bluuebunny/crossref_metadata_2025_split huggingface dataset:
In vivo locus coeruleus imaging in Alzheimer’s and Parkinson’s disease
Authors: Betts Matthew J. , Pape Johanna , Spottke Annika , Teipel Stefan J. , Kilimann Ingo , Galazky Imke , Jessen Frank , Düzel Emrah 
Published: December 2020

AbstractBackgroundThe locus coeruleus (LC) plays an important role in numerous cognitive functions such as working memory, learning and attention. Novel magnetic resonance imaging (MRI) techniques now provide an opportunity to quantify structural features of the LC in vivo which may help to understand the contribution of LC neurodegeneration to clinical and pathological manifestations in Alzheimer’s disease (AD) and Parkinson’s disease (PD). In this study we aimed to use in vivo T1‐weighted Fast Low Angle Shot (FLASH) imaging to visualize and quantify LC MRI contrast in AD and PD and to determine the relationship between LC MRI contrast and cognition.MethodBaseline data from the DZNE Longitudinal Cognitive Impairment and Dementia (DELCODE) study comprising 48 healthy elderly adults, 27 individuals with subjective cognitive decline (SCD), 16 individuals with mild cognitive impairment (MCI), 11 individuals with AD together with 30 patients with idiopathic PD were analysed. All subjects were scanned at 3T using a 3D T1‐weighted FLASH sequence (0.75mm isotropic resolution whole brain acquisition). FLASH images were sinc interpolated and upsampled to 0.375mm3 resolution prior to manual segmentation of the LC. Median LC signal intensity was determined relative to reference regions delineated in the rostral pontomesencephalic area.ResultA significant decrease in LC MRI contrast in AD and PD was observed compared to healthy controls. However no significant decrease in LC MRI contrast was observed in SCD and MCI compared to healthy controls or between AD and PD patients. In AD, a linear regression analysis across groups (n=102), revealed a significant negative correlation between LC MRI contrast and performance in the backward digit span (DS)/total (DS) test. In PD, a significant positive correlation between LC MRI contrast and slower performance in the Trail Making Test (TMT)‐A and B, was observed.ConclusionThe results confirm that T1‐weighted FLASH imaging using 3 T MRI can identify substantial LC degeneration in vivo and is associated with impaired working memory and attention in AD and PD, respectively. Collectively these results indicate that in vivo LC imaging may help to track LC degeneration and understand the pathological underpinnings of cognitive dysfunction in neurodegenerative disease.
Tau pathology in posterior DMN is related to aberrant SN‐DMN network connectivity in atypical Alzheimer’s disease
Authors: Putcha Deepti , Eckbo Ryan , Touroutoglou Alexandra , Dickerson Brad C. , Collins Jessica A. 
Published: December 2020

AbstractBackgroundCircumscribed patterns of pathological tau propagation along functional networks have been observed in normal aging and amnestic Alzheimer’s disease (AD), including in two cognition‐relevant networks: the default mode network (DMN) and the salience network (SN). It remains unclear if atypical phenotypes of AD demonstrate a direct relationship between tau and functional connectivity within and between these networks.MethodTwenty‐six amyloid‐positive patients diagnosed with atypical phenotypes of AD (12 PCA, 10 lvPPA, and 4 dysexecutive; mean age = 66 years, 9M/17F) were examined with tau (18F‐AV‐1451) PET and resting state functional MRI (rs‐fMRI). Hub regions within the DMN and SN were defined from the literature within the bilateral posterior cingulate cortex (PCC) and anterior insula (aI), respectively. ROI‐to‐ROI connectivity was calculated to determine within‐ and between‐network connectivity. Bivariate correlation analyses were conducted to determine if the magnitude of partial volume corrected tau PET signal in each network’s hub region was related to the within‐network functional connectivity of the DMN and SN, as well as between the hub regions of the DMN and SN.ResultWe found that higher tau signal in bilateral PCC was associated with diminished DMN connectivity (PCC to posterior angular gyrus) in both hemispheres (left: r = ‐0.50, p = 0.009; right: r = ‐0.47, p = 0.01). We did not observe any relationship between tau and functional connectivity within the SN. Our novel observation was that higher tau signal in the PCC was associated with increased connectivity between the DMN and SN within both hemispheres (left: r = 0.55, p = 0.004; right: r = 0.47, p = 0.02), with some patients demonstrating pathologically positive functional connectivity between the DMN and SN.ConclusionOur findings support the posited relationship between tau pathology and aberrant functional network connectivity reported in aging and amnestic AD by demonstrating that higher tau burden within the PCC is related to fractured DMN connectivity and pathologically increased DMN‐SN connectivity in a group of non‐amnestic AD patients. These findings may help explain how tau deposition in key hub regions of the DMN bring about dysfunctional inter‐network connectivity with the SN, likely contributing to the cognitive and affective dysfunction observed across the clinical spectrum of AD.
Predicting future rates of tau accumulation on PET
Authors: Jack Clifford R. 
Published: December 2020

