao Yuyang , Qi Xiuying , Xu Weili 
Published: December 2023

AbstractBackgroundThe association between kidney function (KF) and dementia risk and the mechanisms underlying this relationship remain unclear. We aimed to examine the association of impaired KF with dementia and structural brain differences on magnetic resonance imaging (MRI).MethodWithin the UK biobank, 191,970 dementia‐free participants aged ≥60 (mean age: 64.1 ± 2.9 years) were followed for 16 years to detect incident dementia. Serum creatinine and cystatin C were measured at baseline to calculate estimated glomerular filtration rate (eGFR, mL/min/1.73 m2) using the Chronic Kidney Disease Epidemiology Collaboration equation. KF was categorized as normal (eGFR ≥ 90), mildly impaired (60 £ eGFR < 90), or moderately to severely impaired (eGFR < 60). Dementia was assessed based on self‐reported medical history and medical records. During the follow‐up, a subsample of 12,637 participants underwent brain MRI scans. Volumes of total brain, gray matter, white matter, hippocampus, and white matter hyperintensities were assessed. Data were analyzed using Cox regression, Laplace regression, and linear regression.ResultOf all participants, 122,463 (63.8%) had mildly impaired KF and 8,670 (4.5%) had moderate to severely impaired KF at baseline. Over the follow‐up (median [interquartile range]: 12.8 [11.9‐13.5] years), 5,327 (2.8%) participants developed dementia. In multi‐adjusted Cox regression, eGFR was dose‐dependently associated with dementia (per 1‐standard‐deviation decrease in eGFR; hazard ratio [HR] 95% confidence interval [CI]: 1.10 [1.07‐1.14]). Compared to normal KF, there was an increased risk of dementia with moderate to severely impaired KF (HR 1.53, 95% CI 1.32‐1.76) but not mildly impaired KF. In Laplace regression, dementia onset among people with moderate to severely impaired KF occurred 1.53 (95% CI: 0.98–2.08) years earlier than those with normal KF. Moderate to severely impaired KF was related to significantly lower gray matter volume (β = ‐0.11, 95% CI: ‐0.19– ‐0.03), but not to other brain MRI measures.ConclusionImpaired KF is associated with about 50% increased risk of dementia and anticipates dementia onset by more than 1.5 years. Brain neurodegeneration may underlie the KF‐dementia association.
Clinical effects of Lewy body pathology in clinically unimpaired and cognitively impaired individuals – A prospective longitudinal study
Authors: Hansson Oskar , Palmqvist Sebastian , Parchi Piero 
Published: December 2023

AbstractBackgroundAggregates of misfolded α‐synuclein are the underlying pathology of Lewy body (LB) disease. Little is known about the early effects of LB pathology in preclinical (i.e., pre‐symptomatic) individuals. Further, there is poor knowledge about the independent clinical effects of Lewy body (LB) pathology in patients with cognitive decline, especially when coexisting with Alzheimer’s disease (AD) pathology.MethodHere, we examined the effects of LB pathology using a cerebrospinal fluid α‐synuclein seeding aggregation assay in 1,182 cognitively and neurologically unimpaired participants as well as 882 participants with mild cognitive impairment or dementia from the BioFINDER‐1 and BioFINDER‐2 studies.ResultIn clinically unimpaired individuals, we found that 8% were LB‐positive, 26% Aβ‐positive (12% of those were also LB‐positive), and 16% tau‐positive. LB pathology had independent and significant negative effects on cross‐sectional and longitudinal global cognition and memory. These were similar in magnitude to the effects of tau pathology and more pronounced than those of Aβ pathology. Participants with both LB and AD (Aβ and tau) pathology exhibited faster cognitive decline than those with just LB or AD pathology. LB, but not AD, pathology was associated with reduced sense of smell.In cognitively impaired individuals, we found that 23% of participants had LB pathology, of whom only 32% fulfilled clinical criteria of Parkinson’s disease or dementia with Lewy bodies, and 54% exhibited AD pathology (amyloid‐β+ and tau+). Within the LB‐positive group, 48% also had AD‐pathology. In the AD‐positive group, 17% of patients with mild cognitive impairment and 24% of those with dementia were also LB‐positive. LB pathology was associated with worse attention/executive, visuospatial, and motor function independently of AD pathology. Moreover, LB pathology was also independently associated with a faster longitudinal decline in all examined cognitive functions.ConclusionThis study highlights the cognitive effects of LB pathology, independent from AD pathology, in clinically unimpaired individuals, which will be important to consider for prognosis and design of both preclinical AD and LB disease trials.Further, analyzing LB status, in addition to amyloid‐β and tau, in cognitively impaired individuals provides a better precision medicine approach identifying patient subgroups with different clinical trajectories.
A systematic review of measures of social connection for people living in long‐term care homes
Authors: Dewan Neha , Chapman Hannah , Sommerlad Andrew , Liougas Madalena , Livingston Gill , McGilton Katherine S , Bethell Jennifer 
Published: December 2023

