bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impairment in recall after contextual fear conditioning and activity dependent protein translation in ovariectomized Alzheimer’s disease mouse model
Authors: Kommaddi Reddy Peera , Diwakar Latha , Gowaikar Ruturaj , Karunakaran Smitha , Ravindranath Vijayalakshmi 
Published: December 2020

AbstractBackgroundFemale sex is one of the major risk factor for developing late‐onset Alzheimer’s disease (AD). Human studies have demonstrated that the prevalence of AD is higher in women compared with men. Although neuroprotective effect of estrogen is well recognized, the underlying pathogenic mechanisms explaining the higher burden of AD in women are unclear, taking into account the longer lifespan in women. Thus, we attempted to investigate the gender‐specific differences during the progression of the disease in an AD mouse model. We examined behavioural and activity dependent protein translation in female AD mice after ovariectomy and compared it with sham‐operated female mice of similar age in order to study the effect of female sex hormones in female AD mouse.MethodsWild type and APP/PS1 female mice underwent an ovariectomy and sham surgery. The cognitive task we used in AD mouse model is the recall following contextual fear‐conditioning (cFC). After ovariectomy and behavioural assessment we prepared synaptoneurosomes from hippocampus and performed 35S methionine incorporation assay without or with KCl stimulation.ResultsFemale APP/PS1 mice did not show deficient recall upon cFC at 2, 4 and 6 months of age. However, female APP/PS1 mice showed deficient recall following cFC only after 8 months of age and this was sustained as mice aged further. Activity dependent synaptic protein translation was affected only at 8 months of age and no deficits were observed in 4 months old APP/PS1 female mice. In contrast, ovariectomized APP/PS1 mice displayed deficient recall upon cFC at 4 months of age and this recall deficits were sustained until 8 months of age as examined. Further, activity dependent protein translation was also impaired in 4 months old ovariectomized APP/PS1 mice compared with sham female APP/PS1 mice and this impairment was persistent until 8 months of age in these ovariectomized APP/PS1 mice.ConclusionsOur results indicate that deficits in recall following cFC and loss of activity dependent protein translation occurred in female APP/PS1 mice only as they aged or if they were ovariectomized at younger age. Thus, estrogen plays a protective role even in the presence of relatively higher levels of β‐amyloid.
Synaptosomal actin interactome analysis in an Alzheimer’s disease mouse model
Authors: Kommaddi Reddy Peera , Verma Aditi , Chandran Mahesh , Jaleel Abdul , Ravindranath Vijayalakshmi 
Published: December 2020

AbstractBackgroundFilamentous actin (F‐actin) is the major cytoskeleton protein present in dendritic spines and it is an essential element for defining dendritic spine structure. We have shown that synaptosomal F‐actin levels were significantly decreased in APP/PS1 mice as early as 1 month of age. Further, reduced form of F‐actin is diminished and glutathionylated F‐actin is significantly increased in synaptosomes of 1 month old APP/PS1 mice. Synaptic neurotransmission and synaptic plasticity are dependent on the dynamic regulation of the actin through actin‐interacting and actin‐modulating proteins. Recent studies highlight that F‐actin nanoarchitecture is susceptible to several key regulators such as reactive oxygen species, cofilin and drebrin that are present in the dendritic spines. Yet, how synaptosomal F‐actin organization is regulated remains poorly understood. To address this, we characterized actin interactome in synaptosomes prepared from wild type and APPSwe/PS1ΔE9 (APP/PS1) mice.MethodsWe utilized age matched wild type (WT) and APP/PS1 mice for our experiments. Synaptosomes and highly enriched F‐actin and G‐actin fractions from synaptosomes were isolated from WT and APP/PS1 mice. We performed immunoprecipitation using all these fractions with an anti‐actin polyclonal antibody and eluted in Laemmli sample buffer. The IP elutes were resolved using SDS‐PAGE gels, all proteins purified from gels, and analysed by LC‐MS/MS spectrometry.ResultsWe detected approximately 620 synaptic proteins in synaptosomes from both wild type and APP/PS1 mice at the age of six months. About 110 proteins were upregulated and 198 proteins down regulated in synaptosomes of APP/PS1 mice. We identified 69 proteins that were associated with F‐actin in WT mice while only 26 proteins interacted with F‐actin in APP/PS1 mice in synaptosomal F‐actin fraction. Further, we detected G‐actin‐interaction only with 10 proteins in WT and 15 proteins in APP/PS1 mice in synaptosomal G‐actin fraction. However, we were able to identify 401 proteins in WT and 444 proteins with F/G‐actin‐association in synaptosomes of APP/PS1 mice compared with WT mice.ConclusionsOur result defines a provisional synaptosomal actin interactome in mouse brain cortex of WT and APP/PS1 mice and identifies several critical regulator proteins that may be involved in the progression of AD pathogenesis.
Genetic (APOE, BDNF) influences on functional language network connectivity in healthy older adults
Authors: Pietzuch Manuela , Bindoff Aidan , Sforazzini Francesco , Vickers James C 
Published: December 2020

