bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of the Snellen Memory Test (SMT): An episodic memory test to screen for AD risk in a clinical optometry/ophthalmology setting
Authors: Aker Ryan , Arthur Edmund , Thompson Louisa I , Maruff Paul T , Snyder Peter J , Alber Jessica 
Published: December 2020

AbstractBackgroundAlthough we have been working to discover and validate retinal imaging biomarkers for preclinical AD risk, the cognitive assessment of episodic memory function remains the most commonly relied on screening approach. Here, we sought to develop a brief screening test for episodic memory, to augment retinal biomarkers in the early detection of AD. By relying on the standard Snellen Eye Chart as the stimulus field, we aim to create an instrument that can be seamlessly incorporated into standard clinical optometry/ophthalmology practices. This pilot study sought to identify episodic memory questions of equivalent difficulty, based on the Snellen Eye Chart, that can eventually be scored using a mobile application.Method12 cognitively normal (CN) older adults (24‐56 years) completed the SMT, consisting of 2 x 11 question forms, with both free‐ and cued‐recall components: one form immediately after encoding and one form after a 20‐minute delay. Item analysis was performed for each test question at immediate and delayed recall, and the mean difficulty index (DI) of all questions was computed along with a 95% confidence interval (CI).ResultThe mean DI for all questions at immediate recall was 0.66 (95% CI: 0.53‐0.79) with two questions falling below the 95% CI lower bound (0.53). The mean DI at delayed recall was 0.70, (95% CI: 0.57, 0.82) with one question falling below and one falling above the 95% CI upper bound. We eliminated 4 questions, leaving a pool of 18 questions of equivalent difficulty at immediate and delayed recall.ConclusionMany of the items for the SMT were moderately difficult for CN individuals. These questions may be further developed to screen for AD risk in CN older adults in a clinical setting. We are currently collecting data in a cohort (N=100) of CN older adults (55‐80) at both low‐ and high‐risk for preclinical AD, which will be used to further refine this novel memory test. Our next step is to validate the SMT against gold standard neuropsychological assessments of episodic memory, and to examine the added prognostic value of this test in conjunction with our panel of retinal imaging AD risk biomarkers.
Cross‐sectional and longitudinal associations of white matter hyperintensities and cortical thickness in the biomarkers of Alzheimer’s Disease in Down Syndrome (ADDS) study
Authors: Lao Patrick J , Luo Linggang , Igwe Kay C , Rizvi Batool , Sathishkumar Mithra , Rosas H. Diana , Lai Florence , Mapstone Mark , Head Elizabeth , Silverman Wayne , Lott Ira T , Schupf Nicole , Yassa Michael A , Brickman Adam M 
Published: December 2020

AbstractBackgroundThere is a general consensus that cerebrovascular change plays a role in the clinical presentation of Alzheimer’s disease (AD) but considerable debate about its role in disease pathogenesis. Adults with Down syndrome (DS), like those with autosomal dominant mutations for AD, develop AD pathology and symptoms by their 40s and 60s, respectively. Unlike the general population, individuals with DS have low prevalence of classical vascular risk factors, like hypertension, but high prevalence of cerebrovascular disease in AD. We examined the association of cerebrovascular disease and cortical thinning in adults with DS.MethodTo date, 66 adults (50±7yrs, 38% women, 33% MCI‐DS/dementia) enrolled in the ADDS study have undergone longitudinal processing of MRI (1.3±2yrs follow‐up) and clinical evaluation at three US sites. The ADDS study is a natural history study investigating biomarkers relevant to the transition into dementia in older adults with DS. Participants were classified as cognitively‐stable, MCI‐DS, possible AD dementia, definite AD dementia, or indeterminate based on consensus conference diagnosis. Cerebrovascular disease was operationally‐defined as white matter hyperintensity (WMH) volume measured at baseline. Neurodegeneration was defined as cortical thickness, measured with FreeSurfer at baseline and follow‐up. We examined the association of baseline WMH with baseline and longitudinal [%/yr] cortical thickness.ResultCross‐sectionally, there was higher cortical thickness in cognitively‐stable individuals in the parietal lobe compared with MCI‐DS/dementia (p=0.02). Higher global WMH was associated with lower global cortical thickness (p=0.004), mostly driven by parietal and frontal lobe WMH distributions. The association of WMH with global cortical thickness was stronger among MCI‐DS/dementia than in cognitively‐stable (interaction; p=0.04). Longitudinally, higher baseline global WMH was associated with faster cortical thinning in cognitively‐stable compared with MCI‐DS/dementia (interaction; p=0.02), such that there was observable cortical thinning with WMH in cognitively‐stable compared to little‐to‐no cortical thinning with WMH in MCI‐DS/dementia.ConclusionHigher WMH burden is associated with lower cortical thickness in adults with DS, particularly in parietal lobe and among those with MCI‐DS/dementia. However, higher WMH burden is more strongly associated with cortical thinning in those who are cognitively‐stable, suggesting that effect of vascular disease on neurodegeneration occurs prior to the onset of cognitive symptoms.
The effects of Mediterranean diet on memory and Alzheimer's disease biomarkers
Authors: Ballarini Tommaso , Schröder Alina , van Lent Debora Melo , Wolfsgruber Steffen , Priller Josef , Teipel Stefan J , Buerger Katharina , Laske Christoph , Peters Oliver , Wiltfang Jens , Düzel Emrah , Spottke Annika , Perneczky Robert , Fließbach Klaus , Schneider Anja , Heneka Michael T , Jessen Frank , Wagner Michael 
Published: December 2020

