bluuebunny/crossref_metadata_2025_split huggingface dataset:
The difference in apathy estimates between the patient and caregiver predicts dementia in individuals with amnestic MCI
Authors: Massa Federico , Grisanti Stefano Giuseppe , Chincarini Andrea , Pretta Stefano , Rissotto Roberto , Serrati Carlo , Monacelli Fiammetta , Serafini Gianluca , Calcagno Pietro , Brugnolo Andrea , Pardini Matteo , Nobili Flavio , Girtler Nicola ,   Dementia Disease Management Team# of the IRCCS Ospedale Policlinico San Martino (Genoa, Italy)
Published: December 2023

AbstractBackgroundIn Alzheimer’s disease, apathy is a common behavioral sign (AD). The Apathy Evaluation Scale (AES) is a measure that investigates caregivers' (CG‐AES) and patients' (PT‐AES) perceptions of apathy, and the discrepancy in their evaluations is a proxy for patients' illness unawareness. We aimed to determine whether apathy and awareness of apathy predict dementia development and timing in a cohort study of individuals with amnesic mild cognitive impairment (aMCI).MethodWe acquired two main indices for analysis from the global AES scores of 110 patients with aMCI and their caregivers: i) ‘Apathy,’ the mean of PT‐AES and CG‐AES, and ii) ‘Discrepancy,’ obtained by subtracting CG‐AES from PT‐AES. Patients were seen every six months for three years, or until they developed dementia. The AES indices and the major demographical/neuropsychological variables were filtered for multicollinearity, and the most robust variables were entered into a logistic regression model and survival analyses (Cox regression, log‐rank test of Kaplan‐Meier curves) to estimate which variables predicted the risk and timing of progression, respectively.Result60 patients (54.5%) showed signs of dementia (57 AD) after 6.0‐36.0 months, whereas 28 patients (25.5%) dropped out and 22 patients (20%) were still in an MCI stage. The “Discrepancy” index was a reliable and accurate predictor of the probability of progression (AUC = 0.73) and, after binarization in accordance with a calculated cutoff, of the time to dementia.ConclusionA structured assessment of apathy, both by the patient and by the caregiver, can reveal important details about the likelihood and timing of the transition from aMCI to dementia. The difference between the two estimations serves as a reliable predictor of illness unawareness by patients.
Standard resting state electroencephalographic power density computed from posterior bipolar channel characterizes patients with Alzheimer’s disease
Authors: Lizio Roberta , Percio Claudio Del , Lopez Susanna , Tucci Federico , Noce Giuseppe , Güntekin Bahar , Yener Görsev , Babiloni Claudio 
Published: December 2023

AbstractBackgroundAbnormalities in cortical sources of resting‐state eyes closed electroencephalographic (rsEEG) rhythms recorded by hospital settings (10‐20 montage) with 19 scalp electrodes characterized Alzheimer’s disease (AD) from preclinical to dementia stages. An intriguing rsEEG application is the monitoring and evaluating of AD progression in large populations with few electrodes in low‐cost devices. Here we assessed whether the above‐mentioned abnormalities could be observed from fewer scalp electrodes in patients with mild cognitive impairment (ADMCI) or dementia (ADD) due to AD.MethodClinical and rsEEG data acquired in hospital settings (10‐20 montage) from 88 ADD and 75 ADMCI participants and 70 age‐, education‐, and sex‐matched normal elderly controls (Nold) were available in an Italian‐Turkish archive (PDWAVES Consortium; www.pdwaves.eu). Standard spectral Fast Fourier Transform (FFT) analysis of rsEEG data for individual delta, theta, and alpha frequency bands was computed from 6 monopolar scalp electrodes to derive bipolar C3‐P3, C4‐P4, P3‐O1, and P4‐O2 markers.ResultThe ADMCI and ADD groups showed increased delta/alpha and theta/alpha power density at the C3‐P3, C4‐P4, P3‐O1, and P4‐O2 bipolar channels compared to the Nold group (Figure 1). The best classification accuracy (area under the receiver operating characteristic curve) between the ADD and ADMCI vs Nold individuals was reached using alpha2/theta power density computed at the C3‐P3 bipolar channel (AUROC for ADMCI vs Nold = 81%; AUROC for ADD vs Nold = 90%; Figure 2).ConclusionStandard rsEEG power density computed from six posterior bipolar channels characterized AD status from preclinical to dementia stages. These results may pave the way toward diffuse clinical applications in the health monitoring of dementia using low‐cost EEG systems with a strict number of electrodes in lower‐ and middle‐income countries.
Brain and Neural Reserve Mediate Associations Between Lifestyle and Cognition: The Maastricht Study
Authors: De Jong Nathan R. , Jansen Jacobus F.A. , van Boxtel Martin P.J. , Schram Miranda T. , Stehouwer Coen D.A. , van Greevenbroek Marleen M.J. , van der Kallen Carla J.H. , Koster Annemarie , Eussen Simone J.P.M. , de Galan Bastiaan B.E. , Backes Walter H. , Köhler Sebastian 
Published: December 2023

