bluuebunny/crossref_metadata_2025_split huggingface dataset:
The relationship between the frailty of the older adults and cognitive function, activities of daily living, and life satisfaction
Authors: Lee Gyeong A , Park Ji‐Hyuk 
Published: June 2023

AbstractBackgroundFrailty belongs to the pre‐disability stage and is closely related to the transition to disability. It is more fatal when frailty occurs in older adults than in other age groups. By understanding the negative negative outcomes of frailty on the health of older adults, they will be able to manage their own health and prevent disability. This study aims to examine whether the frailty of older adults contributes to cognitive function, activities of daily living, life satisfaction.MethodThe study sample was 9,885 community‐dwelling older adults aged 65 years and older. Data obtained from the 2020 survey of living conditions and welfare needs of older Koreans. Hierarchical regression analysis was used to determine whether frailty and cognitive function, activities of daily living, life satisfaction are significantly related even after controlling for factors influencing dependent variables. Life‐course determinants factors (i.e. age, sex, spouse, education, living environment, life events, lifestyle) were entered in block 1, the number of chronic diseases was entered in block 2, and frailty factors(physical, psychological, social) was entered in block 3.ResultThe analysis results are as follows. First, cognitive function decreased significantly as physical, psychological, and social frailty (β = 0.100, p<0.001; β = 0.104, p<0.001; β = 0.112, p<0.001, respectively) increase. Second, as physical, psychological, and social frailty (β = 0.063, p<0.001; β = 0.283, p<0.001; β = 0.032, p = 0.003, respectively) increase, the basic activities of daily living decreased significantly. Third, as physical, psychological, and social frailty (β = 0.140, p<0.001; β = 0.304, p<0.001; β = 0.028, p = 0.008, respectively) increase, the instrumental activities of daily living decreased significantly. Fourth, as physical, psychological, and social frailty (β = 0.041, p<0.001; β = 0.209, p<0.001; β = 0.076, p<0.001, respectively) increase, life satisfaction decreased significantly.ConclusionIn this study, it was investigated whether frailty (physical, psychological, and social) contributes to cognitive function, the activities of daily living, and life satisfaction among older adults. This finding suggests that frailty may be related to health‐related variables of older adults.
The neuronal pentraxin receptor (NPTXR) as a candidate biomarker of synaptic dysfunction in mild cognitive impairment
Authors: Dulewicz Maciej , Kulczynska‐Przybik Agnieszka , Borawska Renata , Slowik Agnieszka , Mroczko Barbara 
Published: June 2023

AbstractBackgroundEarly deficits of cognitive symptoms have molecular background closely related to Alzheimer’s Disease (AD). Before developing full‐blown AD, mild cognitive impairment (MCI) develops. It has been suggested that synaptic pathology is closely associated with memory impairment in the early phase of the disease and may be monitored by assessment of the synaptic proteins in cerebrospinal fluid (CSF), like neuronal pentraxin receptor (NPTXR). The highest expression of NPTXR and involvement in neuronal processes have been observed in the hippocampus and cortex. This candidate biomarker of synaptic dysfunction may have a crucial role in synaptic transmission and modulation of memory processes with other synaptic proteins. The purpose of the our investigation was to assessed the neuronal pentraxin receptor (NPTXR) level in cerebrospinal fluid (CSF) in MCI patients.MethodThe study included 17 patients with MCI and 17 non‐demented controls. The CSF levels of NPTXR and classical AD biomarkers, such as Aβ‐42, Aβ‐42/Aβ‐40, Tau, and pTau181, were assessed by commercially available immunoenzyme assays.ResultThe CSF concentration of NPTXR was significantly lower in MCI patients compared to non‐demented controls. Moreover, NPTXR level was positively correlated with Tau181, Aβ‐42, and total Tau proteins in MCI patients.ConclusionOur results suggest that Neuronal Pentraxin Receptor may be one of the biomarker reflecting synaptic dysfunction in MCI patients. These preliminary results seem very promising, particularly for the early diagnosis of Alzheimer’s disease. Future research concerning NPTXR is necessary to understand better the role of the protein in early pathological processes of the disease.
