bluuebunny/crossref_metadata_2025_split huggingface dataset:
Relationship between occupation and cognitive performance in patients with cognitive impairment. Preliminary study
Authors: Dorman Guido Santiago , Boccazzi Julian Fernandez , Flores Ignacio , O'Neill Santiago 
Published: December 2023

AbstractBackgroundPrevious studies showed the protective effect of cognitive reserve for the development of cognitive impairment and dementia symptoms. Some factors have been postulated that may influence cognitive reserve, including education, participation in cognitively stimulating activities, and occupation. It has been observed that certain occupations have better cognitive performance and different professions may generate better functioning in certain cognitive domains than others. The aim of this study is to assess whether there is greater strength in certain cognitive domains related to the occupations of patients with subjective memory complaints or mild cognitive impairment diagnosis.MethodRetrospective observational study with patients under follow‐up in a memory clinic in Buenos Aires, Argentina. Patients with >17 education years, > 50 years with a diagnosis of subjective memory complaint and/or mild cognitive impairment of any origin were included. Subjects with dementia were excluded. The occupations were classified according to the ISCO‐88 (2008 International Labor Organization) utilizing professionals’ subcategory. A complete cognitive evaluation was performed in all the patients, including memory, attention, language, executive functions, and visuospatial domains. For the statistical analysis, the z scores of the results of the different cognitive tests were used and parametric student`s‐t tests were performed using the Graphpad software,ResultA total of 57 patients from our center were included to date. The mean age was 71 (55‐85), years of education 19 (17‐25) and a total of 35 (61%) women. The mean of Addenbrooke’s Cognitive Examination (ACE) was 91.3 (82‐99). The predominant occupation was in the health category with a total of 24 (42%) patients. No statistically significant differences were obtained in the values of the different cognitive tests of each occupational category and the value of the total population.ConclusionThe study has not shown significant differences between specific cognitive variables and occupation in patients with cognitive impairment. However, a larger number of subjects would be needed to support this statement. It is important to note that extra‐work activities of patients that can also influence their cognitive performance have not been taken into account.
Triage through motoric cognitive risk syndrome: Is it possible to assess the risk of developing dementia in fast‐paced acute care settings?
Authors: Gonzaga Marilia Cristina de Oliveira , Takahashi Silvia de Fatima , Ferraz Ana Carolina , Suemoto Claudia Kimie , Aliberti Marlon Juliano Romero 
Published: December 2023

AbstractBackgroundMotoric cognitive risk syndrome (MCR) is a practical tool for identifying independent community‐dwelling older people at risk of developing dementia.1 Whether this tool could be efficient in fast‐paced acute care settings, where clinicians have limited resources, remains to be discovered.2 We investigated the performance of MCR to identify acutely ill older outpatients at risk of developing dementia. We also estimated associations of MCR with incident disability, an age‐related condition highly associated with cognitive impairment.MethodCohort comprising older people in need of intensive management (intravenous therapy, laboratory test, radiology) to avoid hospitalization in Brazil. We excluded those with dementia diagnosis or experiencing disability. MCR was defined as presence of memory complaints and slow gait (one standard deviation below age‐ and sex‐specific gait speed means). Over a 3‐year follow‐up, investigators blinded to baseline data assessed the outcomes: (1) dementia diagnosis through detailed reviews of medical records and (2) incident disability (need for help) to execute basic activities of daily living (ADL) and take medications through structured telephone interviews. To investigate associations of MCR with outcomes, we used Fine‐Gray models (considering death as competing risk) adjusted for routine measures (sociodemographic factors, comorbidities, depressive symptoms, and weight loss). We also computed differences between Harrell’s C‐indexes to estimate whether MCR improves outcome discrimination when added to the routine measures.ResultAmong 610 patients (mean age = 77±8 years, women = 63%, non‐white = 40%), the MCR prevalence was 8% (Table 1). Patients with MCR presented a 3‐fold increased risk of developing dementia compared to those without the syndrome (27% vs. 8%; adjusted sub‐HR = 3.2; 95%CI = 1.6‐6.7) (Table 2). MCR was also associated with higher risks of incident disability in ADL and taking medications–an activity highly related to cognitive functioning. When added to routine measures, MCR remarkably improved the discrimination of models predicting dementia (Harrell’s C‐index = 0.76 vs. 0.69, p = 0.03) (Table 3).ConclusionMCR showed excellent performance in predicting the risks of developing dementia and disability among acutely ill older outpatients. The increase in dementia prevalence worldwide demands tools like MCR to expand the identification of high‐risk older people, even in fast‐paced acute healthcare settings where clinicians have limited time and resources.
Sex differences for clinical correlates of substantia nigra neuron loss and Lewy body pathology
Authors: Bayram Ece , Coughlin David G 
Published: December 2023

