bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of UDSNB 3.0 normative data with those developed in a diverse community cohort of older adults: Results from the Einstein Aging Study
Authors: Wang Cuiling , Katz Mindy J. , Chang Katherine H , Derby Carol A. , Lipton Richard B. , Rabin Laura 
Published: December 2021

AbstractBackgroundNormative data for the Uniform Data Set, Version 3 Neuropsychological Battery (UDSNB3.0), from the database of the University of Washington’s National Alzheimer’s Coordinating Center (NACC), are limited by an overrepresentation of white, female, and highly‐educated older adults. Original norms, based on >3000 cognitively normal participants from US Alzheimer’s Disease Centers (ADCs), did not divide the sample by race/ethnicity as the sample is 83% White (Weintraub et al., 2018). In the current study, we compare the originally reported UDS norms with those derived from a systematically‐recruited, community‐residing, racially/ethnically diverse cohort of older adults and provide expanded norms for Black‐Americans and Whites.MethodsThe Einstein Aging Study (EAS) is a longitudinal cohort of racially/ethnically diverse community‐dwelling individuals, ≥ age 70, who reside in the Bronx, NY. Analyses include data from 225 cognitively normal EAS participants and 1759 cognitively normal participants ≥ age 70 from the NACC database. Descriptive statistics are in Table 1. Linear regression models were used to examine the effects of demographic factors—including sex, age, education, and further including race—on UDSNB3.0 test performance in the two samples and to develop demographically adjusted z‐scores for the EAS cohort.ResultsIn both EAS and NACC samples, higher scores were observed for those with more years of education. Both samples demonstrated lower scores for non‐Hispanic Blacks and other racial/ethnic groups compared to non‐Hispanic Whites (Table 2). After accounting for sex, age, education, and race, mean performance was lower in the EAS sample compared to that of NACC across neurocognitive domains, including memory, visuospatial skills, attention, language, processing speed, and executive function (Tables 3‐4).ConclusionRacial differences in UDSNB3.0 tests were observed in both EAS and NACC samples. These differences between the UDSNB 3.0 normative data and the EAS sample, after adjusting for age, sex, education, and race, suggest that normative data from samples of optimally healthy, well‐educated individuals are not generalizable to those in diverse, urban communities. Furthermore, results suggest a need for local norms for community‐dwelling, racially/ethnically diverse cohorts to improve diagnostic accuracy and the ability to distinguish cognitive impairment from healthy cognitive aging.
Metabolic and cerebrovascular effects of gemfibrozil treatment: A randomized, placebo‐controlled, double‐blind, phase II clinical trial for dementia prevention
Authors: Jicha Gregory A , Kryscio Richard J , Nelson Peter T 
Published: December 2021

AbstractBackground“Fibrates” (PPAR‐alpha agonists) are lipid lowering agents that are widely known to improve metabolic parameters and potentially reduce cerebrovascular (CVD) disease burden. We conducted a parallel‐design, double‐blind, placebo‐controlled clinical trial of gemfibrozil targeting predementia AD (NCT02045056). An administrative supplement funded by the NIH/NIA allowed us to evaluate metabolic and CVD outcomes that may contribute to mixed AD‐CVD cognitive decline.MethodPatients with prodromal AD (CDR 0‐0.5) were randomized to receive gemfibrozil (600 mg twice daily) or placebo for 48 weeks. Metabolic and CVD endpoints included: 1) metabolic parameters including plasma glucose, HgbA1c, cholesterol, triglyceride levels, and inflammatory plasma biomarker profiles and 2) MRI imaging biomarkers including white matter hyperintensity (WMH) volumes, DTI, and ASL measures.ResultPrimary outcomes of the study reported previously include an excellent safety profile, CNS penetration, as well as trends for reducing Ab42 levels (0=0.063), hippocampal atrophy (p=0.15), and decline on the CANS‐MCI cognitive battery (MMTM p<0.01). Metabolic and cerebrovascular effects of gemfibrozil treatment included significant improvements in plasma glucose (p<0.001), lipid levels (p<0.001), and trends in CVD imaging biomarkers including reductions in WMH volumes (p=0.33), accompanied by ASL perfusion increases in the dorsolateral prefrontal cortex (p=0.13), hippocampus (p=0.10) and posterior cingulate cortex (p=0.16). Attenuation of reductions in the anti‐inflammatory cytokine IL‐13 (p<0.05) and increases in proinflammatory TNFa (p=0.08) were evident in the treatment group.ConclusionThe overlap in disease mechanisms and possible therapeutics for prevention of dementia caused by AD and or CVD is remarkable. These pathologies frequently coexist in the aging population and appear to act additively as well as synergistically, It is quite possible that the beneficial effects seen on cognitive outcome measures in this study might be more related to metabolic and CVD influences than on the direct effects influencing AD pathways that were the target of this clinical intervention. Strong consideration of incorporating metabolic and CVD outcomes in AD trials may help us disentangle the conundrum of risks and treatments for both CVD and AD that are the leading causes of dementia worldwide today.
