bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Alzheimer's Disease Assessment Scale–Cognitive Subscale (ADAS‐Cog): Validation of Slovenian version for detecting mild cognitive impairment or Alzheimer's dementia
Authors: Ulbl Janina , Rakusa Martin 
Published: December 2021

AbstractBackgroundWith the increasing number of elderly, it is necessary to have a brief screening tool for detecting people with cognitive impairment. Our study aimed to standardise and validate the Slovenian version of ADAS‐Cog for a cognitive screening of people with MCI or AD.MethodWe included 26 people with MCI, 20 with AD, and 45 healthy controls. All participants completed the Slovenian version of ADAS‐Cog. We calculated the mean age, years of education, and ADAS‐Cog score for each group and compared them ANOVA. In the end, we draw the Receiver operator curve (ROC), calculated sensitivity, specificity, and likelihood ratio.ResultPeople with AD had the highest total ADAS‐Cog score, followed by MCI and healthy controls (26 SD 12 vs 19 SD 7 vs 8 SD 2 points, p<0.001). There were no statistically significant differences between groups in age or years of education.The area under the ROC for MCI was 0.97 (CI 0.9 to 1; p<0.0001) and for the AD was 0.98 (CI 0.95 to 1; p<0.0001). Optimal the cut‐off for the ADAS‐Cog for MCI was 11/12 points. Sensitivity was 92% (CI 76% to 99%), specificity 96% (CI 85% to 99%), and likelihood ratio 21. The optimal cut‐off for AD was 14/15 points. Sensitivity was 95% (CI 76% to 100%), specificity 100% (CI 92% to 100%).ConclusionThe optimal cut‐off score for Slovenian population is 11/12 points for MCI and 14/15 points for people with AD dementia. We may conclude that ADAS‐Cog is a reliable screening tool in our population.
COVID‐19 and older adults with Down syndrome: Presentation, complications and risk for mortality
Authors: Baksh Asaad , Strydom Andre , Sherman Stephanie , Dierssen Mara , Costa Alberto , Huels Anke ,   T21RS COVID‐19 Initiative
Published: December 2021

AbstractBackgroundHealth conditions (including high rates of Alzheimer's disease, AD), immune dysfunction, and premature aging associated with trisomy 21 (Down syndrome, DS) may impact the clinical course of COVID‐19.MethodThe T21RS COVID‐19 Initiative launched an international survey for clinicians or caregivers on patients with COVID‐19 and DS. Data collected between April and October 2020 (N=1046) were analysed and compared with the UK ISARIC4C survey of hospitalized COVID‐19 patients with and without DS.ResultMortality rates in individuals with DS diagnosed with COVID‐19 showed a rapid increase from age 40 and were considerably higher in patients with DS (T21RS DS versus non‐DS patients: risk ratio (RR)=3.5 (95%‐CI=2.6;4.4), ISARIC4C DS versus non‐DS patients: RR=2.9 (95%‐CI=2.1;3.8)) even after adjusting for known risk factors for COVID‐19 mortality. Similar to the general population, the most frequent signs and symptoms of COVID‐19 were fever, cough, and shortness of breath. Joint/muscle pain and vomiting or nausea were less frequent (p<0.01), whereas altered consciousness/confusion were more frequent (p<0.01). Risk factors for hospitalization and mortality included age, male gender, diabetes, obesity, and AD, with the addition of congenital heart defects as a risk factor for hospitalization.ConclusionIndividuals with DS and COVID‐19 present with significantly higher rates of medical complications and mortality compared to general population peers, especially from age 40. The signs/symptoms of COVID‐19 and risk factors for severe disease course are similar to the general population. Those with dementia are at even greater risk, despite being younger than typical patients with AD. Individuals with Down syndrome should be prioritised for SARS‐Cov‐2 vaccination at younger ages than their peers in the general population.
Longitudinal associations of regional cortical tau and apathy in mild cognitive impairment and Alzheimer’s disease dementia: Findings from the Alzheimer’s Disease Neuroimaging Initiative
Authors: Premnath Pranitha Y , Gonzalez Christopher , Properzi Michael J , Rosenberg Paul B. , Marshall Gad A , Gatchel Jennifer R 
Published: December 2021

