bluuebunny/crossref_metadata_2025_split huggingface dataset:
Relationships between locus coeruleus structural integrity and nocturnal awakenings in the context of AD biomarkers: A 7T MRI study
Authors: Van Egroo Maxime , van Hooren Roy W.E. , Jacobs Heidi I.L. 
Published: December 2021

AbstractBackgroundThe brainstem locus coeruleus (LC) may constitute the intersection of the initial pathophysiological and clinical phenotypes of Alzheimer’s disease (AD). Tau protein accumulation starts early in the LC and sleep‐wake disruption occurs in early stages of AD, potentially reflecting arousal dysregulation in wake‐promoting neurons of the LC. Here, we sought to investigate whether LC structural integrity could be related to subjective sleep‐wake measures in the context of AD biomarkers.MethodWe used an in‐house developed LC‐specific MRI sequence at 7T in 72 cognitively normal older participants (mean age = 65.2 ± 8.2y; 37 women), and we identified sub‐portions of the LC using intensity‐based cluster analyses. Participants’ reports on habitual sleep quality and nocturnal awakenings were collected. In addition, blood‐based biomarker of total tau was measured, and APOE genotype was determined.ResultTwo distinct LC segments were identified, with one covering the middle‐to‐caudal LC and displaying lower intensity compared to the middle‐to‐rostral cluster (t(70) = ‐4.40, p < .0001). Generalized linear mixed models adjusted for age, sex, depression, and APOE status showed that subjective sleep quality was not related to any LC integrity measures. However, we found that lower MRI signal intensity within the middle‐to‐caudal LC, but not in the middle‐to‐rostral LC, was associated with a higher number of self‐reported nocturnal awakenings (F1,63 = 4.89, p = 0.03). Furthermore, this association was mostly evident in individuals with elevated levels of total tau (F1,61 = 4.23, p = 0.04).ConclusionOur findings provide in vivo evidence that worse LC structural integrity is associated with more frequent nocturnal awakenings in the context of neurodegeneration, in cognitively normal older individuals. In addition, they further emphasize the role of the LC in the arousal‐ascending system as an important neurobiological correlate of sleep‐wake regulation, and hold promise for the identification of at‐risk populations for preventive interventions.
Personality factors as cognitive resilience against early‐life disadvantage: Results from the Mexican Health and Aging Study
Authors: Saenz Joseph , Milani Sadaf Arefi , Arango Silvia Mejia 
Published: December 2021

AbstractBackgroundEarly‐life disadvantage, including low socioeconomic position (SEP), few resources, and limited education, has downstream effects on cognitive ability. However, personality‐related factors such as having an internal locus of control or a more conscientious personality have been related with greater resilience and ability to cope with adversity. Our objective is to determine if personality‐related factors position individuals to overcome the negative effects of early‐life adversity on late‐life cognitive ability.MethodData comes from the 2015 Mexican Health and Aging Study. First, we estimate each respondents’ expected cognitive ability (ŷ) given their markers of early‐life disadvantage by regressing observed, age‐normed, late‐life cognitive ability (y) on markers of early‐life disadvantage (own and parental education, parental occupation, and markers of early‐life SEP) to identify a subsample expected to be in the lowest quartile of cognitive ability given their early‐life. Second, we use this subsample (n=2,214) to investigate how personality‐related factors (locus of control and conscientiousness) relate with one’s odds of ultimately having above median observed cognitive ability (y) using logistic regression.ResultRespondents in the lowest quartile of expected cognitive ability based on early‐life disadvantage had an average of less than a year of education, had parents with little education, and endorsed more markers of low early‐life SEP. However, 21% ultimately ended up above median cognitive ability. Among those in the lowest quartile of expected cognitive ability, having a more internal locus of control (OR: 1.09, 95% CI: 1.06‐1.13) or more conscientious personality (OR: 1.09, 95% CI: 1.05‐1.12) were independently related with having above median cognitive ability. Living in an urban area, and greater wealth were also associated with having above median cognitive ability.ConclusionOur findings suggest that individuals with an internal locus of control and a conscientious personality are better able to “break the link” between early‐life disadvantage and poor cognitive function later in life.
Association of adverse childhood experiences and late‐life cognition in Black Americans from the Study of Healthy Aging in African Americans (STAR)
Authors: Lor Yi , Gilsanz Paola , George Kristen M , Hayes‐Larson Eleanor , Peterson Rachel L , Meyer Oanh L , Barnes Lisa L , Whitmer Rachel A 
Published: December 2021

