bluuebunny/crossref_metadata_2025_split huggingface dataset:
Memory markers can help trace the Alzheimer’s disease continuum: Evidence from the GERO Cohort
Authors: Forno Gonzalo , Parra Mario A , Lillo Patricia , Villagra Roque , Parrao Teresa , Thumala Daniela , Slachevsky Andrea 
Published: December 2021

AbstractBackgroundCognitive assessments able to detect impairments as early as neuropathological changes that occur in neurodegenerative diseases initiate are urgently needed. The Visual Short‐Term Memory Binding Test (VSTMBT) and the Free and Cued Selective Reminding Test (FCRST) have been recently recommended by the Neurodegenerative Diseases Working Group (Costa et al., 2017) as promising preclinical markers of AD. They have never been used before to assess elderlies with cognitive complain recruited from the community.MethodA total of 271 subjects (37 healthy controls (HC), 112 subjective cognitive complain (SCC), 96 mild cognitive impairment (MCI) and 26 Alzheimer’s disease dementia (ADD)), recruited from Geroscience Center for Brain Health and Metabolism (GERO) Cohort and the Memory and Neuropsychiatric Clinic (CMYN), underwent assessment with the VSTMBT and the Visual Version of the FCRST (FCRST‐Visual). Two memory loads were used for the VSTMBT (low and high). The ability of these tests to discriminate between groups.ResultSignificant differences were found between HC, MCI and ADD using the VSTMBT and the FCRST‐Visual version. Notably, the STMB was the only test that “marginally” differentiated between HC from SCC (p = 0.055). Moreover, whereas the FCRST‐Visual showed a gradient (HC = SCC) > MCI > AD, the VSTMBT’s gradient was HC > (SCC = MCI = ADD) suggesting that the function assessed by the latter test may be sensitive to the very early stages of the disease dropping to levels that cannot decline further.ConclusionOur results suggest that the VSTMBT and FCSRT are sensitive to the early stages of dementia. Whereas the former detects changes in the early subjective stages, the latter is more sensitive to later objective stages of cognitive decline. The latter but not the former could help monitor disease progression. These results raise important questions about the usefulness of cognitive screening tools to detect and monitor disease progression and to separate normal and abnormal ageing trajectories. We propose the need of cognitive assessments that detect subtle differences as early as neuropathological changes occur in the brain, which will lead to the development of new “cognitive biomarkers” for dementia.
Examining older adults’ perceived workload, motivators, and barriers experienced during an exergame study — a mixed methods approach
Authors: Crane Breanna M , Drazich Brittany , Moored Kyle D , Taylor Janiece , Carlson Michelle C 
Published: December 2021

AbstractBackgroundThere is increasing interest in using exergames to promote physical and cognitive functioning. Examining the perceived workload and various motivators/barriers associated with enrollment and retention in exergame studies is needed to design engaging and sustainable exergame interventions. In this study, we examined the perceived workload, motivators, barriers, and general feedback from older adults participating in an exergame study.MethodWe conducted 3 semi‐structured focus groups among 14 older adults from a senior living center to evaluate motivators and barriers associated with joining and remaining in the Stimulation with Intricate Movements (SWIM) study. The SWIM study was designed to assess the impact of an exergame called “Bandit the Dolphin” which simultaneously integrates cognitive and physical activity within an immersive, interactive environment. The NASA‐TLX scale was used to assess perceived workload during gameplay, and ratings ranged from 0‐100 (low to high workload). An exit survey assessed participants’ experiences and perceived changes in activity following the study (e.g., social, cognitive, physical).ResultMotivators for joining were self‐improvement, generativity, peer referrals, and curiosity. Motivators for retention involved immersion during gameplay, gaining a sense of accomplishment, and exercise. Barriers included exhaustion/pain from standing and frustration from lack of level advancement. Perceived effort [M=62.5,SD=13.0] and physical demand [M=57.9,SD=13.8] were the highest ranked categories on the NASA‐TLX scale, followed by mental demand [M=49.3,SD=17.2]. Frustration received the lowest ranking [M=37.9,SD=26.5]. From the exit survey, 100% would recommend the study to a friend, 53% said participating in the study changed their physical activity levels, and 40% reported changes in their comfort with video games/technology.ConclusionPrimary motivators for study initiation and retention align with the Self‐Determination Theory which posits intrinsic motivation arises when autonomy, competence, and social relatedness are achieved. NASA‐TLX results show that perceived effort and physical demand of gameplay ranked highest, followed by mental demand, with frustration ranking the lowest. Notably, all participants would recommend the study to a friend. Overall, participants perceived “Bandit the Dolphin” as a cognitively and physically demanding, enjoyable, and effortful exergame. These results will guide future efforts to design engaging and sustainable exergames aimed at improving cognitive and functional health among older adults.
