bluuebunny/crossref_metadata_2025_split huggingface dataset:
Meeting the needs of care partners of people living with ADRD from historically underserved communities
Authors: Gelmon Sherril B , Reed Jenn Hollandsworth , Colon Anaeliz Mina , Lara Sofia Chapela , Prince Devlin , Dawson Walter D 
Published: December 2023

AbstractBackgroundCare and support for people living with Alzheimer’s disease and related dementias (ADRD) is mostly provided unpaid by family, friends, or neighbors. The multiple stressors associated with caregiving often produce substantial care partner burdens. The responsibility for caregiving falls disproportionately on those who rely on and provide unpaid care and support, such as women, individuals of low socioeconomic status, and historically and currently underserved racial and ethnic populations. This study was designed to learn from individuals with lived experience of caregiving, with an emphasis on historically and currently underserved communities, for whom culturally appropriate services for people living with ADRD may be non‐existent or difficult to access.MethodThe study population was care partners of people living with dementia who identify with historically and currently underserved communities. The four communities identified for this study were Black, Indigenous, Asian, and Latin Americans. The team developed strategies for recruitment of focus group participants with input from community‐based organizational leaders who provide ADRD support services in Portland, Oregon. Focus groups were convened with care partners from each of these four communities, as well as one with individuals who identified with other communities.ResultCare partners from all populations reported lacking supports to help manage care‐related activities. Specific needs and types of supports varied across populations, due to cultural traditions, multiple systemic inequities, and legacies of structural racism. The findings suggest multiple unmet care partner needs across all populations, including information on ADRD, financial and psychological supports, leisure activities, in‐home health, and respite. While many care partners were generally satisfied with their clinical care and involvement in research studies, nearly all identified potential areas of additional supports.ConclusionThe findings suggest a need for changes in policy and practice to better support care partners of people living with ADRD from underserved populations. Policymakers must take a collaborative approach with care partners in developing and implementing new policies that can improve care partner experiences. To ensure equitable service provision, specific and unique supports for care partners from underserved communities that may have difficulties accessing culturally appropriate services should be offered.
Feasibility of a Non‐pharmacological Intervention for Impaired Financial Capacity in Mild Cognitive Impairment
Authors: Nowrangi Milap A. , Outen John D. , Rosenberg Paul B. , Kim John 
Published: December 2023

AbstractBackgroundA pilot trial of financial literacy training (FL) and computerized cognitive training (CCT) was conducted to assess tolerability, feasibility, and the effect on financial capacity (FC) in participants with normal cognition and MCI.MethodsCognitively normal and MCI participants were randomized to receive either targeted FL content (N = 4) (Savvy Saving Seniors (“SSS”) workshop) narrated and presented online or the active control CCT (N = 3) (BrainHQ, ©Posit Science) over 6‐weeks. “SSS” participants were instructed to complete 25‐minute sessions twice per week and BrainHQ participants were instructed to complete 60‐minute sessions three times per week.ResultsNo significant differences were found between baseline and follow‐up in either group. Table 1. Two out of 3 BrainHQ participants reported that their processing speed had improved and they felt challenged and experienced positive cognitive benefits. Three out of 4 “SSS” participants reported that they felt stimulated and challenged and that the activities were a good use of their time. All “SSS” participants agreed their financial literacy had improved. The most common reported benefits were accomplishment, enjoyment, and increased alertness. The most common reported discomforts were frustration, boredom and one participant complained of eye strain.Discussion/ConclusionsWe demonstrated good efficacy, tolerability, and adherence in delivering FL education and CCT interventions in cognitively normal and MCI participants.
The effect of BDNF Val66Met on memory, CSF total‐tau, CSF ptau181 and CSF Aβ42 in early sporadic Alzheimer’s disease
Authors: Thomson Diny , Rosenich Emily , Maruff Paul , Lim Yen Ying 
Published: December 2023

