bluuebunny/crossref_metadata_2025_split huggingface dataset:
Accelerated long‐term forgetting over six months in cognitively normal APOE ɛ4 carriers
Authors: Tort‐Merino Adrià , Laine Matti , Fortea Juan , Martinez‐Lage Pablo , Sanchez‐Valle Raquel , Rami Lorena , Rodríguez‐Fornells Antoni 
Published: December 2020

AbstractBackgroundAccelerated long‐term forgetting (ALF) refers to an abnormally rapid loss of information over days or weeks despite normal acquisition and encoding. The potential usefulness of ALF in the early detection of subtle cognitive difficulties in asymptomatic stages of familial (Weston et al., 2018) and sporadic (Zimmermann & Butler, 2018) Alzheimer’s disease (AD) has attracted particular attention. However, research on the relationships between ALF and AD biomarkers is still lacking, and forgetting curves have not been followed up over an extended period of time. We aimed to fill these gaps by administering a particularly demanding memory task, correlating task results with AD biomarkers, and registering forgetting curves over a 6‐month follow‐up.MethodTwenty‐two cognitively healthy subjects were included: 11 APOE ɛ4 carriers (heterozygous for ɛ3 and ɛ4) were age‐, sex‐, and education‐matched with 11 APOE ɛ4 non‐carriers (homozygous for ɛ3). All subjects underwent APOE genotyping, standard neuropsychological assessment, a lumbar puncture for determining CSF Aß42, tau and ptau levels, and the demanding Ancient Farming Equipment Test (AFE‐T). The AFE‐T calls for learning 24 novel object/name pairs through two learning sessions of seven runs performed on two consecutive days (range 0‐24 points per run). Free and cued long‐term recall was examined at one week, three months and six months after the initial learning.ResultDemographics and CSF levels are shown in Table 1. The AFE‐T showed no group differences in the learning scores, but a significant group difference (F(1,19) = 4.99; p < 0.05) emerged in the cued recall at 3 months. The APOE ɛ4 carriers showed ALF in their cued forgetting rate at 3 months (F(1,19) = 5.60; p < 0.05) and the forgetting rate between the 1‐week and 3‐month recall (F(1,19) = 8.70; p < 0.01) (Figure 1B). Correlation analyses showed a significant association between the cued forgetting rate at 3 months and the ratio CSF Aβ42/ptau (Figure 2A; r = .614; p < 0.01). Also, a significant correlation was found between the cued forgetting rate at 3 months and subjective cognitive ratings (Figure 2B; r = .636; p < 0.01).ConclusionAccelerated long‐term forgetting is detectable in at‐risk individuals and is linked with CSF AD biomarkers. We strongly recommend the use of demanding memory tests coupled with long‐term forgetting measures for identifying and tracking the earliest cognitive manifestations in presymptomatic Alzheimer’s disease.
White matter integrity linked to memory retrieval deficits in posterior cortical atrophy
Authors: Overman Margot Juliette , Zamboni Giovanna , Butler Christopher , Ahmed Samrah 
Published: December 2020

AbstractBackgroundPosterior cortical atrophy (PCA) is an atypical form of Alzheimer’s disease characterised by visuospatial abilities, with episodic memory traditionally thought to be relatively preserved. However, recent work suggests that verbal memory is impaired at clinical presentation (Ahmed et al., 2016) associated with changes in functional connectivity of parietal attention networks (Veldsman et al., 2018). It is currently unclear how structural connectivity changes may contribute to memory functioning within this patient group. Here, we examine the relationship between white matter integrity and verbal episodic memory in PCA.MethodEighteen patients with PCA and eighteen healthy controls underwent diffusion tensor imaging (DTI) MRI scanning. Episodic memory of patients was assessed with the Free and Cued Selective Reminding Test with Immediate Recall (FCSRT‐IR). Voxel‐wise statistical analyses of fractional anisotropy and mean diffusivity measures in patient and control groups were carried out using tract‐based spatial statistics. Relationships between white matter microstructure and memory performance were examined with partial correlations controlling for age.ResultThere was no difference in encoding of verbal items between patients and healthy controls. However, PCA patients presented with significant impairments of memory retrieval on the FCSRT‐IR. In line with previous neuroimaging research, white matter degeneration in PCA was restricted to posterior regions of the cortex. Within the patient group, reduced integrity of the splenium of the corpus callosum was associated with less free recall of task items.ConclusionThis study demonstrates that splenial atrophy may contribute to deficits in episodic memory retrieval in PCA. The findings have implications for supporting diagnostic profiling in PCA. References: Ahmed, S., Baker, I., Husain, M., Thompson, S., Kipps, C., Hornberger, M., Hodges, J.R., & Butler, C.R. (2016). Memory impairment at initial clinical presentation in posterior cortical atrophy. Journal of Alzheimer’s Disease, 52: 1245 – 1250. Veldsman, M., Zamboni, G., Butler, C., & Ahmed, S. (2018). Attention network dysfunction underlies memory impairment in posterior cortical atrophy. NeuroImage: Clinical, 22: 101773.
Cerebral autoregulation in patients with MCI and dementia due to Alzheimer's disease: Effects of blood pressure lowering on CBF
Authors: Claassen Jurgen A.H.R. , de Heus Rianne A.A. , Rikkert Marcel G.M. Olde , de Jong Daan LK , Sanders Marit 
Published: December 2020

