bluuebunny/crossref_metadata_2025_split huggingface dataset:
[18F]RO‐948 Tau PET Retention and Correlation with Fluid Tau Biomarkers in the Early AD Continuum
Authors: Shekari Mahnaz , Milà‐Alomà Marta , Falcon Carles , Niñerola‐Baizán Aida , Tonietto Matteo , Borroni Edilio , Klein Gregory , Ashton Nicholas J. , Karikari Thomas K , Rodriguez Juan Lantero , Snellman Anniina , Ortiz‐Romero Paula , Vanmechelen Eugeen , Minguillón Carolina , Fauria Karine , Perissinotti Andrés , Molinuevo Jose Luis , Zetterberg Henrik , Blennow Kaj , Grau‐Rivera Oriol , Suárez‐Calvet Marc , Gispert Juan Domingo 
Published: December 2022

AbstractBackgroundTau positron emission tomography (PET) imaging enables the in vivo visualization of tau aggregates occurring during the progression of Alzheimer’s disease (AD). Tau PET imaging is a promising biomarker for clinical diagnosis and tracking of disease progression. However, the sensitivity of tau PET in detecting early tau pathology within the early AD continuum and its association with fluid tau biomarkers remains to be established.MethodForty‐seven cognitively unimpaired individuals from the ALFA+ cohort had [18F]RO‐948 and [18F]flutemetamol PET, T1‐weighted magnetic resonance imaging (MRI), cerebrospinal fluid (CSF), and plasma tau biomarkers available (Table1). CSF amyloid(A) and tau(T) positivity were defined using CSF Aß42/40 ratio and ptau181 measured by the exploratory NeuroToolKit and Elecsys® immunoassays, respectively, according to pre‐established thresholds (Milà‐Alomà et al., 2020). Centiloid (CL) values were obtained from [18F]flutemetamol PET scans using a validated pipeline. [18F]RO‐948 uptake was measured in entorhinal (BraakI/II), limbic (BraakIII/IV), and neocortical (BraakV/VI) regions and normalized to the inferior cerebellum to render SUVR values. Regional positivity thresholds per Braak stage were calculated as the median plus two robust standard deviations. Associations between [18F]RO‐948 SUVRs and fluid tau biomarkers were evaluated using Spearman’s rho correlations. P‐values<0.05 were considered statistically significant. [18F]RO‐948 SUVRs were modeled against CL values using the data‐driven robust LOWESS method.ResultIn BraakI/II, 5 cases were considered to be positive, 3 in BraakIII/IV and 2 in BraakV/VI (see Table2 for thresholds), all of them being A+T+. Significant correlations with fluid biomarkers were observed in all Braak stages (Table3, Figure1). [18F]RO‐948 SUVR in BraakI/II showed a linear trend with CL values and inflection points between 20 and 30 CLs were observed for all Braak stages (Figure2).ConclusionA progressively lower number of [18F]RO‐948 PET‐positive cases were detected for more advanced Braak stages as expected from neuropathological studies. [18F]RO‐948 uptake started increasing around 20‐30 CLs and correlated with wet tau biomarkers in cognitively unimpaired individuals, suggesting that [18F]RO‐948 PET can be more sensitive to initial tau pathology than previously thought. These preliminary findings demonstrate that the ALFA+ cohort is well‐suited to study early pathophysiological alterations in preclinical AD stages.
Association between nutritional status and dementia staging among Alzheimer’s disease patients in Peru: Preliminary results of the Genetic of Alzheimer’s Disease in Peruvian Population Study
Authors: Montesinos Rosa , Chambergo‐Michilot Diego , Malaga Diego , Ore‐Gomez Maria Fernanda , RIVERA‐FERNANDEZ CLAUDIA , Soto‐Añari Marcio , Reyes‐Dumeyer Dolly , Failoc‐Rojas Virgilio E , Casavilca‐Zambrano Sandro , Custodio Nilton , Tosto Giuseppe 
Published: December 2022

