bluuebunny/crossref_metadata_2025_split huggingface dataset:
Using Natural Language Processing to identify psychiatric symptoms related to Alzheimer’s disease: a novel tool to enhance molecular brain research in Alzheimer’s disease
Authors: Vogelgsang Jonathan , Jiang Weiqian , Dan Shu , Vempati Sangeetha , Chatigny Michael , Abston Joshua , Durning Peter , McCoy Thomas , Klengel Torsten , Berretta Sabina 
Published: December 2023

AbstractBackgroundNeuropsychiatric symptoms (NPS), such as anxiety, depression, or agitation, are common across different stages of Alzheimer’s disease (AD). However, their molecular course is still poorly understood. While post‐mortem brain research provides a unique source to study brain‐specific molecular changes, clinical characterization of post‐mortem brain donors is challenging and primarily subject to case‐control designs. Here, we present a novel approach to post‐mortem brain donor characterization using natural language processing (NLP).MethodWe analyzed electronic health records (HER) of 92 brain donors (46 males, 46 females, mean age 81.9 years, B&B 0 ‐ VI) using NLP‐based NIMH Research Domain Criteria (RDoC) quantification. Individual RDoC scores were regressed to their neuropathological findings or RNAseq data from two independent brain regions, BA32 and insula.ResultNeuritic plaques (NP) in all four cortices show a high association with RDoC “cognition”, controlled for age and sex (frontal: ß = 0.38, p < 0.001; parietal: ß = 0.35, p < 0.001; temporal: ß = 0.37, p < 0.001; occipital: ß = 0.37, p < 0.001). These findings align with prior clinicopathological correlation studies where cognitive examinations were performed within one year before death (Nelson et al., J Neuropathol Exp Neurol, 2012). At pFDR<0.05, we identified 492 differentially expressed genes (DEGs) in the insula and 333 DEGs in the BA32. We have further built a model regressing individual RDoC levels against their DEGs in the two brain regions. In each domain, we observed a cluster of genes that is up‐ or downregulated in relation to their RDoC score (higher/lower domain burden). In addition, we saw that the majority of DEGs are RDoC‐specific. 223 DEGs were uniquely related to one domain (170 DEGs in the insula and 53 DEGs in BA32), while a total of 211 DEGs were associated with at least two domains (151 DEGs in the insula and 60 DEGs in BA32).ConclusionNLP‐based analysis of RDoC can be applied to post‐mortem case collections to phenotype brain donors and show promising associations with neuropathology or RNAseq data that can be used to discover novel molecular pathways related to psychiatric symptoms.
Fine semantic segmentation of hands for human functional pattern recognition in IADLs using deep learning
Authors: Babatope Eyitomilayo Yemisi , Acosta‐Franco Jesus Alejandro , García‐Vázquez Mireya Saraí , Ramírez‐Acosta Alejandro Álvaro 
Published: December 2023

AbstractBackgroundAlzheimer’s Disease (AD) is an irreversible degenerative brain disease and the most common cause of dementia, in the elderly population (age 65 and above) although people younger may develop the disease (Clemmensen, 2020). AD is characterized by impairment in behavior and cognition which eventually obstruct the Instrumental Activities of Daily Living (IADL) (Kumar, 2022). Researchers have predicted functional capacity by assessing IADL as they are strongly associated with cognitive impairment. With the availability of big data and public repositories of multimedia data such as images and videos, artificial intelligence algorithms have been used in classifying and making informed decisions that could help in disease prediction and monitoring. In the context of early diagnosis of Alzheimer, researchers have worked with machine learning techniques applied to neuroimaging for AD classification (Lama, 2021). Researchers and practitioners often use Activity of Daily Living to monitor independent‐living senior citizens’ self‐care ability, wellness status, and disease progression (Zhu, 2021). Automating the assessments of IADL will ease the evaluation of functional and cognitive function and strengthen the prediction of AD.MethodOur work approaches the timely detection and diagnosis of AD by exploring the deficiency in hand dexterity and visuospatial skills while performing IADL using egocentric videos. Therefore, in this work, we propose a fine semantic segmentation of hands, optimizing the predictions at the level of the relationship between pixels in a deep learning method. We trained the optimized RefineNet‐Pix convolutional neural network, obtaining a higher accuracy in the segmentation of semantic maps of hands.ResultWith the optimization of RefineNet‐Pix we obtained an accuracy higher than 87.9% (Urooj, 2018) in the semantic segmentation of hands. By integrating the RefineNet‐Pix results to the base model for human functional pattern recognition, we obtain an accuracy higher than 74% with respect to the base model (Yemisi, 2022).ConclusionThe optimized RefineNet‐Pix model segments pixel‐wise the hand regions in egocentric videos, providing hand motion information that can be used to classify impairment based on human functional patterns. Optimization of these models is a way forward in building a technological device for the support of Alzheimer’s diagnosis.
Cognitive functioning predicts learning and performance of syncopated rhythms in healthy aging adults
Authors: Colverson Aaron 
Published: December 2023

