bluuebunny/crossref_metadata_2025_split huggingface dataset:
Using the Everyday Cognition Scales (ECog), depression, and vascular risk to predict conversion to cognitive impairment in different ethnoracial groups
Authors: Chan Michelle L , Weakley Alyssa , Harvey Danielle J , Carsey Jane , Farias Sarah 
Published: February 2022

AbstractBackgroundOur previous work found that greater subjective cognitive concerns (SCC) at baseline was associated with increased risk of developing mild cognitive impairment (MCI) or dementia in Caucasians and African Americans, but not Hispanics. The present study examined whether medical co‐morbidities or depression may account for some of these differences.MethodsParticipants included 205 Caucasians, 101 African Americans, and 95 Hispanics, all cognitively normal at baseline, who are part of the University of California, Davis Alzheimer’s Disease Center longitudinal cohort. SCC was measured using the self‐reported Everyday Cognition Scales (ECog) Memory domain. Over an average of 4.7 years, 116 developed MCI or dementia. Associations with incident cognitive impairment were assessed using Cox proportional hazards models, adjusting for age and education. Models considered the interaction between race/ethnicity and the ECog score, as well as either depression (Geriatric Depression Scale) or vascular risk (proportion present out of hypercholesterolemia, diabetes, hypertension). Models were then run separately in each racial/ethnic group.ResultsIn models that included depression and vascular risk separately, there was a significant interaction (p<0.05) between racial/ethnic group and SCC, consistent with our earlier findings. GDS was not associated with progression for any racial/ethnic group (p>0.1), SCC was associated with progression in African Americans (HR=2.05, 95% CI=1.20, 3.50; p=0.009), but not Caucasians (p=0.08) or Hispanics (p=0.34). In contrast, vascular risk was marginally associated with progression in Hispanics (HR=3.4, 95% CI=0.98, 11.72; p=0.054), but not Caucasians (p=0.8) or African Americans (p=0.4). When accounting for vascular risk, SCC was associated with progression in Caucasians (HR=1.7, 95% CI=1.1, 2.6; p=0.01) and African Americans (HR=2.04, 95% CI=1.27, 3.26; p=0.003), but not Hispanics (p=0.4).ConclusionsResults suggest there are differences in the degree to which SCCs and vascular risk are associated with developing cognitive impairment across different ethnoracial groups. SCC was generally associated with incident impairment in Caucasians and African Americans, but not Hispanics. Medical co‐morbidities were more associated with incident impairment in Hispanics compared to Caucasians.
Modifiable determinants of physical functioning among LGBT older adults with cognitive impairment
Authors: Kim Hyun‐Jun , Fredriksen‐Goldsen Karen , Jung Hailey 
Published: February 2022

AbstractBackgroundHeightened risks of cognitive impairment are a critical health concern for lesbian, gay, bisexual, and transgender (LGBT) older adults. The physical and functional declines associated with cognitive impairment are known to increase risks of injury and decrease independent mobility.MethodGuided by the Health Equity Promotion Model, this study analyzed longitudinal data (T0 to T2, N=646) to examine risk and protective factors predicting changes in physical functioning over time among LGBT older adults with cognitive impairment.ResultAccording to the results of multilevel mixed models, social support, physical, recreational, and wellness activities, and nutrition were associated with improvement in physical functioning over two years while stigma contributed to decline in physical functioning.ConclusionLGBT older adults with cognitive impairment face unique challenges due to social stigma and isolation. The findings suggest that enhancing their access to community resources and their participations in physical, social, community, and recreational activities would improve their physical functioning.
Meta‐analysis of the associations of biomarkers of amyloid and tau with cognition in cognitively normal older adults
Authors: Ferreira‐Atuesta Carolina , Piendel Lydia A , Emerson Jacqueline M , Joshi Nandita , Hedden Trey 
Published: February 2022