AbstractBackgroundBlood pressure (BP) lowering is a promising strategy to prevent dementia, including AD (SPRINT‐MIND). BP lowering should therefore be explored as a secondary prevention strategy in patients with early stages of AD (MCI due to AD and preclinical AD). However, if cerebral autoregulation is impaired in (older) patients with AD, BP lowering could cause cerebral hypoperfusion and lead to progression of diseaseMethodwe studied cerebral autoregulation at baseline in 40 patients with amnestic MCI and 50 patients with AD dementia, compared with 40 age matched cognitively normal controls (controls, aMCI and AD aged 70 years SD 5). Next, we studied the effects of BP lowering on CBF using a) one year exercise intervention (in aMCI) and b) BP lowering treatment with a calcium channel blocker (in AD dementia).Resultat baseline, we found no evidence of impaired dynamic cerebral autoregulation in aMCI and AD compared to controls. BP lowering (on average ‐10 mmHg systolic BP) did not reduce global nor regional CBF in aMCI and AD. Of interest, BP lowering led to an increase in hippocampal CBF.ConclusionNo evidence for impairment of cerebral autoregulation was found. BP lowering did not reduce CBF, in contrast, BP lowering may even improve regional and possibly global CBF. Further studies should extend these findings to a larger population and to earlier stages of AD.
Evaluation of the effectiveness of the neuro‐nutraceutical SYNAID® on a broad‐spectrum sample (subjects with dementia, cognitively preserved and with depression): Results of a 24‐month prospective clinical trial
Authors: Veneziano Massimo 
Published: December 2020

AbstractBackgroundthe increasing number of subjects with dementia in the world and the failure of drug therapies, has inspired the scientific community undertake new forms of intervention to tackle the disease such us primary prevention (reduction of risk factors, cognitive reserve). Neuro‐nutraceutical research and resulting treatments are increasingly affirming, preventing or slowing down cognitive impairment; contributing to achieve neuroplasticity. The purpose of this study was to assess the efficacy and safety of neuro‐nutraceutical SYNAID® (INPHA Duemila Srl) in patients with cognitive impairment (combination with anticholinerasic drugs) and in cognitively preserved subjects with or without anxiety and depression.MethodExclusion criteria: 1) psychiatric diagnosis; 2) severe sensory deficits. Inclusion criteria: 1) subjects with MCI (amnestic and vascular), 2) subjects with Alzheimer’s dementia, with vascular dementia, with mixed dementia; 3) cognitively preserved subjects with or without anxiety and depressive disorders. The enrolled patients (280) were divided into 2 groups by open‐randomised method: the treatment group (grT) with the administration of SYNAID® one tablet/day for 24 months and the control group (grC) that did not take the neuro‐nutraceutical. The groups were analysed by Student and compared at baseline, 6, 12, 18, 24 months from the beginning of treatment. The cognitive outcome was evaluated by administration of the following tests: MMSE; CDR; CDT; RAVLT; FVL. The result of psychic state evaluated through CES‐d, the result psycho‐behavioural symptoms associated with dementia via NPI. Functional outcome via IADL scale. The quality of life outcome through QoL‐SF12.ResultgrT compared to the grC showed a significant increase in scores at the MMSE, RAVLT, FVL, CDT, IADL and QoL‐SF12 tests and a significant reduction in scores at CES‐d and NPI. There were no side effects, no adverse events following the intake of neuro‐nutraceuticals. The dropouts were 20 (9 grT and 11 grC).ConclusionThe study demonstrates that prolonged intake of SYNAID® improves memory and other neuropsychological functions in cognitively preserved subjects (neuro‐protective effect), and in patients with Alzheimer’s and/or vascular dementia and in patients with mild cognitive impairment (MCI). Furthermore, significant improvements were found in the mood outcome, in the daily functional capabilities and in the quality of life outcomes in all treated subgroups.
Cerebrospinal fluid amyloid status and affective symptoms in mild cognitive impairment
Authors: Wiels Wietse , Nous Amber , Engelborghs Sebastiaan 
Published: December 2020

