bluuebunny/crossref_metadata_2025_split huggingface dataset:
TOMM40‐APOE haplotypes are associated with cognitive decline in non‐demented blacks
Authors: Deters Kacie D , Mormino Elizabeth C , Yu Lei , Lutz Michael W , Bennett David A , Barnes Lisa L 
Published: December 2020

AbstractBackgroundThe poly‐T alleles at the TOMM40‐’523 locus are in linkage disequilibrium with APOE alleles (E3 and E4). However, the pattern of this association varies across race and may influence cognition over time. Contrary to those who identify as non‐Hispanic White, few studies have investigated the role of APOE‐‘523 genotypes in the Black population. Thus, the goal of our study was to investigate the impact of APOE and TOMM40‐‘523 haplotypes on cognitive decline in non‐demented non‐Hispanic Black (NHB) participants, and determine whether effects differ from non‐Hispanic White (NHW) participants.MethodDistributions of APOE and TOMM40‐‘523 poly‐T alleles were examined across NHB and NHW individuals without dementia at baseline, from three cohort studies of aging and dementia at the Rush Alzheimer’s Disease Center. The impact of zero, one, or two copies of the ’523‐Short (S) variant (poly‐T alleles<20) within APOE genotype on a composite measure of global cognition and five separate domains (global, episodic memory, episodic memory, semantic memory, visuospatial ability, and perceptual speed) derived from 19 individual tests, was examined with linear‐mixed models.ResultIn NHB with E3/E3 (N=294), ‘523‐S/S was associated with faster decline in global cognition, episodic memory, and visuospatial ability (Global: β=‐0.048, p=0.017; Episodic: β=‐0.05, p=0.031; Visuospatial: β=‐0.037, p=0.034) relative to those who did not have a copy of ‘523‐S. In contrast, for NHB E4+ (E3/E4 + E4/E4; N=182), ‘523‐S/S was associated with slower decline in global cognition and visuospatial ability (Global: β=0.047, p=0.042; Visuospatial: β=0.07, p=0.0005) relative to those without ‘523‐S. Further, results indicated a racial difference in E4+ such that NHB with ‘523‐S had a slower rate of decline than NHWs with ‘523‐S. ‘523‐S/S was not statistically different than one copy of ‘523‐S in E3/E3 or E4+ analyses.ConclusionOur findings suggest ‘523‐S/S has a different effect on cognitive decline among NHB dependent on APOE allele, and that ‘523 variation may aid in better prediction of early cognitive decline in NHB individuals. Further, racial differences in the effect of E4‐‘523‐S may explain prior mixed findings on E4 and decline in this population.
Incident MCI and dementia in Hispanic and non‐Hispanic whites: Implications for ethnic comparisons of risk in Alzheimer’s Disease Center data
Authors: Salazar Hector , Norton Derek L , Zuelsdorff Megan , Wyman Mary F , Carter Fabu P , Benton Susan Flowers , James Taryn T , Johnson Adrienne L , Lambrou Nickolas H , Cordova Susie Fernandez , Pinzon Maria C Mora , Asthana Sanjay , Gleason Carey E 
Published: December 2020