Open RoAD: Design and baseline characteristics of an open‐label rollover study evaluating long‐term safety and tolerability of subcutaneous gantenerumab in participants with early Alzheimer’s disease
Authors: Neve Anuja , Bullain Szofia , Das Bibha , Huang Zhiyue , Watkin Michelle , Delmar Paul , Klein Gregory , Bittner Tobias , Lott Dominik , Smith Janice , Kerchner Geoffrey A. , Fontoura Paulo , Baudler Monika , Doody Rachelle S. 
Published: June 2023

AbstractBackgroundGantenerumab, a human monoclonal antibody targeting aggregated beta‐amyloid (Abeta), is a potential disease‐modifying treatment for early (prodromal‐to‐mild) Alzheimer’s disease (AD). SCarlet RoAD (SR) (NCT01224106) and Marguerite RoAD (MR) (NCT02051608) were two Phase III trials which assessed the efficacy and safety of subcutaneous (SC), low‐dose gantenerumab in participants with prodromal and mild AD, respectively, for up to 2 years. Following a gap period gantenerumab treatment was continued with uptitration to a dose of 1,200 mg monthly in open‐label extensions (OLE), which demonstrated substantial Abeta removal by positron emission tomography without new or unexpected safety findings. Here, we describe the study design, present baseline characteristics, and safety data from an additional open‐label, multicenter, rollover study, Open RoAD (OR) (NCT04339413), collecting long‐term safety and tolerability data for gantenerumab in participants who completed the SR OLE or MR OLE.MethodParticipants who completed either OLE study and were treated with doses up to 1,200 mg of gantenerumab for up to 5 years continue to receive the same dose of SC gantenerumab (every 4 weeks [q4w]) for 2 additional years in OR. The primary objective is to evaluate long‐term safety and tolerability by assessing adverse events, including amyloid‐related imaging abnormalities, and injection‐site reactions. Exploratory efficacy objectives include Mini‐Mental State Examination (MMSE) total score. The long‐term effect of gantenerumab on pharmacodynamic measures and biomarkers will also be explored.Result
Baseline characteristics
Fifty‐nine participants from SR OLE and 56 participants from MR OLE received at least one dose of gantenerumab in OR. The median participant age at baseline was 78 years, and the majority of the participants were female (61%). Sixty‐seven percent of participants were apolipoprotein‐E‐e4 (APOE e4) carriers. The median total MMSE score at baseline was 16.
Safety data will be presented.
ConclusionThe RoAD studies are among the longest‐duration OLEs of an anti‐amyloid monoclonal antibody. Data from the OR study demonstrate that gantenerumab at doses of 1,200 mg administered SC q4w is well tolerated, with no new or unexpected safety findings in patients with early AD.
