bluuebunny/crossref_metadata_2025_split huggingface dataset:
Levels of insulin pathway proteins in persons with concomitant Alzheimer’s disease dementia and type 2 diabetes mellitus
Authors: Grigoli Marina Mantellatto , de Oliveira Danielle dos Santos Maia Salheb , Manzine Patricia Regina , Cominetti Marcia Regina 
Published: June 2023

AbstractBackgroundAlzheimer’s disease (AD) is a gradual and progressive neurodegenerative disease characterized by predominant cortical atrophy in the medial temporal lobe. Since the results of the Rotterdam study in 1992, it has been known that type 2 diabetes mellitus (T2DM) increases the risk of dementia. Persons with T2DM have structural brain changes and cognitive impairment, with a high risk of developing AD. These data suggest that insulin may play a key role in brain activity and memory formation. The objective of this study was to verify if there are alterations in the levels of proteins of the insulin pathway in cognitively healthy individuals, with AD, with T2DM and with the concomitant presence of AD and T2DM.MethodThe study was approved by the UFSCar’s ethics committee (CAAE: 31634720.9.0000.5504) and recruited participants aged 60 years or older. The AD diagnosis was obtained using the criteria of the National Institute Aging Alzheimer’s Association (NIA/AA). T2DM was defined as self‐reported use of oral antidiabetic drugs. Specific inclusion and exclusion criteria and cognitive assessment of the MMSE and CDR were applied to all participants. Plasma was collected by venepuncture and protein levels of ISNR, IRS1, Akt1, PI3KCD, MAPK1, MAPK8, PTP1B and IDE (Life‐Span Biosciences) were analysed using ELISA (Enzyme Enzyme‐Linked Immunosorbent Assay).ResultSeveral proteins of the insulin pathway were found to be significantly different among patients with AD, T2DM and AD+T2DM, compared with healthy controls (figure 1), reinforcing the strong correlation between T2DM and AD. Main alterations were found for INSR, IRS1, Akt1, PIK3, MAPK, PTP1b and IDE among healthy participants and those with AD+T2DM.ConclusionThe peripheral alterations found in the levels of insulin pathway proteins confirm the possible relationship between T2DM and AD and reinforce the importance of the insulin signalling pathways, as they can play a fundamental role in AD. The clinical impact of this study is related to a new approach that could be used in the treatment of this type of dementia, also observing the metabolic and inflammatory states of the patients, in addition to contributing to a better understanding of the biology of the disease itself.
Association of Apolipoprotein E ε4 with Tau and Amyloid‐β PET in a memory clinic cohort
Authors: Peretti Débora Elisa , Ribaldi Federica , Stampacchia Sara , Tomczyk Szymon , Blouin Jean‐Louis , Wyss‐Dominguez Carine , Abramowicz Marc , Frisoni Giovanni B , Garibotto Valentina 
Published: June 2023

AbstractBackgroundThe Apolipoprotein E ε4 (ApoE4) is the strongest genetic risk factor for Alzheimer’s disease (AD). Previous studies have found a link between ApoE4 genotype and tau (T) deposition in the medial temporal lobe (MTL). However, further studies disentangling the influence of genotype on tau deposition and amyloid (A) are still needed. The aim of this study was to assess tau and amyloid deposition depending on subject genotype in a memory clinic cohort.Method89 subjects from the Geneva Memory Center underwent amyloid and tau PET imaging, and ApoE genotyping (ApoE2 carriers, ApoE3 homozygotes, ApoE4 carriers). The remaining subjects were classified as ApoE3. Amyloid uptake has been calculated as centiloid values and tau uptake as standardized uptake value ratio (SUVR), normalized to cerebellar uptake. Positivity for each biomarker was based on thresholds published by previous studies. Correlation between amyloid centiloid and tau SUVR in general and by genotype was calculated. ANOVA with Tuckey correction for multiple comparisons was used to assess differences between tau or amyloid PET uptake across different genotypes.Result85% of the A+T+ subjects were carriers of the ApoE4 gene. The association between neocortical amyloid and MTL tau stratified by genotype showed that these measures are correlated in ApoE4 carriers (r = 0.52, p = 0.001). The correlation was not significant in non‐carriers. MTL tau SUVR was higher in ApoE4 carriers and significantly different when compared to non‐carriers. Furthermore, tau SUVR from lateral and superior temporal lobes were also significantly different in ApoE4 carriers vs. non‐carriers even when not considering the centiloid value, showing an amyloid‐independent association between tau SUVR and genotype is not limited to the MTL. Centiloid values showed similar differences when comparing ApoE4 carriers with non‐carriers.ConclusionApoE4 gene carriers present a significant increase of both tau and amyloid load with respect to non‐carriers. Furthermore, increased tau deposition independent from amyloid load is not limited to the MTL, with the entire temporal lobe showing higher tau pathology in ApoE4 carriers.
Continuous wave 670nm LED light therapy improves short‐ and long‐term object recognition, locomotion, and reduces phosphorylated tau burden in 3xTgAD mice
Authors: Johnson Kevin J , Johnson Kathia M , Taglialatela Giulio , Micci Maria‐Adelaide 
Published: June 2023

