bluuebunny/crossref_metadata_2025_split huggingface dataset:
Factors associated with emotional and social loneliness among Latin American family care partners of people with dementia and other long‐term conditions during Covid‐19
Authors: Tapia‐Muñoz Thamara , Leon Tomas , Slachevsky Andrea , Beber Bárbara Costa , Nubia Carla , Vilar‐Compte Mireya , Gaitan Pablo , Olavarria Loreto , Castro Loreto , Pinto Alejandra , Chen Yaohua Sophie , Grycuk Emilia , Leroi Iracema , Lawlor Brian , Duran‐Aniotz Claudia , O'Sullivan Roger , Miranda‐Castillo Claudia 
Published: December 2023

AbstractBackgroundCOVID‐19‐related restrictions led to an increase in loneliness and social isolation Historically, dementia care partners present worse mental health and higher burden than non‐dementia care partners. We aimed to analyse the during‐COVID‐19 loneliness levels of Latin American care partners and explore differences between care partners of people with dementia compared to those of people with other enduring health conditions.MethodThis was a sub‐study of the ‘Coping with Loneliness and Isolation during COVID‐19’ (CLIC) Study, an international self‐report survey of 5236 care partners during the COVID‐19 pandemic. People living at home in one of three Latin American countries: Mexico, Chile, Brazil and others. We analysed data from 241 care partners living in Latin American countries who responded to the CLIC Study survey. We used linear regression models to identify factors associated with loneliness and compared care partners of people living with dementia with care partners with other chronic deseases.ResultCompared to pre‐pandemic, there was a significant increase in the prevalence of self‐reported total loneliness reported by the care partners. The levels of social and emotional loneliness between care partners of people with dementia vs other conditions did not differ. Low education and low perception of mental health was associated with emotional and social loneliness during the COVID‐19 pandemic.Conclusionloneliness during the pandemic was similar across care partners. Some groups are at special risk for higher levels of loneliness and should be considered when planning public health interventions for major societal disruptions, such as a pandemic, in the future.
Spatial navigation, physical activity, and Alzheimer disease biomarkers
Authors: Stojanovic Marta , Allison Samantha L. , Schindler Suzanne E. , Head Denise M 
Published: December 2023

AbstractBackgroundElevated levels of amyloid are associated with worse performance on cognitive mapping (CM), a spatial navigation task reliant on the hippocampus. Prior animal work found that exercise is associated with better learning in CM tasks. Hence, the first goal of the study was to examine whether physical activity moderates the relationship between amyloid deposition and CM. In addition, spatial navigation ability predicts Alzheimer disease (AD) clinical progression but there is a need to examine whether it also predicts subsequent levels of amyloid and tau. Hence, the second goal was to examine whether CM predicts later levels of PET‐Tau and longitudinal trajectories of PET‐Amyloid.MethodCognitively normal individuals (n = 65; age range 50‐84 years) were administered a CM task in a virtual environment and a self‐report measure of physical activity. For cross‐sectional analyses, amyloid deposition was estimated via cerebrospinal fluid levels of Aβ42. One assessment of PET‐Tau (n = 49) and repeated assessments of PET‐Amyloid (n = 59) were obtained following the CM session.ResultConcurrent amyloid deposition was associated with reduced learning (p = 0.002) and retention of the environment (p = 0.002) while greater physical activity was associated with better learning (p = 0.004). There was no moderation by physical activity (all p’s > 0.156). CM performance was not associated with longitudinal trajectories of PET‐Amyloid (all p’s > 0.330) or the subsequent levels of PET‐Tau (all p’s > 0.572).ConclusionThese results suggest that both current physical activity and levels of amyloid can be important predictors of spatial navigation skills. However, CM might be a limited predictor of AD biomarker accumulation. Future studies should use a larger sample size and greater number of assessments to examine these questions.
The association between Aβ aggregation and age depends on APOE genotype: Findings from the AMYPAD cohort
Authors: Régy Mélina , Quenon Lisa , Collij Lyduine E. , García David Vállez , Gérard Thomas , Frisoni Giovanni , Scheltens Philip , Schöll Michael , Vandenberghe Rik , Boada Mercè , Marquié Marta , Payoux Pierre , Nordberg Agneta K , Kivipelto Miia , Walker Zuzana , Dubois Bruno , Boutoleau‐Bretonnière Claire , Pasquier Florence , Dugravot Aline , Gabelle Audrey , Visser Pieter Jelle , Grau‐Rivera Oriol , Martinez‐Lage Pablo , Ritchie Craig W , Wolz Robin , Farrar Gill , Lhommel Renaud , Barkhof Frederik , Dumurgier Julien , Hanseeuw Bernard J 
Published: December 2023

