bluuebunny/crossref_metadata_2025_split huggingface dataset:
Creatinine and body mass index influence on plasma amyloid ratio, p‐tau217 and neurofilament light
Authors: Binette Alexa Pichet , Janelidze Shorena , Cullen Nicholas , Mattsson‐Carlgren Niklas , Hansson Oskar 
Published: December 2021

AbstractBackgroundWith the advent of blood‐based biomarkers, it is important to consider whether measurements of such markers are affected by factors related to blood filtration or volume. Previous studies suggested that amyloid‐beta (Aβ) and neurofilament light (NfL) measured in blood are related to creatinine levels. Here we first investigated whether creatinine and body mass index (BMI) were related to various blood‐based biomarkers, and then evaluated whether these markers affected the associations between plasma and cerebrospinal fluid (CSF), or conversion to dementia.MethodParticipants with plasma, CSF, creatinine, and BMI data from BioFinder1 (n=748) and BioFinder2 (n=560) cohort were included in the study and analyzed separately (Table 1). In both cohorts, the plasma and CSF biomarkers of interest were Aβ42/Aβ40, p‐tau217, and NfL. Linear regression models were first used to assess plasma associations with BMI and creatinine. Subsequent models compared whether plasma estimates predicting corresponding CSF levels or conversion to dementia within a 4‐year period (BioFinder1 only) were improved if creatine and BMI were added as covariates.ResultIn both cohorts, creatinine levels were positively correlated with plasma p‐tau217 and NfL, while BMI was negatively correlated with the same markers. No associations were found with the Aβ42/Aβ40 ratio (Table 2). In both cohorts, looking at plasma‐CSF associations, plasma NfL coefficients were significantly higher in models including creatinine and BMI as covariates, but plasma p‐tau217 coefficients were unchanged (Figure 1). For Aβ42/Aβ40, only in BioFinder2 was the plasma estimate higher with creatinine and BMI as covariates. In BioFinder1, where longitudinal data was available, plasma p‐tau217 and NfL estimates were somewhat higher in discriminating participants who developed AD or any cause dementia respectively when including creatinine and BMI as covariates (Figure 2; AUC change of only 0.01).ConclusionIn two cohorts covering the full spectrum of AD, creatinine and BMI were related to plasma levels of almost all markers. BMI and creatinine improved some plasma estimates of associations with the CSF counterparts and conversion to dementia, but to a low magnitude. Although creatinine and BMI relate to plasma levels, the clinical relevance of including such factors seems to be minor.
Corneal nerve fiber measures independently predict progression from MCI to dementia: Follow‐up of the Qatar Longitudinal Study Cohort
Authors: Ponirakis Georgios , Malik Rayaz A 
Published: December 2021

AbstractBackgroundThere is an urgent need for biomarkers of neurodegeneration to identify individuals with MCI at higher risk for developing dementia. Corneal confocal microscopy (CCM) is a non‐invasive imaging biomarker which has identified corneal nerve loss in individuals with mild cognitive impairment (MCI) and dementia. This study assessed the predictive capability of CCM and MRI brain volumetry for progression from participants with MCI to dementia.MethodIn this prospective study, participants aged 50‐85 with MCI underwent assessment of clinical dementia rating (CDR), Montreal cognitive assessment (MoCA), MRI brain volumetry and CCM at baseline and CDR and MoCA at 1‐4 year follow‐up.ResultThe study cohort comprised 107 participants with MCI aged 68.4±7.7 years. Over a median follow‐up of 2.4 years, 33 of 107 participants (30.8%) with MCI progressed to dementia. Corneal nerve fibre density (P<0.0001), branch density (P<0.0001) and length (P<0.0001) were significantly lower in MCI participants who progressed to dementia. Reduced baseline corneal nerve fiber density (≤25 fiber/mm2), length (≤15 mm/mm2) and branch density (≤44 branches/mm2) accurately predicted future dementia (area under the curve (AUC) = 71‐74%, P≤0.0001). Reduced baseline intra‐cranial volume percentage (ICV %), hippocampus (≤0.44%), whole brain (≤69.4%), frontal lobe (≤10.8%), amygdala (≤0.17%), cortical gray matter (≤29%), thalamus (≤0.90%) and increased ventricle (≥3.0%) volume predicted future dementia (AUC = 65‐78%, P<0.05), whilst temporal, parietal, occipital lobe, entorhinal cortex, cingulate gyrus and brainstem did not. The adjusted odds ratios (AOR) for progression to dementia were 5.1‐11.1 times higher with abnormal corneal nerve fiber measures (P<0.05), 5.9 higher with abnormal hippocampal volume (P<0.05) and 10.8 times higher with whole‐brain volume (P<0.05).ConclusionThe predictive capability of CCM is comparable to hippocampal and whole brain volume for progression to dementia in individuals with MCI.
Adiponectin as a biomarker in dementia: A systematic review and meta‐analysis
Authors: Salcido‐Montenegro Alejandro , Quintanilla‐Sanchez Carolina , Nañez‐Terreros Homero 
Published: December 2021

