bluuebunny/crossref_metadata_2025_split huggingface dataset:
Risk factors and interventions for Alzheimer's disease: A systematic review
Authors: Almeida Jose Roberto , Almeida Maysa Cunha , Cunha Maria Eduarda , Silva Ana Gabriela Correia 
Published: December 2020

AbstractBackgroundRisk of developing Alzheimer´s Disease (AD) is increased by older age, family history, sex, genetic factors (especially the presence of the APOE‐4 allele; a history of head trauma, midlife hypertension, education, obesity, diabetes and hypercholesterolemia. In the absence of medications that can halt or prevent AD, lifestyle interventions that could improve maintain cognitive function have become increasingly important.MethodWe developed evidence‐based guidelines using systematic literature searches, with criteria for study selection and quality assessment decision‐making process was selected studies published from February 2008 to June 2019 that met the following criteria: dementia, risk factors and prevention.ResultAn estimated one‐third of AD cases can be attributed to modifiable risk factors. Studies have show that certain dietary (in contrast with high‐glycemic and fatty diets, a healthy diet is associated with decrease in beta‐amyloid burden, inflammation and oxidative stress); lifestyle habits such as physical exercise (regular exercise has been showed to have direct neuroprotective effects); meditation/spiritual activity; mental and social activity (higher levels of complex mental activities measured across the lifespan, such as education, occupation, reading and writing are correlated with significantly less hippocampal, volume shrinkage over time).ConclusionThere is increasing evidence that combining multiple lifestyle modifications may yield better out comes in maintaining to improving cognition. A combination of healthful diet steps and regular physical exercise may reduce the risk of developing AD. These lifestyle changes body weight, cardiovascular health and diabetes risk, and essentially no risk for harm.
Correlation between depressive symptom and executive function decline in amyloid positive mild cognitive impairment
Authors: Choo IL Han , Chung Ji Yeon , Chong Ari , Ha Jung‐Min , Choi Yu Yong , Kim Hoowon 
Published: December 2020

AbstractBackground
VDepression is a risk factor of Alzheimer’s disease dementia. We aimed to explore the correlation between depressive symptom and neuropsychological test results in mild cognitive impairment by amyloid positivity.MethodSixty‐eight individuals with MCI were recruited. All participants received a Clinical Dementia Rating score of 0.5 and met the Petersen’s criteria. Comprehensive neuropsychological assessment was performed using the SNSB II. The [18F]Florbetaben PET and MRI scans were performed. T1‐weighted MR 3D volumes were acquired for co‐registration with PET. All participants underwent Geriatric depression scale (GDS). Participants were classified as amyloid positive when the mean cortical SUVR was 1.20 and over. Correlation analyses between GDS score and each neuropsychological test standard score (z‐score based on age‐, education‐, and gender specific normative information) were performed.ResultSignificant negative correlation between GDS score and Rey Complex Figure Test Copy z score was found in all MCI participants (r = ‐0.299, p = 0.013). For amyloid positive MCI group (n = 30), we found GDS scores were significantly correlated with Rey Complex Figure Test Copy z score (r = ‐0.364, p = 0.048) and Trail Making Test A z score (r = ‐0.473, p = 0.008). However, for amyloid negative MCI group (n = 39), there was no significant correlation.ConclusionOur results suggest that amyloid positive MCI patients have significant correlation between depressive symptoms and executive function decline.
[11C]MPC‐6827: A microtubule‐based pet imaging tracer for AD and related dementias
Authors: Macauley‐Rambach Shannon , Damuka Naresh , Whitlow Christopher T. , Mintz Akiva , Craft Suzanne , Sai Kiran Solingapuram 
Published: December 2020

