bluuebunny/crossref_metadata_2025_split huggingface dataset:
Attention processing speed impairment in early dementia with Lewy bodies correlates with white matter damage on volumetric and diffusion tensor imaging
Authors: Botzung Anne , Mondino Mary , Noblet Vincent , Philippi Nathalie , Blanc Frédéric 
Published: December 2020

AbstractBackgroundAttentional deficit is a prominent and distinguishing neuropsychological feature of Dementia with Lewy Bodies (DLB) since the prodromal stages. Our group recently highlighted, using voxel based morphometry (VBM), the importance of the basal ganglia grey matter (GM) integrity for attention processing speed, however, one can hypothesize that white matter (WM) would also be affected. Accordingly, this study aimed at investigating, in early DLB patients, the relationship between impaired attention processing speed and white matter changes using WM‐VBM and diffusion tensor imaging (DTI).MethodSeventy‐three prodromal to moderate DLB patients (mean MMSE = 26.4) and thirty healthy elderly subjects (mean MMSE = 28.9), matched in terms of age and educational level, were selected to participate in the study. The Trail Making Test A (TMTA) was used to assess attention processing speed. Behavioral performances were compared between patients and control subjects. Three‐dimensional (3D) MRI and diffusion tensor images (DTI) were acquired and correlational analyses were performed in the patient group using GM‐ and WM‐VBM, fractional anisotropy (FA) and mean diffusivity (MD) DTI.ResultAs expected, DLB patients took significantly more time to achieve completion of the TMTA in comparison to control subjects (p = .004), indicating an impairment in speed of processing. Correlational analyses using VBM revealed negative GM correlations in the basal ganglia bilaterally (p < .001), and negative WM correlations in a bilateral but left‐predominant cluster including mainly the corpus callosum and the anterior cingulate region and a smaller cluster in the right anterior cingulum (p < .05 FDR corrected). Using DTI in correlation with TMTA scores (p < .05 FDR corrected), we found reduced FA in bilateral frontal and posterior regions, and increased MD in widespread lateral and medial anterior and posterior regions.ConclusionWM‐VBM analysis revealed the involvement of the anterior corpus callosum and cingulum in processing speed, which could indicate a disruption of the loops connecting striatal regions and the prefrontal cortex. Changes in both FA and MD were also found: their distribution suggest that attention processing speed might be particularly dependent on the integrity of white matter connections throughout the brain.
Awareness of cognitive decline through the continuum of Alzheimer’s disease and its association to APOE‐ε4 and amyloid load
Authors: Cacciamani Federica , Valladier Arnaud , Maheux Etienne , Koval Igor , Durrleman Stanley , Epelbaum Stéphane 
Published: December 2020

AbstractBackgroundAnosognosia is a common symptom of Alzheimer’s disease (AD) dementia. However, the trajectory of the awareness of cognitive decline (ACD) across the predementia phases remains unclear. This study aimed to outline ACD changes through the entire course of AD, and study the impact of APOE‐ε4 genotype and amyloid load on the ACD evolution.MethodWe included 1280 subjects (7403 visits) from ADNI cohort, aged from 55 to 91 (M=73.7). They are progressors from cognitively‐normal and MCI stages, but also subjects with stable MCI and AD. ACD was measured as the subject‐informant discrepancy on the Everyday cognition (ECog). Using a non‐linear Bayesian mixed‐effects model (Schiratti et al., 2015, NIPS), we recombined the short‐term individual measurements into a long‐term progression of ACD. This allows to map the individual visits onto a common disease timeline, so that the real ages are reparametrized into comparable physiological ages. From each individual trajectory, we extracted the physiological age of (i) maximum hypernosognosia, (ii) accurate awareness, and (iii) anosognosia ‐ whose value corresponded to the upper 20th percentile cut‐off (normalized discrepancy of 0.3). These ages were correlated to the number of ε4 alleles and amyloid status (Aβ+ and Aβ‐) on PET or CSF.ResultAn early phase of hypernosognosia (subject's > informant's ECog) preceded a gradual decrease in ACD, eventually leading to a clear anosognosia (Figure 1, with 100 bootstrapped runs). Unawareness started on average 5 years before diagnosis. APOE‐ε4 carriers reached the peak of hypernosognosia and the anosognosia cut‐off earlier than the non‐carriers (all p<.001; Figure 2). Aβ+ subjects reached the peak of hypernosognosia later than Aβ‐, but their ACD started to decline earlier (all p<.05; Figure 3).ConclusionThe role of cognitive complaints and low ACD in AD is currently highly debated. Our study showed that both are associated with AD pathology, being two conditions that occur in temporal succession. This has strong implications in terms of timely and accurate diagnosis, and in patients’ treatment. Further analyses may study the longitudinal trajectory of ACD in relation to additional AD features, such as brain atrophy and metabolism, especially in the predementia phases.
Biomarker testing in MCI patients: Deciding who to tap
Authors: van Maurik Ingrid S. , Meester Hanneke F.M. Rhodius‐ , Teunissen Charlotte E. , Scheltens Philip , Barkhof Frederik , Palmqvist Sebastian , Hansson Oskar , van Der Flier Wiesje , Berkhof Johannes 
Published: December 2020