AbstractBackgroundLewy body pathology staging and substantia nigra neuron loss levels are associated with clinical features in Lewy body dementia (LBD). Compared to women, neocortical Lewy body pathology is more common and co‐pathologies are less common in men. Clinical features of people with limbic and neocortical Lewy body also differ based on sex, although sex differences for additional Lewy body pathology stages or nigral neuron loss are unclear.MethodData was obtained from the National Alzheimer’s Coordinating Center Uniform Data Set (UDS) and Neuropathology Data Set for UDS visits conducted between September 2005 and August 2019. Analysis included 31 women and 62 men from 25 AD Research Centers with Lewy body pathology and substantia nigra neuron loss data, excluding those with other neuropathologic diagnoses including moderate/severe Alzheimer’s disease. Linear models assessed the sex differences for clinical associations of nigral neuron loss level and Lewy body pathology staging controlling for age at last visit.ResultWomen were older at last visit and at death, had less years of education than men (Table 1). Men were more likely to have a clinical LBD diagnosis, had cognitive decline at a younger age, worse dementia at last visit, and higher levels of Lewy body pathology staging and nigral neuron loss. Higher Lewy body pathology stage was associated with more nigral neuron loss more for men compared to women (Table 2). Higher Lewy body pathology stage and greater degrees of nigral neuron loss were associated with more severe dementia and behavioral symptoms and a higher likelihood for a clinical Lewy body diagnosis in men compared to women.ConclusionLewy body pathology staging and the level of substantia nigra neuron loss may be worse for men compared to women. These data also suggest that Lewy body pathology and nigral neuron loss affect men more severely than women in terms of dementia severity and behavioral profiles associated with LBD. The blunted clinical manifestations of these pathological features in women add to the difficulty in accurate diagnosis and future work on the reasons for women’s resilience to these pathological features is needed.
Using the RE‐AIM framework to help implement an educational intervention for improving the care of persons with behavioral and psychological symptoms of dementia in primary care
Authors: Stone Jonathan A , Schroeder Molly , Albrecht Tammi , LeCaire Tamara J. , Carlsson Cynthia M , Walaszek Art 
Published: December 2023

AbstractApproximately 90% of persons living with dementia (PLWD) experience behavioral and psychological symptoms of dementia (BPSD) over the course of their illness, including aggression, psychosis, and depression. With a growing lack of access to specialty geriatric care, most people with BPSD will receive care from their primary care providers. Many primary care practices lack knowledge, self‐efficacy, and established pathways to expert advice for managing these complex behaviors. We have developed a comprehensive educational intervention for primary care providers and clinical staff to help them better address BPSD. The educational intervention combines two complementary approaches: the academic detailing model and the DICE ApproachTM (DICE). In a recent pilot with two primary‐care integrated memory clinic teams, we noted improvements in provider knowledge and clinical staff self‐efficacy and comfort in BPSD and dementia care after 6‐months of participation in academic detailing and DICE training. In our current study, we use the RE‐AIM framework to guide the implementation planning for our educational intervention for primary care providers and clinical staff to help them better address BPSD. The RE‐AIM framework is a widely used tool for evaluating the implementation of health interventions to ensure they are both effective and sustainable. Twenty semi‐structured interviews will be completed among providers practicing in one of two primary care integrated memory clinics who participated in the pilot program (champions) and among their generalist primary care colleagues with no to minimal program experiences (novices), in one urban and one rural healthcare system. The RE‐AIM framework informed the design of our semi‐structured interviews and will help to frame content analysis for identifying potential barriers to implementation, for scale‐up to generalist primary care teams. Five interviews have been completed to date. Qualitative analyses are also underway, and results will be presented. Findings from this study will be used to develop an implementation plan for a future randomized controlled trial to measure the effectiveness of this intervention on health outcomes in PLWD and BPSD.
Discovery‐based proteomics identifies plasma proteins that predict longitudinal cognitive decline in older adults over a 7‐year follow‐up period
Authors: Kresge Hailey A. , Patterson Khiry L , Libby Julia B. , Robb W Hudson , Arul Albert B , Choi Min Ji , Oliver Nekesa , Whitaker Marsalas D , Moore Elizabeth E. , Houston Michelle L , Pechman Kimberly R. , Dumitrescu Logan C , Gifford Katherine A. , Hohman Timothy J. , Robinson Renã AS , Jefferson Angela L. 
Published: December 2023

