bluuebunny/crossref_metadata_2025_split huggingface dataset:
The impact of APOE genotype disclosure on lifestyle behaviors and decisions about future directives
Authors: Popescu Dominique L , Alber Jessica , Thompson Louisa I , Arthur Edmund , Oh Hwamee , Correia Stephen , Salloway Stephen P. , Lee Athene KW 
Published: February 2022

AbstractBackgroundStudies have shown apolipoprotein E (APOE) genotype disclosure to be safe and well tolerated in cognitively unimpaired (CU) older adults. Genotyping can be valuable to modifiable lifestyle intervention studies as it provides important Alzheimer’s disease (AD) risk information. As such, the goal of this study is to examine the impact of the disclosure process itself on lifestyle behaviors and decisions about future directives in community‐dwelling CU older adults from the Butler Alzheimer’s Prevention Registry (BAPR).MethodCognitively unimpaired APOE &epsilon;4 non‐carriers (n= 106) and carriers (n= 80) aged 58‐78 from the BAPR first completed in‐person psychological readiness screening and genotyping followed by APOE disclosure. Follow‐up assessments were completed online 3 days, 6 weeks and 6 months post disclosure. The primary outcomes were scores on self‐reported measures of physical activity, diet, and decisions about future directives.ResultPost‐disclosure, non‐carriers were more likely to report future directive change towards decisive action on will or estate planning at 3 days follow‐up, healthcare proxy and long‐term living arrangement planning at 6 weeks, and life insurance planning at 6 months. Further, non‐carriers were more likely to report having a long‐term planning discussion with their families at 6 months than carriers. No significant differences were found between non‐carriers and carriers on any of the self‐reported measures of modifiable lifestyle factors (all p> .10).ConclusionIn a clinical research setting, APOE genotype disclosure has been shown to be safe, well tolerated, and in one study, to increase enrollment in ongoing clinical AD research studies. Disclosure led to more decisive actions on future directives in non‐carriers. Disclosure did not lead to changes in modifiable lifestyle factors, an indication that disclosure alone may not be sufficient to inspire behavioral change. Future work will investigate whether pairing disclosure with education about the role of lifestyle factors in AD risk and providing guidelines on making risk‐lowering lifestyle modifications as an intervention approach engenders positive change.
Longitudinal [18F]flortaucipir PET: Comparison of quantitative and semi‐quantitative parameters
Authors: Visser Denise , Tuncel Hayel , Ossenkoppele Rik , den Hollander Marijke E. , Coomans Emma M. , Wolters Emma E. , Timmers Tessa , van der Flier Wiesje M. , Boellaard Ronald , Yaqub Maqsood , Van Berckel Bary N.M. , Golla Sandeep S.V. 
Published: February 2022

AbstractBackgroundDynamic [18F]flortaucipir PET imaging allows for more accurate quantification of specific binding compared to static imaging in Alzheimer’s disease (AD). Besides, with dynamic imaging flow is taken into account, which is especially important in longitudinal studies, because disease progression or drug intervention may lead to flow changes. We aimed to compare semi‐quantitative (SUVr) and quantitative (BPND) parameters for [18F]flortaucipir PET in a longitudinal study.MethodWe included subjects with subjective cognitive decline (SCD; n=38) and AD patients (n=24). All subjects underwent baseline (BL) and 2‐year follow‐up (FU) dynamic [18F]flortaucipir PET. BPND and R1 (relative cerebral blood flow) were calculated (RPM; reference region cerebellar gray). SUVr was derived 80‐100 min p.i.. (Trans)entorhinal, limbic and neocortical regions‐of‐interest (ROIs) were assessed. For each parameter %change was calculated (100*(FU‐BL)/BL). Regional SUVr was compared against respective DVR (BPND+1) using paired T‐tests. Additionally, simulations were performed to model effects of flow changes on BPND and SUVr in high, medium or low binding categories. For each category, R1 values were varied to mimic 5‐25% increase or decrease in flow. Thereafter, %bias for SUVr with respect to underlying binding and its association with respect to change in flow were evaluated.ResultIn SCD, there was a significant difference between %change in DVR (2.56%) and SUVr (1.85%) in the (trans)entorhinal ROI (p<0.05) only. In AD, differences in %change were found in the limbic ROI (DVR 6.61% vs. SUVr 7.52%; p<0.05) only. R1 changes were small (+0.7% in SCD and ‐1.6% in AD). Simulations showed varying %bias in SUVr depending on underlying binding. With increasing flow a decreased bias in low binding conditions was observed, whereas in high binding conditions an increased bias was seen. DVR remained relatively stable under different flow conditions, irrespective of underlying binding.ConclusionCompared to BPND, SUVr provided a good estimate of specific binding for [18F]flortaucipir over a two‐year follow‐up. However, simulations showed that [18F]flortaucipir SUVr is subject to variable bias in case of larger flow changes, which seemed to be depending on underlying tau load. Therefore, BPND should be preferred over SUVr, especially in the context of pharmacotherapeutic interventions that could induce significant changes in flow.
snoRNAs in plasma extracellular vesicles of AD patients are differentially associated with APOE genotype
Authors: Fitz Nicholas F , Nam Kyong Nyon , Koldamova Radosveta , Lefterov Iliya 
Published: February 2022

