bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Look AHEAD Aging Study: design, cohort characteristics, and cognitive function
Authors: Espeland Mark A. , Wagenknecht Lynne E , Bahnson Judy , Barnes Jerry , Beckner Tara , Harris Darrin , Hayden Kathleen M. , Houston Denise K , Neiberg Rebecca H. , Pleasants Debbie , Rapp Stephen R. , Sachs Bonnie C. , Walkup Michael , Yang Mia 
Published: December 2023

AbstractBackgroundData on cognitive trajectories and characteristics associated with cognitive resilience among older individuals with type 2 diabetes and overweight or obesity are scant. To date, the NIA‐funded Action for Health in Diabetes (Look AHEAD) Aging Study has enrolled 1245 individuals, ages 64 to 95 years, who have been richly characterized over 18 years of prior follow‐up with factors associated with cognitive aging.MethodVolunteers from the Look AHEAD clinical trial of a multidomain lifestyle intervention and its subsequent clinic‐based post‐trial observational phase were invited to join a 4‐year telephone‐based observational study that includes annual cognitive assessments to assess memory, attention/processing speed, executive function, and global cognitive function. A composite measure of cognitive function based on the average standardized cognitive function tests was used to capture global cognitive function. Mild cognitive impairment and probable dementia will be centrally adjudicated. Additional measures include depressive symptoms, physical function and abilities, medical events, medication use, and health related quality of life. Recruitment will be completed in early 2023.ResultThe enrolled cohort to date (N = 1590) includes 62% women, 32% individuals from traditionally under‐represented racial/ethnic minorities, 49% without college education, and 52% who had been randomly assigned to the lifestyle intervention. The mean (SD) age is 76.3 (5.6) and years of diabetes is 25.5 (5.5). When last measured, the mean BMI was 33.8 (6.3) kg/m2 and 4 m walk speed was 0.86 (0.22) m/sec. Of 1060 who were tested, 20.6% have one apoE‐e4 allele and 1.1% have two apoE‐e4 alleles. Modified Telephone Interview for Cognitive Status (TICSm) scores ranged from 12 to 48, with mean 34.7 (4.7), with no difference between intervention groups (p = 0.66). While TICSm scores tended to be lower for older participants, many still demonstrated relatively high levels of cognitive functioning, even into the 8th decade of life (attached figure).ConclusionThe Look AHEAD Aging study holds great promise to identify factors across two decades of follow‐up that are associated with cognitive resilience in a large cohort with type 2 diabetes and overweight or obesity. Our presentation will provide data on the full cohort and cognitive battery.
Moderation effects of APOE‐ε4 on marine omega‐3 fatty acids and its relation to change in cognitive function among community‐dwelling older adults
Authors: Vyas Chirag M. , Mischoulon David , Kang Jae Hee , Cook Nancy R , III Charles F Reynolds , Chang Grace , Mora Samia , De Vivo Immaculata , Okereke Olivia I. 
Published: December 2023

AbstractBackgroundIn a recent trial, we observed no effect of omega‐3 fatty acids (omega‐3s) supplementation on cognitive decline. However, brain concentrations and metabolism of lipid molecules in response to omega‐3s may be regulated by apolipoprotein E (APOE)‐ε4 allele status. Further, while APOE‐ε4 is an established risk factor for Alzheimer disease, its association with cognitive decline is uncertain, especially in more diverse samples. The few randomized clinical trials (RCTs) addressing the moderation of effects of omega‐3s on cognitive decline by APOE‐ε4 have yielded inconsistent findings. Thus, we examined moderation by APOE‐ε4 on effects of omega‐3s vs. placebo for global and domain‐specific cognitive change over 2 years in a well‐characterized, diverse sample of older adults.MethodsVITamin D and OmegA‐3 TriaL (VITAL) is a 2×2 factorial RCT of vitamin D3 (2000 IU/day) and/or omega‐3s (1 g/day including 460 mg of eicosapentaenoic acid and 380 mg of docosahexaenoic acid) for cardiovascular disease and cancer prevention. We included 743 VITAL in‐clinic sub‐cohort participants who completed all cognitive tests at baseline and had APOE genotype data. The primary outcome was change in global cognition (averaging z‐scores of 9 tests) over 2 years; episodic memory and executive function/attention were examined separately. We used multiplicative interaction terms in general linear models of response profiles to examine moderation by APOE‐ε4 carrier status on effects of omega‐3s vs. placebo for cognitive change outcomes over 2 years.ResultsThe mean age (standard deviation) of participants was 67.1 (5.3) years; 50.6% were females; 13.5% were from racial and/or ethnic minority backgrounds; and 24.9% were APOE‐ε4 allele carriers. Over 2 years, compared with APOE‐ε4 non‐carriers, APOE‐ε4 carriers had faster declines in global cognition and episodic memory but not in executive function/attention; e.g., the mean difference in change (95% confidence interval) for episodic memory comparing APOE‐ε4 carriers vs. non‐carriers was ‐0.18 (‐0.33 to ‐0.03). There were no significant interactions between APOE‐ε4 carrier status and randomization status (omega‐3s vs. placebo) on change in global, episodic memory, or executive function/attention scores.ConclusionAPOE‐ε4 significantly predicted cognitive decline but did not modify the effect of omega‐3s on global and domain‐specific cognitive change over 2 years.
Sporadic behavioral phenotype of Right Temporal Variant of Frontotemporal Dementia: a case report
Authors: Fernandez Paulo Eduardo Lahoz , Curti Nayara Christina de Lima , Bertolucci Paulo Henrique Ferreira 
Published: December 2023

