bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functionality and socio‐demographic factors in chilean’s community‐dwelling elderly with subjective cognitive complaints . The GERO Cohort
Authors: Loyola Walter Sepúlveda , Lillo Patricia , Zitko Pedro , Cerda Mauricio , Villagra Roque , Parrao Teresa , Gomez Rodrigo , Barría Silvia , Demanet Michele , Amieva Helene , Thumala Daniela , Henriquez Fernando , Slachevsky Andrea 
Published: December 2023

AbstractBackgroundSubjective cognitive complaints (SCCs), defined as cognitive concerns of people who may or may not have deficits in objective, is considered a predictor for cognitive and functional decline and incident to dementia risk of progression to dementia. SCC is a heterogeneous condition associated. Most of the studies have been carried out in populations other than those of Latin America. The objective of this study was to analyze the socio‐demographic and functional profile in SCC elderly with and without cognitive impairment.MethodThe GERO cohort is a prospective cohort study of community‐dwelling elderly with SCC, without dementia, aged 70 or older living in Santiago, Chile. Participants were identified by a household census and information on demographics, biomedical, psychosocial, neuropsychological, neuropsychiatric, and motor function were collected by means of questionnaires and evaluations. Montreal Cognitive Assessment (MOCA) was used to compare individuals with and without cognitive impairment (MOCA score ≤ 21 and > 21 respectively). Functionality was measured with the Pfeffer Functional Activities Questionnaire (FAQ) and Technology Activities of Daily Living Questionnaire (T‐ADLQ) that yield a global score and score by domain of activities of daily living (ADL), i.e basic (BADL), instrumental (IADL), and advanced ADL (a‐ADL).ResultFrom May 2017 to December 2020, a total of 17,759 households were successfully approached, identifying 2,533 eligible subjects, of which 299 individuals were included. After evaluation, 7 individuals were excluded for different reasons and 291 individuals were analyzed, female 80% (n = 243). The age of the individuals was 76.8 ± 5 years old, 60% of the participants were older than 75 years old. Participants with cognitive impairment compared to those without it were older (p = 0.003), with lower education years (p = <0.001), lower income (p = 0.036), lower MMSE score (p = <0.001), decline in a‐ADL (p = 0.006) and with more hypertension prevalence (p = 0.009)ConclusionFew other studies addressed cognitive complaint and functionality decline in recruited elderly at home. Older adults with cognitive impairments are characterized by less years of education, income, poor functionality and more comorbidities. Future multidimensional and prospective analysis of this cohort could bring more information about this association.
Genetic variants underlying the neuro‐anatomical signatures of hypertension measured on structural MRI
Authors: Govindarajan Sindhuja Tirumalai , Mamourian Elizabeth , Cui Yuhan , Wen Junhao , Erus Guray , Abdulkadir Ahmed , Melhem Randa , Bryan R Nick , Shou Haochang , Wolk David A. , Nasrallah Ilya M. , Davatzikos Christos 
Published: December 2023

AbstractBackgroundHypertension (HTN) is associated with gray matter (GM) atrophy and increased white matter hyperintensity (WMH) burden, increasing their susceptibility to Alzheimer’s disease and related dementias. We developed a machine learning based model to quantify spatial patterns of abnormality recognizing HTN‐related brain changes (SPARE‐HTN) from structural magnetic resonance images (sMRI). We performed a genome wide association study (GWAS) to identify the genetic variants and associated biological traits that underlie the “expression” of HTN‐related brain changes, i.e., the individualized SPARE‐HTN index.MethodSPARE‐HTN model was trained on the large multi‐study iSTAGING dataset, with regional GM volumes from T1‐weighted images and lobar WMH volumes from T2‐weighted FLAIR images used as imaging features. GWAS was carried out in a subset of N = 7490 (46% Female, Age = 65.5±7 years) hypertensive participants from UK‐Biobank. A GWAS of SPARE‐HTN scores was run using linear regression with Plink, correcting for the top 40 genetic principal components, age, sex, and intracranial volume. Significant SNPs were identified and mapped to functional genes using the Functional Mapping and Annotation (FUMA) platform; and candidate SNPs were mapped to the GWAS catalog.ResultSPARE‐HTN was associated with regional atrophy most prominent in perisylvian and temporal cortex and increased WMH volumes, particularly in frontal white matter. SPARE‐HTN scores showed better discriminative power between normal and stage 1 participants (Cohen’s‐d effect size, d = 0.2) and stage 2 (d = 0.71) hypertensive participants when compared to total WMH volume (d = 0.04 and 0.38, respectively). GWAS identified N = 321 independently significant SNPs, of which a subset N = 46 candidate SNPs were mapped to 6 genes (ICA1L, CARF, WDR12, NBEAL1, KRT8P15, CYP20A1) in Chromosome 2 (Figure 2). These genes were previously reported to be associated with several cardiovascular conditions including coronary artery disease and stroke, and with increased WM damage on sMRI and diffusion MRI (Figure 3).ConclusionThe individualized imaging marker, SPARE‐HTN, was associated with genes relevant to HTN with traits including cardiovascular conditions and higher prevalence of WMH, and was more sensitive to HTN than total WMH volume. SPARE‐HTN is a useful tool to characterize HTN‐related brain changes and monitor treatment effects at an individual level.
