bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predicting change in semantic fluency performance over time in patients with progressive speech and language disorders
Authors: Meade Gabriela , Martin Peter R. , Clark Heather M , Duffy Joseph R , Whitwell Jennifer L , Josephs Keith A , Utianski Rene L 
Published: June 2023

AbstractBackgroundThe semantic fluency task involves naming as many items as possible in a given category (e.g., animals) in one minute. It is often interpreted as a measure of word retrieval, but also draws on executive function abilities to organize responses and develop task‐specific strategies. Indeed, both language skills and dementia severity ratings have recently been found to correlate with semantic fluency performance in patients with primary progressive aphasia (Riello et al., 2022; Scheffel et al., 2021). Here, we focused instead on how performance on language and executive function measures predicts longitudinal change in semantic fluency performance in patients with progressive agrammatic aphasia and/or apraxia of speech (AOS).MethodPatients with isolated agrammatic aphasia (n = 10), isolated AOS (n = 42), or a combination of the two (n = 59) with 1‐7 visits (mean = 2.19) were included. We used Bayesian hierarchical linear models to investigate whether baseline measures of executive function or language were associated with the rate at which semantic fluency performance changes over time while accounting for baseline diagnosis group, sex, education, age at baseline, and baseline disease duration.ResultSemantic fluency performance declined over time, at a similar rate irrespective of diagnostic group (isolated or combined aphasia or AOS; Figure 1). Across all patients, higher executive function abilities at baseline, as indicated by faster Trails Making Test B completion times, predicted higher baseline semantic fluency performance and also a steeper annual rate of decline (Figure 2). Similarly, higher fluency ratings during the Western Aphasia Battery‐Revised picture description at baseline were associated with higher baseline semantic fluency performance and faster decline. Baseline performance on the Boston Naming Test and Token Test were also associated with baseline semantic fluency, but not with longitudinal change.ConclusionThese results better delineate how language and executive function abilities support performance in the semantic fluency task. Higher abilities in those areas at baseline do not appear to be protective over time. Rather, the differences in semantic fluency that are present at baseline disappear as the disease progresses.
The influence of age on cognitive test performance as measured by the original and extended version of the Alzheimer’s disease assessment scale in the SIU longitudinal cognitive aging study
Authors: Agamah Alikem Miriam , Zec Ronald F , Kohlrus Stephanie R. , Ala Tom , Hollinshead Madison G. , Bakir Danah , Porter Nicholas , Unnam Pavani , Chaulagain Suchana , Hascup Erin R. , Trivedi Mehul Alkesh 
Published: June 2023

AbstractBackgroundSince the 1980s, the Alzheimer’s Disease Assessment Scale (ADAS) has been used to evaluate cognitive aging in Alzheimer’s disease (AD) and is considered the gold standard for assessing the efficacy of medications for treatment of AD. One criticism of the original ADAS (oADAS) is that this measure is not sensitive to pre‐dementia syndromes such as mild cognitive impairment (MCI). Previous studies have found that increasing age is associated with poorer neuropsychological functioning. In the present study, we examined the influence of age on the oADAS. We hypothesized that increasing age would be associated with increased error scores on both the oADAS and an extended version of this measure (eADAS) after controlling for gender and education.MethodWe included data from 938 adults who were enrolled in the SIU Longitudinal Cognitive Aging Study (LCAS) as normal controls. The vast majority of the cohort was White/Not‐Hispanic (98.9%) and female (72.4%). Mean age and education were 67.3 years and 14.9 years, respectively. Participants who met the diagnostic criteria for MCI, dementia, and/or other neurological or psychiatric conditions at baseline or developed these conditions within three consecutive study visits were excluded. The oADAS was administered using standardized methods. The eADAS included short‐delay recall and recognition trials for the first word‐list, a short‐delay true‐false word recognition trial for the second word‐list, a letter‐digit timed psychomotor test, supermarket fluency, spontaneous clock drawing, three additional items to the object naming subtest, three additional figures to copy, and a similarities test.ResultThe mean oADAS and eADAS scores were 3.9 and 8.7, respectively. Linear regression analysis revealed that both gender and education were associated with higher error scores for both the oADAS and eADAS (p < 0.001). After controlling for gender and education, increasing age was also found to be associated with higher error scores for both the oADAS and eADAS (p < 0.001).ConclusionOur results are consistent with previous literature showing age effects on oADAS scores and also extend these findings to the eADAS. Future research determining the sensitivity of the extended ADAS to the transition from normal aging to MCI and dementia are ongoing.
Comparison of skin carotenoid content scores and dietary intake between cognitively normal older adults and older adults with Alzheimer’s Disease: A matched‐pair analysis
Authors: Keller Jessica E , Taylor Matthew K , Smith Aaron N. , Burns Jeffrey M. , Swerdlow Russell H , Sullivan Debra K 
Published: June 2023