AbstractBackgroundRhythmic music making may be beneficial for maintenance of healthy executive functioning and processing speed throughout the aging process. However, little is known about how engagement with rhythmic music making associates with healthy executive functioning and processing speed. This study aimed to determine the predictive potential of learning and performance of rhythms upon performance in executive functioning and processing speed tasks.MethodThis study involved a cross‐sectional, non‐randomized within subjects design, defined by a rhythmic musical activity (RMA), and executive functioning (EF) and processing speed (PS) tasks. The RMA involved thirty progressively syncopated rhythms, operationalized via three learning trials and a performance trial. The EF and PS tasks included multiple subtests of the Weschler Adult Intelligence Scale (WAIS) Working Memory and Processing Speed Indices (WMI & PSI), and Trail Making Parts A&B.ResultHealthy younger (ages 18‐35) and elderly (ages 55‐89) individuals provided informed consent and participated (N = 60; 46 female; 78.3% Caucasian). Learning and performance of syncopated rhythms between age groups significantly predicted scores on the WAIS PSI (t = 2.227/2.101, p = 0.030/0.040) and Trails A&B (t = ‐3.431/‐4.155, p = 0.003/<0.001; t = ‐3.636/‐4.256, p = <0.001/<0.001). Only rhythm learning predicted scores on WAIS WMI (t = 2.821, p = 0.007), with a trend shown for rhythm performance (t = 1.934, p = 0.059).ConclusionThis study is one of few to show relationships between rhythm perception and executive functioning in healthy aging. The results suggest the potential value of rhythmic music making upon maintenance of healthy executive functioning and processing speed throughout the aging process. A longitudinal study involving a control group and a larger sample size may enhance the findings of this study. Additionally, application to the Alzheimer’s disease and related dementias populations may provide comparative evidence to the healthy aging population.
Impact of midlife intake of flavonoid‐rich fruits on dementia risk in the Framingham Heart Study
Authors: Lyu Chenglin , Jacques Paul F , Doraiswamy P. Murali , Gurnani Ashita S , Au Rhoda , Hwang Phillip H 
Published: December 2023

AbstractBackgroundConsumption of foods with high flavonoid content may be protective against dementia in older adults, but it is unclear whether this relationship is consistent earlier in life. We investigated the relationship between consumption of flavonoid‐rich fruits in midlife and risk of dementia, including Alzheimer’s disease (AD).Method1,642 participants from the Framingham Heart Study Offspring cohort who were aged 45‐59 years and did not have prevalent dementia at Exam 5 (1991‐1995), and had a valid food frequency questionnaire data were included. Intake of 12 fruit items with high flavonoid content or are important contributors to overall flavonoid intake at Exam 5 were examined. Total fruit intake was calculated by summing intake of each fruit item. Diagnoses of all‐cause dementia and AD dementia were adjudicated by a multi‐disciplinary consensus committee through 2019. Cox models were used to evaluate the association between higher intake (>30th percentile) versus lower intake (≤30th percentile) of total fruit consumption, as well for each fruit item, and incident dementia, adjusting for demographic, behavior and lifestyle, dietary, genetic, and clinical factors.ResultThe sample was, on average, 52 years of age, 53% female, and had 14 years of education, with an average follow up time of 24 years in the study. Higher intake of total fruits was associated with decreased risk of all‐cause dementia (HR = 0.56; 95% CI = 0.32 – 0.98), but not with AD dementia. Decreased risk of all‐cause dementia was associated with higher intake of apples or pears (HR = 0.47; 95% CI = 0.27 – 0.81), and oranges (HR = 0.55; 95% CI = 0.32 – 0.95). Higher intakes of apples or pears (HR = 0.50; 95% CI = 0.25 – 1.00), and oranges (HR = 0.43; 95% CI = 0.22 – 0.85), were also associated with decreased risk of AD dementia. Sex modified the association between total fruit intake in midlife and dementia risk (HRfemale = 0.46; 95% CI = 0.21 – 0.97; HRmale = 0.65; 95% CI = 0.27 – 1.60).ConclusionGreater consumption of flavonoid‐rich fruits in midlife, particularly apples or pears, as well as oranges, were significantly associated with reduced dementia risk.
Aggregated amyloid‐beta1‐42 infusion following pinealectomy induces Alzheimer’s diseases in rats in a week:behavioral and biochemical impairments
Authors: Tchekalarova Jana Dimitrova , Georgieva Irina , Tzoneva Rumiana , Angelova Violina T 
Published: December 2023