AbstractBackgroundLoss of microtubule (MT) network and impairment of MT function are considered to be part of pathophysiology of several CNS disorders, including AD, Parkinson disease and other ADRS and tauopathies. A BBB penetrating MT‐based PET ligand would permit imaging a variety of CNS disorders. Our lab reported the first brain‐penetrant PET radiotracer [11C]MPC‐6827 to image MTs in vivo, in both wild and transgenic AD mice. Here, we report a pilot longitudinal [11C]MPC‐6827 PET imaging study with early, middle and late stages of Aβ and tau progression in APP/PS1 and P301S mice respectively. PET imaging in NHP brains was performed to test translational utility.MethodDynamic brain microPET/CT imaging was performed with [11C]MPC‐6827 in APP/PS1 mice at 3, 18 and 22 months and in P301S mice (n=4) at 5, and 10 months. Regions of interests (ROIs) were drawn in whole brain, cortex, cerebellum and hippocampus and time‐activity curves (TACs) were determined. Basic distribution volume ratios (DVRs) between high‐ and low‐uptake regions were calculated. Dynamic 2h PET/CT imaging was performed in adult male vervet monkeys (n=8).ResultBased on ROIs and TACs in whole brain, cortex and hippocampus, the radioactive uptake of 3 month‐old TG APP/PS1 mice was ∼30% higher compared to the uptake at 18 months, which in turn was ∼18% higher over 22 month‐old mice. Radioactive uptake of TG P301S mice at 5 months was ∼24% higher compared to 10‐month old mice. DVRs from cortex and hippocampus to cerebellum were ∼2‐fold higher in younger APP‐PS1 and P301S mice compared to their older littermates. Radioactive changes in all experiments were statistically significant, substantiating our preliminary imaging data. NHP‐PET brain analyses indicated brain penetration and high retention of the tracer.Conclusion[11C]MPC‐6827 demonstrated decreased radioactive uptake with increased brain Aβ and tau loads. A MT‐based PET imaging tracer could be a potential early imaging biomarker for AD and other ADRDs. PET imaging studies in monkey brains showed high BBB penetration. Binding distribution is in good agreement with the known MT‐mice distribution. Next steps are to correlate radioactive uptake with tau pathologies and in an NHP model of AD.
Higher empirical dietary inflammatory pattern scores are associated with worse cognitive performance in the Nurses’ Health Study
Authors: van Lent Debora Melo , Samieri Cécilia , Grodstein Francine , Seshadri Sudha 
Published: December 2020

AbstractBackgroundWe evaluated whether higher cumulative Empirical Dietary Inflammatory Pattern (EDIP) scores were associated lower cognitive function, in the Nurses’ Health Study.Method16,058 post‐menopausal women (mean age 74 (Standard deviation, 2)) completed a validated 116‐item Food Frequency Questionnaire. The EDIP score, previously derived with the use of reduced rank regression to predict circulating inflammatory markers (i.e. C‐reactive protein, tumor necrosis factor α receptor 2 and interleukin‐6), consists of ten anti‐inflammatory and nine pro‐inflammatory components. A cumulative EDIP score was calculated by averaging across five exams (1984‐1998) taking the first exam (1984) or second exam (1986) as baseline exams. The EDIP score was categorized into five quintiles, taking the first (anti‐inflammatory) quintile as the reference category. Cognitive testing was performed through telephone interviews over four follow up exams (1995‐2008). A composite global cognition score, a composite verbal memory score and the Telephone Interview for Cognitive Status (TICS) were calculated and averaged across the four exams.ResultHigher cumulative EDIP scores (i.e. more pro‐inflammatory) were significantly associated with worse performance on global cognitive function (p for trend <0.01) and TICS (p for trend <0.001) after adjustment for age, education and body mass index, physical activity, energy intake, smoking, multivitamin use, depression. The relationship between higher cumulative EDIP scores and TICS remained (p for trend 0.04) following additional adjustments for hypertension, high cholesterol, myocardial infarction, diabetes, menopausal hormone use and nonsteroidal anti‐inflammatory drugs. But the association between the EDIP score and global cognitive function attenuated and became non‐significant. No association was observed between the EDIP score and verbal memory.ConclusionHigher cumulative EDIP scores strongly associated with worse performance on averaged TICS regardless of the model among older women. But the relationships between the EDIP score and global cognitive function and verbal memory were mainly explained by potential confounders and intermediates leaving findings attenuated and not significant. Our study shows that pro‐inflammatory diets not only are detrimental for risk factors of cognitive decline but also for cognitive function itself. Future studies are encouraged to investigate the relationships in men and over a long follow up period.
Determinants of early diagnosis of cognitive impairment in older Indian adults
Authors: Kumar Pramod , Dey Aparajit Ballav 
Published: December 2020

