bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chronic low‐grade inflammation predicts greater decline in verbal fluency and word‐list learning on 10 years' follow‐up
Authors: Kipinoinen Teemu , Toppala Sini , Viitanen Matti , Rinne Juha O. , Jula Antti , Ekblad Laura L. 
Published: December 2021

AbstractBackgroundProcesses leading to the clinical presentation of Alzheimer´s disease (AD) start to develop years or even decades beforehand. Chronic low‐grade inflammation is suggested to play a role in the pathogenesis of many aging‐related chronic illnesses, including AD. The aim of this study was to evaluate whether low‐grade inflammation, commonly associated with obesity and the metabolic syndrome, is associated in cognitive decline after 10 years. We hypothesized that low‐grade inflammation at midlife, estimated by tumor necrosis factor alpha (TNF‐α), Interleukin‐6 (IL‐6) and high‐sensitivity CRP (hs‐CRP), predicts cognitive decline.Method915 subjects aged 45 to 74 years (median age 54, 55% women) participated a Finnish nationwide, population‐based Health 2000 Examination Survey, its supplemental cardiovascular and metabolic examinations in 2000‐2001 and the follow‐up Health 2011 Survey. Associations between baseline low‐grade chronic inflammation and cognitive performance at follow‐up in 2011 and the change in cognition from baseline to follow‐up were evaluated. TNF‐α, IL‐6 and hs‐CRP were measured in 2001. Categorical verbal fluency (VF), word‐list learning (WLL) and word‐list delayed recall (WLDR) were used as measures of cognitive performance at baseline and at follow‐up. Statistical analyses were performed with multivariable linear models adjusted for age, sex, education, APOEε4 genotype, type 2 diabetes, hypertension, hypercholesterolemia, body mass index, depressive symptoms and smoking, and for the change in cognition also baseline cognition.ResultHigher TNF‐α and IL‐6 at baseline individually predicted poorer performance in all three cognitive tests at follow‐up (VF: TNF‐α slope:‐2.29, p=0.003, IL‐6 slope:‐1.71, p<0.0001; WLL: TNF‐α slope:‐1.02, p=0.02, IL‐6 slope:‐0.80, p=0.002; WLDR: IL‐6: slope:‐0.30, p=0.02). TNF‐α and IL‐6 predicted also a greater decline in VF (TNF‐α slope:‐1.69, p=0.009, IL‐6 slope:‐1.34, P=0.0009) from baseline to follow‐up. IL‐6, but not TNF‐α predicted greater decline in WLL (IL‐6 slope:‐0.71, p=0.02) and WLDR (IL‐6: slope:‐0.30, p=0.01). Baseline hs‐CRP was not associated with cognitive performance or decline after 10 years.ConclusionIn this middle‐aged population, low grade inflammation measured with TNF‐α and IL‐6 predicts worse cognitive performance and IL‐6 predicts greater decline in cognitive function over a 10‐year follow‐up. Potentially, developing interventions that target these inflammatory processes could help reduce cognitive decline in the future.
Effects of vitamin B12 on cognitive function in elderly patients
Authors: Kimura Atsushi Michael , Kinnno Ryuta , Tsuji Mayumi , Ono Kenjiro 
Published: December 2021

AbstractBackgroundEstablishing preventive and therapeutic methods for Alzheimer's disease (AD) is an urgent issue. Because Vitamin B12(VB12) has a neuroprotective effect on the central nervous system, it has begun to receive attention. Recently, we found that VB12 can suppress β‐amyloid toxicity in vitro. Besides, it has been reported that VB12 might be useful for keeping memory in Mild Cognitive Impairment (MCI). To clarify the effects of VB12 in AD and MCI patients, we examined the effects of the VB12 on cognitive function and regional cerebral blood flow (rCBF).MethodWe examined 46 participants who consulted to our memory clinic. They were divided into three groups: Alzheimer's disease (AD), mild cognitive impairment (MCI), and healthy controls (HC) based on the National Institute on Aging‐Alzheimer’s Association (NIA‐AA) diagnostic criteria. We used Wechsler Memory Scale‐Revised(WMS‐R) to assess the cognitive function and evaluate what kind of function is degraded. Three‐dimensional stereotactic surface projection(3D‐SSP)was used to quantify the rCBF of hippocampus, thalamus, and callosomarginal regions, which had a well‐established connection with AD. Multiple regression analysis was conducted to examine the correlations among serum VB12, WMS‐R, and rCBF in each group.ResultRegarding the correlations between VB12 and memory function, we found that the VB12 was significantly correlated with the WMS‐R scores of visual paired association I/II in the MCI group and the verbal paired associates I in the AD group (all, p<0.05). Besides, there were significant correlations between VB12 and WMS‐R scores of the visual reproduction I, logical memory I, and visual memory span in the HC group (all, p<0.05). Regarding the correlations between VB12 and rCBF, VB12 concentration was significantly correlated with the rCBF of the left hippocampal in the MCI group (all, p<0.05). Neither AD nor HC groups showed significant correlations between rCBF and VB12. Finally, the rCBF of the left hippocampus was positively correlated with visual paired association I/II(all, p<0.05).ConclusionThese results suggested that VB12 affects memory function and rCBF, especially in the MCI. Considering the relationship between WMS‐R and rCBF, VB12 may affect the progression of dementia. The early intervention with VB12 can be more effective in AD treatment strategies.
Modeling the pathological cascade of Alzheimer’s disease and related dementia markers: The MEMENTO cohort
Authors: Lespinasse Jérémie , Chêne Geneviève , Mangin Jean‐Francois , Chupin Marie , Habert Marie‐Odile , Dufouil Carole , Proust‐Lima Cécile ,   MEMENTO Cohort Study Group
Published: December 2021

