bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biochemical Characterization of LINC00298, a Non‐Protein Encoding RNA, which when Expressed, Plays a Role in the Development of Early‐Onset Alzheimer’s Disease
Authors: Whitaker Rachel A Hellmann 
Published: June 2023

AbstractBackgroundLINC00298 gene was identified through whole‐genome sequencing experiments as an important factor in the development of early‐onset Alzheimer’s disease. The LINC00298 RNA gene product has not been biochemically characterized and it’s physiological role in the development of Alzheimer’s disease remains unknown.MethodLINC00298 RNA was in vitro transcribed and then bound to Mg2+. The Mg2+ binding event was characterized by gel electrophoresis and UV‐Vis spectroscopy. The LINC00298 RNA was then biotinylated on its 3' end and bound to streptavidin chromatography beads. Affinity chromatography was utilized to determine binding partners for LINC00298 RNA from hippocampal neuronal cell lysate. These binding partners were identified with mass spectroscopy.ResultLINC00298 RNA undergoes signification structural changes upon binding to Mg2+. Biophysical analysis indicates that these structural changes are secondary and tertiary in nature. Additionally, LINC00298 RNA does have binding partners within neuronal cells, which may shed light on its physiological role in the development of early‐onset Alzheimer’s disease.ConclusionLINC00298 RNA is an important gene product in the development of early‐onset Alzheimer’s disease. Though it does not encode for a protein product, this RNA has three‐dimensional structure and has binding partners within neuronal cells.
Nutritional interventions for brain health in patients with Alzheimer’s disease: An expert consensus
Authors: Jiang Jiwei , Xu Jun , Shi Hanping 
Published: June 2023

AbstractBackgroundAlzheimer’s disease (AD), the leading cause of dementia in the elderly, is the greatest and sharp increasing challenge for global public health and social care in the 21st century. Being limited options for early diagnosis and the exact pathophysiology of AD, effective therapeutic strategies are still a great challenge. AD is among the least well‐served therapeutic areas for drug treatments. Recently, there has been accumulating evidence that malnutrition and weight loss are frequent and serious presentations of patients with AD, and they also affect the development and progression of this disease, which forms a vicious circle. Accordingly, Mediterranean‐like diet as a protective factor against memory decline and mediotemporal atrophy may be related to a decrease of amyloidosis and tau‐pathology. Moreover, the latest reviews and meta‐analyses have demonstrted that together the modifiable risk factors, including dietary and lifestyle changes, could theoretically prevent or delay 40% of worldwide AD and related dementia. The evidence suggests that nutrition as an important environment factor of AD may participate in the whole stage through multifaceted pathways.It is of further interest how to manage the nutritional status in patients with AD, and whether supplementation of energy and/or specific nutrients could be able to prevent the onset or the development of cognitive decline.MethodWe established a Chinese multidisciplinary working group consistent with officially accepted standards, discussing the nutrition‐related prevention, diagnosis and management in patients with AD based on the international research evidence currently.ResultWe proposed primordial‐primary‐secondary‐tertiary prevention strategies in accordance with the continuous pathological process of AD, and emphasized the important role of nutrition in this new four‐level prevention strategy. Furthermore, we provided the first expert consensus of nutritional interventions for brain health in patients with AD including 26 evidence‐based recommendations, focusing on the nutrition‐related prevention, diagnosis and management.ConclusionThis consensus emphasizes that nutritional intervention should be early, collaborative, holistic and long‐term. Focusing on the social determinants of health in populations, including diet and nutrition, to maintain optimal brain health and reduce the development of risk factors of dementia have great significance.
A comparative analysis of different cognitive reserve estimates and their relation to connectivity in resting‐state functional MRI
Authors: Ersoezlue Ersin , Buerger Katharina , Dechent Peter , Haynes John‐Dylan , Ewers Michael , Fliessbach Klaus , Kleineidam Luca , Laske Christoph , Peters Oliver , Priller Josef , Ramirez Alfredo , Schneider Anja , Spottke Annika , Teipel Stefan , Wiltfang Jens , Wolfsgruber Steffen , Yakupov Renat , Duzel Emrah , Jessen Frank , Rauchmann Boris‐Stephan , Perneczky Robert 
Published: June 2023