AbstractBackgroundAllelic variation in the brain‐derived neurotrophic factor (BDNF) Val66Met polymorphism has been shown to moderate rates of cognitive decline in preclinical sporadic Alzheimer’s disease (i.e., Aβ+ older adults), and pre‐symptomatic dominantly inherited Alzheimer’s disease (DIAD). In DIAD, Met66 was also associated with greater increases in CSF levels of total‐tau and phosphorylated tau (p‐tau181). This study sought to determine the extent to which BDNF Val66Met is also associated with changes in episodic memory and CSF total‐tau and p‐tau181 in Aβ+ older adults in early‐stage sporadic AD.MethodAβ+ Met66 carriers (n = 94) and Val66 homozygotes (n = 192) enrolled in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) who did not meet criteria for AD dementia were included. Only participants with at least one follow‐up neuropsychological and CSF assessment were included. Episodic memory was measured by the ADNI Memory Composite and CSF samples were collected via lumbar puncture to determine levels of total‐tau, p‐tau181 and Aβ42. A series of linear mixed models were conducted to investigate changes in each outcome variable over 10 years, covarying for CSF Aβ42 (except when examining changes in CSF Aβ42), APOE ε4 status, sex, age, baseline diagnosis and years of education.ResultWhen followed over 10 years, Aβ+ Met66 carriers demonstrated significantly faster memory decline (d = 0.33) and significantly greater increases in CSF total‐tau (d = 0.30) and p‐tau181 (d = 0.29) compared to Val66 homozygotes, despite showing equivalent rates of change in CSF Aβ42 (Table 1; Figure 1).ConclusionIn non‐demented Aβ+ older adults, Met66 carriers showed greater memory decline and greater increases in both CSF total‐tau and CSF p‐tau181 over 10 years compared to Val66 homozygotes, despite showing equivalent changes in CSF Aβ42. This suggests that Met66 carriage, which is associated with lower BDNF availability and lower neurotrophic support, may confer greater vulnerability to Aβ‐related increases in tau compared to Val66 homozygosity in the early stages of sporadic AD.
Relationship among cerebral Aβ burden, cognitive function and diabetes
Authors: Yi Hyon‐Ah 
Published: December 2023

AbstractBackgroundDiabetes mellitus (DM) increases the risk of brain atrophy and dementia. We aimed to reveal whether DM could affect cognitive function and the pattern of amyloid retention in cognitively impaired patients. Also we tried to show whether the existence of DM could cause subcortical structural abnormalities with cognitive dysfunction.MethodWe included consecutive 56 controls and 145 cognitively impaired people (CI, 50 MCI and 95 mild to moderate Alzheimer’s disease (AD) patients). All participants of this cross‐sectional study underwent blood tests, detailed neuropsychological evaluations, 3D T1‐weighted MRI at 3‐Tesla and 18F‐FBB‐PET. We estimated the cerebral Aβ burden quantitatively using volume‐of‐interest analysis and segmented the volumes of six subcortical structures, using FMRIBs integrated registration and segmentation tool Multiple linear regression analysis adjusted for age and gender was performed to evaluate the relationship among cerebral Aβ burden, cognitive function and diabetes.ResultAll subcortical structures, except for the globus pallidus, were smaller in CI compared with controls on adjusting for age and gender. CI with DM was associated with the lower volumes of caudate nucleus and putamen than CI without DM patients. Although there was no significant difference of MMSE score within two groups, the performance of frontal‐executive and memory functions was negatively correlated with subcortical structural volume loss in CI with DM. There was no difference between cerebral Aβ burden using composite SUVR and MMSE score in CI patients. However we found higher amyloid retention in CI with DM patients.ConclusionThe co‐morbidity of DM in AD patients might cause more specific subcortical volume loss beyond diffuse cerebral atrophy and the resultant cortical‐subcortical dysfunction could make cognitive dysfunction worse, especially frontal‐executive and memory functions. Also, CI with DM patients showed higher cerebral amyloid retention, which might be the accelerating factor of cognitive deterioration.
Allostatic load profiles of stress to predict Alzheimer’s disease: an accessible opportunity to identify risk at early stages
Authors: Souza‐Talarico Juliana Nery , Perkhounkova Yelena , Hein Maria 
Published: December 2023