AbstractBackgroundAlzheimer’s Disease Related Dementias (ADRD) is estimated to increase up to 152 million in 2050. Dementia‐related mortality increases with older age, male sex, neuropsychiatric symptoms, faster cognitive decline, physical impairment and disease severity. Malnutrition is an important ADRD complication due to its impact on several domains. Prior studies showed that malnutrition is associated with behavioral and cognitive impairment (emotional disinhibition and behavior disturbance, memory impairment) and higher mortality risk among ADRD patients. Prevalence of malnutrition is heterogeneous and may depend on disease severity. We aimed to assess the association between malnutrition and dementia severity in an outpatient cohort of Peruvians, part of the Genetic of Alzheimer’s Disease in Peruvian Population (GAPP) Study.MethodA cross‐sectional study was carried out in three different sites of different altitude in Peru. We included individuals aged >50 years who attended memory clinics. We used the Mini‐Nutritional Assessment (MNA) scale to assess the nutritional status, and the Clinical Dementia Rating (CDR) to grade the dementia. We stratified the nutritional status in normal (MNA score: 12‐14) and malnourished or risk of malnourished (MNA: 11 or less).ResultWe assessed 295 patients; mean age was 71.9 (SD: 8.3) and 68.8% were females; proportion of demented (CDR> = 1) was 23%. Prevalence of malnourishment and risk of malnourishment was 6.4% and 35%, respectively. When adjusted by demographic covariates and geographical recruitment site, we found malnourishment scores significantly associated with CDR scores (e.g. CDR 2‐3: PR 2.27, 95% CI: 1.95‐2.62). Malnourishment was not associated with cardiovascular risk factors or diseases.ConclusionIn our Peruvian cohort, malnourishment or risk of malnourishment was found associated with higher risk of ADRD. Prevalence of malnourishment or risk of malnourishment was in line with those reported in other South American countries. Further longitudinal studies should confirm this association.
Examining brain structural and functional changes in mTBI with biomarkers of neurodegeneration
Authors: Cordero Indira Ruth Garcia , Vasilevskaya Anna , Taghdiri Foad , Khodadadi Mozhgan , Tator Charles , Mikulis David , Tarazi Apameh , Mushtaque Asma , Colella Brenda , Green Robin , Tartaglia Carmela 
Published: December 2022

AbstractBackgroundMild traumatic brain injury (mTBI) in former contact sports athletes is a risk factor for dementia. However, it is unknown why only some individuals with mTBI develop dementia, suggesting that head injury exposure alone is not sufficient to produce the condition. We hypothesize that mTBI could be associated with neurodegenerative processes that target specific brain structures and connectivity networks and increase vulnerability to dementia.Method46 male former professional athletes with a history of multiple concussions were recruited. To compare participants with evidence of underlying pathology versus participants without any evidence, the sample was divided into neurodegenerative biomarker positive (N+, n = 25) and negative (N‐, n = 21) groups. The division was based on the positivity in at least one of these biomarkers: cerebrospinal fluid total tau (> 300 pg/ml), cortical positron emission tomography tau standardized uptake value ratio (>1.30) and serum neurofilament light‐chain (> 12.5 pg/ml). Groups were matched for age and number of concussions. Cognitive profiles were assessed by comparing the following scores between groups: Trail Making Test ratio, Digit Span Backwards, Paced Auditory Serial Addition Test, verbal fluency, and Rey Auditory Verbal Learning Test (RAVLT). Grey matter volume was calculated by voxel‐based morphometry and compared between groups. Functional connectivity differences were evaluated for the default mode (DMN), the salience (SN) and the dorsal attention (DAN) networks.Results(N+) presented more number of intrusions at immediate (p = 0.04, FDR corrected) and short delay recall (p = 0.02, FDR corrected) and worse recognition discrimination index (p = 0.02, FDR corrected) in the RAVLT in comparison to (N‐). In addition, (N+) displayed more atrophy in the left frontal superior and middle gyrus (p < 0.001, extended threshold = 50 voxels) and disconnection of the DAN (p < 0.001, FWE cluster correction) versus (N‐). No significant differences were obtained for the DMN and SN.ConclusionFrontal atrophy and DAN abnormal connectivity may underlie cognitive deficits in the (N+) group. Biomarkers of neurodegeneration provide a sensitive tool to detect participants with structural and functional changes and may associate with higher risk to develop dementia after mTBI.
Functional connectivity of basal nucleus of Meynert, locus coeruleus and ventral tegmental area in MCI and mild dementia in Alzheimer’s disease
Authors: Burle dos Santos Guimaraes Fernanda , Balthazar Marcio Luiz Figueredo , de Campos Brunno 
Published: December 2022