AbstractBackgroundStandardized disease specific PET patterns correctly classify 95% of AD MCI patients. The cost of PET, however, is still prohibitive as a widespread AD diagnostic test. Diagnostic tests using CSF have also been established to measure the levels of Aβ and hyperphosphorylated tau for early diagnosis of AD or to monitor the effects of therapeutics and progression of the disease. CSF biomarkers show a good agreement with amyloid imaging and a combination of CSF Aβ42/Aβ40 increases the agreement between markers of amyloid pathology. Plasma extracellular vesicles (EVs) and their cargo present an opportunity to isolate and profile molecules associated with human pathological conditions. We have recently found small nucleolar non‐coding RNAs (snoRNAs) of box C/D (SNORDs), transcribed from imprinted chromosomal domains SNURF‐SNRPN at human chromosomal region 15q11q13 and DLK1‐DIO3 at region 14q32, highly enriched in plasma EVs of AD patients compared to non‐demented individuals.MethodDuring the discovery phase of the study, using RNA‐seq we profiled four major classes of ncRNAs in EVs isolated from early stage AD patients and control non‐demented individuals: miRNAs, snoRNAs, tRNAs and piRNAs. We verified the results by Digital Droplet PCR in plasma samples of independent group of AD and control plasma samples.ResultWe report a significant enrichment of SNORDs in AD samples compared to controls. Through verification assays we confirmed these results and identified SNORD115s & SNORD116s with the highest discriminatory power to differentiate AD samples against Controls.ConclusionThe results of our study present evidence that AD is associated with changes in enrichment of SNORDs, transcribed from imprinted genomic loci, in plasma EVs and provide a rationale to further explore validity of snoRNAs as plasma biomarkers for AD.
Compensation training and lifestyle modifications to promote healthy aging in persons at risk for Alzheimer's disease: A digital application supported intervention
Authors: Farias Sarah , Weakley Alyssa , Chan Michelle L , Beech Brooke F , Luna Catherine , Schmitter‐Edgecombe Maureen 
Published: February 2022

AbstractBackgroundThe protocol for ‘Brain Boosters’, a novel combined compensatory training and lifestyle modification intervention aimed at Alzheimer’s disease (AD) risk reduction is presented. Training in compensation will focus on a calendar and tracking system, organizational strategies, and goal setting, all aimed at supporting independent function. These same compensatory tools will be employed to facilitate adoption of lifestyle changes that support brain health (e.g., physical exercise, cognitive exercise, wellbeing exercise) through behavioral monitoring and feedback. A comprehensive suite of digital tools encapsulated in the Electronic Memory and Management Aid (EMMA), an easy to use, interactive application, will be used to facilitate behavioral change and enhance participant motivation. EMMA also allows collection of real‐time data to track intervention adherence and factors that influence adherence.MethodsTo capitalize on a critical window of opportunity to intervene, we will target cognitively normal older adults with subjective cognitive concerns (SCC), an established risk for AD and cognitive impairment. The trial will enroll 200 older adults with SCC who will be randomized to our digital application‐supported compensation training and lifestyle modification intervention or to an education only control group that will not use the EMMA app or be taught how to implement the educational material into their daily lives. Both intervention arms will be delivered in a group setting over 6 months, followed by 12 months of unsupervised follow‐up.ResultsSpecific aims of the project include to: 1) evaluate intervention efficacy on primary outcomes (global cognition and everyday function); secondary outcomes focus on indicators of well‐being, cognitive domains (memory and executive function), physical function, compensation, and health behaviors; 2) evaluate characteristics of treatment responders; 3) evaluate adherence and identify the effective components of the target intervention using a mixed‐method approach; and 4) design machine learning algorithms that use patterns of change in real‐time data metrics to identify incipient declines in treatment adherence and changes in health status.ConclusionsThe project is expected to expand understanding of factors that may impact adherence to and outcomes of a preventative intervention leading to optimization of a scalable intervention to reduce dementia risk applicable to diverse populations.
Spousal caregiver burden in patients with cognitive impairment: Effects on nutrition and other related factors with cognition
Authors: Jeon So Yeon , Kim Jeong Lan 
Published: February 2022