TMS‐EEG as a measure of cortical hyperexcitability in motor and parietal cortex in Alzheimer’s disease: A pilot study
Authors: Buss Stephanie S. , Ross Jessica , Hagan Brenna , Press Daniel Z. , Shafi Mouhsin 
Published: December 2021

AbstractBackgroundPatients with Alzheimer’s disease (AD) have abnormally high cortical excitability, with an increased risk of seizures and epileptiform discharges. Transcranial magnetic stimulation with electroencephalography (TMS‐EEG) can noninvasively measure cortical excitability in local brain regions, and has shown increased excitability in motor cortex in AD. However, practical applications of TMS‐EEG measures are currently limited by a dearth of data from brain regions involved early‐on in AD, such as the parietal cortex. This pilot study investigated the feasibility of using TMS‐EEG to compare "Excitability Gain" across multiple brain regions in AD.MethodThree biomarker‐confirmed AD participants (mean age 71, 1 female) and 4 healthy control participants (HC, mean age 68, 2 female) enrolled in this pilot study. Single‐pulse TMS stimulation was applied to left primary motor cortex (M1) and inferior parietal cortex (IPL), with 120 pulses given at both 120% and 135% resting motor threshold (RMT). We assessed tolerability of this protocol. TMS‐evoked potentials (TEPs) were measured as the average EEG response after a TMS pulse. The percent change in TEP between the two stimulation intensities was calculated (TEP Excitability Gain, %change). A power calculation for two sample means was performed to determine the number of subjects needed to demonstrate a between‐group difference in IPL excitability.ResultThe procedure was well‐tolerated; one HC participant complained of a mild positional neck discomfort. In HCs, TEP Excitability Gain was 12 (±19 SD) percent in M1, and ‐5 (±12 SD) percent in IPL. In AD participants, TEP Excitability Gain was 39 (±50 SD) percent in M1, and 31 (±31 SD) percent in IPL (Figure 1). Assuming a SD of 31 for IPL stimulation, a sample size of 13 in each group would have a >80% power to detect a between‐group difference of 36% in TEP Excitability Gain with an alpha of 0.05.ConclusionTMS‐EEG measures of "Excitability Gain" are feasible in AD participants. A sample size of 13 in each group will be required to test for a between‐group difference of cortical excitability in the parietal lobe. TMS‐EEG may be a useful tool to measure cortical excitability across multiple brain regions in AD.
Brainwaves correlate with senior moments in preclinical older adults: Towards a cognitive screening protocol using a wireless device
Authors: Jiang Yang , Wang Baoxi , Borhani Soheil , Gottschalk Karah E. , Kelly Margaret , Zhao Xiaopeng , Jicha Gregory A. 
