bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of social integration with cognitive status: results from the Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE) study
Authors: Calmasini Camilla , Swinnerton Kaitlin N , Zimmerman Scott C , Peterson Rachel L , George Kristen M , Gilsanz Paola , Hayes‐Larson Eleanor , Mungas Dan M , Whitmer Rachel A , Glymour M Maria 
Published: December 2021

AbstractBackgroundLack of strong social ties is associated with numerous morbidities including adverse late‐life cognitive outcomes. Prior work on social integration and cognition has been conducted in predominantly White cohorts. We evaluated the relationships between social integration and cognition in diverse older adults from major racial/ethnic groups in the United States using data from the Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE) study.MethodKHANDLE is a multi‐ethnic study of 1712 Kaiser Permanente Northern California members age 65+. Social integration was assessed using the Berkman‐Syme Social Network Index. A score ranging from 0 to 6 was calculated by assigning 1 point for each of the following domains: being married/partnered, volunteer activity, having monthly contact with children, relatives, and friends and daily contact with confidante (Figure 1). Cognition included three domains derived from the Spanish and English Neuropsychological Assessment Scales: verbal episodic memory (for White, Black and Latino participants), semantic memory and executive function. Covariate‐adjusted linear mixed‐effects models estimated a single association of social integration with cognition applicable to all three cognitive domains for the full sample and by race/ethnicity. Core models adjusted for age, gender, race, and education (years); expanded models further adjusted for variables that could either be determinants or consequences of social integration, including weekly alcohol use, average score for combined activities of daily living (ADL) and instrumental ADL, and income. We repeated these analyses using frequency of contact with confidante as the primary exposure.ResultHigher social integration score was associated with better cognition in core covariate‐adjusted models (β=0.065 (0.039, 0.091)); the association attenuated slightly when adjusting for expanded covariates (β=0.045 (0.019, 0.071)). In race‐stratified core models, higher social integration scores were associated with better cognition among Asian, Black, Latino, and White participants. In expanded models patterns were similar, but the association remained statistically significant only for Black participants (Table 1). Seeing a confidante daily was associated with higher cognition in the pooled model and for Asian participants (Table 2).ConclusionOur findings suggest that social integration and seeing a confidante daily were associated with better cognition across the four racial/ethnic groups.
Risk of falling in mild cognitive impairment: Relationships with diminishing regional cerebral metabolism and clinical parameters in a long‐term prospective longitudinal multi‐center study
Authors: Zhang Lorena , Liu Stephen , Silverman Daniel H 
Published: December 2021

AbstractBackgroundWe recently identified visual cortex and cerebellar vermis as the cortical and non‐cortical brain areas, respectively, in which declining metabolism was most predictive of falling (Soc. Nucl. Med. Molec. Imaging, 2021.) We now describe alterations in relationships between rates of change in their metabolism, and cognitive/functional performance.MethodOf 226 FDG‐PET brain scans from 113 Alzheimer’s Disease Neuroimaging Initiative MCI subjects analyzed, 122 were from subjects (MCI‐F ,n=61) suffering a fall subsequent to baseline PET, while 104 were from age‐matched subjects (MCI‐N, n=52) having no documented falls. MCI‐F scans were taken from baseline and last time point preceding date of first fall; MCI‐N scans were taken from baseline and last time point available. Magnitudes of regional metabolism in standardized volumes of interest (sVOI’s) were normalized to metabolism of each subject’s pons. Rates of longitudinal change were calculated as the interval difference in magnitudes between each sVOI pair divided by interval time. Significance of associations between metabolic changes and changes in overall cognition (MMSE), function (FAQ) and four individual domain scores were assessed following Bonferroni‐type statistical correction for multiple comparisons.ResultIn the vermis of MCI‐N subjects, changes in metabolism correlated with changes in overall cognition and function (p=0.00007, p=0.00003, respectively); among individual cognitive domains, metabolic changes most significantly correlated with changes in visuospatial (p=0.005) and language (p=0.001) scores. Interestingly, among MCI‐F subjects, vermis metabolism declined severalfold faster than in their MCI‐N counterparts, while significant associations with changes in MMSE and FAQ (both p>0.30) as well as with visuospatial changes (p>0.99) were entirely lost, yet language changes remained strongly correlated (p=0.00004). Similarly, in bilateral visual cortex of MCI‐N, changes in metabolism correlated with changes in MMSE and memory, and those associations were lost in MCI‐F.ConclusionMetabolism of cerebellar vermis ‐ critical for maintenance of upright posture and locomotion ‐ and of visual cortex ‐ known to diminish in patients with Lewy body involvement (associated with orthostatic hypotension and gait disturbance, both in turn increasing fall risk) ‐ not only underwent accelerated decline, but metabolic decline also became dissociated from cognitive and functional performance in MCI‐F, prior to their first documented fall.
Clinical factors contributing to functional change over time in individuals with subjective cognitive concerns and mild cognitive impairment
Authors: Lin Pinghsiu , LaMonica Haley , Naismith Sharon L , Mowszowski Loren 
Published: December 2021

