bluuebunny/crossref_metadata_2025_split huggingface dataset:
Risk factors of young‐onset dementia: a UK Biobank study
Authors: Hendriks Stevie , Ranson Janice M , Peetoom Kirsten , Tai Xin You , Lourida Ilianna , de Vugt Marjolein , Llewellyn David J , Köhler Sebastian 
Published: December 2023

AbstractBackgroundWhile age is the main risk factor for developing dementia, in young‐onset dementia (YOD) symptoms can already start before the age of 65 years. Genetic factors figure more prominent in the onset of YOD than late‐onset dementia but still only account for 5‐10% of the clinical YOD cases. It is therefore important to understand how modifiable risk factors, such as lifestyle or cardiovascular factors, and their interactions with genetic factors are associated with risk for YOD. The aim of this study was to examine a comprehensive set of factors and their association with the incidence of YOD.MethodWe used data from individuals aged under 65 years (n = 356,052) in the UK Biobank, a prospective population‐based cohort, to investigate risk factors related to YOD. Incidence of dementia was determined from hospital and death records. Potential risk factors were identified from systematic reviews on late‐onset dementia and YOD, including socio‐demographic, genetic, lifestyle, environmental, blood markers, cardiometabolic, psychiatric and other factors. These were analyzed in multivariable Cox proportional hazards regression.ResultDuring 2,891,409 person‐years of follow‐up, 485 cases of YOD were reported. Incidence rates for women increased from 1.88/100,000 person‐years in age 40‐44 to 53.38/100,000 person‐years in age 60‐64. In men incidence rates increased from 5.41/100,000 person‐years in age 45‐49, to 79.54/100,000 person‐years in age 60‐64. A total of 38 variables were analyzed. In univariable analyses, 30 factors were associated with YOD, of which 15 were significantly associated with the incidence of YOD in multivariable analyses. These variables included lower formal education, lower socioeconomic status, carrying the apolipoprotein ε4 allele, no alcohol use, alcohol intoxication, social isolation, vitamin D deficiency, high c‐reactive protein levels, lower handgrip strength (i.e., higher physical frailty), hearing impairment, orthostatic hypotension, stroke, diabetes, heart disease and depression.ConclusionThis study found potentially modifiable risk factors for YOD. While further exploration of these risk factors is necessary to validate our findings and identify potential underlying mechanisms, addressing these modifiable factors may prove effective in mitigating the risk of developing YOD.
Effects of a short‐term Mediterranean diet on mental health, cognition and cerebral blood flow in UK adults: MediMood study protocol
Authors: Esgunoglu Latife , Liaquat Marrium , Gillings Rachel , Lazar Alpar , Brooks Jon , Penny William , Hornberger Michael , Jennings Amy , Minihane Anne‐Marie 
Published: December 2023

AbstractBackgroundDementias and mental health disorders (i.e. depression, anxiety) are significant public health challenges. Chronic consumption of a Mediterranean diet (MD) has been associated with lower incident dementia, improved cognitive performance, and reduced brain atrophy. Yet, short‐term studies and randomised clinical trials (RCT) are lacking. Our systematic review of RCTs showed that in only four available studies, a MD can improve attention, alertness and contentment in up to 10 days (1). In a controlled efficacy study with all foods provided, we aim to explore postprandial, 24‐h and 5 days impacts of a MD and a Western diet (WD) on mood, anxiety and cognition, cerebral blood flow as assessed by MRI.MethodMediMood is an efficacy crossover RCT. Individuals (n = 25) over 18 years with mild to moderate anxiety and/or depression will complete a 5‐day MD and a 5‐day WD intervention with a 4‐week wash‐out period, with foods, meal plans and instructions provided. Biological samples (blood, urine, faeces) will be collected. The primary outcomes are mood and anxiety assessed using Bond‐Lader and POMS questionnaires. Secondary outcomes include cognitive outcomes assessed through computerised neuropsychology tests, brain perfusion assessed by MRI, select cardiometabolic and inflammatory biomarkers, ketones, brain‐derived neurotrophic factor, several hormones (e.g. serotonin, dopamine), gut microbiome speciation, sleep quality and behaviour change. The assessment time points during each arm are baseline (day 1 morning), postprandial (post day 1 lunch), 24‐h (day 2 morning) and day 6 morning.ResultNAConclusionThis will be the first well‐controlled RCT examining the acute and short‐term impacts of a MD and a WD on mental health and cognition in a targeted risk group. MediMood considers interfaces between sleep quality and the gut‐brain axis as modifiable determinants of mental health. We expect the findings to provide novel insights in efficacy of a MD on daily and short‐term well‐being in those with existing mild‐moderate mental health difficulties and to provide an initial mechanistic understanding of any observed benefits.
Funding:Medical Research Council (MRC, UK), NuBrain Consortium (MR/T001852/1); Turkish Government personal PhD scholarship
References:1. Esgunoglu L, Jennings A, Connole ES et al. (2021) Br J Nutr
Effectiveness of a multicomponent lifestyle intervention against cognitive decline and dementia in an at‐risk‐population in Germany – Preliminary results of the cluster‐randomized AgeWell.de‐trial
Authors: Zülke Andrea , Pabst Alexander , Luppa Melanie , Czock David , Haefeli Walter E. , Wiese Birgitt , Hoffmann Wolfgang , Frese Thomas , Gensichen Jochen , König Hans‐Helmut , Kaduszkiewicz Hanna , Thyrian Jochen René , Riedel‐Heller Steffi G. 
Published: December 2023