AbstractBackgroundSocial connection is important for quality of life and care in long‐term care (LTC) homes. However, measuring social connection in LTC residents is challenging due to the high prevalence of dementia and the distinct care environment and activities, so research is limited by a lack of consensus on best approaches to measurement. The objective of our study is to systematically review measures of social connection developed for LTC residents, including those with dementia, by evaluating their measurement properties including structural validity, internal consistency, reliability and construct validity.MethodWe are following COnsensus‐based Standards for the selection of health Measurement INstruments (COSMIN) systematic review methods. We searched multiple bibliographic databases to November 2021 for studies conducted in LTC residents, which quantified any aspect(s) of social connection, and reported at least one psychometric property for the measure(s) of social connection. We conducted a second targeted search in April 2022 using our list of identified measures, supplemented with a list of measures used in previous research in this population. We are using COSMIN guidelines to evaluate the measurement properties reported for each identified measure.ResultWe identified 68 studies reporting on 35 measures that assess social connection in LTC homes. Twenty‐five were measures of quality of life, wellbeing or life satisfaction and included a social connection subdomain. Only 10 measures specifically targeted social connection. From our pooled evaluation of 20 measures to date, we found that 20% (n = 4) have sufficient structural validity, 15% (n = 3) have sufficient internal consistency, 25% (n = 5) have sufficient reliability, and 15% (n = 3) have sufficient construct validity.ConclusionMany measures have assessed social connection in LTC settings for people living with dementia, but few are designed for this purpose and they often have insufficient psychometric properties. This review will provide detailed evidence of the quality of these measures to enable researchers to prioritize valid and reliable tools. Our results will inform our development of a new person‐centred social connection measurement tool for LTC residents in the Alzheimer’s Association/Brain Canada‐funded Social Connection in Long‐Term Care Home Residents (SONNET) study.
The visibility of retinal amyloid deposits as a biomarker of Alzheimer’s disease when imaged in polarized light through the cornea
Authors: Campbell Melanie CW , Potsiluienko Yurii , Mason Erik L , Redekop Rachel , Kitor Monika , Emptage Laura , Hirsch‐Reinshagen Veronica , Hsiung Ging‐Yuek Robin , MacKenzie Ian R 
Published: December 2023

AbstractBackgroundWe previously reported a novel, dye‐free method to image amyloid deposits in the retina. Using polarized light interactions to create deposit contrast, the number of deposits in ex vivo retinas predicted the severity of brain amyloid found in association with Alzheimer’s disease (AD). Here we describe the effect of the potential range of corneal interactions with polarized light on the visibility of these retinal deposits when imaged in vivo.Method52 retinal amyloid deposits, positive for thioflavin (Fig 1) and with a range of visibility in polarized light were imaged ex vivo in retinas of 12 participants with a moderate (2) or high (10) likelihood of Alzheimer’s disease, based on brain pathology. New images of each deposit were created by combining the polarized light interactions of the deposit and surrounding retina with the known range of interactions of human corneas with polarized light. The varying contrasts of each deposit with 45 different sets of corneal properties (a total of 2340 deposit images) were compared to the initial ex vivo images.ResultAs a function of the modelled corneal properties, the root mean square (RMS) contrast of each deposit both increased and decreased from that without a cornea (Fig 2). On average, RMS contrast across deposits combined with a cornea decreased 12% from that without a cornea. For 3% of deposit images, there was a corneal property that reduced the deposit contrast by over 50% (Fig 2). However, even in these cases, because of the variation in interaction with polarized light across the deposit (Fig 3), the deposit remained visible against the background retina.ConclusionAlthough the cornea interaction with polarized light will affect images of amyloid deposits in the retina taken with our non‐invasive method, all cases investigated are predicted to remain visible against the background retina. In addition, during in vivo imaging, an established method of compensating for an individual’s corneal interaction with polarized light, would guarantee 100% visibility. Thus, in vivo, our retinal imaging method is predicted to give a biomarker of the severity of amyloid in the brain found in association with Alzheimer’s disease.
Distribution of APP in endo‐lysosomal system induced by Aβ is modulated by Gβγ signaling
Authors: Antonino Magdalena , Marmo Paula , Almirón Romina , Lorenzo Alfredo , Bignante Elena Anahi 
Published: December 2023