AbstractBackgroundAccumulating research suggests individuals with subjective cognitive concerns (SCC) and Mild Cognitive Impairment (MCI) experience subtle but noticeable functional changes, despite diagnostic criteria emphasising predominantly intact daily functioning to differentiate them from more severe stages of decline, i.e. dementia. This study investigates how factors associated with cognition, general health, and psychosocial wellbeing relate to functional change longitudinally in older adults with early‐stage cognitive change.MethodOne hundred and thirty‐seven participants with SCC or MCI (mean age=70.4 years, SD=8.0) completed standardised neuropsychological, medical and psychosocial assessments, and the self‐report Healthy Brain Ageing ‐ Functional Assessment Questionnaire (HBA‐FAQ) at baseline and again at follow‐up at least one year later (mean time to follow‐up= 25.5 months, SD=8.0). Correlational and linear regression analyses were used to explore relationships between subjective functional change over time and cognition, general health, and psychosocial wellbeing, where p was set at .05.ResultOlder people with SCC and MCI reported a similar amount of functional change (p = .13) and were therefore analysed as one ‘at risk’ group. Overall, greater subjective functional change over time was significantly and most markedly correlated with poorer baseline cognitive performance on tests of new learning (r = ‐.23), memory (r = ‐.25), processing speed (r = ‐.25), and cognitive flexibility (r = ‐.21), as well as poorer baseline psychosocial wellbeing including subjective disability (r = .56), quality of life (r = ‐.54), sleep quality (r = .29), mood disturbance (r = .51) and subjective memory complaints (r = .51). Of these factors, greater subjective memory complaints and greater mood disturbance at baseline significantly predicted increased functional change at follow‐up, accounting for 9.7% and 3.3% respectively of the unique variance in the model.ConclusionThese results suggest that functional change over time is evident in older adults with early‐stage cognitive change and is associated with poorer cognition and psychosocial wellbeing. This has important implications for early intervention, as this research highlights key clinical factors predictive of functional decline that clinicians can look out for when assessing older adults in primary practice. Targeted early intervention and management strategies may then help to maximise and maintain day‐to‐day functioning.
Circulating cystatin‐C is associated with dementia in a racial and ethnically diverse cohort: An interaction decomposition analysis
Authors: Higgins Cesar , Ware Erin B , Hicken Margaret , Zawistowski Matthew , Bakulski Kelly M 
Published: December 2021