AbstractBackgroundLanguage is a crucial function that is preserved in healthy ageing. Broca’s and Wernicke’s area are known to be parts of the language network associated with speech production and comprehension, respectively. Pathological alterations that are identified in Alzheimer’s disease (AD) can be assessed using resting‐state fMRI. In particular, levels of oxygen in blood flow is measured as a proxy marker of brain activity. Functional connectivity with the Broca’s and Wernicke’s areas may be potential biomarkers of early brain changes associated with AD‐related genes, such as APOE and BDNF. Therefore, the objective of this study was to investigate age‐related differences in functional connectivity in the language networks (Broca’s and Wernicke’s area) associated with BDNF Val66Met and APOE polymorphisms in cognitively healthy older persons (n = 76).MethodData was pre‐processed using FSL. First level MELODIC (motion correction, brain extraction, and high‐pass filtering (100)) was applied for each dataset using Independent Components Analysis (ICA). Seed‐based correlation analysis was performed to investigate functional connectivity between the regions of interest and the rest of the brain.ResultThere were no significant differences in functional connectivity between the seed regions and other regions for APOE or BDNF (adjusted for age), but in a model with APOE + BDNF, age was positively correlated with functional connectivity between left Broca’s area and left frontal gyrus p = .003, as well between Wernicke’s area and right putamen and right supramarginal gyrus p = 0.02. Significant interactions indicating stronger functional connectivity in Met/ε3 than Met/ε4, p = 0.007, in Met/ε3 than in Val/ε3, p < .0001, and in Val/ε3 than Val/ε4 carriers, p < .0001, between the language networks and various brain regions, such as pre‐ & postcentral gyrus, parahippocampal gyrus, and precuneus.ConclusionThese finding suggest that the degree to which the language network is interconnected may be associated with genetic interactions in the absence of clinical signs of disease. Disconnections within the functional language network may contribute to the loss of speech and comprehension in Alzheimer’s disease.
Evolution of clinical‐pathological correlation of early‐onset Alzheimer's disease: 1994–2009 vs 2010–2017
Authors: Sarto Jordi , Mayà Gerard , Molina Laura , Balasa Mircea , Gelpi Ellen , Aldecoa Ivan , Borrego Sergi , Contador José , Ximelis Teresa , Guasp Mar , Archilla Iban , Sanchez‐Valle Raquel , Lladó Albert 
Published: December 2020