AbstractBackgroundAlzheimer’s Disease (AD) is a systemic metabolic disease with a variable number and type of clinical symptoms mostly impacting the brain. Skin carotenoid content (SCC) is an objective measure of carotenoid‐containing fruit and vegetable intake that has been validated in diverse populations. Our previous findings suggest SCC scores are impacted by various metabolic disease states. Therefore, our objective was to analyze SCC scores and dietary intake across matched pairs including unimpaired adults and those with AD.MethodBaseline data from two dietary interventions (NCT03860792, NCT03841539) were analyzed. Pairs are exact matches for sex, race/ethnicity, and education and are matched within two years of age and 4 kg/m2 body mass index. Each pair (n = 12 pairs) includes one cognitively normal (MMSE > 25), community dwelling older adult (‘CN’) and one community dwelling older adult with AD (‘AD’). Baseline self‐reported dietary intake data (3‐day food records) were collected, reviewed, and entered into the Nutrition Data System for Research (NDSR 2019) database by a Registered Dietitian. SCC scores were collected through pressure‐mediated reflection spectroscopy via VeggieMeter® (Longevity Link Corporation, Holladay, UT). Two‐sample independent t‐tests assuming unequal variances were used to compare differences in SCC scores and dietary intake. Significance was set at p = 0.05.ResultThere was a significant difference in SCC scores between matched pairs (SCC scores: CN 284.25, AD 207.67, p = 0.008). There was no difference between pairs for total daily energy (kcal/day; p = 0.60), fat (g/day; p = 0.91), carbohydrate (g/day; p = 0.85), or protein (g/day; p = 0.26) intake. Both groups had similar food group intake (p‐value range 0.09‐0.79), including all fruit and vegetable groups except CN had higher intake of non‐citrus fruit (p = 0.046). Total fruit (p = 0.09) and fruit plus vegetable (p = 0.24) were not different between pairs. Dietary intake by individual carotenoid was not significantly different (total vitamin A, p = 0.48; beta‐carotene, p = 0.49; alpha‐carotene, p = 0.57; beta‐cryptoxanthin, p = 0.60; lutein plus zeaxanthin, p = 0.07; lycopene, p = 0.37).ConclusionIndividuals with AD have lower carotenoid skin content compared to matched cognitively unimpaired individuals. These differences are not explained by differences in diet suggesting that AD may be associated with disease‐associated biochemical features that are metabolism‐related and not limited to the brain.
A multianalyte plasma protein signature associated with cognitive function in a healthy ageing population
Authors: Mehta Kanika , Gupta Veer Bala , Mohebbi Mohammadreza , Pasco Julie A , Williams Lana J , Walder Ken , Ng Boon 
Published: June 2023

