bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of a self‐help behavioural activation intervention INVOLVERA for people with dementia: a qualitative study
Authors: Blomberg Oscar , Svedin Frida , Brantnell Anders , Farrand Paul , von Essen Louise , Åberg Anna Cristina , Woodford Joanne 
Published: December 2023

AbstractBackgroundDespite dementia being highly prevalent there is a lack of interventions to support people with dementia, and their informal caregivers, to live well. A guided, self‐help, behavioural activation‐based intervention (INVOLVERA), designed to support people with dementia to re‐engage with pleasurable, routine, and self‐care activities they have stopped doing, may represent a solution (Svedin et al., 2021). An innovative aspect of INVOLVERA is that support to the person with dementia to use INVOLVERA is provided by an informal caregiver, who themselves receives guidance from a healthcare professional. To enhance intervention acceptability and relevance interventions should meet the needs and preferences of the target population. Following Phase I (Development) of the Medical Research Council’s Framework for the development of complex interventions (Skivington et al., 2021), this study explores the needs and preferences of people with dementia, informal caregivers, and professional stakeholders to enhance the acceptability and relevancy of INVOLVERA for people with dementia.MethodsSemi‐structured interviews and focus group discussions were held with people with dementia (n = 8), informal caregivers (n = 19), healthcare professionals (n = 18), and community stakeholders (n = 7). A written draft of INVOLVERA and proposed intervention delivery model were provided to participants. Open‐ended questions explored intervention content, language and intervention delivery preferences. Data were analysed using manifest content analysis.ResultsOne overarching theme: Tailoring and flexibility, and three categories: Intervention process, material and context; Support and guidance; and Time derived from analysis. Results informed the following adaptations: (1) increased flexibility of intervention delivery (e.g., outside of traditional healthcare settings); (2) additional guidance and training to informal caregivers; (3) reduced written material (to minimise treatment burden); (4) modernisation of design and illustrations; (5) improved relevance of case stories and illustrations to the Swedish context; and (6) increased diversity of persons in case stories.ConclusionThis study highlights the importance of developing interventions alongside stakeholders. We anticipate the approach will optimise the acceptability and relevancy of INVOLVERA. Next, we will examine the acceptability and feasibility of INVOLVERA.
Cognitively Healthy Centenarians are genetically protected against Alzheimer’s disease
Authors: Tesi Niccoló , Van Der Lee Sven J , Hulsman Marc , van Schoor Natasja , Huisman Martijn , Pijnenburg Yolande A. L. , Flier Wiesje M. , Reinders Marcel JT , Holstege Henne 
Published: December 2023