AbstractBackgroundLife‐course exposure to risk and protective factors impacts brain macro‐ and micro‐structure, which in turn affects cognition. Brain Age Gap (BAG) directly measures brain reserve by comparing an individual’s neuroimaging‐based predicted age with their calendar age. Higher BAG implies accelerated brain aging and lower brain reserve. In this study, we comprehensively modeled mutual associations between brain risk and protective factors, reserve, and cognition in a large, middle‐aged population using structural equation modelling (SEM).MethodsCognitive test scores, lifestyle, and 3T MRI data for n = 4881 participants (mean age(±SD) = 59.2(±8.6), 50.1% male) were available from The Maastricht Study, a population‐based cohort study with extensive phenotyping. Whole brain volumes (gray matter (GM), cerebrospinal fluid (CSF), white matter hyperintensity (WMH)), cerebral microbleeds (CMB), and structural white matter connectivity were calculated. Lifestyle factors were combined into the Lifestyle for BRAin health (LIBRA) weighted sum score, with higher score indicating greater dementia risk (Figure 1). Cognition was calculated by averaging z‐scores across three cognitive domains (executive function and attention, memory, information processing speed). BAG was calculated by comparing calendar age to predictions from a neuroimaging‐based multivariable regression model. Paths between LIBRA, BAG and cognitive function were tested using linear regression and SEM, adjusting for confounders. LIBRA was split into tertiles for SEM analysis.ResultsCSF, GM, WMH and CMB best predicted BAG (R2 = 0.455, RMSE = 6.44). In regression analysis higher LIBRA scores (greater dementia risk) were associated with higher BAG (standardized regression coefficient ß = 0.127, p<0.001), lower connectivity (ß = ‐0.071, p = 0.002) and worse cognition (ßlinear = ‐0.044, p = 0.017, ßquadratic = ‐0.047, p = 0.018). Higher BAG was associated with lower connectivity (ß = ‐0.418, p<0.001) and worse cognition (ß = ‐0.165, p<0.001). Lower connectivity was associated with worse cognition (ß = 0.086, p<0.001). In mediation analysis (Figure 2), 21% of the total differences between the highest and lowest LIBRA tertile on cognition was mediated by BAG (ßindirect = ‐0.019, p<0.001; ßtotal = ‐0.092, p<0.001), and an additional 4.1% was mediated via connectivity (ßindirect = ‐0.003, p<0.001; ßtotal = ‐0.073, p<0.001).ConclusionAssociations between health‐ and lifestyle‐based risk/protective factors (LIBRA) and cognition is partially explained by maintenance of brain reserve (BAG) and neural reserve (connectivity). Lifestyle interventions promoting brain and neural reserve may help maintain cognitive function into older age.
Associations of adherence to a dietary index based on the EAT–Lancet reference diet with cognition, brain volumes, and ecological sustainability parameters: Results from the Rhineland Study
Authors: Tavares Juliana F. , Conzen Christina‐Alexandra , Estrada Santiago , Etteldorf Rika , Landstra Elvire Nadieh , Boenniger Meta M. , Nöthlings Ute , Breteler Monique M.B. 
Published: December 2023

