bluuebunny/crossref_metadata_2025_split huggingface dataset:
A nuanced portrait of how race/ethnicity and nativity influence cognitive trajectories among older adults in the United States
Authors: Garcia Marc A , Tarraf Wassim 
Published: December 2021

AbstractBackgroundCognitive decline and Alzheimer Disease and Related Dementias (ADRDs) represent significant public health challenges that affect the quality of life and independence of older adults. Previous research documents large racial/ethnic disparities in cognition; However, less is known about variation in cognitive functioning trajectories within minority populations, specifically among older Latinos. Understanding how demographic and socioeconomic factors influence cognitive health in later life is particularly important given the rapidly growing and diversifying United States population.MethodWe use 18‐years of biennial Health and Retirement Study data (1998‐2016) to estimate Generalized Estimating Equations (GEE) modeling sex specific age graded changes in global cognition and memory (based on Modified Telephone Interview for Cognitive Status) among White, Black, and U.S.‐ and foreign‐born Latino adults aged 51 years and older.ResultAdjusting for socioeconomic factors, health behaviors, and chronic health conditions, we find consistent evidence for curvilinear (quadratic) associations between age and cognitive change across race/ethnic and nativity groups (bage=028; SE=0.010; p<0.01 and bage2=‐0.005; SE<0.0001; pp<0.0001), regardless of sex. Among males, racial/ethnic and nativity differences in cognitive function were mainly evident at younger ages, particularly for Blacks compared to Whites (see Figure below). We found no evidence to support male racial/ethnic or nativity differentials in trajectories of cognitive aging. For women, older Black and US‐Born Latina adults, and to a lesser degree foreign‐born Latinas, had lower cognitive function at younger ages (see Figure). Moreover, White women showed more pronounced cognitive aging in comparison to U.S.‐ and foreign‐born Latinas (see Figure). These results were consistent for both global and memory specific outcomes.ConclusionOur findings support current calls for more nuanced considerations of racial/ethnic and nativity effects on cognitive aging and ADRDs. Understanding minority and immigrant differences in cognitive decline has implications for assessing the burden of cognitive disease and the development and implementation of culturally‐appropriate programs to promote healthy brain aging.
Age at menopause relates to later‐life hippocampal volume in an APOE4‐specific manner
Authors: Sundermann Erin E , Saelzler Ursula G , Jacobs Emily Goard , Banks Sarah J , Shadyab Aladdin H , Taylor Caitlin M , Gleason Carey E , James Taryn T , Jonaitis Erin M , Panizzon Matthew S 
Published: December 2021

AbstractBackgroundThere are important sex differences in Alzheimer’s disease (AD) including two‐fold higher prevalence and stronger association of the apolipoprotien‐ε e4 allele (APOE4) with AD risk in women versus men. Given the central role of sex hormones in brain structure/function, examining factors influencing lifetime exposure to sex hormones is critical to understanding sex differences in AD. Menopause is characterized by a marked reduction in ovarian hormones, leading to loss of sex hormone‐related neuroprotective effects and AD‐like changes in brain bioenergetics. Earlier age at menopause is associated with higher AD risk; however, the brain mechanisms by which menopausal age contributes to AD etiology and the role of APOE4 in this association are unclear. Among non‐demented, older female participants of the Wisconsin Registry for Alzheimer’s Prevention (WRAP) cohort, we examined the associations of age at menopause with later‐life hippocampal and whole brain volumes and the moderating role of APOE4 in these associations.Method177 postmenopausal women ≥ 60 years of age (age range:60–76, age mean=65.8, 96% White) with MRI volumetric data and APOE4 genotype data were examined. Multivariable linear regressions were used to examine associations of self‐reported age at menopause and its interaction with APOE4 carrier status with hippocampal and whole‐brain volumes. Models were adjusted for intracranial volume, MRI scanner, age, education, BMI at MRI, smoking, age at menarche, number of pregnancies, natural versus surgical menopause and ever‐use of hormone therapy or hormonal contraception.ResultA significant age at menopause × APOE4 interaction on hippocampal volume (p=.05) revealed that earlier age at menopause related to smaller hippocampal volume (p=.016) among APOE4 carriers but not non‐carriers (p=.86; Figure 1). Age at menopause did not relate to whole brain volume regardless of APOE4 status. In the multivariable model, older age, less education and smaller intracranial volume also related to smaller hippocampal volume.ConclusionResults suggest that early menopause may be a risk factor for neurodegeneration among APOE4 carriers particularly in the AD‐sensitive hippocampus. The specificity of this relationship to APOE4 carriers indicates mechanistic interactions between APOE4 and sex hormones and offers a potential contributing factor to the more adverse effect of APOE4 in women.
Identifying obstructive sleep apnea in geriatric outpatients with neuropsychological testing
Authors: Przybelski Anna Gabriel , Irwin Alissa M , Rumble Meredith E , Jones Jana , Plante David T , Przybelski Robert J 
Published: December 2021