AbstractBackgroundIn the absence of effective therapies against Alzheimer's disease (AD), the identification of modifiable risk/protective factors is crucial. Many studies have shown the influence of diet on aging and diseases of late life, including neurodegenerative disorders. However, the mechanisms underlying these effects are largely unknown. Here we investigated the effects of Mediterranean diet (MD) on memory performance and on biomarkers for AD in a large cohort of non‐demented individuals from the German multicenter Longitudinal Cognitive Impairment and Dementia Study (DELCODE). Specifically, we aimed to test if the know association between adherence to MD and improved memory is mediated by effects on hippocampal volume and biomarkers of AD pathology in cerebrospinal fluid.MethodThe sample included memory clinic patients with subjective cognitive decline (n=235) or mild cognitive impairment (n=100), cognitively normal siblings of AD patients (n=56), and healthy volunteers (n=179). A MD score was computed for each subject by means of an established Food Frequency Questionnaire. Linear regression models adjusted for age, gender and education were run to investigate the association between MD and 1) memory performance, 2) total‐tau, phosphorylated‐tau and amyloid‐beta 42 levels from cerebrospinal fluid and 3) bilateral hippocampal volumes obtained via segmentation of 3T MRI data in Freesurfer.ResultOverall, higher MD scores were associated with better memory function, lower levels of total and phosphorylated tau proteins and increased volume in bilateral hippocampi. In contrast, no significant effects of MD on amyloid were identified. Subsequent mediation analyses revealed that the effect of MD on memory performance was mediated by both hippocampal volumes and tau protein levels.ConclusionOur results support the view of Mediterranean diet as a protective factor against memory decline and AD‐related neurodegeneration. Moreover, we propose that MD acts on hippocampal volume and tau protein accumulation, which in turn leads to preserved memory performance. Further studies are needed to validate and expand our findings, especially investigating the effects of specific combinations of nutrients and their interplay with AD‐biomarkers and cognitive decline during follow‐up.
Six‐month decline in language, but not other cognitive domains, identifies increased risk of conversion from MCI to AD in ADNI
Authors: Tommet Douglas , Choi Seo‐Eun , Rabin Laura , Sikkes Sietske A.M. , Jutten Roos J. , Grandoit Evan , Foldi Nancy , Jones Richard N. , Lamar Melissa , Gibbons Laura E. , Mukherjee Shubhabrata , Lee Michael L. , Sanders R. Elizabeth , Saykin Andrew J. , Trittschuh Emily H. , Mez Jesse , Risacher Shannon L. , Crane Paul K. ,   the Alzheimer's Disease Neuroimaging Initiative
Published: December 2020