AbstractBackgroundThough Black Americans are more likely to experience adverse childhood experiences (ACEs) not much is known how these experiences are associated with late‐life cognitive outcomes in Black Americans. We examined the association between ACEs and late life cognition in the Study of Healthy Aging in African Americans (STAR).MethodsLaunched in 2018, STAR is a cohort study of cognitive aging and brain health in 764 Black Americans ages ≥50 years. ACEs were self‐reported via a nine‐item questionnaire. Executive function, semantic memory, and verbal episodic memory were measured using the Spanish and English Neuropsychological Assessment Scales (SENAS) and scores were z‐standardized. Linear regression models were used to associate ACEs exposure with cognitive domains adjusting for age, gender, participant education, and parental education (proxy for childhood socioeconomic status).ResultsThe majority of participants were female (69%) and the mean age was 69 years (SD=8.7) Table 1. Most of the respondents (73%) reported having one or more ACEs with parental separation (39%), serious family illness (36%), and witnessing domestic violence (31%) being most common. Other ACEs included parent remarried (26%), substance abuse by a family member (25%), parental job loss (15%), parental incarceration (8%), maternal death (6.5%), and paternal death (10.4%). Most ACEs were not significantly associated with domain specific cognitive scores, except experiencing the death of a father, which was associated with lower semantic memory (β=‐0.36; 95% CI: ‐0.56, ‐0.15; Table 2). Gender‐stratified models showed that the association between death of a father and lower semantic memory was significant for female (β=‐0.45; 95% CI: ‐0.69, ‐0.21) but not males (β=‐0.17; 95% CI: ‐0.54, 0.20). There was no evidence that the relationship between other ACEs and domain‐specific cognitive scores varied by gender.ConclusionsACEs were common among Black Americans in this cohort, but only death of a father in early life was associated with lower late life semantic memory, especially among women. Mechanisms of this association are unclear. Future studies with longitudinal data are needed to understand whether ACEs are related to cognitive decline over time in this population.
Active deep learning to detect cognitive concerns in electronic health records
Authors: Magdamo Colin G. , Hong Zhuoqiao Mia , Noori Ayush , Sheu Yi‐Han , Deodhar Mayuresh , Ye Elissa M , Ge Wendong , Sun Haoqi , Brenner Laura , Robbins Gregory K. , Mukerji Shibani , Zafar Sahar F. , Benson Nicole , Moura Lidia Maria V. , Hsu John , Arnold Steven E. , Hyman Bradley T. , Serrano‐Pozo Alberto , Westover M Brandon , Blacker Deborah , Das Sudeshna 
Published: December 2021

AbstractBackgroundTimely diagnosis of dementia is important to patients and their caregivers for advanced planning, yet dementia is under‐diagnosed by healthcare professionals and under‐coded in claims data. Sensitive and specific tools to detect cognitive concerns in diverse clinical settings could prompt referral for cognitive evaluation and specialist care.MethodWe developed a deep learning natural language processing (NLP) method to detect cognitive concerns in unstructured clinician notes from electronic health records (EHR). We leveraged a gold‐standard set of ∼1000 patients sampled randomly from three strata: patients with diagnosis codes, patients with specialist visits but no code, or patients with neither. The physician performed a detailed chart review and adjudication of cognitive status, noting "cognitive concern" (i.e., any evidence of cognitive difficulties) and rating patients on a 5‐point scale: normal, normal vs. MCI, MCI, MCI vs. dementia, and dementia. We used 10% of the labeled data as a test set and the remaining 90% for training and validation of the model to classify patients with any cognitive concerns (normal vs. other). We also built a web‐based chart review annotation tool that facilitates labeling and enables an active learning loop to scale up labeling to thousands of charts.ResultIn a random sample from the gold‐standard dataset, 30 out of 80 patients with cognitive concerns had no diagnosis code or medication related to dementia; we hypothesized that our deep learning tool could leverage clinical text to improve detection of cognitive concerns. Indeed, a model with codes and medications had an area under the receiver operating characteristic (AUROC) curve of 0.79, sensitivity of 0.59, and specificity of 1.00 for the binary classification task. The deep learning model improved the AUROC to 0.90, increased sensitivity to 0.79, and maintained specificity of 0.98. Notes from primary care, specialties such as neurology and psychiatry, and social workers had the highest likelihood of containing information.ConclusionThe deep learning model was successful in detecting cases without a dementia‐related diagnosis code or medication. Automatic processing of electronic medical records with a deep learning tool can be used for early detection of cognitive concern to optimize patient care and predict hospital readmission.
Risk for hospitalization surrounding dementia diagnosis: A national registry‐based study
Authors: Shahar Rotem , Lutski Miri , Zucker Inbar , Weinstein Galit 
Published: December 2021