AbstractBackgroundCholinergic, noradrenergic and dopaminergic dysfunction plays an important role in Alzheimer’s disease (AD). Basal nucleus of Meynert (BNM), locus coeruleus (LC) and ventral tegmental area (VTA) are its main producer nuclei, respectively. Neuropathological studies have shown that structural changes are present in these areas from the beginning of the disease. As such, we aim to identify changes in the functional connectivity (FC) from these nuclei in patients with mild cognitive impairment (MCI) and dementia (DA) in AD, compared with healthy controls (HCs).MethodWe analyzed data from 43 subjects with altered beta‐amyloide in the cerebrospinal fluid (23 MCI; 20 mild to moderate dementia) and 16 controls. Participants underwent rs‐fMRI and neuropsychological evaluation. FC maps to the whole brain were generated (UF²C‐toolbox) using the BNM, LC and the VTA as seeds separately. The second level analysis was performed with an ANCOVA test including the individual FC maps, transformed to z‐score (Fischer R‐Z transformation) generated with each seed and group and regressing for age and years of education using SPM12‐toolbox. The significance level was defined as p<0.001 at the voxel level and p<0.05 FDR corrected at the cluster‐level. In addition, only anatomical regions with more than 60 voxels were described.ResultRegarding BNM, compared to HCs, patients with MCI showed significantly decreased FC in the left precentral gyrus and left anterior insula (volume 62.05 and 61.59 voxels, respectively, Figure 1). Similarly, DA patients, when compared to HCs, showed significantly decreased FC in the left and right medial precentral gyrus (volume 104.06 and 82.75 voxels, respectively) and in the right supramarginal gyrus (volume 64.68 voxels, Figure 2). Regarding VTA, unexpectedly, we found that, compared with MCIs, DA patients showed increased FC in the left central operculum (volume 92.29 voxels, Figure 3). There were no other between‐group changes that reached statistical significance for right and LC and VTA.ConclusionAD patients present changes in the NBM‐FC to the precentral gyrus, insula and supramarginal gyrus. These findings may embase new research for cholinergic dysfunction and possible biomarkers.
Home health staff knowledge and experience of delirium and delirium superimposed on dementia in older adults
Authors: Fick Donna Marie , Shrestha Priyanka , Boltz Marie , Doan William 
Published: December 2022

AbstractBackgroundPrevious studies have shown delirium is common in the home setting and can indicate a medical emergency. Many older adults come into the hospital or ER with delirium. However, little is known about the recognition of delirium by home health workers and community nurses. The purpose of this study is to explore the experience of home health staff caring for an older adult with delirium and delirium superimposed on dementia (DSD), with a focus on capturing rich details of these experiences and their knowledge of recognition and management of delirium.MethodStory circle methodology was employed. Data were collected from 20 staff members (age x̄ = 50, SD = 12.33) of a home health agency that serves 18 counties across rural Pennsylvania via Zoom video conference. Qualitative content analysis was utilized (Sandelowski, 2010). The reporting of this study followed the criteria for reporting qualitative studies in the (COREQ) 32‐item checklist.ResultNine themes emerged: (i) Negative emotions; (ii) A sudden change; (iii) Knowing the person with dementia; (iv) Potential causes of delirium; (v) Fear of delirium and staff fear; (vi) Lack of protocol; (vii) Distancing and redirecting for management; (viii) Role of family and care partners; and (ix) Barriers to identification.ConclusionThis is one of only a few studies that have explored delirium and DSD in the home health setting. This study had several innovations, including the use of story methodology and exploring the views of interdisciplinary team members. Importantly, delirium was a common occurrence in the stories they shared. Delirium often resulted in an ER visit or hospitalization. One of the most important findings was that home health staff had training for dementia and depression, but no training, agency protocol, or standardized assessment tool for delirium. A second important finding was the contribution of family and care partners in the assessment and management of delirium in persons with dementia. Implications for practice, research, and policy will be discussed.
Impact of bilingualism on prevalence of dementia and MCI: A community study from India
Authors: Paplikar Avanthi , Venugopal Aparna , Ballal Divya , Varghese Feba , Ramappa Renuka , Shekar Revathy , Manae Tejaswini , Hoskeri Rakshith , Thanissery Nithin , Arshad Faheem , Banavaram Aravind , Rao Girish , Arora Narendra , Alladi Survana ,   AADAR Dementia Science Research Group, India
Published: December 2022