AbstractBackgroundApathy is among the earliest and most clinically distressing neuropsychiatric symptoms (NPS) in Alzheimer’s Disease (AD). Examining the relationships between apathy and AD pathology is needed to better understand neurobiological mechanisms for therapeutic intervention that could delay disease progression. Research has shown that tau may correlate more closely with cognitive and behavioral manifestations in AD than amyloid. In the current study, we examined the relationship between regional tau burden and longitudinal change in apathy in older adults with mild cognitive impairment (MCI) and AD dementia from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database.MethodA total of 319 ADNI participants (233 with MCI; 86 with AD dementia; age: 75.5 ±8.2; 56% female) underwent flortaucipir (FTP) tau positron emission tomography (PET) and clinical assessment with the Neuropsychiatric Inventory (NPI) every 6‐12 months (average follow up= 39.1 months). The NPI Apathy (NPI‐A) score was examined in relation to tau PET signal in four FreeSurfer defined regions of interest implicated in AD and mood regulation: entorhinal cortex (EC), precuneus, inferior temporal cortex and rostral anterior cingulate cortex (rACC). Separate linear mixed models examined the association between NPI‐A (for each study visit) and FTP SUVR in the above regions and their interactions with time as predictors of interest. Age and sex were included as covariates.ResultHigher precuneus, EC and inferior temporal cortex tau were each significantly associated with greater NPI‐A over time (precuneus: ß=0.0273; t=5.01; 95 % CI (0.016, 0.04); p<0.001; EC: ß=0.023; t=5.05; 95 % CI (0.014, 0.032); p<0.001; inferior temporal: ß=.018; t=4.92; 95 % CI (0.011, 0.026); p<0.001. rACC tau was marginally associated with higher NPI‐A over time: ß=.013; t=1.93; 95 % CI (‐0.00, 0.027) p=0.05.ConclusionThese findings suggest that tau burden in brain regions associated with AD, and less so with mood regulation, is associated with increasing apathy over time in individuals with MCI and AD dementia. Further study of emergent apathy in relation to core AD pathology and other neurobiological mechanisms will provide insight into opportunities for interventions that could slow clinical progression and alleviate patient and caregiver burden.
Pharmacodynamic assessment of orally available Mas agonists
Authors: Raman Dhanalakshmi Shankara , Reyes‐Reyes Elsa M , Trial Michael , Hurst Chelsie , Hallquist Austin , Rodgers Kathleen E 
Published: December 2021

AbstractBackgroundOxidative stress (OS) plays a crucial role in driving Alzheimer’s disease (AD) pathogenesis. Angiotensin II (A‐II), the ligand for AT1R (pathological axis of the renin angiotensin system [RAS]), promotes the development of AD in part by increasing OS. Mas receptor and its ligand angiotensin (1‐7) (A(1‐7); protective axis of RAS) inhibits A‐II's pathological actions. Two orally available small molecule Mas agonists, RASRx1902 and RASRx1911, were developed to overcome shortcomings of A(1‐7). Both RASRx1902 and RASRx1911 reduce brain OS 90 days after transaortic constriction surgery (TAC), suggesting that both drugs might reduce neurodegeneration. To understand their pharmacodynamics, RASRx1902 and RASRx1911 were tested in the TAC model to determine their optimal dose and dosing regimen, and biological activity.MethodC57BL/6J mice underwent TAC or sham surgery. After echocardiography performed, mice were randomized based on their TAC gradient. Mice received one dose of saline, RASRx1902, or RASRx1911 at a range of subcutaneous or oral doses and euthanized at 0.5, 1, 2, 4 and 6 hours post‐treatment. After dose and route of delivery optimization, mice were treated 1x/day, 2x/day, 2x/week or 3x/week for 2 weeks. Brain tissues were isolated and analyzed for pharmacokinetics, functional markers for OS, and Akt/ERK activation.ResultsOne to three weeks after TAC surgery, the levels of mitochondrial superoxide were increased in microglia, but not in neurons, oligodendrocytes, and astrocytes compared with sham surgery. Treatment with RASRx1902 and RASRx1911, administered either subcutaneously or orally, reduced microglial superoxide levels compared to saline‐treated TAC mice. RASRx1902 showed a stronger inhibitory activity on TAC‐mediated superoxide production than RASRx1911. RASRx1902 and RASRx1911 treatment reduced the TAC‐mediated decreased Akt/Erk activity in brain compared to saline treatment.ConclusionsMicroglial mitochondrial superoxide is the main contributor to promote OS, a contributor to AD neurodegeneration. Our data clearly show that our metabolically stable small molecule Mas agonists have the capacity to decrease ROS levels in microglia and might mediate neuronal survival through Akt/Erk signaling pathway. Therefore, RASRx1902 and RASRx1911 are promising novel drug for the treatment of AD.
Efficacy of cognitive stimulation therapy virtual program for older adults with dementia in COVID‐19 isolation
Authors: Sanchez Cintia P 
Published: December 2021

