bluuebunny/crossref_metadata_2025_split huggingface dataset:
Visual memory scores are associated with lateralization of tau in the medial temporal lobe
Authors: Arias Jaime Fernandez , Lussier Firoza Z , Therriault Joseph , Mathotaarachchi Sulantha , Tissot Cécile , Wang Yi‐Ting , Benedet Andréa Lessa , Pascoal Tharick A. , Stevenson Jenna , Rahmouni Nesrine , Bezgin Gleb , Gauthier Serge , Rosa‐Neto Pedro 
Published: December 2021

AbstractBackgroundAggie Figures Learning Test (AFLT) is a visual memory test that was conceived as an analogue of the widespread Rey Auditory Verbal Learning Test (RAVLT), which tests verbal memory. Previous research has indicated that performance may rely on the left medial temporal lobe (lMTL) for RAVLT and on the right medial temporal lobe (rMTL) for AFLT, although evidence is inconclusive. The present study looks into the association between delayed recall (DR) scores in both tests and tau binding in the brain.MethodTau PET ([18F]‐MK6240) was acquired for 130 individuals for analysis involving AFLT, and 139 for analysis involving RAVLT. Demographic data is shown on Tables 1 and 2. MRI were segmented into probabilistic grey (GM) and white (WM) maps, non‐linearly registered to the ADNI template using Dartel and smoothed with an 8mm FWHM gaussian kernel. Voxel‐wise linear regression models were applied, using VoxelStats, with either DR AFLT or DR RAVLT as dependent variables and tau as a predictor. We corrected for age, diagnosis, and amyloid load. All other variables that were tested did not significantly contribute to predict DR scores.ResultsWe found negative associations between tau binding and DR RAVLT in the MTL bilaterally. Interestingly, we found a negative correlation between tau binding and DR AFLT scores that is remarkable in the rMTL and barely reaches significance in the lMTL.ConclusionOur findings provide evidence in support of the lateralization of memory in the brain based on the learning modality. This dissociation is in line with previous findings; namely, that the rMTL is responsible for visual memory. However, these findings are not entirely in line with previous research since associations with RAVLT are found bilaterally. Of note, most of the previous research has been made in the context of epilepsy and/or patients with anterior MTL lesions. Here, however, we are investigating a totally different population and we are looking at a parameter that is specific to this population.
Addressing dementia challenges through international networks: Evidence from the Latin American and Caribbean Consortium on Dementia (LAC‐CD)
Authors: Parra Mario A , Garcia Adolfo M , Ibanez Agustin ,   LAC‐CD
Published: December 2021

AbstractBackgroundLAC‐CD has recently reported that challenges faced by LAC countries are very similar to those experienced by HIC, and that regional networks will be needed to bridge gaps. ReDLat is a US‐LAC multi‐partner consortium aimed at expanding dementia research in LAC. The UK‐Latin America Brain Connectivity Research Network (UL‐BCRN) focuses on developing new affordable EEG‐based biomarkers for dementia. The Language and Brain Health Network (LBHN) integrate international multidisciplinary efforts to reveal linguistic markers of neurodegenerative diseases.MethodsReDLat is collecting genomic, neuroimaging, clinical, cognitive, and socioeconomic data from a first‐in‐class cohort anchored in six LAC (Argentina, Chile, Colombia, Brazil, Mexico, and Peru) and will compare these to US data (> 4200 participants, including 2100 controls, 1050 AD patients, and 1050 FTD patients). The 5‐year project will develop innovative, harmonized, and cross‐nation approaches on two of the most prevalent neurodegenerative diseases, Alzheimer’s disease (AD) and Frontotemporal Dementia (FTD). The UL‐BCRN currently links seven EEG labs from Colombia, Argentina, Chile, Brazil and the UK. The network’s vision is to forge strong relationships between labs through which new methodologies, EEG plus multidimensional datasets, and experience will be developed and shared. The LBHN will analyze speech samples from massive AD, FTD, and control cohorts across LAC, Spain, and the US. This effort aims to identify low‐cost disease‐specific markers in diverse Latino and English‐speaking patients.ResultsReDLat will aims to reveal unique risk factors for AD and FTD in LAC compared to US populations. Data collection strategies have been adapted to face the challenges brought by the COVID‐19 pandemic. The UL‐BCRN has now standardised recording protocols across LAC and UK labs and is collecting data from longitudinal cohorts of patients at risk of dementia relying on novel culture‐free cognitive paradigms. Preliminary LBHN data shows that, automated speech analyses can identify Latinos with AD and FTD, with good generalization across socio‐biological profiles, dialects, and languages.ConclusionBy broadening our understanding of dementia phenotypes, risk factors, and affordable diagnostic approaches in LAC, adding new evidence on variability across HIC and LMIC, the above networks will contribute unique knowledge that will help enhance future global dementia strategies.
The BIN1 rs744373 Alzheimer’s disease risk SNP is associated with faster Aβ‐associated tau accumulation and cognitive decline
Authors: Franzmeier Nicolai , Ossenkoppele Rik , Brendel Matthias , Rubinski Anna , Smith Ruben , Kumar Atul , Mattsson‐Carlgren Niklas , Strandberg Olof , Duering Marco , Buerger Katharina , Dichgans Martin , Hansson Oskar , Ewers Michael ,   Alzheimer’s Disease Neuroimaging Initiative (ADNI)*,   the Swedish BioFINDER study
Published: December 2021