AbstractBackgroundDiagnosis of cognitive impairment at an early stage is vital to the management of dementia like Alzheimer’s disease. Recent studies have proved that multi‐modal non‐pharmacological therapy does decrease the progression of cognitive decline in patients with subjective cognitive decline (SCD) and mild cognitive impairment (MCI). In this study, we evaluated the determinants of presentation at an early stage of cognitive impairment, to our memory clinic.MethodPatients presenting with cognitive impairment were evaluated in our memory clinic. After reversible causes and depression were ruled out, patients were classified as those with early disease (SCD and MCI) or major neurocognitive decline (MNCD). A retrospective analysis of the data was done to evaluate the association of baseline characteristics (age, sex, education, region, occupation and cardiovascular diseases) with the stage of presentation of cognitive decline.ResultData of 415 patients, evaluated from 2017 to 2019, was analyzed. Reversible causes were identified in 29.2 % of the patients, including 24.1% with depression. SCD, MCI and MNCD were identified in 29.6%, 16.4%, and 24.8%, respectively. Demographic factors like male sex (p value < 0.001), higher education (p value < 0.001) and occupational skill (p value = 0.006), were significantly associated with early presentation to the memory clinic.ConclusionIn this study, we observed 65% of the patient presented at an early stage of cognitive decline (SCD and MCI). With development of possible disease modifying agents in near future, this can be an important stage of intervention. Female patients with lower educational and occupational status, associated with late presentation, can be an important target for screening.
Resting‐state functional connectivity modulation through a combined a TDCS‐visuospatial training on object‐location memory in healthy older adults and patients with mild cognitive impairment
Authors: Antonenko Daria , Thams Friederike , Külzow Nadine , Flöel Agnes 
Published: December 2020

AbstractBackgroundThe combination of transcranial direct current stimulation (tDCS) with memory training has gained attention as a means for cognitive enhancement in the older population. Neuroimaging studies have identified changes in local brain activity and functional network connectivity as potential underlying mechanisms of tDCS‐induced performance improvement. Resting‐state functional magnetic resonance imaging (rs‐fMRI) revealed that memory improvement via multi‐session object‐location memory (OLM) training was associated with increased connectivity within the default mode network (DMN). This increase was higher in participants who received additional anodal tDCS compared to those who received sham stimulation in combination with OLM training. No previous studies assessed this association in older adults with mild cognitive impairment (MCI).MethodWe analyzed resting‐state fMRI data of 47 older adults with age‐associated cognitive decline (15 MCI patients and 32 healthy older adults) before and after a combined tDCS‐training intervention. All participants underwent a 3‐day visuospatial object‐location memory training paired with either anodal tDCS over the right temporoparietal cortex (1 mA, 20 min) or sham (1 mA, 30 sec), using a cross‐over design. In order to examine the effect of the combined tDCS‐training‐approach on functional connectivity, a seed‐based analysis was conducted between the stimulation target and the DMN using the CONN toolbox. The change from before to after training was compared between tDCS and sham stimulation conditions in all participants using linear mixed‐model analysis.ResultROI‐to‐ROI functional connectivity between the stimulation target (region of interest: middle temporal gyrus, temporo‐occipital part right) and the DMN (region of interest: posterior cingulate cortex of the DMN) showed higher increases in functional connectivity in anodal tDCS compared to sham stimulation condition over the entire cohort (F(1,43)=4.126, p=0.048; mean difference: 0.086, 95%‐confidence interval: 0.001 to 0.171).ConclusionOur findings lend support to the hypothesis that neuronal modulation of functional coupling between the stimulation target and the DMN may be one of the mechanism underlying tDCS‐accompanied OLM enhancement in older adults. Modulation in rs‐fMRI metrics assessing intrinsic functional brain connectivity may constitute a sensitive biomarker for the investigation of intervention‐induced changes in healthy and pathological aging, and may even guide long‐term interventional approaches on an individual level.
The role of Alzheimer’s disease polygenic risk scores in changes of cognitive function in older adults: A longitudinal cohort study
Authors: Pan Gongbu , King Anna E. , Bindoff Aidan , Summers Mathew J. , Vickers James C. ,   Tasmania Healthy Brain Project
Published: December 2020