AbstractBackgroundIt is unlikely that biomarker testing contributes to a more accurate prognosis in every patient with Mild Cognitive Impairment (MCI). We therefore aimed to derive a stepwise approach to select MCI patients for cerebrospinal fluid (CSF) testing and determine the optimal proportion of patients to receive CSF testing.MethodsWe selected n=402 MCI patients from the Amsterdam Dementia Cohort (ADC) and n=221 from the BioFinder study, with available demographic information, Magnetic Resonance Imaging (MRI) and CSF data. Three‐year progression probabilities to dementia were predicted for all patients, using previously published model (van Maurik et al. 2019, The Lancet Neurology) based on 1) patient characteristics (age, sex, MMSE; demographic model), or 2) additional MRI (hippocampal volume; MRI model). We incrementally augmented the proportion of patients to receive CSF testing, first the most uncertain 10% of patients (percentile 45‐55 of demographic‐ or MRI model derived probabilities), then 20% (percentile 40‐60), and so on. Prognostic performance of this stepwise model was measured with Harrell’s C. The optimal proportion was selected as the point where the stepwise model performed similar to testing all patients. This proportion provides the range of probabilities where additional CSF testing would be indicated (Table 1). To study generalizability, we replicated this approach in BioFINDER.ResultsOn top of demographic characteristics, the stepwise approach showed that 60% of the patients required CSF testing in both cohorts in order to reach optimal prognostic performance (i.e. similar to CSF model; Figure 1A). This proportion corresponded with progression probability between 32%‐56%. This range was similar in BioFINDER (34%‐56%; Table 1). If we took the MRI model as a starting point, the optimal proportion was 60% in the ADC and 70% in BioFINDER (i.e. similar to ATN model; Figure 1B). This corresponded with a probability range of 19%‐40% in the ADC and 19%‐48% in BioFINDER (Table 1).ConclusionWe showed that CSF biomarker testing adds prognostic value on clinical and/or imaging information in 60‐70% of the MCI patients that had less certain probability of progression between 32%‐56% or 19%‐48%. As such, we achieve a generalizable CSF saving recommendation with optimal prognostic accuracy.
The prevalence of young onset dementia: A systematic review and meta‐analysis
Authors: Hendriks Stevie , Peetoom Kirsten , Verhey Frans RJ , de Vugt Marjolein , Koehler Sebastian ,   PRECODE‐Consortium
Published: December 2020