AbstractBackgroundAlzheimer’s disease (AD) can start decades before symptoms appear, yet detection at preclinical stages remains a challenge due to a lack of screening tools that are both accurate and accessible. The multi‐system Allostatic Load index (AL), a stress‐related marker of cumulative biological risk, is associated with β‐amyloid (Aβ), tau proteins, and hippocampal atrophy, potentially linking AL to AD. If this is correct, a low‐cost and readily accessible peripheral blood AL‐based screening tool can offer an opportunity to identify individuals at risk for AD in primary care facilities. Here, we determined the AL profiles that predict the conversion risk from mild cognitive impairment (MCI) to AD by 36 months before diagnosis and associated with hippocampus volume (HV) reduction.MethodsUsing the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database, we analyzed longitudinal data from 385 older adults with MCI at baseline, 12, and 36 months. Blood neuroendocrine (cortisol, LH, prolactin, testosterone) and immunologic (C‐reactive protein,fibrinogen,IL‐13,IL‐16,IL‐18,IL‐3,IL‐6,MCP‐3,MCP4,TNF‐alpha,insulin‐like growth factor) stress‐related biomarkers obtained at baseline and 12 months were transformed into AL indexes to generate the following profiles: 1)Decreasing AL: high at baseline and decrease over 12‐months; 2)Increasing AL: low at baseline, increase; and 3)Sustained High AL: high at baseline, remain high or increase. The ADNI consensus diagnosis determined the AD conversion and brain MRI assessed HV. Models were adjusted for socioeconomic and APOE4 covariates.Results41.6% of participants with Sustained High AL converted to AD, while 27.9% with Decreasing profiles remained MCI (p = 0.01). Increasing AL showed higher conversion risk than Decreasing profile (OR: 3.96). Sustained High AL was associated with faster HV reduction (p = 0.04). AL and blood Aβ models were compared for prediction accuracy.ConclusionThe odds of converting to AD were almost four times higher among participants with Sustained High AL profiles with faster hippocampus reduction than Decreasing AL profiles, suggesting that elevated AL profiles might be a risk factor and a potential mechanism explaining MCI conversion to AD. These findings set the foundation for exploring accessible bio‐behavioral screening tools to sign risk in vulnerable individuals in primary care facilities and refer them to specialized clinics for timely intervention.
Dynamic Changes in Quantitative MRI‐based Biomarkers of Alzheimer’s Disease and Its Association with Cognitive Decline – A Longitudinal Study
Authors: Fan Xiang , Cai Yuan , Zhao Lei , Liu Wanting , Luo Yishan , Shi Lin , Mok Vincent Chung Tong 
Published: December 2023

AbstractBackgroundAlzheimer’s disease (AD) resemblance atrophy index (AD‐RAI) is an MRI‐based machine learning‐derived composite index reflecting the multi‐region atrophy severity of AD. We investigated the association between the serial change of AD‐RAI and cognitive progression overtime among cognitive unimpaired (CU) and mild cognitive impairment (MCI) subjects and compared it with other conventional MRI biomarkers (i.e., hippocampal volume (HV), hippocampal fraction (HF), brain parenchymal volume (BPV) and fraction (BPF)), which have been used in the past as imaging biomarkers for AD.MethodWe selected eligible subjects from the Alzheimer’s Disease Neuroimaging Initiative [ADNI] databases and included those aged 55 to 90 years, diagnosed with CU and MCI at baseline with 4‐year follow‐up. We defined converters as those who had significant clinical cognitive progression in the 4‐year follow‐up (i.e., CU to MCI, or MCI to AD dementia), while non‐converters were those who remained stable in the 4‐year follow‐up. A total of 318 subjects, including 203 non‐converters and 115 converters, were recruited in total. The following data were extracted for further analysis: AD‐RAI, HV, HF, BPV, and BPF. We used a linear mixed‐effects model (LMM) and generalized linear mixed‐effects models (GLMM) in SPSS 26.0 to explore the serial changes of the imaging biomarkers and interaction effects over time.ResultLMM showed that AD‐RAI of converters increased significantly faster than non‐converter over time (P < 0.001), and HV, HF, and BPF of converters decreased significantly faster than non‐converters over time (P < 0.001, P < 0.001, P = 0.004, respectively). Besides, the annualized hippocampal atrophy rate was 1.2% for non‐converter and 3.3% for non‐converter when using the corresponding HV at baseline as the reference. Figures showed the means with error bars of 95% CI of each biomarker. In GLMM, we further found that dynamic AD‐RAI over time had the highest classification accuracy (74.2%) for predicting converters when compared with other imaging biomarkers (≤ 70.2%).ConclusionSerial AD‐RAI outperforms other conventional biomarkers in correlating with cognitive progression. It may be used as a surrogate marker for monitoring disease progression or treatment response in AD.
Baseline demographic and clinical characteristics of Longitudinal study of Early onset dementia And Family members
Authors: Jung Na‐Yeon , Kim Hee Jin , Lee Sun Min , Park Kee Hyung , Cho Hanna , Kim Yeshin , Jang Jae‐Won , Kang Heeyoung , Lee Jin San , Kang Sung Hoon , Yoon Soo Jin , Kim Hang‐Rai , Park Kyung Won , CHUNG EUNJOO , Park Young Ho , Jang Hyemin , Lim Jae‐Sung , Kim Geon Ha , Jeong Jee Hyang , Choi Seong Hye , Cho Su Hyun , Kim Seung Joo , Kwon Jay Cheol , Lee Juyoun , Kang Kyunghun , Kim Jaeho , Kim Hee‐Jin , Kim Si Eun , Yi Hyon‐Ah , Park Ji Yoon , Moon So Young , Kim Eun‐Joo 
Published: December 2023

