bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Study of the Usefulness of Self‐Assessment Memory Scale (SAMS) for the Elderly in the Community
Authors: Kowa Hisatomo , Oki Yutaro , Imamura Miki , Suzuki Yuka 
Published: December 2023

AbstractBackgroundIt is very important to detect a slight cognitive decline and start therapies at the very early stage as soon as possible. We have established a new method named the Self‐Assessment Memory Scale (SAMS), consisting of 8‐picture recall and 16‐word recognition test. This study examined the usefulness and validity of SAMS in older adults participating in a dementia prevention (J‐MINT PRIME Tamba) study.MethodThe subjects were 97 older adults aged 65 year or older (24 men). The subject was administered a test consisting of an 8‐picture recall and a 16‐word recognition test on a tablet twice on separate days. The SAMS index was calculatedby adding up the ratio of correct responses to both tests (max point is two). The correlation with the WMS‐R logical memory II (LMII) score was examined.ResultThe mean and standard deviation of SAMS for the subjects in this study by age groups 65‐69, 70‐74, 75‐79 and 80‐ were 1.71 ± 0.24, 1.55 ± 0.25, 1.36 ± 0.29 and 1.36 ± 0.29, respectively. The first and second attempt of SAMS showed a significant correlation with the LMII score. (R = 0.56 and R = 0.63 respectively, both showed p<0.001). Comparing the first and the second score, the latter had better for more than 90% of the participants.ConclusionSAMS showed the good correlation with LMII in older people in this community‐based study. The result that the second score of the SAMS was better and correlated better with the LMII compared to the first one suggests that it is important to provide some trial opportunities for this test administered on a tablet in order to accurately assess cognitive function in elderly subjects.
Aged mice lacking interaction between FKBP51 and Hsp90 have normal cognition and memory
Authors: Zhao Zhe , Sun Xuelian , Wang Lisha , Wojcieszak Jakub , Winblad Bengt , Pavlov Pavel F. 
Published: December 2023

AbstractBackgroundFK506‐binding protein 51 kDa (FKBP51) is a heat shock protein 90 (Hsp90) associated co‐chaperone that has recently emerged as a possible AD therapeutic target. Increased expression of FKBP51 was found in brains of aged mice and AD patients and overexpression of FKBP51 in mice impairs cognitive function in vivo. Role of HSP90‐FKBP51 complex in cognition and memory remains to be characterized.Methods• Using CRISPR/Cas9‐mediated genome engineering we have created a new mouse strain (Fkbp5TPRmut) harboring point mutations disrupting FKBP51 binding to Hsp90.• Genotype of mice was confirmed using PCR‐based assay.• Behavior of adult was assessed at 12 months of age using a battery of tests, including open field, novel object recognition, Y‐maze, and fear conditioning.Results• Mutation of FKBP51 leads to reduced interaction with Hsp90.• Mutation of FKBP51 is stable and inherited in Mendelian‐like manner. Mutant homozygotes, heterozygotes and wild type mice can be clearly distinguished.• Fkbp5TPRmut mice do not suffer from any health or fertility issues.• At 12 months of age Fkbp5TPRmut mice do not display any impairment in behavior, cognition or memory.Conclusion• Two‐point mutation of FKBP51 render it incapable of interacting with Hsp90.• Fkbp5TPRmut mice do not display harmful phenotype, allowing for a broad use of this model.Further research is granted to reveal functional significance of FKBP51‐Hsp90 interactions, especially in Alzheimer’s disease or stress‐related disorders.
First genome‐wide association study on Alzheimer’s disease in the Argentinian and the Chilean populations
Authors: Dalmasso Maria Carolina , de Rojas Itziar , Olivar Natividad , Muchnik Carolina , Angel Bárbara , Gogler Sergio , Sanchez‐Avalos Mariana S , Chacon Maria Victoria , Aránguiz Rafael , Orellana Paulina , Cuesta Carolina , Galeano Pablo , Campanelli Lorenzo , Novack Gisella V , Medel Nancy , Lisso Julieta , Sevillano Zulma , Irureta Nicolas , Castaño Eduardo M , Montrreal Laura , Heilmann‐Heimbach Stefanie , Mintz Ines , Villella Ivana , Lambert Jean‐Charles , Solis Patricia , Politis Daniel , Mangone Carlos A , Gonzalez‐Billault Christian , Boada Mercè , Tárraga Lluís , Slachevsky Andrea , Albala Cecilia , Fuentes Patricio , Kochen Silvia , Brusco Luis Ignacio , Ruiz Agustin , Morelli Laura , Ramirez Alfredo 
Published: December 2023

