bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multi‐modal MR and synaptic PET changes in dementia with Lewy bodies
Authors: Mak Elijah , Carter Stephen F , Savulich George , Holland Negin , Swann Peter , McKiernan Elizabeth , Chouliaras Leonidas , Malpetti Maura , Su Li , Jones P Simon , Rowe James B. , O'Brien John T 
Published: December 2023

AbstractBackgroundNovel, validated imaging biomarkers for assessing disease severity and progression in dementia with Lewy Bodies (DLB) are needed as standard neuroimaging changes such as atrophy are not pronounced. Both multi‐modal MR and PET offer opportunities, for example cortical microstructure and dendritic imaging can be assessed using advanced MR diffusion weighted imaging (DWI) methods such as neurite orientation dispersion and density imaging (NODDI) and PET with UCB‐J can assess synaptic density. We applied these and other markers to people with DLB and controls.MethodIn linked studies, people with probable DLB and similarly aged controls (n = 10‐30 per group depending on study) underwent multimodal 3T‐MRI (including structural, multi‐shell DWI and arterial spin labelling imaging) and PET imaging with AV1451 (for assessment of tau), PiB (for amyloid status) and [11C]UCB‐J PET/MR. For MR, T1‐MRI and DWI datasets were processed using FreeSurfer 7.2 and FSL 6.0.4 respectively with whole‐brain ODI derived from the Microstructure Diffusion Toolbox. The [11C]UCB‐J and [18F]AV1451 binding potentials (BPND) were assessed using a simplified reference tissue model (reference centrum semiovale for UCBJ and cerebellum for AV1451). Group differences in ODI, UCB‐J and AV1451 BPND were examined and correlated with structural changes and clinical and cognitive variables (ACE‐R score).ResultCompared to controls, people with DLB showed significantly thinner neocortex (T = ‐2.8, p = 0.01) in temporo‐parietal regions but more widespread reductions in cortical microstructure (ODI, T = ‐3.9, p < 0.001)(Figure 1). Within the DLB group, hippocampal ODI was positively correlated with cognitive performance (robust linear regression: p < 0.001)(Figure 2). Reduced synaptic density (UCB‐J BPND) was found for the DLB group in posterior regions (p<0.05, FWE corrected)(Figure 3), with a trend for greater reductions in those who were amyloid positive. ACE‐R scores significantly correlated with synaptic density (p<0.05, FWE corrected). There were no significant differences in AV1451 binding between DLB and controls.ConclusionExtensive reductions in ODI and reduced synaptic density, both associated with cognitive impairment and occurring in regions without significant atrophy or tau deposition, suggests that NODDI and synaptic PET imaging are promising biomarkers for DLB which merit further investigation, including in longitudinal studies.
Thalamocortical dysrhythmia in patients with delirium: an EEG possible marker of prodromal dementia with Lewy bodies
Authors: Bonanni Laura , Carrarini Claudia , Calisi Dario , De Rosa Matteo , Iorio Angelo Di , D'Ardes Damiano , Gazzina Stefano , Pilotto Andrea , Arighi Andrea , Carandini Tiziana , Cagnin Annachiara , Gallucci Maurizio , Costa Cinzia , D'Antonio Fabrizia , Bruno Giuseppe , Cipollone Francesco , Babiloni Claudio , Onofrj Marco , Padovani Alessandro 
Published: December 2023

AbstractBackgroundEEG in DLB is characterized by pre‐alpha dominant frequency (DF) [6–7.5] Hz. The appearance of prealpha rhythm in the cortex is linked to a dysfunctional thalamocortical connection, the thalamocortical dysrhythmia (TCD). The hypothesis that TCD is implicated in DLB has been demonstrated by several structural, functional, and molecular imaging studies. TCD has been implicated in the appearance of altered conscious states, including fluctuating cognition and delirium, two clinical core features of DLB. Delirium can represent the onset of DLB and is listed among the symptoms of prodromal DLB. We aimed to assess specific QEEG abnormalities akin to those found in DLB, also in delirium, to detect a prodromal stage of DLB.MethodCross‐sectional multicentre cohort study and longitudinal prospective study, nested in the multicentre. rsEEG activity was compared in hospitalized patients with delirium vs. patients without delirium. In a subset of 23 patients, rsEEG was also recorded in patients with delirium at resolution of symptom and and at 1‐month follow‐up. DF and DF variability (DFV) were analysed.
ResultCross‐sectional multicentre study: 65 subjects with acute delirium were matched for age/sex with 41 controls. Abnormal EEGs were found in 100% delirium patients vs. 34% no‐delirium patients. DF was lower in delirium group (p<0.001), which showed pre‐alpha DF; no‐delirium group had alpha DF. DFV was higher in delirium group (p<0.001). Single‐centre longitudinal study: After delirium resolution, 21 patients had EEG normalization and were cognitively unimpaired. 2 patients had abnormal EEG and were respectively diagnosed as DLB and MCI.ConclusionAcute delirium was characterized by pre‐alpha rhythm, expression of TCD. In most patients EEG normalized after resolution, making EEG a state marker of acute delirium, when the thalamocortical system becomes unstable, but it is still able to recover. TCD may become unrecoverable when the neurodegenerative process of DLB progresses.
Ultra‐processed food consumption and risk of dementia and Alzheimer’s disease: the Framingham Heart Study
Authors: Weinstein Galit , Koijs Daniel , Walker Maura , Beiser Alexa S. , Seshadri Sudha 
Published: December 2023