AbstractBackgroundAffective and cognitive symptoms are common in old age, and frequently overlap in clinical practice. Mild cognitive impairment (MCI), for example, is a risk state for later dementia where neuropsychiatric symptoms such as depression and anxiety are common. The exact nature of this overlap remains unclear ‐ affective symptoms may be both causative of cognitive issues, they may be related to an underlying neurodegenerative disease, or may stem from common risk factors. Biomarkers of brain diseases such as Alzheimer’s can help determine the etiology of MCI and aid in predicting the risk of progression to dementia.AimsTo determine whether CSF‐based amyloid positive and amyloid negative individuals with MCI differ in the nature and prevalence of affective symptoms.MethodAn existing database of 476 individuals with MCI will be used. All subjects underwent extensive cognitive and behavioural assessment at baseline and follow‐up (up to 7 years). Behaviour was assessed covering a period of 2 weeks prior to inclusion and at each follow‐up visit using a battery of behavioural assessment scales: Middelheim Frontality Score (MFS), Behave‐AD, Cohen‐Mansfield Agitation Inventory, Cornell Scale for Depression in Dementia and Geriatric Depression Scale (30 items). In a significant subgroup of these patients, the standard AD CSF biomarkers (Aβ, T‐tau, P‐tau181) have been analysed. We will evaluate whether subgroups with differing amyloid status (i.e. normal vs. abnormal CSF biomarkers) are significantly different in the nature and prevalence of affective symptoms as determined by several scales (Behave‐AD, Geriatric Depression Scale, Cornell Scale for Depression in Dementia).ResultsWe will compare prevalence, nature and severity of affective symptoms between subgroups of MCI patients (amyloid positive versus amyloid negative; AD CSF biomarker profile suggestive for AD versus not suggestive for AD). Presence and severity of affective symptoms will be related to (rate of) cognitive decline using neuropsychological data (e.g. yearly decline of total MMSE score).ConclusionWe expect to find more (severe) affective symptoms in MCI due to AD (as compared to MCI not due to AD) and to find an association between these symptoms and rate of cognitive decline. The results will be presented at AAIC 2020 in Amsterdam.
Integration of large‐scale molecular networks and exomic data can identify Alzheimer's disease genes
Authors: Lagiesetty Yashwanth , Bourquard Thomas , Lichtarge Olivier 
Published: December 2020

AbstractBackgroundWe introduce a new approach to identify gene variants linked to common complex diseases. This method combines whole exome sequencing and large‐scale molecular network analysis. For proof of principle, we studied the Alzheimer’s Disease Neuroimaging Initiative (ADNI) and the Alzheimer’s Disease Sequencing Project (ADSP) cohorts. In each, we evaluated the coding variants of 16,087 genes in the context of their ∼6,471,000 gene‐gene interactions, and prioritized genes that sorted cases from controls.MethodThe deleterious functional effect of every coding variant was quantified based on an Evolutionary Action (EA) model for the impact of similar variants across evolutionary history. For each gene, this impact was averaged over every individual from the ADNI (or the ADSP) cohort, and this average was used to modulate the edge weights of the STRING network of protein‐protein interactions. This process was carried out in cases and separately in controls, to yield two modified copies of the original STRING network, one representing the mutational perturbation from individuals affected with Alzheimer’s and, the other, representing those found in healthy individuals. We systematically compared these two graphs in order to identify, region by region and gene by gene, which parts of the network was significantly mutationally perturbed.ResultAmong the 100 top‐ranked in ADSP and, separately, in ADNI, a quarter are identical. This overlap indicates a robustness surpassing Genome‐wide association studies. One such gene, for example, is TOMM40, which is known to be relevant to AD. More broadly, these top‐ranked genes also significantly overlap, are significantly enriched for, or significantly diffuse to known gold standard AD genes and AD‐related diseases and pathways. These criteria for success show the top‐ranked genes are not random and are relevant to AD.ConclusionThis approach to integrate sequencing data with network information promises to be a useful new tool to elucidate disease genes in AD and other complex, common diseases.
Phenotypes associated with MAPT duplications
Authors: Wallon David , Bonnevalle Antoine , Rovelet‐Lecrux Anne , Lagarde Julien , Sarazin Marie , Bottlaender Michel , Sellal François , Jonveaux Therese , Heitz Camille , Magnin Eloi , Ber Isabelle Le , Epelbaum Stéphane , Quillard‐Muraine Muriel , Chastan Mathieu , Hannequin Didier , Boluda Susana , Rousseau Stéphane , Richard Anne‐Claire , Quenez Olivier , Charbonnier Camille , Duyckaerts Charles , Campion Dominique , Nicolas Gaël 
Published: December 2020