Impact of baseline daily physical activity on cognitive and physical effects of lifestyle multidomain intervention: The SUPERBRAIN study
Authors: Choi Muncheong , Song Hong‐sun , Chun Buong‐O , Lee Sun Min , Hong Chang Hyung , Park Yoo Kyoung , Na Hae Ri , Kim Byeong C. , Park Kyung Won , Park Hee Kyung , Jeong Jee Hyang , Choi Seong Hye , Moon So Young 
Published: December 2021

AbstractBackgroundIn the South Korean study to prevent cognitive impairment and protect brain health through lifestyle intervention in at‐risk elderly people (SUPERBRAIN), we explored impact of baseline daily physical activity on cognitive and physical effects of 24‐week lifestyle multidomain intervention.MethodA total of 152 participants, aged 60‐79 years without dementia but with ≥ 1 modifiable dementia risk factor, were randomly assigned to the facility‐based multidomain intervention (FMI), and home‐based MI (HMI), or control groups. Among them, 82 participants (27 FMI, 34 HMI, and 21 control) took their physical activity for 7 days using the accelerometer (Actigraph GT3X+, FL, USA) at baseline. We divided 61 participants in the FMI or HMI into two groups according to their physical activity at baseline: Group I who met WHO physical activity guidelines for older adults (more than 150 minutes of moderate activity per week) and Group Ⅱ who did not meet the guidelines. We compared changes of cognitive and physical measures after 24‐week intervention between group I and Group Ⅱ. Cognitive function was measured using the total sale index score of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and the physical fitness was measured by the hand grip strength test, 30 s sit‐to‐stand test, 3 m sit–walk‐and‐return test, sit‐and‐reach test, 2‐min stationary march, and Figure‐8‐walks. Due to not satisfying the normality test, the nonparametric tests Mann‐Whitney and Wilcoxon were analyzed using IBM SPSS Statistics25.ResultGroups I and II had no significant difference in the baseline total sale index score of the RBANS, whereas the group I had a higher physical fitness at baseline (sit‐and‐reach test and 3m sit‐walk‐and‐return test <0.05; Figure‐8‐walks <0.01). After the intervention, only Group I showed significant improvement in the total sale index score of the RBANS. Both groups were significantly improved in 30 s sit‐to‐stand test, 2‐min stationary march, and Figure‐8‐walks. However, hand grip strength was improved in only Group I.ConclusionSignificant improvement in both cognitive and physical function in at‐risk but active elderly without substantial impairment in the SUPERBRAIN suggest that preventive strategies may be more beneficial on cognitive and physical function in active older adults.
A post‐mortem study of melanin‐concentrating hormone (MCH) neurons in Alzheimer’s disease and progressive supranuclear palsy: The complex degeneration pattern of the lateral hypothalamic area
Authors: Mladinov Mihovil , Oh Jun Yeop , Petersen Cathrine , Eser Rana April , Li Song , Theofilas Panos , Spina Salvatore , Seeley William W. , Bittencourt Jackson Cioni , Neylan Thomas , Grinberg Lea T. 
