bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nutritional status is associated with cognitive function among the elderly at hospital admission in Southwest China
Authors: Wuhan Yu , Lü Yang 
Published: December 2020

AbstractBackgroundThe evidence regarding the effect of nutritional status in aging and cognitive impairment has not been proved yet although the effects of malnutrition on progression in AD and dementia is becoming established.Method2365 participants aged 60 years or above were recruited from January 2013 to September 2019. They were divided into three age groups: young older (60–69 years), middle older (70–79 years), and old older (≥80 years). Nutrition status was analyzed via the Mini Nutritional Assessment Short Form (MNA‐SF). Global cognitive function was assessed with the Mini Mental State Examination (MMSE). Nutrition‐associated factors were analyzed, including Barthel Index (BI), Body mass index (BMI), social factors (education status, marital status).ResultThe mean age was 76.24±7.91 years and 45.9% were males. 33.45% were identified as malnutrition risk and 5.54% malnourished. In the old older group (≥80 years), 48.63% were malnutrition or at risk for malnutrition and 53.65% have cognitive impairment. In middle older group (60–69 years), 31.79% were at risk of malnutrition and 4.62% were malnourished, while 32.24% of them had impaired cognitive function. However, prevalence of malnutrition and at risk for malnutrition was 3.49% and 25.25% in young older group (60–69 years), respectively; moreover, only 18.77% of participants have cognitive impairment. MNA‐SF score was positively correlated with MMSE score (R= 0.392, P < 0.0001) and BI (R=0.398, P< 0.0001) in old older group. Participants who were at risk of malnutrition or malnourished had significantly poorer performance in the cognitive test (P < 0.001) in comparison to those who were well nourished. In particular, the association of the orientation (R= 0.381, P < 0.0001) and the language (R= 0.302, P < 0.0001) with nutritional status were most pronounced in old older group.ConclusionThe prevalence of malnutrition and cognitive impairment increases with age, especially in patients over 80 years old. Malnutrition is associated with cognitive impairment. There was also a moderate correlation between nutritional status and cognition domain including orientation and language. The implication of this is the possibility that malnutrition is an important driving factor of cognitive decline. Thus, patients with cognition impairment should pay more attention to nutritional status.
Determinants of subjective cognitive decline in dementia‐free older adults: A population‐based study
Authors: Zullo Leonardo , Clark Christopher , Popp Julius ,   CoLaus/PsyCoLaus Investigators
Published: December 2020

AbstractBackgroundSubjective cognitive decline (SCD) is common in older adults and may represent the earliest clinical manifestation of cognitive decline evolving to dementia. Still little is known about factors related to SCD.MethodWe conducted a cross‐sectional analysis on 1567 community‐dwelling, dementia‐free participants aged 64 years and older from CoLaus/PsyCoLaus, a population‐based study from an urban area in Switzerland. SCD was assessed using a validated 10‐item questionnaire. Quality of life, socioeconomic status, depression, personality, professional activity, and perceived social support were measured, and a comprehensive neuropsychological test battery was administered. Multivariate regression models were used to explore the data. Furthermore, we investigated whether SCD predicts cognitive decline in a subgroup with available longitudinal data.ResultMean age was 70.9 ± 4.7 and SCD was present in 18.5%. Younger age, higher socioeconomic status, neuroticism, depression, and their interaction as well as poorer performance in memory and verbal fluency tasks were associated with SCD. Exploratory analysis revealed associations between SCD and interaction of neuroticism with quality of life. Two items from the SCD questionnaire predicted cognitive decline five years later in a subgroup with mild cognitive impairment at baseline.ConclusionBesides cognitive performance, specific psychosocial factors are associated with SCD in dementia‐free older people. These findings suggest possible intervention targets to reduce cognitive complaints and prevent cognitive decline.
Quality of life and quality of care: A pilot mobile app to promote the psychosocial well‐being of informal caregivers of older adults with Alzheimer's disease and related dementias
Authors: Lee Kathy , Jaworski Justyn ,   UTA Bioengineering Department Senior Design Research Team (Tanzim Choudhury, Debbie Vang & Kristen Duke)
Published: December 2020