AbstractBackgroundConflicting evidence exists on the in vivo relationship of amyloid and tau levels to cognition among cognitively normal older adults. We conducted a meta‐analysis of reported relationships of biomarkers of amyloid or tau levels with baseline and change in cognition in cognitively normal older adults.MethodWe performed a literature search that returned studies between 2005 and January 2021 for studies reporting a relationship between amyloid or tau biomarkers measured via PET ligands, CSF, or plasma assays, with episodic memory or global cognition. Effect sizes were obtained for each study and weighted by sample size. For studies examining the same cohort, we selected effect sizes from the largest sample size available for each relationship of interest.ResultOne hundred and seven studies (89% reporting cross sectional measures and 62% reporting longitudinal) representing 26968 adults (82% characterized with amyloid measures and 23% with tau) were included. Amyloid levels showed a significant correlation with baseline and longitudinal global cognition (r=0.05, p<0001; r=0.05, p=0.021, respectively), and with baseline episodic memory (r=0.05, p=0.001). Tau was significantly correlated with baseline and longitudinal global cognition (r=0.08, p=0.004; r=0.08, p=0.01, respectively), and with longitudinal episodic memory (r=0.02, p=0.04), whereas the interaction of amyloid and tau was significantly correlated only with baseline global cognition (r=0.09, p=0.024). The overall estimated correlation between amyloid and tau was r=0.17.ConclusionIn older adults with normal cognition, there is a very small but significant relationship between baseline global cognition and amyloid, tau, and their interactive effect. Episodic memory had a very small but significant relationship with amyloid at baseline and with tau longitudinally. These findings could help determine power estimations for future clinical trials evaluating cognition in asymptomatic older adults. Effect size and power estimations from this meta‐analysis may be limited by unmeasured variability among studies in the timing of biomarker measurement, differences in cognitive assessments, or other cohort‐specific differences.
Clinical outcomes of increased regional amyloid uptake in patients with subthreshold global amyloid levels
Authors: Kim Jaeho , Choe Yeongsim , Park Yuhyun , Kim Yeshin , Kim Junpyo , Seo Younghoon , Jang Hyemin , Kim Hee Jin , Na Duk L. , Cho Soo‐Jin , Moon Seung Hwan 
Published: February 2022

AbstractBackgroundAlthough the standardized uptake value ratio (SUVR) method is objective and simple, cut‐off optimization using global SUVR values may not reflect focal increased uptake in the cerebrum. The present study investigated clinical and neuroimaging characteristics according to regionally increased β‐amyloid (Aβ) uptake and global Aβ status.MethodWe recruited 973 patients with Alzheimer's disease ‐related cognitive impairment (ADCI). All patients underwent neuropsychological tests and 501 18F‐florbetaben (FBB) amyloid positron emission tomography (PET) and 472 18F‐flutemetamol (FMM) PET. Each PET scan was assessed in 10 regions (frontal, temporal, parietal, posterior cingulate, and striatum) by regional quantitative SUVR‐based cutoff values for each region using an iterative outlier approach.ResultA total of 64 (6.6%) subjects showed increased regional Aβ uptake with subthreshold global Aβ status [focal (+) and global (‐) Aβ group, F(+)G(‐) group]. The F(+)G(‐) group showed worse performance in memory impairment (P < 0.001) and greater hippocampal atrophy (P = 0.024) but not global cognition and cortical thickness, compared to those in the F(‐)G(‐). Participants with diffuse Aβ involvement in the whole region [diffuse (+) and global (+) Aβ group, D(+)G(+)] showed worse neuropsychological (P = 0.008‐0.042) and neuroimaging features (P <0.015) than those with focal Aβ involvement F(+)G(+).Conclusion] Our findings suggest that individuals show distinctive clinical outcomes according to regionally increased Aβ uptake and global Aβ status. Thus, clinicians should pay more attention to regional increased Aβ uptake in addition to global Aβ status.
Amyloid, but not tau, is associated with longitudinal change in white matter hyperintensities in a sample of cognitively normal older adults from the Baltimore Longitudinal Study of Aging
Authors: Shaikh Faysal , Resnick Susan M. , Bilgel Murat 
Published: February 2022

AbstractBackgroundWhite matter hyperintensities (WMH) are associated with a greater risk of developing dementia. Hallmark neuropathologies of Alzheimer’s disease (AD), namely, amyloid plaques and tau tangles, begin to aggregate in the brain prior to signs of cognitive impairment. To better understand the relationship between WMH and AD neuropathology in preclinical AD, we assessed via positron emission tomography (PET) and magnetic resonance imaging (MRI) if amyloid and tau are associated with the rate of change in WMH burden among cognitively normal older adults.Method89 cognitively normal participants (mean age at PET=76.7 years, 35 men) of the Baltimore Longitudinal Study on Aging underwent 3T fluid attenuated inversion recovery (FLAIR) MRI to assess global WMH burden, 11C‐Pittsburgh compound B PET to assess global amyloid status, and 18F‐flortaucipir PET to assess entorhinal cortex tau. 85 participants had additional FLAIR scan(s) prior to PET visit (mean follow‐up between first and last FLAIR=6.4 years, standard deviation=2.2 years). We assessed the associations of amyloid and tau with retrospective longitudinal WMH burden (in cm3) at and prior to PET scan via a linear mixed effects model (350 observations total). Global amyloid status, entorhinal cortex tau, and their interactions with time from PET were our explanatory variables; our model was adjusted for age at PET, sex, total white matter volume, APOE‐e4 allele carrier status, and vascular risk.ResultHigher cross‐sectional endpoint global WMH burden was associated with amyloid positivity (estimate=3.050, standard error [SE]=1.366, p=0.028), but not with entorhinal tau SUVR (estimate=−3.233, SE=4.301, p=0.456). Amyloid positivity was also associated with steeper increases in WMH burden in years preceding PET (estimate=0.277, SE=1.366, p=0.037), whereas entorhinal tau was not (estimate=−0.378, SE=0.408, p=0.354).ConclusionAmyloid, but not tau, is associated with greater global WMH volume and greater rates of global WMH volume change in our sample of cognitively normal older adults.
Quantifying perivascular space in Alzheimer's disease by MRI relaxometry
Authors: Zhou Liangdong , Nguyen Thanh D. , Wegiel Jarek , Li Yi 
Published: February 2022