AbstractBackgroundThe present study aimed to explore the association between Apolipoprotein E (APOE) genotype, the main genetic risk factor for sporadic Alzheimer’s Disease (AD), age, and cerebral β‐amyloid (Aβ) aggregation, the earliest pathological event in AD in a large, multicenter, European cohort, the AMYPAD study.MethodWe included 876 participants from the AMYPAD cohort who had known APOE genotype and went through at least one Aβ PET imaging. We first looked at the association between Aβ deposition and age according to sex, APOE genotype, and cognitive status. We then used linear regression models to look at the association between Aβ aggregation and APOE genotype in different cerebral regions with age, sex, history of dementia, MMSE score, CDR score, depression, hypercholesterolemia, diabetes and center as covariates.ResultOur participants had a mean age of 67 years old with a mean MMSE score of 28.9/30 and counted 60% of women. We found a positive association between Aβ deposition and age with a gradually stronger association in heterozygous ԑ4 carriers (β (SD) = 1.94 (0.27)) and homozygous ԑ4 carriers (3.18 (0.52)) compared to non‐carriers (0.99 (0.12), p<0.001; Figure). We found similar results when restricting the analyses to cognitively unimpaired participants (heterozygous ԑ4: 1.65 (0.27), p<0.001; homozygous ԑ4: 3.01 (0.52), p<0.001), however Aβ aggregation was less associated to age in participants with mild cognitive impairment (heterozygous ԑ4: 1.33 (1.4), p = 0.33; homozygous ԑ4: 2.34 (1.9), p = 0.29). Moreover, we found an effect of sex on the association between Aβ aggregation and age in ԑ4 non‐carriers characterized by a stronger association in men (1.61 (0.22)) compared to women (0.63 (0.13)). Finally, we observed that the effect of APOE genotype on Aβ aggregation remained similar in the different cerebral regions, with less discernable differences between genotypes in the medial temporal and occipital regions.ConclusionThe number of APOE4 alleles has an impact on the association between age and Aβ aggregation, such that high amyloid was observed at younger ages in homozygous APOE4 carriers than in heterozygous APOE4 carriers and in non‐carriers. The effect of APOE4 on Aβ deposition was global rather than regional in our analysis.
Dementia caregiver burden and its toll on caregiver health
Authors: Mehdipanah Roshanak , Malvitz Madelyn , Briceno Emily M , Chang Wen , Lewandowski‐Romps Lisa , Heeringa Steven G , Zahuranec Darin B , Levine Deborah A , Langa Kenneth M , Gonzales Xavier , Garcia Nelda M , Morgenstern Lewis B 
Published: December 2023

AbstractBackgroundIn 2019, more than 16 million U.S. family members and friends provided 18.6 billion hours of unpaid care to people with cognitive impairment. Mexican Americans (MAs) make up two thirds of the Latinx population and research shows that MA caregivers report more caregiver burden compared to non‐Hispanic Whites (NHW). The purpose of this study is to examine the underlying mechanisms influencing caregiver burden on the physical and mental health of caregivers by ethnicity and familism.MethodWe recruited adults 65 and older with cognitive impairment (Montreal Cognitive Assessment score>25), and their caregivers living in Nueces County, Texas. Caregiver burden was measured using the Zarit Burden Interview. Familism was measured using a 18‐item scale. Caregiver’s mental and physical health were derived from the 36‐Item Short Form Survey. Covariates included caregiver’s age, sex, ethnicity, education and care recipient’s cognitive function and physical impairment, including the ability to eat, dress or go to the toilet without assistance. We used weighted path analysis to test effects of ethnicity, familism and caregiver burden on caregiver’s mental and physical health. Covariates with p‐values>0.15 were excluded to attain a parsimonious reduced model.ResultWe included data from 516 caregivers and those they cared for. MA caregivers were younger, female, had less education and scored higher on the familism scale compared to NHW (Table 1). Figure 1 includes results from our reduced weighted path model which presented a good model fit. Increased caregiver burden was associated with worse mental (B = ‐0.53;p<0.001) and physical health (B = ‐0.14;p = 0.003). Familism had indirect positive effects on mental and physical health outcomes mediated by lowering caregiver burden (B = ‐0.15;p = 0.001). Being a MA caregiver was associated with a stronger level of familism (B = 0.49;p<0.001). Findings indicate that MA caregivers have better physical and mental health due to reduced caregiver burden because of stronger family relations.ConclusionResults show that increased caregiver burden is associated with worse caregiver’s mental and physical health. However, among MA, familism can be a protective factor against caregiver burden. Findings can contribute to early identification, intervention and coordination of services to help reduce caregiver burden, particularly in the growing MA informal caregiver population.
Early morning naps are correlated with incident Alzheimer’s Dementia in older adults
Authors: Gao Chenlu , Zheng Xi , Yu Lei , Buchman Aron S , Bennett David A. A , Leng Yue , Gao Lei , Hu Kun , Li Peng 
Published: December 2023