AbstractBackgroundAn increasing number of people with Alzheimer’s disease and related dementias (ADRD) live in their own homes with intensive assistance from informal caregivers (e.g., family or friends). Progressive symptoms of ADRD can affect the quality of life of the caregivers as well as people with ADRD. Mobile technology shows great potential to fill this gap with its accessibility, affordability, and repository for information. The purpose of this study was to develop a pilot mobile app (QLQC Tracker) that helps caregivers track and review their psychosocial well‐being and to test its reliability and usability.MethodOur methodology in developing QLQC Tracker leverages existing Google cloud data services for logging of encrypted data. The Android Studio development environment was utilized for designing, building, and testing the app while Matlab was utilized for decryption, parsing of data, and development of the multilayer perceptron to process the data received from the app. The app entails four categories: mental health, social activities, frequently asked questions, and helpline information. The app informs the caregivers with trends in their overall psychosocial well‐being on a weekly basis. College students were invited to test the reliability and usability of the app (N=45). Questions were asked using the USE (Usefulness, Satisfaction, and Ease of use) questionnaire (Gao, Kortum, & Oswald, 2018).ResultFirst, each participant was asked to enter data and click each tab up to 10 times. In total, the app was run 310 times and the reported crash rate was 0.84%. The overall satisfaction score of the app was 6.07 (SD=1.23; range 1‐9). Lastly, the mean value of the usability score of the app was 6.22 (SD=1.15; range 1‐9). The students aged between 20‐49 (n=27) scored 6.04 (SD=1.34) and the students aged 50+ (n=18) scored 6.50 (SD=0.71) for the usability of the app.ConclusionQLQC Tracker helps informal caregivers understand their psychosocial well‐being by tracking their perceived burdens and levels of social activities. Effective care planning for people with ADRD should include informal caregivers, and the cumulative well‐being data of the caregivers will support the care planning process.
Cerebrovascular reserve differentiates cognitively normal older adults from individuals with mild cognitive impairment
Authors: Rane Swati , Grabowski Thomas J 
Published: December 2020

AbstractBackgroundAbnormal cerebral blood flow (CBF) is observed in early Alzheimer’s disease. Cerebrovascular reserve (CVR) represents the ability of the vasculature to maintain normal CBF. While CBF abnormalities can indicate a primary vascular dysfunction, it could also arise secondary to neurodegeneration and reduced metabolic demands. CVR, on the other hand, is a specific marker of vascular insufficiency. Our goal was to evaluate the associations between CVR, CBF, and cognition in older adults with and without MCI.Methods70 older adults (>65 years 77.3 ± 8.32 years old, 42F, 46 controls i.e., NC and 24 MCI) were scanned in compliance with Institutional Review Board guidelines. Besides a T1 scan, we performed pCASL to quantify baseline CBF and a breath‐hold BOLD fMRI experiment to quantify CVR. We use a mixed‐effects model in FSL to test CVR and CBF differences between groups as well as association with cognitive tests, i.e., Montreal Cognitive Assessment (MoCA), Immediate and Delayed recall (CRAFTi/d) and Trails‐B, using Gaussian random field theory for a cluster‐wise threshold of p = 0.05. All comparisons were adjusted for age and gender.ResultsOnly CVR was significantly (p<0.05) different between NC and MCI (Figure 1). While there was no group difference in CBF, the group difference between CVR was no longer significant when adjusted for baseline CBF. Investigating further, high CBF was significantly associated with lower CVR in the MCI group only. A high CBF was very weakly related to high CVR in NC (Figure 2). A high CVR was associated with a high MoCA score (Figure 3) and CRAFTi/d (Figure 4).ConclusionWe demonstrated the utility of a simple breath‐hold based CVR measurement in understanding the association between vascular mechanisms and cognition. It is likely that CBF is not different between groups because MCI participants utilize their vascular reserve to maintain baseline CBF. Consequently, an additional vascular challenge results in a lower CVR measurement. Furthermore, a higher CVR in MCI subjects such as that seen in association with cognitive tests could be a result steal phenomenon to redirect perfusion from degenerating tissue to viable tissue. However, these mechanisms need to be further investigated.
The BPSDPLUS Program: Efficacy of a novel person‐centred care approach to reduce neuropsychiatric symptoms in residents with dementia
Authors: Mortby Moyra E. , Sargent‐Cox Kerry , Beattie Elizabeth , Lautenschlager Nicola T. , Doyle Colleen , Anstey Kaarin J. 
Published: December 2020