AbstractBackgroundThe perivascular space (PVS) is a known key route of glymphatic clearance for the drainage of interstitial fluid and solutes such as soluble amyloid beta (Aβ) from the brain. Perivascular space dilation in aging could indicate abnormal protein accretion, such as Aβ accumulation. Recent studies indicate that dilation of PVS is associated with blocked cerebrospinal fluid (CSF) bulk flow, which is considered as free water. We propose to use MR T2 relaxometry‐based water compartment model for the quantification of free water in brain parenchyma and hence to infer the change of PVS.MethodWe filtered the 22 Aβ positive MCI subjects with three echo T2‐star data and amyloid PET from ADNI database. The three‐echo data was fitted to a two‐water compartment model (CSF and intro‐extracellular water), in which the water compartments were distinguished by the T2 relaxometry time. CSF fraction (CSFF) values were then extracted in the brain region masks generated from FreeSurfer. Mean CSFF for each subject was then calculated. The SUVr of cerebral cortex was used to evaluate brain amyloid load. Linear regression model between Aβ deposition and CSFF was built with age and gender controlled.ResultThe results from ADNI data show that CSFF is linearly related to the Aβ deposition in brain. Fig. 1 presents a map of CSFF and the amyloid PET for the same subject. Fig. 2 shows linear relationship (p<0.05) between CSFF and the SUVr in the cerebral cortex area.ConclusionThe relation between CSFF and amyloid load in brain cortex shows that CSFF could be a potential biomarker for the amyloid clearance. The CSFF map reflects the percentage of free water in total volume at the water molecular level and can sensitively detect subtle PVS change.
Communication during Covid‐19: Impacts of face coverings on people living with dementia
Authors: Jeong Tina Hyerim , Volkmer Anna , Jiang Jessica , Brotherhood Emilie V , Dobson Lucianne , Harding Emma , Suarez‐Gonzalez Aida , Crutch Sebastian J , Warren Jason D , Hardy Chris JD , Agustus Jennifer L 
Published: February 2022

AbstractBackgroundThe compulsory introduction of wearing face coverings and social distancing to curb the spread of Covid‐19 in the United Kingdom has reduced both the quality of auditory information and availability of visual and non‐verbal cues during conversations with others. This is likely to have a greater impact on efficiency and effectiveness of communication for people living with dementia and particularly those with a language‐led dementia: Primary Progressive Aphasia (PPA).MethodTwenty‐four people living with dementia (PLWD), 95 caregivers (on behalf of PLWD) and 38 healthy older controls anonymously reported their experiences of wearing face coverings and the associated impacts on communication via an online survey that ran between December 2020 and April 2021 (age ranges: PLWD 38‐90 years; controls 32‐100 years). The majority of questions were self‐reflective experiences compared to when not wearing face coverings. Mann‐Whitney U tests were used to compare Likert ratings for impact of wearing face coverings on aspects of speaking, listening and holding conversations between PLWD or diagnosis subgroups (27 PPA; 26 Frontotemporal Dementia, FTD; 29 Alzheimer’s disease, AD; 24 Posterior Cortical Atrophy, PCA) and the controls.ResultWearing a face covering made both speaking (80%) and listening (90%) more effortful for the majority of survey respondents and had a greater impact on people living with PPA. Overall PLWD were more likely to require help communicating and those with PPA relied more on non‐verbal strategies (e.g. body language or gestures) than when not wearing a face covering, compared to controls (p=0.001) and other diagnosis subgroups. People with PPA also experienced greater difficulty understanding across diverse everyday listening conditions and most aspects of conversation than controls (p<0.05). People with PCA (p=0.039) also had more difficulty knowing when it was their turn to speak and those with FTD had more difficulty speaking over others (p=0.032), compared to controls. The use of face coverings during the Covid‐19 pandemic also prevented more PLWD from taking part in activities than controls.ConclusionPLWD, and in particular those with a diagnosis of PPA, are particularly susceptible to the negative impacts of the use of face coverings on communication.
Impact of COVID pandemic on neuropsychiatric symptoms and caregiver distress in cognitively impaired older adults
Authors: Padala Prasad R , Gauss C Heath , McKinney Hannah N , House Samuel J , Padala Kalpana P 
Published: February 2022