AbstractBackgroundThe prevalence of Alzheimer’s Disease (AD) increases with age, yet a small fraction of the population reaches ages beyond 100 years maintaining cognitive abilities, so‐called cognitively‐healthy‐centenarians. We aimed to uncover the genetic factors associated with such protection against AD, and to highlight the effects of AD‐associated variants during advanced aging.MethodPrevious Genome‐Wide‐Association‐Studies (GWAS) identified 86 single‐nucleotide‐polymorphisms (SNPs) associated with AD‐risk. We investigated the frequency of each SNP in 346 cognitively‐healthy‐centenarians (mean age 101.05±2.51), compared to 2,281 AD cases (mean age 67.96±9.84), 3,165 middle‐aged healthy controls (mean age 62.57±8.66), and we combined the SNPs into Polygenic Risk Scores (PRS) for each individual. Finally, we characterized the functional properties of the SNPs enriched/depleted the most in the centenarians.ResultAt the SNP level, centenarians were depleted with risk‐increasing SNPs and enriched with protective SNPs. The AD‐related PRS (excluding APOE SNPs) was significantly lower in centenarians; not only compared to AD (OR = 1.96, p = 4.07×10−26), but also to middle‐aged controls (OR = 1.29, p = 2.61×10−5). When including APOE SNPs these effects were even stronger (OR = 5.07, p = 6.15×10−71, and OR = 1.87, p = 4.67×10−17, for comparisons with AD and normal controls, respectively). The most depleted/enriched SNPs in centenarians functionally mapped to activation/regulation of immune response and endocytosis/phagocytosis. These SNPs were located near ANKH, TMEM106B, CLNK, EPDR1, WDR12, PLCG2, RIN3, CD2AP, MS4A, TREM2, ABCA7 and MAF.ConclusionThe ability to reach advanced age without cognitive decline is influenced by AD‐associated genetic variants. An advantageous regulation of the brain’s immune system, intracellular protein trafficking, and endocytosis/phagocytosis may confer the strongest protection against AD and potentially other age‐related diseases.
Baseline characteristics and study progress of the CITA GO‐ON Study. A FINGER‐like Multidomain Intervention to Prevent Cognitive Decline in Spain
Authors: Ecay Mirian , Tainta Mikel , Iriondo Ane , Altuna Miren , Estanga Ainara , Clerigue Montserrat , Saldias Jon , de Arriba Maria , Lopez Carolina , Garcia‐Sebastian Maite , Barandiaran Myriam , Izquierdo Mikel , de Asteasu MIkel Lopez‐Saez , Reparaz‐Escudero Imanol , Gayoso Lucia , Etxeberria Usune , Gorostiaga Arantxa , Balluerka Nekane , Soroa Goretti , Aritzeta Aitor , Ros Naia , Capetillo‐Zarate Estibaliz , Alberdi Elena , Mar Javier , Vergara Itziar , Mateo‐Abad Maider , Martinez‐Lage Pablo 
Published: December 2023

AbstractBackgroundThe FINGER study demonstrated the efficacy of a non‐pharmacological multidomain intervention to prevent cognitive decline in at‐risk older adults. After a successful pilot feasibility study, in Q3 2021 we launched the CITA GO‐ON study, inspired by FINGER methodology to demonstrate the efficacy of a risk factor and lifestyles multimodal intervention to prevent cognitive decline in southern Europe. Here we describe the baseline characteristics of participants recruited in the study.MethodThe CITA GO‐ON study (ClinicalTrials.gov, NCT04840030) is a two‐year randomized, controlled trial. The primary aim is to reduce the risk of decline in cognitive functioning in the Neuropsychology Test Battery after two years by a multi‐modal intervention on risk factors and protective life‐styles as compared to standard health care. Inclusion criteria are: 60‐85 years old; CAIDE dementia risk score ≥ 6; cognitive frailty; no dementia. The multidomain intervention includes optimized control of cardiovascular risk factors; correction of polypharmacy; cognitive training; physical exercise program; socioemotional intervention; and promotion of adherence to the Mediterranean diet.ResultsTo date, 1964 individuals completed pre‐screening using self‐administered online survey in REDCap (Research Electronic Capture) and 874 (44.5%) fulfilled criteria for an in‐person screening visit. Screening was successful in 477 of participants. Mean (SD) age is 66.24 (4.99), 13.26 (4.43) years of education, MMSE 28.27 (1.78), CAIDE score 7.48 (1.36), and 235 (49%) are men. Based on CAIDE components, at baseline, 287 (60%) showed high systolic blood pressure, 165 (35%) low physical activity, 122 (26%) high BMI, and 101 (21%) with high cholesterol. Regarding cognitive frailty, 144 (31%) presented low performance on brief cognitive testing (Memory Alteration Test ≤ 40 and/or Fototest ≤ 35), 186 (39%) presented memory complaints (Cognitive Change Index ≥ 20), and 147 (30%) showed both criteria. Currently, 191 have been randomly assigned to the control and 192 to the Intervention groups. So far, adherence to intervention activities is high, ranging from 73% to 97%, depending on the modality.ConclusionCITA GO‐ON Study recruitment strategy includes participants with high risk of dementia based on modifiable factors and in situation of cognitive fragility, with might increase the probability of obtaining positive efficacy results.
The natural history of subjective complaints, awareness and metacognition in AD
Authors: Cappa Stefano F , Ribaldi Federica , Chicherio Christian , Frisoni Giovanni B 
Published: December 2023