AbstractBackgroundThe availability of effective non‐pharmacological interventions to ameliorate discomfort of residents with neuropsychiatric symptoms (NPS) living in aged care remains a pressing sector need. The BPSDPLUS Program is a novel person‐centred care training and intervention program developed by the team to provide aged care staff with a structured approach to identify and manage NPS using non‐pharmacological interventions. This pilot and feasibility study evaluates the efficacy of the BPSDPLUS Program to reduce NPS amongst residents over 12 months.Method77 residents (67% female; age range 67‐101) and 69 staff (79% female; age range 19‐63 years) from 3 sites of a non‐for‐profit care provider (includes dementia‐specific units) participated in the program. The Program’s unique “Buddy System” pairs each resident with a staff member who is responsible for completing all aspects of the program with/for their resident. Program components include a two day face‐to‐face staff training, monthly resident assessments and 15‐minute intervention sessions 3‐times a week using one of five non‐pharmacological interventions (meaningful and pleasant activities; reminiscence; music; gentle exercise; massage and touch). Primary outcome was reduction in NPS over time as measured by the Neuropsychiatric Inventory – Nursing Home (NPI‐NH) and assessed using mixed model estimates.ResultImplementation of the BPSDPLUS Program over 12 months resulted in a significant reduction of NPI‐NH total scores over 12 months (β=‐1.07, 95% CI=‐1.62, ‐0.52), with a significant quadratic fixed effect (β=0.05, 95% CI=0.01, 0.09) indicating that the decline in scores slowed over the course of the trial. Similarly, significant fixed linear and quadratic effects were found in the unadjusted models for depression (linear β=‐0.77, 95% CI=‐1.35,‐1.20; quadratic β=0.05, 95% CI=0.01, 0.01), and apathy (linear β=‐0.84, 95% CI=‐1.33,‐0.35; quadratic β=0.05, 95% CI=0.01, 0.09). Further, irritability symptoms showed a significant decline across the trial (β=‐0.74, 95% CI=‐1.32, ‐0.16).ConclusionThis pilot and feasibility study demonstrates the efficacy of the novel BPSDPLUS Program to significantly reduce NPS in residents living in aged care. Evidence‐based training and interventions programs such as the BPSDPLUS Program provide staff with improved skills and knowledge to improve the quality of person‐cantered care provided and manage the clinical consequences of NPS in dementia care.
Potential therapeutic agents from Philippine medicinal plants against Alzheimer's disease
Authors: Tan Mario A , An Seong Soo 
Published: December 2020

AbstractBackgroundNatural products derived from plants have been in the lead of extensive studies in the search of potential anti‐Alzheimer’s disease agents. These plant species comprised a high chemical diversity of compounds. Natural products and plant extracts as therapeutic agents for AD have demonstrated that they favor neuroprotection against amyloid‐beta cytotoxicity and aggregation. Hence, the identification of plants and their bioactive constituents as a possible source of pharmacologically‐relevant compounds against AD is warranted.MethodA total of 25 Philippine plant extracts were used in the experiment. The cytotoxicity of the extracts was initially determined using the ATP cytotoxicity assay utilizing the SH‐SY5Y and HEK‐293 cell lines. The non‐toxic extracts were subjected to our in‐house multimer detection system (MDS) assay. The procedure utilized three mutant cells, namely, Amyloid Precursor Protein (APP) 669, APP 604, and Presenilin 1 (PSE1 232). ELISA was used to establish whether the extracts and compounds have down‐regulated the aggregation of amyloid‐beta in the mutant cells against a positive control (phenol red) and a negative control (no treatment of cells), and in comparison with the normal HEK‐293 cells.ResultSeveral plant extracts prevented the oligomer aggregation of amyloid‐beta in the mutant cells. These include Pandanus amaryllifolius, Pandanus simplex, Pandanus tectorius, Guettarda speciosa, Lasianthus trichophlebus, and Psydrax puberula. The prevention of oligomer aggregation is statistically different from the negative control. Also, these extracts were non‐toxic to the SH‐SY5Y and HEK‐293 cells. These results suggest that these plants may be developed as potential nutraceuticals to minimize the effects of AD. Currently, we are in the process of identification the bioactive compounds from these plant extracts using chromatographic and spectroscopic techniques.ConclusionThe results in this study can pave the way for the development of new drugs with therapeutic value against AD. These drugs can also be candidates for pre‐clinical and clinical trials and licensing. The compounds can be used as chemical markers for the standardization of health products formulated from these plants. The scientific community including scientists, researchers and students can benefit from the new knowledge and discoveries and the validated protocols for the detection of extracts and compounds against AD.
Association between interhemispheric functional connectivity (IFC) and amyloid deposition in patients with different types of dementia
Authors: Cheung Eva YW , Mak Henry 
Published: December 2020