AbstractBackgroundOur objective was to identify variables available in a research setting that predict future rates of tau PET accumulation separately among individuals who were either cognitively unimpaired or cognitively impaired.MethodAll 337 participants in this study were enrolled in one of the three longitudinal cohort studies at the Mayo Clinic that include serial tau PET scanning. For inclusion a person must have had a baseline study visit with MRI, amyloid PET, and tau PET exams, had at least one follow‐up tau PET exam, and have met clinical criteria for membership in one of two clinical diagnostic groups ‐ cognitively unimpaired (n=203) or cognitively impaired (n=134, a combined group of participants with either mild cognitive impairment or dementia with Alzheimer clinical syndrome). A temporal lobe tau PET meta‐region of interest (ROI) was used in our primary analysis but we also examined four additional tau PET ROIs. Linear mixed effects models where used to estimate associations between age, sex, education, APOE genotype, amyloid and tau PET SUVR, cognitive performance, cortical thickness, and white matter hyperintensity volume at baseline, and the rate of subsequent tau PET accumulation. Log‐transformed tau PET SUVR was used as the response and rates were summarized as annual percent change.ResultIn the cognitively unimpaired group only higher baseline amyloid PET was a significant independent predictor (i.e. in a multivariable model) of higher tau accumulation rates in the temporal meta‐ROI (p<0.001). In the cognitively impaired group, younger age (p=0.02), higher baseline amyloid PET (p=0.05), APOE ε4 (p=0.05), and better cognitive performance (p=0.05) were significant independent predictors of higher tau accumulation rates in the temporal meta‐ROI.ConclusionWhile we examined many possible predictor variables, the main independent predictor of high tau PET accumulation rates in cognitively unimpaired persons was amyloidosis. In contrast, in cognitively impaired individuals imaging and clinical variables that are consistent with early onset Alzheimer’s disease phenotype (younger age, amyloidosis, higher tau, APOE, less severe cognitive impairment) were associated with higher rates of tau PET accumulation suggesting this may be a highly advantageous group in which to conduct clinical trials that target tau‐related mechanisms.
Optimizing the memory binding test for detection of aMCI and dementia
Authors: Mowrey Wenzhu , Lipton Richard B. , Katz Mindy J. , Ramratan Wendy S. , Loewenstein David A. , Buschke Herman 
Published: December 2020