AbstractBackgroundMounting evidence suggests that dementia can be prevented. Targeting several risk factors simultaneously constitutes a promising strategy for preserving cognitive function. The AgeWell.de‐study was a cluster‐randomized trial applying a multi‐domain intervention to preserve cognitive function in older adults at risk for dementia in Germany.MethodIndividuals with a Cardiovascular Risk Factors, Aging and Dementia (CAIDE) dementia risk score ≥ 9 points aged 60‐77 years were recruited. According to randomization of their general practitioner (GP) practice, patients received either a multi‐domain intervention (optimization of nutrition and medication, physical, social and cognitive activity, cardiovascular risk management, intervention in case of depressive symptoms and/or grief) or general health advice and GP treatment as usual over 24 months. Primary outcome was global cognitive performance, assessed using a composite score based on z‐scores of domain‐specific neuropsychological tests.ResultOf 1,030 participants at baseline (intervention/control: n = 487/543), n = 819 (intervention/control: n = 378/441) completed the follow‐up assessment. Intervention and control group did not differ regarding global cognitive performance (β = 0·010, 95% CI: ‐0·085; 0·105) at follow‐up. However, post‐hoc analyses revealed beneficial effects for social cognition (β = 0·132, 95% CI: 0·012; 0·252) and health‐related quality of life (β = 0·194, 95% CI: 0·065; 0·323). The intervention improved global cognitive performance (β = 0·221, 95% CI: 0·015; 0·428), social cognition (β = 0·259, 95% CI: 0·024; 0·494) and health‐related quality of life (β = 0·421; 95% CI: 0·114; 0·728) in participants with low education, and reduced depressive symptoms in highly educated participants (β = ‐0·431; 95% CI: ‐0·781; ‐0·082). Younger participants benefitted from the intervention regarding social cognition (β = 0·174, 95% CI: 0·010; 0·337) and health‐related quality of life (β = 0·405, 95% CI: 0·241; 0·570).ConclusionNo effect of the multi‐domain intervention on global cognitive performance was found for the overall sample. The intervention benefitted global cognitive functioning in individuals with low education and social cognition and health‐related quality of life across the sample. Further benefits regarding specific subgroups point towards the usefulness of tailored interventions.
the impacts of language decoding and literacy of adults in the cognition of elderly people and its occupational engagement
Authors: Santos Tomaz Kelle Luisa , Maciel Francisca Izabel Pereira , Resende Elisa de Paula França , Zacarias Ana Paula , Assenção Joanna , Ribeiro Norton Grey , Grinberg Lea T , Rincon Luciana Paula , Friedlander Clarisse , Victor João , Lourandes Rocha Aida , Ruppert Emma Patrice , Caramelli Paulo 
Published: December 2023