AbstractBackgroundPhotobiomodulation (PBM) therapy uses 620‐1100nm red to near‐infrared light to modulate biological processes including neuroinflammation, amyloid and tau oligomerization, and apoptosis. We have shown that 670nm light therapy reduces synaptic vulnerability to amyloid‐β oligomers in wild‐type (WT) mice and reduces tau oligomerization in mouse models of tauopathy. Here we sought to determine if 670nm light therapy could rescue cognitive and motor dysfunction and reduce tau hyperphosphorylation in 14‐to‐18‐month‐old 3xTgAD mice.Method14‐to‐18‐month‐old 3xTgAD mice were treated with continuous‐wave 670nm LED light applied directly to the head for 90s per day, 5 days per week for 4 weeks. 3xTgAD sham and WT controls were held under the LED device with the light turned off for the same amount of time. During the fourth week of treatment, spontaneous locomotor behavior was measured by placing animals in an empty chamber for 10 minutes using ANY‐maze software to track mobility data. Animals were then tested for working memory in the Y maze spontaneous alternation task and short‐and long‐term memory in the novel object recognition task. At the completion of behavioral testing on treatment day 20, brains were collected for western blot analysis of total tau and phospho‐tau (pTau).ResultLight‐treated 3xTgAD mice showed increased distance traveled compared to sham (17.43 ± 3.46 vs. 9.97 ± 3.03, one‐way ANOVA p = 0.03), and decreased immobile episodes (4.50 ± 1.92 vs 10.00 ± 1.83, one‐way ANOVA p = 0.02) in the spontaneous locomotor activity test. Light‐treated animals also showed significant object recognition at 2 hours (DI 32.75 ± 7.71, one sample t‐test p<0.001) and 24 hours (DI 44.14 ± 15.73, one sample t‐test p = 0.001) post‐training. Light treatment also reduced the ratio of hippocampal pTau/Tau in 3xTg AD mice as compared to sham (0.11 ± 0.05 vs. 0.32 ± 0.13, one‐way ANOVA p = 0.04).ConclusionHere we show rescue of locomotor behavior and cognitive dysfunction, and reduction of Tau phosphorylation in the hippocampus of 3xTgAD mice using a non‐invasive transcranial treatment with 670nm LED light. Our data suggest that treatment with 670nm red light could significantly improve cognitive function in AD patients and reduce hyperphosphorylation of tau thus possibly preventing further neurodegeneration.
Using the Integrated Cognitive Assessment (ICA) to improve the efficiency of primary care referrals to memory services
Authors: Kalafatis Chris , Shore Judith , Modarres Mohammad Hadi , Apostolou Panos , Tabet Naji , Khaligh‐Razavi Seyed‐Mahdi 
Published: June 2023