AbstractBackgroundWith the rapid aging process, the number of elderly couple househol is increasing. Accordingly, when a patient with cognitive impairment occurs, the elderly spouse tends to take care of patient, and undergoes physical and psychological stress and changes in nutritional status due to the care, which can be a risk factor for cognitive decline.Therefore, this study aims to evaluate the spousal caregiver`s lifestyle, psychosocial factors and nutritional status related with cognition according to the burden of care for elderly couples.MethodFrom May to December 2020, clinical evaluation and blood tests were conducted for patients who visited Chungnam National University Hospital Geriatric Neuropsychiatric Clinic with their spouse. A total of 39 subjects were included in the analysis. As clinical assessment, we evaluated the care burden(Zait burden interview), depression(Geriatric‐Depression‐Scale), sleep quality (Pittsburgh‐Sleep‐Quality‐Index), cognitive function(Mini‐Mental‐state‐exmination) and subjective cognitive decline, physical activity(International‐Physical‐Activity‐Questionnaire), and dietary habits(Mini‐Nutrional‐Assessment). And, serum total protein, albumin, Hemoglobin and Lipid pannel was measured.ResultAs the patient's cognitive function declined, the burden of care increased(p<0.001). In univariate analysis, the spousal caregiver`s burden was significantly associated with the worse the dietary habits(p=0.003) and increased level of depression(p=0.001) and subjective cognitive decline(p=0.038). The spousal caregiver`s burden showed trend level association with sleep quality(p=0.074), but there was no significant relationship with physical activity(p=0.653). When the age, sex, and caring assistant type were adjusted, dietary habits (p=0.002), depression(p=0.003), and sleep quality(p=0.023) worsened as the spousal caregiver`s burden increased.ConclusionEven if cognitive function in the older adult was normal, the higher the burden among spousal caregivers of patients with cognitive decline, the lower the diet habit and sleep quality, and the higher the level of depression. All of these factors could lower cognitive function. Early intervention on these factors is necessary to prevent the cognitive impairment in spouse due to the burden of care.
Technology‐assisted caregiver matching to address isolation and stress
Authors: Lunde Angela M , Forsberg Leah K , Seifert Sara J , Kramer Kevin M , Knutson Matthew , Lunde Angela , Miller Joel K , Melius Jodi L , Knopman David S , Boeve Bradley F , Petersen Ronald C , Fields Julie A 
Published: February 2022

AbstractBackgroundCaregiving for persons with dementia negatively impacts physical and mental health, including increased risk for chronic loneliness and isolation. This Phase I study aimed to recruit former and current dementia caregivers as engaged partners in the design of a unique, technology‐assisted pairing platform to match caregivers to one another for meaningful connection and support based on characteristics chosen by the caregivers themselves.MethodWe recruited thirty‐two caregivers to participate in two semi‐structured focus groups (audio recorded for qualitative analyses) and complete a survey to understand the characteristics desired in another caregiver for the purpose of emotional support. Participants interacted with a website prototype on their personal device and completed a user experience feedback form. An iterative process was used to design the website and matching questionnaire allowing participants to validate preferences and concerns. Website analytics were captured (e.g. time to answer each question, total time spent on the website).ResultThe efforts culminated in a website ‘look and feel’ that addressed the preferences and criticisms of study participants. Figure 1 shows the home page slider inviting caregivers to join (images 1‐3) and describes the matching process (4); the caregiver answers up to 34 questions to create a profile (5‐7) and the website provides a list of caregivers that best match criteria (8). Overall, 87% of study participants rated a high level of comfort with completing the personal profile questions; 82% felt confident the questions asked would lead to a good match. An algorithm to match caregivers was created using the profile questions which asked participants to self‐select and then rank the characteristics of highest importance. Good and poor matches are scored by the algorithm, with 1 being a “perfect” match (Figure 2). In the current cohort, each participant had at least one match that scored 0.708 or higher.ConclusionOur study established interest in a technology assisted peer‐to‐peer caregiver matching program that is a potential low‐cost, high‐impact resource. The study resulted in a set of matching characteristics and an algorithm prototype within a user influenced website and will be further tested in Phase 2. Research supported from NIA of the NIH.
Identifying mixed Lewy body and Alzheimer’s disease pathologies using functional neuroimaging
Authors: Scharre Douglas W. , Nagaraja Haikady , Icenhour Jennifer , Rawson Kristina , Truelove Jessica , Knopp Michael V. 
Published: February 2022