AbstractBackgroundAlzheimer´s disease is characterized by the deposition of aggregated species of amyloid beta (Aβ) in the brain, which leads to progressive cognitive deficits and dementia. We recently found that Aβ assemblies, oligomers and fibrils, increase APP and BACE1 interaction in recycling endosomes and accumulation of intracellular Aβ42 in human neurons derived from iPSCs by a mechanism dependent of APP/Go/Gβγ signaling (Antonino et al 2022, https://doi.org/10.3389/fcell.2022.852738). Now, we are interested on deepen in the APP trafficking in the endo‐lysosomal pathway in order to understand the mechanism underlying such effect.MethodN2a and human neurons derived from iPSc cultures were transfected with fluorescently tagged proteins (APP‐YFP, BACE‐CH, Rab11‐RFP, LAMP1‐CH, Rab7‐CH, APP‐VN, BACE‐VC). Cultures were treated with vehicle or the Gβγ inhibitor gallein and 30 minutes later with vehicle or 1 µM of Aβ oligomeric or fibrillar. After 24 h of treatment quantitative colocalization analysis and bimolecular fluorescence complementation assays were performed.ResultWe found that Aβ induced an enrichment of APP in recycling endosomes at the expense of a decrement of its levels in lysosomes. This change in APP intracellular distribution is drive by Gβγ signaling. Moreover, we found that the changes on APP distribution correlate with an increase in its interaction with BACE1 and with an increase in the number of recycling endosomes, both events modulated by Gβγ signaling (Figure 1,2).ConclusionTogether, these results suggest that Aβ pathological assemblies induce a re‐direction of APP from its physiological route to lysosomes, to recycling endosomes which favors its encounter with BACE1 and its amyloidogenic processing. These finding elucidate the intracellular process which sustain the feed‐forward mechanisms implicated in the amyloidogenesis induced by pathological assemblies of Aβ.
Relationship between Physical Activity, Handgrip Strength, Depressive Symptoms, and Cognitive Impairment in Korean older adults
Authors: Jin Youngyun , Kim Donghyun , Kim Sehwan , Kim Mingeun , Kim Taewan 
Published: December 2023

AbstractBackgroundPhysical activity, muscle strength, depressive symptoms, and cognitive function are intertwined in later life. This study aimed to investigate the association physical activity (PA), relative handgrip strength (RHGS), depressive symptoms, and cognitive impairment in Korean older adults.MethodThis study consisting of 512 community‐dwelling Korean older adults (417 female, 95 male) aged 65 years and older (74.8±5.4 years) in S‐city, Gyeonggi‐do. PA and handgrip strength were assessed with the Global Physical Activity Questionnaire and using a dynamometer (GRIP‐D; Takei Ltd, Niigata, Japan). Depressive symptoms were evaluated using the Korean form of the Center for Epidemiologic Studies Depression (CES‐D) Scale. Cognitive impairment was assessed with the Mini‐Mental State Examination for Dementia Screening (MMSE‐DS) of Korean version. The PROCESS V3.4 macro for SPSS based on the bootstrap method was used to determine the mediating effects of PA and RHGS on the relationship between depressive symptoms and cognitive impairment.ResultMultiple logistic regression showed that insufficient PA was associated with high odds of a cognitive impairment ((OR = 2.972, 95%CI = 1.749‐5.052, p = .002) compared with sufficient PA (OR = 1). Weak RHGS (OR = 3.540, 95%CI = 2.156‐5.814, p<.001) was associated with high odds of the cognitive impairment compared with normal RHGS (OR = 1). Depressive symptoms (OR = 2.676, 95%CI = 1.594‐4.492, p<.001) were associated with higher odds of the cognitive impairment compared with normal depression status (OR = 1). Particularly, depressive symptoms were found to have both direct and indirect effects on cognitive impairment. As predicted, PA and RHGS partially mediated the relationship between depressive symptoms and cognitive impairment (PA: B = –0.017, 95%CI = –0.028 ‐ –0.009, p<.001; RHGS: B = –0.005, 95%CI = –0.007 ‐ –0.003, p<.001). In addition, serial mediation analysis indicates that the association between depressive symptoms and cognitive impairment was partially mediated by PA and RHGS in a sequential manner (B = –0.004, 95%CI = –0.006 ‐ –0.002, p<.001).ConclusionAccording to the results of the serial multiple mediation model, the elderly should be encouraged to continue their physical activity in daily life, which not only improves and maintaining muscular strength but also reduces the negative impact of depressive symptoms on cognitive impairment.
Effect of resistance exercise on secondary inflammatory insult in Alzheimer’s disease models
Authors: Wong Alvin Ka‐Wai , Chang Raymond Chuen‐Chung 
Published: December 2023