Published: December 2021

AbstractBackgroundMelanin‐concentrating hormone neurons (MCH) are a key component of the subcortical brain circuits controlling sleep and wake states, and integrating them with other vital functions like motivated and feeding behavior into a 24‐hour circadian rhythm. Together with orexinergic neurons (OX), they represent the major neuronal population of the lateral hypothalamic area (LHA). Our group previously reported a profound degeneration of OX neurons in Alzheimer's disease (AD), and a reduction of OX production in progressive supranuclear palsy (PSP). In this report we provide for the first time a comprehensive and quantitative morphological study of MCH neurons in patients with AD, PSP and normal controls.MethodPost‐mortem human brain tissue of subjects with AD, PSP and controls was examined using unbiased stereology. Double immunohistochemistry with MCH‐ and tau‐antibodies on formalin‐fixed, celloidin embedded tissue was performed.ResultThere was no significant difference in the total number of MCH neurons between AD, PSP and controls, but a significant loss of non‐MCH neurons in AD patients (p=0.019). The proportion of MCH neurons was significantly higher in AD (p=0.0047). No such a difference was found in PSP. In PSP, but not AD, the proportion of tau+ MCH neurons was lower than the proportion of tau+ non‐MCH neurons (p=0.002). When comparing AD to PSP, the proportion of tau+MCH neurons was higher in AD (p<0.001).ConclusionHigh burden of tau‐inclusions, but comparably milder loss of MCH neurons in AD, together with previously reported orexinergic neuronal loss may lead to a hyperexcitability of the MCH system in AD. This may contribute to the well‐known impairment of vigilance, reduction of NREM sleep and REM sleep disruption in AD. In contrast, we found virtually no involvement of MCH neurons in PSP, which reflects a specific vulnerability of these neurons to AD pathology. Clinically, PSP features a hyperarousal state, indicating that the activity of the arousal system prevails over a deficient sleep promoting system. We conclude that the involvement of other sleep promoting nuclei contributes to the insomnia in PSP. Further experimental research is needed to understand the molecular pathways involved in the specific vulnerability of MCH neurons in AD.
Plant‐based dietary patterns and cognitive function in U.S. adults: A prospective evaluation
Authors: Liu Xiaoran , Wang Yamin , Dhana Klodian , Agarwal Puja , Cherian Laurel J , Bennett David A. , Schneider Julie A. , Aggarwal Neelum T. 
Published: December 2021

AbstractBackgroundA plant‐based dietary patterns focus on foods primarily from plant sources. However, not all plant‐based foods are necessarily beneficial for health. We aim to examine the relationship between plant‐based diet quality and cognitive function.MethodAnalyses were conducted among 701 participants from the Memory and Aging Project. Food Frequency Questionnaires (FFQ) were incorporated into the studies in 2004 and collected annually thereafter. Individuals with mild cognitive impairment, missing food‐frequency questionnaire (FFQ) at baseline, extreme BMI, and less than two cognitive assessments during 10 years of follow‐up were excluded for these analyses. Plant‐based diet quality were assessed by 3 plant‐based diet indices (score range, 18‐90) including 1) an overall plant‐based diet index (PDI) by assigning positive scores to all plant foods and reverse scores to animal foods; 2) a healthful PDI (hPDI) where positive scores were given to only healthy plant foods, less‐healthy plant foods and animal foods received reverse scores; 3) an unhealthful PDI (uPDI), where less‐healthy plant foods received positive scores and animal and healthy plant foods received reverse scores. Our primary outcome was composite global cognition z score. We used liner mixed model examining the association between PDI (as a continuous and categorical) and cognitive decline.ResultHigher hPDI was associated with a better cognitive functioning during follow‐up. Compared to individuals in the first tertile of hPDI, individuals in the third tertile had slower cognitive decline by 0.03 units per year (β = 0.03, p=0.017). Similarly, when we evaluated the hPDI as continuous variable, each10‐points increase in hPDI was associated with 0.01 units/year slower cognitive decline. In contrast, higher adherence to uPDI was associated with faster cognitive decline. Individuals in the third tertile of uPDI had a faster decline by 0.04 unites per year (β = 0.04 , p=0.017). Every 10‐point increase in uPDI was associated with a 0.01 unit per year faster cognitive decline.ConclusionHigher intake of a plant‐based diet index rich in healthier plant foods was associated with slower cognitive decline. This supports current recommendations to shift to diets rich in healthy plant foods, with lower intake of less healthy plant and animal foods.