Published: December 2021

AbstractBackgroundWe recently reported longitudinal findings that specific frontal memory‐related signatures in cognitively intact older adults, who later (on average 5 years after baseline) were diagnosed as mild cognitively impaired (MCI), had already shown left‐frontal patterns of MCI patients. Older adults who did not show the MCI‐patterns remained normal ten years post baseline testing (Jiang et al. 2021). Here we test the hypothesis that left frontal MCI‐like brainwaves are associated with online poor and slowed memory retrievals (senior moments).MethodTraditional scalp electroencephalogram (EEG) headsets (64‐ or 32 channels), typically used in the research laboratory, are limited for large‐scale clinical and community screening. Using a clinical‐friendly protocol (15‐min) with a wireless headset (eMotiv), we recorded (EEG) during both resting state (eyes‐closed and eyes‐open) and during a working memory task in 43 healthy older adults (median age 68; 23 females) in a clinical setting in central Kentucky.Result“Senior moments” were time intervals of 1‐2 seconds, during which participants’ memory performance dipped, with slower reaction times and less accuracy. Even for trials with accurate memory retrieval, we found that longer reaction times were associated with MCI‐like signatures in left‐frontal sites, compared to trials for which retrieval was both accurate and fast. We divided the memory‐related brainwaves of individuals who were normal cognition (NC) into NC‐like and MCI‐like patterns. We found that trials with MCI‐like patterns were associated with moments of poorer memory performance.ConclusionOur results suggest that the "senior moments" are MCI‐like brain moments. MCI‐like brainwave patterns are mixed with normal brain patterns in a cognitively normal older individual. Our short protocol using a wearable and wireless headset during resting‐state and a working memory task is a real‐time, sensitive, noninvasive, quick, and affordable pre‐screening tool for predicting cognitive decline in a clinical setting.
Visuospatial impairment in logopenic progressive aphasia: Why do we not “see” it?
Authors: Pudumjee Shehroo , Martin Peter R , Bailey Kimberly , Caves Courtney , Sharp Blair , Graff‐Radford Jonathan , Duffy Joseph R , Clark Heather M , Botha Hugo , Josephs Keith A , Whitwell Jennifer L , Machulda Mary M. 
Published: December 2021

AbstractBackgroundLogopenic progressive aphasia (LPA) and posterior cortical atrophy (PCA) have distinct patterns of hypometabolism and atrophy. However, these clinical syndromes overlap: visuospatial impairment has been documented in LPA and aphasia in PCA. Rey‐Osterrieth Complex Figure – Copy (Rey‐O Copy) performance is correlated with parietal‐occipital atrophy in LPA. We explore visuospatial impairment on the Rey‐O Copy in LPA and PCA with the Mayo Older Americans Normative Studies (MOANS; which uses Meyers & Meyers criteria) and the Boston Qualitative Scoring System (BQSS). We also examine the proportion of visuospatial impairment in LPA, an under‐appreciated phenomenon, compared to PCA wherein it is fundamental.MethodPatients with LPA (n=25) or PCA (n=23) were recruited by the Neurodegenerative Research Group. Patients underwent comprehensive neuropsychological testing (including Rey‐O Copy) at baseline visit. Cut‐offs of T‐score=40 (BQSS) or scaled score=7 (MOANS) were used based on normative data. Proportions of patients with low performance were examined across LPA and PCA groups. Individual logistic regressions and AUROC analyses were then conducted to quantify differences in visuospatial impairment in LPA and PCA with both scoring systems. Identical analyses were conducted using raw scores corrected for age and sex, to avoid confounds of adjustments in normative data.ResultLPA and PCA groups were comparable on age, sex, and disease duration (LPA Median = 2.7 years, IQR=1.9‐3.5; PCA Median = 3.6 years, IQR=1.5‐4.9); p=.823). Surprisingly, 52‐72% of LPA participants demonstrated impaired performance across scoring systems, relative to 96% of the PCA group identified by both scoring systems. Odds ratios (OR) for the Rey‐O Copy MOANS (OR = 1.59; p=.008) and BQSS Copy Presence and Accuracy index (CPA; OR = 1.13, p=.002) were significant, persisting for age‐ and sex‐ controlled raw scores, suggesting the odds of a PCA diagnosis increased with decrement on Rey‐O Copy. AUROC values ranged from 0.77 to 0.88 across these indices.ConclusionA substantial number of LPA participants showed visuospatial impairment, despite initial primary language complaints. Differentiation of diagnostic groups by the Rey‐O is likely underscored by relatively uniform, profound, visuospatial impairment in PCA with more variability in LPA. However, the degree of visuospatial impairment overlaps remarkably across diagnoses.