AbstractBackgroundBrazil has a population of 11 million illiterate individuals. This percentage among Brazilians over 60 equals 18%. In view of this, researchers from the Colleges of Medicine and Education from Federal University of Minas Gerais, Brazil, created Alfabetização e Memória (PROAME) – a project that investigates the relations of late literacy with adults’ psychosocial health. The analysis carried out associated the variables of mental and social health to the literacy process, taking into account memory and language aspects.MethodThis study evaluated 130 illiterate adults living in the city of Belo Horizonte, Brazil. 108 participants fitted all criteria and agreed to undergo this survey. There were 31 men (28,4%) and 78 women (71,5%); their average age was 58,5 (±9,6). Regarding race, 91% were black/brown (83,4%), 11 were white (10,1%) and 1 was indigenous (0,1%). 80 of those participants completed all clinical evaluations, interviews and pedagogical diagnoses before and after our intervention through a period of 7 months. The goal was to qualitatively analyze the participants’ discourse, focusing on evidence of the improvement of their autonomy. This was done by associating aspects from occupational engagement to the so‐called social literacy, which consist in the practical application of reading and writing on previously illiterate adults.ResultThe average age of the participants who completed the evaluations was 58,9 (±9,1), and 64 of them were women (80,0%). Both the interviews (made before and after our intervention) and the pedagogic report of 15 random individuals were analyzed. The results show progress in: their engagement in meaningful activities of daily life; their autonomy, sociability and self esteem; their use of technological applications; their occupational repertoire and their reading and writing abilities.ConclusionA pedagogical intervention made up by specific reading and writing activities, carried out with illiterate adults during 6 months, resulted in benefits for the participants. However, in face of the high illiteracy levels in Brazil, it is necessary a broader engagement in developing studies and literacy programs for adults as political, educational and health goals. By raising the literacy levels, we expect to guarantee the rights of marginalized individuals in Brazilian society.
New mitochondrial DNA methylation profiling method confirms epigenetic marker in the brain
Authors: Smith Adam R. , Soanes Darren , Moore Karen , Jeffries Aaron , Lunnon Katie 
Published: December 2023

AbstractBackgroundThere is growing evidence for the role of DNA methylation in regulating the transcription of mitochondrial genes. This is particularly important in neurodegenerative disorders characterised by mitochondrial dysfunction, including Alzheimer’s disease. However, current methods to create genome‐wide, high‐resolution analysis of the mitochondrial DNA methylome are challenging and lack control standards.MethodHere, we present a new methodological approach to interrogate the mitochondrial DNA methylome at single base resolution using Oxford Nanopore technology and the creation of independent controls. Firstly, we isolate enriched mtDNA from SH‐SY5Y cell lines and post‐mortem brain tissue and use long‐range PCR (LR‐PCR) to generate 0%, 50% and 100% methylation controls. These controls were then validated using pyrosequencing and then run on the Oxford Nanopore (OXNP) long read sequencer. Finally, we used data generated by our controls to train existing methylation calling packages to better call mtDNA methylation in a post‐mortem human brain sample.ResultWe present a new and effective method of profiling mtDNA methylation on native DNA. Using this approach, we show that mitochondrial DNA methylation is relatively low but conserved, with peaks in DNA methylation >5% at several sites.ConclusionWe have annotated patterns of DNA methylation at single base resolution across the mitochondrial genome in human brain, using our new laboratory pipeline and Oxford Nanopore technology to profile native DNA. Looking to the future this method could be utilized to further investigate the role of mitochondrial epigenetic mechanisms in neurodegenerative disorders, such as Alzheimer’s disease.
Functional connectome‐based prediction of individual clinical and cognitive scores in midlife population with risk of dementia
Authors: Cao Bolin , Deng Feng , Qi Qing , Muniz‐Terrera Graciela , Malhotra Paresh A , Koychev Ivan , Ritchie Karen , O'Brien John T , Ritchie Craig W , Lawlor Brian , Naci Lorina 
Published: December 2023

