bluuebunny/crossref_metadata_2025_split huggingface dataset:
Different correlates of memory decline in Alzheimer’s diseases and Frontotemporal dementia: evidence from a novel digital biomarker
Authors: Parra‐Rodriguez Mario A , Fernandez Gerardo 
Published: December 2023

AbstractBackgroundOculomotor behaviours (i.e., eye tracking ‐ ET) linked to cognitive performance can differentiate between the trajectories of neurodegeneration that lead to the Alzheimer’s disease Syndrome (ADS) or Fronto‐temporal Dementia (FTD). We recently reported that a novel digital biomarker that combines ET and Short‐Term Memory Binding (STMB) accurately predicted among MCI patients who would develop ADS or non‐AD dementias (Parra et al., 2022). A sub‐group of the latter group developed FTD. We investigated the correlates of these different neurodegenerative pathways.MethodsThe study involved 32 MCI patients of whom 24 developed ADS and 8 FTD in a three‐year longitudinal study. We also recruited 42 controls (HC). Saccade Amplitude and Fixation Duration were measured at baseline while participants performed the STMB Task. This task assesses the ability to detect changes between two consecutive arrays of bicoloured objects. Changes affect either colours (control condition) or colour combinations (binding condition).ResultsSaccade Amplitudes and Fixation Durations were affected in both MCI‐ADS and MCI‐FTD patients. However, patterns of impairment significantly differed between these risk conditions. Mean Saccade Amplitude followed the pattern MCI‐FTD > MCI‐ADS > HC (p <0.0001) with such responses being significantly more pronounced during retrieval than encoding, particularly in the MCI‐FTD group. Mean Fixation Duration followed the pattern HC > MCI‐FTD > MCI‐AD (p <0.0001) which was similar across memory processes.ConclusionWhile memory deficits in MCI‐AD appear to be driven by encoding impairments, as suggested by both ET metrics, deficits in MCI‐FTD appear to be largely accounted for by impairments in retrieval. The fact that such a distinct pattern was more pronounced for Saccade Amplitudes points toward an early involvement of the frontal lobes. Identifying different correlates of memory impairment in MCI patients at risk of these common neurodegenerative diseases would be challenging for pure cognitive assessments. This highlights the role that the novel digital biomarker can play in refining theories of memory decline and in phenotyping dementia risk profiles.Parra, M. A., Juan Granada, J., & Fernández, G. (2022). Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring. https://doi.org/10.1002/dad2.12386. eCollection 2022.
Pesticides and cognitive impairment in older adults: evidence from southern Colombia
Authors: Bonilla‐Santos Jasmin , Gonzalez‐Hernandez Alfredis , Forero Eduardo A , Gomez Duvan , Cala Dorian , Parra‐Rodriguez Mario A 
Published: December 2023