AbstractBackgroundThere are two subtypes of the right Temporal Variant of Frontotemporal Dementia (rtv‐FTD). Semantic dementia (SMD) phenotype is defined by negative familiar history, word‐finding, anomia, comprehension difficulties, prosopagnosia, and topographagnosia. The behavioral frontotemporal dementia (bvFTD) phenotype is defined by personality changes, inappropriate behaviors, positive family history, and relatively poor performance on neurobehavioral testing with better performance on confrontational naming tests. (1) We present a rare interesting case.MethodWe describe the clinical and imaging features of a man who presented a sporadic behavioral phenotype of rtv‐FTD, showing negative genetic results.ResultA 62‐year‐old man with 8 years of progressive behavioral impairment. He showed personality changes, and compulsive‐like / ritualistic behaviors such as excessive unpurposed accumulation of items, washing hands repeatedly every five minutes, and walking and wandering repeatedly in circles. He also had hiperorality, cravings for sweet foods, social cognition impairment, associated with loss of empathy, and inappropriate social behavior (hypersexuality, verbal aggressivity to unrelated people, and talking bad words to neighbors with no reason). After years he followed with mild to moderate apathy. The neuropsychological evaluation showed impairment of executive functioning, episodic memory impairment, and MMSE 19/30. The neurological exam was unremarkable, and the familiar history was negative. Brain MRI revealed frontotemporal atrophy with a marked asymmetry in the right temporal lobe. The genetic testing was negative, illustrating and sporadic case.ConclusionTheoretically, rtv‐FTD is considered a right variant of semantic phenotype, and the general assumption is that is also a sporadic disorder. Although the behavioral phenotype of rtv‐FTD normally has a genetic basis, showing positive family history, It can be presented as a sporadic disorder with non‐familial variants of FTD, as in this case. (2)References:1. Josephs KA, Whitwell JL, Knopman DS, Boeve BF, Vemuri P, Senjem ML, et al. Two distinct subtypes of right temporal variant frontotemporal dementia. Neurology. 2009 Nov 3;73(18):1443‐50.2. Ulugut Erkoyun H, van der Lee SJ, Nijmeijer B, van Spaendonk R, Nelissen A, Scarioni M, et al. The Right Temporal Variant of Frontotemporal Dementia Is Not Genetically Sporadic: A Case Series. J Alzheimers Dis JAD. 2021;79(3):1195‐201.
Cholesterol and matrisome pathways dysregulated by APOE4 in human glia
Authors: TCW Julia , Qian Lu , Rosa Juao‐Guilherme S , Tuck Tony , Scrivo Aurora , Cuervo Ana Maria 
Published: December 2023