AbstractBackgroundIdentifying people with MCI at greatest risk of AD conversion is an important research goal. Our objective was to determine whether changes in domain‐specific cognitive functioning over 6 months could identify people at greatest risk of AD conversion.MethodWe used modern psychometric methods applied to the ADNI cognitive battery to develop composite scores for memory, executive functioning, language, and visuospatial functioning. We considered scores at baseline and 6‐month visits for the 809 participants who had prevalent MCI in ADNI1, ADNIGO, and ADNI2, and characterized people based on quartiles of 6‐month changes in each domain. We used Cox models to determine whether 6‐month changes for each domain associated with risk for conversion to AD. We compared 6‐month changes to APOE genotype and the AD CSF biomarker signature, controlling for age, sex, and years of education.Result305 participants (38%) had zero bottom quartile change scores (most decline); 296 (37%) had one; 138 (17%) had two; 60 (7%) had three; and 10 (1.2%) had all four. Cox model results for 6‐month changes in all four domains without and with APOE genotype are shown in Table 1. There were 173 people with CSF results to characterize the AD biomarker signature. Cox results are shown in Table 2. Compared to people in the top quartile for 6‐month language change (most learning), people in the bottom quartile (most decline) were at increased risk of AD conversion, independent of APOE genotype and the AD biomarker signature. For 6‐month memory change, the hazard ratio for the bottom quartile (most decline) was attenuated when APOE genotype was included in the model, and it was null when the CSF biomarker signature was included. 6‐month changes in executive functioning and visuospatial functioning were not associated with risk of AD conversion.Conclusion6‐month changes in language identify people with MCI at highest risk of AD conversion. This effect is not explained by APOE genotype or CSF biomarkers. 6‐month language scores may identify people to target in AD prevention trials.
Functional status among community‐dwelling older adults is determined by cognitive status
Authors: Gray Michelle , Gills Joshua L. , Glenn Jordan M. , Madero Erica N. , Hall Aidan , Fuseya Nami , Vincenzo Jennifer , Bott Nicholas T. 
Published: December 2020

AbstractBackgroundSince 2008, the number of older adults has increased by 34% and is expected to nearly double by 2060. Among US older adults over 70 years of age, 22‐30% report difficulty performing at least one activity of daily living (ADL). ADL performance is associated with functional fitness parameters. Negative longitudinal changes in functional performance among older adults are associated with cognitive decline and may be able to predict future cognitive impairment. Thus, it is imperative to understand the influence of cognition on functional fitness among older adults.Method84 older adults (80.9+5.4 years) consented to have their functional fitness and cognition assessed. Functional fitness parameters included the following assessments: Short Physical Performance Battery (SPPB), 10‐meter walk (habitual and fast), dual‐task (habitual and fast), power chair stand assessment (average and peak power and velocity). Cognition was assessed using the Montreal Cognitive Assessment (MoCA) and a digital Visual Paired Comparison (VPC) task. Categories of low and high cognitive function were determined using the VPC results. A one‐way ANOVA was conducted to determine differences between cognitive groups.ResultParticipants with high cognitive performance scored significantly better on the SPPB, 10‐meter fast walk, dual‐task fast condition, and average velocity during the power chair stand assessment. SPPB scores were 10.2% lower among older adults with low cognitive performance (p = .04). The high cognition group walked 16.5% (0.16 m/s) faster when compared to the low cognitive group (p = .04). Dual‐task (fast) performance was 13.2% slower among the low cognition group (p = .03). Additionally, low cognitive older adults moved 16.7% slower when rising from a seated position during the power chair stand task (p = .01). MoCA was 2.76 points lower among the low cognition group (p < .001).ConclusionBased on the current results, a relationship exists between functional fitness and cognitive performance in older adults. However, it remains unknown whether functional fitness can influence cognition or vice versa and how these impact ADL performance. Future research is warranted to determine if and how the relationship between cognitive function and functional fitness changes over time in older adults.
The impact of creative engagement in museum activities on the well‐being of people living with dementia, their carers, and family members: The arts programming “Susitikime muziejuje” case in Lithuania
Authors: Petkutė Ieva , Karpavičiūtė Simona 
Published: December 2020