Relationship between baseline levels of subjective cognitive concern and physical, cognitive and social activity in the U.S. POINTER Study
Authors: Sachs Bonnie C. , Baker Laura D , Caudle Brad A , Farias Sarah Tomaszewski , Katula Jeffrey A. , Lee Athene KW , Lovato Laura , Snyder Heather M , Thro Amber Adkins , Papp Kathryn V. ,   The U.S. POINTER Neuropsychology Team and the larger U.S. POINTER Study Group
Published: December 2023

AbstractBackgroundThere has been little investigation into the relationship between physical, cognitive, and social activity and subjective concern about cognition (SCD) in the absence of objective cognitive decline. This concern about subjective change is an important concept in the field of Alzheimer’s disease as it independently confers risk for developing MCI/AD. However, the exact relationship between SCD and engagement in positive daily activities is poorly understood. This project examines the relationship between SCD and self‐reported engagement in these activities.MethodU.S. POINTER is a phase 3, multicenter, 2‐year randomized controlled trial of two lifestyle interventions varying in intensity and format, conducted in older adults living in the U.S. who do not have objective cognitive impairment at study entry, but have increased risk of cognitive decline and dementia. Participants completed myriad measures at baseline, including the Cognitive Function Inventory (CFI) assessing subjective cognitive decline, and the Community Healthy Activities Model Program for Seniors (CHAMPS) which assesses self‐reported engagement in social, cognitive, and physical activities over the past 4 weeks.ResultsBaseline study characteristics of the current sample (N = 1823) are: Mean age = 68.2y (5.2), 73.5% female, 29.8% with less than 18+ years education, and 29.3% from underrepresented groups (URG). In separate multivariate linear models, CFI was associated with weekly caloric expenditure in exercise (p< .001) and cognitive activity (p <.001), such that CFI scores were higher for participants with lower exercise‐related caloric expenditure and lower cognitive activity levels. Higher CFI scores also tended to predict social activity levels (p = .06). The inverse relationship between CFI and all three variables is significant in women (p = .04; .0001; .05, respectively) but not in men, and the CFI‐cognitive activity relationship is significant for URG (p = .005) but not White participants.ConclusionIn sum, SCD and engagement in physical, cognitive, and social activities are inversely related to varying degrees, such that individuals who report lower levels of engagement in these activities report more subjective cognitive concerns. However, different patterns emerged for some subgroups. Additional modeling is needed to demonstrate the directionality of the relationships between these activities and CFI, and the relationship with demographic variables of interest.