AbstractBackgroundFood systems play a major role in both human and planetary health. In 2019, the EAT‐Lancet Commission proposed a universal, healthy reference diet, intending to improve environmental sustainability and prevent non‐communicable diseases (Willet et al, 2019). Adherence to the EAT‐Lancet reference diet (ELR‐diet) has been previously associated with lower cardiometabolic diseases and mortality risk (Knuppel et al, 2019; Stubbendorff et al, 2022). However, the effects of the ELR‐diet on brain‐related outcomes remain largely unexplored. Therefore, we quantified the ELR‐diet adherence and its associations with cognitive function, brain structures and ecological sustainability parameters in a population‐based German cohort.MethodsOur study population consisted of Rhineland Study participants with complete dietary assessment at baseline. We used a semi‐quantitative food frequency questionnaire to estimate ELR‐diet adherence through a 14‐item composite index, based on the EAT‐Lancet Commission recommendations. Diet‐related greenhouse‐gas emissions (GHGEs) and land use (LU) were calculated on the basis of each participant’s total food intake, expressed as kgCO2 equivalents and m2×year, respectively. Cognitive performance was measured in multiple domains (processing speed, executive function, working and episodic verbal memory). These domains were summarized using z‐score averaging, producing a global cognitive function and a total memory score (n = 7017, age 56.2±13.4 years). Brain volumetric measures (total brain, white and grey matter, cortex and hippocampus) were obtained from available T1‐MRI scans (n = 5184, age 55.9±13.4 years) using Freesurfer. We quantified the relationship between ELR‐diet adherence and the outcomes using multivariate linear models adjusted for age, sex, education and BMI.ResultsHigher ELR‐diet adherence (per SD increase) was associated with better global cognitive performance (ß = 0.02, 95%CI = 0.01; 0.03), and executive function (ß = 0.03, 95%CI = 0.01; 0.04), episodic verbal memory (ß = 0.04, 95%CI = 0.02; 0.06) and total memory (ß = 0.02, 95%CI = 0.01; 0.03) domains. Moreover, the ELR‐diet was inversely associated with GHGEs (ß = ‐0.28, 95%CI = ‐0.30; ‐0.25) and LU (ß = ‐0.38, 95%CI = ‐0.41; ‐0.34). No associations between the ELR‐diet and brain volumes were observed.ConclusionOur study shows that adherence to the ELR‐diet is associated with favorable cognitive performance and reduced environmental impact, but not with brain volumetric measures. These findings support the potential health and environmental benefits of the EAT–Lancet Commission recommendations.
Plasma pTau‐217 and NfL concentrations across diagnoses in an unselected memory clinic cohort
Authors: Rousset Rebecca Z. , Verberk Inge M.W. , Lemstra Afina W. , Pijnenburg Yolande A.L. , van der Flier Wiesje M. , Jeromin Andreas , den Braber Anouk , van Harten Argonde C. , Teunissen Charlotte E. 
Published: December 2023

AbstractBackgroundAlzheimer’s Disease (AD) plasma biomarkers have been proposed for amyloid positivity identification and for differentiating between diagnoses. Phosphorylated Tau‐217 (pTau‐217) has demonstrated good predictive ability for AD vs healthy controls. Neurofilament Light chain (NfL) differentiates between Frontotemporal Dementia (FTD) and other dementia. These factors have not be extensively tested in real‐world cohorts. The aim of this study was to investigate how pTau‐217 and NfL concentrations differ across clinical diagnoses in an unselected, real‐world memory clinic cohort.MethodWe included 418 consecutive patients from the Amsterdam Dementia Cohort. Patients were split among 12 diagnoses, including SCD, Mild Cognitive Impairment (MCI), probable AD, Dementia with Lewy Bodies (DLB) and FTD (Table 1). pTau‐217 was measured using the novel AlzPath assay, while NfL was measured using the Quanterix Simoa assay. were used to classify patients as high or low for pTau‐217 and NfL levels. The pTau‐217 cutoff (0.58 pg/mL) was the Youden index cutoff derived from the present data, based on amyloid‐positive AD vs amyloid‐negative SCD diagnosis (n = 57), using amyloid status derived from cerebrospinal fluid or Amyloid positron emission tomography for classification. (18.2 pg/mL) was chosen based on the sample’s median age (64 years) and taking the value associated with the 90th percentile of normal NfL levels (NfL interface for physicians (shinyapps.io)).ResultpTau‐217 levels were highest in patients with AD and Primary Progressive Aphasia (PPA), and lowest in those with Vascular Dementia (VaD) and other neurological diagnosis (Figure 1). NfL levels were highest in patients with VaD and FTD, and lowest in SCD and psychiatric diagnoses. The cutoffs highlighted similar trends, with higher proportions patients with elevated pTau‐217 levels observed in possible and probable AD, MCI, and DLB. Higher proportions of patients with high NfL levels were observed in FTD, PPA, VaD, and possible AD (Figure 2).ConclusionpTau‐217 concentrations vary as expected across the different diagnoses, with highest concentrations in AD pathology diagnostic groups. The elevated levels observed in DLB and PPA could be due to underlying AD co‐pathology. Following previous results, NfL concentrations were highest in FTD and lowest in psychiatry and SCD.
Predicting progression to Alzheimer’s disease dementia using cognitive measures: findings from the Essex Memory Clinic
Authors: Whitfield Tim , Macdougall Amy , Schott Jonathan M , Frost Chris , Walker Zuzana 
Published: December 2023