AbstractBackgroundLewy body dementia (LBD) and Alzheimer’s disease (AD) are the two most common neurodegenerative causes of dementia. Autopsy studies report many cases with these clinical diagnoses having mixed pathology with alpha‐synuclein, tau and amyloid proteinopathies. There is limited research in trying to distinguish these potential mixed pathology conditions prior to death. We used functional neuroimaging methods including FDG PET, amyloid PET, and DaTscan SPECT to evaluate clinically diagnosed subjects with dementia with Lewy bodies (DLB), AD and PD to investigate how often potential mixed pathologies could be present.MethodEighteensubjects (all Caucasian, male/female ratio 15:3) so far were recruited from Ohio State University Memory Disorder and Movement Disorder Clinics in this currently enrolling study. Subjects were diagnosed based on standard clinical criteria for DLB, PD and AD by fellowship trained cognitive and movement disorders faculty. Cognitive testing including Mini‐Mental State Examination (MMSE) and Self‐Administered Gerocognitive Examination (SAGE) were performed. Neuroimaging evaluations performed by neuroradiology faculty were blinded to clinical diagnosis.ResultNine subjects with clinical diagnosis of Lewy body disease (5 DLB and 4 PD) and nine subjects with clinical diagnosis AD were compared. The Lewy body subjects were 71.3 ± 7.4 years old, MMSE 22.3 ± 5.4, and SAGE 9.7 ± 4.8. AD subjects were 67.1 ± 9.6 years old, MMSE 18.6 ± 5.2, and SAGE 9.0 ± 5.2. One subject (11%) of the clinical AD cases showed mixed LBD and AD features, one subject (11%) of the clinical AD cases was negative for amyloid with normal DaTscan uptake, two subjects (40%) of the clinical DLB cases showed mixed LBD and AD features, one subject (20%) of the clinical DLB cases was positive for amyloid with normal DaTscan uptake, and all four subjects with clinical PD showed neuroimaging findings consistent with PD.ConclusionBased on functional neuroimaging, 21% of clinically diagnosed AD or DLB subjects had evidence of potential mixed pathologies and 14% were misdiagnosed. Although the sample size is small, functional neuroimaging studies revealed possibly incomplete or incorrect diagnoses in about one third of subjects clinically diagnosed by subspecialists using standard clinical diagnostic criteria. Larger studies are required to confirm these findings.
Blood pressure is associated with advanced brain aging patterns on MRI in midlife: The CARDIA Study
Authors: Dintica Christina S. , Habes Mohamad , Erus Guray , Vittinghoff Eric , Davatzikos Christos , Nasrallah Ilya M , Launer Lenore J. , Sidney Stephen , Yaffe Kristine 
Published: February 2022