AbstractBackgroundCaring for people living with dementia presents profound challenges to families and society, and the growing global burden is vastly underestimated. WHO (2019) recommends to integrate the arts in the social care and health sectors to support health and well‐being throughout the life course and across the continuum of care. In museum programming “Susitikime muziejuje we are tackling this challenge by developing cross‐sectorial partnerships that create access to the art for people living with dementia, their carers and family members.MethodThe programme “Susitikime muziejuje” includes training for museum staff, museum tours, workshops in residential care settings and the evaluation of the programme’s impact on the well‐being of people living with dementia, their carers and family members. Evaluation carried out in 2019 included observation of the museum activity sessions and focus group interviews with the participants after the sessions. The qualitative data was analysed using the thematic analysis.ResultThe project “Susitikime muziejuje“ in Lithuanian Art museums provides opportunity for people living with dementia, their carers and family members to engage in art activities. The programme created a platform to experience the art in a safe, failure free and friendly environment; stimulated learning and self – expression in equal participation; increased self‐esteem; helped to relax; enhanced participants’ mood while experiencing a meaningful and joyful here and now moment; increased a sense of community and improved communication. Participants experienced a range of positive emotions, learned new things about each other with no negative experiences of the participation in the programme were stated.ConclusionMuseum arts programme “Susitikime muziejuje” had a positive impact on the well‐being of people living with dementia and their carers. The study contributes to the research in dementia care and supports the evidence the cultural sector can play an active role in cross‐sectorial partnerships development and supporting person‐centered approach in dementia care.
An extensive plasmid library for preparing tau variants and studying their functional biochemistry
Authors: Karikari Thomas K. , Rodríguez‐Lantero Juan , Olsson Maria , Hill Emily , Moffat Kevin G. , Zetterberg Henrik , Blennow Kaj 
Published: December 2020

AbstractBackgroundWhile tau supports axonal transport by modulating microtubule stability, pathologically it can form neurofibrillary tangles, a key hallmark of Alzheimer’s disease and other tauopathies. Significantly, familial mutations and specific truncations regulate the biochemical processes involved in tau pathology. With the complexity and limited supply of human brain samples for research purposes, recombinant protein technology has become vital for studying tau structure and function. However, open‐source and well‐characterized plasmids and methods for expressing and purifying tau variants are lacking.MethodWe generated 58 plasmids, encoding different tau variants and verified their identities by DNA sequencing. Purification of E. coli‐expressed constructs was achieved by immobilized metal affinity chromatography followed by size exclusion chromatography. Subsequently, tau monomers were utilized to prepare oligomers and paired helical filaments (PHFs), characterized by circular dichroism (CD), transmission electron microscopy and dot blotting. Cellular uptake and cytotoxicity of stabilized oligomers were studied in neuroblastoma cells and stem cell‐derived neurons.ResultTwo sets of plasmids were generated: (i) tau fragments (14 plasmids; Figure 1), including disease‐associated fragments identified directly from human brain samples. The constructs include full‐length (FL) tau‐441 (Uniprot#P10636‐8) as well as FL tau‐441 truncated at 224, 368, 391 and 421, and their respective control fragments, and (ii) tau mutation variants (44 plasmids; Figure 2), including those encoding FL tau‐441, its four‐repeat microtubule‐binding (K18) fragment, and their respective selected familial pathological variants (N279K, V337M, P301L, C291R and S356T). Since cysteine content and locations can affect biochemical properties of tau, plasmids for expressing single (C291A), double (C291A/C322A) and triple (C291A/C322A/I260C) cysteine‐modified variants were also generated. Dot blotting with specific anti‐tau antibodies were used to verify purified fragments. Beta‐sheets in purified monomers increased with aggregation. Oligomers were granular‐shaped and reacted strongly with the anti‐oligomer antibody T22. PHFs had paired‐helical structures. Oligomer stabilization was achieved by cysteine‐labelling with fluorescent/non‐fluorescent maleimide derivatives. Fluorescent‐stabilized oligomers were internalized by neurons and co‐localized with endogenous tau.ConclusionWe anticipate that the plasmid library and the associated purification and characterization methods will facilitate future studies including microtubule‐binding assays, aggregation, cellular uptake, intra‐cellular toxicity, and extracellular release. Plasmids can be requested at: shorturl.at/ABDM3
Perceived control attenuates the relationship between experiences of discrimination and left amygdala volume in older adults
Authors: Rosario Michael A , Ayoub Amara , Alotaibi Razan , Clark Uraina S , Schon Karin 
Published: December 2020