AbstractBackgroundCystatin‐C has an important role in the pathogenesis of dementia, as evidenced by expression in the brain and co‐localization with beta‐amyloid deposits. Circulating Cystatin‐C may be directly implicated in neurodegeneration, or the result of a compensatory mechanism of neuroprotection. Our study aims to understand the relationship between circulating Cystatin‐C and dementia, and to test the interaction between Cystatin‐C and race/ethnicity.MethodsWe performed a cross‐sectional analysis of serum Cystatin‐C levels with dementia and cognitive impairment non‐dementia (CIND) in two waves (2006 and 2008) of the Health and Retirement Study (n=9,984). We used Poisson regression with robust variance to estimate the interactive effect of race/ethnicity and Cystatin‐C >75th on dementia. We calculated three measures of interaction in the additive scale: the excess risk due to interaction (RERI), the attributable proportion, and the synergy index (SI). We decomposed the interaction to calculate the percentage of the excess risk attributable to the effects of race/ethnicity and Cystatin‐C alone.ResultsAfrican Americans and Hispanics had higher levels of Cystatin‐C at every decade of life except for the 80s with respect to Whites (see Figure 1). The prevalence ratio for dementia among African Americans with levels of Cystatin‐C >75th was 7.33 (95%CI: 5.43, 9.89) times of White Americans with Cystatin‐C <75th. A RERI of 1.89 (95%CI: ‐0.17, 3.95) indicates more than an additive interaction; and attributable proportion of 0.26 (95%CI: 0.02, 0.50) suggests than roughly a quarter of the excess risk was due to the interaction of both race and Cystatin‐C; and a synergy index of 1.43 (95%CI: 0.97, 2.10) provided evidence of synergism between the two exposures. We found 26% (95%CI: 2%, 50%) of the excess risk among the doubly exposed group (i.e., African Americans with levels of Cystatin‐C >75th) was attributable to the interaction between Cystatin‐C and race. Similar patterns were observed for Hispanics in relation to Whites.ConclusionElevated levels of circulating Cystatin‐C are implicated in impaired cognition, and the association between Cystatin‐C and cognition varies dramatically by race/ethnicity.
Circadian rhythm disturbance in agitation of Alzheimer's disease
Authors: Rosenberg Paul B. , Outen John D. , Spira Adam P. , Zipunnikov Vadim , Wanigatunga Sarah K. , Wu Mark N. 
Published: December 2021

AbstractBackgroundAgitation in Alzheimer’s Disease (Agit‐AD) is a major cause of burden for caregivers and may be driven by disrupted circadian rhythms and sleep. The circadian clock that generates these rhythms regulates patterns in mood, wakefulness, and other physiologic processes, such as body temperature and hormone levels. This project aims to examine if agitated AD subjects (AgitAD+) exhibit delayed circadian phase and lower rhythm strength compared to non‐agitated AD subjects (AgitAD‐) and healthy controls. We will additionally compare sleep amount, sleep quality, and degree of sleep disordered breathing among AgitAD+ vs. AgitAD‐ and healthy controls.MethodParticipants completed wrist actigraphy for one week to quantify rest/activity rhythms and sleep; consumed an ingestible, disposable temperature sensor for 1‐2 days to quantify core body temperature rhythms; and completed a single night of home sleep testing (HST). Inclusion criteria were diagnosis of AD and age 55‐90 years, and exclusion criteria include seizures, significant tremors, delirium, CPAP use for sleep apnea, restless legs syndrome, and circadian rhythm disorders. Due to the COVID‐19 pandemic, we implemented hybrid visits with telemedicine to limit in‐person interactions.ResultTo date, 26 participants have enrolled. There were no statistically significant differences observed in actigraphic sleep parameters between groups (Table 1). However, AgitAD+ participants had lower levels of activity in the morning and greater activity in the afternoon and evening (Figure 1). After adjustment for age, agitation was associated with lower activity in the morning and a trend towards greater activity in the afternoon and evening (Figure 2). This preliminary finding may suggest that AgitAD+ participants express lower and delayed activity rhythms. HST results show a trend toward less REM sleep and longer initial REM latency in the AgitAD+ group (Table 2). Updated results will be presented at AAIC (estimated 6‐10 additional participants).ConclusionThis study could provide evidence for CRD/sleep disturbance as a driver of Agit‐AD and could identify Agit‐AD subtypes who are most likely to from chronobiotic or sleep interventions.
Extracellular vesicular lipids as biomarkers for the diagnosis of Alzheimer’s disease
Authors: Su Huaqi , Rustam Yepy H. , Masters Colin L. , Makalic Enes , McLean Catriona , Hill Andrew F. , Barnham Kevin J. , Reid Gavin E. , Vella Laura J. 
Published: December 2021