AbstractBackgroundCognitive reserve (CR) is a concept that addresses the differences in trajectories of cognitive decline while facing neurodegenerative changes in the brain. Common proxies of CR include demographic or socio‐behavioral measures such as sex and educational/occupational attainment. Recent studies have quantified CR using a residual approach, a direct and cross‐sectional measurement of the discrepancy between estimated cognition and neurodegenerative burden. The associations between these two approaches remain largely unclear.MethodsData of 801 participants from the German DELCODE study was used, including 215 healthy controls and 586 individuals with increased risk of AD dementia (61 subjective cognitive decline, 150 mild cognitive impairment and 75 aged 80 years and older with a first‐degree relative with AD). To differentiate similar clusters in tested lifestyle factors, we conducted a dimension reduction method using principal component analysis and consequently derived 8 component factor scores. A residualized memory CR score (CRMEM) was calculated as residuals from a multilinear regression model. Functional connectivity was analyzed using resting‐state fMRI data.ResultsPartial correlation analyses revealed significant positive correlations between CRMEM and component factors 1 (retirement and living), 3 (educational attainment) and 4 (social network and occupational attainment) in the entire cohort and at risk for AD dementia individuals. Higher CRMEM was associated with higher functional connectivity between the hippocampus and regions related to the default‐mode network. Factor scores 3 and 4 were associated with increased rostral hippocampus‐right angular gyrus functional connectivity. A mediation analysis showed a significant indirect effect of factor 3 on the relationship between CRMEM and rostral hippocampus‐right angular gyrus functional connectivity.ConclusionCR‐favorable socio‐behavioral factors are correlated with higher CRMEM in healthy aging and AD‐risk groups. Educational attainment might present a rather specific proxy of CR for individuals at AD‐risk. In contrast, mid‐life (occupational attainment) and late‐life factors (retirement years, social network and living status) predict CR both in AD‐risk and healthy aging groups. However, only in the AD‐risk group, hippocampal functional connectivity was higher in individuals with higher CRMEM, mediated in favor of higher educational and female sex, suggesting a close relationship to neural reserve.
Poor oral health predicts cognitive impairment in elders
Authors: Chen Jung‐Tsu , Tsai Stephanie Di‐Shan , Tseng Ching‐An , Chiou Jeng‐Min , Chen Ta‐Fu , Chen Yen‐Ching , Chen Jen‐Hau 
Published: June 2023

AbstractBackgroundTooth loss, periodontal disease, dementia, and Alzheimer’s disease share several risk factors in older adults. Several previous studies have reported positive associations between these dental problems and global cognitive defects. However, limited is known about the relationships among multiple dental/periodontal statuses and different cognitive domains.MethodThis six‐year (2011‐2017) cohort study includes 515 older adults (65+). Global cognition was assessed by Montreal cognitive assessment‐Taiwan version (MoCA‐T). For cognitive domains, we used logical memory tests (immediate and delayed theme and free recall) in Wechsler Memory Scale‐Third Edition (WMS‐III) to assess memory. Trail Making Test A and B was used to assess attention and executive function, respectively. Digit span‐forward and backward was used to evaluate attention and working memory/short‐term memory, respectively. Verbal fluency tests were used to assess category/semantic fluency. A Z‐score was calculated for each cognitive domain‐specific test according to baseline mean and standard deviation. Oral health status includes tooth defect (dental caries, tooth wear, cervical abrasion, retained root or crown fracture), periodontal health (disease severity from healthy periodontal status, gingivitis to periodontitis), and arch integrity (no tooth loss nor retained root or crown fracture). Generalized linear mixed models were used to assess the associations above adjust important covariates.ResultAt baseline, periodontitis was associated with poor performance in executive function [Trail Making Test A: b = ‐0.14, 95% confidence interval (CI) = ‐0.27 to ‐0.01]. The association between baseline severity of tooth defect and poor memory decreased (logical memory‐immediate theme recall: b = ‐0.05, 95% CI = ‐0.10 to ‐0.01); similarly finding was found for attention domain (digit span‐forward: b = ‐0.04, 95% CI = ‐0.07 to ‐0.001). At baseline, loss of arch integrity was associated with a better working memory/short‐term memory (digit span‐backward: β = 0.18, 95% CI = 0.01 to 0.36); as follow‐up time increased, this association decreased over six years (β = ‐0.04, 95% CI = ‐0.07 to ‐0.003).ConclusionPeriodontitis, tooth defects, or arch integrity was associated with poor performance of cognitive domains (memory, attention, and executive function) over time. A oral health evaluation may serve as predictors of the preclinical phase of dementia in its upcoming years.
Functional hyperconnectivity is associated with higher levels of sPDGFRβ, a marker of blood brain barrier breakdown, in older adults
Authors: Contreras Joey A , Fujisaki Kimiko , Ortega Nancy E , Barisano Giuseppe , Sagare Abhay P , Zlokovic Berislav V , Toga Arthur W. , Pa Judy 
Published: June 2023