AbstractBackgroundPrevious studies show evidence that more than 21 genetic variants and polygenic risk were associated with Alzheimer’s disease (AD). But the relationship between AD polygenic risk scores (ADPRS) and cognitive function/decline was unclear due to the lack of longitudinal data. This study investigated the potential association between ADPRS and changes in cognitive function.MethodThe TBHP is an ongoing longitudinal prospective study of 459 healthy older adults. Participants with available genotype data (N = 325) were included in analysis. ADPRS was calculated by using sets of AD susceptibility variants identified by a meta‐analysis of GWAS data. The cognitive function domain scores at baseline and year 1, 2, 3 and 5 were calculated using factor analysis (principal components extraction method). Single factor scores for episodic memory, working memory, executive function, and language processing domains were combined by using factor coefficients via regression analysis. Linear mixed‐effects model analysis was performed to investigate the association between ADPRS and cognitive function longitudinally.ResultThe ADPRS was significantly associated with an increase of working memory and executive function over 60 months, particularly in APOE ε4 carriers. In BDNF met carriers, ADPRS was associated with the decline of executive function. There were no direct associations between ADPRS and longitudinal changes in cognitive function.ConclusionThe relationship between ADPRS and changes in specific cognitive domains were highly being driven by APOE and BDNF status. These findings strongly support the potential role of common variants in predicting the changes in cognitive function before AD.
Ethnic and socioeconomic determinants of dementia risk: A nested case‐control study in the population of East London
Authors: Bothongo Phazha LK , Jitlal Mark , Parry Eve , Foote Isabelle F , Waters Sheena , Dobson Ruth , Noyce Alastair J , Bestwick Jonathan P , Marshall Charles R ,   Preventive Neurology Unit, Wolfson Institute of Preventive Medicine
Published: December 2020

AbstractBackgroundThe influence of ethnicity and socioeconomic status on dementia risk, and the extent to which this is mediated by known risk factors remain incompletely understood. We addressed this issue using health records data from the diverse and deprived population of East London (<50% White and >50% in the most deprived quintile of the UK).MethodWe performed a nested case‐control study in over 1,000,000 East London inhabitants. We identified 4137 cases of all cause dementia, and matched on age and gender to controls with ratio 1:4. Logistic regression was used to calculated odds ratios (ORs) for exposures of ethnicity and UK Index of Multiple Deprivation (IMD), before and after inclusion in the model of established modifiable risk factors (type II diabetes, hypertension, smoking, body mass index, depression and hearing loss). In order to reflect the relative importance of known modifiable risk factors in this deprived multiracial population, we calculated weighted population attributable fractions (PAF) for each factor.ResultRisk of dementia was higher in the Black and South Asian groups relative to White (ORs (95%CI) Black 1.43 (1.31, 1.56), South Asian 1.17 (1.06, 1.29)). Risk of dementia was reduced in all IMD quintiles relative to the most deprived (ORs (95%CI) 2nd 0.71 (0.66, 0.77), 3rd 0.52 (0.44, 0.60), 4th 0.71 (0.53, 0.94), 5th 0.59 (0.38, 0.87)). The effects of ethnicity and deprivation persisted after adjusting for known risk factors. Weighted PAFs for modifiable risk factors were notably higher in this population for depression (9.2%) and diabetes (6.2%) than those estimated in the Lancet Commission meta‐analyses (4% and 1.2% respectively).ConclusionMembership of non‐White ethnic groups and socioeconomic deprivation are important determinants of dementia risk, with effects larger than many of the more established risk factors. These effects cannot be completely accounted for by known modifiable risk factors and further work is required to establish the responsible mechanisms. Depression and diabetes are of greater relative importance, and should be prioritised as targets for dementia prevention in more diverse and deprived populations.
The prevalence of limbic‐predominant age‐related TDP‐43 encephalopathy in the Sydney brain bank
Authors: Jeżewski René C. , Poljak Anne , Mather Karen A. , Sachdev Perminder S. , Shepherd Claire E. 
Published: December 2020