AbstractBackgroundEnvironmental exposure to specific chemical groups of pesticides (Carbamates, Organophosphates, Pyrethroids, and Organochlorines), as well as the non or inadequate use of personal protective equipment during pest management, have been associated to cognitive decline and increased risk of dementia (Hayden et al., 2010). This study investigated cognitive functioning in older adults exposed to pesticides in southern Colombia.MethodsA sample of 353 older adults was recruited. Of these, 279 had not been exposed to pesticides (n‐Exp) and 74 had (Exp). They were matched according to age [n‐Ex: 63.80 (3.25), Ex: 63.30 (6.96), t = 0.618, p = 0.538] and years of education [n‐Ex: 9.29 (6.28), Ex: 8.95(6.35), t = 0.418, p = 0.676]. They were assessed with a battery of cognitive tests including CERAD (Aguirre‐Acevedo et al., 2016), The Addenbrooke’s Cognitive Examination (ACE‐R), the Free and Cued Selective Reminding Test (FCSRT) and questionnaires.ResultsFDR corrected comparisons revealed overall lower cognitive abilities in the Exp group (ACE‐R, q = 0.027). They also displayed Memory (FCSRT, q = 0.020; World List Learning q = 0.014) and Constructional Praxis (q = 0.007) impairments. Of those exposed, 73% reported no use of personal protective equipment, and neither the participants nor their family members reported concerns about cognitive decline [Self‐reported: n‐Exp: 14.27 (7.44), Exp: 14.92 (7.98), t = ‐0.654, p = 0.513; Family‐reported: n‐Exp: 10.43 (7.12), Exp: 10.26 (7.45), t = ‐0.182, p = 0.856].ConclusionOlder adults from southern Colombia who have been exposed to pesticides show significant cognitive impairments, which have gone unnoticed by both the affected individuals and their family. Cognitive abilities found to be affected have been associated with risk of dementia caused by Alzheimer’s Disease or Parkinson’s Disease (FCSRT and Constructional Praxis). These types of dementia have been previously associated with this environmental risk factor (Chin‐Chan et al., 2015). More awareness about environmental factors and actions to mitigate their risk are urgently needed, and should be considered by future recommendations (e.g., Livingston et al., 2020).Aguirre‐Acevedo et al. (2016). Int. Psychogeriatr, 28(3), 503‐510. https://doi.org/S1041610215001660.Chin‐Chan et al. (2015). Frontiers in Cellular Neuroscience, 9. https://www.frontiersin.org/articles/10.3389/fncel.2015.00124Hayden et al. (2010). Neurology, 74(19), 1524‐1530. https://doi.org/10.1212/WNL.0b013e3181dd4423Livingston et al. (2020). Lancet, 396(10248), 413‐446. https://doi.org/10.1016/S0140‐6736(20)30367‐6
How to perform a general population‐based recruitment strategy for a multidomain intervention trial for dementia prevention—the CITA GO‐ON trial experience
Authors: Tainta Mikel , Ecay Mirian , Iriondo Ane , Barandiaran Myriam , Estanga Ainara , Altuna Miren , Clerigue Montserrat , de Arriba Maria , Lopez Carolina , Saldias Jon , Marta Cañada , Reparaz‐Escudero Imanol , Domper Jara , Mateo‐Abad Maider , Ros Naia , Garcia‐Sebastian Maite , Martinez‐Lage Pablo 
Published: December 2023

AbstractBackgroundFINGER trial has demonstrated the potential for dementia prevention by targeting different lifestyle domains in older adults. It highlighted the importance of selecting the correct window of opportunity for preventive actions by including participants at high risk of dementia. This approach is being tested worldwide to support future public health interventions, where the selection of the appropriate target population is crucial. Here we share our approach and results in recruiting older adults with increased dementia risk and cognitive frailty from the general population for the CITA Go‐On trial.MethodCITA GO‐ON is a single‐center randomized controlled trial in which non‐demented‐adults between 60‐80y will be allocated to receive standard care or a risk factor control and lifestyle‐based multidomain intervention. It replicates FINGER trial inclusion criteria, but the recruitment strategy is based on the community level in Gipuzkoa (Spain) instead of a previous health registry. Together with press and social media releases, mailing, and small group talks, the main recruitment strategy has been coordinated with local governments. Interested people fulfill an online form that allows identifying those who meet the pre‐established requirements (CAIDE dementia risk score ≥6) prior to attending an individualized face‐to‐face cognitive screening visit (evaluation of exclusion criteria and brief cognitive testing).ResultBy December 2022, we have reached and informed about the trial more 24000 people including all citizens older than 60 in three small municipalities in collaboration with the local town halls. Of these, 1919 completed the pre‐screening questionnaire using REDCap, 868 were screened and 450 recruited (mean age: 68,57 (6,58), 50,87% female, and mean CAIDE: 7,49 (1,39)). In person calculated (mean (sd): 6,98 (1,70)) and self‐reported (mean (sd): 7,23 (1,77)) CAIDE score is similar (p = 0,062) in our experience. Table 1 resumes age, sex, CAIDE and MMSE of the interested sample. Recruitment period is still opened.ConclusionCITA GO‐ON recruitment is a multi‐disciplinary population oriented efficient strategy to identify adults at high risk of dementia understanding and willing to participate in a multi‐modal intervention prevention trial. It allows to select candidates from the whole population, and not only those linked to specialized health care systems or registries.
Telomeres are associated with markers and regions sensitive to aging and not Alzheimer’s disease in cognitively unimpaired older adults
Authors: Lehodey Asrar , de Flores Robin , Palix Cassandre , Touron Edelweiss , Mézenge Florence , Landeau Brigitte , Chocat Anne , Kaliman Perla , la Sayette Vincent De , Vivien Denis , Chetelat Gael , Poisnel Géraldine , Group Medit‐Ageing Research 
Published: December 2023