AbstractBackgroundStudies show that incident dementia is associated with an increased risk of hospitalization. Recent evidence also suggests that hospitalization may be a risk factor for dementia. We aimed to capture the changes in hospitalization rates, annual number of admissions and length of stay (LOS) during 4 years surrounding dementia diagnosis in a national population‐based sample. In addition, we examined the association of sociodemographic and clinical factors with hospitalization measures in the immediate years before and after dementia diagnosis.MethodThe sample for this retrospective cohort study included 11,625 individuals aged 65 years and older, who were identified as incident cases of dementia in the Israel dementia national registry during 2016 (mean age= 81.21±7.19y; 61% women). Hospitalization data were obtained from National Hospital Discharge Database (NHDD) of the Israeli Ministry of Health, and clinical and sociodemographic data were extracted from the national registry database. Mixed regression models were used to assess within‐subject changes in the likelihood of hospitalization, the number of hospitalizations and LOS among survivors of the entire follow‐up period (N=8,000). We also tested for possible interactions of time respective to diagnosis with age, sex, ethnicity, socioeconomic status, BMI and comorbidity with regard to hospitalization indices.ResultThe risk for hospitalization as well as the number of visits and LOS were highest during the year preceding dementia diagnosis (OR =3.19, 95%CI 2.51‐4.06; OR= 3.69, 95%CI 2.86‐4.76; OR=3.53, 95%CI 2.75‐4.54, respectively, compared to the reference period of 2 years prior dementia diagnosis). These hospitalization measures slightly decreased with time after dementia diagnosis, but remained high, compared to the reference period (figure 1). The associations between age, sex, comorbidity and BMI with odds of hospitalization differed significantly depending on the time respective to dementia diagnosis (figure 2‐5). Similar associations were found for annual number of hospitalizations and LOS.ConclusionThis study points to an increased burden due to hospitalizations during the year prior to dementia diagnosis and the years proceeding it. Our findings also highlight the need to consider the time surrounding dementia diagnosis in the prediction of hospital burden based on factors such as age and comorbidities.
Smoking and the risk of dementia in the oldest‐old: The Monzino 80‐plus study
Authors: Lucca Ugo , Tettamanti Mauro , Riva Emma , Mandelli Sara , Forloni Gianluigi , Galbussera Alessia A 
Published: December 2021

AbstractBackgroundNicotine is a cholinergic agonist that can enhance short‐term cognitive performance. After initial findings suggesting a possible protective effect of smoking against dementia, subsequent research has pointed out smoking as a risk factor for dementia and Alzheimer’s disease. However, very few data are available on this relationship in the oldest‐old. Objectives: To explore the association of smoking with the development of dementia in advanced age in a prospective population‐based study of 80‐years or older residents in Varese province, Italy (Monzino 80‐plus Study).MethodInformation on smoking habit was obtained from the subject and/or a primary informant, mostly a family member, using a standardized questionnaire. Diagnosis of dementia fulfilled DSM‐IV criteria. Logistic regression and Cox proportional hazard models were used to investigate cross sectional and longitudinal associations between smoking and dementia risk.ResultThe initial population consisted of 2,193 individuals (mean age: 90.2 years; women: 72.7%). At first visit oldest‐old who had never smoked represented the large majority of the population (1778, 81.1%), while current smokers were very few (n=49, 2.2%). On average, they currently smoked 9.7±7.9 cigarettes daily, started smoking at 22.8±11.7 years of age, and had been smoking for 67.1±10.3 years. Former smokers (n=366; 16.7%) had quit smoking on average 29.6±18.0 years before initial interview. Prevalence of dementia was lower among current smokers (18.4%) compared to never smokers (40.0%; p=0.0036), but this difference was no longer significant after adjustment for age, sex, and education (adjusted p=0.2435). There were 1,138 individuals without dementia at first visit with at least one follow‐up available (mean age: 88.4 years; women: 69.2%). In the following 15.5 years, current smokers (n=28) had a higher occurrence of dementia (60.7%) than never smokers (50.1%; age, sex, and education adjusted HR: 1.30, 95% CI: 0.80‐2.12, p=0.2913) or non‐smokers (never and former) (46.9%; age, sex, and education adjusted HR: 1.34, 95% CI: 0.83‐2.18, p=0.2349). The low proportion of current smokers limited the possibility to investigate the effect of smoking on dementia incidence.ConclusionSmoking habit is very uncommon among oldest‐old and it was not significantly associated with the risk of dementia either in cross sectional or longitudinal analysis.
Subjective cognitive decline is associated with higher anxiety and depression during the COVID‐19‒related confinement
Authors: Sánchez‐Benavides Gonzalo , Akinci Muge , Minguillón Carolina , Deulofeu Carme , Salvadó Gemma , González‐de‐Echávarri José María , Brugulat‐Serrat Anna , Suarez‐Calvet Marc , Sala‐Vila Aleix , Grau‐Rivera Oriol , Fauria Karine , Molinuevo Jose , Gispert Juan Domingo , Arenaza‐Urquijo Eider M ,   ALFA study
Published: December 2021