AbstractBackgroundAlzheimer’s disease and related dementia (ADRD) are characterized by a progressive alteration of clinical (Cognitive and Physical functions) and subclinical (Neuroimaging, blood and CSF markers) features. Understanding the sequence and timing of these alterations is of primary importance to understand the natural history of ADRD and ultimately change its course. Pathological processes underlying ADRD evolve over years prior to dementia diagnostic on a time scale that is still hypothetical before any diagnosis is made. The objective of this work was to describe the sequence of markers changes in the Memento cohort by realigning the individual marker trajectories according to a latent disease time to overcome this issue.MethodMemento cohort is a French nationwide clinic‐based study which aims at better understanding the natural history of ADRD. Participants with mild cognitive impairment or subjective cognitive complaint were enrolled and followed‐up intensively for a maximum of 5 years. In an analytical sample of 2186 participants, we considered repeated measures of 12 ADRD markers including cognitive performances (memory, verbal fluency, executive function), neuroimaging measures (hippocampal volume, cortical thicknesses, white matter hyperintensities, glucose metabolism of region of interest of FDG‐PET), and CSF (Aβ42, p‐tau, t‐tau). We defined the latent disease time by an individual shift of the observed time, and simultaneously analyzed the ADRD marker trajectories according to this latent disease time using a multivariate mixed model adjusted on potential confounders.ResultAfter individual realignment of the trajectories according to the latent disease time, the temporal sequence of alterations suggested that neurodegeneration preceded cognitive decline. However, such sequence largely depended on education and ApoE4 status as illustrated in the figure. Cognitive decline appeared to be delayed among participants with high level of education, whereas changes in Aβ42 and tau proteins levels in CSF seemed to appear prior to neurodegeneration and cognitive decline mainly among ApoE ε4 carriers.ConclusionUsing longitudinal multidimensional data from a large cohort, we were able to stage participants along the pathological progression of ADRD. Our results show a large heterogeneity in temporal order markers changes which could suggest the existence of several subtypes of ADRD.
Plasma biomarkers distinguish clinical diagnostic groups in memory clinic patients
Authors: Gerards Michelle , Schild Ann‐Katrin , Meiberth Dix U. , Rostamzadeh Ayda , Vehreschild Jörg Janne , Wingen‐Heimann Sebastian , Adami Pamela V. Martino , Onur Oezguer A. , Ramirez Alfredo , Karikari Thomas K. , Ashton Nicholas J. , Zetterberg Henrik , Blennow Kaj , Maier Franziska , Jessen Frank 
Published: December 2021