AbstractBackgroundRecent technological advances have enabled large‐scale proteomic profiling of plasma and especially in studies of Alzheimer’s disease. However, studies that have comprehensively examined longitudinal cognitive decline as an outcome from plasma protein levels prior to the onset of clinical dementia are limited. This project aimed to identify plasma proteins predictive of cognitive decline across a robust neuropsychological protocol over a 7‐year follow‐up period.MethodsVanderbilt Memory and Aging Project participants (n = 333, 73±7 years, 41% female) free of clinical dementia at study entry underwent fasting blood draw and comprehensive serial neuropsychological assessment over a 7‐year period (mean follow‐up = 5.8 years). Plasma samples were subjected to multiplex liquid chromatography tandem mass spectrometry analysis to quantify cross‐sectional protein abundances for each participant at study entry. Normalization of proteomic data adjusted for batch effects, high levels of missingness, and log2 transformation. Linear mixed‐effects regressions related protein levels to longitudinal neuropsychological outcomes, adjusting for age, sex, race/ethnicity, education, baseline cognitive status, apolipoprotein E ε4 status, and follow‐up time. False discovery rate correction was applied to the a priori significance threshold.ResultsInitial proteomics analyses yielded 3,784 proteins, of which 686 were used as analytical predictors following quality control, post‐acquisition filtering, and data normalization. Regression analyses resulted in 86 proteins which predicted longitudinal decline in global cognition, as assessed by the Montreal Cognitive Assessment. In analyses with individual neuropsychological domains as outcomes, 144 proteins predicted longitudinal decline in at least one neuropsychological domain [episodic memory (40 proteins), language (72 proteins), information processing speed (99 proteins), executive function (22 proteins), visuospatial skills (55 proteins)]. There was a smaller number of proteins (i.e., five) that were predictive of longitudinal cognitive decline across all domains.ConclusionWe conducted large‐scale proteomics analyses and identified 144 plasma proteins at study entry among a cohort of older adults free of clinical dementia that predict subsequent decline in cognition over a 7‐year follow‐up period. Five of these proteins were predictive of decline across all domains suggesting these proteins may represent biological pathways that adversely affect brain health with increasing age. Replication is needed to validate identified proteins as potential biomarkers of cognitive decline.
Amyloidosis at Putamen Predicts Vulnerability to Alzheimer’s Disease
Authors: Yang Zhengshi , Cummings Jeffrey L. , Cordes Dietmar ,   Alzheimer’s Disease Neuroimaging Initiative
Published: December 2023