AbstractBackgroundIt is well acknowledged that Alzheimer’s Disease (AD) neuropathology start decades before clinical manifestations, but the brain mechanism of sporadic AD in midlife remains unclear. Resting‐state functional connectivity (FC) is increasingly used to understand early brain changes in Alzheimer’s disease (AD) (Sperling, 2011; van den Heuvel & Sporns, 2019). We asked whether risk for late‐life dementia impacts functional connectivity in cognitively healthy middle‐aged individuals.MethodFunctional Magnetic Resonance Imaging and detailed neuropsychological assessments were obtained for 585 (207/378 female/male) cognitively healthy individuals, aged 40‐59 years (mean = 50.9), from the PREVENT‐Dementia study. Dementia risk was calculated with the Cardiovascular Risk Factors, Aging, and Dementia (CAIDE) score. A novel connectome‐based predictive method called NBS‐Predict was used to investigate the association between FC and CAIDE score and its role in cognition.ResultFC significantly predicted CAIDE scores across the whole cohort (r = 0.207, p < 0.001). FC within and between the cingulo‐opercular network (CON) and sensorimotor network (SMN), as well as between CON and fronto‐parietal network (FPN), and between SMN with default mode network (DMN), and FPN contributed the most (Figure 1). Furthermore, we found that, in the high dementia risk group (CAIDE > 6) only, FC, mainly in DMN‐SMN and DMN‐CON (Figure 2), significantly predicted multisensory processing cognitive score (r = 0.114, p<0.05).ConclusionOur results show that FC can be used to detect early brain changes associated with risk of future dementia in cognitively healthy individuals. This method has implications of the early detection of dementia in preclinical populations.
Ameliorative effects of Aqueous Fruit Pulp Extracts of Adansonia digitata on the Hippocampus of Aluminium Chloride‐treated Adult Wistar Rats
Authors: Suleiman Sadiya , Musa Sunday Abraham , Adebisi Samuel , Oderinde Gbenga Peter 
Published: December 2023

AbstractBackgroundThis study evaluated the effects of aqueous extract of Adansonia digitata fruit pulp (AEAD) on the hippocampus of Aluminium chloride Alzheimer model Wistar rats.MethodThirty Wistar rats (110‐150g) were randomly divided into six groups (n = 5). The animals in Group 1 were administered 2ml/kg distilled water. Group 2 were administered 100mg/kg AlCl3. Groups 3 were administered 595mg/kg ascorbic acid. Group 4 and 5 were administered 100mg/kg AlCl3 + 500mg/kg AEAD and 100mg/kg AlCl3 + 1500mg/kg AEAD respectively. Group 6 were administered 100mg/kg AlCl3 + 595mg/kg ascorbic acid. Once daily, for four consecutive weeks, behavioral tests for spatial memory using the Morris water maze test were carried out. Experimentation lasted for 28 days after which the animals were humanely sacrificed.ResultAnimals treated with A. digitata and Ascorbic acid following Aluminium exposure showed significant decrease (11.67±1.74) in the time taken for the experimental rats to locate the escape platform. The result of the oxidative stress study showed a significant increase Malondialdehyde concentration and decrease in Superoxide dismutase (SOD) and reduced glutathione (GSH) in groups exposed to aluminium chloride, however, treatment with A. digitata and Ascorbic acid following Aluminium exposure did not show any significant difference when compared to the control group. Histopathological studies revealed degenerating pyramidal cells, Karyolysis, Pkynosis, were observed in the hippocampus of the aluminium treated group. Treatment with Adansonia digitata and Ascorbic acid ameliorated the changes observed in groups exposed to aluminium. The histoarchitecture of the aqueous extracts treated groups were preserved, particularly the 1500mg/kg doses.ConclusionA. digitata fruit pulp possess vital antioxidant properties that could ameliorate the toxic effects of aluminium on the Hippocampus of adult Wistar rats and as such could be used as a treatment of aluminium toxicity.
Race/ethnic disparities in mis‐identification of dementia in Medicare claims
Authors: Zhu Carolyn W , Gu Yian , Cosentino Stephanie , Hernandez Michelle , Stern Yaakov 
Published: December 2023