Biomarkers for Alzheimer’s disease in Black populations: A scoping review
Authors: Moeller Stacey , John Samantha E 
Published: December 2021

AbstractBackgroundBlack/African American (B/AA) older adults have roughly double the risk of developing Alzheimer’s disease (AD) and greater risk for being undiagnosed compared to non‐Hispanic whites (NHW)(2020 Alzheimer’s Disease Facts and Figures). There is a dearth of research on AD biomarkers in the B/AA community. Biomarkers identify those at risk for or in the preclinical stages of AD, establish clinical trial eligibility, and inform diagnosis and treatment. This study reviews current literature on AD biomarkers in the B/AA population.MethodA scoping review was conducted of B/AA study samples that examined three widely accepted AD biomarkers and the risk of disease conferred by each. Apolipoprotein E (APOE) and the e4 allele, cerebrospinal fluid (CSF) values of aBeta and tau, and amyloid positron emission tomography (PET) were included. Articles were reviewed independently by two researchers using the Colquhoun et al. (2014) method.ResultInitial searches yielded 326 APOE results, 46 CSF, and 33 amyloid PET. After review, 64 remained for APOE, 4 for CSF, and 8 for amyloid PET. Within APOE, e4 presence conferred similar (Graff‐Radford 2002; Sawyer 2009) or lower (Evans 2003; Rajabli 2018) AD risk in B/AA versus NHW, with no consensus on the protection offered by e2 (Allred 2016; Graff‐Radford 2002). CSF literature highlighted that B/AA had lower levels of total tau and phosphorylated tau 181 (Morris 2019; Howell 2017; Garrett 2019), with lower (Garrett 2019; Howell 2017) or similar (Morris 2019; Babulal 2020) levels of beta amyloid. In amyloid PET, B/AA amyloid burden was similar (Morris 2019; Amariglio 2020) to or above (Gottesman 2016; Hughes 2018) NHW, but longitudinal investigation suggested faster decline among B/AA (Amariglio 2020). The role of APOE e4 in amyloid burden is incompletely understood. One study found increased amyloid in both races (Morris 2019) among e4 carriers, while another study identified greater amyloid among B/AA even after adjusting for APOE status (Gottesman 2016).ConclusionUnique AD biomarker profiles among B/AA relative to NHW may be a contributor to diagnostic inequities across groups, particularly missed or late diagnoses among B/AA. These differences warrant in‐depth investigation and highlight the need for inclusive outreach and engagement approaches in research.
Subjective cognitive complaints in Chinese‐ and English‐speaking older adults
Authors: Li Clara , Zeng Xiaoyi , Yang Xiao , Zhu Carolyn W , Neugroschl Judith A. , Aloysi Amy , Cai Dongming , Martin Jane , Sewell Margaret , Loizos Maria , Greenberg Jonathan , Xu Mengfei , Evans Kirsten , Pun Kelly , Tocco Carly , Ardolino Allison , Meuser Caroline , Sheppard Faye , Gamino Juliana , Velasco Nelly , Sano Mary 
Published: December 2021

AbstractBackgroundResearch increasingly suggests that subjective cognitive complaints (SCC) in cognitively healthy older adults may be a harbinger of cognitive decline and dementia. However, there is virtually no investigation on SCC across language groups (English and Chinese). This study examines SCC in Chinese American older adults who are monolingual Chinese speakers. This population has a high risk of being misdiagnosed with cognitive loss and dementia due to cultural and language barriers.MethodThe Alzheimer’s Disease Research Center at Icahn School of Medicine at Mount Sinai evaluates diverse older adults using the National Alzheimer’s Coordinating Center’s Uniform Data Set. Each participant receives a research diagnosis of normal control, mild cognitive impairment, and dementia at consensus. SCC was measured by the Cognitive Function Instrument (CFI). The instrument covers changes in cognition with yes(1)/no(0)/maybe(0.5) as available responses. Total score ranges from 0 to 14, with higher scores indicating greater SCC. The development of Chinese version of CFI was modeled after a protocol for multinational translations, which includes two independent forward translations and a back translation. Multivariate analysis of variance was conducted to examine group differences in SCC using CFI scores as