Automated Analysis of REM Sleep without Atonia in the Lewy Body Disease Spectrum
Authors: Strainis Emma P. , Jagielski Jack T. , LeClair‐Visonneau Laurene , Przybelski Scott A. , Feemster John C , McCarter Stuart J , Carvalho Diego Z. , Silber Michael H , Vemuri Prashanthi , Jack Clifford R. , Miyagawa Toji , Forsberg Leah K. , Fields Julie A. , Savica Rodolfo , Graff‐Radford Jonathan , Jones David T. , Botha Hugo , Ramanan Vijay K , Knopman David S. , Graff‐Radford Neill R , Ferman Tanis J , Petersen Ronald C. , Lowe Val J. , Boeve Brad F. , Kantarci Kejal , Dredla Brynn , Louis Erik K St 
Published: December 2023

AbstractBackgroundQuantitative rapid eye movement (REM) sleep without atonia (RSWA) recorded during polysomnography (PSG) represents loss of normal REM sleep atonia. RSWA is the neurophysiologic signature of REM sleep behavior disorder (RBD). Visually scored RSWA is a candidate biomarker for synucleinopathies. However, visual RSWA scoring requires expert scoring, limiting widespread application. We comparatively analyzed RSWA in DLB and iRBD using the automated Ferri REM Atonia Index (RAI).MethodWe quantitatively analyzed the RAI in 12 DLB and 20 iRBD patients, compared to 20 controls using Hypnolab Software for Sleep Analysis (SWS Soft, Inc, Colognola ai Colli, Italy). PSG data were converted to European Data Format (.EDF), and the submentalis surface electromyogram (EMG) signal was notch‐filtered at 60 Hertz and rectified. Automatically calculated RAI scores were comparatively analyzed across groups (DLB, iRBD, controls) using Kruskal Wallis H tests for group comparisons, and regression analyses determined relationships between diagnosis, age, and sex. Logistic regression ROC determined optimal RAI for distinguishing iRBD from DLB. When interpreting RAI, lower values represent greater amounts of RSWA, and higher values represent more normal REM atonia.ResultMean age was older in DLB than in iRBD or controls (72.6 vs. 68.7 vs. 66.5 years). All 12 DLB participants were men, the iRBD group had 18 men and 2 women, and controls were comprised of 16 men and 4 women. Mean RAI was lowest in DLB (0.46), intermediate in iRBD (0.71) and highest in controls (0.96), indicating a gradient in RSWA amounts from DLB patients (highest) to controls (lowest) (Figure). Regression demonstrated diagnosis independently predicted RAI, controlling for age and sex (adjusted R2 = 0.49, p = 0.0001). The RAI that optimally distinguished iRBD from DLB was 0.46 (specificity 85%, sensitivity 58%, AUC = 0.75).ConclusionThe RAI demonstrated a clear gradient throughout the Lewy body spectrum; highest (indicating lowest RSWA amounts) in controls, intermediate in iRBD, and lowest (indicating greatest RSWA) in DLB. The RAI is a promising, time efficient and broadly applicable candidate biomarker for DLB and iRBD. Automated quantitative RSWA could be a valuable tool for deep phenotyping throughout the Lewy body disease spectrum.
Community support service use and Black family caregiver mental health outcomes
Authors: Johnson Florence U , Robinson‐Lane Sheria G , Veliz Philip 
Published: December 2023

AbstractBackgroundFamily and friends provide 83% of dementia patients’ essential personal care needs without compensation or training. More than 11 million Americans provided care in 2020, totaling an estimated 15.3 billion hours of assistance valued at nearly $250 billion. The stress associated with caring for a person living with dementia (PLWD) can significantly affect the caregiver’s physical and mental health. Caregiver stress is a significant problem that proportionately affects Black family caregivers. Adult day programs, support groups, help‐seeking, respite, and dementia training can assist Black family caregivers in avoiding stress‐related mental health issues. CSS aids caregivers in keeping PLWD safe at home and postponing or avoiding institutionalization. This study examines how CSS affects Black family caregivers' mental health.MethodThe secondary analysis of data from the National Health and Aging Trends Study (NHATS) Round 5 and the National Study of Caregiving (NSOC) Rd II, 2015, n = 2,204 caregivers. The dementia classification (those with probable or possible dementia) caregivers was n = 1,027. Descriptive statistics and logistic regression analyses evaluated caregiver stress (based on the relationship and interaction with the PLWD) and the use of CSS.ResultFindings indicated that most caregivers were females (66%) between 55 to 65+ years old. Analysis of the stress measures derived from questions about the caregiver’s relation with the PLWD suggests that overall, the caregivers enjoy spending time with the PLWD (96%). Stress measures did not indicate that caregivers experienced much stress. Black caregivers received less dementia training than their White counterparts: 13% vs. 29%. A small percentage of caregivers attended support groups (5% and less).ConclusionThe results of this secondary data analysis do not distinguish Black and White family caregiver stress or their use of support services to address stress. The reason is not apparent, but it may be that the most vulnerable groups did not participate in the NHATS/NSOC research, which may account for these results. Qualitative research is required to explore Black caregivers’ stress and support utilization perspectives deeply.