AbstractBackgroundObstructive sleep apnea (OSA) is common in geriatric patients and has been associated with neurocognitive disorders such as Alzheimer’s disease and other dementias. Dexter and Ebert (2019) reported a unique pattern of lower scores for immediate memory relative to delayed memory was observed in patients with OSA on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). The aim of the current investigation was to examine the frequency of confirmed OSA diagnosis in persons with snoring and immediate memory scores less than delayed memory scores in ambulatory geriatric patients referred for memory assessment.MethodPatients were initially assessed for memory complaints at the University of Wisconsin‐Madison Geriatric Memory Assessment Clinic (2016 ‐2020). All patients completed the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS, Randolph, 1998, 2012) as part of a multidisciplinary evaluation. Patients were referred for a sleep evaluation if sleep disordered breathing was reported and the score difference was noted with immediate memory being less than delayed memory on RBANS. Sleep evaluations consisted of either home sleep testing or polysomnography, based on clinical indication. Board‐certified sleep medicine physicians interpreted all sleep studies, and graded the severity of OSA as mild, moderate, or severe.ResultResults are depicted in Table 1. There were 251 patients referred for sleep evaluation (mean age 75.5 years). Of these, 158 patients completed sleep testing (93 males; 65 females), of which 127 (80.4%) were ultimately diagnosed with OSA. Among sleep study completers, 72 (57%) had moderate or worse sleep apnea. The proportion of cases with moderate or worse sleep apnea was similar for male (59%) and female (53%) completers.ConclusionThis retrospective investigation involved geriatric memory clinic patients with RBANS scores that were lower in immediate memory compared to delayed memory and evidence of snoring that resulted in a referral for a sleep study. The finding of OSA in 80% of the patients evaluated, and the comparable results of male and female patients suggests that all patients who snore and have this unique RBANS profile should be assessed for OSA.
Cognitive, neuropsychiatric and imaging comparisons between early‐onset and late‐onset Alzheimer’s disease participants from LEADS and ADNI3
Authors: Apostolova Liana G. , Eloyan Ani , Gao Sujuan , Iaccarino Leonardo , Touroutoglou Alexandra , Aisen Paul S , Beckett Laurel , Borowski Bret J , Donohue Michael C , Fagan Anne M , Foroud Tatiana M. , Gatsonis Constantine , Jack Clifford R. , Kramer Joel H , Koeppe Robert A. , Saykin Andrew J. , Toga Arthur W. , Vemuri Prashanthi , Day Gregory S , Graff‐Radford Neill R. , Honig Lawrence S , Jones David T. , Masdeu Joseph C , Mendez Mario , Onyike Chiadi U , Rogalski Emily J , Salloway Stephen P. , Wolk David A. , Wingo Thomas S. , Carrillo Maria C. , Rabinovici Gil D. , Dickerson Brad C. 
Published: December 2021