Characterizing the phenomenology of anxiety in older adults with subjective cognitive decline
Authors: Mah Linda , Murari Geetanjali , Vandermorris Susan , Verhoeff Nicolaas Paul L.G. , Herrmann Nathan 
Published: December 2021

AbstractBackgroundSubjective cognitive decline (SCD), defined as perception of memory or other cognitive decline with normal test performance, is conceptualized as a preclinical stage of Alzheimer’s disease. Formulations of SCD typically include presence of worry or concern regarding the perceived cognitive decline. Accordingly, SCD is associated with anxiety, but its underlying etiology remains unclear. In the current study, we compared mood, anxiety, and personality amongst SCD, mild cognitive impairment (MCI), and cognitively unimpaired (CU) older adults to characterize anxiety in SCD.Methods146 older adults received psychiatric/medical assessments, self‐report measures of subjective memory, and neuropsychological (NP) tests to establish diagnosis. MCI [n=33,17F, age 72.3(SD6.7)] had subjective memory/other cognitive complaints, impaired NP performance, and functional independence. SCD [n=71,49F, age 71.1(SD6.3)] endorsed subjective memory decline with worry and normal NP performance. CU [n=42, 27F, age 70.6(SD6.8)] had normal NP performance and absence of subjective memory decline with worry. Participants were free of lifetime history of psychiatric illness and neurological conditions. They completed the State Trait Anxiety Inventory (STAI), NEO Five‐Factor Inventory (NEO‐FFI) which includes neuroticism, Health Anxiety Inventory (HAI), and Geriatric Depression Scale (GDS). Multivariate ANOVA was used to examine group differences, followed by post hoc comparisons with Sidak correction.ResultsGroups differed in STAI‐trait, NEO‐FFI neuroticism, HAI, and GDS [F(2,143)=5.26, P=.006; F(2,143)=3.26, P=.041; F(2,143)=4.61, P=.011; F(2,143)=7.66, P=.046, respectively]. Relative to CU, STAI‐trait and HAI scores were elevated in SCD and MCI (P’s<.05). NEO‐FFI neuroticism was higher in SCD compared to CU (P=.024). No differences between SCD and MCI were detected on any measure. Differences in GDS scores did not survive Sidak correction.ConclusionsAnxiety symptoms in SCD without lifetime history of psychiatric illness are best conceptualized as neuroticism, a personality trait that increases proneness to negative affect. Based on non‐elevated levels of state anxiety and depression, anxiety in SCD does not appear to represent an emotional reaction to cognitive decline nor epiphenomena of subclinical depression. Health anxiety, or belief that one has a serious illness, was comparable in SCD and MCI. Future research is needed to clarify the role of neuroticism and its links with subjective and objective memory in SCD.