AbstractBackgroundThe association of Apolipoprotein E (APOE) ɛ4 risk with Alzheimer’s disease (AD) is well‐established. However, the impact of APOE ɛ4 on human brain cell function remains unclear. We hypothesized that human APOE ε4/ε4 (APOE 44) genotype contributes to disease risk through cell autonomous and non‐cell autonomous mechanisms in a human cell specific manner.MethodGlobal transcriptomic analyses were performed on astrocytes, microglia, mixed cortical cultures (neurons and astrocytes) and brain microvascular endothelial cells derived from human induced pluripotent stem cells (iPSCs) and post‐mortem AD brains. Lipid pathway dysregulation identified through GSEA, WGCNA and cell type deconvolution was validated in vitro using Gas Chromatography‐Mass Spectrometry (GC‐MS), filipin staining, autophagy fluorescent reporters with immunocytochemistry and western blotting to determine the subcellular compartment that accumulates cholesterol in iPSC‐derived astrocytes, and further confirmed by immunohistochemical analysis in human APOE4 post‐mortem brain. Matrisome pathway dysregulation was validated by Luminex multiplex immunoassays and intracellular protein levels in pure astrocytes and mixed cortical cultures.ResultGlobal transcriptomic analyses reveal that APOE 44 drives cholesterol metabolic dysregulation in astrocytes and microglia from human iPSCs and cell type‐deconvolved post‐mortem AD brain. APOE ε4 leads to elevated de novo cholesterol synthesis despite the intracellular accumulation of free cholesterol in lysosome and cholesterol ester in lipid droplets coupled with reduced efflux due to impaired lipophagy in iPSC‐derived astrocytes. Lysosomal cholesterol accumulation is found in astrocytes from APOE ε4 human brain. Activation of LXRs and induction of lipophagy ameliorates the lipid phenotypes in APOE ε4 astrocytes. Further, matrisome dysregulation is associated with upregulated chemotaxis, glial activation, and lipid biosynthesis in astrocytes co‐cultured with neurons, which recapitulates altered astrocyte matrisome signaling in human brain.ConclusionThus, human APOE ε4 causes human glia‐specific, cell autonomous and non‐cell autonomous cholesterol and matrisome pathway dysregulation that may increase AD risk.
Glia‐Selective Replacement of APOE4 with APOE2: Implications for AD‐Associated Pathologies
Authors: Johnson Lance A 
Published: December 2023

AbstractBackgroundCompared to the ‘neutral’ E3, the E4 allele of Apolipoprotein E (APOE) confers up to a 15‐fold increase in Alzheimer’s Disease (AD) risk. Conversely, the neuroprotective E2 allele decreases AD risk by a similar degree. APOE’s strong risk profile and multitude of effects make it a promising therapeutic target. Here, we aimed to assess the therapeutic potential of allelic ‘switching’ by investigating the physiological changes associated with an inducible, in vivo APOE4 to APOE2 transition in a novel transgenic mouse model.MethodsThe APOE “switch mouse” (APOE4s2) uses the Cre‐loxP system to allow for inducible APOE allele switching from APOE4 to APOE2. These mice express a floxed human APOE4 coding region followed by the human APOE2 coding region. To study the effects of full body APOE switching, APOE4s2 mice were crossed to ubiquitous ROSA26‐CreERT1 mice. Gene expression and proteomic analyses were used to validate that the model worked as expected. Lipidomics and single‐cell RNAseq were used to measure physiological changes following the APOE4 to APOE2 allele switch.ResultmRNA and protein analyses confirm that APOE4s2 mice synthesize full‐length human APOE4/ApoE4 pre‐switch and that the inducible switch results in successful and efficient recombination and expression of human APOE2/ApoE2. Single‐cell RNAseq shows that global, genetic replacement of APOE4 with APOE2 results in distinct alterations to glial cell transcriptomes affecting pathways involved with lipid and mitochondrial metabolism, inflammation, blood‐brain barrier integrity, and amyloid beta. Excitingly, differentially expressed genes associated with an E4 to E2 ‘switch’ included several AD GWAS, and both aging‐ and AD‐associated pathways. Additionally, untargeted lipidomics reveals changes to several lipid classes in the brain, in particular glycerophospholipids.ConclusionTogether, these data suggest that a successful transition from APOE4 to APOE2 has broad impact on the cerebral transcriptome as well as peripheral and cerebral metabolism. Ongoing studies aim to determine whether cell‐specific replacement of APOE4 with APOE2 will rescue E4‐associated metabolic dysfunction, disease‐associated gene signatures, and AD pathology.
Attitudes toward dementia and cognitive aging among Syrian refugees resettled in Jordan: A qualitative study
Authors: Bridi Lana , Kaki Dahlia A. , Al‐Rousan Tala 
Published: December 2023