dependent variables, while accounting for age, gender, and education.ResultData analysis included English‐ (n=63) and Chinese‐speaking older adults (n=30) who received a diagnosis of normal cognition, with no psychiatric symptoms/diagnosis at consensus. The two groups did not differ in age (Chinese=73.43+6.83 years; English=74.75+7.12 years) and gender (Chinese=70.0% female; English=65.1% female), but Chinese‐speaking older adults (13.83+3.12 years) had lower levels of education compared to English‐speaking older adults (16.49+2.47years). Results show that Chinese‐speaking older adults endorsed more SCC (3.52+2.68 items) than English‐speaking older adults (1.74+1.67 items) (p<0.01). For 7 of the CFI items (i.e., rely more on written reminders, need help to remember appointments, trouble driving, less social, trouble following news/TV/books, difficulty with hobbies/activities, become disoriented/get lost), frequency of endorsement was higher in Chinese‐speaking older adults than English‐speaking older adults (p<0.05).ConclusionOur findings highlight potential differences in SCC reported by Chinese‐speaking older adults who have immigrated to the USA. A longitudinal follow up is needed to evaluate contributing factors to such differences.
Mapping associations across multiple aspects of Alzheimer disease and the role of CSF biomarkers in individuals without dementia
Authors: Waterink Lisa , Zwan Marissa D. , Barkhof Frederik , de Boer Casper , Ingala Silvia , Lorenzini Luigi , Muñiz‐Terrera Graciela , Ritchie Craig W. , Visser Pieter Jelle , van der Flier Wiesje M , Teunissen Charlotte E. , van Deun Katrijn , Vermunt Lisa ,   for the EPAD Consortium
Published: December 2021

AbstractBackgroundAlzheimer disease (AD) is a complex disorder involving biological, clinical, and lifestyle aspects. Assessing all these aspects simultaneously allows to better disentangle the position of CSF marker abnormalities across AD stages. Here, we employ a novel statistical method specifically developed to reveal meaningful associations across multiple aspects that can occur simultaneously within individuals.MethodWe selected the baseline data from the European Prevention of Alzheimer Disease cohort of individuals without dementia (www.ep‐ad.org; n=1243, mean±SD age = 65±7 years old, 57% female, 18% CDR ≥0.5) covering ten aspects: demographics including APOE‐genotype, cerebrospinal fluid (CSF) biomarkers, MRI visual rating scales, MRI regional volumes, MRI white matter lesions, cognition, function, psychological factors, general physical health, and comorbidities. We used regularized simultaneous component analysis (regSCA), a statistical technique that extracts relevant components which explain variation within and across these aspects, and robustly selects the appropriate variables [1, 2].ResultThe optimal model revealed eight components explaining 51% of the total variance. Figure 1 presents an overview of all components, showing the strengths and directions of the associations between variables. Five components included CSF biomarkers, which were (1) Abeta42‐dominant, (2) Tau‐dominant, (3) function‐dominant, (4) age‐dominant and, (5) white matter lesion‐dominant. In (3) and (4), Abeta42 and Tau related to cognition and function. Only (3) was independent of age, and may represent purely AD. In (5), Abeta42 related to white matter lesions, and may represent the degree cerebral amyloid angiopathy (CAA). Abeta42 in (1) and Tau in (2) related to APOE‐genotype, suggesting these may be independent effects. The three components unrelated to CSF biomarkers were: (6) sex‐dominant, (7) psychological factors‐dominant, and (8) life‐style‐only.ConclusionAnalysis of robust associations across multiple aspects of AD simultaneously implicated CSF biomarkers in five components. These components may represent risk‐profiles and AD disease processes in cognitively normal and mildly impaired individuals. Our next step is to investigate the stability of the components and their co‐expression within individuals. This overview of complex relationships between AD‐related aspects, helps to understand the disease mechanisms in of AD. This novel approach can be a solution for analyses of large and complex datasets in AD.