AbstractBackgroundUltra‐processed foods (UPFs) are industrialy‐processed formulations that constitute a large and increasing amount of the food supply in high and middle‐income countries. Accumulating evidence suggests that UPFs are related to increased risk of mortality and morbidity, including cardiovascular and metabolic health conditions, however its association with dementia risk has rarely been studied. We investigated the association of UPF sonsumption with risk of dementia and Alzheimer’s disease (AD) in the Framingham Heart Study.MethodThe sample for this cohort study included participants of the Offspring cohort who were ≥60y of age, completed a food‐frequency questionnaire (FFQ) and were dementia‐free at baseline. Food items included in the Harvard semi‐quantitative FFQ were classified as UPFs using the NOVA classification system. Participants were followed‐up for dementia incidence starting from exam 7 for a mean duration of 12.7±6.0 years. Cox regression models were used to assess the link of UPF levels with dementia and AD risk while adjusting for potential confounders, including diet quality and total calorie consumtion. Effect modification by age, BMI, diabetes and ApoEɛ4 genotype were additionally assessed.ResultThe study sample included 1,519 participants (mean age 68±6 years, 53% women). The average consumption of UPF at baseline was 6.1±3.4 servings per day. During the follow‐up, 253 and 196 were diagnosed with dementia and AD, respectively. Overall, no statistically significant associations were observed between UPF consumption and dementia or AD risk. However, an effect‐modification by age was identified (p‐for interaction = 0.016 and 0.007, for dementia and AD, respectively). Among participants younger, but not older than 68 years of age (i.e. median), the risk of dementia was increased comparing individuals at the top four quartiles to the bottom quartile (HR = 2.9; p‐value = 0.015). Each serving per week of UPF derived from low‐calorie soft drinks was significantly associated with 4% increase in risk of AD (HR = 1.04; p‐value = 0.012), but not all‐cause dementia (HR = 1.03; p = 0.074). However, the association of total UPF with dementia risk remained robust after omitting UPF from low‐calorie soft drinks (HR = 2.4; p‐value = 0.029).ConclusionOur findings suggest that UPF consumption in middle‐age and young‐old adulthood may be related to increased risk of all‐cause dementia.
Use of α‐synuclein seed amplification assays to assess how clinical features relate to the diagnosis of Dementia with Lewy Bodies
Authors: Middleton John , MacLeod Karen R , Bozoki Andrea , Galvin James E , Irwin David J , Lippa Carol , Litvan Irene , Lopez Oscar L. , Berman Sarah , Tsuang Debby W , Zabetian Cyrus P , Honig Lawrence S. , Marder Karen , Fleisher Jori E , Sabbagh Marwan , Wint Dylan , Taylor Angela , Bekris Lynn M. , Leverenz James B , Galasko Douglas R. 
Published: December 2023