AbstractBackgroundPlasma biomarkers as a new approach in Alzheimer’s screening and diagnostics are time‐ and cost‐saving. Blood sampling is easier, less risky, and less invasive than other well‐established diagnostic tools, such as cerebrospinal fluid biomarkers (CSF), and is well tolerated by patients. The goal of this study was to test whether and to what extent plasma biomarkers are suitable for the differentiation between the clinical diagnostic groups dementia of Alzheimer’s type (DAT), mild cognitive impairment (MCI) and subjective cognitive decline (SCD) in a routine care memory clinic.MethodWe examined plasma samples of 144 memory clinic patients. Plasma biomarkers were measured through ultrasensitive Single molecule array (Simoa) immunoassay technology. The concentrations of amyloid‐beta42 (Aß42), amyloid‐beta40 (Aß40), phospho‐Tau181 (pTau181), total‐Tau (tTau) and neurofilament‐light (NF‐L) were determined. Statistical analysis, including receiver operating characteristics (ROC) analyses, were performed. Possible cut‐off values are discussed.ResultThrough Aß40 a weak differentiation between SCD and DAT (AUC=0.64) and through Aß42/Aß40 a weak differentiation between SCD and MCI (AUC=0.64), SCD and MCI+DAT (AUC=0.66) and SCD and DAT (AUC=0.67) was possible. PTau181 was able to distinguish between diagnostic groups and showed a weak differentiation between MCI and DAT (AUC=0.69), a strong differentiation between SCD and MCI+DAT (AUC=0.78) and SCD and MCI (AUC=0.72) and an excellent differentiation between SCD and DAT (AUC=0.85). NF‐L weakly distinguished between SCD and MCI+DAT (AUC=0.70) and MCI and DAT (AUC=0.72), but strongly distinguished between SCD and DAT (AUC=0.81). At a cut‐off point of 10.2pg/ml pTau181 showed a sensitivity of 89% and a specificity of 73% to distinguish between SCD and DAT.ConclusionPlasma Aß40, Aß42/Aß40, pTau181 and NF‐L analyzed with the Simoa technology proved to be promising future diagnostic and screening tools in a routine memory clinic setting outside of specific research studies. While amyloid markers showed only moderate discrimination between the groups, pTau181 and NF‐L clearly distinguished between SCD and the more progressed stages of MCI and DAT. These findings agree with the current model of amyloid build‐up already before significant clinical symptoms, and pTau and neurodegeneration correlating with symptomatic progression. In our data, pTau181 provided the best discrimination between the diagnostic groups.
Sex differences in neuropsychiatric symptoms in Alzheimer’s disease dementia: A meta‐analysis
Authors: Eikelboom Willem S. , Pan Michel , Ossenkoppele Rik , Coesmans Michiel , Gatchel Jennifer R , Ismail Zahinoor , Lanctôt Krista L. , Fischer Corinne E. , Mortby Moyra E , van den Berg Esther , Papma Janne M. 
Published: December 2021

AbstractBackgroundAlthough the majority of individuals with Alzheimer’s disease (AD) dementia exhibit neuropsychiatric symptoms (NPS), there is substantial heterogeneity in NPS manifestation. Sex is increasingly recognized as an important factor in explaining clinical variability within AD; yet, prior studies on sex differences in NPS have reported mixed findings. Therefore, we aimed to review the existing literature on sex differences in NPS in AD dementia using a meta‐analytic approach.MethodEffect sizes were extracted from 54 studies (N=19,730; N=12,092 females [61.3%], N=7,638 males [38.7%]). Random‐effects models were used to investigate sex differences in both NPS prevalence and severity for all studies combined, NPS total scores, and for specific NPS separately. Furthermore, meta‐regression analyses were conducted to examine the effects of study characteristics and demographic and clinical variables.ResultThe majority of the included studies were of fair quality and we found no indications of publication bias. When combining all studies, female sex was associated with overall greater NPS severity (k=17, g=0.07[0.01–0.14], p<0.05), while no sex‐related differences were observed for NPS prevalence (k=41, OR =1.07[0.89–1.28], p=0.46). Meta‐regression analyses showed that younger age (QM
=6.44, p<0.05) and longer disease duration (QM
=4.27, p<0.05) were associated with more prevalent NPS for females with AD dementia. Regarding specific NPS, female sex was associated with more prevalent psychotic symptoms (k=4, OR=1.62[1.12–2.33], p<0.01), aberrant motor behaviors (AMB; k=5, OR=1.61[1.15–2.25], p<0.01), depressive symptoms (k=18, OR=1.56 [1.22–1.99], p<0.001), and delusions (k=11, OR=1.56 1.27–1.92], p<0.001). In addition, female sex was related to more severe depressive symptoms (k=10, g =0.20[0.08–0.29], p<0.001), disinhibition (k=6, g=0.16[0.03–0.28], p<0.05), and AMB (k=6, g=0.14[0.01–0.27], p<0.05).ConclusionFemale sex was associated with more severe overall and specific NPS in AD dementia and a higher prevalence of specific NPS. These associations are generally not affected by study setting, measurement type, age, education, disease duration, MMSE score, and APOE status. These findings support the existing literature on sex differences in the clinical manifestation of AD, which could reflect sex‐related differences in neurobiological and psychosocial factors. Determining sex differences in NPS may guide personalized assessment and tailored treatment.
Unravelling drivers of age‐ and beta‐amyloid‐related neurodegeneration in medial temporal lobe atrophy in cognitively normal older adults
Authors: Wuestefeld Anika , Berron David , van Westen Danielle , Stomrud Erik , Mattsson‐Carlgren Niklas , Strandberg Olof , Smith Ruben , Palmqvist Sebastian , Glenn Trevor , Hansson Oskar , Wisse Laura 
Published: December 2021