AbstractBackgroundSubjective cognitive decline (SCD) is often related to affective symptoms and both predict cognitive decline. We investigated whether SCD status predicted higher anxiety/depression during the Covid19‐related confinement, along with amyloid positivity in cognitively unimpaired older adults.MethodWe included 205 participants from the ALFA+ study (Table 1). During the confinement, anxiety and depression (Hospital Depression and Anxiety scale, HADS), perceived stress (Perceived Stress Scale) and stress resilience (Brief Resilience Scale) were measured. Participants completed HADS, SCD‐Questionnaire, and underwent a [18F]flutemetamol‐PET scan on average 2.4 years before confinement (baseline). We ran linear analyses with (i) cross‐sectional HADS scores during the confinement as well as (ii) change from baseline to confinement (delta scores) as dependent variables. SCD and amyloid status (+/‐, defined with a Centiloid threshold of 12) and their interaction were considered as predictors, and demographics, APOE‐ε4 status, and baseline HADS (for longitudinal analyses) as covariates. In a second step, perceived stress and stress resilience were considered in the models among covariates.ResultTwenty‐seven percent (n=56) of the participants were classified as SCD and 12.7% as amyloid positive. When main effects were tested, both SCD (p=0.03) and amyloid positivity (p=0.003) were associated with higher HADS scores during confinement (Table 2a). Further, a significant SCD*amyloid interaction was observed (p=0.001) such that only SCD participants with an amyloid positive scan showed higher HADS scores (p=0.001). SCD participants showed higher perceived stress than non‐SCD participants (p=.044), but no differences were found in stress resilience (p=0.6). The inclusion of perceived stress and stress resilience as covariates reduced the SCD effect to a trend (p=0.06) but not the effect of amyloid (p=0.003). Longitudinal analyses with delta scores showed similar results for amyloid but not for SCD main effects (Table 2b). The amyloid*SCD interaction was also significant in longitudinal analyses (p=0.002) with amyloid status predicting an increase in HADS scores only in participants with SCD (p=0.003) (Fig. 1).ConclusionHaving SCD and being amyloid positive is synergistically related to increased anxiety/depression during the Covid19‐related confinement. Longitudinal studies are warranted to investigate the impact of higher confinement related anxiety/depression in the clinical prognosis of the SCD population.
Atrophy and partial volume related bias in cortical region of interest NODDI metrics
Authors: Veale Thomas , Parker Christopher S , Bocchetta Martina , Malone Ian B , Slattery Catherine F , Schott Jonathan M , Fox Nick C , Zhang Hui , Cash David M 
Published: December 2021