AbstractBackgroundThe medial temporal lobes (MTLs), which exhibit neuropathology in Alzheimer’s disease (AD), are modulated by experience. Animal models of environmental enrichment and chronic stress have shown structural plasticity in the amygdalae and hippocampi. Experiences of discrimination (EoD; e.g., sexism, racism, ageism) are salient chronic psychosocial stressors that affect physical and mental health. Perceived control, one’s perception of environmental and psychological control, may attenuate the impact of EoD by increasing resilience. Although aberrant amygdala activity has been implicated in relation to EoD, research has yet to investigate the structural correlates of EoD.MethodsData from 36 participants (58% female, 55‐86 years, 31% African American) were used to investigate the moderating effect of perceived control on EoD and MTL volume. T1‐weighted MR images were captured on a 3T Philips Achieva scanner and analyzed using FreeSurfer's automatic segmentation protocol. Models were adjusted for age, sex, education, and intracranial volume.ResultsMultiple regression models showed an association between left (t(30) = ‐4.073, p < 0.001) and right (t(30) = ‐2.116, p < 0.05) amygdala, but not hippocampal, volume and EoD scores. Additionally, perceived control significantly interacted with EoD for the left (b = 10.66, t(28) = 2.776, p < 0.01), but not right (b = 2.096, t(28) = 0.514, p > 0.05), amygdala. At lower levels of perceived control, higher EoD (b = ‐108.57, t(28) = ‐4.509, p < 0.001) predicted smaller left amygdala volume. However, EoD (b = ‐11.77, t(28) = ‐0.562, p = 0.58) did not predict left amygdala volume at higher levels of perceived control.ConclusionThis cross‐sectional study of cognitively healthy, older adults, provided evidence that greater EoD was associated with smaller amygdala volumes bilaterally. Further, participants with lower perceived control at higher levels of EoD showed a greater reduction in left, but not right, amygdala volume. This suggests that the interaction between chronic stress and resilience might contribute to neuropathology or reserve of AD‐sensitive regions, specifically in populations that face higher discriminatory experiences. Future studies are needed to examine whether interventions that increase perceived control (resilience) have beneficial effects on neural structure and function.
Nativity differences in lifecourse socioeconomic position and late‐life cognition among KHANDLE participants
Authors: Peterson Rachel , George Kristen M , Gilsanz Paola , Mayeda Elizabeth Rose , Glymour M Maria , Mungas Dan M , DeCarli Charles , Whitmer Rachel A 
Published: December 2020

AbstractBackgroundSocioeconomic position (SEP) in childhood and adulthood is associated with late‐life cognition. Less is known about how SEP changes may be associated with late‐life cognition in diverse cohorts.MethodsThe Kaiser Healthy Aging and Diverse Life Experiences Study (KHANDLE) is a cohort of community‐dwelling Kaiser Permanente members who reside in the San Francisco Bay area and Sacramento valley (n=1,708; Asians (24%), Blacks (26%), Latinos (20%) and Whites (30%)). KHANDLE aims to evaluate how lifecourse and sociocultural factors influence late‐life brain health and cognitive decline and contribute to race/ethnic disparities. We used linear regression to test the association between lifecourse SEP trajectories and late‐life cognition and tested if these associations differed by US vs. foreign nativity. Childhood SEP is a composite of parents’ education (≥HS vs. <HS), childhood hunger, and self‐reported family financial status. Adult SEP included participants’ education (≥HS vs. <HS), late‐life low income status (e.g. qualified for low‐income welfare programs), and self‐reported social status. Participants were classified as having consistently high SEP (HH), low childhood/high adult SEP (LH), high childhood/low adult SEP (HL), or consistently low SEP (LL). Executive function, semantic memory and verbal episodic memory measured with the Spanish and English Neuropsychological Assessment Scales (SENAS) were z‐standardized and averaged for overall cognition. Pooled analyses adjusted for age, race/ethnicity, gender, and foreign nativity.ResultsOverall, participants classified as LH did not differ from HH (ref.) in any cognitive domain, while those classified as HL and LL had lower cognition than HH in all domains (see table). We observed a significant interaction of US vs. foreign birth and lifecourse SES trajectory for semantic memory (p=0.01), but no other domain. Stratified analyses demonstrated a similar pattern to pooled. However, foreign‐born participants HL participants had significantly lower overall cognition (p=0.03), and verbal memory (p=0.02) than US‐born HL participants. By contrast, foreign‐born LH participants performed significantly better than US‐born LH in semantic memory (p=0.01).ConclusionsThose with high Adult SEP had the best cognitive function, regardless of childhood SEP or nativity. In some measures of cognition, foreign‐born HL participants performed worse than US‐born, while foreign‐born LH performed better.