Modifiable dementia risk factors are associated with greater subjective cognitive concerns but not perceived susceptibility to dementia in late middle‐aged adults: Baseline characteristics of the BetterBrains Trial
Authors: Rosenich Emily , Bransby Lisa , Pirotta Stephanie , Ayton Darshini , Buckley Rachel F. , Maruff Paul , Lim Yen Ying ,   BetterBrains Research Group
Published: June 2023

AbstractBackgroundA range of lifestyle factors in midlife can increase risk for developing dementia in late‐life.1 However, it remains unclear whether the presence of such risk factors (RFs) is associated with individuals’ insight into their risk of developing dementia. In a group of middle‐aged adults with a family history of dementia enrolled in a lifestyle prevention trial, we measured associations between modifiable RF prevalence, subjective cognitive concerns, and perceived susceptibility to dementia.MethodParticipants (n = 456) enrolled in BetterBrains (betterbrains.org.au)2 completed a comprehensive self‐report RF assessment at baseline. Modifiable dementia risk was determined across four domains (vascular health, social/cognitive engagement, mood, sleep) and trial eligibility required risk in at least one domain. Participants were grouped according to the number of domains in which they reported high‐risk (ranging from 1‐4). Participants completed the Cognitive Function Instrument, and a brief questionnaire to assess perceived susceptibility to dementia (Motivation to Change Lifestyle/Health Behaviours for Dementia Risk Reduction scale). Linear regressions examined associations between modifiable RF prevalence, subjective cognition, and perceived susceptibility to dementia, adjusting for age, sex, education, negative beliefs about ageing, and beliefs about protective health behaviours on dementia risk.ResultParticipants were mostly female (80%), with an average age of 59.4 years and 15.2 years of education. Of the sample, 29.6% reported risk in all domains (29.6%) and 16.9% in three domains. Risk in a higher number of RF domains was significantly associated with greater subjective cognitive concerns (β(SE) = 0.18(0.06), p = <.001), but not with greater perceived susceptibility to developing dementia (β(SE) = 0.62(0.35), p = .08). Increasingly negative beliefs about ageing and weaker beliefs in the protective effect of health behaviours were the only significant predictors of perceived susceptibility to dementia (both p’s <.05).ConclusionIn middle‐aged adults, dementia RFs are associated with greater subjective cognitive concerns, but not with an increased perception of susceptibility to dementia. Incongruence between participants’ self‐report of subjective cognitive concerns and susceptibility to dementia may be due in part to poor knowledge on modifiable dementia RFs.3 Perceptions of personal susceptibility to dementia may also be tied more closely to negative ageing stereotypes typically associated with older age and family history of disease.
Inverse relationship between education and amyloid burden in individuals with subjective cognitive decline plus and mild cognitive impairment
Authors: Hönig Merle C. , Caprioglio Camilla , Collij Lyduine E. , Frisoni Giovanni B , Barkhof Frederik , Farrar Gill , Scheltens Philip , Delrieu Julien , Molinuevo Jose Luis , Grau‐Rivera Oriol , Walker Zuzana , Nordberg Agneta K , Demonet Jean‐François , Stephens Andrew W. , Battle Mark R , Buckley Christopher , Gispert Juan Domingo , Jessen Frank , Altomare Daniele , Drzezga Alexander ,   the Amypad consortium
Published: June 2023

AbstractBackgroundHigher educated patients with MCI can tolerate more neuropathology than lower educated patients with similar clinical impairment. It is not known whether this observation also accounts for potential preclinical stages of AD, namely subjective cognitive decline plus (SCD+).MethodData of 197 SCD+ individuals, 227 MCI and 157 AD patients were included, which were collected as part of the AMYPAD‐DPMS cohort (https://amypad.eu/). First, median education in years was computed across the AD‐spectrum groups for each of the 8 European sites. Next, using a median split, the SCD+, MCI and AD cohort were separately categorized into a higher and lower educated group, excluding subjects with median education. Afterwards, the higher and lower educated AD‐spectrum groups were matched for age, sex and cognitive function (MMSE) using propensity score matching in R, leading to the following sample (low/high education): 54/54 SCD+, 70/81 MCI and 56/65 AD patients. Global amyloid load was compared between education groups using Centiloid (CL) information derived from Flutemetamol and Florbetaben PET scans. To confirm the results of the stringent group comparison, partial correlations between years of education and CL values correcting for age, sex and tracer type were performed for each AD‐spectrum group. All analyses were conducted in SPSS 28 and significance level was set to p < .05.ResultHigher educated SCD+ subjects presented significantly (p <. 001) lower CL values (M(CL) = 16.48) than lower educated SCD+ subjects (M(CL) = 32.17), whereas the opposite effect (p < .046) was observed in the MCI cohort with higher educated MCI patients presenting greater CL values (M(CL) = 57.08) compared to the lower educated MCI group (M(CL) = 41.74). No difference was found in the AD group. Results were further confirmed by the correlation approach across the unmatched sample yielding a negative association between years of education and CL values in the SCD+ group (r = ‐.159, p = .027) and a positive association in the MCI group (r = .153, p = .022).ConclusionThese results indicate that sensitivity to early amyloid accumulation may possibly increase with higher education in potential preclinical stages of AD, whereas in clinical stages of AD higher education may support compensatory mechanisms against amyloid burden.