AbstractBackgroundApolipoprotein E4 (APOE4) has toxic effects on the cerebrovascular system, neuronal function, and functional connectivity of brain networks (e.g., default‐mode, frontal‐attention, and salience networks). The thalamus, a vital structure that acts as a relay station between many networks, has become of interest in AD research with studies showing atrophy among those with early AD and diminished cortical‐thalamic connections among those with vascular impairment. Additionally, CSF soluble platelet‐derived growth factor receptor‐β (sPDGFRβ), a marker of blood‐brain barrier breakdown, has been associated with AD risk, especially in APOE4 carriers. The present study investigated the relationship between CSF sPDGFRβ and functional connectivity in APOE4 carriers and non‐carriers.MethodOne hundred sixty‐six older adults from the Los Angeles area were selected from a larger cohort (96 females, mean age±SD = 67.4±10.7, 68 APOE4 carriers) based on availability of rsfMRI data. Image data was processed using CONN‐toolbox v19c. Grey matter was parcellated using Harvard/Oxford brain atlas, excluding cerebellum. ROI‐to‐ROI analyses were conducted selecting the thalamus as seed region averaging mean connectivity between the left and right structure of other parcellated brain regions. Linear regression models evaluated significant associations between blood oxygen level‐dependent (BOLD) and network connectivity among seed‐target regions and CSF sPDGFRβvalues, while covarying for age and sex. Comparison of averaged functional connectivity values between seed and all target regions among APOE4 carriers and non‐carriers was also examined.ResultHigher functional connectivity between the thalamus and resting state network hub regions were associated with higher CSF sPDGFRβ (Fig 1A, 1C). Cortical regions within the networks included posterior cingulate gyrus, anterior cingulate gyrus, and frontal eye field. Averaged functional connectivity between these areas was significantly higher in APOE4 carriers compared to non‐carriers (Fig 1B).ConclusionThe thalamus is a key subcortical structure for relaying signals across the brain for memory, attention and sleep/wakefulness cycles, and more recently with relevance to AD. These findings suggest a link between early BBB breakdown and elevated functional connectivity in brain regions known to have high synaptic activity and early pathology among non‐demented older adults at risk for AD.
A single baseline amyloid PET could be sufficient for predicting Alzheimer’s disease conversion in mild cognitive impairment
Authors: Choo Il Han , Chung Ji Yeon , Chong Ari , Ha Jung‐Min , Choi Yu Yong , Kim Hoo Won 
Published: June 2023