AbstractBackgroundPrevious findings suggest that frequent and longer naps during daytime are associated with elevated risks of Alzheimer’s dementia among older adults. This study aims to further examine whether naps during a particular time of a day are differentially linked to risk of Alzheimer’s dementia.MethodA total of 1,203 participants from the Rush Memory and Aging Project (mean age at actigraphy = 80.85±7.30 years; 77% female) wore accelerometers (Actical) for up to 14 (mean = 9.57±1.17) days and completed annual neurocognitive assessment for up to 17 (mean = 6.92±4.12) years. A validated algorithm was used to identify daytime naps between 9am and 7pm. We categorized participants into those who napped versus those who did not nap during each time period, i.e., morning (9‐11am), noon (11am‐1pm), early afternoon (1‐3pm), late afternoon (3‐5pm), and early evening (5‐7pm). We conducted Cox proportional hazards models to test whether napping at a specific time of day is correlated with incident Alzheimer’s dementia, adjusting for age, sex, education years, length of actigraphy recording, body mass index, intradaily variability of rest‐activity rhythms, and nighttime sleep duration.ResultAmong all participants, 357 developed Alzheimer’s dementia during follow‐up (mean time to incidents = 6.34±3.98 years). Compared to those who did not nap in the morning (9‐11am), participants who napped in the morning had 1.4‐fold (HR[95%CI] = 1.43 [1.07‐1.93], p = 0.01) risk for developing Alzheimer’s dementia. This association was attenuated after further adjusting for total nap duration and frequency (HR[95%CI] = 1.32[0.97‐1.79], p = 0.07). However, napping during other time periods was not associated with risk for Alzheimer’s dementia, after adjusting for the covariates (noon: HR[95%CI] = 1.26[0.94‐1.68], p = 0.12; early afternoon: HR[95%CI] = 1.22[0.81‐1.84], p = 0.33; late afternoon: HR[95%CI] = 1.22[0.81‐1.84], p = 0.34; early evening: HR[95%CI] = 0.84[0.62‐1.13], p = 0.24).ConclusionNapping in the morning may link to an increased risk of Alzheimer’s dementia in older adults. A potential explanation is that individuals who nap more in the morning are more likely to experience disturbances in sleep‐wake regulation. Future studies should investigate this underlying mechanism and test whether interventions to reduce morning naps or consolidate naps can benefit neurocognitive outcomes.
Social cognition and emotion inference abilities in healthy aging and Mild Cognitive Impairment
Authors: Gasparre Daphne , Pepe Ilaria , Abbatantuono Chiara , Introna Alessandro , Biasi Madia Marika , Paparella Giulia , De Caro Maria Fara , Defazio Giovanni , Taurisano Paolo 
Published: December 2023