AbstractBackgroundThe overarching goal of the Longitudinal Early‐onset Alzheimer Disease study (LEADS) is to optimally characterize early‐onset AD (EOAD) and establish an EOAD clinical trials network. Here we report the baseline demographic and imaging biomarker comparisons of the LEADS cohort to late‐onset AD (LOAD) subjects from the Alzheimer’s Disease Neuroimaging Initiative (ADNI3).Method123 amyloid‐positive EOAD, 47 amyloid‐negative EOnonAD, 60 cognitively normal young controls were compared to 130 amyloid‐positive LOAD, 110 amyloid‐negative LOnonAD and 286 amyloid‐negative cognitively normal older controls. To account for the effect of cognitive aging between EO and LO populations, each cognitive measure was Z‐transformed. Cortical and hippocampal atrophy were quantified using W‐scores adjusted for age, sex and total intracranial volume. Z‐scores and W‐scores were compared using t‐test or Wilcoxson rank test as appropriate. All p‐values were corrected for multiple comparisons using the false discovery rate correction.ResultEOAD showed greater pathology burden and greater cortical atrophy (AD signature) relative to LOAD. EOAD also showed greater cognitive impairment across all cognitive tests. EOAD showed greater functional impairment, more depression but less neuropsychiatric behaviors overall compared to LOAD (Table 1 and Figure 1, all ps<0.05). Repeating the analyses stratified by cognitive stage (MCI/dementia) or CDR global rating (0.5/1) did not result in any major differences.EOnonAD differed from LOnonAD by also showing greater impairment on all cognitive and functional measures There were no significant differences in amyloid and tau burden, or atrophy W‐scores between these groups. EOnonAD were more depressed and showed more functional impairment compared to LOnonAD (Table 2 and Figure 2, all ps<0.05). Repeating the analyses split by cognitive stage (MCI/dementia) or CDR global rating (0.5/1) did not result in any major differences.ConclusionConsistent with our preexisting hypotheses, EOAD and EOnonAD perform much worse relative to their LO counterparts. EOAD also show greater pathological burden as expected. The reported analyses were done in chronological rather than disease time (time since disease onset). Benchmarking individuals along the disease spectrum might prove to be a better strategy especially when conducting analyses on rate of disease progression.
Cancer is inversely related to Alzheimer’s disease dementia independent of amyloid and tau
Authors: Kapoor Arunima , Nation Daniel A. ,   Alzheimer's Disease Neuroimaging Initiative
Published: December 2021

AbstractBackgroundEmerging evidence suggests an inverse relationship and common biological mechanism between cancer and Alzheimer’s disease (AD), with reduced risk of cancer among individuals with AD and reduced risk of AD among cancer survivors. Yet, few prior studies have explored the shared mechanism between the two diseases and examined whether amyloid and tau differ among cancer survivors.MethodParticipants included community‐dwelling older adults (age range 55‐90 years, M = 74.9 years; SD = 6.7; 52.4% male) from the Alzheimer's Disease Neuroimaging Initiative, who were cognitively normal (CN) or had AD at baseline assessment (N = 756). Cancer history was obtained from participant’s medical history. Lumbar puncture was performed to determine cerebrospinal fluid levels of phosphorylated tau (p‐tau), total tau (t‐tau), and β‐amyloid 1‐42 (Aβ1‐42). Prevalence of cancer history and CSF levels of AD pathology biomarkers in those with and without history of cancer were examined in the CN and AD groups.ResultA total of 176 (23.3%) patients had history of cancer. Patients with history of cancer were older (M = 76.5, SD = 6.7) compared to those without (M = 74.4, SD = 6.7, p <. 001) and more likely to be male (62.5% vs. 49.3%, p = .002). Those with AD were significantly less likely to have history of cancer compared to CN (36.9% vs. 63.1%, χ2(1) = 5.8, p = .016). Among those with AD, there was no significant difference in p‐tau, t‐tau and β‐amyloid levels between those with history of cancer compared to no history. Similarly, p‐tau, t‐tau and β‐amyloid levels did not differ between those with or without history of cancer in CN.ConclusionConsistent with previous studies, we observed a lower incidence of cancer in individuals with AD compared to CN. However, we observed no difference in levels of traditional AD pathology biomarkers, suggesting the shared mechanism between cancer and AD may not be driven by β‐amyloid and tau. Alternative mechanisms, such as angiogenesis, are known to play a key role in both diseases and future studies are warranted to explore the role of vascular contributions to improve our understanding of the pathophysiology of both AD and cancer.
Education, white matter hyperintensities, and cognition in diverse cohorts of older adults
Authors: Eng Chloe W , Gilsanz Paola , Fletcher Evan M , Kornak John , George Kristen M , DeCarli Charles S , Barnes Lisa L , Glymour Maria M , Whitmer Rachel A 
Published: December 2021