AbstractBackgroundExisting primary care cognitive assessment tools are crude or time‐consuming screening instruments which can only detect cognitive impairment when it is well established, impacting carers and patient quality‐of‐life.We initiated the Accelerating Dementia Pathway Technologies (ADePT) study to develop a real‐world evidence basis to support the adoption of the Integrated Cognitive Assessment (ICA), a 5 minute computerised cognitive test that employs artificial intelligence to improve its accuracy, as an inexpensive screening tool for the detection of cognitive impairment and improving the efficiency of the dementia care pathway.MethodPatients referred to memory clinics from primary care General Practitioners (GPs) were recruited. Participants completed the ICA either at home or in the clinic along with medical history and usability questionnaires. The GP referral and ICA outcome were compared with the specialist diagnosis obtained at the memory clinic.The clinical outcomes as well as costing data were used as part of an economic analysis to assess the potential health economic benefits of the use of the ICA in the dementia diagnosis pathway in the United Kingdom.Result87 participants referred to memory clinics were recruited who completed all assessments (40 dementia, 19 mild cognitive impairment, 12 inconclusive, 5 healthy, 3 non‐dementia conditions). From these patients the ICA was able to identify cognitive impairment with a sensitivity of ∼90%.The results of the health economics model, utilising real world data collected from the ADePT study estimates that if the ICA were introduced in a primary care setting then it could result in a cost saving to the health and social care system of approximately £147 per patient over a lifetime horizon (∼£44m of direct costs to the health care system) or £283 per patient if introduced into a secondary care setting.ConclusionThe results from this study demonstrate the potential of the ICA as a screening tool to support accurate referrals from primary care settings to memory clinics. The introduction of disease modifying treatments for Alzheimer’s and dementia will further improve the case for earlier detection of the condition and therefore increase the cost‐effectiveness of more accurate screening using tests such as the ICA tool.
Neuropsychiatric inventory questionnaire scores are predictive of dementia progression
Authors: Rao Sumedha R , Housini Mohammad , Royall Donald R. , Palmer Raymond F. , Barber Robert 
Published: June 2023

AbstractBackgroundIn ageing adults, the most common form of dementia is Alzheimer’s disease (AD). AD pathogenesis involves the accumulation of beta‐amyloid (Aβ) protein aggregation in plaques and tau proteins in neurofibrillary tangles that are associated with a decreased number of synapses in the brain, altered neuronal function and cell death via neurotoxicity, as well as learning and memory deficits. Clinically, the presence and severity of neuropsychiatric symptoms that AD patients present with can be reliably measured by the Neuropsychiatric Inventory Questionnaire (NPIQ). This study aims to explore the association between baseline mental health and the severity of AD progression.MethodTo measure baseline mental health, NPIQ scores were used while the change in deq was used to represent the severity of AD progression within the TARCC cohort. deq is a homolog of d, a reliable latent dementia proxy that represents cognitive correlates of functional status and is specific for distinguishing cases with AD from other dementia‐related presentations. Most crucially, the deq homolog has been adjusted for equivalence across ethnicities. Using stratified analysis and structured equation models, the association between baseline mental health and change in was investigated.ResultThe first model exploring NPIQ and the change in deq was only adjusted for baseline deq; it showed NPIQ explaining 19% of the variance in delta deq and was statistically significant at p = 0.016 for Non‐Hispanic Whites. With the second model, age, sex, and education were adjusted for in addition to baseline deq. NPIQ was shown to explain 25% of the variance in delta deq while being statistically significant at p = 0.037 for Non‐Hispanic Whites. This model was replicated in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort; NPIQ was shown to be predictive for delta deq at p = 0.013.ConclusionIn Non‐Hispanic Whites, worse baseline mental health has been shown to predict increased severity and progression of AD. This makes it a clinical therapeutic target with the possible benefit of impacting the course of AD in patients. The fascinating interplay between mental health and its relationship to Alzheimer’s disease should be studied further with an additional focus on ethnicity.
Brain insulin resistance and Alzheimer’s molecular changes induced by Western diet
Authors: Domańska Justyna Marta , Mietelska‐Porowska Anna , Want Andrew , Wieckowska‐Gacek Angelika , Wojda Urszula 
Published: June 2023