AbstractBackgroundSocial cognition (SC) is a neurocognitive domain that can be affected by the pathophysiological changes of aging, and deteriorate in individuals diagnosed with Mild Cognitive Impairment (MCI) and Alzheimer’s Disease. This social‐cognitive function involves the attribution of one’s mental states, including intentions (IA) and emotions (EA). As mentalization abilities may impact on daily functioning, research is focusing on SC processes in individuals at risk for age‐related neurocognitive decline. The present study aimed to 1) investigate SC abilities in MCI, compared to healthy individuals; 2) explore whether specific SC sub‐domains could be associated with MCI diagnosis.MethodN = 468 outpatients referred to Bari University Hospital for neuropsychological assessment were classified into two groups: i) a cognitively spared (n = 166; Mage = 61); ii) MCI (n = 302; Mage = 67), characterized by objective deficits one or more neurocognitive domains (other than SC) not interfering with daily functioning. Sample classification resulted from multidomain, cognitive‐functional assessment procedures consistent with Petersen’s criteria (Petersen et al., 2014). A total of 185 subjects also completed the Story‐Based Empathy Task (SET), yielding four social cognition scores (i.e., global score [GS]; IA; EA; causal inference [CI]). After testing the distribution of the SET variable through the Shapiro‐Wilk test, the Mann‐Whitney U test was used to analyze mean differences between the two groups. Additionally, a binary logistic regression was conducted to assess whether impaired SC could be associated with MCI diagnosis.ResultPatients with MCI showed significantly lower SC performances in all SET sub‐tests, compared to controls (SET‐GS: Z = ‐5.25; p<.001; SET‐IA: Z = ‐3.98; p<.001; SET‐EA: Z = ‐4.02; p<.001; SET‐CI: Z = ‐3.22; p<.001). Binary logistic regression with backward elimination revealed that among all SC sub‐domains, the inability to infer emotional states resulted being associated with MCI diagnosis (B = ‐.678; exp(B) = .507; p<.001). Regression analysis was overall significant (χ2 = 16.68; p<.001), and correctly classified 66% of cases.ConclusionOur findings highlighted significantly poorer SC performances in MCI, notably in the emotional inference sub‐domain. This preliminary evidence may contribute to the clinical understanding of social‐cognitive functioning in elderly individuals with mild/initial cognitive deficits, emphasizing the importance of accounting for SC in neuropsychological assessment to improve early diagnosis and strategies for dementia prevention.
Multimodal investigation of the early associations between sleep‐wake regulation, cognition and Alzheimer’s disease neuropathology and risk
Authors: Gilles Vandewalle 
Published: December 2023

AbstractBackgroundAlterations in sleep‐wake regulation are hallmarks of the ageing process and emerge as risk factors for Alzheimer’s disease (AD). While the fine‐tuned coalescence of sleep microstructure elements may influence age‐related cognitive trajectories, its association with AD‐related processes is not fully known. Likewise, whether markers of sleep‐wake regulation assessed during wakefulness are associated with the risk of developing AD is not established.MethodHere, we sought associations between key elements of the electrophysiology of sleep microstructure and of sleep‐wake regulation and hallmarks of AD neuropathology (early Aβ/Tau/neuroinflammation brain burden) or the polygenetic risk in 360 young adults (18‐31y) and 100 late‐midlife healthy individuals (50‐70y). We further investigated relationships with cognitive performance.ResultWe first found that spontaneous arousal during sleep are heterogenous and differently associated with Aβ and cognition. We further found the young‐like co‐occurrence of sleep spindles and slow‐depolarisation slow waves was associated to lower early burden of Aβ and was predictive of memory decline at 2‐year follow‐up. We also find that the dynamics of the daily change in cortical excitability and EEG markers of sleepiness are respectively not associated with early Ab burden and associated with the polygenic risk of developing AD. Cortical excitability dynamics is, however, association with cognitive performance.ConclusionThese findings unravel early links between sleep‐wake regulation, AD‐related processes or genetic risks and their association with cognitive performance. Spontaneous arousals and the altered coupling of sleep microstructure elements that are key to its mnesic functions may contributes to poorer brain and cognitive trajectories in ageing. In addition, associations between markers of sleep‐wake regulation and AD can be detected during quiet wakefulness.Support: ULiège, Wallonia‐Brussels Federation, Fonds de la Recherche Scientifique (FNRS Belgium), Fondation Recherche Alzheimer (SOA‐FRA Belgium), Fondation Léon Fredericq, EU FEDER programme
Identifying change on the CERAD Word List with standardized regression‐based scores
Authors: Duff Kevin , Hanna Elise J , Mattek Nora , DeCapo Madison , Hantke Nathan , Pierce Aimee , Kaye Jeffrey A 
Published: December 2023