AbstractBackgroundThe BIN1 rs744373 SNP is a key risk locus for Alzheimer’s disease (AD). Cross‐sectional studies showed BIN1 rs744373 to be associated with higher tau pathology, i.e. a key AD pathological hallmark that is associated with Aβ. Whether carriage of the BIN1 rs744373 risk SNP accelerates the association between Ab and the rate of tau accumulation is unclear. Here, we examined whether BIN1 rs744373 risk‐allele‐carriers show faster Aβ‐related tau accumulation and thus faster cognitive decline.MethodWe included two independent samples (ADNI, n=153; BioFINDER, n=63) characterized with longitudinal 18F‐Flortaucipir tau‐PET (mean follow‐up ∼2years), Aβ‐biomarkers (i.e. Ab‐PET in ADNI vs. cerebrospinal fluid Aβ1‐42 in BioFINDER) and longitudinal cognitive assessments (i.e. ADNI only). We assessed whether BIN1 rs744373 was associated with faster tau accumulation at a given level of Aβ and whether BIN1 rs744373‐associated tau accumulation mediated faster cognitive decline.Result
BIN1 rs744373 risk‐allele‐carriers showed faster global tau‐PET accumulation (ADNI/BioFINDER, p<0.001/p<0.001, Fig. 1A&B). We found significant Aβ by rs744373 interactions on global tau‐PET accumulation rates (ADNI: b/SE=0.42/0.14, p=0.002; BioFINDER: b/SE=‐0.35/0.15, p=0.021, Fig. 1C&D), showing accelerated tau accumulation in BIN1 risk‐allele‐carriers at higher Aβ‐levels. In ADNI, rs744373‐effects on cognitive decline were mediated by faster global tau‐PET accumulation (b/SE=0.20/0.07, p=0.005, Fig. 2).Conclusion
BIN1 rs744373 risk‐allele carriers show accelerated Aβ‐related tau accumulation rates and cognitive decline. These findings suggest that BIN1‐associated risk for AD dementia is specifically driven by accelerated tau accumulation, suggesting that BIN1 may be specifically involved in the progression of tau pathology.
Engagement with a preventive eHealth intervention in older adults (the HATICE trial): Predictive factors and associations with dementia and cardiovascular risk
Authors: Coley Nicola , Andre Laurine , Hoevenaar‐Blom Marieke P , Ngandu Tiia , Beishuizen Cathrien , Barbera Mariagnese , van Wanrooij Lennard , Kivipelto Miia , Soininen Hilkka , Brayne Carol , van Charante Eric P Moll , Richard Edo , Andrieu Sandrine 
Published: December 2021