AbstractBackgroundEarly onset Alzheimer disease (EOAD) (age at onset < 65 years) represents an important cause of early‐onset dementia. EOAD has some clinical, pathologic and neuroimaging differences compared to the late onset form of the disease that makes this subset of patients more difficult to diagnose and manage. Our objectives are to describe the clinical‐pathological correlation of a cohort of pathology‐confirmed EOAD, and to compare the findings with our antecedent EOAD cohort.MethodClinical and neuropathological data of subjects from the Neurological Tissue Bank‐Hospital Clínic/IDIBAPS (Barcelona, Spain, 2010‐2017) with postmortem confirmation of AD and age of onset before 60 years were collected retrospectively and analyzed. Patients with PSEN1, PSEN2 and APP mutations or insufficient clinical data were excluded. The findings were compared with those of our previously reported EOAD cohort (n = 40, 1994‐2009).ResultA total of 36 new patients (44% women) were included. The mean age at onset was 55 years (SD ± 3.5), the mean of diagnostic delay was 2.8 years (SD ± 1.8) and the mean duration of disease was 10.4 years (SD ± 4.2). An onset with typical/episodic memory impairment was observed in 83% of the subjects. There was a lack of clinico‐pathological correlation on initial and final clinical diagnosis in 11% and 8%, respectively. Initial misdiagnoses were frontotemporal dementia (n = 1) and non‐neurodegenerative causes (n = 3), while final misdiagnoses were dementia with Lewy bodies (n = 1), frontotemporal dementia (n = 1) and progressive supranuclear palsy (n = 1). Three patients underwent AD biomarker analysis (3 CSF, 1 amyloid PET), and were consistent with AD profile. The former cohort had less typical/amnestic presentations (χ2 = 4.1, p = 0.04), a trend towards higher percentage of misdiagnoses (23% on initial diagnosis and 20% on final diagnosis, p non‐significant) and a similar diagnostic delay (3.1 years). Neuropathology showed, in addition to AD‐pathology, cerebral amyloid angiopathy in 94% and Lewy‐body copathology in half of patients; these data was similar to the previous cohort.ConclusionThere is a trend towards diagnostic improvement in EOAD, that might be explained by improved diagnostic criteria, increasing experience on EOAD, a higher number of typical presentations and the beginning of use of biomarkers, although diagnostic delay and neuropathological findings remain similar.
Associations of olfaction with mild cognitive impairment and cognitive function in older adults: A population‐based study
Authors: Dong Yi , Wang Yongxiang , Liu Keke , Hou Tingting , Ren Yifei , Cong Lin , Tang Shi , Zhang Qinghua , Qiu Chengxuan , Du Yifeng 
Published: December 2020

AbstractBackgroundOlfactory function might be impaired in the early stage of the dementing process, and thus, olfactory test may be useful for identifying elderly persons at an increased risk. However, previous studies that investigate the relationship between olfactory function and cognitive phenotypes have been scarcely conducted among older people living in the rural communities and the associations of olfaction with specific cognitive remains unclear. We sought to examine the relationship of olfactory function with global cognitive ability and various domains of cognitive function among rural‐dwelling Chinese older adults.MethodThis population‐based cross‐sectional study included 3003 dementia‐free participants (age ≥65 years; 57.3% women; 37.7% illiterate) in the baseline examination (March‐September 2018) of the Multidomain Interventions to Delay Dementia and Disability in Rural China (MIND‐CHINA) study. The 16‐item Sniffin’ Sticks identification test (SSIT) was performed to assess olfactory function. Global cognitive function was evaluated with the Chinese version of the Mini‐Mental State Examination (MMSE) and a neuropsychological battery was used to assess memory, language, attention, and executive function. We followed the Petersen’s criteria to define mild cognitive impairment (MCI). Data were analysed with multiple logistic regression and the general linear regression models.ResultOf the 3003 participants, MCI was defined in 335 persons (11.2%). Multiple logistic regression analysis suggested that SSIT score (range 0‐16) was associated with an odds ratio of 0.90 (95% CI 0.87‐0.93) for MCI. Multiple general linear regression analysis showed that SSIT score was significantly associated with the scores of MMSE test (β coefficient=0.07, 95% CI 0.03‐0.11), z‐score of memory (β coefficient=0.28, 95% CI 0.12‐0.45), language (β coefficient=0.35, 95% CI 0.17‐0.52), and attention (β coefficient=0.59, 95% CI 0.38‐0.78), but not with the z‐score of executive function (β coefficient=0.05, 95% CI ‐0.11‐0.22).ConclusionA greater olfactory identification ability is associated with a lower likelihood of MCI and better performances in global cognitive function, attention, memory, and language function, but not in executive function, among Chinese older adults who are living in the rural communities with limited education.
The effect of multimodal comprehensive care methodology training on oral health care professionals’ empathy for patients with dementia
Authors: Kobayashi Masaki , Ito Mio , Iwasa Yasuyuki , Motohashi Yoshiko , Edahiro Ayako , Shirobe Maki , Hirano Hirohiko , Honda Miwako 
Published: December 2020