AbstractBackgroundGenome‐wide association studies (GWAS) are fundamental for identifying loci associated with diseases. However, they require replication in other ethnicities.MethodWe performed a GWAS on sporadic Alzheimer’s disease (AD) including 540 patients and 852 controls from Argentina and Chile. We explored the variants associated with AD in European GWAS from European Alzheimer’s and Dementia Biobank (EADB), and tested their genetic risk score (GRS) performance in this admixed population.ResultWe detected APOE4 as single genome‐wide significant signal (OR = 2.93[2.37‐3.63], p = 2.6×10−23), and fifteen additional suggestive signals previously undetected. Nine of the 83 variants reported by EADB in Europeans were replicated, and the AD‐GRS presented similar performance in this Latin population, despite the score diminishes when the Native American ancestry rises.ConclusionWe report the first GWAS on AD in a population from South America. It shows shared genetics that modulate AD risk between the European and the Latin American populations.
Identifying the optimal age to intervene in Alzheimer’s disease prevention trials: Validation of Emax modelling in sporadic Alzheimer’s disease
Authors: Baksh Asaad , Hithersay Rosalyn , Ritchie Karen , Carter Ben , Strydom Andre 
Published: December 2023

AbstractBackgroundMany clinical trials of disease‐modifying therapies which seek to delay or prevent Alzheimer’s disease (AD) currently exist. However, a limitation of these trials is the absence of considering the earliest age groups at which decline in cognition can be detected to guide optimal participant recruitment.Previous work has shown that in people with Down syndrome, Emax modelling can be used to identify the trajectory of cognitive decline in the preclinical and prodromal stages of AD. We aimed to validate Emaxmodelling to identify the earliest age of change in cognition in people who developed sporadic AD and compare these individuals to healthy controls without AD.MethodOur sample consisted of participants aged 65 years old from the Enquête Sante ́ Psychologique – Risques, Incidence et Traitement (ESPRIT) study. Participants were categorised into two groups based on whether they were ever diagnosed with possible and probable AD while enrolled in the study (n = 101) or did not receive a diagnosis of any subtype of dementia (n = 1392, our healthy control group). We included measures of general cognitive functioning (Mini Mental State Examination; MMSE), verbal fluency, visual memory (Benton Visual Retention Test) and executive functioning (Trail Making Test).ResultIn people with AD, the earliest decline in general cognitive functioning could be detected in the 67‐71 age band while verbal fluency appears to decline from the 41‐45 age band and visual memory in the 82‐86 age band according to our model. In healthy controls, general cognitive functioning shows early change in the 87‐91 age band while verbal fluency starts to decline in the 43‐47 age band and executive functioning in the 85‐89 age band. Models for Trail Making Models for people with AD and visual memory for controls were not well fitted to the data.ConclusionWe have shown that sensitivity to change depend on the primary outcome so authors designing trials need to ensure the research question, population and primary outcome are consistent. This has implications particularly for trials targeting the stages of disease before dementia diagnosis.
Poor cognition is associated with increased abundance of Alistipes and decreased abundance of Clostridium genera in the gut
Authors: Muhammad Jazmyn A , Ngouongo Yannick Joel Wadop , Ramirez Sophia , Kautz Tiffany F , Satizabal Claudia L. , Himali Jayandra Jung , Seshadri Sudha , Fongang Bernard 
Published: December 2023