AbstractBackgroundAlzheimer disease (AD) and Vascular dementia (VaD) are the most common causes of dementia. At mild stages, clinical differentiation is frequently not possible, creating the requirement of complex laboratory test and imaging technique that may not be available worldwide. Therefore, more practical, and effective biomarkers are need. Serum adiponectin is a modulating hormone of vasculature structure and function. Altered serum adiponectin levels had been reported in patients with AD and VaD compared to controls. To determine if serum adiponectin levels could be used to differentiate between AD and VaD, we conducted a systematic review and meta‐analysis.MethodA systematic review following PRISMA guidelines was conducted. The search strategy included terms related to dementia and adiponectin and was conducted in 4 databases (MEDLINE, Ovid, Scopus, and EMBASE) up until April 2021. The studies were screened by 2 authors in a two‐step approach. Original studies comparing serum adiponectin between AD and VaD patients were included. Risk of bias was assessed using QUADAS. In the meta‐analysis, we compared the mean difference values of adiponectin between AD and VaD patients.ResultA total of 917 studies were screened. After applying eligibility criteria, 72 studies were fully screened, and 3 articles were reviewed and included in the meta‐analysis. A total of 454 patients with AD and 148 with VaD were analyzed. Although patients with AD have slightly higher mean adiponectin values than VaD patients, there were no statistically significant differences (mean difference, 1.61, 95% CI ‐0.61 to 3.84; P=0.16, I2
=96%) (Fig. 1). The main risk of bias concerns was the retrospective study design in most of the studies, the heterogeneity in dementia diagnosis, and the lack of report and consideration of factors that could alter adiponectin.ConclusionThere was no difference in the serum adiponectin levels between patients with AD and VaD. Nevertheless, factors that could alter serum adiponectin such as metabolic comorbidities (e.g., hypertension, type 2 diabetes, cardiovascular disease), weight and medicaments were not considered when comparing adiponectin levels between AD and VaD patients. Hence, further studies should account and adjust for these factors when comparing serum adiponectin in different types of dementia.
Falls risk among high‐ and low‐ frequency sleep medication users with and without dementia
Authors: Anderson Loretta R , Wennberg Alexandra MV 
Published: December 2021

AbstractBackgroundSleep disturbances and falls are common in older adults, particularly in people living with dementia (PLWD). Increasing sleep disturbances occur with increasing age (M. Ohayon, 2002), and one third of those 65 and older experience falls at least once per year (World Health Organization, 2007). Sleep medication use is associated with falls in older adults, but little is known about its impact in PLWD. This study seeks to determine if there is a differential association between high‐ and low‐ frequency sleep medication use among those with and without dementia.MethodUsing data from the 2011 National Health and Aging Trends Study (n=8,245), we used logistic regression models to examine the association of high‐ versus low‐ frequency sleep medication use with falls in community‐dwelling older adults with and without self‐reported dementia.ResultIn our fully adjusted model, PLWD (n=176), high‐frequency sleep medication users were more likely to fall than low‐frequency sleep medication users (OR=3.86, 95% CI: 1.31, 11.37). Among those without self‐reported dementia (n=6,658), high‐frequency sleep medication users were more likely to fall than low‐frequency sleep medication users (OR=1.40, 95% CI: 1.11, 1.77).ConclusionAfter controlling for potential confounders, PLWD who have high ‐ frequency sleep medication use are almost 4 times more likely to experience falls than PLWD who have low‐frequency sleep medication use. Reducing sleep medication use in older adults with and without dementia may help reduce the risk of falls and fall‐related outcomes in older adults. Future studies to examine sleep medication alternatives are warranted.
Preliminary assessment of the clinical effects of lecanemab following 18 months of treatment in the open label extension of the phase 2 proof of concept study, BAN2401‐G000‐201, in subjects with early Alzheimer’s disease
Authors: Swanson Chad J , Dhadda Shobha , Irizarry Michael C , Kanekiyo Michio , Li David JianJun , Kaplow June , Gordon Robert , Heanue‐Travers Helena , Hodgkinson Mark , Kramer Lynn D 
Published: December 2021