AbstractBackgroundDuplication of the 17q21.3 region, leading to increased MAPT expression, causes a rare atypical early‐onset dementia (EOD) mimicking Alzheimer’s Disease (AD) clinical presentation. Since our initial report in 2016, the same duplication has been identified in additional patients including 2 progressive supranuclear palsy (PSP) patients. It remains unclear whether MAPT duplication‐associated phenotypes are purely cognitive and if clinical and neuroimaging data are suggestive of a pure tauopathy or an amyloid plus tau underlying pathology.MethodWe report in this study clinical and paraclinical data from 10 MAPT duplication carriers, including 8 with a clinical EOD presentation and two recently identified during the screening of a series of PSP cases. All clinical data were collected as well as family history, neuropsychological assessment, 3D‐structural MRI (n = 7 patients), fluorodesoxyglucose‐PET (n = 5), DaTSCAN SPECT (n = 2), Amyloid‐PET (n = 3) and Tau‐PET (n = 2). Six patients had AD cerebrospinal fluid (CSF) biomarkers measured. Results were interpreted following Amyloid/Tau/Neurodegeneration (A/T/N) classification.ResultAmong the 10 patients, 6 had a positive family history of EOD, with cosegregation in one family. In one of the 4 sporadic patients, we could demonstrate that the duplication occurred de novo. Mean age of onset was 50.4 years [37‐58]. Eight presented a pure cognitive decline with an initial episodic amnesic syndrome. A behavioral dysexecutive syndrome was found in 5 patients (50%). Two patients were diagnosed as PSP but no or minor extrapyramidal signs were found among the 8 cognitive patients, despite 2 DaTSCANS showing presynaptic dopaminergic denervation. MRI of 6 cases (86%) showed hippocampal and temporoparietal bilateral atrophy. All CSF biomarkers were T+ and N+. Amyloid CSF biomarkers were abnormal in 3/6, suggestive of A+, however all three had negative amyloid‐PET. Interestingly, both Tau‐PET imaging showed strong deposits of Tau pathology within mesiotemporal regions and mild frontal cortex uptake in one patient (Figure). The neuropathology of two patients is currently being examined and will be presented.ConclusionThis largest series of MAPT duplications carriers shows a heterogeneous expression with clinical and neuroimaging data suggesting mixed cortical and subcortical impairment with diverse clinical consequences. We will confront these data to the results of the neuropathological examinations.
Early‐onset Alzheimer’s disease is related to differential spatial patterns of tau pathology and cognitive impairment
Authors: Verfaillie Sander C.J. , Visser Denise , Wolters Emma E. , Coomans Emma M. , Timmers Tessa , Tuncel Hayel , Boellaard Ronald , Golla Sandeep S.V. , Windhorst Albert D. , Scheltens Philip , van Der Flier Wiesje , Ossenkoppele Rik , Van Berckel Bart N.M. 
Published: December 2020