AbstractBackgroundCognitive stimulation virtual therapy (CSVT) is an evidence‐based psychosocial intervention for people with mild‐to‐moderate dementia due to various etiological factors.ObjectiveThe aim of the present study was to assess the efficacy of a cognitive stimulation virtual therapy CSVT program, in individuals who have vascular or Alzheimer dementia in COVID‐19 isolation.MethodsOlder adults with mild vascular or Alzheimer dementia (N = 20) were assigned to one of two programs: one group (N = 10) attended during six months, two sessions per week program of the cognitive stimulation virtual therapy CSVT program, while the other, active control group (N = 10) took part in alternative activities. The following tests were applied to their primary caregivers. A short form of the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) and quality of life (Quality of Life (QoL)ResultsCompared with the active controls, the cognitive stimulation virtual therapy CSVT program showed a greater improvement in general cognitive functioning after the intervention (i.e. score increase on the IQCODE test). A trend towards improvement was also identified in short term/working memory and perceived quality of life (Quality of life (QoL) of elderly with dementia). The primary caregivers also perceived an improvement in mood, stress, anxiety and quality of sleep after the start of the virtual therapy during COVID‐19 isolation.ConclusionThe present results support the efficacy of cognitive stimulation virtual therapy CSVT program in people with dementia during COVID‐19 isolation.
Targeted microRNA characterization in various brain cell‐derived exosome subtypes to identify novel biomarkers for Alzheimer’s disease
Authors: Kumar Ashish , Su Yixin , Kumar Pawan , Hughes Tim M. , Craft Suzanne , Deep Gagan 
Published: December 2021

AbstractBackgroundMicroRNAs (miRs) offer exciting diagnostic and therapeutic opportunities for Alzheimer’s disease (AD). However, most information about human miRs is from either plasma or CSF of uncertain cellular origin or from postmortem AD brain, which suffers significantly for miR integrity and expression. The discovery of brain cells‐derived exosome (BCDEs) in plasma has led to studies examining their role as ‘liquid biopsies’ for AD. Here, we simultaneously isolated 6 BCDE subtypes from plasma and characterized them for specific miRNAs regulating synaptic plasticity, memory, Aβ, tau, ischemia, and neuroinflammation related signaling pathways.MethodTE were isolated from plasma samples obtained from the Wake Forest Alzheimer’s Disease Research Center: normal cognition (NC; n=8), mild‐cognitive impairment (MCI; n=3), MCI to AD (n=6), and AD (n=11). Next, following 6 BCDE subtypes were extracted using streptavidin‐coated magnetic beads and specific biotin‐tagged antibodies: neuron‐derived exosomes (L1CAM‐biotin antibody), astrocytes‐derived exosomes (GLAST‐biotin antibody), microglia‐derived exosome (TMEM119‐biotin antibody), oligodendrocyte‐derived exosomes (PDGFRα‐biotin antibody), endothelial‐derived exosomes (PECAM1‐biotin antibody), and pericyte‐derived exosomes (PDGFRβ‐biotin antibody). The purity, concentration and size of TE and each BCDE subtype was assessed by flow cytometry, nanoparticle tracking, immunogold labeling, and electron microscopy. The expression of 8 specific miRs (miR‐9a‐5p, miR‐29‐5p, miR‐106‐5p, miR‐107, miR‐125b‐5p, miR‐132‐5p, miR‐135b‐5p, and miR‐210) was measured by TaqMan assays on real‐time PCR.ResultWe observed statistically significant changes in the expression of all 8 miRs in various BCDE subtypes at MCI, MCI‐AD and AD stages. Importantly, we did not observe significant change for most miRNAs in TE, except for miR‐107 and miR‐135b‐5p, highlighting the importance of studying BCDE. Moreover, basal expression of several miRNAs was significantly different between TE and BCDEs. Interestingly, miR‐106b‐5p, miR‐135b‐5p, miR‐107, and miR‐9a‐5b consistently showed significantly higher expression at MCI, MCI‐AD and AD stages for most BCDE subtypes. While the expression of miR‐125b‐5p, miR‐29a‐5p, and miR‐132‐5p showed statistically significant differences based upon BCDE subtype (either an increase or a decrease); for hypoxiamir ‘miR‐210’, expression was higher at MCI stage but decreased with AD progression.ConclusionBCDEs characterization in plasma offers a less invasive opportunity to better understand AD pathogenesis at the cellular level, and to discover novel theranostic targets.
Associations between air pollution exposure and subtypes of cognitive performance in older women
Authors: Petkus Andrew J , Wang Xinhui , Younan Diana , Beavers Daniel P , Espeland Mark A , Millstein Joshua , Chui Helena C , Gatz Margaret , Chen Jiu‐Chiuan 
Published: December 2021