AbstractBackgroundOnset of dementia before the age of 65 years is usually referred to as young onset dementia (YOD). Out of the total prevalence of dementia, it is estimated that 6‐9% are accounted for by YOD, but data to build robust estimates on is very limited in this specific dementia subgroup. Valid epidemiological data on the prevalence of people with YOD is needed to adequately provide dedicated services and care. This systematic review aimed to collate data from published literature and estimate the prevalence of YOD.MethodA comprehensive literature search in PubMed, Embase, CINAHL and PsychINFO was conducted to identify population‐based studies on the prevalence of dementia in a population aged under 65. Articles published between 1990 and 30 November 2018 were screened independently by two authors in two phases: 1) screening titles and abstracts, 2) screening full texts, according to the PRISMA‐guidelines. Data were extracted and all articles were assessed on quality and risk of bias. Study authors were contacted when data was missing or to obtain full texts. Random‐effect meta‐analyses were pooled estimates and assessed sources of between‐study differences. The study is registered with PROSPERO, number CRD42019119288.ResultThe systematic search yielded 10,370 articles. After screening and cross‐referencing 88 articles were included in the review. Eligible articles were pooled together in meta‐analyses. Subgroups were made amongst others for type of dementia, age ranges and sex. The overall pooled estimate for young onset dementia over all age ranges and all types of dementia was 0.20% (95%CI = 0.15‐0.26). The prevalence for females was 0.25% (95%CI = 0.16‐0.35), whereas the prevalence for males was 0.16% (95%CI = 0.10‐0.23). Prevalence ranged from 0.01% (95% CI= 0.00‐0.01) in the age group 30‐34, to 0.98% (95% CI = 0.72‐1.28) in the age group 60‐64. Heterogeneity across studies was high, articles differed in many methodological aspects. Meta‐regression and subgroup analyses into sources of between‐study differences in prevalence estimates are currently analyzed and will be presented.ConclusionArticles eligible for meta‐analysis showed an overall prevalence of 0.21%, with females having a slightly higher prevalence compared to males, and an increased prevalence with increasing age.
Prevalence and pattern of neuropsychiatric conditions among community‐dwelling older Lebanese adults and their relation to cognitive function
Authors: Hachem Rita El , Chaaya Monique , Elbejjani Martine 
Published: December 2020

AbstractBackgroundNeuropsychological and behavioral changes are an important source of burden for older adults and present a high and complex co‐morbidity with cognitive decline. Several reports suggest that these constructs may differ in their manifestations across cultures yet the vast majority of data come from higher‐income countries. Data on mental and cognitive health are particularly scarce in Lebanon. We examined the prevalence and overlap of depression, anxiety, and sleep disturbances at older age and their association with cognitive functioning in a community‐dwelling cohort of older adults (65 and above) in Lebanon (n=502; mean age=75.52 (SD=7.22); 56% women).MethodDepression, anxiety, and reported sleep problems or changes were measured using the Geriatric Mental State (GMS) Agecat Package. Using adjusted linear regression models, we estimated how the presence of these conditions is related to cognitive function, measured with the Community Screening Instrument for Dementia (CSI‐D). Data processing is still ongoing to include more participants.ResultPreliminary results showed that in our sample, 13.1% had at least one neuropsychological problems and 4.4% had two or more. Estimated prevalence was 10.6% for depression, 1.6% for anxiety, and 10.6% for the presence of sleep disturbances. With regards to overlap, all participants with anxiety had concomitant depression and 50% had sleep problems. Among participants with depression, 15% had anxiety and 33% had sleep disturbances. Among participants with sleep disturbances, 33% had depression and 7.5% had anxiety. The odds of depression, anxiety, or sleep disturbances were 2.9, 2.3, and 1.7 times higher for women than they were for men, respectively. Socioeconomic indicators were not associated with depression, anxiety, or sleep disturbances. The presence of any neuropsychological problem was not related to cognitive scores, and depression and sleep disturbances were not related to cognitive scores; in contrast participants with anxiety symptoms had lower cognitive scores (beta=‐3.28 (95% CI=‐5.074,‐1.492)).ConclusionResults suggest an important overlap in the presence of neuropsychological problems in this cohort and a potential differential relationship between anxiety – which was highly correlated to the presence of other mental health problems – and cognitive functioning in Lebanese older adults.
Taxifolin is a novel therapeutic agent for Alzheimer’s disease and cerebral amyloid angiopathy
Authors: Saito Satoshi , Tanaka Masashi , Satoh‐Asahara Noriko , Carare Roxana O. , Weller Roy O. , Ihara Masafumi 
Published: December 2020