AbstractBackgroundHigher education predicts better late‐life cognition among older adults, but mechanisms are poorly understood. We examined whether education modified the pathway between vascular injury and late‐life cognition.MethodAnalyses pooled imaging data from the multiethnic Kaiser Healthy Aging and Diverse Life Experience Study (KHANDLE; n=219) and the Study of Healthy Aging in African Americans (STAR; n=132), two parallel studies of older adult long‐term Kaiser Permanente members. Self‐reported education was considered as continuous years of completed education. White matter hyperintensities (WMH) were obtained through 3T MRI. Cerebral WMH volume to total cerebral volume ratio was log transformed and regressed on age; residuals were z‐standardized for measure of age‐adjusted WMH volume. Cognitive domains of verbal episodic memory (VRMEM), semantic memory (SEM), and executive function (EF) were measured using the Spanish and English Neuropsychological Assessment Scales (SENAS) and z‐standardized. Domain‐stratified regression models examined (1) independent effect of WMH adjusting for education, and (2) effect modification by education on the relationship between WMH and cognition. All models were adjusted for age, race/ethnicity, gender, and study.ResultParticipants were on average 73.2 years of age with 14.7 years of education, with 57.8% of the sample identifying as female and 49% of the sample identifying as Black. Education was significantly associated with all late‐life cognitive domains but for WMH volume (B: ‐0.02, 95% CI: ‐0.06, 0.02, p‐value: 0.38). In models adjusting for education and all covariates, effect of WMH on cognition was largest for EF (B: ‐0.09, 95% CI: ‐0.17, ‐0.01, p‐value: 0.03) followed by VRMEM (B: ‐0.06, 95% CI: ‐0.15, 0.03, p‐value: 0.18) and SEM (B: 0.00, 95% CI: ‐0.08, 0.08, p‐value: 0.97). Effect modification was suggested for VRMEM (WMH x education B: ‐0.03, 95% CI: ‐0.06, 0.00, p‐value: 0.09) but not EF (WMH x education B: ‐0.01, 95% CI: ‐0.04, 0.03, p‐value: 0.74) or SEM (WMH x education B: 0.00, 95% CI: ‐0.04, 0.03, p‐value: 0.79).ConclusionThe relationship between WMH and late‐life cognition differed by cognitive domain with the strongest effect of WMH independent of education for executive functioning, and effect modification by education for the relationship between WMH verbal episodic memory.
Association of frailty with cognitive impairment in Mexican older adults from the open population
Authors: Ruiz‐Castillo Karla Paulina 
Published: December 2021

AbstractBackgroundFrailty and mild cognitive impairment are highly prevalent and disabling conditions in the older adult population, which can coexist. Since fragility represents wear and tear of multiple systems that put the subject in a condition of physical, cognitive, and social vulnerability,MethodThis report contains information from an observational cohort design study, the inclusion criteria included adults older than 65 years or older at the beginning of follow‐up, who completed the baseline evaluations and three years of follow‐up, within the protocols of the GID 10 / 66. Data from 1,823 adults older than 65 years without dementia were analyzed in the initial evaluation. Frailty was evaluated by modified Fried criteria (excluding grip strength), the presence of 3 of the 4 remaining criteria was considered fragility. They were considered for the analysis of variables such as sex, age, education, marital status, occupation, diabetes, hypertension, depression, anxiety, and cognitive impairment level in the initial evaluation. The incidence of cognitive impairment was determined by the presence of MCI or dementia at the follow‐up evaluation.ResultThe prevalence of frailty in the baseline evaluation was reported in 6.1%. Frailty was more prevalent in older ages. The occupation was also found to be associated with frailty, more prevalent in unemployed older adults. Comorbidities such as diabetes, a history of cerebral vascular disease, depression, and anxiety were found to be associated with frailty. The incidence of cognitive impairment in the total sample was 14.6%, in the group with frailty in the baseline evaluation it was 30.0%, which translates into a risk ratio of 2.2, which is reduced to 1.8 when adjusted for risk variables for incident cognitive impairment such as age, schooling, diabetes, depression, and anxiety.ConclusionIn older adults from the open population, frailty is associated with the incidence of cognitive impairment independently of some of the known risk factors for dementia and mild cognitive impairment.
Extracellular vesicle miRNA from cerebrospinal fluid as potential biomarkers for neurodegeneration
Authors: McFarland Trevor J. , Sandau Ursula S. , Smith Sierra J. , Baker Sarah Catherine , Saugstad Julie A. 
Published: December 2021