AbstractBackgroundNeuropsychiatric symptoms (NPS) are cardinal symptoms of dementia. They are often associated with functional decline, poor quality of life, and caregiver burden. Anecdotal reports have suggested increase in NPS during the COVID pandemic. However, decreased time demands on the caregivers could be hypothesized to have improved relationships and indirectly NPS. There has been limited literature on whether NPS improved or worsened during the current pandemic. The current study examines the prevalence of NPS and changes in NPS profile during the pandemic. Loneliness, cognition, function, and caregiver distress were also studied.MethodsThe COVID Dementia study is an ongoing cross‐sectional study of community dwelling cognitively impaired older adults (N=102). Loneliness was assessed with the 3‐item loneliness questionnaire, cognition with the Tele‐Montreal Cognitive Assessment (T‐MoCA), and functional status with the Functional Activities Questionnaire (FAQ). Neuropsychiatry symptoms including severity and distress were collected using the Neuropsychiatric Inventory (NPI) and change during COVID was also recorded for each symptom.ResultsMean age was 73.0 (±8.0) years, 96.1% male, 42.2% rural, 75.2% Caucasian, and 24.8% non‐Caucasian. T‐MoCA and FAQ mean scores were 15.2 (±4.6) and 8.0 (±9.3), respectively. Loneliness was prevalent in majority of participants (53.5%). Mean loneliness score was 4.7 (±2.1). Mean NPI total severity and total distress were 7.5 (±6.5) and 10.9 (±8.8), respectively. Irritability and night‐time behavior were most frequently reported symptoms (45.7% each), followed by anxiety (45.3%), and agitation (41.1%).Majority of the participants reported worsening of neuropsychiatric symptoms during COVID (61.5%). Irritability, agitation, and anxiety was the cluster that was reported as most frequently worsened symptoms during the pandemic followed by depression and apathy cluster (Fig. 1). Among those that reported worsening of neuropsychiatric symptoms, 66.1% noted an increase in ≥ two symptoms.ConclusionsOlder adults with pre‐existent cognitive impairment may be at high risk for loneliness and worsening of neuropsychiatric symptoms during the COVID pandemic. Some NPS might worsen more frequently during the pandemic and need particular attention.
Amygdala tau pathology in preclinical autosomal dominant Alzheimer’s disease
Authors: Sanchez Justin S. , Martinez Jairo E. , Rubinstein Zoe B. , Baena Ana Y. , Vila‐Castelar Clara , Fox‐Fuller Joshua T. , Gatchel Jennifer R. , Ramirez‐Gomez Liliana A. , Aduen Paula , Guzman‐Velez Edmarie , Pluim Celina F. , Jacobs Heidi I.L. , Sperling Reisa A. , Johnson Keith A. , Lopera Francisco , Quiroz Yakeel T. 
Published: February 2022