AbstractBackgroundSubjective cognitive decline (SCD) is the self‐reported experience of decrease in cognitive function in absence of cognitive impairment. This condition is common in elderly subjects and is a frequent reason for referral to memory clinics. SCD is often considered as a stage antedating objective impairment, and an at‐risk condition for subsequent dementia. Recent large‐scale studies, however, support an increased risk only in subjects positive for Alzheimer’s disease (AD) biomarkers, confirming that SCD can be due to multiple mechanisms, including functional cognitive disorders.MethodThis work have reviewed the current research on the awareness of cognitive decline (ACD), with a focus on metacognitive abilities and on assessment tools. The findings from studies of ACD during the course of AD are also reviewed for their possible impact on clinical management.ResultWe propose that, in presence of normal cognitive performance, a subjective overestimation of objective cognitive performance may be a negative prognostic marker, while subjective overestimation of cognitive decline may be compatible with healthy aging or the presence of a functional cognitive disorder.ConclusionLongitudinal studies are needed to test the usefulness of metacognition measures to select SCD subjects for biomarker assessment and/or metacognitive training.
Early detection of mild cognitive impairment due to Alzheimer’s disease using combinations of an online cognitive assessment and blood biomarkers
Authors: Pei Zhong , Chen Weineng , Liu Ganqiang , Lin Cha , Su Fengjuan 
Published: December 2023

AbstractBackgroundAccessible measurements to a large screening and early differentiation of mild cognitive impairment due to Alzheimer’s disease (MCI‐AD) from healthy elderly is increasing urgent with the prevalence of Alzheimer’s disease (AD) expanded.Methodan online cognitive assessment (Memtrax) and MoCA were performed, on 99 clinically diagnosed cognitively normal (CON) and 101 MCI‐AD participants. The plasma levels of phosphorylated tau (p‐tau)181 and neurofilament light (NfL) and amyloid beta (Aβ)42/40 were measured using Simoa assay. The relevance between Memtrax and blood biomarkers were conducted by Spearman correlation analysis. Discrimination models were built using assorted machine learning approaches combining Memtrax with blood biomarkers, and model performance was measured using Area Under the Receiver Operating Characteristic Curve (AUC).ResultThe AUC of Memtrax and MoCA in differentiating MCI‐AD from CON was similar. Memtrax has a strong correlation with phosphorylated tau (p‐tau)181 and neurofilament light (NfL), while less related to amyloid beta (Aβ)42/40. Combining Memtrax and blood biomarkers, the AUC of best model reach to 0.975 (95% CI: 0.950‐0.999).ConclusionThe combination of Memtrax and blood biomarkers is promising to the large screening and early detection in MCI‐AD.
Psychometric evaluation of the A‐NKS – a diagnostic instrument to assess impairment of activities of daily living in mild and severe Neurocognitive Disorder according to DSM‐5
Authors: Grothe Jessica , Kropidlowski Adam , Elgner Melanie , Luppa Melanie , Pabst Alexander , Schomerus Georg , Funke Katja , Dietzel Jens , Saur Dorothee , Luck Tobias , Riedel‐Heller Steffi G. 
Published: December 2023