AbstractBackgroundThe prevalence of oral diseases in people with dementia has increased, and such patients have worse oral health than do people without dementia. However, in the provision of oral care, they often exhibit care‐resistant behaviours. Empathy is an important element of health care professionals who provide dental care for people with dementia. A study was conducted to assess whether a multimodal comprehensive care methodology training programme is associated with an improvement in empathy for people with dementia among oral health care professionals.MethodsThis research was a pre‐post prospective study. A total of 45 dentists and dental hygienists participated in a 7‐hour multimodal comprehensive care methodology training programme. The empathy of the participants for their patients was evaluated by the Jefferson Scale of Physician Empathy‐Health Professionals Version (JSPE‐HP) before and one month after the training (primary outcome). Each participant listed 3 patients from his or her clinical practice about whom he or she felt that providing dental care to them was difficult due to dementia. The oral health of the 3 patients refusing care provided by each participant was evaluated by the Oral Health Assessment Tool (OHAT) before and one month after the training (secondary outcome).ResultsThe post‐training response rates were 87% (21 dentists, 18 dental hygienists). Over the course of the programme, the multimodal comprehensive care methodology training significantly increased the empathy score from pre‐training to post‐training (from 113.97 to 122.95, P<0.05, effect size=0.9). Regardless of gender, profession and years of clinical experience, all post‐training subgroup scores were higher than the pre‐training subgroup scores. The oral health of patients, as assessed by the OHAT, was significantly improved compared with their oral health before the training (from 6.54 to 5.71, P<0.05).ConclusionsMultimodal comprehensive care methodology training was associated with an improvement in oral health professionals’ empathy for patients with dementia and an improvement in the oral health of their patients.
The association between ambient air pollution and cognitive impairment in community‐dwelling older adults: Six‐year cohort study TIGER
Authors: Tsao Shu‐Ping , Chen Jen‐Hau , Yu Hwa‐Lung , Chiou Jeng‐Min , Chen Ta‐Fu , Lai Liang‐Chuan , Chen Yen‐Ching 
Published: December 2020

AbstractBackgroundAmbient air pollution exposure has been related to cognitive impairment. Several studies have started to explore the association of particulate matter and nitrogen oxides with cognitive impairment, studies evaluated the effect of long‐term exposure to ozone(O3), carbon monoxide (CO) and sulfur dioxide (SO2) are sparse.MethodThis study is part of the ongoing Taiwan Initiative for Geriatric Epidemiological Research (TIGER). A total of 605 participants (Age 65+) were recruited from a teaching hospital in northern Taiwan in 2011 and followed up biennially. After exclusion and loss to follow‐up over 6 years, a total of 292 participants were included for analyses. Global cognition was assessed by Montreal Cognitive Assessment‐Taiwanese version; domain‐specific cognition (logical memory, attention, verbal fluency, and executive function) were assessed by a battery of neuropsychological tests. The data of three air pollutants (O3, CO and SO2) were obtained from 27 monitor stations of Taiwan Environmental Protection Administration (EPA) between 1993 and 2010. Air pollutants were tertiled into low, moderate, and high levels. Spatial‐Time Analysis Rendering with Bayesian Maximum Entropy was utilized to establish the spatial‐temporal model. Logistic regression model was utilized to assess the association of exposure to air pollutants and global or domain‐specific cognition over 6 years adjusting for important covariates.ResultThe 17‐year average level was 39.40ppb for 8‐hour O3, 1.47ppm for 8‐hour CO, and 4.70ppb for daily SO2, which were below the EPA standards. Exposure to high‐level O3 (>40.83 ppb) was associated with poor executive function [adjusted odds ratio (aOR)=2.14, 95% confidence interval (CI)=1.05‐4.35] compared with low‐level O3. No significant association was observed between O3 or CO and global cognition or other cognitive domains. SO2 were not associated with cognitive function over 6 years.ConclusionLong‐term (17 years) exposure to O3, CO and SO2 lower than the EPA standards showed significant association with cognitive domains in a 6‐year cohort of community‐dwelling older adults. Future revisions of air standards may need to consider epidemiologic studies exploring the relation between exposure to these air pollutants and cognitive impairment.
Relationship between sleep structure, memory and size of the hippocampus
Authors: Silhan David , Holla Marie , Dudysova Daniela , Evansova Katarina , Koprivova Jana , Miletinova Eva , Buskova Jitka , Bartos Ales 
Published: December 2020