Towards a universal cortical tau sampling mask
Authors: Dore Vincent , Bohorquez Sandra Sanabria , Leuzy Antoine , Shimada Hitoshi , Bullich Santiago , Bourgeat Pierrick , Burnham Samantha C , Huang Kun , Krishnadas Natasha , Fripp Jurgen , Takado Yuhei , Stephens Andrew W , Weimer Robby , Rowe Christopher C , Higuchi Makoto , Hansson Oskar , Villemagne Victor L 
Published: December 2021

AbstractBackgroundThe introduction of the AT(N) framework raised several issues in regards to the definition of T+. What brain regions should be sampled? Based on one or on multiple tracers? In this work, we developed a “universal” cortical tau mask for the AD continuum derived from all the major tau ligands. This “universal” cortical mask will serve as the common tau area for all tracers over which several different regional sampling VOI or composites can be then applied. Guaranteeing sampling of the same common regions is the first step to develop a common scale for all tau tracers: the CenTauR.Method464 participants underwent tau scans with either 18F‐AV1451 (CN=54/AD=24), 18F‐MK6240 (CN=157/AD=22), 18F‐PI2620 (CN=10/AD=21), 18F‐PM‐PBB3 (CN=30/AD=28), 18F‐GTP1 (CN=15/AD=38) or 18F‐RO948 (CN=35/AD=30). All CN were Aß‐ and all AD were Aß+. The tau scans were spatially normalized using CapAIBL and the cerebellar cortex was used as reference region. For each tracer, a difference image between the means of the Aß‐ CN and Aß+ AD patients was generated. Difference images were subsequently thresholded at 1/3 of the difference between Aß‐ CN and Aß+ AD in the inferior temporal lobe. A single tau specific mask was then constructed from the intersection of all the specific tau tracer masks.A MRI‐derived grey matter mask at PET resolution was applied to the composite mask only sampling grey matter regions. Finally, the mask was mirrored and fused to remove the hemispherical asymmetry of tau pathology. Agreement between masks was assessed by dice‐scores.ResultVisually, all the tracer‐specific masks appeared very similar. None of the known off‐target binding regions were discernible in the resulting masks (Figure 1). There was good agreement between all masks, with dice‐scores of 0.60 and 0.66 for cortical regions.ConclusionWe constructed an “universal” tau mask for the AD continuum based on all the commonly used tau tracers aiming at standardizing tau sampling and quantification across tracers and across centres. The “universal” tau mask demarcates a tau specific space that can then be sub‐segmented into smaller regions to focus on specific areas or composite regions that might better capture early tau deposition and spreading.
Longitudinal characterization of mild cognitive impairment and dementia in World Trade Center responders at midlife
Authors: Clouston Sean A.P. , Mann Frank P , Diminich Erica D , Kritikos Minos , Pellecchia Alison , Mejia‐Santiago Stephanie , Carr Melissa , Kotov Roman , Gandy Samuel , Sano Mary , Bromet Evelyn , Luft Benjamin J 
Published: December 2021

AbstractBackgroundThough the Montreal Cognitive Assessment (MoCA) is validated for cross‐sectional assessment, there is limited guidance as to methods for reliably identifying incident cases of Mild Cognitive Impairment (MCI) and dementia. The goal of this study was to examine characteristics of individuals identified as having MCI and dementia using different diagnostic routines.MethodsWorld Trade Center (WTC) responders are a unique population, not only because of the historic significance of the traumatic exposures many endured while onsite following the terrorist attacks in New York City on 9/11/2001 but also given responders participation in a long‐term monitoring program established by the Centers for Disease Control (CDC) in 2002 to monitor the long‐term effects of WTC exposures on health outcomes. Since 2014, we have administered the MoCA to responders over at least three assessments (n=2,370). The MoCA was administered by trained research staff; alternate versions were used to account for learning. Seven diagnostic routines were examined that variably examined adjusting for learning, objective evidence of functional limitations, and cognitive decline to identify one with the least variability in outcome. Stability of diagnostic outcome was the primary outcome. Follow‐up studies in subsets of the population included a detailed computer‐assisted neuropsychological examination, measures of physical functional limitations, a cross‐sectional sample of plasma based biomarkers measured using Simoa (e.g., b‐Amyloid1‐40, b‐Amyloid1‐42, Total‐Tau, Glial Fibrillary Acidic Protein, and Neurofilament‐Light), a cross‐sectional assessment of cortical thickness, and a self‐reported version of the Mild Behavioral Checklist.Results8.0% of responders were male, 4.3% were Black, and 7.7% were Hispanic. The mean age at initial MoCA assessment was 52.6 years old (SD=8.1). There was enormous variability in longitudinal stability in MCI and dementia diagnostic outcomes between different longitudinal diagnostic routines (Spearman’s r=0.22‐0.86). Though domain‐specific sub‐scales with high internal consistency (a=0.92‐0.97) were available, the most stable definition relied on MoCA scores adjusted for learning and expected within‐person test‐retest score distributions. MCI and dementia identified using all diagnostic routines were variably associated poorer cognitive functioning and with biomarkers.ConclusionThis study gives guidance about differences between methods relying on the MoCA to longitudinally screen WTC responders for MCI and dementia at midlife.