AbstractBackgroundTimely diagnosis of Alzheimer’s disease (AD) is important for patients, carers and healthcare systems. It is therefore imperative to identify measures with the greatest power to predict future AD dementia. In contrast to research settings, expensive biomarkers are not always available in memory clinics. It is therefore vital to identify predictive measures which can be used in ordinary clinical settings.MethodThis study utilized clinical assessment data from 328 patients assessed in the Essex Memory Clinic between 2002 and 2019. Only patients with a diagnosis of subjective cognitive decline (SCD) or mild cognitive impairment (MCI) at baseline and a minimum of two follow‐up visits were included in analyses. Lasso logistic regression (using AD at visit 3 as the outcome) and Lasso Cox proportional hazards models (using time to AD at visit 3 and beyond as outcome) were fitted in two stages. The first stage included baseline cognitive scores only, while the second stage also included change scores for these measures (derived by subtracting scores at baseline from those at the first follow‐up visit).ResultIn the first stage models, lower Mini‐Mental State Examination (MMSE) and Logical Memory Test (LMT) delayed recall scores, and longer Trail‐Making Test part A (TMT‐A) time were associated with greater odds (logistic regression) and hazards (Cox proportional hazards) of progression to AD. In addition, in the Cox model (only), lower baseline Cambridge Cognitive Examination‐Revised (CAMCOG‐R) score was associated with greater hazard of AD. In the second stage models, worsening CAMCOG‐R and LMT (delayed recall) scores were independently associated with both the odds/hazards of AD.ConclusionIn this memory clinic cohort, the cognitive scores most predictive of progression to AD were the delayed LMT, TMT‐A, CAMCOG‐R and MMSE. These results are in‐keeping with earlier work conducted in research cohorts. The inclusion of cognitive change scores over one year follow‐up improved predictive accuracy versus baseline scores alone.
Association between the COVID‐19 restrictions, educational level and depression with the Subjective Memory Complaints in aging people from Latin American countries
Authors: Rivera‐Fernandez Claudia , Soto‐Añari Marcio F. , Lopez Norman , Ramos‐Henderson Miguel , Guinea Sara Fernández 
Published: December 2023

AbstractBackgroundThe subjective memory complaints (SMC) are associated with an increased risk of Alzheimer´s disease. Its prevalence has linked to emotional status, demographics factors and family neuropsychiatric history (Rabin et al, 2017). In addition, some recent studies have associated it with the restrictions during the pandemic of COVID‐19 (Prommas et al, 2022). Our objective was to analyze these factors with SMC in Latin‐American older people during the lockdown of COVID‐19.MethodA cross‐sectional study was developed in 10 Latin‐American countries: Argentina, Bolivia, Chile, Colombia, Ecuador, Guatemala, Mexico, Peru, Dominican Republic and Venezuela. We evaluated 5245 older adults (66.14% women y 33.86% men). The mean age was 69. 6 (SD = 7.28) and the years of schooling was 11 (SD = 5.85). All participants completed the short version of the Yesavage Geriatric Depression Scale, the functional scale AD8 (Alzheimer’s Disease 8) and completed ah‐doc questionnaire about family neuropsychiatry history, demographics and clinical factors. The SMC was tested with the item: ¿Do you think that are you experiencing more forgetfulness than people of your same age? We performed binary logistic regression considering SMC as dependent variable and demographics, family neuropsychiatry history and emotional status as predictors.Result1291 (24.61%) of participants manifest SMC, with higher prevalence in Peru and Colombia (x2 = 70.37, p<.001). The family history of depression (OR 1.43, p = .022) and dementia (OR 1.34, p = .038), higher scores of depression (OR 1.37, p<.001) and more age (OR 1.01, p = .028); increase the risk of SMC. On the other hand, having more years of schooling (OR 0.95, p<.001) and more days in confinement (OR = .99, p = .001) seem to reduce the risk of SMC.ConclusionThe emotional status and the family history of neuropsychiatry disorders, are more associated with SMC. In the opposite way, more years of schooling and more days in quarantine reduced the risk of SMC. We suggest to follow‐up the sample and use wider instruments related to memory complaints and other cognitive domains.
Memory markers in preclinical Alzheimer’s disease
Authors: Seo Eun Hyun , Yoon Hyung‐Jun , Lee Kun Ho 
Published: December 2023