AbstractBackgroundThe hormone melatonin has an advantage compared to other available antioxidants for the therapeutic strategy of Alzheimer diseases (AD) because of its protective activity against amyloid‐beta (Ab1‐42) accumulation, low toxicity effect, and readly passage through the blood‐brain barrier. The beneficial role of melatonin supplementation on Ab neurotoxicity in rat models of AD was reported in many studies. Recently, we reported that melatonin could compensate AD pathology in the icvAb1‐42 rat model via antioxidant activity in the hippocampus. The present study aimed to propose a new rat model of AD‐like pathology induced by pinealectomy followed by icvAb1‐42 infusion a week later.MethodThe theraupetic ffect of melatonin treatment (10 mg/kg, i/p/ for 20 days), starting simultaneously with pinealectomy until decapitation of animals, was assesed on behavioral impairments.Circadian oscillations of motor activity were assesed for 24 h by actimeter. Cognitive functions were explored bt the Y maze and the object recognition test (ORT). The expression of abeta‐amyloid and the activity of the enzyme responsible for Abeta accumulation ‐ gama‐secretase were studied in the frontal cortex and the hippocampus by ELISA method.ResultRats with pinealectomy+icvAβ1‐42, treated chronically with vehicle, demonstrated reduced motor activity with blunted circadian rhythms of locomotion in the actimeter concomitant with impaired spatial working memory and reference memory. Melatonin supplementation corrected those mentioned above behavioral and biochemical abnormalities to the control values.ConclusionOur results suggest that the modified pinealectomy+Aβ1‐42 rat model produces AD pathology as early as a week after icv Aβ1‐42 infusion. In contrast, melatonin treatment had a beneficial effect on behavioral and biochemical impairments. Therefore, this model might be helpful in the exploration of novel melatoninergic analogs with potential activity against AD pathology.
Acknowledgements: This work was supported by the National Science Fund, project KP‐06‐H63/11 and KP‐06‐Н31/16.
A machine learning model to predict progression from subjective cognitive decline to mild cognitive impairment and dementia: a 12‐year follow‐up study
Authors: Mazzeo Salvatore , Lassi Michael , Padiglioni Sonia , Moschini Valentina , Vergani Alberto Arturo , Scarpino Maenia , Giacomucci Giulia , Buralli Rachele , Morinelli Carmen , Fabbiani Carlo , Balestrini Juri , Galdo Giulia , Bagnoli Silvia , Emiliani Filippo , Ingannato Assunta , Nacmias Benedetta , Sorbi Sandro , Grippo Antonello , Mazzoni Alberto , Bessi Valentina 
Published: December 2023

AbstractBackgroundSubjective cognitive decline (SCD) represents a target population to be screened for dementia. Previous studies identified demographic, cognitive and generic features associated with higher risk of progression to mild cognitive impairment (MCI) and Alzheimer’s disease (AD). We aim to test the accuracy of a machine learning model, trained on features derived from non‐invasive and easily accessible techniques, in predicting conversion from SCD to MCI and AD.MethodWe included 150 SCD patients who underwent neuropsychological examination, assessment of cognitive complaint, mood disorders and cognitive reserve, APOE genotyping at baseline. All the patients underwent clinical‐neuropsychological follow‐up every 12‐24 months for a mean time of 12 years.ResultDuring follow‐up, 63 patients were classified as progressive SCD (p‐SCD, 42.0%[95% C.I. = 34.1:49.9], including 41 MCI (27.3% [95%C.I. = 20.2:34.5]) and 22 AD (14.7% [95%C.I. = 9.0:20.3]). 87 patients were classified as non‐progressive SCD (np‐SCD, 58.0% [95%C.I. = 50.1:65.9]). We split the whole sample into a training (80%) and a test group (20%). A gradient boosted trees algorithm was trained on 15 selected features including: age, APOE, education, test assessing for global cognition, immediate and delayed verbal, ecological memory and working memory, language, visuospatial abilities, phonemic fluency and cognitive reserve (Fig.1). This model showed a good accuracy (0.83, AUC = 0.78) in distinguishing p‐SCD and np‐SCD in the test group (Fig.2 and Fig.3).ConclusionOur machine learning models might represent a reliable, cost‐effective and globally scalable tool for a first step screening of SCD patients before confirmation of AD pathology via more invasive and expensive tests.
Analysis of lifestyle factors affecting life satisfaction and depression of the super‐aged in South Korea: Using the Korean Longitudinal Study of Aging (KLoSA)
Authors: Kim Ah‐Ram , Lim Young‐Myoung , Lim Seung‐Ju , Park Ji‐Hyuk , Park Kang‐Hyun 
Published: December 2023