AbstractBackgroundAir pollution exposure is a novel environmental risk factor in brain aging. It remains unclear whether long‐term exposure in older adulthood is associated with profiles of cognitive performance across multiple domains.MethodParticipants included 2,185 women (aged 66‐83 years) without dementia from the Women’s Health Initiative Study of Cognitive Aging. Baseline neuropsychological assessment included tests of verbal episodic memory (California Verbal Learning Test), figural memory (Benton’s Visual Recognition Test), language (letter and category fluency), attention (Digit Span Forward and Backwards), and visuospatial ability (Card Rotations Test). Testes were adjusted for demographic age, education, and race/ethnicity. Average annual levels of particulate matter of aerodynamic diameter<2.5 (PM2.5) and nitrogen dioxide (NO2) were estimated at the participant’s residence using regionalized national universal kriging models and averaged over the 3‐year period before the baseline assessment. Latent class structural equation models (SEM) were constructed to identify latent classes of women who had similar patterns of performance across cognitive tests. After identifying the number of latent classes extract in the model, we constructed a second SEM to examine associations between air pollution exposure and latent class membership using multinomial regression while adjusting for demographic, lifestyle, and clinical confounders.ResultFive significant latent classes were identified (Figure 1): multidomain cognitive impairment (n=247; 11%), amnestic cognitive impairment (n=263; 12%), superior memory (n=407; 19%), superior attention (n=351; 16%), and average cognitive ability (n=917; 42%). Women living in locations with higher levels of PM2.5 (per interquartile range [IQR] = 3.63 μg/m3) or NO2 (per IQR = 10.33) were more likely to be classified as having amnestic cognitive impairment compared to having average cognitive ability (OR=1.27; p=.021). One IQR increase in NO2 was also associated with decreased likelihood of having superior memory (OR=.81; p=.024) compared to average cognitive ability.ConclusionOur cross‐sectional study illustrates that long‐term exposure to PM2.5 and NO2 may be associated with specific patterns of cognitive performance; mainly worse episodic memory relative to performance in other domains. Our findings provide further evidence that air pollution may exert neurotoxic effects on brain areas underlying episodic memory in older women.
Neuroimaging and clinical characteristics of cognitive migration in community‐dwelling older adults
Authors: Duran Tugce , Bateman James R. , Williams Benjamin J. , Okonmah‐Obazee Stephanie , Craft Suzanne , Lockhart Samuel N. 
Published: December 2021