AbstractBackgroundMounting evidence is revealing disparities in cognitive function and heightened dementia risk among refugees, yet research in this area remains scant. Despite hosting the majority of the world’s refugee burden, limited‐resource countries like Jordan are facing challenges supporting older migrants’ needs. Syrian refugees experience high rates of dementia risk factors including cardiovascular disease, mental ill‐health, and traumatic exposures. The attitudes toward dementia amongst refugees in Jordan and what cognitive healthcare gaps this population faces remain a research gap. This study’s objectives are to identify refugees’ knowledge and attitudes toward dementia and cognitive aging, and to explore factors that facilitate or prevent access to cognitive healthcare in resource‐limited settings.Method32 older Syrian refugees were recruited through a local community‐based organization and interviewed in four gender‐concordant focus groups. Interviews were transcribed and translated, then coded using inductive thematic analysis.ResultAll refugees were 55 years or older and lived below the Jordanian poverty line. Results were organized using the Social Ecological Model of Health: 1) At the individual level, participants believed high levels of stress, including low socioeconomic status, poor health, and traumatic history from their refugee experience increased their dementia risk. 2) Interpersonally, there is a fear of dementia due to its possible impact and caregiving burden on loved ones, particularly with the stigma that surrounds the disease. 3) At the community level, participants noted that resettlement in Jordan – with shared language, religion, and culture – offered protective effects due to facilitated access to social connection, information, and mental health self‐care. 4) Finally, at the policy level, participants believed older refugees faced restrictive policies for economic aid, healthcare, and employment, presenting a significant barrier to healthy aging.ConclusionFindings from this study are the first to examine the perceptions of aging Syrian refugees in Jordan toward their cognitive aging. These results could provide essential data as the country develops its national dementia plan. Overall, participants understand their risk factors for dementia and endorse poor cognitive aging in a country that struggles to support its own population’s basic needs.
CASBA neurological assessment: Noninvasive EEG biomarkers classify amyloid‐PET, clinical diagnosis, cognitive dementia rating, and FCSRT free recall scores in patients with cognitive decline
Authors: Rauchmann Boris‐Stephan , Kleinsasser Maxwell , Hamet James , Paschall Courtnie , Perneczky Robert 
Published: December 2023

AbstractBackgroundAlzheimer’s Disease (AD) is difficult to diagnose and stage, often relying on burdensome clinical tests for neural protein aggregation and cognitive performance. Delays and errors in the accurate diagnosis of AD reduce patient outcomes and prevent early therapeutic intervention. The CASBA electroencephalography (EEG) system leverages a custom sequence of dynamic visual stimuli to elicit and translate novel and noninvasive neural signals biomarkers into accurate estimates of amyloid burden, cognitive performance, and clinical diagnosis, to facilitate clinical decision‐making in patients with cognitive decline.MethodIn a board‐approved study, human patients with mild cognitive impairment (MCI; 71.2 ± 8.2 years old), subjective cognitive decline (SCD; 70.7 ± 6.3 years old), and AD diagnosis (71.2 ± 6.6 years old), alongside amyloid PET (Anti‐Serum Amyloid P Antibody), cognitive testing (i.e. FCSRT), and clinical dementia rating (CDR). Neural signals were collected on a 64‐channel equidistant EEG system (2048Hz, Ag/AgCl; ANT Neuro, Enschede)]. Automated preprocessing and machine learning classification pipelines were developed to extract EEG features and calculate estimates of physiological and cognitive AD metrics from these EEG biomarkers.ResultCASBA accurately classified normal vs. subnormal FCSRT free recall score (threshold of 18, 77.3% balanced accuracy, 84.0% specificity, 70.6% sensitivity), SCD v. MCI/AD clinical diagnosis (79.4% balanced accuracy, 77.3% specificity, 81.5% sensitivity), CDR (threshold of 1, 79.2% balanced accuracy, 76.9% specificity, 81.5% sensitivity), and amyloid‐PET (composite threshold of 1.25, 83.0% balanced accuracy, 75.0% specificity, 91.9% sensitivity).ConclusionThe CASBA neurological assessment accurately predicts important clinical data including patient diagnosis and staging, amyloid burden, and performance on key evaluations of cognition in AD. CASBA supports physician decision making and patient stratification and suggests a new method for noninvasive tracking and repeat assessment during clinical trials. As such, the CASBA neurological assessment offers a promising new tool to advance clinical care and innovation for patients with neurodegenerative disease.
Emergency department care transitions for persons living with cognitive impairment and care partners: development of a novel artificial intelligence and care coach intervention
Authors: Galske James , Gil Heidi , Dorai Chitra , Keefe Kate , Stern Edith , DeFrancesco Erica , Gettel Cameron 
Published: December 2023