AbstractBackgroundActivities of daily living functioning (ADL) are relevant in the diagnosis of neurocognitive disorders (NCD). Currently, however, there has been no standardized and validated instrument based on DSM‐5 diagnosis criteria. Our aim was to psychometrically evaluate the differentiated assessment of ADL impairments due to NCD (A‐NKS).MethodWe interviewed 92 dyads of individuals with either mild NCDs, major NCDs, or cognitively healthy individuals and a relative each and examined reliability, validity, and acceptability of the A‐NKS.ResultBoth versions had excellent internal consistency and are correlated with other (I)ADL instruments (patient [informant]: Barthel Index: rs = ‐0.26, p ≤ .05 [rs = ‐0.30, p ≤ .01]; Amsterdam IADL: rs = 0.59, p ≤ .01 [rs = 0.48, p ≤ .01]; SIDAM ADL: rs = 0.46, p ≤ .001 [rs = 0.47, p ≤ .001]). Aditionally, there are correlations with the scale autonomy of the WHOQOL‐OLD (rs = ‐0.50, p ≤ .001 [rs = ‐0.37, p ≤ .001]) and physical, as well as cognitive activities (rs = ‐0.39, p ≤ .001 [rs = ‐0.50, p ≤ .001]). All participants found the questionnaire acceptable.ConclusionThe A‐NKS shows promise as a valid, reliable and acceptable measure to assess ADL due to neurodegenerative decline in healthy individuals, individuals with mild NCDs and those with major NCD.
Cognitive trajectories in prevalent and incident hearing impairment: A 12‐year follow‐up of the Maastricht Ageing Study (MAAS)
Authors: Soons Lion M. , Deckers Kay , van Boxtel Martin P.J. , Köhler Sebastian 
Published: December 2023

AbstractBackgroundHearing impairment (HI) is a common and often treatable condition that is associated with increased risk of cognitive impairment and dementia. However, little is known about the cognitive course of individuals with incident HI. The objective of this study was to investigate the temporal association between prevalent and incident HI and change in cognition over 12 years.MethodData was used from the Maastricht Ageing Study (MAAS), a Dutch cohort of 1823 cognitively healthy individuals aged 24‐82 years. Individuals were repeatedly assessed at baseline, 6 and 12 years. Hearing acuity was assessed using pure‐tone audiometry thresholds in decibel (dB). Prevalent (baseline) HI was categorized into no HI (average acuity <20 dB), mild HI (≥ 20 and <35 dB) and moderate to profound HI (≥35 dB). The presence of incident HI was defined by an average threshold of 20 dB at 6‐ or 12‐years in those without HI at baseline and follow‐up data (n = 1071). Verbal memory, information processing speed, and executive function were assessed. Linear mixed models were used to test the association between HI and change in cognitive function over time, adjusted for age, sex, education, and a composite score of 11 modifiable dementia risk factors.ResultParticipants with mild prevalent HI (n = 322; 17.8%) and moderate to profound prevalent HI (n = 198; 10.9%) showed more decline over time in verbal memory, information processing speed, and executive function than participants without prevalent HI, independently of the other demographical and risk factors in the model. Likewise, participants with incident HI (n = 360; 33.6%) showed more decline over time in all cognitive domains than those with normal hearing at follow‐up. Comparing slopes across time showed a steady cognitive decline across all time points for prevalent HI, while for incident HI, a more time‐delayed pattern of increasing decline from 6 to 12 years was observed.ConclusionPrevalent and incident HI predict cognitive decline in adults aged between 24‐82 years. This association is already present in individuals with mild HI. Findings for incident HI suggest that cognitive decline evolves gradually over time and after the onset of HI, possibly opening a window for risk management.
Age‐related cognitive decline and prevalence of MCI in the Iwaki Health Promotion Project
Authors: Kawarabayashi Takeshi , Nakahata Naoko , Nakamura Takumi , Takatama Masamitsu , Shoji Mikio 
Published: December 2023