AbstractBackgroundLecanemab (BAN2401) is a humanized IgG1 monoclonal antibody that preferentially targets soluble aggregated Aβ species (oligomers, protofibrils) and insoluble fibrils. Lecanemab reduced amyloid and slowed clinical decline in an 18‐month Phase 2 proof of concept study in early Alzheimer’s disease (Alz Res Therapy 13; 2021). An Open label extension (OLE) with 10 mg/kg IV biweekly lecanemab dosing was implemented after analysis of the Core study, with an intervening gap period off‐treatment ranging from 9‐54 months (mean 24 months). The present study assesses longitudinal clinical status (CDR‐SB, ADAS‐cog, ADCOMS) for subjects completing the Core and 18 months of treatment in OLE.MethodAt entry into the core study, subjects were required to have early AD (amyloid positive) with global CDR of 0.5 or 1. MMRM analyses modeled clinical scales across the Core, variable gap period off lecanemab, and the OLE period. Analyses were stratified based on subjects who were: (1) global CDR ≤1 at OLE baseline; or (2) who had progressed beyond the early AD stage to CDR global >1 by OLE baseline.ResultIn subjects with global CDR ≤1 at OLE baseline, lecanemab treatment differences relative to placebo observed after 18 months of treatment in the Core were maintained at a 3 month (off drug) follow‐up visit and at the end of the gap period (OLE baseline). In the gap period, the rates of progression were similar between those treated with lecanemab and placebo in the core period. Clinical progression in the OLE appeared to plateau with lecanemab treatment among those who were global CDR ≤1 at the OLE baseline, while those who were global CDR >1 continued to progress.ConclusionClinical data from the gap period suggest that subjects may need continued treatment with lecanemab, even though amyloid PET and plasma biomarker findings indicate amyloid has been removed. Apparent differences in clinical progression between those with global CDR ≤1 and those with global CDR >1 suggest the hypothesis that early AD subjects may be more likely to benefit from treatment. These concepts will be further explored in ongoing Phase 3 lecanemab clinical trials.
Lipophilic statins in cognitively normal subjects: Associations with conversion to mild cognitive impairment in a long‐term longitudinal multi‐center study
Authors: Padmanabham Prasanna S , Liu Stephen , Silverman Daniel H 
Published: December 2021