AbstractBackgroundRecruitment strategies have different levels of success in reaching Hispanic populations, potentially introducing bias in large multicenter datasets, such as the National Alzheimer’s Coordinating Center (NACC). The purpose of this study is to examine differences in incident mild cognitive impairment (MCI) and dementia between Hispanic and non‐Hispanic whites.MethodWe included NACC data from 23,963 participants with >1 follow‐up visit. Additional inclusion criteria were: age 60+, did not have Downs syndrome, ethnicity Hispanic or non‐Hispanic, primary race as white, and cognitively normal or diagnosed with MCI at baseline. An event (i.e., conversion) was defined as the first visit/subject age when diagnosed with MCI or Dementia. To compare age‐of‐conversion between Hispanic and non‐Hispanic whites, we used Cox proportional hazard models with variable entry setup. Separate models were fit for baseline cognitive status (MCI vs. normal). Model covariates included sex; educational attainment; baseline diabetes, hypertension, and cardiac event status; referral source; family history of dementia; and primary etiology (for baseline MCI subgroup only). Unadjusted Kaplan‐Meier curves were calculated between Hispanic and White non‐Hispanic subjects for both baseline cognitive strata and outcome (conversion only vs. combined).ResultNormal cognition Hispanic participants exhibited significant elevated risk of conversion compared to White non‐Hispanic participants (HR=1.316, p=0.005), but risk was non‐significant for the composite event (HR=1.176, p=0.069). For baseline MCI participants, Hispanic ethnicity was significantly associated with reduced risk of both conversion and conversion/death (conversion HR=0.734, p=0.002; conversion/death HR=0.699, p<0.001). In all models, referral sources other than health professional were associated with reduced risk of event. Family history of dementia was associated with increased risk of conversion and conversion/death for those with normal baseline cognition (conversion HR=1.216, p<0.001; conversion/death HR=1.084, p=0.048), but not for those with baseline MCI.ConclusionWhite participants with MCI, referred by clinicians exhibited greater likelihood of disease progression. These data suggest that Hispanic and non‐Hispanic whites in NACC may not be comparable. Therefore, caution should be exercised when interpreting analyses of data examining ethnic differences in incident MCI and dementia.
Alzheimer's disease: Donepezil effects on cholesterol and oxysterol plasma levels
Authors: Costa Alana Caroline , Joaquim Helena Passarelli Giroud , Nunes Valeria Sutti , Kerr Daniel S. , Forlenza Orestes Vicente , Gattaz Wagner Farid , Talib Leda Leme 
Published: December 2020

AbstractBackgroundCholesterol is an essential component in the structure and function of cell membranes and has been associated with the major pathological signatures of Alzheimer's disease (AD). To maintain brain cholesterol homeostasis, it is converted into 24(S)‐hydroxycholesterol (24OHC) which can be driven through the blood‐brain barrier. Several studies have already described a decrease in 24OHC and an increase of 27(S)‐hydroxycholesterol (27OHC) in AD, as a reflection of disease burden, the loss of metabolically active neurons and the degree of structural atrophy. It is also well known that peripheral cholesterol is altered in AD patients. However, there are no data regarding effects of AD treatment in this cholesterol pathway. Since a study from our group indicated a significant increase in membrane phospholipid metabolism by donepezil, the aim of this study was to evaluate the effect of short‐ and long‐term donepezil treatment on cholesterol and metabolites 24OHC and 27OHC in plasma of AD patients and in healthy volunteers.MethodThe sample comprised 30 patients with mild or moderate AD and 33 physically and cognitively healthy elderly controls. In the last 6 months prior to enrolment in the study, patients and the control group did not use AChEi or other drugs. After the completion of baseline assessments, all patients were started on donepezil treatment (5 mg/day). Doses were administered orally and increased to 10 mg/day after 1 month. Patients were monitored monthly, the MMSE was evaluated after 3 and 6 months, and CAMCOG was evaluated 6 months after donepezil treatment. Plasma cholesterol concentrations were measured using commercially available enzymatic–colorimetric methods. Measurements of oxysterols (24‐hydroxycholesterol and 27‐hydroxycholesterol) were performed by gas chromatography–mass spectrometry.ResultAt baseline, we found a decrease of 24OHC (p = 0.003) in AD patients. Cholesterol levels increased with donepezil treatment (p = 0.04) but no differences were observed regarding 24OHC and 27OHC.ConclusionThese results confirm and extend previous studies demonstrating disturbed cholesterol turnover in Alzheimer's disease.
Causal communication between gut microbiota dysbiosis and neuroinflammation in Alzheimer’s disease and therapeutic intervention by oligomannate
Authors: Geng Meiyu 
Published: December 2020