AbstractBackgroundBrain and gut health are intricately connected via the gut‐microbiota‐brain axis. Studies have shown that gut dysbiosis is associated with neurodegenerative diseases, including Alzheimer’s disease. However, how cognitive changes affects the gut microbiome structure is currently understudied. We aimed to assess the association between the gut microbiome and global cognitive scores in the Framingham Heart Study (FHS).MethodOur sample included 1,014 participants (mean age 52, 55% female) of the third generation FHS cohort with available stool samples, cognitive assessments, and no history of dementia or stroke (Table 1). We quantified the gut microbiome composition using 16S rRNA sequencing and performed multivariable association and differential abundance analyses, adjusting for age, sex, education, BMI, and other confounders. The global cognitive score (GCS) was built using neuropsychological assessments of four cognitive domains: Executive function (trails‐making B); Processing speed (visual reproduction immediate and delayed); Language (similarity test); and Memory (logical memory immediate and delayed). Participants were additionally stratified by GCS with lower and higher scores indicating poor and normal cognition, respectively.ResultOur results (Figure 1) showed that individuals with poor cognition have a decreased abundance of genera Clostridium (OR = 0.69, 95% CI [0.55, 0.86]) and Ruminococcus (0.93, [0.93, 0.94]). Meanwhile, the genus Alistipes, previously connected to anxiety, chronic fatigue syndrome, depression, and hypertension, was more abundant (1.06, [1.05, 1.06]) in the poor cognition group. Moreover, the genus Pseudobutyrivibrio, a butyrate‐producing bacteria from the rumen, was also found to be highly abundant (1.12, [1.11, 1.14]) in the poor cognition compared to normal. Finally, there was no difference in alpha and beta diversity between cognitive groups (Figure 2).
ConclusionOur study suggests that the abundance of several genera, including Pseudobutyrivibrio, Alistipes, Ruminococcus, and Clostridium is associated with cognition in middle‐age. Clostridium was previously proposed as novel probiotics for human health, and increasing its abundance was viewed as an effective strategy to regulate and maintain the homeostasis of the gut microbiota. As all these bacteria have neuroprotective effects, manipulating their abundance through diet and pre/pro‐biotics could be a research path for preserving global cognitive function in the future.
Nutritional intake and adherence to dietary recommendation for patients with prodromal Alzheimers disease within a multimodal lifestyle trial
Authors: Levak Nicholas , Lehtisalo Jenni , Thunborg Charlotta , Westman Eric , Sindi Shireen , Rosenberg Anna , Andersen Pia , Andrieu Sandrine , Broersen Laus M. , Coley Nicola , Irving Gerd Faxén , Mangialasche Francesca , Pantel Johannes , Ngandu Tiia , Soininen Hilkka , Hartmann Tobias , Solomon Alina , Kivipelto Miia 
Published: December 2023

AbstractBackgroundMultimodal lifestyle interventions have proven successful with at‐risk populations; however, little is known of the interventions effect on patients with prodromal Alzheimer’s disease. Even less is known of feasibility and adherence to dietary recommendations within the population.MethodA 6‐month pilot trial was conducted with 93 participants randomized into three intervention arms. Two groups received physical exercise, cognitive training, nutritional guidance, monitoring and management of vascular and metabolic risk factors, and social stimulation, with one group receiving a medical food product. The third group was a self‐guided control group. Intake of individual macro‐ and micronutrients were analyzed from 3‐day food records. Adherence to recommendations assessed from food frequency questionnaires and by using a healthy diet index.ResultFor macro‐ and micronutrient intake there were no differences at the end of the intervention and intake was in line with other national food surveys. The group who received intervention and medical food product has significantly better healthy diet index score compared to the other groups.ConclusionThere were few longitudinal significant differences on macro‐ and micronutrient intake, however, dietary intake improved significantly in itself when the intervention was complemented with a medical food product.
Structural Brain Correlates of Physical Activity in Offspring of Parents with and without Exceptional Longevity
Authors: Delpratt Natalie A , Barzilai Nir , Milman Sofiya , Verghese Joe , Blumen Helena M 
Published: December 2023