AbstractBackgroundEmergency department (ED) presentation by persons living with cognitive impairment (PLWCI) often represents a sentinel event in the care continuum, yet little data exists to date regarding effective interventions to improve ED‐to‐community care transitions for PLWCI and their care partners. Therefore, we sought to develop and refine the innovative pairing of artificial intelligence (AI)‐enabled digital advisors and an occupational therapist‐led care coach intervention to improve ED‐to‐community care transitions for PLWCI and their care partners.MethodsWe used a mixed methods, multi‐phased approach to develop the intervention, with PLWCI and care partners sampled from the LiveWell Dementia Specialists network. In the first phase, we developed and iteratively revised a codebook and conducted recorded, semi‐structured focus groups using a standardized guide. Two researchers coded the professionally transcribed data using a combined deductive and inductive approach and analyzed transcripts to identify dominant themes and representative quotations. In the second phase, we performed a 2‐day design thinking workshop using a user‐centered design approach, involving PLWCI, care partners, health care professionals, community‐based partner organizations, technologists, and AI experts. Integration of findings from the two phases provided takeaways for refinement and optimization of the intervention for eventual pilot testing.ResultsIn the first phase, we performed two focus groups, involving a total of 16 participants, and generated empathy maps regarding the ED experience, the subsequent ED‐to‐community care transition, and the role of technology. PLWCI and care partners expressed: 1) concerns that their unique needs related to cognition were not addressed in the ED setting, 2) frustration with the ED discharge process and their perceived ability to follow‐up in the outpatient setting and obtain desired resources, and 3) openness to the incorporation of AI to facilitate successful ED‐to‐community care transitions. In the second phase, we identified perceived barriers and facilitators for intervention adoption during open forum discussions, depicted the current ‘As Is’ and the desired ‘To Be’ states regarding ED‐to‐community care transitions, and provided a demonstration of the AI‐enabled digital advisors and care coach intervention.ConclusionPLWCI and care partners were integrally engaged in the co‐creation of a two‐component novel intervention to improve ED‐to‐community care transitions.
Using the Allen Cognitive Levels to determine level of supervision needed for those with mild to moderate cognitive decline
Authors: Evans Rebecca J 
Published: December 2023

AbstractBackgroundA comparison was made of the common screening tools for Alzheimer’s disease (AD).MethodThe Mini‐Mental State Examination (MMSE) is one of the most commonly used screening tools but has an emphasis on verbal skills and because it is so widely used, some patients with minimal cognitive decline are able to remember many of the answers from one assessment to the next. The benefits of using the Allen Cognitive Levels (ACL) became apparent as it is a functional based assessment and can be administered without the patient having to say anything.ResultUsing the Allen Cognitive Level screening tool as well as the ACL task activities to narrow a patients level to a number between 0‐6 to the nearest .2 of a point. For example, if a patient scores between 4.6‐4.8, it is recommended that the patient may live alone in the community, provided they have a safe environment with well‐established routines and rehearsed safety plans including daily and weekly supervision. Specific recommendations are available to educate family on safety equipment needs, and executive functioning strategies. For example in the 4.6‐4.8 level, verbal skills are often stronger than a patient’s ability to complete novel tasks, something that is not as easily picked up on a verbal or memory related screener.ConclusionThe Allen Cognitive Level screener and task analysis kits are very helpful for healthcare providers including doctors or therapists to obtain specific information about a clients current cognitive level and what can be expected and how to modify the environment for the client safety and greatest level of independence. Because the levels are structured sequentially, caregivers can compare the current cognitive level to the subsequent level in order to know what to watch out for in the future and clinicians can complete the lacing screener or the task activities as the disease progresses to provide the most accurate information about a clients current cognitive level.