AbstractBackgroundEarly‐onset Alzheimer’s disease (AD) dementia is characterized by a heterogeneous cognitive profile consisting of language and visuo‐spatial impairment. Spatial patterns of tau pathology measured with [18F]flortaucipir may help to explain the heterogeneity within early‐onset AD.MethodSeventy‐one patients with Alzheimer’s disease dementia patients (n=28 early‐onset age=58, MMSE=22; n=43 late‐onset age=71, MMSE=23), of whom 6 patients with posterior cortical atrophy, 2 behavioral of AD (bvAD). All patients had available 130 minutes [18F]flortaucipir PET scans and extensive neuropsychological assessment. We generated parametric images and non‐displaceable binding potentials (BPnd) were extracted using receptor parametric mapping in the following brain regions; frontal, occipital, parietal, medial and lateral temporal cortex. We performed principal component analyses to reduce 12 cognitive tests into latent variables which reflect (uncorrelated) cognitive functions. ANOVA and linear regressions were performed to investigate between [18F]flortaucipir group differences and associations with cognition functions.ResultEarly‐onset AD dementia patients showed increased [18F]flortaucipir BPnd in occipital, parietal and frontal cortex (all p<0.001) compared to late‐onset AD. Across all AD patients, adjusted for education, sex and age, frontal [18F]flortaucipir BPnd was associated with attention (p=0.003), occipital [18F]flortaucipir BPnd with visual scanning and memory (both p=0.01), parietal [18F]flortaucipir BPnd with attention and visual scanning (p=0.002 and p=0.02 respectively). Lateral temporal [18F]flortaucipir BPnd was associated with attention (p=0.006) and medial temporal [18F]flortaucipir BPnd with memory (p=0.01). Interaction effects were found for occipital and parietal [18F]flortaucipir BPnd and visual scanning for early‐onset AD, and parietal [18F]flortaucipir BPnd and attention for late‐onset. Frontal [18F]flortaucipir BPnd was associated with visual scanning in late‐onset AD. In an exploratory analysis, we found higher [18F]flortaucipir BPnd in parieto‐occipital cortices in PCA compared early‐ and late‐onset AD (both p<0.001).ConclusionDifferential spatial patterns of tau pathology were found depending on age‐of‐onset. Tau pathology may help to explain the clinical phenotype of early and late‐onset AD.
Memory assessment in illiterate patients: The diagnostic value of the TNI 93
Authors: Foucard Cendrine , Palisson Juliette , Bereaux Chloé , Dumurgier Julien , Paquet Claire , Degos Bertrand , Amar Elodie Bouaziz , Maillet Didier , Belin Catherine , Garcin Béatrice 
Published: December 2020

AbstractBackgroundAssessment of cognitive functioning in illiterate patients is challenging because only few validated tests are available. The “test des neuf images ‐93” (TNI‐93) is a short test (5 to 10 minutes) based on nine black and white drawings, that was developed to assess episodic memory in this specific population (Maillet, 2016). Subjects are asked to learn the nine pictures using the principle of encoding specificity. It has been shown that the TNI‐93 is a suitable test to detect dementia in the elderly low educated population, but it remains unknown whether it is specifically altered in Alzheimer’s disease (AD). The objective of the present study was to examine the diagnostic value of the TNI 93 and its sub‐scores for the screening and diagnosis of biologically confirmed AD in patients explored for cognitive impairment.MethodWe retrospectively collected data of all patients seen in the memory center of Avicenne Hospital between January 2009 and November 2019 who underwent lumbar puncture, brain imaging, and neuropsychological assessment including the TNI 93. We classified patients into two groups: AD/ Non‐AD (NAD) according to the criteria AT(N) proposed by the working group "National Institute on Aging ‐ Alzheimer's Association”(Jack, 2018). We then compared scores at the TNI‐93 between AD and NAD patients.ResultAmong the 113 patients included, 52 presented with AD. Age (mean: 67.5 ± 10.1), gender (49.6% women), and education (mean: 9.2 ± 5.5 years) did not differ between both groups. On the TNI‐93, AD patients were significantly more impaired than NAD patients in immediate recall [mean AD: 5.5; mean NAD: 7; p=0.003], free recall [mean AD: 3.51; mean NAD: 4.78; p=0.018] and total recall [mean AD: 5.53; mean NAD: 6.93; p = 0.031]. In the AD group, there were more intrusions both during encoding (mean AD: 1.23; mean NAD: 0,67; p= 0.056) and restitution (mean AD: 1.22, mean NAD: 0.34; p=0.007).ConclusionThe TNI 93 seems an interesting tool to discriminate between Alzheimer's disease and other causes of cognitive impairment notably in low educated population.