AbstractBackgroundPrevious studies have demonstrated that accumulations of amyloid fibrils (AF) altered the cognitive performance in patients suffered from Alzheimer’s disease (AD) and Mild cognitive impairment (MCI).Method85 participants (25 healthy controls HC, 16 AD, 21 MCI, 10 Mixed dementia (MD), 13 vascular dementia (VD) )were recruited to undergo Resting state functional MRI (rs‐fMRI) scanning and 18F‐Flutemetamol Positron Emission Tompography Computed Tomography (PETCT) scanning. Voxel Mirrored Homotopic Connectivity (VMHC) was calculated based on the method used by Kelly et al 2011 [1] and Zuo et al 2010 [2]. Standardized uptake value (SUV) were recorded from the PET images. With reference to the SUV of pons, SUV ratio (SUVR) were obtained. Association between IFC and SUVR were calculated based on the Spearman’s correlation test.ResultIFC was negatively associated with SUV in AD at lingual gyrus (r=‐0.552, p=0.027) and cuneus (r=‐0.609, p=0.012) within visual network, VN; and MCI in Inferior frontal gyrus (IFG) triangular (r=‐0.488, p=0.02) within default mode network (DMN). For MD, IFC was positively associated with SUVR at angular gyrus (r=0.662 ,p =0.037), middle frontal gyrus (r=0.817 ,p =0.004), superior frontal gyrus (r=0.669 ,p =0.035) within DMN; at middle temporal gyrus MTG (r=0.554 ,p =0.049), Middle frontal gyrus orbital (r=0.742, p =0.014) within central executive network (CEN); at supplementary motor area, SMA (r=0.654 ,p =0.040) within sensory motor network (SMN); at IFG orbital (r=0.856 ,p =0.002) within dorsal attention network (DAN). For VD, IFC was positively associated with SUVR at posterior cingulate (r=0.611, p =0.026) within DMN; at middle temporal gyrus (r=0.563 ,p =0.045), rolandic operator (r=0.603 ,p =0.029), Precentral Gyrus (r=0.554 ,p =0.049) and Posterior central gyrus (r=0.653 ,p =0.019) within CEN; inferior temporal gyrus (r=0.605 ,p =0.028) within DAN.ConclusionThe findings demonstrated the accumulation of AF decreases IFC in VN for AD and SRN for MCI. While for MD and VD, accumulation of AF increases with the IFC in DMN, CEN, SMN and DAN, suggesting that there is compensation of brain function, through recruiting other networks for non‐amyloid dominant dementia.
Neurotensin agonist alleviates metabolic disturbance, neuropathology, and cognitive decline in high‐fat diet–induced obese rats
Authors: Saiyasit Napatsorn , Chunchai Titikorn , Apaijai Nattayaporn , Pratchayasakul Wasana , Sripetchwandee Jirapas , Chattipakorn Nipon , Chattipakorn Siriporn C. 
Published: December 2020