AbstractBackgroundHigh blood pressure has been associated with cognitive outcomes such as dementia. Most studies have focused on blood pressure in mid or late life, thus this association in early adulthood is undefined. We aimed to investigate the relationship between sub‐clinical blood pressure in early adulthood and brain aging in midlife.MethodFrom the prospective study of Coronary Artery Risk Development in Young Adults, 662 Black and White participants were identified with follow‐up of 30 years (age 18–30 years at baseline) and brain MRI at Year 30. Cumulative exposure of systolic and diastolic blood pressure (BP) from baseline through Year 30 were estimated by areas under the curve and analyzed as time‐weighted averages. We used a previously‐validated high dimensional machine learning pattern analysis method to derive brain aging indices that quantify individual differences in spatial patterns of age‐related atrophy: the SPARE‐BA index (Spatial Pattern of Atrophy for Recognition of Brain Aging). Cognitive function was assessed at year 30 with the Rey Auditory Verbal Learning Test (RAVLT), Digit Symbol Substitution Test (DSST), Stroop Test, and Verbal Fluency. We used linear regression models to estimate the associations between cumulative BP and predicted brain age and cognitive function at year 30.ResultCumulative systolic and diastolic BP were positively associated with higher predicted brain age (β: 0.10, 95% CI: 0.04‐0.17, β: 0.10, 95% CI: 0.02‐0.19, respectively), adjusted for chronological age at year 30, sex, education, and race. Participants with cumulative systolic or diastolic BP over the recommended guidelines (systolic BP>120, diastolic BP>80), had on average 3‐years older predicted brain age (95% CI: 1.00‐4.67; 95% CI: 1.45‐5.13, respectively), compared to those with normal levels. Moreover, higher predicted brain age was associated with poorer performance on the RAVLT (p= 0.009), DSST (p<0.001), Stroop Test (p<0.001) and Verbal Fluency (0.009).ConclusionElevated blood pressure from early to middle adulthood, especially above recommended guidelines, is associated with worse cognition in midlife and advanced brain aging. Elevated sub‐clinical blood pressure could be an important target for early intervention in order to prevent cognitive impairment.
Effects of diet and social status on white matter integrity in female cynomolgus monkeys
Authors: Kim Jeongchul , Barcus Richard A. , Frye Brett M. , Lockhart Samuel N. , Craft Suzanne , Register Tom , Andrews Rachel N. , Appt Susan E. , Vitolins Mara Z. , Uberseder Beth , Chen Haiying , Corbitt Sarah E. , Solingapuram Sai Kiran K. , Shively Carol A. , Whitlow Christopher T. 
Published: February 2022

AbstractBackgroundMounting evidence suggests that diet may influence risk for cognitive impairment and neurodegenerative disease, including Alzheimer’s disease. Nonhuman primates are important models of cognitive aging and Alzheimer’s disease‐like neuropathology given their complex central nervous systems and susceptibility to diet‐induced diseases. Diffusion magnetic resonance imaging (MRI) studies in humans report age‐related increases in mean diffusivity (MD) and decreases in fractional anisotropy (FA). Whether nonhuman primate models of Alzheimer’s disease‐like neuropathology show similar changes in diffusivity, and whether diet affects these changers is unknown. As such, the purpose of this study was to determine the longitudinal effects of diet (Mediterranean vs Western) and social subordination stress on diffusion MRI measures of white matter structural integrity in a nonhuman primate model of aging.MethodIn this IACUC approved study, thirty‐seven middle‐aged cynomolgus monkeys (Macaca fascicularis) were evaluated longitudinally with diffusion MRI measures (FA, MD, axial diffusivity [AxD], and radial diffusivity [RD]). Monkeys were scanned at baseline and after 31 months of diet consumption (∼ equivalent to a 9‐year follow up in humans). Diffusion MRIs were preprocessed (corrected for eddy current and geometric distortion) and co‐registered to high resolution T1w MRI to derive diffusion measures. For statistical analyses, cerebral white matter and 9 bilateral regions of interest (ROIs) were selected from NeuroMaps nonhuman primate atlas. Statistical analyses were performed with repeated measures analysis of variance.ResultWe observed social status differences in frontal (p=0.021) and occipital (p=0.029) white mater ROIs, with greater longitudinal increase or smaller longitudinal decrease in FA among subordinates compared to dominants. Diet and social status interacted to impact AxD in the genu of the corpus callosum (p=0.028). Finally, subordinates in the Mediterranean group demonstrated greater longitudinal diffusivity increases compared to 1) dominants in the Mediterranean group, 2) dominants in the Western group, and 3) subordinates in the Western group (Figure below).ConclusionWhile the biological mechanisms underlying these findings require future investigation, our observations suggest that diet and social subordination stress illicit changes in structural white matter integrity that could modify vulnerability to Alzheimer’s disease‐like neuropathology in middle‐aged nonhuman primates.