AbstractBackgroundRecently, increasing evidence has demonstrated the dynamic interaction between gut microbiota dysbiosis and Alzheimer’s disease (AD) progression, yet major knowledge on how gut microbiota pathogenic attacks AD remains obscure.MethodWe provide a multi‐dimensional profiling of gut microbiota, metabolomics and peripheral and central immune patterns in AD transgenic mice, to decipher the pathogenic outcomes of gut microbiota dysbiosis and its potential mechanistic linkage to neuroinflammation in AD progression.ResultWe discovered that, during AD progression, the dynamic alteration of gut microbiota composition and associated metabolites profoundly affected the peripheral immune pattern of the gut and that of the brain. Furthermore, the brain‐infiltrated peripheral immune cells crossed with the microglia activation, contributing to AD‐associated neuroinflammation and then neuronal injury. Importantly, similar alteration in microbiota‐derived metabolites and immune cell subtypes in the blood were also observed in the cohorts of patients with mild cognitive impairment (MCI) due to AD and AD. Interestingly, sodium oligomannate that has demonstrated a consistent cognition improvement in a phase 3 clinical trial in China and approved for the treatment of mild‐to‐moderate AD, was found to suppress gut microbiota dysbiosis and the associated abnormal metabolites, which harnessed peripheral inflammation and neuroinflammation and reversed the cognition impairment in AD transgenic mice.ConclusionOur findings highlight the role of gut microbiota dysbiosis‐promoted neuroinflammation and neurodegeneration in AD progression, and further suggest a novel strategy for AD therapy by targeting gut‐brain axis.
Lifetime endogenous estrogen exposure in women influences risk of dementia
Authors: Panizzon Matthew S. , Sundermann Erin E , Jacobs Emily Goard , Karlsson Ida , Pedersen Nancy L. , Gatz Margaret 
Published: December 2020

AbstractBackgroundThe female reproductive period – menarche to menopause – can serve as a proxy for lifetime endogenous estrogen exposure. A foreshortened reproductive period, either naturally or secondary to medical intervention, has been associated with an increased risk of Alzheimer’s disease (AD), supporting the hypothesis that estrogen exposure is neuroprotective. Prior studies have been limited by small sample sizes, and confounding effects of exogenous hormone exposure (e.g., oral contraception or hormone replacement therapy). In the present study, we examined the association between the length of the reproductive period and dementia in a large, population‐based sample of exogenous hormone naïve women from the Swedish Twin Registry (STR).MethodParticipants were 7,630 women who provided self‐reported health and reproductive history data as part of the Screening Across the Lifespan Twin (SALT) project. Subsequent dementia diagnoses were obtained through follow‐up studies that leveraged either in‐house clinical assessments or national health registry data. Mixed effects logistic regression models examined the effect of length of the reproductive period on all‐cause dementia and AD diagnoses while controlling for the non‐independence of the twin data. Analyses controlled for birth year, number of pregnancies, and history of surgical menopause (i.e., oophorectomy).ResultThe prevalence of all‐cause dementia and AD within the sample was 15.2% and 7.7%, respectively. The mean age at participation in SALT was 65.6 years (SD=9.9), and mean age at dementia diagnosis was 83.4 (SD=7.3). Reproductive span averaged 35.4 years (SD=5.2), and 7.4% of the sample reported surgical menopause. Shorter reproductive span was significantly related to increased likelihood of all‐cause dementia (p=.0008) and AD (p=.0012). Relationships were non‐linear, such that the added benefit of longer reproductive span on dementia/AD risk waned within the higher range of reproductive span. Premature menopause (prior to age 40), significantly increased likelihood of all‐cause dementia (OR=1.42 (1.02‐1.99) but not of AD (OR=1.38 (0.88‐2.17). Number of pregnancies and history of oophorectomy were not significant predictors.ConclusionThese results demonstrate that endogenous estrogen exposure in women is indeed a significant predictor of all‐cause dementia and AD, lending support to an endocrine‐related mechanism that may contribute to sex differences in AD risk.
Assessment of emerging mobile connected technologies to promote outdoor mobility and transit in older adults and in those with Alzheimer’s disease and related dementias: Usability, stressors, barriers, and implications for policy
Authors: Zanwar Preeti , Lee Chanam , Ham Youngjib , Chaspari Theodora , Kim Jinwoo , Tan Shuman , Manser Michael , Ahn Changbum 
Published: December 2020