AbstractBackgroundThe Memory Binding Test (MBT) Version 1 demonstrated good discriminative validity for distinguishing persons with dementia and amnestic mild cognitive impairment (aMCI) from cognitively normal elder controls (CN). Version 2 of the MBT test was developed to improve brevity, which is essential for screening. We aimed to compare these two versions in terms of cross‐sectional discriminative validity to distinguish A. aMCI vs. CN, B. aMCI and dementia vs. CN, and C. dementia vs. CN and aMCI.MethodVersion 1 and Version 2 (for differences see Table 1) of the MBT were administered to independent and systematically recruited samples between May 2003 and December 2007 (Age: 70+; Version 1: 20 dementia cases, 31 aMCI, 246 CN; Version 2: 13 dementia cases, 29 aMCI, 236 CN). Scores on the MBT indices were compared between the versions. The partial area under the receiver operating characteristic curve (ROC AUC) for specificities ≥ 0.70 was compared between indices and versions (Table 1). Specificities were compared between versions when the sensitivity values were comparable.ResultThe MBT indices were not significantly different between versions for the diagnosis groups of aMCI and dementia. In CN, Version 2 yielded higher scores on number of items Cued Recall for List 1 (CR‐L1), number of Pairs In the Paired condition (PIP), and number of Total Items recalled in the Paired condition (TIP) (14.8±1.5 vs. 14.4±1.7, 11.0±3.2 vs. 9.9±3.8, 26.3±4.0 vs. 24.9±5.0, respectively, p=0.005) and PIP and TIP remained higher (p=0.02) when adjusting for potential confounders of age, gender, education and global cognitive function. Partial AUC comparison shows that TIP was the optimal index for Version 1 and TIP partial AUCs were not significantly different between two versions (Figure 1, Table 2). The specificities were higher in Version 1 vs. Version 2 in Comparisons A and B, while the specificities were comparable in Comparison C (Table 3).ConclusionMBT Version 1 is better at distinguishing aMCI, or aMCI and dementia combined, from cognitively normal elderly. To distinguish dementia vs. cognitively normal elder controls and aMCI, Version 1 and Version 2 are comparable. We recommend using Version 1 for future studies.
Perceptions of research burden reported by study partners of longitudinal ADC cohort participants
Authors: Edwards Dorothy Farrar , Lingler Jennifer , Chin Erin , Gabel Matthew , Coble Dean W , Grill Josh D , Stark Susan 
Published: December 2020

AbstractBackgroundStudy partners are required for all ADC Clinical Core participants, they provide valuable information about cognitive and functional status of enrolled participants, which is essential for CDR ratings and documentation of perceived cognitive changes over time. Retention of participants and their SPs is essential for unbiased longitudinal data, yet little is known of SP attitudes and beliefs and how these attitudes influence missed visits or overall attrition. This mixed methods study identified SPs perceived barriers and facilitators related to participant retention in longitudinal ADC studiesMethodMethods: A 57 item survey with 2 open ended questions was administered by telephone to randomly selected study partners (N=210) from four NIA funded Alzheimer’s disease Centers. The Perceived Research Burden Assessment (PeRBA) was included in the survey. Respondents were 51% female, mean age was 72±8.6 ( 52‐92yrs), 92% were spouses. Response frequencies were computed for each item, open ended responses were transcribed, and thematically coded.ResultStudy partners report high levels of trust in medical researchers (88%), high levels of altruism they believe their participation is valuable (96%) and society benefits from their research participation (98%). Low levels of overall burden were associated with ADC participation. Most negative attitudes were associated with travel (14%), inconvenience reaching the research center (15%) and length of study visits (17%). They also reported that their last LP (18%) and memory testing (19%) visits were difficult, with physical pain (13%) and fatigue (16%) as most common post‐assessment problems. A substantial number (83%) had difficulty keeping track of different study procedures. Only 37% reported being invited to participate in additional ADC‐sponsored studies. Thematic analyses identified common concerns/suggestions across ADC sites including: more frequent feedback and information about study results, evidence‐based caregiving advice, more complete disclosure of individual findings, better coordination and communication around multiple study visits and high praise for research staff.ConclusionStudy partners are critical to longitudinal retention of ADC participants. SP loss accounts for a significant proportion of missed visits or outright attrition. Changing study partners contributes to greater variability in longitudinal data. Our findings emphasize the importance of attending to the concerns of study partners in retention programs.
Perceptions of research burden among participants in ADC cohorts
Authors: Lingler Jennifer , Coble Dean W , Bollinger Rebecca , Edwards Dorothy Farrar , Gabel Matthew , Grill Josh D , Knox Melissa , Stark Susan 
Published: December 2020