AbstractBackgroundPatients with early‐onset dementia (EOD) tend to be different from patients with late‐onset dementia in their rarities, atypical presentations, higher genetic predisposition and diverse etiologies. Although EOD has devastating impacts on patients and families, and their societies, there are few longitudinal observational studies providing sophisticated clinical, biomarkers and genetic information of EOD. Here, we introduce a Longitudinal study of Early onset dementia And Family members (LEAF) which was launched in April 2021.MethodLEAF was originally designed to enroll at least 400 patients with EOD consisting of patients with Aβ‐positive EOAD (LEAF‐AD), FTD (LEAF‐FTD), and other EOD (LEAF‐Others) with annual follow‐up. Family members with a clear family history have also been enrolled in family cohort. Participants undergo a standardized clinical assessment and brain MRI and amyloid PET. We collect plasma, serum, and DNA for biomarkers and genetic studies. Clinical evaluations and blood collections are annually performed, and brain MRIs are followed up every two years.ResultWe have currently recruited a total of 296 participants with EOD. Aβ‐positive AD spectrum (n = 202) consists of EOAD dementia (82%), MCI (17%), and SCD (1%). FTD (n = 61) includes bvFTD (59%), svPPA (31%) and nfvPPA (10%). Other EOD (n = 33) is composed of leukodystrophy (12%), early onset neurodegenerative dementia other than EOAD, or FTD (66%), and EOD with unclear etiology (22%). The mean age was 60.4 for EOAD, 64.3 for FTD, and 58.2 for other EOD. The prevalence of women was higher in the EOAD and FTD, while the prevalence of men was higher in other EOD. The prevalence of APOE 4 was significantly higher in EOAD than in FTD and other EOD. Family histories of dementia were reported 32% in EOAD, 35% in FTD, and 44% in other EOD. We have, so far, identified 8 pathogenic variants (1 of EOAD, 3 of FTD, and 4 of other EOD) and enrolled two families as family cohort.ConclusionLEAF is the first nationwide multicenter, hospital‐based longitudinal study for EOD in Korea, and this will ultimately shed light on prevention and management of EOD and EOD‐related social issues.
Association between Grip Strength and Future Cognitive Function in male
Authors: Soung YongGwon , Kim Yeshin , Hong Jin Yong , Park Kyung Won , Kim Eun‐Joo , Yoon Soo Jin , Jeong Jee Hyang , Yoon Bora , Kim Hee Jin , Lee Jong‐Min , Choi Seong Hye , Jang Jae Won 
Published: December 2023