AbstractBackgroundThe amygdala has been found to be pathologically affected in early stages of Alzheimer’s disease (AD), with particular amygdala subnuclei being especially vulnerable. We used in vivo positron emission tomography (PET) imaging to examine whether amygdala tau accumulation could be observed in cognitively unimpaired PSEN‐1 mutation carriers who carry an autosomal‐dominant mutation in the Presenilin‐1 (PSEN‐1) gene and are determined to develop dementia in their early 50s. We further aimed to investigate associations between amygdala tau, age, amyloid deposition, and cognition in mutation carriers and non‐carrier family members.MethodA total of 29 PSEN‐1 mutation carriers (M age = 37.4 +/‐ 5.8 years) and 35 age‐matched non‐carriers (M age = 35.9 +/‐ 5.8 years) were recruited from the Colombia‐Boston (COLBOS) Longitudinal Biomarker Study, which follows Colombian families with autosomal‐dominant AD. Participants underwent PET, using Pittsburgh Compound B to measure mean cortical amyloid‐β and Flortaucipir for regional tau, and episodic memory testing (CERAD Word List Learning). Amygdala subnuclei were automatically segmented with FreeSurfer7. Spearman correlations were used to examine associations among amygdala tau, age, mean amyloid‐β, and memory performance.ResultCompared to non‐carriers, cognitively unimpaired mutation carriers had greater tau accumulation in the amygdala (p<0.001). Unimpaired carriers had greater tau burden in amygdala compared to neocortical regions (vs. inferior temporal: t=2.3, p=0.03), suggesting early involvement of amygdala tau. Among amygdala subnuclei, basal and accessory basal nuclei had greater tau burden compared to the other subregions (vs. lateral nucleus: t=5.5, p<0.0001) in unimpaired carriers. Greater amygdala tau burden was associated with older age (r=0.649, p<0.0001), greater mean cortical amyloid (r=0.597, p=0.001) and worse memory performance (r=‐0.433, p= 0.019) in carriers. No significant associations were observed in the non‐carrier group.ConclusionAmygdala tau burden is associated with greater age, cortical amyloid burden, and worse memory in preclinical autosomal dominant Alzheimer’s disease. These results suggest that amygdala tau accumulation is evident in preclinical Alzheimer’s disease. Future studies should determine if amygdala tau (including subnuclei) can be used as an early indicator of Alzheimer’s disease progression. Longitudinal studies are needed to examine the associations between amygdala tau and onset of neuropsychiatric and behavioral symptoms.
Accounting for lack of representation in dementia research: Generalizing KHANDLE study findings on the prevalence of cognitive impairment to the California older population
Authors: Hayes‐Larson Eleanor , Mobley Taylor M. , Mungas Dan , Seamans Marissa J. , Glymour M. Maria , Gilsanz Paola , DeCarli Charles , Whitmer Rachel A. , Mayeda Elizabeth Rose 
Published: February 2022

AbstractIntroductionMost dementia studies are not population‐representative; statistical tools can be applied to samples to obtain critically‐needed population‐representative estimates, but are not yet widely used.MethodsWe pooled data from the Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE) study and the California Behavioral Risk Factor Surveillance System (CA‐BRFSS), a population‐representative study. Using weights accounting for sociodemographic/health differences between KHANDLE and CA‐BRFSS, we estimated cognitive impairment prevalence and age‐ and sex‐adjusted racial/ethnic inequalities in California adults 65+ without prior dementia diagnosis.ResultsAfter weighting KHANDLE, the estimated cognitive impairment prevalence in California was 20.3% (95% confidence interval 17.8–23.0); unweighted prevalence was 24.8% (23.1%–26.6%). Inequalities (larger prevalences) were observed among Black and Asian groups versus whites.DiscussionWe used a novel statistical approach to estimate population‐representative cognitive impairment prevalence and inequalities. Such statistical tools can help obtain population‐representative estimates from existing studies and inform efforts to reduce racial/ethnic disparities.
Mortality at 180‐days is affected by serum haptoglobin levels in septic patients with high magnitude serum high mobility group box‐1 levels
Authors: Mizuno Takayoshi , Eguchi Yutaka , Tsujita Yasuyuki , Imashuku Yasuhiko , Tabata Takahisa , Kitagawa Hirotoshi 
Published: February 2022

AimHigh mobility group box‐1 (HMGB1) is a lethal mediator of sepsis that binds to haptoglobin (Hp) and is associated with its prognosis. We investigated the effect of the combination of HMGB1 and Hp on sepsis prognosis.MethodsThis single‐center, retrospective study registered 78 patients with sepsis according to Sepsis‐3 criteria on day 1 of diagnosis from July 2016 to November 2018. We divided the patients into four groups according to the serum concentration of 6.2 ng/mL HMGB1 and the median value of Hp. The 180‐day mortality rates and cytokine concentrations of the low and high HMGB1 groups were compared.ResultsThere was no difference in the 180‐day mortality rate between the low Hp group and the high Hp group in the low HMGB1 group (P = 0.691). In the high HMGB1 group, a statistically significant difference was found between the low Hp group and the high Hp group (P = 0.002). In the high HMGB1 group, high Hp was associated with a better prognosis in univariate analysis (odds ratio, 0.131; 95% confidence interval [CI], 0.027–0.629; P = 0.011), and multivariate analysis (adjusted odds ratio, 0.086; 95% CI, 0.013–0.582; P = 0.009). In addition, in the high HMGB1 group, interleukin‐8 levels were significantly higher in the low Hp group than in the high Hp group (P = 0.004).ConclusionPatients with sepsis‐induced high serum HMGB1 levels and low serum Hp levels could have a poor long‐term prognosis.