AbstractBackgroundStudies of the relationship between the use of statins (HMG‐CoA reductase inhibitors) and subsequent cognitive performance have been variously reported to demonstrate beneficial, harmful, or no significant effects. We aimed to help clarify the relationship between statin use and long‐term trajectory in subjects cognitively normal at baseline, comparing users of statins with known moderate (atorvastatin) or high (simvastatin) lipophilicity and blood‐brain barrier penetrance (LS), to non‐users (nonS), or users of other statins (OS).MethodFrom a consecutive series of 2305 subjects enrolled in the Alzheimer’s Disease Neuroimaging Initiative, 69 were excluded for taking combination statin drugs. Excluding statin users with less than 66 months of usage resulted in 340 CN subjects ( 189 nonS, 121 LS, and 30 OS) who were further studied. Subjects were stratified into groups with low (<175mg/dl), medium (175‐207mg/dl), or high ( ≥207mg/dl) baseline cholesterol levels. The significance of differential conversion rates was assessed by Chi‐Squared tests for homogeneity. Survival trajectories were created using the Kaplan‐Meier method, where an event was defined as conversion to mild cognitive impairment (MCI), and the significance of difference was assessed by the log‐rank test.ResultWhile serum cholesterol levels at baseline ranged widely (112‐174 mg/dl), among 112 subjects with low baseline cholesterol, levels did not significantly differ between those who did convert to MCI within 72 months (157 mg/dl) vs. those who did not (155 mg/dl), but their rates of conversion to MCI significantly differed according to LS use: 39.5% among LS vs. 14.8% among nonS+OS converted (p=0.025). The 6‐year event‐free survival of the nonS+OS group (88.7%; 95% CI 0.785‐1) and the LS group (64.0%; 95% CI 0.519‐0.789) also differed significantly (p=0.019). LS usage was associated with an increased absolute (+24.7%) and relative (+167%) risk.ConclusionLipophilic statin use was associated with more than double the risk of declining to MCI over 72 months of follow‐up in cognitively normal patients with low baseline cholesterol. In separate analyses, no such risk was observed among other statin users, nor among subjects with medium or high baseline cholesterol levels.
Non‐alcoholic fatty liver disease, liver fibrosis and patterns of regional amyloid and tau pathology in middle‐aged adults: The Framingham Study
Authors: Weinstein Galit , O’Donnell Adrienne , Zelber‐Sagi Shira , Beiser Alexa S , Seshadri Sudha 
Published: December 2021

AbstractBackgroundNonalcoholic fatty liver disease (NAFLD) is the most common chronic liver condition. Accumulating evidence points to an association of NAFLD with cognitive impairment, brain aging and decreased brain activity, yet the association with Alzheimer’s disease is unclear. Evidence suggests that liver fibrosis, rather than the existence of hepatic steatosis per se, is a strong prognostic factor for long‐term extra‐hepatic complications. We examined whether NAFLD and risk for advanced fibrosis assessed using a non‐invasive index, are associated with in vivo quantification of brain amyloid and tau pathology.MethodThe study sample included participants from the Offspring and Third generation of the Framingham Study. We included participants who underwent positron emission tomography (PET) imaging for assessment of amyloid and tau deposition who do not consume excessive amount of alcohol. Additionally, we included those with information on NAFLD from CT imaging (n=169) or those with all components of the FIB‐4 index (i.e. age, platelets count, aspartate aminotransferase and alanine aminotransferase; n=177). Linear regression models were performed to assess the relationship of NAFLD and risk of advanced fibrosis with amyloid FLR and amyloid and tau regional measures, adjusting for age, sex, time between exposure and PET, and camera, and additionally for body mass index, alcohol consumption, systolic blood pressure, smoking, cardiovascular disease, physical activity, C‐reactive protein, cholesterol, insulin resistance, diabetes, hypertension and visceral adipose tissue.ResultOf the subsample with NAFLD information (mean age 52±9y; 57% males), 57 (34%) had NAFLD. Prevalent NAFLD was not associated with PET amyloid and tau. Of the subsample with information on liver fibrosis (mean age 50±10y; 51% males), 34 (19%) had increased risk of advanced fibrosis (FIB4>1.3). One unit increment of FIB‐4 index (but not advanced fibrosis) was significantly associated with increased tau in the inferior temporal, parahippocampal, entorhinal and rhinal brain regions (table 1). Among individuals with prevalent NAFLD (n=57), liver fibrosis (both continuous and using the 1.3 cutoff) was related to all amyloid and tau measures except for entorhinal amyloid (table 2).ConclusionThis pioneering study suggests a possible association between liver fibrosis and early Alzheimer’s disease markers, independently of vascular risk factors.
The significance of reticulon‐4A in Parkinson’s disease
Authors: Mroczko Barbara , Kulczynska‐Przybik Agnieszka , Mroczko Piotr , Dulewicz Maciej , Borawska Renata , Slowik Agnieszka 
Published: December 2021