AbstractBackgroundUsing merely cortical amyloid burden in a binary approach was commonly adopted for determining if an individual is under AD pathology in both clinical trials and basic research. Subcortical amyloid, compared to cortical amyloid, showed a larger inter‐subject heterogeneity, which may provide valuable insights to their vulnerability to Alzheimer’s disease beyond cortical amyloid.MethodA total of 1344 individuals from ADNI database had 18F‐AV45 amyloid PET scans available. Regional AV45 signal was computed by averaging the signal from gray matter voxels in each region and then normalized to the mean signal in the composite reference region [1, 2]. The cortical AV45 was averaged over extensive regions consisting of frontal, anterior/posterior cingulate, lateral parietal, and lateral temporal regions. The AV45 signal in the subcortex, including putamen and caudate, were also computed. Only the participants under AD pathology, determined based on cortical amyloid positivity, were included in the analysis. The association analysis between subcortical AV45 and cognition was conducted before and after adjusting cortical AV45. A linear fitting of cortical AV45 and AV45 at putamen was conducted and participants were categorized into high (HighP), middle (MidP) and low (LowP) putamen amyloid group thresholded with ±0.5 standardized residuals. Statistical analysis was carried out to evaluate the difference of clinical diagnosis, hippocampal volume and APOE ε4 genotype. The relevance of amyloid at putamen with the rate of cognitive decline was examined.ResultPutamen, compared to caudate, had a stronger association with ADAS‐cog13 and MoCA, such an association remained exist after adjusting cortical AV45. Despite distinct AV45 at putamen, participants in LowP, MidP and HighP groups had no cortical AV45 difference. The AV45 at putamen was significantly higher in individuals with more ε4 alleles (ε4 homozygous > ε4 heterozygous > non‐ ε4) and more advance clinical stages (Dementia > MCI > CN). The individuals with higher AV45 at putamen had smaller hippocampal volume and faster cognitive decline.ConclusionOur finding suggested that amyloidosis at putamen is a valuable imaging marker beyond cortical amyloid in predicting if a participant is more vulnerable to Alzheimer’s dementia.
Lexical features for repetition task: Turkish language perspective
Authors: Öz Didem , Gorno‐Tempini Marilu , Tee Boon Lead 
Published: December 2023

AbstractBackgroundPrimary Progressive Aphasia (PPA) is a neurodegenerative syndrome that presents with speech and language impairments and is commonly classified into three variants based on varying symptomatology and pathology: semantic (svPPA), nonfluent/ agrammatic (nfvPPA), and logopenic variants (lvPPA). While more than 85% of the world population don’t speak English language as their first or second language, PPA research has largely focused on English speakers. Thus, we may lack adequate understanding to PPA symptoms of typologically different languages. Turkish language is an agglutinative language that commonly combines multiple morphemes in a word. Therefore, Turkish words are frequently high in syllables, morphemes, and words. Repetition test is a frequently used tool to diagnose lvPPA patients by assessing auditory verbal short‐term memory function. However, the capacity for auditory verbal short‐term memory has been known to be influenced by time and morphological structure, which are generally more complex in Turkish. Our study investigates the lexical features critical for repetition task for Turkish language speakers.MethodIn this study, Turkish‐speaking participants are tasked to repeat six lists of words. List 1 and 2 consist of real and pseudo‐words with one morpheme and one word but increasing in syllables; List 3 and 4 comprised of real and pseudo‐words with increasing number of morphemes and syllables; and List 5 and 6 contained words with increasing morphemes, syllables and words. We then studied the performance of cognitively normal and PPA participants when repeating these lists of words and investigated the effect of number of morphemes, syllables and words.ResultsA total of 15 Turkish‐speaking controls and 12 PPA individuals (7 lvPPA, 1 nfvPPA, 4 svPPA) completed the repetition task. Individuals with svPPA and lvPPA scored significantly lower than controls when repeating List 5 and 6 (p = 0.05 and p = 0.03 respectively). Using general linear model, when covarying for number of words, morphemes, and syllable, we found that repetition performance in Turkish‐speaking participants is predicted by the number of words, morphemes, and syllables in both real and pseudo‐word lists.ConclusionWhen designing repetition task for speakers of agglutinative or polysynthetic languages, lexical features such as number of morphemes and syllables might need to be accounted.
Exploratory research on Neurogranin ratios for biomarkers of neurodegeneration
Authors: Kaneko Naoki , Takahashi Ryota , Kato Takashi , Arahata Yutaka , Sekiya Sadanori , Iwamoto Shinichi , Tanaka Koichi , Nakamura Akinori ,   BATON study group
Published: December 2023