Quantum crystallographic method improves the accuracy of screening of inhibitors: A set of Alzheimer’s disease responsible protein‐ligand complexes
Authors: Kandasamy Saravanan , Srinivasan Sugarthi 
Published: June 2023

AbstractBackgroundIn drug design and development, identification of lead structure is a crucial step to predict the ligand binding affinity and functional potency with any of target enzyme/protein. The recently developed quantum crystallographic method (fragment‐based approach) has been used as a substitutional way to calculate the interaction energies. This quantum mechanical level information gives a deeper understanding of structural facts with the position of hydrogen atoms and valence electron distributions. It is very much essential to understanding the electronic properties of drug‐receptor interactions. Therefore, the quantum crystallographic based interaction energy calculation is a better alternative method to docking score‐based modelling.MethodA set of AD responsible protein‐ligand complexes were selected for the quantitative analysis. Molecular docking of selected compounds with four different enzymes (AChE/BChE/BACE1/GSK3β) was carried out and then, all the selected complexes have been subjected to MD simulation. Later, the 3D coordinates of ligand with active site residues (around 4Å from the ligand) were used for quantum crystallographic studies.ResultThe screened molecules are forming strong hydrogen bonding and hydrophobic interactions with active site residues of all four enzymes; particularly, π‐π stacking, π‐cationic, π‐alkyl and π‐σ types of interactions, which are highly stable during dynamic behavior. After the quantum crystallographic studies, the interaction energies of selected compounds with different active site residues of all four enzymes were analyzed; it is ranged from ‐20.83 to ‐3.92 kcal/mol and the total interaction energies of each complex are higher than binding energy gained from MD simulation. And, the RMSD of each molecule was compared with the corresponding geometry of solid‐state and dynamic state; it is found to be significantly low (>0.5Å) and similar. Interestingly, the correlation between experimental IC50 and averaged interaction energies of selected compounds exhibits good agreement.ConclusionThe in‐silico results revealed conformational flexibility, high stability and compactness, binding affinity and orientation of the target molecules in the active site residues of all enzymes in the physiological nature (water‐medium). Quantum crystallographic method is a novel approach that opens new window to delineate the different type of interactions at electronic level. And, it may allow us to design new drug against target disease.
Testing the brain maintenance and cognitive reserve hypothesis of cognitive aging: Application to vascular and metabolic risk factors
Authors: Neth Bryan J. , Lesnick Timothy G. , Castillo Anna , Przybelski Scott A. , Graff‐Radford Jonathan , Machulda Mary M. , Mielke Michelle M. , Petersen Ronald C. , Lowe Val J. , Jack Clifford R. , Knopman David S. , Vemuri Prashanthi 
Published: June 2023

AbstractBackgroundTwo pathways that help explain cognitive health are 1) brain maintenance – referring to the relative absence of brain changes over time; 2) cognitive reserve – a property of the brain that allows for sustained cognitive ability in the presence of brain pathology. Both pathways influence cognitive aging and are best understood using longitudinal data. Our goal was to assess the effect of modifiable vascular/metabolic and lifestyle enrichment factors on these pathways using longitudinal brain changes measured on structural magnetic resonance imaging (MRI) and longitudinal cognitive decline. Lastly, we combined these pathways and their relationships in the same model.MethodWe identified 1250 participants from a well‐characterized sample of older adults from the Mayo Clinic Study of Aging with both longitudinal MRI and cognitive data. Linear mixed models were performed to assess the impact of modifiable factors on brain maintenance and cognitive reserve. Latent growth curve models (SEM) were used to assess the impact of brain structure and cognitive reserve on longitudinal cognition.ResultThe mean age of our sample was 78.8 years, with 45.4% female, and 27.1% APOE4 carriers. Mean follow‐up time was 4.0 years with a mean of 3.2 MRI scans per participant. Linear mixed models showed that poorer vascular/metabolic health (presence of vascular/metabolic conditions) was associated with lower cross‐sectional temporal region cortical thickness (‐0.014 (0.003), p<0.001) and lower global cognition (‐0.042 (0.018), p = 0.024). Higher estimated cognitive reserve at baseline as assessed by education/occupation composite (0.103 (0.01), p<0.001) was associated with higher global cognition. Unexpectedly, late‐life physical activities were related to lower global cognition (‐0.05 (0.007), p = 0.004). Our final latent growth curve SEM fit the data well showing temporal associations between unmodifiable characteristics, cognitive reserve, and brain structural pathways, as well as the influence of modifiable vascular/metabolic factors.ConclusionWe found that brain maintenance and cognitive reserve pathways were related to better cognition over time. We further showed that vascular/metabolic health impacts long‐term cognitive outcomes (i.e. cognitive aging) primarily through the brain maintenance pathway. These data provide a modeling scheme for future studies and can aid in assessing the pathways by which individual factors may influence cognitive aging.