AbstractBackgroundTelomeres (protective chromosomal ends) gradually shorten over the lifespan and have been associated with the development of age‐related diseases such as Alzheimer’s disease (AD). Most studies use median telomere length as a biomarker of cellular aging, but their dysfunction is rather reflected by the load of short telomere. No study to date has assessed the links between the percentage of short telomeres (ST) and blood, neuroimaging markers of aging, neurodegeneration, amyloid and tau pathologies in healthy elderly.MethodBaseline data from 125 cognitively unimpaired older adults (65 to 83 years old; mean ± SD: 68.9 ± 2.8) from the Age‐Well trial (NCT02977819), who completed multimodal neuroimaging and blood sampling, were analyzed. Neuroimaging data included structural T1‐weighted MRI, T2‐weighted high‐resolution scan of the hippocampus, DKI, FDG‐PET and AV45‐PET (perfusion and amyloid load). ST, as well as neurodegeneration, amyloid, and tau biomarkers (NFL, GFAP, Aβ42/40 ratio and pTau181) were measured in blood samples. Multiple linear regressions between ST and each marker were conducted corrected for age, sex, education and body mass index. Additional adjustments for APOE and amyloid status were made. Statistical significance was set to p<0.05, except for voxelwise analyses (puncorrected<0.005, kuncorrected = 500 voxels).ResultST was associated with lower white matter integrity (measured by kurtosis fractional anisotropy (kFA)) in prefrontal and temporal regions (Fig.1), and with the hippocampal subiculum volume, but not with total gray matter volume, mean kurtosis, glucose metabolism, brain perfusion or amyloid load; nor with blood markers of neurodegeneration, amyloid, or tau. Additional adjustments for APOE/amyloid status gave similar results.ConclusionTelomere dysfunctions were associated with lower white matter integrity in regions vulnerable to aging, but not to AD, nor with neurodegeneration, amyloid or tau biomarkers, and neither with AD risk factors (APOE or amyloid status). When we focused on the hippocampus, a specific link was found with the subiculum volume, an hippocampal subfield known to be the most sensitive to aging, which is not the case in AD. These results give further evidence for the tight connection between cellular and cerebral aging, but not with AD in cognitively unimpaired older adults.
Circulatory proteins relate cardiovascular disease to cognitive performance: a Mendelian randomisation study
Authors: Huang Jian , Gill Dipender , Zuber Verena , Matthews Paul M , Elliott Paul , Tzoulaki Ioanna , Dehghan Abbas 
Published: December 2023

AbstractBackgroundMechanistic research suggests synergistic effects of cardiovascular disease (CVD) and dementia pathologies on cognitive decline. The objective of this study was to investigate the causal relationship between cardiovascular disease (CVD) related proteins and cognitive decline.MethodWe applied Mendelian randomisation (MR) and colocalization analysis to investigate the causal relationships of 90 CVD‐related proteins measured by the Olink CVD I panel with cognitive traits. Genetic instruments for circulatory protein concentrations were obtained from a genome‐wide association study (GWAS) meta‐analysis from the SCALLOP consortium (N = 17,747) based on three sets of criteria: 1) protein quantitative trait loci (pQTL); 2) cis‐pQTL (pQTL within ±500kb from the coding gene); and 3) brain‐specific cis‐expression QTL (cis‐eQTL) which accounts for coding gene expression based on GTEx8. Genetic associations of cognitive performance were obtained from GWAS for either: 1) general cognitive function constructed using Principal Component Analysis (N = 300,486); or, 2) g‐Factor constructed using genomic structural equation modelling (N = 11,263‐331,679). Findings for candidate causal proteins were replicated using a separate protein GWAS in Icelanders (N = 35,559).ResultA higher concentration of genetically predicted circulatory myeloperoxidase (MPO) was nominally associated with better cognitive performance (P<0.05) using different selection criteria for genetic instruments. Particularly, brain‐specific cis‐eQTL predicted MPO, which accounts for protein coding gene expression in brain tissues, was associated with general cognitive function (βWald = 0.22, PWald = 2.4×10−4). The posterior probability for colocalization (PP.H4) of MPO pQTL with the g Factor was 0.58. Findings for MPO were replicated using a GWAS on cognitive score in an Icelandic population. Although we did not find evidence for colocalization, we found that higher genetically predicted concentrations of cathepsin D and CD40 were associated with better cognitive performance and higher genetically predicted concentration of CSF‐1 were associated with poorer cognitive performance.ConclusionThe study suggests that proteins primarily identified for their role in cardiovascular diseases may be involved in shared pathways with cognitive reserve or cognitive decline, and may confer therapeutic targets for neurodegenerative diseases such as Alzheimer’s disease.
AD risk variants in APOE differentially affect lipid metabolism in iPSC derived neurons, astrocytes and microglia
Authors: Feringa Femke M , Elmagd Amir Abou , Kruijff Iris Daphne , Heijneman Jorin , Koppes Sascha , Mohammed Yassene , Giera Martin , van der Kant Rik 
Published: December 2023