Changes in wall thickness of retinal arterioles as a surrogate marker of intracranial vascular pathology
Authors: Abdelhak Ahmed , Solomon Isaac , Saias Alexandra , Montes Shivany Condor , Cordano Christian , Asken Breton , Fonseca Corrina , Oertel Frederike Cosima , Arfanakis Konstantinos , Staffaroni Adam M. , Geschwind Michael , Elahi Fanny M. , Green Ari J. 
Published: December 2021

AbstractBackgroundMicrovascular injury is a significant contributor to cognitive impairment. Conventional neuroimaging is inadequate for assessing microvascular changes in the brain. Intensity‐based Retinal Arteriolar Visualization in OCT (I‐bRAVO) is a novel method that enables rapid, direct and non‐invasive visualization of retinal arterioles using standard optical coherence tomography images. We aimed to assess retinal microvascular changes using I‐bRAVO and compare it to measures of arteriolosclerosis, white and grey matter damage, and cognitive function.MethodWe included 500 eyes from 250 subjects with sporadic (n=91) and genetic (i.e., Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy, n=21) cerebral small vessel diseases (CSVD), non‐vascular neurodegenerative diseases (NVND, n=113), and healthy controls (HC, n=25). Mean Wall Thickness (MWT) and Wall to Lumen Ratio (WLR) were analyzed in association with imaging and cognitive markers of vascular pathology, including novel imaging classifier of brain arteriolosclerosis (ARTS), MRI markers of white matter injury (Fazekas scale), and grey and white matter atrophy, as well as the Uniform Data Set (v3.0) executive function (UDS3‐EF) score. Linear mixed‐effect models with subject‐specific intercepts were fitted using restricted maximum likelihood estimation.ResultARTS score correlated with MWT (ρ =0.44, P<0.001) and WLR (ρ=0.48, P<0.001). MWT and WLR were higher in CSVD (MWT: 28.18µm, WLR: 0.30) compared with NVND (MWT: 26.72µm, WLR: 0.29) and HC (MWT: 25.17µm, WLR: 0.25) (P<0.001). MWT and WLR were positively associated with superficial white matter disease burden (B= 0.07, 95% CI [0.05 – 0.1], and 5.63 [4.03 – 7.22], respectively, P<0.0001). A similar association was observed between MWT, WLR and deep white matter lesion load. WLR correlated inversely with grey (ρ =0.40, P<0.05) and white matter volume (ρ =0.48, P<0.01) in subjects with vascular cognitive impairment. WLR differentiated cognitively healthy individuals with vascular white matter lesions from those without (AUC= 0.81, P<0.001) with 94% specificity (cutoff value: 0.275). In asymptomatic CSVD, higher WLR was associated with a lower age‐, sex‐ and education‐adjusted UDS3‐EF (β=‐3.1 [‐6.3 – ‐0.01], P<0.05).ConclusionWe describe a rapid, inexpensive novel technique for assessing retinal arterioles as a surrogate marker for intracranial vascular pathology and as a tool for early recognition of presymptomatic CSVD.