AbstractBackgroundDementia with Lewy Bodies (DLB) is defined by abnormal deposits of alpha‐synuclein (Lewy bodies), in the brain. DLB may be accompanied by variable co‐pathology, especially Alzheimer’s Disease (AD). DLB is diagnosed clinically, with definitive diagnosis only possible at autopsy. Misdiagnosis may occur due to overlapping symptoms in different dementias.The alpha‐synuclein (αSyn) seed amplification assay (SAA) is a qualitative test that detects misfolded aggregates of αSyn in synucleinopathies, including DLB, with high sensitivity and specificity. In autopsy‐confirmed AD with limbic or neocortical synuclein pathology, SAA was positive even when DLB phenotypic features were mild (Arnold et al., 2022).We are now evaluating SAA in cerebrospinal fluid (CSF) samples and clinical features in patients with DLB followed through a multi‐Center DLB Consortium (NINDS U01NS100610), which is part of the NINDS Parkinson’s Disease Biomarkers Program (PDBP).MethodCSF from 3 groups: 1) analytical controls: youngest available age, no neurological symptoms, normal neurological exam; 2) clinical controls: no symptoms/signs, age and gender match to DLB; 3) DLB. SAA will be run blind to diagnosis using standardized assay methods by Amprion. We will compare Core clinical features of DLB patients and SAA. We hypothesize that SAA‐ patients will have less clear clinical features for DLB, and will be likely to meet clinical and/or CSF biomarker criteria for other diagnoses, e.g., AD.Core clinical features will be defined as strongly or weakly present, e.g., REM Sleep Behavior Disorder: PSG‐proven (strong); +questionnaire (weak); Parkinsonism: ≥ 2 cardinal features (strong); 1 feature (weak). Hallucinations and fluctuations are described in standardized rating scales/interviews. CSF AD biomarkers (Aβ42, t‐Tau and p‐Tau181) were analyzed for almost all DLB subjects.Sensitivity and specificity of each Core clinical feature will be calculated in relation to SAA+ and SAA‐ results.ResultSubjects were recruited at 8 clinical sites across the USA from 2017‐2021. Demographics of subjects with available CSF are shown in Table 1. Demographics, clinical features and CSF AD biomarker results will be presented in SAA+ and SAA‐ groups .ConclusionResults will inform how well different core clinical features predict pathological αSyn (CSF SAA+) in people diagnosed with DLB.
Genetic characterization of NOTCH2NLC repeat expansion in patients with neuronal intranuclear inclusion disease (NIID)
Authors: Fitrah Yusran Ady , Higuchi Yo , Hara Norikazu , Kasuga Kensaku , Miyashita Akinori , Ikeuchi Takeshi 
Published: December 2023

AbstractBackgroundNeuronal intranuclear inclusion disease (NIID) is a neurodegenerative condition that which is caused by abnormal expansion of GGC repeat in NOTCH2NLC. Despite the increase of the reported patients with NIID, how the repeat sequence and length in NOTCH2NLC affect the development of NIID remains unclear. We report the genetic characterization of repeat expansion and sequence of NOTCH2NLC in Japanese patients with NIID.MethodsFifteen patients clinically diagnosed with adult‐onset NIID were genetically analyzed. Repeat expansion in NOTCH2NLC was examined by repeat‐primed PCR. Repeat length was determined by amplicon length PCR. Repeat length and sequence were analyzed by Nanopore long read sequence.ResultsRepeat primed PCR analysis revealed a sawtooth pattern in 15 patients who were clinically suspected as having NIID. This suggests the presence of repeat expansion in NOTCH2NLC. Next, we performed amplicon‐length PCR to determine the repeat size. The mean repeat length of was 8.2±1.5 (range 7 to 10) in normal allele and 92.5±12.8 (range: 71 to 110) in expanded allele. To define the repeat length and sequence, we performed Nanopore long read sequencer. The repeat size was 138.6±69.0 (range: 95 to 361) in expanded allele. The GGC repeat length was 114.5±36.6 (range: 44 to 194). One patient carried pure GGC repeat expansion, and remaining patients carried others trinucleotide repeat including GGA, AGC, and GAC. Most frequent trinucleotide insertion was GGA at the end of GGC repeat, which is commonly observed in normal allele. We identified two patients who carried bi‐allelic GGC expansions.ConclusionAbnormal repeat expansion in NOTCH2NLC was identified as heterozygous or bi‐allelic state in patients with NIID. There was heterogeneity of length and sequence in expanded repeat expansion of NOTCH2NLC. The further study is required to understand how genetic heterogeneity correlates with clinical presentations of patients with NIID.
Suitability of Computerised and Pencil‐and‐Paper Neuropsychological Assessments in Healthy Older Culturally and Linguistically Diverse Australians: The CogSCAN Study
Authors: Page Zara A , Croot Karen , Brodaty Henry , Sachdev Perminder S. , Lam Ben C. P. , Kochan Nicole A. 
Published: December 2023