AbstractBackgroundPrevious studies demonstrated that chronic high‐fat diet (HFD) consumption caused the development of obesity with metabolic disturbance, systemic inflammation, neuropathologies, including cognitive impairment and the disruption of brain neurotensin (NT) signaling. Moreover, exogenous NT treatment showed the neuroprotective effects and improved cognitive function in genetic‐induced obese models. However, the effect of NT agnoist on peripheral/brain pathologies following long‐term HFD consumption has not been investigated. The present study hypothesizes that NT agonist alleviates the aforementioned adverse effects in both periphery and brain in HFD‐fed rats.MethodMale Wistar rats were received either a normal diet (ND) or HFD for 16 weeks. At week 13, ND‐fed rats were received the saline solution as a vehicle group (n=4‐6). HFD‐fed rats were randomly divided into 2 subgroups to receive either a vehicle or 1 mg/kg of PD149163 (NT agonist) via subcutaneous injection consecutively for 2 weeks (n=4‐6/group). At week 15, Morris water maze (MWM) test, and blood collection were performed, then animals were sacrificed. The metabolic parameters and peripheral inflammation were examined. Reactive oxygen species (ROS) production, dendritic spine density, number of microglia, and Alzheimer’s‐related protein expression in hippocampus were also determined.Result16‐week HFD‐fed rats developed obesity with peripheral insulin insensitivity, and increased level of serum lipopolysaccharide (LPS). Furthermore, a cognitive decline as demonstrated by the increased time to reach the platform and decreased time spent in the target quadrant from the MWM test (Figure 1A), increased number of Iba1+ cells (Figure 1B), elevated the levels of hippocampal ROS (Figure 1C), and increased the expression of p‐TauThr181 protein (Figure 1D), as well as reduced dendritic spine density were observed when compared to ND‐fed rats. Interestingly, the administration of NT agonist restores the aforementioned negative parameters in both periphery and brain in HFD‐fed rats (Figure 1A‐D).ConclusionThese findings suggest that the administration of NT agonist alleviates peripheral pathologies and exerts neuroprotective effects by decreasing the expression of Alzheimer’s‐related protein, reducing brain inflammation/oxidative stress, and restoring cognitive function in obese insulin‐resistant rats. Therefore, NT should be a therapeutic target to prevent cognitive impairment in obese people.
Optimization of in vitro gene delivery to neurons containing an APP gene with a mutation responsible for familial Alzheimer’s disease for the development of a base editing therapy
Authors: Tremblay Jacques P. , Guyon Antoine , Joël Rousseau P. 
Published: December 2020

AbstractBackgroundThe Amyloïd Precursor Protein (APP) is preferentially cut by the α‐secretase enzyme in healthy individuals. However, an abnormal cleavage by β‐secretase leads to the accumulation of β‐amyloid peptides. Numerous APP genetic mutations cause Familial Alzheimer Disease (FAD). However, a rare APP gene variant (A673T) found in Icelanders drastically reduces cleavage by the β‐secretase. We hypothesized that the insertion of this A673T mutation in a patient’s genome using the CRISPR/Cas9 Base‐Editing Technology (Komor et al. Nature 2016) could be an effective method to slow down the progression of familial and sporadic forms of Alzheimer’s disease. The objective of this study is to eventually compare the efficiency by which a lentiviral or a dual‐AAV‐based vector could deliver a base‐editing complex (SpCas9VQR‐Target‐AID) into neurons in vitro.MethodNeurons were obtained using two methods. The first method involved differentiating fibroblasts from a FAD patient or a mouse model with a London (V717I) mutation into neurons (Shrigley et al. JoVE 2018) (Figure 1), while the second method involved isolating hippocampal neurons from prenatal NL/F/G mice (Seibenhener et al. JoVE 2012). The dual AAV complex was designed to deliver two parts of the base editor gene separated by inteins (Villiger et al. Nat Med 2018). Hippocampal or induced neurons were transduced with lentivirus or AAV1. Cas9 detection was performed by immunofluorescence and Western Blot. The β‐amyloid peptides in supernatant were characterized and quantified by Meso Scale Discovery’s Aβ kit.ResultWe have been able to detect the Cas9 protein in neurons by western blot and immunofluorescence (Figure 2). In subsequent experiments, we will determine which delivery method will reduce more the β‐amyloid peptide.ConclusionOur approach aims to confirm the protective effect of the A673T mutation against the development of familial and sporadic forms of Alzheimer’s disease as well as develop an efficient delivery method for the base editing complex which will lead to an in vivo application. Long‐term perspective: We aim to develop a completely new therapeutic approach for AD and FAD using base editing or the new PRIME editing technique (Anzalone et al. Nature 2019). This may eventually lead to a Phase I clinical trial.