AbstractBackgroundEpisodic memory impairment is a widely known core clinical symptom of Alzheimer’s disease (AD). However, it is still uncertain if it is possible to detect meaningful signs or changes in memory in the preclinical stage of AD due to their within‐normal‐range performance. In the current study, we investigated both verbal and visuospatial memory as markers to track the disease progression in the preclinical AD.MethodWe selected cognitively normal (CN) participants from the Gwangju Alzheimer’s Disease and Related Dementia Cohort in Korea. We included a group of CN individuals who showed a significant amyloid‐beta (aß) deposition, defined by amyloid PET, at baseline and completed at least two follow‐up evaluations. In the final analysis, we included 130 individuals in the preclinical stage of AD. Episodic memory measures were delayed recall scores from the Rey Complex Figure Test (RCFT_delayed) and Seoul Verbal Learning test (SVLT_delayed). We performed logistic regression analysis with stepwise selection to examine associations between memory tests and progression.ResultThe mean follow‐up month was 36.21. Twenty‐one (16.2%) participants were converted to MCI (n = 19) or AD dementia (n = 2), while the rest stayed as CN. When both RCFT_delayed and SVLT_delayed at baseline were entered in the logistic regression model, only the RCFT_delayed was significantly associated with the progression (OR = 0.288; 95% CI, 0.138‐0.602; p = 0.001). When change scores were added to the model, RCFT_delayed at baseline (OR = 0.223; 95% CI, 0.101‐0.496; p < 0.001), RCFT_delayed change score (OR = 0.470; 95% CI, 0.258‐0.857; p = 0.014), and SVLT_delayed change score (OR = 0.523; 95% CI, 0.290‐0.942; p = 0.031), were significant.ConclusionOur results suggest that visuospatial, not verbal, memory measures may play an important role in sensitively detecting the relevant sign of future progression in asymptomatic individuals. In terms of verbal memory, the longitudinal decline was associated with progression. Our study suggests that the inclusion of a visuospatial memory test and repeated evaluation can help to detect the earliest decline in the preclinical stages of AD.
Longitudinal retinal microvascular changes in preclinical Alzheimer’s disease
Authors: Curro‐Tafili Katie R. , Bouwman Femke H. , den Braber Anouk , Verbraak Frank D. , van Nispen Ruth , van de Kreeke Aleid , van de Giessen Elsmarieke , Tan H. Stevie 
Published: December 2023

AbstractBackgroundThe retina has become an area of increasing interest as a potential biomarker for neurodegeneration, as it is easily accessible and patient friendly. Previous studies have shown changes in the vasculature of the retina in patients with mild cognitive impairment (MCI) and Alzheimer’s disease (AD) in a cross sectional design. In this study we explore longitudinal retinal microvascular changes in amyloid beta positive (AB +) participants compared with amyloid beta negative (AB‐) participants.MethodWe analysed data from 159 cognitively normal participants (mean age 70.6 SD ± 5.91, 55% females) for changes in four microvascular parameters at baseline and 2 year follow up. (mean time between visits 2.2 years ± 0.23 SD) (Table 1) Amyloid status was obtained from positron emission tomography scans (PET) performed in both 2015 and 2019. The Cirrus 5000 Optical Coherence Tomography Angiography (OCT‐A) was used to obtain baseline and follow up measurements of the optic nerve head (ONH) and macula.ResultIn total, data from 123 AB‐ participants and 37 AB+ participants were included in the analysis. AB (+) participants were further divided into converters (AB‐+,n = 19) and those positive on both PET scans. (AB ++, n = 18) A decrease in vessel density (VD) of the ONH in AB++ participants was demonstrated over time, (p = 0.04) however no change over time was found for VD in the macula inner and outer ring or foveal avascular zone (FAZ). (Figure 2) The VD was found to be consistently higher amongst AB++ participants in the macula inner and outer rings (p<0.05) and the FAZ area was higher in AB‐+ participants. (p<0.05)ConclusionThis study showed change in VD over time for the ONH region in participants who have been AB + for 4 years or longer. These participants further demonstrated a higher VD in the macula inner and outer rings compared to AB—and AB‐+ participants. Additional longitudinal studies where amyloid status is present for longer periods of time amongst cognitively healthy participants should be undertaken to see if these OCTA microvascular changes could be used as a biomarker in preclinical AD.