AbstractBackgroundWestern diet (WD) is a type of nourishment based on ultra‐processed foods, rich in simple sugars and saturated fats. Long‐term consumption of WD may lead to disruption of insulin signaling and development of insulin resistance. It is supposed that insulin resistance is a probable risk factors for Alzheimer’s disease (AD). The aim of this study was to verify this hypothesis in wild type mice by checking the WD effect on initiation and propagation of main neuropathological AD features such as amyloid‐β (Aβ) plaques and neurofibrillary tangles, which start from the entorhinal cortex in the temporal area, and progresses to the hippocampus, resulting in the loss of memory and cognition.MethodMales of wild type C57BL/6J mice were fed WD diet or standard diet (SD; CTR). Mice experimental groups (WD and CTR) were divided into age subgroups 4‐, 8‐, 12‐ and 16‐month‐old. In the first step, the WD‐diet dependent insulin signaling was analyzed, and the levels of the insulin pathway components: p‐IRS‐1(Ser616), p‐Akt(473), p‐GSK‐3β(Ser9) in the entorhinal cortex and hippocampus were assessed. To analyze further whether WD‐derived impairments in insulin signaling may induce neuropathological AD features, p‐Tau(Thr231) and APP/Aβ were analyzed by immunoblotting and immunofluorescence of mouse brain tissue sections from entorhinal cortex and the hippocampus.ResultEntorhinal cortex proved to be more sensitive to WD‐dependent insulin impairments than the hippocampus: immunoblotting analysis of mouse entorhinal cortex brain lysates revealed an increase in p‐IRS‐1(Ser616) levels, indicating the development of insulin resistance under WD diet. Moreover, a change in the localization of p‐Tau(Thr231) in cellular compartments from fibers to nerve cell bodies indicated a progressive tauopathy. In addition, we also observed an age‐dependent decrease in APP protein levels correlating with the appearance of Aβ peptides in the cytoplasm of neurons under the WD diet.ConclusionObtained results suggest that the WD diet, by inducing abnormalities in insulin signaling in the brain, promotes the development of AD, and may be consider as a significant modifiable risk factor for AD, additional to the genetic risk factors.
Prediction of sleep quality scores using dynamic functional network connectivity of young adults: A reproducibility analysis
Authors: Sendi Mohammad S.E. , Dini Hossein , Zendehrouh Elaheh , Salat David H , Calhoun Vince D 
Published: June 2023

AbstractBackgroundDynamic functional network connectivity (dFNC) estimated from resting‐state functional magnetic resonance imaging (rs‐fMRI) is a potentially powerful approach to investigate human behavior and cognition. However, previous studies barely investigate the reproducibility of dFNC features links with cognition. This study aims to examine whether the data collected in four different sessions reproduce the same results using the sleep scores by applying a dFNC method to resting‐state fMRI (rs‐fMRI) data from the Human Connectome Project (HCP) Young Adult.MethodWe used the Pittsburgh Sleep Quality Index (PSQI) scores and four sessions of rs‐fMRI (15 minutes each) from 833 young adults (age between 22 to 37yrs). We calculated the dFNC for each participant using a fully automated Neuromark independent component analysis and a sliding window technique to estimate dFNCs. A k‐means clustering approach partitioned dFNCs into two group‐level distinct states and subject‐level state vectors. Next, we estimated dFNC features from each individual’s state vector and dFNCs. Finally, we trained a 10‐fold support vector regression model to predict the sleep scores based on the dFNC features. We applied all the procedures mentioned above to all four sessions separately.ResultWe found dFNC features can successfully predict each participant’s night sleep time. The correlation between the actual score and the predicted one was R = 0.0853 (p = 0.0182) for session1, R = 0.0696 (p = 0.0485) for session2, R = 0.0764 (p = 0.0393) for session2, and r = 0.0788 (p = 0.0285) for session4. The dFNC features for none of four sessions could predict other sleep scores.ConclusionWe showed that the dFNC feature could predict the amount of sleep during the night in the HCP Young Adult population. Additionally, we showed the prediction result replicates across all four rs‐fMRI sessions. Future studies are needed to explore the reproducibility of the result within the age range of the HCP dataset.
Microbiome‐associated metabolic determinants of neurodegeneration and cognitive resilience
Authors: Matz Lisa M , Shah Nisarg S. , Urban Randall J , Kayed Rakez , Buffington Shelly A 
Published: June 2023