AbstractBackgroundSeveral studies have been conducted towards the identification of biomarkers for Alzheimer’s disease (AD); however, there are limited biomarker studies investigating the preclinical phase prior to the incidence of AD. The present study aims to identify a multianalyte panel of blood biomarkers associated with overall cognitive function in a healthy ageing male population.MethodA multiple reaction monitoring (MRM)‐based targeted proteomic analysis was conducted using plasma samples of 448 male participants. The abundance levels of 269 plasma proteins known to participate in several physiological processes such as lipid transport, oxidative stress, inflammation, cytoskeleton signalling and complement pathway were measured. Protein concentration values outside the limit of quantitation were assigned as missing and proteins with greater than 10% missing values were removed from the analysis. Consequently, 125 proteins were included in the statistical analysis. In order to build a multimarker model, the least absolute shrinkage and selection operator (LASSO) regression analysis was conducted. This was followed by pathway mapping of the proteins selected by the model.ResultPreliminary analysis revealed a 12‐marker model (R‐squared = 32%) comprising age and the following proteins: Apolipoprotein A‐I, Apolipoprotein C‐I, Alpha‐1‐acid glycoprotein 1, Carboxypeptidase N catalytic chain, Coagulation factor XI, Complement C1q subcomponent subunit B, Glutathione peroxidase 3, Neuropilin‐2, Insulin‐like growth factor‐binding protein complex acid labile subunit, Protein AMBP and Lysozyme C.ConclusionA multianalyte panel consisting of plasma proteins was built for predicting cognitive function using cross‐sectional analysis methods. Furthermore, to predict long‐term cognitive changes, follow‐up assessments will be required.
Long‐COVID causal impacts on cognitive ability of mild‐cognitive impaired population from large‐scale electronic health record using heterogeneous causal effect model
Authors: Alam Mohammad Arif Ul , Mahi Atqiya Munawara , Rahman Md Mahmudur , Alam Saima , Nunes Anthony 
Published: June 2023

AbstractBackgroundIdentification of long‐COVID impacts on human cognitive ability is important but Randomized Controlled Trial (RCT) is not possible. Virtual RCT (VRCT) can be done from electronic health record (EHR) which requires to address heterogeneity appropriately.MethodWe design new method for VRCT on COVID intervention among Mild Cognitive Impaired (MCI) population. We select patients (n = 71,900) from National COVID Cohort Collaborative (N3C) data who meet our inclusion criteria (Table‐1 and Table‐2). We compute 28 Cognitive Impairment (CI)‐related covariates (Table‐3). Final outcome is CI and COVID‐19 diagnosis is intervention. To formulate a placebo like intervention virtually, we compute covariates: (i) For COVID positive patients, consider pre‐COVID histories, (ii) For Non‐COVID having transition MCI‐to‐CI, consider 6 months before first CI diagnosis, (iii) For Non‐COVID having no transition MCI‐to‐CI, consider 6 months before last recorded data. We utilize Heterogenous Causal Effects using Random Forest (HCE‐RF) model[1] to estimate COVID‐19 effects on 7 different CI outcomes. HCE‐RF, proven method in machine learning (ML)‐based VRCT, estimates conditional average causal effect (CATE) where 0 and 1 mean no and highest risk.ResultCOVID‐19 causes (details Table‐4) 54% (CATE:0.5489 CI[0.5428, 0.5618]) higher risk of developing any kind of dementia within 6‐months LongCOVID given the patient has prior MCI which is higher for severe (0.6498 CI: [0.6066, 0.6817]) and little bit lower, for mild COVID‐19 (0.5489 CI: [0.5428, 0.5618]). Similarly, COVID‐19 with different severity (mild‐to‐severe) causes significant higher risks of developing mixed dementia of any two types, Alzheimer’s disease or Vascular dementia without behavioral disturbance among MCI patients compared with COVID‐19 uninfected population. On the other hand, COVID‐19 infection causes no significant risk of developing presenile, senile and vascular dementia without behavioral disturbance for MCI patients in 6 months LongCOVID.ConclusionWe proposed new method of developing VRCT cohort on observational data to identify disease intervention effect on disease progression in presence of heterogeneity of causes and effects and it on EHR data to identify LongCOVID (6 months) causal risks on MCI patients in developing different CIs. Our method can be utilized to uncover many hidden effects of COVID‐19 on observational data.[1] https://doi.org/10.3386/w24678
Benefit of plasma exchange with albumin replacement on individual items of the quality of life‐Alzheimer’s disease score
Authors: Stewart Walter F , Lipton Richard B. , Gomez‐Ulloa David , Runken M Chris , Grifols Carlota , Iaconangelo Charlie , Serrano Daniel 
Published: June 2023