AbstractBackgroundImpaired amyloid‐β clearance from brain along intramural periarterial drainage (IPAD) is key in the pathogenesis of Alzheimer’s disease (AD). Facilitating IPAD would delay or prevent cerebral amyloid angiopathy (CAA). Taxifolin, a flavonol with strong anti‐oxidative and anti‐glycation activities, has been reported to disassemble amyloid‐β. Here, we test the hypothesis that taxifolin has therapeutic potential in reducing AD and CAA.MethodTg‐SwDI mice, as a model of AD and CAA, were treated with either taxifolin or vehicle alone from the age of one month. Wild type and Tg‐SwDI mice aged eight to thirteen months were used for the investigation of the amyloid‐β metabolism in vivo, amyloid‐β pathology, cerebral blood flow, cerebrovascular reactivity and cognitive function. Cerebral blood flow and cerebrovascular reactivity were evaluated by using laser speckle flowmetry. Cognitive function was assessed by Morris water maze. Thioflavin‐T fluorescence assay and transmission electron microscope were to examine the effect of taxifolin on amyloid‐β disaggregation.ResultThere was reduced accumulation of amyloid‐β in the cerebrovasculature in the hippocampus in taxifolin‐treated Tg‐SwDI mice compared to the mice treated with vehicle alone (n = 5). Tg‐SwDI mice treated with taxifolin exhibited decreased expression of amyloid‐β precursor protein in the hippocampus, suppressed oligomerization of amyloid‐β in the brain and increased levels of amyloid‐β40 in the blood (n = 4‐6). Taxifolin completely restored the cerebral blood flow and cerebrovascular reactivity in Tg‐SwDI mice (n = 4‐6). Spatial reference memory returned to normal levels following treatment with taxifolin (n = 10‐17). Amyloid‐β aggregation was suppressed by taxifolin treatment in vitro.ConclusionTaxifolin prevents overproduction and oligomerization of amyloid‐β and facilitates its clearance into the blood. Taxifolin thus appears to be a promising therapeutic agent for AD and CAA.
A case study of frontal variant of Alzheimer disease
Authors: Jia Ziyan , Xu Jun , Shi Jiong , Chen Qidong , Zhang Qian 
Published: December 2020

AbstractBackgroundWith the further understanding of AD, we found that it has heterogeneous clinical presentations. It is typical of early and progressive impairment of episodic memory, but we also recognized a special type—fv‐AD,which shows obvious executive cognitive impairment. We report a male patient, aged 60 years, who was clinically diagnosed with fv‐AD. He had memory impairment in the early stage of the disease, but had executive dysfunction that did not match with memory impairment, resulting in the early loss of social function. He had a history of personality change, stubbornness, delusion and hallucination.MethodChose an fv‐AD patient and collect his clinical manifestation, neuroimaging data and cognitive assessment.ResultIn clinical manifestations, it coincides with behavioral‐variant frontotemporal dementia (bvFTD), and has difficulties in differential diagnosis. Positron emission tomography(PET) with fluorodeoxyglucose showed marked hypometabolism in frontotemporal and parietal regions. The PIB‐PET showed hypermetabolism in frontotemporal, parietal and occipital regions, which was consistent with in vivo amyloid deposition neuroimaging evidence of AD pathology.ConclusionThis report mainly discusses the similarities and differences between fv‐AD and bvFTD, which is helpful for clinical differential diagnosis, enriching the clinical manifestations of this kind of patients and improving our understanding.
Associations between cognition and neuropsychiatric symptoms in people with dementia: Protocol for a systematic review and multilevel meta‐analysis
Authors: Sabates Julieta M. , Lampit Amit , Malmberg Gavelin Hanna , Loi Samantha M. , Brodtmann Amy , Chong Terence W.H. , Goh Anita M.Y. , Lautenschlager Nicola T. , Bahar‐Fuchs Alex 
Published: December 2020