AbstractBackgroundNeurite Orientation Dispersion and Density Imaging (NODDI) provides in‐vivo indices of neurite density (NDI) and orientation dispersion (ODI) within the tissue compartment of each voxel. However, NDI and ODI are treated equally when calculating region of interest (ROI) means, despite tissue fraction (TF) varying within regions undergoing neurodegeneration. Covariation between TF and cortical NODDI measures bias these conventional means and we recommend using tissue‐weighted averages to address this.MethodIn this study, we included 22 healthy controls and 33 individuals affected by Young‐Onset Alzheimer’s disease (YOAD, see Table 1 for demographics) with suitable diffusion‐weighted and T1‐weighted 3T MR images. Diffusion data were corrected for eddy currents, motion and susceptibility artefacts before fitting the NODDI model to produce NDI, ODI, isotropic volume fraction (ISO) and TF maps (TF=1‐ISO). T1w images were parcellated into cortical ROIs using Geodesic Information Flow (Cardoso et al., IEEE Trans.Med.Im.; 34:1976‐1988, 2015). Five bilateral ROIs expected to undergo neurodegeneration were analysed (Precuneus, Fusiform Gyrus, Superior Parietal, Middle and Inferior Temporal cortex). ROIs were resampled into native diffusion space and two regional measures calculated: 1) conventional, unweighted NDI and ODI averages and 2) tissue‐weighted averages using voxel TF as weights. Within‐participant differences between conventional and tissue‐weighted measures were calculated. Spearman’s rank tested correlations and Wilcoxon tests evaluated within‐ and between‐participant differences (Bonferroni adjusted for multiple comparisons).ResultTF positively correlated with GM volume (rs range=0.33‐0.68,p<0.05) in all ROIs except the left fusiform gyrus (rs=0.31,p=0.06) (Figure 1). YOAD individuals had lower TF than healthy controls in all ROIs (Figure 2a), and lower volumes in all ROIs except the right fusiform gyrus (W=475,p=0.27) (Figure 2b). NDI showed small positive/negative biases in six of the ten ROIs (Figure 3a), while ODI showed significant positive biases across all ROIs (Figure 3b). Biases decreased as TF increased towards its maximum of one (Figure 4a‐4b).ConclusionLower cortical volumes in YOAD were associated with lower TF and higher bias, suggesting a greater risk for misestimation of cortical region NODDI metrics in studies involving neurodegenerative disease. We recommend tissue‐weighted averages to account for varying intra‐regional TF in NODDI measures.
Alcohol consumption and the risk of dementia in the oldest old: The Monzino 80‐plus study
Authors: Lucca Ugo , Tettamanti Mauro , Riva Emma , Mandelli Sara , Forloni Gianluigi , Galbussera Alessia A 
Published: December 2021

AbstractBackgroundWine, beer, spirits or liqueurs are widely popular beverages worldwide. Several studies have investigated the association between alcohol consumption and dementia with inconsistent results, however very few data are available on this relationship in the oldest‐old. Objectives: To investigate the association of alcohol consumption with the development of dementia in advanced age in a prospective population‐based study of 80‐years or older residents in Varese province, Italy (Monzino 80‐plus Study).MethodInformation on alcohol consumption (wine, beer, spirits or liqueurs) was obtained from the subject and/or a primary informant, mostly a family member, using a standardized questionnaire. Diagnosis of dementia fulfilled DSM‐IV criteria. Covariates entered in the fully adjusted logistic and Cox regression models: age, sex, education, diabetes, hypertension, heart failure, myocardial infarction, COPD, ictus, TIA, parkinsonism. Since former drinkers stopped drinking on average 12.4±13.7 (cross‐sectional study) and 16.0±17.0 (longitudinal study) years before interview, they were categorized, together with the never drinkers, in the group of non‐drinkers.ResultAmong the 2,195 participants (mean age: 90.2 years; women: 72.7%) interviewed at first visit, 1,107 (50.4%) were current drinkers (wine, only or together with other alcoholic beverages: 99.8% in cross‐sectional and 100% in longitudinal studies), 318 (14.5%) former drinkers, and 770 (35.1%) never drinkers. Consumers on average currently drank 18.2±15.5 g/day of ethanol, started drinking at 21.4±16.2 years of age, and have been drinking for 68.1±11.2 years. Prevalence of dementia was lower among current drinkers (27.8%) compared to non‐drinkers (47.2%; fully adjusted p<0.0001). There were 1,139 individuals without dementia at first visit with at least one follow‐up available (mean age: 88.4 years; women: 69.3%). In the following 15.5 years, current drinkers (n=675) had a lower occurrence of dementia (43.3%) than non‐drinkers (53.0%; fully adjusted HR: 0.8372, 95% CI: 0.7008‐1.0002, p=0.0503). When current drinkers were divided according to daily intake into two groups (>0‐24 and >24 g/day of ethanol), results of both cross‐sectional and longitudinal analyses gave analogous results.ConclusionAlcohol consumption, mostly of moderate amounts, is common among oldest‐old and is associated with a marginally non‐significant lower risk of incident dementia.