AbstractBackground‘Limbic‐predominant age‐related TDP‐43 encephalopathy’, or ‘LATE’, is a recently identified neuropathological entity that may account for up to 25% of clinically diagnosed dementias in the oldest‐old (Nelson et al., Brain. 2019;142:1503).MethodWe analysed the clinical records and pathology from all prospectively followed cases held by the Sydney Brain Bank (SBB) to determine the association between the presence of limbic‐predominant TDP‐43 pathology and age, clinical diagnosis and pathological co‐morbidities. The study cohort was stratified into six age groups: 50‐54y, 55‐64y, 65‐74y, 75‐84y, 85‐94y and 95‐105y. Cases were assigned into broad clinical groups: asymptomatic, dementia and movement disorders. TDP pathology was assessed blindly and cases were categorised as either limbic TDP‐positive or limbic TDP‐negative according to the presence or absence of pathological TDP in the amygdala, hippocampus and entorhinal cortex, regardless of other contributing pathologies. Cases with neuropathologically confirmed primary TDP proteinopathies, i.e. motor neuron disease and the TDP variant of frontotemporal lobar degeneration, as well as those with known genetic mutations were excluded.ResultIn the total SBB cohort (n=427, mean age=80.0y ±10.3), 70% of cases fulfilled the criteria for positive limbic TDP pathology. The presence of limbic TDP pathology correlated significantly with age (r=0.220, p<0.01) and was 1.3‐fold more likely to occur after the age of 85 years (n=114). Concomitant Alzheimer’s disease neuropathology (46.5%) was most common in this 85+ subcohort (mean age=91.5y ±4.9) and was present in 75.9% of cases with clinically diagnosed dementias. ‘Pure’ LATE neuropathology was identified in 8.8% of cases over the age of 85 years (10/114, mean age=94.4y ±5.0) and was predominantly clinically asymptomatic (8/10, mean age=93.8y ±5.4). Only 3.7% of clinical dementias could be attributed to ‘pure’ LATE (2/54, mean age=97.0y), while concomitant tau pathology and Lewy body pathology explained the majority of remaining dementia cases.ConclusionOur data suggests that ‘pure’ LATE occurs less frequently than expected and only accounts for a small proportion of clinical dementias over the age of 85 years. Whether the severity of TDP pathology can discriminate early, transitional and advanced stages of the disease process and whether these stages correlate with clinical diagnosis is yet to be elucidated.
Global system segregation enhances reserve in normal aging and Alzheimer’s disease
Authors: Ewers Michael , Frontzkowski Lukas , Neitzel Julia , Rubinski Anna , Habeck Christian , Gordon Brian A , Benzinger Tammie LS , Levin Johannes , Cruchaga Carlos , Goate Alison M , Fagan Anne M , Karch Celeste M , Morris John C , Holtzman David M , Bateman Randall J , Stern Yaakov , Franzmeier Nicolai ,   ADNI
Published: December 2020

AbstractBackgroundEpidemiological studies suggest that reserve capacity is associated with a significant delay of cognitive decline by up to 4 years in aging and dementia. Identifying brain substrates of reserve is a pivotal step to define potential intervention targets for brain stimulation in order to enhance reserve. We previously showed that higher global connectivity of specific richly connected hub regions contribute to reserve (Franzmeier et al. Brain 2018, Neitzel et al. Neurology 2019). However, apart from the role of local hubs, functional mechanisms at the level of major functional networks that support reserve are poorly understood. The segregation of the brain’s major functional network is a fundamental brain property that supports higher cognitive function (Chan et al. PNAS 2014, 2018). We hypothesized that higher system segregation is associated with attenuated cognitive decline in normal aging and Alzheimer’s disease (AD).MethodWe included 255 cognitively normal elderly subjects (age=52.48±16.12) from the RANN study, 108 individuals with autosomal‐dominant AD and their sibling non‐mutation carriers (n=71) from DIAN, and 152 amyloid‐positive subjects across the clinical AD‐spectrum from ADNI. Based on resting‐state fMRI‐assessed 400‐ROI functional connectivity matrix, we computed system segregation as the difference of within‐network and between‐network connectivity normalized to the within‐network connectivity. Higher segregation scores indicate higher segregation between the networks. In linear regression analyses, we tested whether higher system segregation was associated with 1) higher cognitive performance in elderly subjects, and 2) for AD, attenuated cognitive decline at a given level of disease severity (as measured by “estimated years from dementia symptom onset” (EYO) in autosomal‐dominant AD, and by 18F‐AV1451 tau‐PET in early‐Braak‐stage ROIs in sporadic AD).ResultIn cognitively normal subjects, higher system segregation was associated with higher composite scores of global cognition (p=0.001, Figure 1). For AD, higher system segregation was associated with an attenuated effect of disease severity on global cognition in autosomal‐dominant AD (interaction EYO by system segregation: p = 0.007, Figure 2), and an attenuated association between tau‐PET and ADAScog in sporadic AD (p=0.0009, Figure 3).ConclusionSystem segregation is associated with higher cognitive abilities in aging and enhances reserve capacity in Alzheimer’s disease.