AbstractBackgroundType 2 diabetes (T2D) is a common antecedent of pathological neurodegeneration and accompanying dementia, including Alzheimer’s Disease (AD); however, the mechanistic link between metabolic and neurodegenerative disorders remains unresolved (1‐3). Study of a small cohort of dementia patients revealed divergent gut microbiota composition, increased gut permeability, and inflammation, implicating a microbial determinant in neuroimmune dysregulation (4), an emerging player in neurodegeneration (5). Notably, the microbiome is a source of neuroprotective metabolites (6), highlighting the need to elucidate the role of the microbiome and realize the potential for its therapeutic modulation in AD. We recently began a clinical trial focusing on individuals of Mexican descent living in Southern Texas, a population with increased prevalence of co‐morbid T2D and early onset AD (7‐8), with the working hypothesis that diet‐driven shifts in gut microbiome composition contribute to T2D and AD pathophysiology in this population (9‐11).MethodWe will perform metagenomic 16S rRNA gene amplicon sequencing and compare within (alpha) and between (beta) sample diversity as well as quantitative phylogenetic and taxonomic comparisons. Using 3xTg‐AD and hTau mouse models, we will determine the impact of microbial depletion via broad spectrum antibiotics on AD pathology and cognitive function. Data will be analyzed separately for each sex using nested t‐tests, nested one‐way ANOVA, or a mixed effects model to account for litter effects.ResultData resulting from our preclinical animal and clinical human studies will inform future experiments in which we will transplant fecal microbiota samples derived from T2D versus non‐diabetic human subjects into microbially‐depleted, “humanized” AD mice. We will then perform metabolomic, molecular, electrophysiological, and behavioral analyses to determine the impact(s) of T2D gut microbiota on host AD‐like pathology and behavioral phenotypes.ConclusionCharacterizing gut microbiome signatures of T2D individuals of Mexican descent living in Southern Texas could identify key actors among “disease state” microbiota which may exacerbate or accelerate neurodegenerative disorders, as well as gut microbiota present in healthy controls lost in the T2D population which contribute to molecular mechanisms of cognitive resilience. Consequently, our approach may lead to novel immunotherapeutic approaches to target or limit neuroinflammation in AD.
The brain health champion study: A health coaching intervention with mobile technology in older adults with mild cognitive impairment or risk factors for dementia – An update
Authors: McFeeley Brittany M , Krivanek Taylor , Nicastri Casey M , Ramirez‐Salazar Sergio , Babazadeh Demsina , Altman Abby , Daffner Kirk R , Gale Seth A 
Published: June 2023

AbstractBackgroundExtensive evidence suggests that adherence to brain‐healthy behaviors can slow the rate of cognitive decline and decrease risk of dementia. We previously demonstrated that a health coaching intervention, including weekly phone calls, facilitated adherence to recommendations for brain‐healthy behaviors in older adults with mild cognitive impairment (MCI) or mild dementia. The current study extends this research to include cognitively normal, older adults at risk for dementia and adds a mobile health platform, two‐way texting, and wearable fitness trackers, to the health coaching intervention. Although subjects are still enrolling, the number of participants has increased substantially from our earlier report and data show promising trends.MethodParticipants, age 60‐79, with MCI or dementia risk factors are being randomized to the Brain Health Champion (BHC) intervention or a counseling and education (CE) control. In BHC, with guidance from a health coach, participants set personalized goals, reinforced by weekly video calls, mobile messaging, one dietitian consult, and 30‐minute in‐person or virtual visits every six weeks. In CE, educational materials sent every six weeks supplement usual care. Changes in physical activity, diet, social/cognitive engagement, neuropsychological test scores, and metrics of behavioral health are being measured over six months using questionnaires, wearable fitness trackers, and photographed food logs. Maintenance of behavior changes is also being assessed six months post‐intervention.ResultThirty‐four participants have enrolled in the study, with 27 (15 BHC, 12 CE) completers to date. All participants successfully operated the mobile technology by themselves or with caregivers’ assistance. Current trends show BHC participants increased participation in cognitive activities and adherence to a Mediterranean diet based on photographed food logs compared to CE. Participants in both arms show significantly increased scores on the composite neuropsychological assessment (pre‐ and post‐study), quality of life measures, and an increase in active minutes from pre‐ to post‐assessments.ConclusionTrends in the data indicate that the BHC program may be effective for promoting brain‐healthy behaviors, particularly increasing cognitive activities and Mediterranean diet adherence. Additionally, participating in a brain health study, regardless of intervention, may promote meaningful changes in quality of life and improved cognition.