AbstractBackgroundEngagement with digital health tools ihas not been well‐studied in older populations. We aimed to describe engagement with a preventive eHealth intervention designed to reduce dementia and cardiovascular risk, identify factors associated with engagement, and examine associations between engagement and changes in dementia and cardiovascular risk factors.MethodWe analyzed data from the 18‐month randomized controlled ‘Healthy Ageing Through Internet Counselling in the Elderly’ (HATICE) trial. Participants, enrolled in Finland, France, and the Netherlands, were aged 65+ with at least basic computer literacy and either ≥2 cardiovascular risk factors or history of cardiovascular disease/diabetes. The intervention group (N=1389) received access to an interactive Internet platform, designed to encourage lifestyle changes, with remote support from a lifestyle coach. The control group (N=1335) received access a static Internet platform containing basic health information. Engagement with the intervention platform was assessed via number of logins, lifestyle goals set, messages sent to the coach, monitoring measurements entered, and amount of advice and education materials read. These metrics were combined into a composite engagement score.ResultMost intervention group participants engaged with the platform to some extent: 90% set ≥1 goal, 86% sent ≥1 message and 80% entered ≥1 measurement. The median (IQR) number of logins per participant during follow‐up was 29 (16‐48). Regular computer use was the strongest baseline predictor of engagement. Those already working on or with short‐term plans for lifestyle improvement, and better cognition also engaged more. Compared to the control group, after adjustment, intervention group participants who engaged more with the platform showed significantly more improvement over 18‐months in systolic blood pressure, BMI, physical activity, Mediterranean diet score, and cardiovascular/dementia risk scores. Intervention group participants with a low engagement score showed no improvement compared to the control group.ConclusionEngaging older people in a digital lifestyle self‐management intervention was feasible. Better engagement led to more improvement in dementia and cardiovascular risk factors. Older adults who are infrequent computer users, have poorer cognition, and no concrete plans to change their lifestyle may need extra support for digital lifestyle interventions. Disparities in engagement may be further emphasized in real‐world settings.
Effects of APOE genotype, age and sex on cerebrospinal fluid biomarkers measured with NeuroToolKit in the Longitudinal Swedish Biofinder Cohort
Authors: Cicognola Claudia , Janelidze Shorena , Palmqvist Sebastian , Suridjan Ivonne , Kollmorgen Gwendlyn , Mattsson‐Carlgren Niklas , Hansson Oskar 
Published: December 2021

AbstractBackgroundThe exploratory NeuroToolKit (Roche Diagnostics International Ltd.) is a panel of automated robust prototype assays measuring cerebrospinal fluid (CSF) Alzheimer’s disease (AD) biomarkers. NeuroToolKit includes core AD biomarkers Aβ42, Aβ40, p‐tau181 and t‐tau, markers of synaptic dysfunction (α‐synuclein and neurogranin), astrocytosis (S100b, YKL‐40, glial fibrillary acidic protein [GFAP]), microglial activation and inflammation (sTREM2, IL‐6) and axonal injury (neurofilament light [NfL]). In this study, we investigated additional effects of APOE e4 genotype, age and sex on the change of the biomarkers over time in CSF samples from the longitudinal Swedish BioFINDER cohort.MethodCSF samples were collected at baseline and then at 2‐, 4‐, 6‐, 8‐ and 10‐years’ follow‐up from 1324 patients who were cognitively unimpaired (CU, n=801) or had mild cognitive impairment (n=265) or non‐AD dementias (n=258). Groups were stratified as Aβ positive (Aβ+) or negative (Aβ‐) according to CSF Aβ42/40 ratio (cut‐off<0.07). Linear mixed‐effect models were used to assess interaction between time and APOE e4 genotype (no e4 allele, heterozygous e4, homozygous e4), sex and age stratified by cognitive status (CU<65 years, CU≥65 years; cognitively impaired [CI] <65 years, CI≥65 years).ResultAPOE e4 homozygous genotype was associated with a significant increase in Aβ42 and YKL‐40 levels in the Aβ+ group over time (versus subjects with no e4 allele) (Table 1A, Figure 1A‐B). In the Aβ‐ group, male sex was associated with a significant increase in IL‐6 and sTREM2 levels over time (Table 1B, Figure 1C‐D). Regardless of Aβ status, increased age was associated with increase in neurogranin, p‐tau181 and T‐tau over time and decrease in sTREM2 in the cohort as a whole (Table 2A). However, when stratified for age and clinical diagnosis, there was an increase in sTREM2 levels in the CI group (versus CU<65 years) over time (Table 2B, Figure 1E). No significant effects of age, sex and APOE genotype were observed in the other biomarkers.ConclusionThe longitudinal change in most biomarkers in the NeuroToolKit is not affected by APOE e4 genotype, age and sex; however, significant effects of these factors on the measurement of some biomarkers warrant adjustment in such studies.
Serum‐based inflammatory biomarker profiles and structural brain measures in older adults without dementia
Authors: Gu Yian , Guo Jing , De Jager Philip L. , Schupf Nicole , Manly Jennifer J. , Mayeux Richard , Brickman Adam M. 
Published: December 2021