AbstractBackgroundPhysical exercise improves cognition in human and animal studies associated with Alzheimer’s Disease (AD). However, resistance‐type regimes remain poorly investigated. Acute illness or injury can influence the rate AD progression and trigger accelerated cognitive decline.MethodTo evaluate the role of RE in modulating pre‐existing cognitive impairment, female 3xTg and 5xFAD mice underwent a five‐week RE training protocol. An acute systemic inflammatory insult: laparotomy or intraperitoneally‐injected LPS, was performed to investigate the effect of RE under these challenges. Behavior tests was used to probe for cognition and learning. Brain homogenates were harvested for western blot analysis, qPCR, or post‐fixed in neutral‐buffered formalin solution for immuno‐histochemical exploration.ResultRE showed improved cognitive function, reduced P‐S396‐tau, decreased ionized calcium‐binding adapter molecule 1 (Iba‐1), and decreased inflammatory cytokine transcripts compared to sedentary controls. RE significantly reduced anxiety‐like behavior and cognitive deficit stimulated by acute systemic inflammation episode.ConclusionRE attenuates exaggerated cellular responses and improves cognitive functions in AD and accelerated cognitive impairment triggered by secondary inflammation insult.
Caregiving for a spouse with cognitive impairment: Effects on serum homocysteine level
Authors: Jeon So Yeon , Kim Jeong Lan 
Published: December 2023

AbstractBackgroundAmong older adults, being a spousal caregiver (SCG) for a patient with cognitive impairment is well known to be associated with increased risk for cognitive decline and cardiovascular disease. It is important to understand the caregiving‐related risk factor for caregiver’s health outcome. Elevated total serum homocysteine also has been linked to cognitive impairment and is a risk factor for cardiovascular disease. Therefore, this study aims to examine the relationship between caregiver burden with serum homocysteine level in older adults couples.MethodFrom May 2020 to December 2022, clinical evaluation and blood tests were conducted for patients who visited Chungnam National University Geriatric Neuropsychiatric clinic with their spouse. A total of 92 individuals were included in the analysis. As clinical assessment, we evaluated the care burden using Zarit burden interview and blood samples were collected from the subjects after overnight fasting.ResultIn linear regression analysis adjusted for age, sex, care‐recipient’s clinical diagnosis, vascular risk score and apolipoprotein E ε4 positivity. The SCG’s burden was significantly associated with the level of homocysteine (β = 0.289, t = 2.670, p = 0.009). As SCG’s burden increased, the serum homocysteine level also increased. The results were unchanged after excluding care‐recipient with normal cognition (n = 8) (β = 0.266, t = 2.432, p = 0.018)ConclusionThis finding suggest that SCG’s burden for patients with cognitive impairment might raise homocysteine levels among SCGs which can further affect cardiovascular disease and cognitive decline. As such, homocysteine level should be well monitored among SCGs for patient with cognitive impairment.
Incorporating Mindfulness Based Strategies in CarePRO‐Virtual Spanish (CarePRO‐VS): A Multicomponent Intervention for the Latino Community
Authors: Manzo Alma A , Coon David W. , Gonzalez Maria S , Glinka Allison , Carbajal Berta , Gómez‐Morales Abigail 
Published: December 2023

AbstractBackgroundA recent report estimates Latinos in the U.S. living with Alzheimer’s Disease (AD) could reach as high as 3.5 million by 2060 and are 1.5 times more likely to develop AD than non‐Latino Whites. Consequently, Latino caregivers of people with Alzheimer’s Disease or other related dementias (ADRD) face significant risks to their physical and mental well‐being. Due to the immense increase of ADRD in Latinos, it is important for research to highlight the ways in which caregivers can learn mindfulness based skills to support challenges they may face.MethodU.S. Latina caregivers of people with ADRD (n = 18) were analyzed from the CarePRO‐VS program. CarePRO‐VS is a multicomponent skill‐focused intervention conducted in Spanish that manages stress, tension and frustration associated with caregiving. This pilot project was conducted over ten weeks via telephone and Zoom including: (1) screening to determine eligibility, (2) pre‐ and post‐ intervention assessments conducted within approximately two weeks of the intervention, (3) individual “coach calls” and (4) the five‐week CarePRO‐VS program.ResultBy week five, 60% of caregivers used mindful breathing 3 or more times a day. In comparison to week one, only 18.8% of caregivers used mindful breathing 3 or more times a day. As an example of a frequent user, coach call notes showed that one participant in particular self‐reported use of the relaxing techniques every week with an average of 3‐4 times a day. Mindful breathing helped her destress, stay positive, and focus on the present moment. Body scans helped her bring awareness to how she felt during stressful situations involving her father, the care recipient. She also extended the use of mindful breathing to situations beyond caregiving. At five weeks, she used mindful breathing with her father to ease his anxiety.ConclusionThese Latina caregivers implemented a new strategy that shows promising results and future research can expand on aspects of mindfulness as an equitable and accessible strategy to increase relaxation for caregivers and care recipients. To date, there are few published studies incorporating mindfulness techniques that also included Latino caregivers of people with ADRD in the U.S.