AbstractBackgroundStudies have shown that mis‐identification of dementia in Medicare claims is quite common. We extend the literature by examining potential race/ethnic disparities in mis‐identification of dementia in Medicare claims in a diverse cohort of older adults who underwent careful clinical assessment.MethodParticipants were enrolled the Washington Heights‐Inwood Columbia Aging Project (WHICAP), a multiethnic, population‐based, prospective study of cognitive aging in which dementia status is assessed using a rigorous clinical protocol. The current study included 1,178 participants clinically diagnosed with dementia and 3,048 never diagnosed with dementia. ICD‐9‐CM diagnosis codes in all available Medicare claims (1999‐2019) were compared to clinical dementia diagnosis, and categorized into 3 mutually exclusive groups: (1) congruent identification, (2) over‐identification (no clinical dementia, claims‐identified dementia), and (3) under‐identification (clinical dementia, no claims‐identified dementia) during the study period. Race (White, African American/Black, Other) and ethnicity (Hispanic/Latinx, non‐Hispanic/Latinx) were self‐reported. Multinomial logistic regression model was used to examine the relationship between race/ethnicity and congruency of dementia identification after controlling for clinical (cognition, function, comorbidities) and demographic characteristics (age, sex, education), and inpatient and outpatient utilization. Estimated average marginal effects are reported.ResultThe study included 1,520 White, 1,333 African American/Black, and 1,373 participants of other races. 1,985 participants self‐identified as Hispanic, 2,241 non‐Hispanic. Among participants clinically diagnosed with dementia, the proportion who were accurately identified with dementia in Medicare claims were 83.2%, 77.8%, and 73.2% in White, African American/Black, and other races, respectively; 75.9% and 79.7% in Hispanics and non‐Hispanics, respectively. Among participants clinically diagnosed without dementia, the proportion of participants who were accurately identified without dementia in Medicare claims were: 86.1%, 87.3%, and 82.3% in White, African American/Black, and other races, respectively; 82.4% and 87.5% in Hispanics and non‐Hispanics, respectively. After controlling for participant characteristics, multinomial logistics regression results show the probability of over‐identification with dementia was 2.2% higher for African American/Black participants than White (p = 0.05) and 2.7% higher for Hispanic participants than non‐Hispanics (p = 0.03). Differences in under‐identification by race/ethnicity were no longer statistically significant.ConclusionAfrican American/Black and Hispanic participants were more likely to be over‐identified with dementia in Medicare claims.
The shortened version of a web‐based cognitive test tool, cCOG, retains good accuracy in detecting mild cognitive impairment and dementia
Authors: Landen Sophie M. , Gils Aniek M. , Handgraaf Dédé , Hasselbalch Steen G. , Mecocci Patrizia , Soininen Hilkka , Tolonen Antti , Lötjönen Jyrki , Paajanen Teemu , Lemstra Afina W. , Flier Wiesje M. , Sikkes Sietske A.M. , Rhodius‐ Meester Hanneke F.M. 
Published: December 2023

AbstractBackgroundcCOG, a web‐based cognitive test tool, has been shown to detect mild cognitive impairment (MCI) and dementia accurately. However, the test now takes approximately 25 minutes to complete, which could be burdensome for patients, especially with cognitive impairment. We assumed that shortening certain subtasks leads to a decrease in total test duration and therefore increases the user‐friendliness of cCOG. In this study, we examined whether shortening these subtasks influences the discriminative value of cCOG.MethodFrom the PredictND and Amsterdam Dementia Cohort (ADC) cohort, we included cCOG results of 424 participants (n = 234 cognitively normal (CN), n = 84 MCI, n = 106 dementia) who were on average 70±9 years and 54% were female. cCOG consists of five subtasks: episodic memory learning, reaction time, modified trail‐making A and B and episodic memory recall. Scores for all subtasks except episodic memory recall were abbreviated into shorter versions, e.g. by cutting the number of items/trials. A global cognitive score (GCS) was computed using a linear regression model based on scores of all subtasks for both the original as the short version. To investigate the diagnostic accuracy of both versions, we calculated pairwise area under the curve (AUC) comparisons for differentiating MCI and dementia from CN.ResultShortening of subtasks led to an average decrease of 4.7 minutes of the total test time (20.1%) for the PredictND cohort (n = 314), with even 5.7 minutes decrease in the dementia group (Figure 1). The accuracy of the GCS based on the short version for differentiating MCI from CN was lower than based on the original version though still considered excellent (AUC = 0.87 [0.83‐0.92] original; AUC = 0.86 [0.81‐0.90] short; Figure 2). For differentiating dementia from CN, the short version performed comparable to the original version (AUC = 0.93 [0.89‐0.96] original; AUC = 0.92 [0.88‐0.96] short; Figure 3).ConclusionShortening subtasks decreased the test duration of cCOG with approximately 5 minutes, while the diagnostic accuracy was preserved. An additional pilot study is needed to test the effect of shortening subtasks on episodic memory recall and global cognitive score. Further development of a user‐friendly and accurate web‐based cognitive test tool is crucial to keep dementia care accessible and affordable.