AbstractBackgroundThe Iwaki Health Promotion Project (IHPP) is a community‐based study for the prevention of lifestyle‐related diseases and improvement of quality of life.MethodBetween 2014 and 2017, a total of 4,442 Iwaki town residents from 19 to 93 years of age participated in annual surveys to clarify the natural course of age‐related cognitive decline and mild cognitive impairment (MCI). Modified OLD and SED‐11Q questionnaires, MMSE, Logical Memory II, educational history, and APOE genotypes were examined at the first screening. MCI and dementia were diagnosed at the second examination by detailed neurological examination, CDR, and MRI, and followed for 3 years. Spline regression analyses based on a linear mixed model was adopted for statistical analysis.ResultMMSE scores declined with age from 55 to 64 years. There was also interaction between levels of education and ages. At the second examination, 56 MCI and 5 dementia patients were identified. None of the MCI cases progressed to dementia during the 3 years. During follow‐up examinations, 13 cases showed improved MMSE scores (0.95 point/year), 5 remained stable, and 7 deteriorated (‐0.83 point/year). Five cases showed improved CDR‐SOB scores (‐0.28 point/year), 9 remained stable, and 6 deteriorated (0.3 point/year).ConclusionIHPP revealed that age‐ and education‐related cognitive decline began and advanced from 55 years of age. The prevalence of MCI and dementia was estimated to be 5.9% in the Iwaki town cohort over 60 yeas of age. About 30% of MCI cases showed progression of cognitive decline.
The mediating effect of HbA1c levels on the relationship between education and cognitive function
Authors: Reinke Constantin , Aretz Benjamin , Fink Anne , Doblhammer Gabriele 
Published: December 2023

AbstractBackgroundHigher education has been shown to be positively associated with cognitive performance. However, the pathways, through which education is related to cognitive performance, have not been sufficiently explored. Higher levels of glycated hemoglobin (HbA1c) can lead to deterioration in cognitive performance. Part of the association with education may operate via the HbA1c level.MethodTo evaluate if the HbA1c level mediates the association of education with cognitive performance, we used longitudinal data from the Dutch Lifelines Cohort study (2006‐2015). Lifelines is a multi‐disciplinary prospective population‐based cohort study examining the health and health‐related behaviors of 167,729 persons living in the north of the Netherlands. The analyzed sample contained 19,878 persons observed at the baseline and the follow‐up, who were 50+ at baseline. We measured cognitive function using age‐standardized reaction time from the psychomotor function and attention tasks measured by the Cogstate Brief Battery at follow‐up. Higher reaction times indicate weaker cognitive function. The HbA1c level was measured at baseline by using participants’ blood samples. Linear Structural Equation Models were applied to estimate total, direct and indirect effects of education on cognitive function. We controlled for sex, age, income, physical activity, comorbidities and individual task accuracy.ResultHigher education was associated with faster reaction time respectively better cognitive performance (low: ref; middle: b = ‐0.125 p<0.01; high: b = ‐0.268 p<0.01). An increase in the HbA1c level (%) was associated with slower reaction time respectively poorer cognitive performance (b = 0.031 p = 0.02). Education had a significant effect on the HbA1c level (low: ref; middle: b = ‐0.023 p<0.01; high: b = ‐0.035 p<0.01). Most importantly, we found a significant indirect effect for education (low: ref; middle: b = ‐0.0007 p = 0.06; high: b = ‐0.001 p = 0.03) on cognitive function via the HbA1c level.ConclusionThe education effect of on cognitive performance was partially mediated by HbA1c levels. Early monitoring and regulation of blood glucose levels may be a potential prevention strategy to tackle cognitive impairments and mitigate the disadvantages in cognitive function of lower‐educated people.
Role of brain‐derived extracellular vesicles in bone‐fat imbalance in Alzheimer’s disease
Authors: Shen Lu , Liu Xixi , Chen Chunyuan , Jiao Bin , Wang Zhenxing , Xie Hui 
Published: December 2023