AbstractBackgroundAlzheimer Management By Albumin Replacement (AMBAR) is a multicenter, randomized, placebo‐controlled, Phase IIb/III clinical trial that evaluated the efficacy and safety of Plasma Exchange with Albumin replacement (PE‐A) in patients with mild‐to‐moderate Alzheimer’s disease (Boada et al., Alzheimers Dement. 2020). PE‐A has demonstrated an overall benefit in quality of life as measured by the Quality of Life‐Alzheimer’s disease (QoL‐AD) score (Boada et al., Alzheimers Dement. 2021). We evaluated PE‐A treatment benefit for each of 13 individual patient‐rated QoL‐AD items.MethodA cumulative logistic mixed model was applied on the Full Analysis Set (FAS) population. The odds that a patient receiving PE‐A would have a more favorable response (i.e., higher item score) than a similar subject receiving placebo was estimated at final visit for each QoL‐AD item. Age, baseline MMSE score, and baseline individual QoL‐AD item responses were included as covariates.ResultThe FAS included 76 placebo patients and 229 PE‐A‐treated patients. A significant PE‐A treatment effect vs. placebo at final visit was observed for QoL‐AD item 4: Living situation (“How do you feel about the place you live now?“) [Odds Ratio (OR) = 3.92 (95% CI: 1.38‐11.12), p = 0.010] and for QoL‐AD item 13: Life as a whole (“When you think about your life as a whole, everything together, how do you feel about your life?”) [OR = 3.80 (95% CI: 1.32‐10.91), p = 0.013].ConclusionThe analysis demonstrated that when compared to patients on placebo, patients receiving PE‐A were more likely to have a favorable response for the QoL‐AD items “Living situation” and “Life as a whole”, suggesting that the reported benefit of PE‐A vs. placebo on the full QoL‐AD score is also observed in these individual QoL‐AD items.
Executive function may underlie cognitive reserve: A 3‐year follow‐up study
Authors: Seo Eun Hyun , Yoon Hyung‐Jun , Lim Ho Jae , Lee Kun Ho 
Published: June 2023

AbstractBackgroundThe hypothetical concept of cognitive reserve (CR) has been proposed to explain why someone can manage to function normally even in the presence of brain pathology. However, it still remains to be determined what components constitute such resilience against Alzheimer’s disease (AD) pathology. In the current study we investigated the characteristics of cognitively normal (CN) elders with high CR.MethodWe included CN participants from the Gwangju Alzheimer’s Disease and Related Dementia Cohort in Korea. We selected a group of CN individuals who showed a significant amyloid‐beta (aß) deposition at baseline and stayed CN over the follow‐up period. They were defined as high CR group. For comparison purpose, individuals with a significant aß deposition at baseline but converted to MCI at follow‐up were also included. In the final analysis, 94 high CR group and 24 control group were included. Group comparisons in socio‐demographic, clinical and cognitive variables were performed using χ2 tests and ANOVA controlling for age, education, gender, and follow‐up month.ResultMean follow‐up month were 43.37. There were no group differences in education, gender, socio‐economic status, family history of dementia or stroke, medical conditions, body mass index, subjective memory complaints, and instrumental activities of daily living. However, high CR group was younger and had shorter follow‐up period, therefore such variables were controlled when cognitive tests were compared. High CR group was more religious (p < 0.001), showed higher complexity in former job (p = 0.009), and higher level of executive functoning (Digit Dpan Backward, p = 0.012; Fluency test, p = 0.008; Boston Naming Test, p = 0.014; Trail Making Test part B, p = 0.017) than control group. There were no group differences in episodic memory tests and visuospatial abilities.ConclusionIndividuals with high CR could cope better with AD pathology. Many factors have been suggested to be associated with CR. Regarding cognitive process involved, our findings suggest that executive function plays an important role in constituting high CR. Preserved executive function may, at least in part, underlie CR.
The National Israel Brain Repository: Characterizing those who sign and do not sign intent to autopsy
Authors: Manzali Sigalit , Ravona‐Springer Ramit , Ouyang Yuxia , Lin Hung‐Mo , Heymann Anthony , Greenbaum Lior , Liraz‐Zaltsman Sigal , Beeri Michal Schnaider 
Published: June 2023