AbstractBackgroundThe medial temporal lobe (MTL) is affected in aging and dementia. Aging, small vessel disease, β‐amyloid, tau pathology, and inflammation are hypothesized to play a role in neurodegeneration, but their interplay is still unclear. We investigate potential MTL atrophy mediators of (1) Aβ‐related effects in cognitively normal older adults and (2) aging effects in a β‐amyloid negative (A‐) subgroup.Method401 adults (41‐91 years) from the Swedish BioFINDER‐2 study were included ([mean±SD] 65.5±11.7 years; A‐ n=274, 62.7±11.8 years). Using the Automated Segmentation for Hippocampal Subfields for T1‐ and T2‐weighted MRI, hippocampal subfield volumes (dentate gyrus (DG), subiculum (Sub), cornu ammonis (CA) 1) and thickness of entorhinal cortex (ERC), Brodmann areas (BA) 35/36, and parahippocampal cortex (PHC) were obtained. [18F]RO948‐ and [18F]Flutemetamol‐PET standard uptake value ratios were calculated for mean MTL tau (excluding hippocampus; partial volume corrected (PVC)) and global Aβ (with and without PVC). White matter lesions (WML; log‐transformed) to estimate small vessel disease and cerebrospinal fluid (CSF) Glial fibrillary acidic protein (GFAP) to estimate neuroinflammation were analyzed. Both global Aβ‐PET and CSF Aβ‐42/40 ratio determined amyloid‐β status.ResultAll predictors were negatively associated with Sub volume and BA35/PHC thickness in the whole sample, with roughly similar results for the A‐ subgroup (Table 1, Fig. 1). PVC global Aβ‐PET showed similar results. Mediation analyses therefore focus on these three regions. In the whole sample, MTL tau‐PET and GFAP fully mediated the associations between global Aβ‐PET and Sub/BA35/PHC (Fig. 2). When including age in the model only MTL tau‐PET, not GFAP, remained a significant mediator for Sub.In the A‐ group, MTL tau‐PET partially mediated the age‐Sub/BA35 associations. These mediations survived adjusting for Aβ, except for BA35 (p=.054). Global WML partially mediated the age‐PHC association (Fig. 3). No other predictors were significant mediators.ConclusionAs expected, global Aβ‐PET‐associated neurodegeneration is mediated by MTL tau pathology, but, interestingly, also potentially by inflammation.MTL tau pathology and small vessel disease seemingly drive age effects on the MTL, but in different MTL regions. The mediating effect of MTL tau is supportive of a role for Primary Age‐Related Tauopathy in age‐related neurodegeneration.
Neurocognitive effects of acupuncture in dementia: A brief literature review
Authors: Nicanord Ernst J , Raji Mukaila 
Published: December 2021

AbstractBackgroundDementia, including Alzheimer’s disease, is one of the biggest global public health challenges that stretches through generations. Given the limitations of current pharmacologic interventions, acupuncture has been proposed as a potential alternative to dementia therapy. We review the literature to find studies that illustrate the effects of acupuncture on mild cognitive impairment (MCI), post stroke cognitive impairment (PSCI), Vascular dementia (VD), and Alzheimer’s disease (AD).MethodFive databases, including PubMed, Cochrane database, Google Scholar, CINAHL, and Trip database were searched for Keywords: acupuncture OR acupuncture treatment OR acupuncture therapy and mild cognitive impairment OR dementia OR vascular dementia OR poststroke dementia. Articles’ titles and abstracts were reviewed and selected according to their relevance for this review. Most of the selected papers were systematic reviews (SR) and meta‐analysis dated to 2020 publication. Only randomized controlled trials (RCTs) that are not included in the selected systematic reviews are selected for this review.ResultOf the selected articles, two studies found acupuncture could offer an alternative to conventional treatment of MCI. Three studies showed some cognitive benefits including, improving functional communication and language function in PSCI. One study found that acupuncture might stimulate neurogenesis after a stroke. One RCT revealed acupuncture with routine care may improve cognitive status and activities of daily living (ADLs) but has limited effects on quality of life in those with VD. Four studied showed mixed results of acupuncture in AD. No major adverse reactions from acupuncture were reported.ConclusionAcupuncture may improve cognitive function in those with MCI and PSCI. For VD and AD, the evidence is still lacking. More well‐structured, large scale double blinded RCTs are needed with more focus on the different stages of AD.
Alzheimer’s disease prevention: Within reach by 2025
Authors: Vitali Francesca , Branigan Gregory L , Brinton Roberta Diaz 
Published: December 2021