AbstractBackgroundList learning and memory tests are frequently used to evaluate older adults for Mild Cognitive Impairment and Alzheimer’s disease. One such test, the Word List subtest of the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD), has been widely‐used in clinical trials track such disorders. However, data is lacking on the amount of change that is needed to accurately identify decline.MethodParticipants included 897 older adults (age in years: M = 81.1, SD = 8.1, range 55‐100; 67% women; education in years: M = 14.8, SD = 2.8, range = 7‐24) who were cognitively intact at two annual visits in a longitudinal observational study from the Uniform Data Set of the National Alzheimer’s Coordinating Center. Each participant completed the Word List subtest at two visits, which were approximately 1 year apart (interval in years: M = 1.3, SD = 1.0). Multiple linear regression predicted Time 2 scores from Time 1 scores and simple demographic variables (age, sex, education). The predicted Time 2 scores were compared to observed Time 2 scores to preliminarily validate this change data.ResultFor three primary scores from the Word List subtest (Acquisition Total Correct, Delay Recall Total Correct, Recognition Total Correct), the Time 2 scores were significantly predicted from the other variables, with R2s ranging from 0.16 – 0.41 (p‐values<0.001). When these predicted Time 2 scores were compared to observed Time 2 scores, there were no significant differences (p‐values≧0.19), indicating preliminary support for these prediction scores.ConclusionThe current prediction equations appear to allow clinicians and researchers to accurately track change on the Word List subtest of the CERAD by comparing their patients/participants to the current sample of robustly intact older adults. Consistent with past work in this area, Time 1 cognitive scores were the best predictors of Time 2 cognitive scores, although demographic variables added to that prediction. Future work should consider if additional variables can improve the prediction equations. Future work should also validate these equations in independent samples to examine their clinical utility.
Long term high‐fat feeding induces cognitive impairment, alterations in microglial morphology, and spatial transcriptomic changes
Authors: Elzinga Sarah E , Noureldein Mohamed , Guo Kai , Jang Dae Gyu , Hayes John M , Henn Rosemary E , Webber‐Davis Ian , Mendelson Faye E , Parent Rachel , Rigan Diana M , Glass Emily , Turfah Ali , Zhao Lili , Murphy Geoffrey G , Hur Junguk , Feldman Eva L 
Published: December 2023

AbstractBackgroundObesity and metabolic dysfunction (Metabolic Syndrome, prediabetes, and diabetes) increase the risk of later life cognitive impairment, including dementias such as Alzheimer’s Disease1‐3. One common etiology that might underly this increased risk is immune system dysregulation and inflammation4, 5. Specifically, microglial dependent mechanisms are thought to play an important role in pathology6‐8. However, the precise immune and inflammatory mechanisms promoting cognitive decline secondary to obesity and metabolic dysfunction are unclear.MethodBL6 male mice were fed 60% HFD (high fat diet) or 10% SD (standard diet) for 1 year. Body weight and glucose tolerance were assessed longitudinally. Cognition was repeatedly evaluated using Morris water maze, social recognition, and puzzle box. At study termination, mice were given either an intraperitoneal injection of lipopolysaccharide as an immune challenge or saline as a control. Activation of hippocampal microglia was assessed via immunohistochemistry (IHC) and analysis of microglial morphology. Changes in brain gene expression were measured via spatial transcriptomics using the 10X Visium platform.ResultHFD feeding caused increased weight, impaired glucose tolerance, and cognitive deficits which persisted throughout the study period. Body weight in particular was predictive of cognitive changes, especially for later time points. In response to immune challenge, hippocampal microglia in SD mice had a normal morphological response indicative of activation. However, microglia of HFD mice had no change in their morphology in response to lipopolysaccharide injection. Additionally, changes in morphology significantly correlated with cognition and indicated that a higher percentage of activated hippocampal microglia is associated with a worse cognitive phenotype. Spatial transcriptomics analysis showed changes in gene expression in multiple brain regions of HFD mice, including the hippocampus, many of which were related to neurodegenerative and inflammatory pathways.ConclusionThese data support that HFD feeding causes an early and persistent cognitive impairment, which is associated with obesity. Our data also confirm a role for microglia in HFD‐induced cognitive impairment. Indeed, microglial and transcriptomic data strongly indicate a role for inflammation and inflammatory pathways in HFD‐induced cognitive impairment.