AbstractBackgroundInadequate osteogenesis and excessive adipogenesis of bone marrow mesenchymal stem cells (BMSCs) are key factors in the pathogenesis of osteoporosis. Patients with Alzheimer’s disease (AD) have a higher incidence of osteoporosis than healthy adults, but the underlying mechanism is not clear. The aim of this study was to investigate the role of brain‐derived extracellular vesicles (EVs) from AD mice on the regulation of bone metabolism.MethodBrain‐derived EVs from AD or wide‐type mice was injected into C57BL/6 mice intravenously once a week for two months.ResultHere, we show that brain‐derived EVs from adult AD or wild‐type mice can cross the blood‐brain barrier to reach the distal bone tissue, while only AD brain‐derived EVs (AD‐B‐EVs) significantly promote the shift of the BMSC differentiation fate from osteogenesis to adipogenesis and induce a bone‐fat imbalance. MiR‐483‐5p is highly enriched in AD‐B‐EVs, brain tissues from AD mice, and plasma‐derived EVs from AD patients. This miRNA mediates the anti‐osteogenic, pro‐adipogenic, and pro‐osteoporotic effects of AD‐B‐EVs by inhibiting Igf2.ConclusionThis study identifies the role of B‐EVs as a promoter of osteoporosis in AD by transferring miR‐483‐5p.
Diagnostic utility of culture/language‐specific normative data on the Version 3 of the Uniform Data Set Neuropsychological Battery for differentiating stages of cognitive impairment among Latinos in the United States
Authors: Marquine Maria J. , Kamalyan Lily , Parks Adam , Perales Jaime , Gonzalez David A. , Rosado‐Bruno Mónica , North Rebecca , Amy Werry E , Kiselica Andrew M , Reyes Marcos , Chapman Silvia , Dodge Hiroko H , Rascovsky Katya 
Published: December 2023

AbstractBackgroundAccurate detection of neurocognitive disorders of aging among Latinos in the United States (U.S.) is an important step towards addressing disparities in Alzheimer’s disease and related dementias (ADRDs) and promoting health equity in this group. Federally‐funded Alzheimer’s Disease Research Centers (ADRCs) in the U.S. have utilized the National Alzheimer’s Coordinating Center (NACC) Uniform Data Set Version 3 Neurobehavioral Battery (UDS3‐NB) since 2015. Normative data on this battery adjusted for age, education and sex were published for English‐speakers in 2018 (Weintraub et al., 2018) and expanded to consider differences among non‐Hispanics White and Black people in 2020 (Sachs et al., 2020). We aimed to determine whether the use of newly developed culture/language‐specific neuropsychological normative data for Spanish‐ and English‐speaking Latinos in the U.S. improved diagnostic accuracy of the UDS3‐NB in this group.MethodParticipants included 1,018 Latino adults age 50+ enrolled in ADRCs. Table 1 presents participant demographics by global Clinical Dementia Rating (CDR) score, as indicative of stage of neurocognitive impairment (0 = normal, 0.5 = questionable impairment, 1 = mild impairment, 2‐3 = moderate‐to‐severe impairment). Individual test raw scores were converted to demographically‐adjusted z scores utilizing normative data on the UDS3‐NB developed for Latinos and for other culture/language groups. Individual tests z scores were converted to deficit scores and averaged to compute global deficit scores and determine global neurocognitive impairment (NCI). Rates of NCI based on culture/language specific normative data were compared across the four CDR groups via Chi‐Square tests. Sensitivity and specificity were computed for differentiating participants with CDR = 0 (normal) and CDR = 1 (mild impairment) based on different sets of normative data.ResultsUtilizing culture/language‐specific normative data significantly differentiated CDR groups (p<.001; Figure 1). These culture/language specific normative data performed better in differentiating between CDR = 0 and 1, than utilizing normative data developed for non‐Hispanic English speakers (Table 2).ConclusionCulture/language‐specific normative data improve diagnostic accuracy for neurocognitive impairment among Latinos in the U.S. relative to existing normative data developed for other groups. These culture/language‐specific norms can be used in research and clinical practice to enhance ADRD diagnosis among Latinos and represent an important step towards addressing ADRD disparities in this group.