AbstractBackgroundPopulation aging is known to increase the risk of Alzheimer’s Disease (AD) and AD‐Related Dementias (ADRD). A majority of older adults and those with ADRD prefer to age within their neighborhoods. Maintenance of mobility is important for both older adults and in those with ADRD to sustain independence and to promote quality‐of‐life. However, changes in mobility patterns outside of home can create physical and emotional distress due to infrastructure barriers and lack of accessible transportation.MethodOur overall approach will synthesize learnings from literature review on (1a) commercial technologies that collect, monitor, visualize and analyze data on mobility patterns; (1b) research advances on algorithm developments for mobility, disease pattern detection and prediction and from (2) summary of focused interviews from field experts in several domains: transit technologies, urban planning, assistive technology partners, healthy aging and community environments, and from gerontologists with expertise in dementia care.ResultThe paper aims to understand the how, when, where, and why of walking and travel needs, current barriers, and how technologies can overcome challenges and support healthy aging in community environments and foster dementia‐friendly transportation for older adults and for those with ADRD. The paper aims to review (1) commercial technologies and research advances that can monitor outdoor physical activities (e.g. wearable technologies including wristband type sensors, inertial measurement units, and smartphone to collect physiological responses for electrodermal activity, heart rate, gait patterns, and body balances), (2) stressors and barriers in senior living community environments and the source of physical and emotional distress (e.g. Computer Vision techniques), and (3) mobile transportation technologies (e.g. MEILI, rMove, Itinerum, PEACOX, SmartMo, GPS‐ATD, Future Mobility Sensing, MMMonitor) that allow the understanding of everyday independent mobility patterns and transport needs for older adults, for those with AD+ADRD and their caregivers.ConclusionUnderstanding of mobility patterns and visual appearance of neighborhoods for older adults and for cognitively challenged may aid in the creation of stressor and barrier‐free environments; a pre‐requisite to promote mobility, independence, and for constructing a digital twin city (DTC) model for age‐friendly and dementia friendly transit‐communities.
How does what study partners report differ based on their relationship to the primary subject?
Authors: Stites Shana D , Largent Emily A , Gill Jeanine , Harkins Kristin , Karlawish Jason 
Published: December 2020

AbstractBackgroundStudies of persons with Alzheimer’s disease (AD) and related dementias typically require “study partners” (SPs) to report on the subject’s wellbeing and function. But little is known about how who a SP is might impact on these reports. Knowing this may help inform the interpretation of AD research.MethodsWe analyzed data from 730 older adults and their SPs enrolled in the Aging, Demographics and Memory Study (ADAMS). SPs provided data on their assessment of subjects’ functioning through the following: (1) the Blessed Dementia Rating Scale (BDRS), a multi‐domain informant measure of functional capacity; (2) three single‐item ratings of the subject’s “memory at the present time,” ability “in making judgments and decisions,” and ability to “organize his/her daily activities”; (3) instrumental/basic activities of daily living (IADL/BADL) scales. Subject cognition was assessed in an independent neuropsychological assessment using the mini‐mental status exam (MMSE), Trails A/B, Serial 7s, Boston Naming, and Animal Fluency. Bivariate and multivariable regression analyses were used to examine differences in SP reports based on their relationship to the subject. Demographics of SPs and subjects were also analyzed.ResultsOf SPs, 34.9% (n=255) were spouses, 38.4% (n=281) were adult children, and 26.6% (n=194) had a different relationship to the subject. In bivariate models, adult children were more likely to be college educated and provide care to the subject than spouses. In bivariate analyses, adult children rated subjects as more impaired on the BDRS and single‐item measures of memory, judgment and organizational abilities than did spouses(p<0.05). In multivariable analyses that controlled for differences in cognitive and functional performances, adult children, on average, rated subjects as less impaired on measures of memory, judgment, and organizational abilities than spouses(p<0.05). But, reporting varied in subgroups; in cognitively unimpaired subjects (MMSE>28), only 63.0% of child SPs reported a BDRS that indicated lack of impairment while 90.8% of spousal SPs did so (p<0.05).ConclusionsSpouses and adult children are similarly likely to serve as SPs, but there are differences in how they report on subject functioning. Our findings have important implications for interpreting informant reports, particularly, of persons with no or mild cognitive impairment.
Klüver‐Bucy syndrome due to stroke in the left temporal lobe
Authors: Canella Marcelo , Baptista Rafael Mazzini , de Oliveira Fabricio Ferreira , Bertolucci Paulo Henrique Ferreira 
Published: December 2020