AbstractBackgroundThe purpose of this study was to confirm the correlation between life satisfaction and depression and lifestyle (physical activity, eating habits, frequency of participation, participation diversity) for the super‐aged in South Korea, and to analyze and confirm lifestyle factors that affect life satisfaction and depression.MethodThe independent variables of this study were life satisfaction and depression, and the dependent variables were analyzed including physical activity, regular eating habits, frequency of participation, and diversity of participation as lifestyle factors. For analysis, correlation analysis and multiple regression analysis were performed through SPSS ver 26.0.ResultAs a result of the correlation analysis, it was confirmed that life satisfaction had a quantitative correlation in the order of participation frequency (r = 0.300, p<0.01), participation diversity (r = 0.215, p<0.01), regular eating habits (r = 0.188, p<0.01), and physical activity (r = 0.122, p<0.05). In the case of depression, it was confirmed that there was a quantitative correlation in the order of life satisfaction (r = 0.507, p<0.01), participation frequency (r = 0.297, p<0.01), regular eating habits (r = 0.218, p<0.01), participation diversity (r = 0.128, p<0.05). As a result of multiple regression analysis, participation frequency (t = 6.262, p<0.001) and regular eating habits (t = 4.627, p<0.001) were found to have statistical significance, and participation frequency (t = 6.540, p<0.001), regular eating habits (t = 4.61, p<0.001).ConclusionThrough this study, lifestyle factors that affect the life satisfaction and depression of the super‐aged in South Korea were identified. Therefore, based on the results of this study, a multi‐faceted intervention program based on lifestyle is needed to improve the life satisfaction and depression of the super‐aged.
Feasibility and safety of a nanoporous system for intrathecal pseudodelivery of anti‐amyloid therapies: proof‐of‐concept in mice
Authors: Szilagyi Andrei , Schreiner Thomas Gabriel , Tomas‐Zapico Cristina , Menendez‐Gonzalez Manuel , Tamba Bogdan Ionel 
Published: December 2023

AbstractBackgroundThe cerebrospinal (CSF) sink therapeutic strategy hypothesizes that clearing soluble beta‐amyloid from the CSF results in removing brain beta‐amyloid (Aβ) (1). We proposed a new way of achieving the CSF sink effect by means of an innovative route of drug delivery, named intrathecal pseudodelivery (ITPD) of drugs. ITPD is based on an implantable device endowed with semipermeable nanoporous membranes that are permeable to soluble Aβ but not to monoclonal antibodies (mAb) (2). In this study, we aimed to show proof‐of‐concept of a fully implantable device for ITPD in combination with mAbs for selectively clearing Aβ from CSF in a mouse model of Alzheimer’s Disease (AD)MethodWe encapsulated flat alumina nanoporous membranes of a pore size of 10.0 nm, and we coupled the capsule with a reservoir and a catheter. The system was implanted in symptomatic 34‐week‐old male (n = 6) and female (n = 4) APPswe/PS1dE9 mice and their wild‐type littermates (n = 10), with the capsule/reservoir placed subcutaneously and the catheter connected to the right lateral ventricle. Devices were infused with either artificial CSF (aCSF) (n = 10), or an anti‐Aβ mAb solution (n = 10). After surgery, animal welfare and body weight were monitored for up to 30 days. Behavioral tests were carried out before and 30 days after implantation.ResultImplantation procedure was successful, with a rapid animal recovery period of 15 minutes after the surgery. In 5 of the implanted mice complications related to anesthesia were reported, but none was severe. For the preliminary behavioral analyses, a partial improvement in cognitive functions was evidenced, with no significant adverse effects at any of the time points.ConclusionThese findings provide proof‐of‐concept on nanoporous systems for ITPD of anti‐Aβ therapies that replicate previous feasibility and safety studies and, together with ongoing studies assessing efficacy, provide further validation of this therapeutic route in AD.
Impact of cognitive stimulation on the autonomy of a patient with early‐onset AD
Authors: Mariani Francesca 
Published: December 2023