AbstractBackgroundActive bilingualism provides cognitive reserve/resilience against age‐related neurodegenerative conditions like MCI and dementia. Evidences suggest that bilingualism delay the onset of MCI and dementia by preserving cognitive functioning for a longer period of time. India has a linguistically diverse population where bilingualism is a norm and its effects on cognitive reserve are devoid of immigration, education and socioeconomic status. We conducted a door‐to‐doorcommunity‐based study to investigate the impact of bilingualism on the prevalence of dementia and MCI in healthy older monolingual and bilingual population. The study also examined the effect of bilingualism on cognitive performance.MethodA total of 1145 older adults (366 monolinguals and 779 bilinguals) were recruited. The cognitive functions of elderly persons of ≥ 60 years old residing in urban Bengaluru, India were assessed using Clinical Dementia Rating Scale (CDR), Addenbrooke’s Cognitive Examination (ACE‐III), TNI, Verbal Learning Test (VLT), and Instrumental Activities of Daily Living‐Elderly (IADL‐E). The Language Use Questionnaire (LUQ) scores were used to categorize speakers into monolinguals and bilinguals. Based on the neurologic, neuropsychological, and functional data, participants were classified into 3 categories: normal cognitive functioning, MCI (based on Petersen’s criteria), and dementia (based on DSM‐IV criteria).ResultThere was a significant difference in the proportion of MCI and dementia patients between monolingual (2.10 % dementia and 7.14 % MCI) and bilingual (0.40 % dementia and 4.64 % MCI) elderly (p < 0.001) (Table 1). Healthy elderly bilinguals performed significantly better on global cognition and delayed verbal recall than monolinguals independent of the effects of age, education and gender (Table 2).ConclusionThe findings of this large door‐to‐door community study reveals the protective role of bilingualism in developing cognitive impairment due to MCI and dementia. Furthermore, the study demonstrates the effect of bilingualism as a measure of cognitive reserve/resilience through better cognitive status and episodic memory in older people from a socio‐culturally and linguistically diverse population.
Improving Dementia Care Practices: Implementation of an Innovative Interprofessional Delirium Prevention Program for Hospitalized Older Adults
Authors: Ladak Anila ,   Geriatrics
Published: December 2022

AbstractBackgroundDelirium, an acute decline in cognition and attention, is a common and severe problem for hospitalized older adults, with incidence rates ranging from 11% to 56%, and 1.5 to 4.0‐fold increased risk of death. Delirium in older adults with preexisting Dementia is prevalent. Delirium may worsen the cognitive decline, prognosis, and long‐term outcomes of dementia. Despite its multifaceted nature, delirium is preventable in 30% to 40% of cases. A California academic community hospital experienced a higher incidence of delirium (30% to 40%) in adult non‐critical care units as compared to delirium rates (11% to 29%) in similar hospital settings.MethodThis evidence‐based, quality improvement project was a two‐group, pre‐post design using the educational intervention. The project was implemented in two stages: 1) education on completing the Delirium Prevention Bundle (DPB) including the Delirium Risk Factor Identification (DRFI) tool, targeted delirium prevention strategies, and documentation; and 2) the DPB implementation on a 26‐bed geriatric unit at a 250‐bed academic community medical center. Demographic data on patients and staff were collected. Staff delirium knowledge was assessed. Data on delirium incidence rate were collected pre‐post‐intervention. Statistical analyses included descriptive statistics, t‐tests, and chi2 testResultImplementation of the DPB education, the addition of the DRFI tool, and documentation template in the hospital Electronic Health Record, was effective in reducing delirium incidence rate from 16% to 14% (p = <.001).ConclusionInterprofessional education utilizing the DPB is an effective approach in increasing awareness of preventive care for delirium and decreasing incident delirium in this population.References:1. Inouye S. Delirium in older persons. N Engl J of Med. 2006; 354(11):1157‐1165. https://doi.org/10.1056/NEJMra052321
2. Fong TG, Tulebaev SR, Inouye SK. Delirium in elderly adults: diagnosis, prevention and treatment. Nat Rev Neurol. 2009;5(4):210‐220. https://doi.org/10.1038/nrneurol.2009.24
3. Witlox J, Eurelings LS, de Jonghe JF, Kalisvaart KJ, Eikelenboom P, van Gool WA. Delirium in elderly patients and the risk of postdischarge mortality, institutionalization, and dementia: a meta‐analysis. J Am Med Assoc. 2010;304(4):443‐451. DOI: 1001/jama.2010.1013
Targeting the Correct Population for Trials: A Post‐hoc Analysis of Trial of Solanezumab for Mild Dementia Due to Alzheimer’s disease.
Authors: Ezzati Ali , Petersen Kellen K. , Nallapu Bhargav Teja , Davatzikos Christos , Wolk David A. , Rabin Laura , Habeck Christian , Hall Charles B , Lipton Richard B. 
Published: December 2022