AbstractBackgroundDespite the clear function of APOE as a lipid carrier it is still unclear how Alzheimer’s disease (AD) risk variants of APOE affect the lipidome of individual human brain cell types. In addition, while APOE is crucial for transport of cholesterol from astrocytes to neurons, a role for APOE in lipid transport in the opposite direction from neurons to astrocytes has recently been suggested.MethodTo generate an atlas of the lipidome of the APOE genotype in a cell type specific manner, we performed lipidomic analysis on iPSC‐derived neurons, astrocytes and microglia with a different APOE genetic background. By co‐culture of these different cell types we studied the impact of APOE genotype on lipid transport between neurons and glia. We determined how the glial immune response and neuronal AD pathology are impacted by the changes in lipid transport.ResultWe find that APOE genotype affects the lipidome in all tested brain cell types. Also, we identify cell type specific metabolic adaptations to APOE genotype, emphasizing the need to study APOE biology in the context of individual cell types. In co‐culture we find that iPSC‐derived neurons can transport fatty acids and cholesterol to astrocytes as well as microglia. This neuron to glia lipid transport route is affected by the AD risk variant APOE4, which might impact immune responses in the glia.ConclusionAD risk variants in APOE differentially affect lipid metabolism in iPSC‐derived neurons, astrocytes and microglia and alter neuronal to glial lipid transport.
Development of a blood‐based biomarker signature for detection of cognitive impairment through a targeted metabolomics approach deciphering the association with depression
Authors: Chakraborty Manas , Dhiman Kunal , Gupta Veer 
Published: December 2023

AbstractBackgroundA series of pathological episodes set off the development of cognitive impairment, which precede years before the onset of clinical symptoms. Disrupted glucose and fatty acid metabolism notably contributes to the development of cognitive impairment and further advancement to clinical dementia. Disrupted metabolism leads to the secretion of various inflammatory eicosanoids leading to neuroinflammation. Alteration of some specific metabolites in plasma are noted during these metabolic changes. Depression is a key risk factor of cognitive impairment, and similar changes in plasma metabolites have observed in the pathophysiology of depression. This aim of this project is to establish a blood‐based biomarker signature for early detection of cognitive impairment in individuals with depression through quantifying plasma levels of metabolites associated with glucose and fatty acid metabolism in plasma samples from the participants of the Sydney Memory and Ageing Study (MAS).MethodSamples of 275 participants were randomly collected from baseline and 251 from an 8 year follow up study. At baseline there were 130 healthy participants, 93 participants with MCI, 36 participants with depression and 16 participants had both MCI and depression. Plasma samples were analysed to quantify the levels of fatty acids and carnitines using chemical derivatization – UPLC‐MRM/MS.ResultSignificant correlations were observed between the biomarkers like FA040 butyric acid (P: 0.034), FA224 (P: 0.032), acotinic acid (P:0.027) with MMSE. Biomarkers like C70carnitine (P:0.010), C90carnitine (P: 0.033), C150carnitine (P: 0.016), C160 carnitines (P: 0.004) significantly correlated with GDS scales. Linear regression showed significance between C90 carnitine (P: 0.021; β: 0.139) ad GDS scale. Whereas linear regression showed significant relationship between FA224 (P: 040, β: ‐.122), acotinic acid (P: 0.042, β: ‐.122), FA040 butyric acid (P: 0.036, β: ‐.193) with MMSE indicative of cognitive impairment.ConclusionThe study will help to identify candidate metabolites of perturbed fatty acid metabolism and establish a plasma biomarker signature of early cognitive impairment, by deciphering the association with depression as a risk factor. An association will be established between central AD pathology and peripheral metabolic changes, and potential treatment options targeting the right biochemical pathways will be identified.
Co‐designing a research study with people affected by dementia: the conceptualisation and development of the ActivDem study
Authors: Ardle Ríona Mc , Barker Sandra , Dawson Annabel , Evans Cherry , Htay U Hlay , McKenzie Maisie , Ogden Margaret , Ongley Anne Ward , Pottage Mike , Rutter Ron , Simpson Leslie , Webb Karin , Din Silvia Del , Thomas Alan J , Robinson Louise , Rochester Lynn 
Published: December 2023