AbstractBackgroundLongitudinal studies in cognitively unimpaired older adults have identified a wide range of neuroimaging and clinical biomarkers that predict cognitive decline and clinical progression to mild cognitive impairment (MCI) or dementia. However, early biomarkers associated with progression from normal to impaired brain functioning and cognition (cognitive migration) in ADRD require further validation. We investigated the impacts of baseline neuroimaging and clinical biomarkers on functional and cognitive migration in a community‐dwelling cohort of older adults.MethodParticipants from the Wake Forest Alzheimer’s Disease Research Center (ADRC) Clinical Core cohort who completed their baseline and 1‐year follow‐up clinical visits with available neuropsychological and MRI data were evaluated. Each participant was categorized to a functional/cognitive state based on baseline global CDR (Clinical Dementia Rating); CDR=0 (n=120) indicates normal function and CDR=0.5 (n=57) corresponds to MCI. Cognitive measures included MoCA (Montreal Cognitive Assessment) and preclinical Alzheimer's cognitive composite (PACC5) scores. Oral Glucose Tolerance Testing (OGTT) assessed blood glucose 120‐minute post‐challenge; OGTT >140 mg/dl indicates impaired glucose tolerance. The primary outcome measure was cognitive migration determined by CDR increase/decrease between baseline and follow‐up (mean difference=13.8 months): CDR‐0 Stables (maintained CDR=0), CDR‐0.5 Stables (maintained CDR=0.5), CDR‐0 to CDR‐0.5 (Migrators), and CDR‐0.5 to CDR‐0 (Reverters). Baseline T1 MRI scans were assessed for gray‐matter volume and analyzed using voxel‐based morphometry in SPM12 for group differences. Statistical design was a two‐sample t‐test controlling for age, sex, education and whole brain volume in contrasts of interest (thresholded at k=25 voxels, p<0.01 uncorrected).ResultTable lists the baseline demographic and clinical characteristics for significant differences between groups. CDR‐0.5 Stables and Migrators had lower gray‐matter density (GMD) than CDR‐0 Stables and Reverters, most significantly in hippocampal (HC), temporal pole (BA38) and angular (BA39) regions (Figure).ConclusionOur analyses suggest that lower GMD in HC and BA38/39 may predict cognitive migration in early stages of disease pathology. OGTT tracks cognitive migration status in this cohort with Reverters having the lowest and Migrators having the highest mean OGTT. Validating these biomarkers may guide clinical diagnosis and treatments in ADRD. Cognitive and functional changes identified within one year can inform disease profiling.
Evaluating the relationship between soluble triggering receptor expressed on myeloid cells 2 (sTREM2) and pathological substrates of Alzheimer’s disease (AD)
Authors: Wahdan Malak , Raza Sanara , Livingston Nicholas R. , Nowell Joseph , Edison Paul 
Published: December 2021

AbstractBackgroundDeveloping novel biomarkers of Alzheimer’s disease (AD) is critical for early disease detection and intervention. sTREM2 has proposed to be an early marker of glial activation. However, there has been significant controversy about the function of sTREM2. This study investigated the relationship between cerebral spinal fluid (CSF) sTREM2, and pathological changes in AD.MethodWe included patients with mild cognitive impairment, AD and healthy controls (n= 493, mean age= 73.7, SD= 6.1) were recruited for the Alzheimer’s Disease Neuroimaging Initiative. All participants completed a T1‐weighted MPRAGE MRI, amyloid ([18F]AV45 or [18F]Florbetaben), [18F]AV1451 and [18F]FDG scans. Standard uptake ratio values were calculated in SPM12 to identify the glucose metabolic rate and tau deposition within cortical regions. Amyloid status (Aβ positive/Aβ negative) was determined from processed data using a whole brain cerebellar ratio with a cut‐off value of 1.11. Correlations between CSF measurements, ROI, and voxel‐wise analyses were conducted using data from ADNI.ResultROI analyses demonstrated that increased CSF sTREM2 was associated with increased amyloid load in the whole brain, temporal, parietal, and occipital lobes of MCI patients. Additionally, increased CSF sTREM2 was associated with decreased glucose metabolism in the Posterior cingulate and parietal lobe in MCI patients. On the other hand, CSF sTREM2 was not significantly correlated with pathological changes in AD patients. However, voxel‐wise analysis comparing Aβ+ MCI patients to Aβ‐ CN subjects showed that increased CSF sTREM2 levels were associated with greater Aβ deposition in temporal and motor regions, increased grey matter volume in frontal and parietal regions, and decreased grey matter volume in the MT gyrus.ConclusionsTREM2 levels are associated with amyloid deposition in MCI patients but not in the late stage of AD patients, this suggest that glial activation is associated early on the disease.