AbstractThe relevance of non‐pharmacological cognitive stimulation treatments in patients with MCI and AD is increasingly recognized as tools for slowing the progression of the disease and preserving autonomy. However, the registration and quantification of the impact is diffcult to consign.The objective of the present work is to present the case of a 59 year old woman, with early onset AD who is undergoing cognitive stimulation treatment and its evolution in cognitive and functional performance.Initially he presented with typical subjective memory complaint, he obtained a score of 25/30 in MMSE and a CDR of 1. An 18F‐FDG study was performed that showed the typical hypometabolism pattern and a positive 11C‐PIB PET/CT for cortical amyloid deposits. On functionality scales, he scored 100 on the Barthel index and 8 on the Lawton and Brody scale. He underwent cognitive stimulation treatment, from that moment and uninterruptedly, through biweekly sessions of 45‐60 minutes each. It currently has a CDR of 2 and an MMSE of 15/30. In relation to its functionality, it presents a Barthel Index of 100/100 and a Lawton and Brody scale of 4/8.Although the inevitable progression of the disease has an evident impact on cognitive functions, which is clearly reflected in the neuropsychological tests, the functionality of the patient has been fully maintained for basic activities of daily living, and partially for activities instrumentals. This demonstrates the relevance of personalized cognitive stimulation treatments in patients with Alzheimer’s disease, especially in forms of early presentation, when the disease is more aggressive and when patients are very active at the time of diagnosis.
Sex and APOE differences in Alzheimer’s Disease‐On‐Ramp risk factor profiles: Are all risk factors for Alzheimer’s Disease created equal?
Authors: Merlini Simona , Vitali Francesca , Brinton Roberta Diaz 
Published: December 2023

AbstractBackgroundObesity, diabetes (T2D), hypertension (HTN), cardiovascular disease (CVD), chronic obstructive pulmonary disease (COPD), end‐stage renal disease (ESRD), stroke and hyperlipidemia are known Alzheimer’s Disease (AD)‐on‐ramp risk factors. However, it remains unclear whether the risk conferred by these conditions is modified by other unmodifiable AD risk factors, such as chromosomal female sex and APOE genotype. Therefore, we conducted a retrospective study using the UK Biobank to determine the effect of AD‐on‐ramp risk factors, in combination with sex and APOEε4 carrier status.MethodUK Biobank dataset consisted of 500k participants. Inclusion criteria were age older than 55 years old, no prior history of neurodegenerative disease, neurosurgery, or cancer, and enrollment with at least 3 years of follow‐up. Patients were propensity score‐matched based on age and educational level. We next conducted stepwise regression analysis to investigate the effect of AD‐on‐ramp risk factors. Sensitivity analyses were computed to evaluate the impact of medications prescribed for the risk factors on AD. Finally, we conducted sensitivity analyses on sex‐specific propensity score‐matched cohorts.ResultOf the 181,865 participants who met inclusion criteria, 1,503 had AD and were 1:10‐matched to 15,030 patients without AD. In both cohorts, 56% were females and 44% were males and the AD cohort was predominantly APOEε4 carriers (62%). We found that stroke, T2D, HTN, HLP, and ESRD were associated with increased risk of AD, whereas obesity was a protective factor. When controlling by sex and genotype, the effect of APOEε4 was greater if considered with T2D and HTN respectively. Women exhibited greater OR of APOEε4, T2D, and HTN than men, and cholesterol medication protected against AD risk, especially in men.ConclusionThese findings support previous reports that T2D, HTN, HLP, and ESRD are associated with increased risk of AD. We identified and ranked AD‐on‐ramp risk factors by their impact to explain variation in the AD onset, controlling by sex and genotype. In addition, we found sex‐specific protective factors, where obesity and cholesterol medication were associated with lower risk of developing AD in women and men respectively. Ongoing analyses include evaluation of the age‐dependent effect on AD risk factors, stratified by sex and APOE genotype.