AbstractBackgroundBaseline amyloid burden in mild cognitive impairment (MCI) has been linked to conversion to Alzheimer’s disease (AD), but the comparison of baseline and longitudinal changes in amyloid burden for predicting AD remains unresolved. The objectives of this study aimed to compare the prognostic ability of baseline and longitudinal changes in amyloid burden in MCI patients.MethodSeventy‐five individuals with MCI were recruited and examined annually by clinical interviews for a mean follow‐up of 24 months (Range 11.6 – 42.0). [18F]Florbetaben positron emission tomography (PET) scans were performed. T1‐weighted 3D volumes were acquired for co‐registration, and to define regions of interest (ROIs). We examined whether baseline and longitudinal amyloid burden changes can improve AD conversion by Cox proportional hazard model analysis and receiver operating characteristic (ROC) curve analysis.ResultCox proportional hazards model analysis showed that baseline amyloid burden was significantly associated with increased risk of conversion to AD (hazard ratio [HR] = 10.0; 95% confidence interval [CI], 1.15 – 85.39; p = 0.04), but longitudinal amyloid burden changes was not (HR = 0.2; 95% CI, 0.04 – 1.51; p = 0.13). When predicting AD, longitudinal amyloid burden changes had better ROC accuracy of 65.2% (95% CI, 48.4 – 82.0%) than baseline amyloid burden of 59.6% (95% CI, 40.3 – 79.0%), without statistical significance in pairwise comparison.ConclusionA single baseline amyloid PET could be sufficient in the prediction of AD conversion in MCI.
Association of anosmia with mild cognitive impairment and biomarkers of brain aging
Authors: Dong Yi , Li Yuanjing , Liu Keke , Cong Lin , Zhang Qinghua , Hou Tingting , Song Lin , Tang Shi , Wang Yongxiang , Du Yifeng , Qiu Chengxuan 
Published: June 2023

AbstractBackgroundOlfactory impairment has been associated with neurodegenerative disorders such as Parkinson’s disease and Alzheimer’s disease (AD). We seek to investigate the relationships of impaired olfaction with mild cognitive impairment (MCI), plasma biomarkers of AD and neurodegeneration, and neuroimaging markers of microvascular lesions and neurodegeneration among Chinese older adults.MethodThis population‐based cross‐sectional study included 4214 participants (age ≥65 years; 56.0% women) from MIND‐China who were free of dementia and examined in March‐September 2018. Olfactory function was assessed using the 16‐item Sniffin’ Sticks identification test (SSIT). In the subsamples, we measured plasma concentrations of amyloid‐β40 (Aβ40), Aβ42, total‐tau, and neurofilament light chain (NfL) using the Simoa technology (n = 1054); and quantified hippocampal volume, entorhinal cortex volume, Alzheimer’s disease‐signature cortical thickness, and white matter hyperintensities (WMHs) volume on MRI scans (n = 917). The neuropsychological test battery was used to assess memory, verbal fluence, attention, and executive function. MCI and subtypes of MCI were defined according to the Petersen’s criteria that integrated clinical judgement by neurologists and neuropsychological tests. Data were analyzed with logistic and general linear regression models.ResultOf the 4214 participants, MCI was diagnosed in 1102 persons (26.2%), including 931 with amnestic MCI (aMCI) and 171 with non‐amnestic MCI (naMCI). Olfactory impairment (SSIT score 0‐10) was associated with an increased likelihood of MCI, aMCI, and naMCI in a dose‐response manner (p for trend<.001). In the plasma biomarker or MRI subsample, anosmia (SSIT score 0‐7) was significantly associated with plasma total‐tau (demographic‐adjusted β = 0.26; 95% CI = 0.12‐0.41), NfL (0.12; 0.04‐0.19) and MRI biomarkers of hippocampal volume (‐0.13; ‐0.22‐ ‐0.04), entorhinal cortex volume (‐0.08; ‐0.13‐ ‐0.02), and WMHs volume (0.19; 0.08‐0.30), and marginally associated with Alzheimer‐signature cortical thickness (‐0.02; ‐0.05‐0.00, p = 0.08), but not with plasma Aβ concentrations (P>0.05).ConclusionAnosmia may be a clinical marker for preclinical dementia and neurodegeneration among older adults. Microvascular and neurodegenerative lesions in the brain may be the common neuropathological pathways linking anosmia with cognitive impairment.
Teleconsultation by a nurse as preliminary approach to home visits in older patients affected with dementia
Authors: Gareri Pietro , Pagano Lucia , Nisticò Michelangelo , Armeli Carmela 
Published: June 2023