AbstractBackgroundInflammatory markers may play a crucial role in early stages of Alzheimer’s disease (AD). We previously found C‐reactive protein (CRP) was associated with reduced brain volumes. Whether systemic inflammation profiles using multiple inflammatory biomarkers are associated with brain measures remains unclear.MethodThe study included 662 older (mean age=75.6 years) participants without dementia from the community‐based, multiethnic Washington Heights‐Inwood Columbia Aging Project. Thirty‐six cytokines in serum collected at baseline were quantified with multiplex technology. High‐resolution structural MRI was collected approximately 4 years later. Global brain volumetric measurements, including total brain volume (TBV), total gray matter volume (TGMV), and total white matter volume (TWMV), were quantified from T1‐weighted images via Freesurfer and adjusted for intracranial volume in the analyses. Mean cortical thickness was estimated by the average cortical thickness of 68 regions of interest. Principal component analyses were run to derive cytokine patterns (CPs). Multivariable linear regression models were used to assess the association between cytokines and brain MRI measures, adjusted for demographic and clinical factors.ResultEight different cytokine patterns were derived. The CP8, characterized by high (>0.3) positive loadings of α2‐Macroglobulin (A2MG) (loading=0.55), CRP (0.76), and IP‐10 (0.32), was positively correlated with increasing age (r=0.11, p=0.005). In adjusted model, the CP8 was associated with reduced TBV [β (95% confidence interval), p‐value: ‐6.88 (‐13.17, ‐0.58), 0.032], TGMVR [‐5.34 (‐8.61, ‐2.07), 0.001], and TWMV [‐4.69 (‐8.62, ‐0.76), 0.019]. Other CPs were not associated with any of the brain measures. In secondary analyses on individual cytokines, we found CRP was associated with reduced brain volumetric measures and reduced cortical thickness, but no association with brain was found for A2MG or IP‐10. Additionally, compared to the lowest tertile, moderate level (middle tertile) of platelet‐derived growth factor (PDGF‐AB/BB) was associated with larger TGMV; moderate level of macrophage inflammatory protein 1‐alpha was associated with smaller TBV and TWMV; and moderate level of PDGF‐AA was associated with smaller TWMV.ConclusionIn this cross‐sectional study of non‐demented older adults, we found a cytokine pattern characterized by high CRP, A2MG, and IP‐10 was associated with reduced brain volume, which seemed to be mainly driven by CRP.
At‐home assessment of cognitive performance: Establishing norm scores for the Cognitive Online Self‐Test Amsterdam (COST‐A)
Authors: Visser Leonie N.C. , Dubbelman Mark A. , Verrijp Merike , Wanders Lisa , Pelt Sophie , Zwan Marissa D. , Thijssen Dick H.J. , Wouters Hans , Sikkes Sietske A.M. , Hout Hein PJ , van der Flier Wiesje M 
Published: December 2021

AbstractBackgroundIncreased public awareness of cognitive decline among older adults increases the need for reliable self‐testing of cognitive performance at home. In this study, we aimed to assess the usability of unsupervised, at‐home cognitive testing using the Cognitive Online Self‐Test Amsterdam (COST‐A). We established norm scores in a reference sample and validated them in an independent sample of cognitively normal individuals. In a clinical sample of individuals diagnosed with mild cognitive impairment (MCI) or dementia, we validated the capacity of COST‐A to distinguish normal from impaired cognitive functioning.MethodWe recruited adults who self‐reported to be cognitively normal through the Dutch Brain Research Registry (reference sample), and invited them to complete and evaluate the COST‐A. We computed expected COST‐A scores based on age, sex and education level using multiple linear regression, to obtain demographically‐adjusted, standardized norm scores. We applied ‐1.5 SD units as a cut‐off for (ab)normal performance.ResultOut of 3529 participants who started, 3088 participants (60.6±12.1 years old, 70% women, 68% highly educated) successfully completed the COST‐A (Figure 1). These participants considered COST‐A to be of adequate difficulty and duration (±17 minutes), with clear instructions. Based on the norm scores (Figure 2), and corresponding with our cut‐off definition, 242 participants (7.8%) in the reference sample scored below ‐1.5. Results from the independent validation cohort (N=2444, 58.9±12.1 years old, 42% female, 54% highly educated) corroborated this finding: 186 (7.6%) scored below the cut‐off. In the clinical sample, 75% of MCI and 82% of dementia patients scored below ‐1.5.ConclusionCOST‐A is an easy‐to‐use online test of cognitive performance for individuals worried about their memory that can be used in the comfort of their own home. This is especially relevant in light of the COVID‐19 pandemic, where digital care is increasingly the norm. Moving forward, optimizing user experiences is key to overcome challenges regarding successful completion of the COST‐A at home, even in cognitively normal individuals. With a high accuracy for distinguishing normal from impaired cognition, COST‐A can serve as a screening tool to identify those individuals who require formal assessment by a healthcare professional and/or for research studies.
Examination of cognitive performance and mild behavioral impairment domains of apathy, mood, impulse dyscontrol, social inappropriateness and psychosis in cognitively normal adults aged 50 and over
Authors: Sun Nianqi , Ismail Zahinoor , Aarsland Dag , Brooker Helen , Corbett Anne , Ballard Clive , Creese Byron 
Published: December 2021