AbstractBackgroundNeuropsychiatric symptoms (NPS), including depression, anxiety, apathy, aggression and agitation, among others, are highly prevalent in people with dementia (PWD), and are associated with lower quality of life and greater caregiver distress1.Over recent years there has been a proliferation of research aimed at exploring the cause of NPS and the relationships between them and impairment in specific cognitive abilities. Despite this interest, previous work has been limited mostly to cross‐sectional and longitudinal studies and, until now, systematic reviews on this topic have tended to focus on one symptom or type of dementia. The specific associations between cognitive impairment and NPS in PWD regardless of aetiology are, therefore, still poorly understood. Furthermore, no previous study has investigated whether these associations vary between younger and late‐onset dementia. The aim of our research is to investigate the specific links between cognition and NPS in PWD, and explore the moderators of these relationships, including dementia aetiology and age of onset. This review forms a first step in the design of a novel mHealth intervention for NPS in PWD which will be informed by its findings.MethodWe will search relevant databases for observational and interventional studies investigating these associations. We will convert outcome data from studies to standardised mean difference (SMD, calculated as Hedges’ g)2 with 95% confidence interval of difference in cognitive performance between the exposure groups, correlation coefficient or odds ratios. We will synthesise the data by conducting multilevel random effects analyses.ResultsThe findings from this review will make an important contribution to research by improving the knowledge about the correlates of NPS.ConclusionResults are likely to have important implications for the management and treatment of NPS. Appelhof, B., Bakker, C., Zwijsen, SA., Smalbrugge, M., Verhey, F. R., de Vugt, M. E., … & Koopmans, R. T. (2017). The determinants of quality of life of nursing home residents with young‐onset dementia and the differences between dementia subtypes. Dementia and geriatric cognitive disorders, 43(5‐6), 320‐329. Rosenthal, Robert, H. Cooper, and L. Hedges. “Parametric measures of effect size.” The handbook of research synthesis 621 (1994): 231‐244.
Amyloidogenic nanoplaque levels are increased in the cerebrospinal fluid in Alzheimer’s disease
Authors: Aksnes Mari , Tiiman Ann , Edwin Trine Holt , Terenius Lars , Bogdanovic Nenad , Vukojevic Vladana , Knapskog Anne‐Brita 
Published: December 2020

AbstractBackgroundThe aggregation of amyloid β (Aβ) is a central step in Alzheimer’s disease (AD) pathogenesis according to the amyloid cascade hypothesis. Measures of misfolded or aggregated Aβ are attractive biomarkers for AD, as they could potential reflect an important disease step. Newly, a Thioflavin‐T Fluorescence Correlation Spectroscopy (ThT‐FCS) assay has been developed that allows the quantification of amyloidogenic aggregates, hereby nanoplaques, with single‐molecule sensitivity. Thus far, no study has evaluated the association between cerebrospinal fluid (CSF) nanoplaque levels and core CSF biomarkers of AD.MethodCSF was collected from 118 individuals assessed for cognitive complaints at the Oslo University Hospital Memory Clinic. Levels of CSF core biomarkers: Aβ42, total tau (T‐tau) and phosphorylated tau (P‐tau) were evaluated with ELISA assays (Innotest kits). The CSF nanoplaque concentration was quantified using the ThT‐FCS analysis. All patients received research diagnoses, and were AT(N)‐classified based on all available biomarkers (fluid‐ and imaging biomarkers).ResultSixty‐eight patients were clinically diagnosed with possible or probable AD, and 50 patients were diagnosed with other cognitive disorders. Sixty‐five patients were classified as A+ (on the Alzheimer’s continuum) and 53 patients were classified as A‐ (normal AD biomarkers or non‐AD pathologic changes). Nanoplaque levels were significantly increased in patients with clinically diagnosed possible or probable AD as compared to memory clinic patients with other cognitive disorders, P = .02. Nanoplaque concentration was also significantly increased in A+ patients as compared to A‐, P = .04. CSF nanoplaque levels were inversely correlated with CSF Aβ42 levels (r = − 0.2, P = .03), but did not correlate with CSF T‐ or P‐tau levels.ConclusionCSF concentrations of nanoplaques can be quantified with single‐molecule sensitivity using the ThT‐FCS assay. Increased nanoplaque levels are related to the Alzheimer’s continuum and clinical AD, and correlate inversely with levels of Aβ42 monomers/small oligomers determined by immunoassays. The association between this potential biomarker and disease stage should be further explored.