AbstractBackgroundUp to 50% of placebo treated participants in AD clinical trials do not show clinically meaningful cognitive decline (CMCD) over the course of study. Inclusion of these individuals makes it more difficult to demonstrate the benefits of treatments intended to slow cognitive decline. Here, we used data from the trial of solanezumab for mild AD (EXPEDITION3) to investigate effectiveness of predictive models for enrichment of trials.MethodA total of 1072 patients with mild dementia and biomarker evidence of amyloid by PET or CSF studies were enrolled in the placebo arm of EXPEDITION3 trial. 893 patients completed the trial and had baseline structural MRIs making them eligible for this analysis. We identified cognitive decliners, individuals with CMCD, based on the score of the 14‐item cognitive subscale of the Alzheimer’s Disease Assessment Scale (ADAS‐cog14; Range 0‐90; change of ≥4 from baseline to week 80) versus stable cognition, individuals without CMCD (change of <4 from baseline to week 80). Random forest classifiers were trained to classify participants into cognitive decliners vs. stable cognition groups using 3 feature‐sets: Model‐1) Demographics + Neuropsychological test (NP); Model‐2) Demographics + biomarkers (APOE4 alleles and volumetric MRI); Model‐3) All available measures. 70% of data was used for training and 30% for validation.ResultSample characteristics are summarized in Table 1. CMCD was observed in 55.8% of participants at week 80. In the validation sample, model 2 had the best performance in differentiating the two subgroups (AUC = 0.70), followed by model 3 (AUC = 0.68). Model 1 had poor performance in differentiating the two subgroups with AUC = 0.56. Table 2 summarizes performance metrics of models. Positive predictive value of the best performing model (model 2) was approximately 12% higher than the base prevalence of cognitive decline, and negative predictive value of it was approximately 20% higher than the base prevalence of participants who had stable cognition.ConclusionA large portion of biomarker confirmed AD cases enrolled in this trial did not show CMCD on placebo treatment. Predictive models have the potential to improve the design of AD trials through selective inclusion criteria for participants expected to decline and exclusion of those expected to remain stable.
Three‐dimensional study on morphological changes of arterioles in Cerebral Amyloid Angiopathy
Authors: Antunes Lissa Ventura , Bosworth Allison M , Nackenoff Alex , Shostak Alena , Snider John C , Sturgeon Sarah M , Merryman David W , Solopova Elena , Fernandez Wilber Romero , Lippmann Ethan S , Schrag Matthew 
Published: December 2022

AbstractBackgroundThe accumulation of β‐amyloid plaques in the brain is a hallmark of Alzheimer’s disease. Vascular involvement is also common in the form of cerebral amyloid angiopathy (CAA), a vasculopathy that is produced when the β‐amyloid forms toxic deposits on vessels wall. The accumulation of β‐amyloid makes blood vessels stiff and increases the thickness of the vessel wall, reducing the blood flow and energy supply for the tissue. This predisposes to hemorrhage and contribute to cognitive decline and stroke.MethodWe used the CLARITY method to analyze tissue samples from patients with CAA to characterize changes to vessel morphology associated with vascular degeneration. The blood vessels were stained with isolectin, β‐amyloid with thiazine red, and proteins with primary antibodies associated with the vascular structure. We conducted 3D microscopy using a light sheet microscope and performed surface volume reconstruction to assess the morphology of rupturing vessel. We also measured arteriolar stiffness of vessels damaged using atomic force microscopy (AFM). Finally, we assessed cerebral blood flow and autoregulation in vivo in a novel mouse model of CAA using laser speckle flowetry.ResultVessels with CAA demonstrate an organized ring‐shaped deposits β‐amyloid. At sites, these rings are shattered and the vessel diameter increase. Degenerating vessels also demonstrate depletion of vascular smooth muscle, circumferential luminal dilation, and thickening of the vessel wall. Lysyl oxidase levels and markers of fibrosis are increased in vessels with degenerating features. We found that the arteriolar wall was more than 400% stiffer in CAA than in arterioles without CAA in the mice model. Finally, in a novel mouse model of CAA we are terming the VASC‐FAD model, resting cerebral blood flow and vasoreactivity are both reduced.ConclusionCombining the CLARITY technique associated with surface volume rendering and AFM we have a better overview of microhemorrhages to understand the vascular fragility and morphological changes, and accumulation of myofibroblast markers caused by the β‐amyloid deposition and stiffness. These features combine to alter the physiology of cerebral blood flow. Defining mechanism of microvascular degeneration in AD and CAA may lead to novel treatment targets to restore the ECM and vascular network integrity.