Longitudinal lumbar puncture adherence in the Alzheimer’s Prevention Initiative Autosomal‐Dominant Alzheimer’s Disease Colombia Trial
Authors: Acosta‐Baena Natalia , Ríos‐Romenets Silvia , Giraldo‐Chica Margarita , Espinosa Alejandro , Ramos Claudia , Aguillon David , Aponte Claudia , Leon‐Varela Yudy M , Piedrahita Francisco , Lopez Liliana , Gomez Francisco , Ehrhard Patricia , Sink Kaycee M. , Tariot Pierre N. , Reiman Eric M. , Lopera Francisco ,   API ADAD Colombia Trial Group
Published: June 2023

AbstractBackgroundCerebrospinal fluid (CSF) biomarkers have potentially important roles in Alzheimer’s disease (AD) treatment and prevention trials. The Alzheimer’s Prevention Initiative Autosomal‐Dominant AD (API ADAD) trial protocol (NCT01998841) includes optional CSF biomarker measurements at baseline, 24 months, and 60 months. We determined the adherence to lumbar puncture (LP) procedures and predictors of dropout rates in trial participants who had a baseline LP.MethodAvailable data from cognitively unimpaired 30–60‐year‐old members of the Presenilin 1 E280A kindred were used to characterize LP participation rates at baseline, LP‐related complications and potential factors associated with adherence to 24‐month follow‐up LPs (age, sex, education, place of residence, puncture site, needle gauge, number of attempts, and traumatic puncture). Logistic regression was used to investigate associations.Result130 (51.6%) of 252 trial individuals consented to participate in the CSF biomarkers substudy. Consent was not associated with age, sex, education or location of residence. 43 (33.1%) participants had 49 LP‐related complications at baseline. The most frequent complications were headache in 25 (19.2%) participants and low back pain in 14 (10,8%) participants. Other baseline LP‐related events were dizziness, photopsia, and tremor. Complications at baseline were not associated with puncture site (L3‐L4 or L4‐L5), needle gauge (22 or 24 G), number of attempts or traumatic puncture. Ninety‐eight (75.4%) of the eligible participants consented to have the 24‐month follow‐up LP. Absence of any baseline LP‐related complications was associated with less attrition in this subsequent LP consent (0R = 0.25; 95%CI 0.10‐0.61), after controlling for age, sex, years of schooling, rural home and city of residence.ConclusionAdherence to 24‐month follow‐up LP in API ADAD trial was 75.4%. This clinical trial is conducted in young people, active at work. Although some participants live far from the city where LP’s are performed or in remote areas, this did not affect their willingness to consent to a second LP. However, the presence of any complication did increase the risk of withdrawal for the subsequent procedure since it impacted ability to work. This information could help to inform the design and statistical power of future AD prevention trials using CSF biomarker endpoints.