AbstractBackgroundExtracellular vesicles (EVs) are a diverse group of small membranous particles classified by protein and nucleic acid content, size, method of biogenesis, and cellular origin. The need for predictive biomarkers for neurodegenerative disease is critical for early detection and potential therapeutic intervention. We have previously identified multiple high ranking miRNAs in total cerebrospinal fluid (CSF) in patients with Alzheimer's disease (AD). To investigate whether these miRNAs are released from cells within EVs, we developed a pipeline to isolate and analyze EV miRNA.MethodEVs are isolated by size exclusion chromatography (SEC) from CSF collected from living donors. EV counts and sizes are determined by nanoparticle tracking analysis (NTA). Immunoblots are used to characterize EV composition and assess purity. Transmission electron microscopy (TEM) is used to assess size and EV structural characteristics. EV total RNA is isolated using commercial based methods. Quantitative PCR (qPCR) is performed using TaqMan Low Density Array (TLDA) miRNA cards.ResultThe CSF EV isolation protocol developed here is capable of isolating pure vesicles of the appropriate size and protein composition. Following miRNA qPCR, more than half of the high ranking miRNAs identified in total CSF from AD patients were observed in the isolated EV population.ConclusionThis pipeline is suitable for isolating EVs and assessing miRNA content in lumbar CSF. A large number of miRNAs isolated from EVs appear to correlate well with previously published data from total CSF, indicating a potential role for EV miRNA cargo as biomarkers for neurodegenerative diseases such as AD.
Effect of COVID‐19 in cognitive manifestations in people with dementia of Alzheimer’s type
Authors: Rai Pooja , Singh Indramani L. , Singh Tara , Tiwari Trayambak , Joshi Deepika 
Published: December 2021

AbstractBackgroundThe coronavirus disease 2019 (COVID‐19) has been spreading worldwide and affecting people of all the age groups. Recent studies are claiming that it causes brain fog state in patients. The elderly are more prevalent in this disorder because of higher medical comorbidities and resulting in cognitive impairments.MethodThe present study has taken 2 cases of dementia of Alzheimer’s disease patients with Covid 19 positive as experimental and 2 cases of Alzheimer’s disease patients with Covid 19 negative as control group. A video interview has been structured with few questions to assess their cognitive perspective on Covid 19. They have been matched on cognitive status using Hindi‐ mini Mental State Examination and Cognitive Failure questionnaire. After a period of two month they have been interviewed again to compare the changes.ResultThe findings of the present study revealed a differences in the scores of Cognitive Failure Questionnaire in experimental group as compared to control group.ConclusionThe study showed that there was an effect of Covid 19 on cognitive status of cases of dementia of Alzheimer’s disease patients with Covid 19 positive as compared to dementia of Alzheimer’s disease patients with Covid 19 negative cases.
Lessons from COVID‐19 pandemic: Clinical experiences on telemedicine in patients with dementia in Iran
Authors: Noroozian Maryam , Mohammadian Fatemeh 
Published: December 2021

AbstractBackgroundOne of the impacts of COVID‐19 pandemic on health system has been increasing the burden on the patients with dementia and their families. Telemedicine has shown to be a solution for this vulnerable group and can be used for cognitive assessment, medication adjustment, patient referral, reduces the travel time, cost and caregiver burden. Despite the challenges in acceptance for this novel technology in the elderly 1, it can reduce the burden of disease and increase access to specialised services. All these alongside neurologic visit could be provided with a telephone hotline or preferably video‐platform tele‐visit.2 However, barriers to develop telemedicine include a lack of broadband internet access and the need for insurance coverage.3 The American Academy of Neurology has been developed a comprehensive guideline to implement the tele‐visit approach in the COVID‐19 crisis with a special approach to neurological examination limitations in the patients.4 Numerous studies evaluated this approach to assess patients including dementia.5 Overall, the patients, caregivers, and the neurologists reported a high satisfaction rate.6 Yaadmaan Institution for Brain, Cognition and Memory Studies with a multidisciplinary team including cognitive neurologist, psychiatrist, psychologist, geriatrician, and clinical pharmacist is the first private referral center for cognitive disorders in Iran. After starting quarantine and tight restrictions and because of too many families who were seeking help for their patients via Yaadmaan helpline, we decided to start Telemedicine method. The approach and compatible examinations have been shown in Table 2 and 3 respectively. In addition, we defined a list of serious states to avoid Telemedicine for patients referal to the hospital in Table 4. Based on our one‐year experiences, it seems there are promising results in‐terms of feasibility, acceptability and convenience for the patient, caregiver and physician. However, due to the emergence of this pandemic, Telemedicine and its crucial role in Iran has not yet been identified in the insurance and health system appropriately. Even though Telemedicine was started as a practical and urgent solution against COVID‐19 restrictions, it is necessary to be evaluated as an alternative method for clinical evaluations of the patients with dementia in Iran in the future.