AbstractBackgroundThe burden of participating in research on Alzheimer’s disease and related disorders (ADRD) has been described as extending beyond the direct risks associated with research procedures to encompass the overall hassle of getting to and through study visits. The Perceived Research Burden Assessment (PeRBA) was designed to measure participants’ perceptions of the logistical (e.g., time commitment), psychological (e.g., intrusiveness of interview questions), and physical burden (e.g., perceived risk of injury) associated with enrollment in ADRD research. Initially validated using a pre‐enrollment version of PeRBA to assess the anticipated burden of a hypothetical research study, our team administered a post‐enrollment version of PeRBA to assess research burden as experienced by participants in longitudinal cohort studies of ADRD.MethodPeRBA interviews were administered by telephone to a random sample of 443 participants from the active cohorts at four NIA‐funded Alzheimer’s Disease Centers (ADCs; n=∼110 per site). Survey respondents were on average 73 years old, primarily Caucasian (79%), female (59%), and had been participating in UDS study visits for 5 years. Respondents were instructed to reflect on their most recent UDS study visit as they considered each of the 22 PeRBA items. Principal component (unrotated) factor analysis was performed using STATA 15.0 to estimate the factor structure and confirm the PeRBA burden dimension based on eigenvalues and the pattern of factor loadings.ResultThe factor analysis suggests a single factor solution, with PeRBA items loading constituent with a general perception of burden. Factor structure and fit were consistent across sites.ConclusionThese findings provide cross‐validation for prior research suggesting that the PeRBA is psychometrically valid measure of perceived research burden. Our finding of a single factor solution suggests that perceived research burden is a unidimensional construct and that use of the total PeRBA score is appropriate.
Perceived facilitators and barriers to continued enrollment in longitudinal studies of Alzheimer disease
Authors: Gabel Matthew , Coble Dean W , Bollinger Rebecca , Edwards Dorothy Farrar , Lingler Jennifer , Chin Erin , Grill Josh D , Stark Susan 
Published: December 2020

AbstractBackgroundRetention of study participants is critical to the success of longitudinal studies of Alzheimer Disease (AD). A comprehensive understanding of the factors that influence retention requires knowledge of what motivates study participants to continue to participate and of the perceived challenges of participation. We conducted a survey of current participants in Alzheimer Disease Centers (ADCs) to characterize their perceived facilitators and burdens of participating in longitudinal studies of AD.MethodA 57‐item interview battery with 2 open ended questions was administered by telephone to 443 randomly selected study participants from four NIA funded ADCs. Respondents were 59% female, mean age was 73±8.5 ( 49‐95 yrs), and the mean number of years enrolled was 5.1±3.5 ( 0‐13.5 yrs).ResultSurvey respondents showed strong altruistic motivation for participation. Almost all respondents (>90%) indicated they were motivated by a desire to advance AD research, to benefit society, and to benefit future generations of their families. In contrast, 5% of respondents identified money or gift cards as the reason they participate. Only a small minority of respondents registered complaints about study participation. The most common problems involved fatigue (12%) and the distance/inconvenience of travel to the study visit (11%). These response patterns were broadly consistent across gender, race, and age cohorts. Women and younger respondents were slightly more altruistic in motivation than men and older respondents. Also, African American respondents were more strongly motivated by personal benefit from the study and expressed greater concern about privacy of their personal information than other respondents. They also had lower trust in medical research.ConclusionRetention of participants and their consistent attendance at regular visits is vital to the quality of longitudinal studies of AD. Our results indicate that, while most participants surveyed indicate an altruistic commitment to the study of AD, the organization of study visits could be improved to facilitate participation. In particular, increasing the convenience of both attending and executing the study visit would address the most common complaints. Furthermore, the retention of African Americans requires sensitivity to their relatively low trust in medical research.
Resting state functional connectivity of financial capacity in mild cognitive impairment
Authors: Nowrangi Milap , Naaz Farah , Chen Liuyi , Outen John D. , Bakker Arnold , Rosenberg Paul B. 
Published: December 2020