AbstractBackgroundNeurogranin (Ng) is a cerebrospinal fluid biomarker for synaptic dysfunction at early stage of Alzheimer’s disease (AD). It has been reported that some truncated forms from Ng is increased in AD brain tissue. However, the clinical significance of Ng forms in plasma has remained unclear. We have developed a simultaneous detection method of a plurality of Ng forms in plasma by using immunoprecipitation combined with matrix‐assisted laser desorption ionization time‐of‐flight mass spectrometry (IP‐MALDI‐MS). In this study, we applied the IP‐MALDI‐MS technique to investigate blood‐based biomarkers for neurodegeneration.MethodPlasma samples were obtained from cognitively normal (CN), mild cognitive impairment (MCI), Alzheimer’s dementia (AD) and non‐Alzheimer’s dementia (non‐AD) individuals in National Center for Geriatrics and Gerontology. These subjects were classified as Aβ positive and negative based on PET with PIB tracer. Ng forms were immunoprecipitated from the samples spiked by stable isotope‐labeled (SIL) Ng peptides using magnetic beads coupled with anti‐Ng monoclonal antibody. After the IP was performed two times consecutively, Ng forms eluted from antibody beads were applied on the MALDI plate. SIL‐Ng peptides were used as internal standards for normalizing an intensity of each endogenous Ng form in plasma.ResultWe calculated intensity ratio of a Ng form‐to‐other Ng form (Ng ratio) in all combinations of peaks corresponding to mass of Ng forms. To investigate the possibility of Ng as a biomarker for neurodegeneration, we screened the Ng ratios with the difference between CN and Aβ positive AD or Aβ negative non‐AD. Eleven Ng ratios were significantly higher in the Aβ positive AD and Aβ negative non‐AD groups than the CN group. In ROC analyses, AUC values greater than 0.750 were found in discriminating the Aβ positive AD or Aβ negative non‐AD group from the CN group. Among the eleven Ng ratios, five were significantly correlated with MMSE (ρ←0.400).ConclusionSome Ng forms cleaved at or nearly the IQ domain have been found in the AD brain, which suggests the function loss of Ng in synaptic plasticity. Increasing Ng ratios in plasma may be biomarker candidates for synaptic dysfunction involved in the change of Ng forms in the brain.
Longitudinal cortical thinning is associated with cognitive decline in MCI and Alzheimer’s disease in the Korean population
Authors: Yu Meichen , Risacher Shannon L , Yi Dahyun , Byun Min Soo , Lee Jun‐Young , Craft Hannah , Sohn Chul‐Ho , Nho Kwangsik , Lee Dong Young , Saykin Andrew J. 
Published: December 2023

AbstractUndAlzheimer’s disease (AD) is characterized by cognitive dysfunction likely secondary to progressive neurodegeneration in the brain. However, to what extent regional cortical thickness (CT) changes are related to cognitive decline in the Asian population remains unclear.MethodWe measured CT using Freesurfer v6 from T1‐weighted magnetic resonance imaging (MRI) data in 603 Korean participants, including 71 young and 288 old cognitively unimpaired (CU young and CU old), 149 with mild cognitive impairment (MCI), and 92 AD from the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer’s disease (KBASE). Cognitive function of each participant was quantified by the MMSE. MRI and cognitive data were acquired at baseline (n = 603) and a 2‐year follow‐up visit (n = 380). Linear mixed‐effect models were used to estimate diagnosis group, time, and group‐by‐time interaction effects on CT measurements, with age, sex, and education as covariates. Pearson’s correlations between CT measurements and MMSE total score were computed, corrected for multiple comparisons by false discovery rate (FDR).ResultAt baseline, CU old participants had lower CT values than CU young participants in the inferior parietal cortex and frontal and parietal regions. In comparison with CU old participants, MCI and AD showed widespread lower CT values, more pronounced in the medial temporal lobe (i.e., the entorhinal cortex and parahippocampal gyrus), inferior temporal cortex, medial prefrontal cortex, and medial parietal cortex (i.e., the posterior cingulate cortex and precuneus), with AD lower than MCI in these regions. These regions also showed the most longitudinal atrophy in both AD and MCI over 2 years. AD patients showed faster and more widespread atrophy patterns than MCI and CU old participants. We identified significant (PFDR<0.05) positive linear correlations between cognitive decline and regional CT measurements, particularly in regions showing significant cortical thinning across time.ConclusionIn this study, we replicated the typical cross‐sectional and longitudinal brain atrophy patterns, and relationships with cognitive decline in an Asian cohort. Our findings support the generalizability of atrophy patterns in MCI and AD, suggesting common neurobiological mechanisms underlying AD symptoms across different ethnoracial populations.