AbstractIntroductionTelehealth uses video calling and other technologies to support patients and their caregivers at home. Teleconsultation by a nurse provides advantages for collecting information about older people’s health. The present study was aimed to assess the benefits of teleconsultation by a nurse in older home patients affected with dementia.Patients and MethodsIn the time range between January 1st and December 31th 2021, 851 requests for geriatric home multidimensional assessments were addressed to the Center for Cognitive Disorders and Dementia, Catanzaro Lido, ASP Catanzaro, Italy. Teleconsultation by a nurse was used as preliminary approach to patients affected with dementia when the request for having a home consultation by a geriatrician was not performed yet, due to the great overload even in time of pandemics, or for the difficulties of reaching people living in rural and mountain areas. The call was made to patient’s caregiver who gave an informal and verbal consent to the interview. Tests administered included functional abilities in the activities of daily living (ADL and IADL); main disease and comorbidities, drugs taken by every patient were collected too. A simple questionnaire investigated the extent patient’s caregiver appreciated this way of preliminary contact, according to the following scale: 0 = no appreciation; 1 = poor; 2 = sufficient; 3 = moderate; 4 = good; 5 = very good appreciation.Results130 older patients, 69 women and 61 men, mean age 79.2 ± 4.5 years old were tele‐consulted; mean ADL was 3.45 ± 0.91; IADL 0.96 ± 0.4. People were affected with Alzheimer’s dementia in 39% out of the cases, vascular dementia 34%, mixed dementia 21%, other types of dementia 6%. Teleconsultation was overall appreciated, mean score 4.07 ± 0.23.Discussion and conclusionsTeleconsultation performed by a nurse is a fast and valuable opportunity for helping doctors in a preliminary assessment of older patients suffering from dementia. The opportunity of being monitored remotely may be particularly helpful for older adults with limited mobility and those living in rural areas. This modality of approach represents a new frontier in care and assistance to old frail people with dementia.
Cross‐sectional associations between use of time and cognition in healthy older adults
Authors: Mellow Maddison L , Smith Ashleigh E , Dumuid Dorothea , Stanford Ty , Keage Hannah , Wade Alexandra , Olds Timothy , Hunter Montana , Karayanidis Frini , Dorrian Jillian , Goldsworthy Mitchell R 
Published: June 2023

AbstractBackgroundPhysical activity, sedentary behaviour and sleep are independently associated with cognition in older adults. These time‐use behaviours are not independent, rather, co‐dependent parts of the 24‐hour day. As such, spending more time in one leaves less time for the others. The balance of the three time‐use behaviours in the 24‐hour day (or time‐use composition) should be considered to inform 24‐hour movement guidelines for cognition and dementia risk reduction in older populations. Using a compositional data analysis approach, we investigated the associations between time use and cognition in a sample of healthy older adults.Method347 participants (age 60‐70 years; 68% female) took part in this study. 7 days of 24‐hour time use (time spent in sleep, sedentary behaviour, light and moderate‐vigorous physical activity) were captured using accelerometry. Cognition was measured using Addenbrooke’s Cognitive Examination III (global cognition) and computerized CANTAB tests measuring memory, executive function, fluid reasoning and processing speed.Cognitive outcomes were regressed on isometric log ratios (ilrs) of the time‐use compositions, while adjusting for age and sex demographics, to explore potential associations between cognition and time‐use behaviours. For each outcome, four sets of ilr‐coordinate systems were constructed, each with a different time‐use behaviour as the numerator of a log ratio to the mean of remaining time‐use behaviours. The regression coefficient of the first ilr‐coordinate in each of the four ilr systems therefore represented the association between increasing time in the first behaviour relative to all remaining behaviours.ResultAge was negatively associated with performance on memory, executive function, fluid reasoning and processing speed tests. More time in SB at the equal expense of all other behaviours was associated with better memory (β = 0.65, p<.01), whilst spending more time in sleep was associated with poorer memory (β = ‐0.63, p = .02). Spending more time in moderate‐vigorous physical activity was associated with better processing speed (β = 0.25, p = .01).ConclusionHow older adults use their time is associated with cognition. Findings suggest that moving towards a holistic understanding of time use is important to inform future dementia prevention strategies.