AbstractBackgroundAlzheimer’s disease (AD) is a progressive neurodegenerative disease that affects memory and cognition. Symptoms and onset of AD occur up to 20 years after potential alterations in biology, allowing for a tremendous potential to intervene in disease progression to change the AD course. In 2015, the National Plan to Address Alzheimer Disease as part of the National Alzheimer’s Project Act was signed into law which proposed to effectively prevent AD by 2025 sparking new interested in the clinical and research field to achieve these goals.MethodWe used a novel combination of text‐mining and natural language processing strategies to identify (i) AD risk factors, (ii) therapeutics that can target risk factor pathways and (iii) studies supporting therapeutics in the currently published PubMed database. To classify the literature relevant to AD preventive strategies, we developed a relevance score based on STRING score for protein‐protein interactions and a confidence score on Bayesian inference. This led to generation of a ranked list of candidate therapeutics to reduce AD risk.ResultBased on our strategy, 364 AD risk factors were identified mining 9,625 publications. Next, using drug databases, 694 FDA‐approved drugs were selected based on drug indications with a given risk factor. The computation of ranking scores enabled exclusion of publications that did not meet inclusion criteria and rank 45 drugs associated with reduced risk. Within this list, 22 therapeutics had at least one clinical study supporting AD risk reduction. The top 20 therapeutics included drugs within the categories of lipid‐lowering, anti‐inflammatory, anxiety/psychiatric, and metabolic‐related therapeutics.ConclusionOutcomes of our novel bioinformatic strategy supports therapeutic targeting of biological mechanisms and pathways underlying AD risk factors. Based on our analyses, we propose that early interventions that target pathways associated with increased risk of AD has the potential to achieve the goal of effectively preventing AD by 2025.
The impact of the first wave of the COVID‐19 pandemic on health service use by persons with dementia in Ontario, Canada: A population‐based time series analysis
Authors: Bronskill Susan E , Maclagan Laura C , Wang Xuesong , Guan Jun , Harris Daniel A , Austin Peter C , Maxwell Colleen J , Jaakkimainen Liisa , Iaboni Andrea , Marras Connie , Vedel Isabelle , Sourial Nadia , Godard‐Sebillotte Claire , Swartz Richard H 
Published: December 2021

AbstractBackgroundLittle has been quantified, at a population‐level, about the magnitude of heath service disruption to persons living with dementia in community settings during the COVID‐19 pandemic. Sustained access to health care services is particularly important for persons with dementia and other neurodegenerative diseases as they are vulnerable to decline.MethodHealth administrative data from Ontario, Canada were used to examine patterns of health service use among all persons with Alzheimer disease and related dementias (dementia) who were alive and living in the community. This cohort was compared to persons with Parkinson’s disease (PD) as well as all older adults (age 65+ years) without neurodegenerative diseases. Rates of all‐cause hospital admissions, emergency department visits, primary care and specialist physician visits and home care visits were analyzed for all individuals alive and eligible for provincial health insurance at the start of each weekly period from March 1, 2020 to September 20, 2020 (pandemic period) and from March 3, 2019 to September 22, 2019 (pre‐pandemic period). Rates of health service use during specific weeks in the pandemic period (i.e., lowest week, last available week) were compared to corresponding weeks in the pre‐pandemic period within each cohort using percent changes.ResultsOn March 1, 2020, 128,696 persons with dementia, 30,099 with PD and 2,460,358 older adults were eligible for provincial health services. Across cohorts and services, dramatic declines in use of health services were observed at the lowest week: hospitalization (‐38.7% dementia, ‐72.3% PD, ‐44.2% older adults); emergency department (‐54.9% dementia, ‐57.7% PD, ‐53.6% older adults); home care (‐14.8% dementia, ‐19.4% PD, ‐7.4% older adults). Health services varied in how quickly they rebounded to pre‐pandemic levels within cohorts; notably, by the end of the study period, emergency department visits had increased to a level higher than corresponding 2019 weekly rates (24.2% dementia, 15.2% PD, 7.4% older adults).ConclusionsThe first wave of the COVID‐19 pandemic meaningfully and immediately disrupted use of health care services for persons living with dementia and PD and may have resulted in long‐term consequences that should be monitored.