AbstractBackgroundAn increasing number of studies have revealed that dysregulated lipid homeostasis is associated with the pathological processes that lead to Alzheimer’s disease (AD). If changes in key lipid species could be detected in the periphery, it would advance our understanding of the disease and facilitate biomarker discovery. Global lipidomic profiling of sera/blood however has proved challenging with limited disease or tissue specificity. Small extracellular vesicles (EV) in the central nervous system, can pass the blood‐brain barrier and enter the periphery, carrying a subset of lipids that could reflect lipid homeostasis in brain. This makes EVs uniquely suited for peripheral biomarker exploration.MethodTo determine the potential of EV lipids as biomarkers, we isolated brain‐derived EV (BDEV) from frontal cortex tissue (Vella, et al. JEV. 2017) and performed quantitative mass spectrometry based lipidome analysis (Rustam and Reid. Anal. Chem. 2018). We developed and optimised methods to isolate pure EVs from plasma while minimising co‐isolation of lipoproteins. To confirm the identity of EVs, we are using various techniques including western blot, nanoparticle tracking analysis and transmission electron microscopy. We are mining the mass spectrometric data for brain‐specific signals.ResultWestern blot analysis showed successful isolation and enrichment of BDEV from brain tissue. TEM revealed the typical round and cup‐shaped EV morphology with vesicle size being 50‐150nm. A total of 692 lipids were identified and quantified. Enrichment of glycerophosphatidylserine (PS) lipids, especially the ether PS lipids, alkyl‐ and alkenyl‐, were observed in BDEV. Remodeling in phosphatidylethanoamine (PE) lipid class and polyunsaturated fatty acyl containing lipids (PUFA‐) was observed in AD BDEV. The preliminary experiments demonstrate successful isolation of pure EVs from plasma. Lipidomic and proteomic analysis suggests that plasma EVs contain brain‐specific signals.ConclusionWe, for the first time, characterized the lipid composition of EVs in human frontal cortex. BDEVs offered improved detection of dysregulated lipids in AD and these lipids have previously been reported to play key roles in AD pathogenesis, suggesting BDEV provide a readout of lipid dysregulation in AD and highlighting the potential use of these lipids as disease biomarkers in the periphery.
Specific affective dimensions are associated with a faster rate of cognitive decline in older adults
Authors: Soleimani Laili , Beeri Michal Schnaider , Grossman Hillel , Sano Mary , Zhu Carolyn W 
Published: December 2021

AbstractBackgroundThe relationship between different affective presentations and cognitive outcome is poorly understood and may elucidate subgroups of patients who are more at risk for decline. Here we utilized longitudinal data from subjects ≥ 60 years, enrolled in the National Alzheimer’s Coordinating Center (NACC) study for an average of 5 years and who were not demented at baseline to investigate the relationship between affective dimensions and global cognition and specific cognitive domains over time.MethodSubjects [n=17,385; mean age= 73.73 (SD= 7.72); 59.20% female] completed the 15‐item geriatric depression scale (GDS‐15) and a broad neuropsychological battery at baseline, and approximately every 12 month follow ups. Cognitive domains included episodic memory, attention, executive functions, and language. Global cognition averaged the z‐scores of the four domains. Affective dimensions were defined based on GDS‐15 factors previously described, and included dysphoric mood, Withdrawal‐Apathy –Vigor (WAV) , anxiety, hopelessness and memory complaint. Linear mixed models (LMM) analysis was used to assess associations between the five affective dimensions with global cognition and each cognitive domain. Analyses adjusted for baseline age, sex, race/ethnicity, years of education, baseline Functional Assessment Questionnaire (FAQ), indicators for history of diabetes, hypertension, and hypercholesterolemia.ResultAt baseline, our sample had low reported depressive symptoms (GDS‐15=1.66; SD= 2.23) and were non‐demented (MMSE= 28.34; SD=2.01). Reported subjective memory complaint and hopelessness were associated with faster decline in all cognitive domains (all p<0.001) and , attention and executive function (all p<0.001), but not with episodic memory or language. In contrast, dysphoria and anxiety were not associated with a faster decline in global cognition or any of the cognitive domains.ConclusionIn our large clinical sample of initially non‐demented older adults, different affective dimensions had different degree of associations with the rate of cognitive decline, suggesting distinct pathophysiology and need for more targeted interventions.
Pandemic times: Perception of online cognitive stimulation groups in in older adults with cognitive complaints
Authors: Berardo María Celeste , Martínez Claudia Patricia Múnera , O'Neill Santiago , Sorondo Juan , Sanjurjo Natalia Sierra 
Published: December 2021