AbstractBackgroundCollection of postmortem human brain and spinal cords for research is invaluable, especially in neurodegeneration, since human clinicopathologic data may lead to better understanding their pathophysiology and to new therapeutic targets. The National Israel Brain Repository was established in 2018 and began recruiting donors from two large‐scale community‐based studies of individuals at high dementia risk: older adults with type 2 diabetes (Israel Diabetes and Cognitive Decline study‐IDCD) and middle‐aged offspring of AD patients (The Israel Registry for Alzheimer’s Prevention‐ IRAP).We compared sociodemographic, cardiovascular (CVRFs)and cognitive characteristics of individuals who agreed and did not agree to sign intent to autopsy (ITA)MethodIn the IDCD, of the 750 active participants, we approached 636. Of them, 196 (31%) agreed to sign ITA.IRAP has 480 active participants of whom 395 were approached and of them 176 (45%) agreed to sign ITA. All participants are from the Maccabi Health Services, providing CVRF data since 1998. Using t‐test we compared the groups on sociodemographic and CVRFs. For IDCD, which averages 36‐months cognitive follow ups, mixed regression models adjusting for age, sex and education tested whether signing ITA predicted cognitive trajectories. For IRAP, whose follow‐ups have only recently begun, we used linear regressions adjusting for the same covariates, compared cognitive functioning between those the two groupsResultIn the IRAP sample, participants who signed ITA did not differ from those who did not sign on any of the characteristics except for HbA1c (Table 1). In the IDCD sample, those who signed ITA had higher education, creatinine, and BMI and better motor function (hand grip and 3‐meter walk). Finally, those who signed ITA had a slower rate of decline in episodic memory (Estimate = 0.002, SE = 0.001, p = 0.05)ConclusionOur results suggest that middle‐aged adults at high AD risk willing to donate their brains to science do not differ in sociodemographic or CVRFs from those who do not wish to be organ donors. In contrast, older adults at high dementia risk due to T2D who signed ITA are more educated, have better motor function and a slower rate of cognitive decline suggesting a selection bias towards better health.Development of strategies to diminish this selection bias are warranted.
Association of microbiota‐derived products with astrogliosis and neurodegeneration in patients with Alzheimer’s Disease
Authors: Marizzoni Moira , Mirabelli Peppino , Mombelli Elisa , Coppola Luigi , Lopizzo Nicola , Luongo Delia , Naviglio Daniele , Salamone Dominic , Salvatore Marco , Cattaneo Annamaria , Frisoni Giovanni B 
Published: June 2023

AbstractBackgroundMicrobiota‐derived short chain fatty acids (SCFA) and liposaccharide (LPS) could modulate astrocyte and neuronal activity. Glial fibrillary acidic protein (GFAP) and neurofilament light (NfL) are markers of astroglial activation and neuronal damage, can be measured in blood samples and have been associated with Alzheimer’s disease (AD) pathology. The aim of the present study was to assess the association of SCFAs and LPS with GFAP and NfL in 13 amyloid‐β‐negative cognitively unimpaired individuals (CU), 38 patients with cognitive impairment and no brain amyloidosis (CI‐NAD) and 34 patients with cognitive impairment and amyloid‐β positivity (CI‐AD).MethodBlood levels of 4 SCFAs (acetate, propionate, valerate and butyrate) were measured by GC‐FID gaschromatography, LPS by ELISA, and GFAP and NfL by single‐molecule array technology.ResultPlasma valerate, LPS and GFAP concentrations were increased in CI‐AD compared with CI‐NAD and CU (p<0.034), acetate was increased in CI‐AD as well as decreased in CI‐NAD as compared with CU (p<0.018) and NfL was increased in both CI groups (p<0.023). In the pooled group of CI‐AD and CU, there were significant associations between plasma LPS and valerate with higher GFAP and NfL (p<0.032). Conversely, in the pooled group of CI‐NAD and CU, there were associations between plasma acetate with lower level of GFAP and NfL (p<0.026).ConclusionValerate and LPS were associated with astrogliosis and neuronal damage only in patients with AD. These results suggest that microbiota‐derived molecules might be mediators along the gut‐brain axis and contribute to AD pathology by modulating microglial and neuronal activity.