AbstractBackgroundSleep is important for consolidating declarative memory. Hippocampus is considered an important structure in this process. Our goal was to assess relationship between sleep structure, memory and size of the hippocampus.Method18 patients (4 men, age range 60 ‐ 80 years) underwent polysomnography, neuropsychological examination and brain MRI (3 T). Sleep efficiency, percentages of REM and non‐REM sleep stages were calculated. Delayed recall score in Rey Auditory Verbal Learning Test (RAVLT) was used to assess memory. Size of the hippocampus was evaluated using MRI visual scale named Hip‐Hop (Hippocampal‐Horn percentage). Statistical analyzes were performed using Spearman´s Rank correlation coefficient.ResultWe found strongly positive correlation between sleep efficiency and RAVLT (r = 0,73, p < 0,001). There was also positive correlation between RAVLT and percentage of REM sleep (r = 0,49, p < 0,05), but correlation with percentages of non‐REM sleep stages was not significant. We found positive correlation between sleep efficiency and size of the hippocampus only in the left hemisphere (r = 0,55, p < 0,02). RAVLT was also positively correlated with size of the hippocampus only on the left (r = 0,58, p < 0,01). We did not find significant correlation between size of the hippocampus and percentages of REM neither non‐REM sleep stages.ConclusionSleep efficiency and percentage of REM sleep seem to be important for memory. Sleep efficiency and memory reflect size of left hippocampus according to our results. Supported by grants PROGRES Q35, LO1611, MH CZ DRO 00023752, 260388/SVV/2018, NV18‐07‐00272 and NV19‐04‐00090.
Impact of baseline impaired sleep, depressive symptoms and pain on physical activity in the FINGER multidomain lifestyle trial
Authors: Pietilä Eija Kristiina , Hall Anette , Ngandu Tiia , Kivipelto Miia , Antikainen Riitta , Havulinna Satu , Kulmala Jenni , Laatikainen Tiina , Levälahti Esko , Paajanen Teemu , Soininen Hilkka , Strandberg Timo , Solomon Alina 
Published: December 2020

AbstractBackgroundPhysical inactivity is a major concern for public health. Physical activity (PA) is an important protective factor against Alzheimer’s disease and dementia. Therefore, possible barriers to PA, such as impaired sleep, depressive symptoms and pain may need to be considered in prevention programs. The study aim was to investigate whether impaired sleep, depressive symptoms and pain at baseline would impact PA after a 2‐year multidomain lifestyle intervention in individuals at‐risk of dementia.MethodThe data was from the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) 2‐year randomized controlled trial in 1260 older individuals at‐risk of dementia. PA (active/inactive), sleep duration (hours/night), and sleep quality (composite index based on 6 questions) were self‐reported. Depressive symptoms were assessed using the Zung scale, and bodily pain using RAND‐36. Associations of impaired sleep, depressive symptoms, or pain at baseline with PA at baseline and at the 2‐year visit were assessed using binary logistic regression models, adjusted for randomization group, age, sex, education, marital status, and body mass index.ResultAt baseline, participants sleeping on average ≤6 hours per night (n=268, 21%) reported poorer sleep quality, more depressive symptoms, more pain, and were also less physically active than participants with longer sleep duration. Participants with more depressive symptoms were less likely to be physically active at baseline (OR=0.97, 95%CI 0.95‐0.99). The odds of being physically active at 2‐year visit were increased in the intervention group, compared to control group (OR=1.9, 95%CI 1.4‐2.7). Being physically active at baseline also increased the odds of being physically active at 2‐year visit, (OR=8.4, 95%CI 5.8‐11.2). Compared to normal sleep duration (between >6 and <9 hours per night) at baseline, short sleep duration (≤6 hours per night) reduced the odds of being physically active at the 2‐year visit (OR=0.5, 95%CI 0.4‐0.8).ConclusionThese preliminary findings from FINGER trial suggest that especially impaired sleep may need to be considered in prevention programs. Due to the associations between sleep quality, sleep duration, depressive symptoms and pain, further investigation is highly needed.