AbstractBackgroundMaintaining physical activity(PA) following dementia diagnosis may decelerate decline to disability and dependency. It is unclear which socio‐ecological factors influence PA participation in people with dementia(PwD) and therefore may be effective interventional components for promotion of PA. To address this research gap, the ActivDem study was designed(see Table 1 for initial research aims). To ensure ActivDem met the needs of PwD, we aimed to co‐design the research aims, methodology and grant application with public patient involvement contributors.MethodA call for contributors (i.e. people with cognitive impairment/dementia carers, current and former/dementia care professionals) was advertised via dementia research networks, dementia care facilities (e.g. daycares, memory cafés), charities (e.g. Alzheimer’s Society Research Network Volunteers) and social media. Interested contributors were invited to participate in either participatory workshops held on Zoom or a one‐to‐one phone call. Contributors were asked four broad questions(Table 2). Initial study aims and methods were discussed with contributors. Aims and methods were refined based on contributors’ feedback and themes raised during the discussion. Ten contributors reviewed the grant application to ensure aims, methodology and public patient involvement/engagement plans met the priorities of people affected by dementia.ResultThirty contributors participated in workshops/phonecalls. Contributors described experiences of PA decline in PwD post‐diagnosis; common themes expressed included loss of independence and confidence, increased feeling of burden, greater fall risk, frailty, and worse mental health. They identified potential facilitators/barriers for maintaining PA following dementia diagnosis(Table 2). They highlighted the role carers play in facilitating PA by supporting and motivating PwD to stay active and advocated for inclusion of carer‐focused investigations. Contributors felt that PA research for PwD should be prioritised and findings linked in to information/support services for carers. The study’s aims and methods were adapted to include an exploration of carers’ psychosocial wellbeing and care management strategies(Table 1). Scales relating to proposed facilitators/barriers of PA were identified, approved by contributors and implemented in the methods.ConclusionThis work supported the conceptualisation and development of the ActivDem study. Ten contributors formed the ActivDem Public Patient Advisory Group, advising and supporting study management, data collection and interpretation, and dissemination of results.
Dementia risk reduction in the general practice: a proof‐of‐concept study evaluating the use of a brain health promotion smartphone app
Authors: Van Asbroeck Stephanie , Köhler Sebastian , Muris Jean W.M. , van Boxtel Martin P.J. , Deckers Kay 
Published: December 2023

AbstractBackgroundDuring the last decades, evidence supporting the relevance of brain health promotion and dementia risk reduction has considerably expanded (1). Currently, this evidence is sufficient to take public health action (2, 3). However, implemented interventions are still scarce, especially at a large scale. In the Netherlands, evidence‐based cardiovascular risk management is already implemented in primary care. Since there is a large overlap between modifiable risk factors for dementia and those for cardiovascular disease, discussing dementia risk reduction next to cardiovascular health in the general practice seems a feasible, first step towards future large‐scale implementation of dementia risk reduction strategies.MethodA proof‐of‐concept study is currently being conducted in ten general practices in the Netherlands in which 180 participants between 40 and 60 years old, with room for improvement on at least one modifiable risk factor, will have a consultation with their general practitioner or practice nurse. During this consultation, they will learn about brain health promotion and how they could personally improve their risk profile. Practices have been randomly allocated (1:1) to either provide the consultation only, or to additionally provide the participants with a brain health promotion smartphone app (i.e. MijnBreincoach).ResultFeasibility will be evaluated using validated questionnaires assessing knowledge on dementia risk reduction, health behavior, motivation, usability, satisfaction, and user experience with the smartphone app. Surveys will be administered before the consultation at the general practice and three months thereafter. Further, ten participants and four healthcare professionals will be invited for a qualitative interview to get a more in‐depth view of the intervention’s feasibility.ConclusionDiscussing dementia risk reduction in the general practice may constitute a feasible and effective, scalable approach towards dementia risk reduction. Results of the study are expected by July 2023.
References
1. Livingston G, Huntley J, Sommerlad A, et al. Dementia prevention, intervention, and care: 2020 report of the Lancet Commission. Lancet. 2020;396(10248):413‐46.2. World Health Organization. Risk reduction of cognitive decline and dementia: WHO guidelines. Geneva; 2019.3. Steyaert J, Deckers K, Smits C, et al. Putting primary prevention of dementia on everybody’s agenda. Aging Ment Health. 2020:1‐5.