AbstractBackgroundPrevious studies suggest that frequent participation in physical activities (PA) promotes healthy aging by decreasing late‐life morbidity. Several studies further suggest that the volume of the prefrontal cortex and the hippocampus increases in response to PA. Brain volume is also preserved among offspring of those with exceptional longevity. This research examined associations between self‐reported PA and gray matter volume in older adults without dementia, and as function of parental longevity.MethodsSelf‐reported PA (activity level (low/high); activity rating (low/high); city blocks walked (<10/≥10); weekly aerobic exercise (<4/≥4); flights of stairs (≤5/>5); longest continuous walk (<4/≥4) and structural MRI data from 107 Ashkenazi Jewish older adults (79.08±6.52 years; 57.94% women) was examined. 59.81% of participants were offspring of parents with exceptional longevity (at least one parent lived 95 years or more) and 40.19% were offspring of parents with usual survival (both parents lived less than 95 years). Voxel‐based morphometry and multivariate covariance‐based analyses – adjusted for age, sex, years of education, and total intracranial volume – were used to identify gray matter patterns associated with PA. Linear regression was used to determine if these patterns varied as a function of parental longevity.ResultsSignificant gray matter covariance patterns associated with PA ratings (p = 0.001) and flight of stairs (p = 0.004) were derived. The gray matter pattern associated with flight of stairs were primarily composed of middle cingulate, thalamus, superior frontal gyrus and insula. The gray matter pattern associated with PA level were primarily composed of caudate nucleus, insula, and hippocampus. None of the derived gray matter patterns varied as a function of parental longevity. No significant patterns were observed for city blocks walked, weekly exercise, or longest continuous walk.ConclusionOur results suggest that self‐reported PA – when assessed with activity rating and flight of stairs climbed – are associated with gray matter volume pattern composed of hippocampal, cingulate, insular, and prefrontal regions. Our results further demonstrated that these gray matter patterns do not vary as a function of parental longevity. Participating in PA may benefit the aging brain to a similar extent in offspring of parents with and without exceptional longevity.
Association of self‐reported and objective sleep parameters with hippocampus and white matter hyperintensities volumes in a community‐dwelling older adults
Authors: Cavaillès Clémence , Carriere Isabelle , Jaussent Isabelle , Dauvilliers Yves 
Published: December 2023

AbstractBackgroundNumerous studies report that sleep disturbances are associated with brain alterations; yet, results still remain controversial. Our aim was thus to examine the associations between self‐reported and objective sleep parameters, and volumes of hippocampus and white matter hyperintensities (WMH).MethodThis cross‐sectional analysis used data from the French ESPRIT study. At baseline, 718 participants aged 65‐80 underwent a brain magnetic resonance imaging examination. Among them, 675 had hippocampus volume data and 712 had WMH volume data. They also completed a sleep questionnaire at baseline and 167 participants underwent an ambulatory polysomnography to assess their objective sleep. Logistic regression models were performed and minimally adjusted for age, sex, educational level, and APOE ε4 status to assess the associations between sleep parameters and volumes of hippocampus and WMH.ResultThe participants’ mean age at baseline was 71.4 years (±4.0) and 51.3% were women. We found that a short (≤6 hours) but also a long (≥9 hours) 24‐hour sleep duration, a late (>8 am) get‐up time and a low score at the Epworth Severity Scale were associated with a low hippocampal volume. However, these associations did not remain significant after false discovery rate (FDR) correction. We also observed, even after FDR correction, that an early get‐up time (≤6 am) and having difficulty in initiating sleep were associated with a high WMH volume whereas a late bedtime (≥11 pm) was associated with a low WMH volume. Regarding objective data, longer rapid eye movement sleep and slow wave sleep durations were associated with a low WMH volume, and a higher number of periodic leg movements during sleep was associated with a high WMH volume; but these associations were not significant after FDR correction. All the results remained similar after taking into account intracranial volume.ConclusionIn this population‐based study in older adults, the most robust findings concerned higher WMH volume for participants with early get‐up time, difficulties in initiating sleep or late bedtime. Overall, these results are consistent with the general view that there may be specific types of sleep parameters that can play a role in brain alterations.
Health care service use in the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) during an extended follow‐up period
Authors: Ngandu Tiia , Kulmala Jenni , Lehtisalo Jenni , Nurhonen Markku , Peltonen Markku , Mangialasche Francesca , Laatikainen Tiina , Strandberg Timo , Antikainen Riitta , Tuomilehto Jaakko , Soininen Hilkka , Kivipelto Miia ,   FINGER study group
Published: December 2023

AbstractBackgroundFinnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) is a randomized trial aiming to prevent cognitive decline with a 2‐year multidomain lifestyle intervention. Beneficial effects were detected not only in cognition, but also for co‐morbidity, as reported earlier. Aim of this work was to investigate, if the multidomain intervention also had an impact on the health care use and to evaluate possible cost‐effectiveness of the interventions in terms of health care costs.MethodThe FINGER trial recruited a population‐based cohort of 1259 at‐risk individuals aged 60‐77 living in six areas of Finland. They were randomized into a multidomain lifestyle intervention consisting of diet, exercise, cognitive training and vascular risk management (n = 631) or a regular health advice (control) (n = 628) group for two years and followed on average for 8 years. Health care use was obtained from nationwide registers where all primary and specialized care visits are recorded. We calculated days spent in hospital, ambulatory visits, outpatient visits in hospitals and primary care, and home care. Costs will be evaluated based on national reference prices.ResultAltogether 99% of the population used some health care services and 66% were hospitalized at least for one day during the 8 years. 128 (10%) participants died during the follow‐up. Preliminary data indicated that the intervention group spent less days in the hospital, but there were no differences in outpatient visits. Further analyses are ongoing to evaluate the costs related to these visits.ConclusionMultidomain lifestyle intervention which is effective in prevention of cognitive decline can also help in reducing health care use at least in terms of hospital stays.
miRNAs in Cerebrospinal Fluid Associated with Alzheimer’s Disease: a Systematic Review and Pathway Analysis
Authors: Pereira Jessica Diniz , Teixeira Lívia Cristina Ribeiro , Caramelli Paulo , Veloso Adriano Alonso , da Conceição Izabela Mamede Costa Andrade , Luizon Marcelo Rizzatti , Borges Karina Braga Gomes 
Published: December 2023

AbstractBackgroundApproximately 55 million people live with dementia, and 10 million cases are diagnosed each year worldwide (1). Alzheimer’s disease (AD) is the most common type of dementia and accounts for 60% ‐ 70% of reported cases (1). MicroRNAs are small non‐coding RNAs that present highly conserved sequences, involved in gene modulation and several molecular mechanisms (2). The miRNAs can be found in cerebrospinal fluid (CSF) and they are potential biomarkers for AD diagnosis (3). This study aimed to perform a systematic review about the expression of miRNAs in the CSF of AD patients compared to cognitive controls and carry out an analysis of the biological pathways regulated by these miRNAsMethodA systematic literature search was performed in Medline/PubMed, the Cochrane Central Register of Controlled Trials, Scopus, Lilacs, Web of Science, Embase and gray literature, including observational studies that evaluated patients with AD and healthy individuals, which evaluated the miRNA expression in CSF. To verify the main signaling pathways regulated by the miRNAs, the software Gene Cards was used (table 1).Result2060 studies were retrieved and, after removing duplicates and reading titles, abstracts and full text, 26 studies met the inclusion criteria. We identified 171 differentially expressed miRNAs between AD and controls. Among them, the miRNAs ‐125b, ‐125‐5p, ‐138‐5p and ‐485‐5p presented differentiated expression between the groups commonly in these studies. The evaluation of signaling pathways showed that regulation of gene expression, cell proliferation, and gene silencing, are regulated by these miRNAs.ConclusionOur results suggest that the miRNAs ‐125b, ‐125‐5p, ‐138‐5p and ‐485‐5p are involved in AD‐related biological pathways and are potential CSF biomarkers to AD diagnosis.1. DEMENTIA. World Health Organization, 2022. Available at: <https://www.who.int/news‐room/fact‐sheets/detail/dementia>. Access at 21 jan. 2023.2. CORREIA DE SOUSA, Marta et al. Deciphering miRNAs’ action through miRNA editing. International Journal of Molecular Sciences, v. 20, n. 24, p. 6249, 2019.3. TAKOUSIS, Petros et al. Differential expression of microRNAs in Alzheimer’s disease brain, blood, and cerebrospinal fluid. Alzheimer’s & Dementia, v. 15, n. 11, p. 1468‐1477, 2019.