AbstractBackgroundFinancial capacity (FC) is a complex, multi‐dimensional neurocognitive construct that is commonly impaired and disables older individuals with cognitive impairment but the underlying mechanisms are not well understood. Resting state functional connectivity was measured in individuals with mild cognitive impairment (MCI) and impaired FC compared to cognitively normal controls (NC) in order to identify relevant network components that may help drive future interventions.MethodResting state functional MRI scans were obtained from individuals with MCI (N = 17) and age, gender, and education matched NC (N = 15). Table 1. All participants completed the Financial Capacity Instrument (FCI) and neuropsychological assessment. Based on previously reported imaging findings in this population, the left Angular Gyrus (lAG) was used as the seed region in functional connectivity measurements. Connectivity beta values (Fisher transformed correlation coefficients) were calculated for each connection that showed significantly altered connectivity between control and MCI cases. A Pearson’s correlation was calculated between the connectivity beta values from relevant regions and cognitive measures.ResultA total of 26 brain regions showed significant increased functional connectivity (p <0.05 uncorrected) with the lAG in NC compared to MCI. Of these regions 14 were identified as relevant to higher‐level cognitive function and carried forward in the correlation analysis (Figure 1). Pearson’s correlation showed significant negative association between the FCI and increased connectivity with the right temporal fusiform cortex (rTFC, r = ‐0.455, p = 0.009); negative correlation between Clock drawing and increased connectivity with the intraparietal sulcus (r = ‐0.38, p = 0.03); positive correlation between Trails B and increased connectivity with postcentral gyrus (r = 0.39, p = 0.03) and left central operculum (r = 0.36, p = 0.04). Table 2.ConclusionThere is a significant correlation between a well‐validated measure of FC and increased functional connectivity between the lAG and the rTFC in controls compared to MCI. This novel finding suggests that integration of visuoperception, memory, and mathematical function is critical for FC. No other significant correlation between the lAG and rTFC was found with other tests of executive function or visuospatial cognition.
Cognitive symptoms in early postmenopausal women: Impact on estrogen‐sensitive cholinergic function
Authors: Newhouse Paul A. , Conley Alexander C. , Albert Kimberly , McDonald Brenna C. , Saykin Andrew J. , Dumas Julie 
Published: December 2020

AbstractBackgroundMenopause is associated with increasing cognitive complaints and older women are at increased risk of developing Alzheimer’s disease (AD) compared to men. One proposed reason for this reduced cognitive performance is the loss of estrogen following the menopause transition. Estradiol (E2) has been shown to be important for brain cholinergic functioning, the decline of which is linked to AD and cognitive decline. We have previously shown that E2 can attenuate the impact of cholinergic blockade on cognitive performance in normal postmenopausal women. To further explore these relationships, we examined the relationship of menopausal‐associated subjective cognitive complaints (mCC) with E2 effects on cholinergic functioning in postmenopausal women.Method56 early postmenopausal women (aged 50‐60 years) with differing levels of mCC completed subjective measures of cognitive complaints and postmenopausal symptoms as well as objective cognitive tests of verbal episodic and working memory and completed a 3‐month treatment regimen of either 1 mg oral 17β‐estradiol or placebo. Participants then completed four cholinergic antagonist drug challenges (mecamylamine, scopolamine, combined mecamylamine+scopolamine, or placebo) and completed cognitive performance tasks including working memory (N‐Back), episodic memory (selective reminding), attention (critical flicker fusion, spatial selective attention), and psychomotor tasks (choice reaction time).ResultAll participants performed worse under cholinergic challenge compared to placebo. Higher mCC was associated with greater anticholinergic‐induced impairment on working memory performance and reaction time, but not other measures. E2 treatment did not blunt anticholinergic blockade effects on performance compared to participants who received placebo. On both the CFF and CRT tasks, the performance‐impairing effects of anticholinergic drugs were increased in E2 treated participants compared to placebo treatment.ConclusionmCC was associated with greater negative effects of anticholinergic drugs on some cognitive domains. In this sample recruited for mCC, E2 treatment did not enhance cholinergic functioning as evidenced by the failure to blunt the effects of cholinergic blockade in contrast to our prior work in normal postmenopausal women. The development of significant menopause‐related cognitive symptoms may represent early brain functional and/or cholinergic changes that may indicate increased risk for cognitive decline and is not modifiable by E2 treatment.