AbstractBackgroundKlüver‐Bucy syndrome (KBS) comprises: 1) hyperorality, 2) hypermetamorphosis, 3) hypersexuality, 4) eating disorder, 5) placidity, 6) visual agnosia (psychic blindness) and 7) amnesia (at least three components are described as partial KBS). The classic description involves bilateral injuries to the anterior temporal lobes, but it has been reported that unilateral lesions can also lead to KBS.MethodCase report and analyses of MR Images (T1, Flair and Tractography) of a patient presenting partial KBS due to stroke in the left temporal lobe.ResultMale patient, 69 years‐old, with cognitive deficits that have begun after a left frontotemporal stroke in 2003, with remarkable changes in the temporal pole. In the first months after the stroke, he used to get lost when out of home and had difficulty remembering names and recognizing well known persons due to psychic blindness. During the next years, the patient developed impairment in declarative memory, but preserved visuospatial skills (many times coming to the medical appointments alone, using public transportation). Over time, he developed binge eating (once eating 1 kilogram of cheese, for instance), inability to deal with money (unnecessary loans in banks) and bizarre sexual behavior (such as excessive addiction to porn movies, public masturbation, flirting with women in his neighborhood, and an episode of inappropriate sexual behavior with his daughter‐in‐law). The patient still resists taking bath and changing clothes.ConclusionThe exact anatomic basis of KBS is still controversial. What is remarkable is the main role of the amygdala in the syndrome. However, periamygdalar lesions can cause disconnection syndromes and damage the limbic network that involves the uncus, the hippocampus, the insular cortex, orbitofrontal and cingulate gyri. Patients with KBS can mimic behavioral variant frontotemporal lobar degeneration (bvFTLD) – particularly regarding eating and sexual disorders, probably due to the connections between the amygdala and the orbitofrontal gyri. The integrity of these two regions and their connections probably play an important role in emotional continence, modulating basic desires in the human species. Lesions in the uncinate fasciculus can predispose to KBS. Our patient exhibits lack of fibers connecting temporal lobe and orbitofrontal cortex showed in the tractography.
A meta‐analysis of neurocognition in mild cognitive impairment in Parkinson’s disease and progression to Parkinson’s disease dementia
Authors: Wallace Elizabeth , Balthrop Kullen , Harp Jordan , Segerstrom Suzanne , van Horne Craig , Koehl Lisa , Schmitt Frederick A. 
Published: December 2020

AbstractBackgroundParkinson’s disease (PD) is a neurodegenerative condition resulting in characteristic motor impairments and cognitive changes, including executive functioning (EF) deficits. These cognitive changes worsen for the approximately 30% who develop Parkinson’s disease dementia (PDD). Mild cognitive impairment (MCI) is a transitional state between normal cognition and dementia. Although PD‐MCI and its neurocognitive correlates have been increasingly studied as an indicator of risk for PDD, the typical PD‐MCI neurocognitive profile remains undefined. The present meta‐analysis examined cross‐sectional studies administering neuropsychological testing to PD‐MCI and cognitively normal PD to provide aggregated effect sizes of group test performance by neurocognitive domain. Longitudinal studies examining PD‐MCI to PDD progression were subsequently meta‐analyzed.MethodData were coded from 92 cross‐sectional papers for PD‐MCI vs. cognitively normal PD groups. Data were coded from five longitudinal papers for PD‐MCI converting to PDD vs. PD‐MCI not converting to PDD. Random effects meta‐analytic models were conducted to provide aggregated weighted effect sizes (Hedges’ g), indicating the difference between these groups in their respective analyses.ResultCross‐sectional results indicate that overall cognitive measures produced a large effect size (g = 1.07, 95% CI [0.99, 1.14], p < .05) with tests of visual delayed memory producing the largest effect size (g = 1.90, 95% CI [1.03, 2.77], p < .05). Longitudinal results indicate that overall cognitive measures produced a medium effect size (g = 0.48, 95% CI [0.41, 0.55], p < .05) with tests of executive functioning producing the largest effect size (g = 0.70, 95% CI [0.51, 0.89], p < .05).ConclusionResults of the first PD‐MCI meta‐analysis indicate that, across cross‐sectional and longitudinal studies, measures of cognitive performance have value in differentiating PD‐MCI from cognitively normal PD and PD‐MCI and PDD. Within cross‐sectional studies, tests of visual delayed memory produced the largest effect size, with group performance differing by approximately two standard deviations. This result may further reflect EF deficits common in PD, as well as a temporally mediated process classically more characteristic of other dementia syndromes. Longitudinal results further highlight the importance of EF changes in progressing PD and suggest power to predict progression to PDD.