AbstractBackgroundCognitive reserve is a factor that can modify the clinical expression of different degenerative diseases (Stern, 2012). Some studies have shown that the older who engage in mental activities have a better overall functioning (Aguirre et al., 2013). The Institute of Neurosciences of the Favaloro Foundation offers 6 hours weekly cognitive stimulation groups to patients with cognitive complaints. In Argentina, due to lock down to decrease SARS‐COV 2 infection, the cognitive stimulation groups began to be offered online. The aim of this study is to analyze how our patients perceive the impact of the isolation after 9 months of online cognitive stimulation workshops.Method85 patients with mild executive‐attentional impairments, between 47 and 85 years old, answer a satisfaction questionnaire after attending 9 months to an online cognitive stimulation group. In these groups, patients connected twice a week through the virtual platform Google Meet. After this time, the patients were asked to answer a self‐administered questionnaire, prepared ad hoc. The satisfaction questionnaire consisted of a series of questions about the perceived changes in cognitive performance, emphasizing how they helped to cope with isolation. The study is a descriptive statistical analysis.Result72.9% of the participants reported being satisfied with online cognitive stimulation, with 77.6% believing that it was highly effective. 85.9% indicated that the isolation became more bearable thanks to the assistance. Regarding the perception of performance, 36.5% reported that their performance is better than before, while 33% register stability in their cognitive ability.Conclusionthe patients perceived that online cognitive stimulation allowed positive changes in cognitive performance, making isolation more bearable. In this way, we can conclude that the isolation forced us to develop new strategies and activities of rehabilitation that are likely to continue to be used in the future.
Potential contributions of MRI and blood‐based biomarkers for cognitive status classification based on cognitive performance examinations
Authors: Farina Mateo , Saenz Joseph , Crimmins Eileen M. 
Published: December 2021

AbstractBackgroundThe global burden of dementia is growing from 50 million people in 2020 to 150 million in 2050 (World Health Organization). Health researchers often use national survey studies to understand the social and population dynamics of dementia. Many of these studies have relied on classification algorithms based on cognitive performance exams such as the MMSE and MOCA. However, researchers are concerned about misclassification leading to incorrect conclusions about dementia in the population. This study assesses how the addition of MRI markers, along with blood‐based biomarkers, would improve cognitive status classification based on cognitive performance exams.MethodWe use the data from the Alzheimer’s Disease and Neuroimaging Initiative (ADNI) to assess whether MRI measures (whole brain volume, hippocampal volume, and ventricle volume) along with plasma Aß and P‐Tau improve cognitive status classification accuracy, net of MMSE scores. To assess improvements, nested multinomial logistic regression equations adjusting for sex, age, and APOE alleles are used. In total, we have total of 1,442 respondents.ResultsWe found marginal improvements in cognitive status classification when structural MRI measures and blood‐based biomarkers were included compared to only MMSE scores. The R2 for model with only MMSE (0.401) increased when both structural MRIs, and plasma Aß and P‐Tau were added (0.445, an approximately 10% improvement). Furthermore, while structural MRI measures and blood‐based biomarkers alone did explain a modest amout of variability in dementia status classification (R2 of .182 and 142, respectively), models with MMSE scores alone had by far the largest explanatory power at .401.ConclusionWhile MRI markers and blood‐based biomarkers may lead to novel insight in understanding how brain pathology leads to cognitive impairment, their application to improving cognitive status classification in survey research may be more limited. Our findings do not show large improvements in cognitive status classification when including them in our predictive models of cognitive status classification. Additionally, the marginal improvement may not justify the costs associated with data collection in large nationally representative datasets.