AbstractBackgroundParkinson's disease (PD) is one of the most common causes of dementia worldwide. Cognitive impairment resulting from the development of PD is important not only from a medical but also from a legal point of view. It can affect a person's ability to fully control their behavior and make rational decisions also concerning medical procedures. Consent for the performance of clinical procedures, such as the collection of cerebrospinal fluid by lumbar puncture are regulated by the norms of medical law. This has a significant impact on the patient's criminal responsibility. It is suggested that Reticulon‐4A (RTN4‐A) plays a pivotal role in PD. The myelin‐associated protein Nogo‐A is classified as the potent neurite growth inhibitor, which also takes part in regeneration following injury of the central nervous system. It has been demonstrated that RTN4‐A regulates the neurotoxicity in PC12 cells, commonly used in vitro PD model, via the mTOR/STAT3 signaling pathway. However, little is known about the changes of RTN4‐A levels in CSF patients with PD. Therefore, the purpose of the present study was to measure RTN4‐A levels in the cerebrospinal fluid (CSF) patients with PD and subjects from control group. We also evaluated a relationship between CSF concentrations of RTN4‐A and other markers indicating development of the dementia disorder.MethodThe concentrations of RTN4‐A and amyloid beta 1‐42 (Aß‐42), amyloid beta 1‐40, Tau, as well as pTau181 were measured in 34 subjects, including 18 PD patients and 16 individuals from control group by means of quantitative enzyme‐linked immunosorbent assay (ELISA).ResultThe CSF concentration of RTN4‐A was significantly higher in PD group in comparison with cognitively normal individuals. Furthermore, in group of patients with PD it was observed statistically significant lower CSF levels of Aß‐42 than in control group. Additionally, the CSF levels of RTN4‐A significantly correlated with tau proteins and age in whole study group.ConclusionOur preliminary study indicates a potential role of RTN4‐A protein in the pathology of PD and its potential usefulness as a candidate biomarker of PD, but these investigations need to be further clarified using a larger study group.
The association between sleep apnea and neurodegenerative disorders: A systematic review and meta‐analysis with an emphasis on precision‐medicine
Authors: Guay‐Gagnon Martin , Desmarais Philippe 
Published: December 2021

AbstractBackgroundPrevious meta‐analyses that assessed the possible link between sleep apnea (SA) and dementia included cohorts with patients having self‐reported diagnoses of SA as exposures and nonspecific cognitive diagnoses as outcomes, undermining clinical implications. We aimed to assess the association between SA and specific neurodegenerative causes of dementia and to review the use of precision‐medicine tools supporting clinical diagnoses in studies.MethodWe performed a systematic review and meta‐analysis in conformity with the PRISMA guidelines. Two investigators searched the Web of Science Core Collection databases from inception to March 1st, 2021. Cohort studies were included if they: 1) used either polysomnography (PSG) or International Classification of Diseases (ICD) codes for SA diagnosis, and 2) measured the risk of all‐cause dementia, mild cognitive impairment, Alzheimer’s disease (AD), vascular dementia (VaD), Parkinson’s disease (PD), Lewy body dementia (LBD), frontotemporal dementia (FTD), and/or mixed dementia. The use of biomarkers to support clinical diagnoses in eligible studies was collected. Studies of cross‐sectional design, that used self‐administered questionnaires for the diagnosis of SA, or that measured solely cognitive scores as outcomes were excluded. Pooled analyses of hazard ratios (HR) were obtained for every type of dementia using a random effects model.ResultAmong the 1,191 records identified, 8 studies were included, representing a total of 1,249,975 patients. Patients with SA had a 43% increased risk of developing any of the aforementioned types of dementia (HR: 1.43 [1.26‐1.62], 95% CI). They were 34% more likely to develop all‐cause dementia (HR: 1.34 [1.15‐1.57], 95% CI), 28% more likely to develop AD (HR: 1.28 [1.16‐1.41], 95% CI) and 54% more likely to develop PD (HR: 1.54 [1.30‐1.84], 95% CI). No statistically significant association was found with VaD. One study reported a two‐fold increased risk of LBD with SA. No study used biomarkers such as regional cortical atrophy on brain imaging or genetic testing. Results remained consistent after sensitivity analyses.ConclusionWhile SA appears to be associated with an increased risk of all‐cause dementia, notably for AD, PD and LBD, future studies will have to be conducted using more rigorous precision‐medicine tools in order to better characterize the specific associations between these conditions.