AbstractBackgroundFrailty is an aging‐related syndrome of physiological decline, and has been associated with cognitive function.Grip strength, could be used as a marker for frailty and older adult health status. Frailty has been associated with cognitive function. However, its mechanism has not been fully investigated.We aimed to investigate the association between grip strength with cognitive function.MethodWe prospectively recruited 184 participants who underwent a grip strength test, cognitive function test. Data was collected from the Korean Aging Study for the Early Diagnosis and Prediction of Alzheimer’s Disease (KBASE), an ongoing prospective cohort study which started in 2014. Frailty was represented by grip strength (kg). Cognitive function was assessed using Mini‐Mental State Examination(MMSE) and The Consortium to Establish a Registry for Alzheimer’s Disease‐K(CERAD‐K).Multiple linear regression models were used to analyze the associations between grip strength and cognitive function. We adjusted age, gender, years of education, and BMI.ResultAmong 184 participants, 119 (64.7%) were cognitively normal. 32 (17.4%) were diagnosed with mild cognitive impairment and 33 (17.9) were a probable AD. Mean age of the participants was 69.4 (8.2) years. 43.5% of the participants were female. Grip strength was positively associated with MMSE at 1 year later in male (ß = 0.182 p = 0.004). In terms of cognitive domain, verbal and visual memory, language, visuospatial, and frontal‐executive functions were related to grip strength (vebal memory: ß = 0.037 p = 0.022, visual memory: ß = 0.046 p = 0.002, language: ß = 0.055 p<0.001, visuospatial: ß = 0.068 p = 0.0213, frontal‐executive: ß = 0.050 p<0.001).ConclusionWeakness of grip strength is associated with decreased future cognitive function. This support concept that grip strength could be a marker for cognitive decline.
Longitudinal Effective Connectivity Changes in the Default Mode Network in Young‐Onset Alzheimer’s Disease Variants
Authors: Kantar Mahasen El , Novelli Leonardo , Schott Jonathan M , Razi Adeel 
Published: December 2023

AbstractBackgroundYoung‐Onset Alzheimer’s disease (YOAD), a rare form of Alzheimer’s disease occurring before the age of 65, presents as a typical amnestic variant (memory problems) and posterior cortical atrophy ([PCA], visuospatial problems). The DMN is a core resting state network that increases activity during rest but decreases activity during external focused tasks (Buckner et al., 2008). Whilst functional connectivity studies demonstrate altered default mode network (DMN) connectivity in YOAD, the directional influence of one brain region on another, i.e., effective connectivity, remains uncharacterised (Lehmann et al., 2013).This study investigated the DMN’s effective connectivity changes from baseline to 12 months in amnestic and PCA variants. The association between connectivity and cognition was also examined at follow‐up.MethodResting‐state functional MRI data of 28 amnestic and 14 PCA patients was included.Regions of interest included: medial prefrontal cortex, posterior cingulate cortex, bilateral angular gyrus and bilateral hippocampus. Spectral dynamic causal modelling (Friston et al., 2014) and Parametric Empirical Bayes (PEB, Friston et al., 2016) were used to infer individual and group level effective connectivity, respectively. PEB was also used to examine the association between connectivity and cognition at follow‐up. Cognition was measured via the Mini‐Mental State Examination (MMSE).ResultIn the amnestic variant, mostly decreased longitudinal effective connectivity was found, suggesting network dysconnections (disrupted brain connections; Delbeuck, 2013). In the PCA variant, a combination of increased and decreased longitudinal effective connectivity was found, suggesting early DMN changes. These changes may indicate early Alzheimer’s disease‐like brain and cognitive changes (Zhong et al., 2014). The PEB analysis demonstrated associations between the DMN effective dyconnections and cognition, illustrating brain‐behaviour dependencies.ConclusionThe findings of this study indicate diverse longitudinal DMN effective connectivity patterns across YOAD variants. Our findings support the model of amnestic Alzheimer’s disease and PCA onset and progression, whereby the amnestic variant targets the DMN connectivity early, but PCA targets the network in later stages (Seeley, 2017). This accounts for differences in memory deficits amongst variants. Long term clinical implications of this study include the increased knowledge of YOAD network spread and its effect on cognition, which may ultimately contribute to drug development and network‐based biomarkers.