Vascular risk factors are a major contributor to cognitive impairment and degenerative dementia in India
Authors: Kumar S Sandeep , Mekala Shailaja , Somaraj Aparna , Thanissery Nithin , Arshad Faheem , Ramakrishnan Subasree , Kaul Subhash , Alladi Suvarna 
Published: December 2023

AbstractBackgroundThe burden of vascular contribution to cognitive impairment and dementia is high in low and middle‐income countries (LMIC) like India. It is crucial to determine burden of vascular contribution to dementia in India, to develop effective preventive and treatment strategies. The aim of the study was to determine the prevalence of vascular risk factors across the spectrum of cognitive impairment and dementia in a large dementia cohort in South India.MethodPatients with cognitive impairment and dementia from the dementia registries of two University referral hospitals in South India were included. All patients underwent clinical, cognitive and imaging study and standard criteria were used to diagnose MCI, AD, FTD, VaD and mixed dementia. Vascular risk factor profile was determined in patients, and the presence of hypertension, diabetes, cardiac disease, stroke, smoking and chronic alcoholism were noted.ResultOf a total 1811 patients with cognitive impairment, 180 (9.9%) patients were diagnosed to have MCI, 517 (28.5%) AD, 205 (11.3%) FTD, 844 (46.6%) had VaD & 64 (3.5%) had mixed dementia. Overall, hypertension was the most prevalent vascular risk factor (62.7%) followed by stroke (46.6%). 35.5% of patients had diabetes mellitus(DM), 15.2% had chronic alcoholism, 14.4% were smokers and 14.2% had history of cardiac disorders.Hypertension was most commonly encountered in patients with AD (76.4%), followed by mixed Dementia (68.75%), VaD (63.4%), MCI (44.4%) and FTD (39.5%).DM was present in a high proportion of all subtypes of cognitive impairment and dementia (24.4% to 46.8%). The proportion of patients with stroke was highest in VaD (82.1%), but was also associated with one‐fourth of patients with AD and 15% of patients with mixed dementia. Frequency of smoking, chronic alcoholism and cardiac disease was highest in mixed dementia and VaD.ConclusionOur results demonstrate that a large burden of vascular risk factors exist in all forms of cognitive impairment and dementia in the Indian context. Hypertension and diabetes were found to be commonly associated with neurodegenerative dementia, in addition to vascular and mixed dementia. This large burden of vascular contribution represents needs and an opportunity to implement strategies to reduce burden of dementia in India and other LMICs
Psychometric properties and diagnostic utility of the Technology‐Activities of Daily Living Questionnaire (T‐ADLQ) for illiteracy in Lima, Peru
Authors: Custodio Nilton , Henriquez Fernando , Montesinos Rosa , Delgado Carolina , Malaga Marco , Chambergo‐Michilot Diego , Slachevsky Andrea 
Published: December 2023

AbstractBackgroundFunctional decline (FD) is defined as the deterioration of the ability to perform activities of daily living (ADLs). This FD is a critical dimension that allows determining the threshold between dementia disorders and previous stages of cognitive impairment. ADLs include activities that are divided into three main dimensions: basic (BADL), instrumental (IADL), and advanced (AADL). The Technology‐Activities of Daily Living Questionnaire (T‐ADLQ) (1) assesses these different ADL dimensions. To date, the dimensions of ADLs have not been assessed in the continuum ranging from healthy controls (HC), amnestic mild cognitive impairment (a‐MCI), to Alzheimer’s disease dementia (ADD) in the illiterate population. The study aimed is to validate the T‐ADLQ and evaluate FD across the three dimensions of ADL in healthy and cognitively impaired illiterate adults >50 years.MethodA cross‐sectional study of illiterate subjects in Peru. Inclusion criteria: men and women over 50 years of age; with less than one whole year of formal education and unable to read and write and grouped into 1 of 3 cognitive categories: healthy controls (HC) (n = 64), a‐MCI (n = 60), and early ADD (n = 63). Neuropsychological measures included the RUDAS, MMSE, and IFS. FD was assessed with the FAQ and the T‐ADLQ. The latter questionnaire, assessed by informants, evaluated the different dimensions of ADLs.ResultThe results on the global FD (T‐ADLQ total score) and the three ADL dimensions differed significantly among the three groups (Table 1). The T‐ADLQ total score correlated significantly with the FAQ (Table 2) and had high internal consistency (Cronbach’s alpha = 0.966). In addition, the T‐ADLQ total correlated significantly with instruments of global cognition and executive functions (Table 2). Finally, receiver operating characteristic (ROC) analyses, through the calculation of the area under the curve (AUC), showed that the total T‐ADLQ and the different dimensions discriminated better between HC vs. ADD and HC vs. a‐MCI but not between a‐MCI and ADD (Table 3).ConclusionThe total T‐ADLQ scale and its three dimensions have good psychometric properties (validity and reliability) and excellent diagnostic utility. This result demonstrates that the T‐ADLQ is a good instrument to evaluate FD in illiterate populations.