AbstractBackgroundMild Behavioral Impairment describes a spectrum of later‐life onset sustained neuropsychiatric symptoms which are a risk state for dementia. Symptoms which constitute MBI can be grouped into apathy, mood, impulse dyscontrol, social inappropriateness and psychosis. While previous studies have shown the presence of any MBI symptoms (i.e. a global measure) to be associated with worse cognitive performance over one‐year, little is known about the individual constituent domains. In this study we examined the cognitive correlates of each of the five MBI domains over two years in a cognitively normal sample.MethodData from 8,001 participants aged 50 or over taking part in the PROTECT study were analysed. Cognitive performance was assessed at baseline and after two years via completion of a battery of four tests broadly assessing working memory and elements of executive function (paired associates learning, digit span, self‐ordered search and verbal reasoning). MBI status was ascertained at baseline using the MBI‐C at the same time as performance on the first cognitive test. Change in cognitive performance was calculated was a difference score (year 2‐baseline) and analysed in a regression model with MBI domain score as the predictor and controlling for relevant medical and demographics covariates.ResultThe mean age of the sample was 62 and ∼75% were women. Apathy, mood and impulse dyscontrol were associated with worse cognitive performance across all four cognitive tests, the largest effects were observed for impulse dyscontrol on self‐ordered search and verbal reasoning (β= ‐0.05, p=<0.001; β= ‐0.12, p=0.005 respectively). Social inappropriateness was only associated with worse performance on digit span and self‐ordered search (β= ‐0.08, p=0.005; β= ‐0.11, p=0.018) while there were no cognitive changes associated with psychotic symptoms.ConclusionWe present the first longitudinal analysis of the relationship between individual MBI domains and cognition. The worse cognitive performance over two years associated with impulse dyscontrol and social inappropriateness highlight the importance of non‐affective symptomology in later life.
Low‐dose lithium treatment of behavioral complications in Alzheimer’s disease: Lit‐AD randomized clinical trial
Authors: Devanand Davangere P , Crocco Elizabeth , Forester Brent P. , Husain Mustafa , Lee Seonjoo , Huey Edward D. , Pelton Gregory H 
Published: December 2021

AbstractBackgroundTo evaluate low‐dose lithium treatment of agitation in Alzheimer’s disease (AD).MethodIn a four‐site trial, patients with AD and agitation/aggression on the Neuropsychiatric Inventory (NPI) were randomized, double‐blind, to lithium carbonate 150‐600 mg daily or placebo for 12 weeks. Primary efficacy outcome was change in NPI agitation/aggression; secondary efficacy outcome was treatment response defined by 30% reduction in NPI combined score for agitation/aggression plus psychosis and a Clinical Global Impression (CGI) score of much or very much improved. Somatic, cognitive, metabolic, and neurological side effects were assessed.ResultFifty‐eight of 77 patients (75.3%) completed the trial. In linear mixed effects model analyses, lithium did not differ from placebo in agitation/aggression change scores. Proportion of responders was 31.6% on lithium and 17.9% on placebo (χ2=1.26, p=0.26). Moderate or marked improvement on global CGI change, which incorporated behavior, cognition, and function, was greater on lithium (10/38=36.8%) than placebo (0/39=0%, Fisher’s exact test p<0.001). In exploratory analyses, improvement on lithium was greater than placebo on NPI delusions and irritability/lability (p’s<0.05). Lithium showed greater reduction than placebo in patients with high Young Mania Rating Scale scores (β=5.06; 95%CI, 1.18 to 8.94, p=0.01). Oral dose and serum lithium levels demonstrated similar associations with efficacy outcomes. Lithium did not differ significantly from placebo on any safety outcome.ConclusionLow dose lithium was not efficacious in treating agitation but was associated with global clinical improvement and excellent safety. A larger trial may be warranted with precision pharmacological targeting of likely lithium‐responsive behavioral symptoms that overlap with mania.