AbstractBackgroundComputerised neuropsychological assessments (CNAs) are proposed as more accessible and culturally appropriate alternatives to traditional pencil‐and‐paper neuropsychological assessments (PnPAs) for diagnosing dementia in diverse populations. Whilst some PnPAs have demonstrated cultural and linguistic bias, research investigating the suitability of CNAs for culturally and linguistically diverse (CALD) individuals is limited, especially outside of the United States.MethodThis study compared cognitive performance in a heterogenous sample of older Australian CALD English‐speakers and an L1 English‐speaking background (ESB) sample. Cross‐sectional data were drawn from the ongoing CogSCAN Study. Participants were 212 community‐dwelling individuals aged 60‐95 years without a dementia diagnosis (159 ESB/53 CALD). Participants completed a PnPA and/or CNAs, sessions were counterbalanced accordingly. CNA sessions involved two of four commercially‐available CNAs in a randomised order. Differences in the level and pattern of cognitive performance between groups on two CNAs (CANTAB/Cogstate) and a comprehensive PnPA in English, controlling for sociodemographic and health factors, are reported here. Selection of key variables for examination were based on previous findings (PnPA) and test developer recommendations (CNAs).ResultSample characteristics are summarised in Table 1. CALD participants’ cognitive performance on individual tests (Figure 1) was largely comparable to ESB participants on PnPA and each CNA. Significant differences between groups, after Bonferroni correction for multiple comparisons, were observed for the Boston Naming Test (PnPA; a language test widely criticised for use with CALD populations due to culturally biased stimuli) and Rapid Visual Information Processing (CANTAB; a test of attention/processing speed). Among participants who completed PnPA and Cogstate, a significant interaction between group and assessment type on global cognitive performance was observed; ESB participants outperformed CALD participants on PnPA, but not on Cogstate (Figure 2). No significant main effects or interaction were observed in PnPA versus CANTAB.ConclusionThese results showed fewer and smaller discrepancies across groups and assessment types than has been found in previous literature with other CALD samples, perhaps reflecting higher levels of English proficiency, acculturation, and education in English than previous cohorts. Work in progress is investigating the influence of linguistic and acculturation factors on cognitive performance in a larger and more diverse sample.
Usefulness of the Visual Cognitive Assessment Test (VCAT) in detecting mild cognitive impairment in the community
Authors: Soo See Ann , Kumar Dilip , Leow Yi Jin , Koh Chen Ling , Saffari Seyed Ehsan , Kandiah Nagaendran 
Published: December 2023

AbstractBackgroundA delay in the detection of Mild Cognitive Impairment (MCI) in the community delays the opportunity for early intervention. Accurate tools to detect MCI in the community are lacking. The Visual Cognitive Assessment Test (VCAT) is a visual based cognitive test useful for multilingual populations without the need for translation. Here, we evaluate the usefulness of VCAT in detecting MCI in a community population in Singapore.MethodWe recruited 469 participants from the community who completed a detailed neuropsychological assessment and 261 of them completed a 3T Magnetic Resonance Imaging (MRI) brain scan. We performed a ROC analysis to test the diagnostic performance of VCAT compared to MoCA in distinguishing mild cognitive impairment (MCI) from cognitively normal (CN) by measuring area under the curve (AUC). To test for the association of VCAT with structural MRI, we performed a Pearson’s correlation analysis for VCAT and MRI variables.ResultWe recruited 39 CN, 168 subjective cognitive decline and 262 MCI participants from Dementia Research Centre (Singapore). Mean age of the cohort was 62.77, SD = 9.57, mean education years was 13.97, SD = 3.41 and majority were women (57.8%). VCAT was effective in detecting MCI from CN with an AUC of 0.794 (95% CI 0.723‐0.865) which was slightly higher than MOCA 0.699 (95% CI 0.621‐0.777). Among subjects with MCI, VCAT was associated with medial temporal lobe atrophy (MTA) (ρ = ‐0.265, p = 0.001).ConclusionThe VCAT is useful in detecting MCI in the community in Singapore and may be an effective measure of neurodegeneration.
The detrimental effects of apathy on cognition, frailty and quality of life
Authors: Soo See Ann , Leow Yi Jin , Lee Faith Phemie Hui En , Ghildiyal Smriti , Koh Chen Ling , Kandiah Nagaendran 
Published: December 2023