The immune cytokine granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) is an effective treatment for both Alzheimer’s disease and the viral diseases caused by West Nile Virus and SARS‐CoV‐2 infection, indicating that inflammation and viral infection may be partners and therapeutic co‐targets in many brain disorders
Authors: Potter Huntington , Boyd Timothy D. , Woodcock Jonathan H , Sillau Stefan H , Ahmed Md. Mahiuddin , Wang Athena Ching‐Jung , Chial Heidi J , Coughlan Christina M , Kendall Lon V. , Bosco‐Lauth Angela , Markham Neil , Stonedahl Sarah , Fong Derek , Clarke Penny , Tyler Kenneth L. 
Published: December 2023

AbstractBackgroundGM‐CSF has been considered a potential therapeutic target in many disorders associated with inflammation because it is upregulated and upregulates other inflammatory molecules such as IL‐1, IL‐6, and TNF‐a. However, its ability to increase the number and activation of phagocytic cells in the periphery and brain suggested to us that its upregulation in rheumatoid arthritis (RA) might underlie the finding that RA protects against another inflammatory disorder, Alzheimer’s disease (AD) by aiding phagocytosis of amyloid deposits. Treatment of mouse models of AD with GM‐CSF reverses amyloid deposition and normalizes cognition. A double‐blind placebo‐controlled phase II trial showed that three weeks of treatment with human recombinant GM‐CSF (sargramostim) in mild‐to‐moderate AD participants led to improved cognition (MMSE) and blood biomarkers of amyloid, Tau, and neurodegeneration (A+T+N). GM‐CSF/sargramostim treatment is also efficacious in humans and/or animal models with other inflammation‐associated diseases/disorders (Parkinson’s disease, Down syndrome, chemo‐brain, and normal aging).MethodBased on findings that innate immunity and microglia underlie viral control, we investigated GM‐CSF in a mouse model of West Nile Virus encephalopathy and a mouse model of SARS‐CoV‐2/COVID‐19. C57BL/6 mice were infected by footpad injection of 1,000 pfu of WNV (TX2002‐HC strain). ACE2 receptor Tg mice were infected with 4,000 pfu of SARS‐CoV‐2 by nasal instillation. Mice were treated IP daily with 5 mg of recombinant GM‐CSF starting the day after infection and analyzed for pathology, morbidity, and mortality at death or at sacrifice at 2 weeks. The SARS‐CoV2‐infected mice were also analyzed for viral titers in brain and lung.ResultGM‐CSF treatment improved survival in both the WNV and SARS‐CoV‐2 models. SARS‐CoV‐2 viral titers in affected tissues, including brain, were greatly reduced by GM‐CSF treatment.ConclusionBy activating both the innate and adaptive immune systems, GM‐CSF may be an effective therapy for viral diseases and may protect against viral re‐infection more effectively than antiviral drugs or monoclonal antibodies, a serious concern during the COVID‐19 pandemic. These results also challenge the belief that inflammation in these disorders contributes essentially to the disease. It is possible that the anti‐viral activity of GM‐CSF may also underlie some of its efficacy in AD.