AbstractBackgroundApathy is defined as the lack of motivation and has been found to be associated with incident dementia in western populations (Dalen, 2018). Little is known about the impact of apathy in Asians. Apathy is a prevalent behavioural symptom of pre dementia and current literature shows that apathy increases the risk of dementia (Bock, 2020). Apathy is also linked to an increased risk of frailty(Ayers, 2018) and found to impair executive function and processing speed(Lohner, 2017). We aim to evaluate the association of apathy with cognitive function, frailty and lifestyle factors in a pre‐dementia community population in Singapore.MethodWe recruited 534 participants from the community who completed a detailed neuropsychological assessment. Apathy was measured using the mild behavioural impairment checklist (MBI‐C). To test for the association of apathy with the different variables, we performed a multiple generalized linear model controlling for covariates age, sex and education.ResultThe study population included 186 participants with subjective cognitive decline and 348 mild cognitive impairment participants from Dementia Research Centre (Singapore). Mean age of the cohort was 62.55, SD = 9.55, mean education years was 13.97, SD = 3.45 and majority were women (57.1%). The prevalence of apathy among our cohort was 23.5%. Compared to participants without apathy, those with apathy had poorer cognitive scores in processing speed (test of coding) (β = ‐4.60, p<0.001), executive function (colour trails 2) (β = 9.71, p = 0.020), episodic memory on the RAVLT Delayed (β = ‐0.738, p = 0.026), RCFT Delayed (β = ‐1.941, p = 0.009) and FCSRT delayed (β = ‐0.616, p = 0.030). Participants with apathy were also more frail (β = 0.316, p<0.001) on the Fried Phenotype frailty assessment test and had poorer quality of life (β = ‐12.49, p<0.001), had lower levels of physical activity (β = 0.163, p = 0.017), and had poorer sleep (β = 2.25, p<0.001).ConclusionApathy is associated with worse cognitive performance, higher frailty, lower physical performance and poorer sleep in an Asian pre‐dementia community cohort. Screening for apathy and appropriate early intervention could reduce incidence of dementia and frailty.
What do elevated cerebrospinal fluid p‐tau levels signify in the absence of beta‐amyloid pathology?
Authors: Wisse Laura , Binette Alexa Pichet , Strandberg Olof , Palmqvist Sebastian , Stomrud Erik , Janelidze Shorena , Mattsson‐Carlgren Niklas , Blennow Kaj , Hansson Oskar 
Published: December 2023

AbstractBackgroundThe introduction of the A/T/(N) (β‐amyloid/tau/neurodegeneration) framework has revealed an A‐T+ (β‐amyloid‐negative/tau‐positive) group which has been named suspected non‐Alzheimer’s pathophysiology. Cerebrospinal fluid (CSF) markers are often utilized to divide individuals in the A and T categories, but it is unclear what elevated CSF p‐tau levels signify in the absence of β‐amyloid. We aim to better understand A‐T+ as defined by CSF markers in two independent samples of cognitively unimpaired and impaired individuals by assessing baseline and longitudinal change in CSF, magnetic resonance (MRI), positron emission tomography (PET) and cognition measures.MethodCognitively normal (CN) and Mild Cognitive Impairment subjects from BioFINDER‐1 and 2 were included. A status was based on two CSF measures of β‐amyloid 42/40 (Aβ42/40) where A‐ individuals had to be negative on both measures using previously established cut offs. T status was determined by the 75th, 80th and 85th percentile of A‐ CN subjects for Roche Elecsys p‐tau181 (Table 1). Analyses of covariance and linear mixed models were performed to assess baseline and change differences in CSF (p‐tau181, Aβ42/40 ratio, neurofilament light (NFL)), MRI (hippocampal volume, entorhinal cortex and temporal meta‐region of interest thickness), cognition (modified Preclinical Alzheimer’s Cognitive Composite and delayed recall), and PET measures (entorhinal cortex Tau‐PET and early and global Alzheimer’s Disease composite β‐amyloid‐PET uptake) over 8 years (10 for cognition) for BioFINDER‐1 and 4 years for BioFINDER‐2.ResultIn A‐T+ versus A‐T‐, higher baseline NFL levels were found. No other baseline differences were found except for p‐tau181 and Aβ42/40 ratio by design. A‐T+ did not show significant change compared to A‐T‐ on any measure. Using different cut offs for p‐tau181 did not notably change the results. Comparisons with the A+ groups are shown in Figures 1‐2.ConclusionOur results indicate that A‐T+ as determined by p‐tau181 does not seem to be clinically meaningful as this group shows no decline on any of the biomarkers or cognitive measures over several years. The high NFL levels in the A‐T+ group suggest the presence of a latent factor that affects both NFL and p‐tau levels. Analyses will be repeated with other p‐tau isotopes and assays.