bluuebunny/crossref_metadata_2025_split huggingface dataset:
Determinants of polypharmacy in patients with behavioral and psychological symptoms of dementia
Authors: Zarei Shadi , Choudhury Samira , Burhan Amer M. , Chu Li , Colman Sarah , Derkach Peter , Elmi Sarah , Hussain Maria , Ismail Zahinoor , Zarei Shadi , Nair Vasavan , Rej Soham , Rostas Aviva , Rajji Tarek K. , Streiner David , Kumar Sanjeev ,   StaN Study Group
Published: December 2021

AbstractBackgroundPolypharmacy is common in patients with dementia and is associated with several adverse effects. Factors associated with polypharmacy in patients with behavioral and psychological symptoms of dementia (BPSD) are unclear. This study examined the factors associated with general and psychotropic polypharmacy in patients with BPSD.MethodBaseline data was obtained from the Standardizing Care for Neuropsychiatric Symptoms and Quality of Life in Dementia (StaN) study, a multisite trial currently underway in Canada at long‐term care and inpatient sites. The Cohen‐Mansfield Agitation Inventory (CMAI) was used to assess agitation and aggression and Cumulative Illness Rating Scale for Geriatrics (CIRS‐G) was used to assess medical burden. General polypharmacy was defined as concomitant use of five or more scheduled medications of any kind, and psychotropic polypharmacy was defined as concomitant use of two or more scheduled psychotropic medications. Correlation, and linear and logistic regressions were performed to investigate the associations of agitation/aggression and polypharmacy.Result120 participants were enrolled [50.4% female; mean (SD) age= 80.25 (9.75) years]. 80.2% of participants had general polypharmacy and 56.2% had psychotropic polypharmacy. Total number of medications was positively correlated with CIRS_G (Spearman's r = 0.28, p = 0.002). In linear regression models, CMAI‐frequency (R2 = 0.137, p = 0.003, B = 0.269, p = 0.003) and CMAI‐disruptiveness (R2 = 0.136, p = 0.003, B = 0.268, p = 0.004) were significant predictors, whereas age, current psychiatric diagnosis and setting (inpatient versus long‐term) did not predict the number of psychotropics. Similarly in logistic regression models, CMAI‐frequency (R2 = 0.142, p = 0.002, Wald = 6.93, p = 0.008) and CMAI‐disruptiveness (R2 = 0.141, p = 0.002, Wald = 6.86, p = 0.009) were significant predictors, whereas age, current psychiatric diagnosis and setting did not predict psychotropic polypharmacy.ConclusionAs expected, medical burden was positively correlated with general medication use. On the other hand, BPSD (agitation and aggression) were associated with total number of psychotropic medications, rather than psychiatric morbidity, age or setting. Improving the management of agitation/aggression might be an important factor in addressing polypharmacy in patients with BPSD.
Pattern separation and pattern completion for human face identity recognition in prodromal Alzheimer’s disease
Authors: Quenon Lisa , Rossion Bruno , Woodard John L. , Hanseeuw Bernard J , Dricot Laurence , Lhommel Renaud , Ivanoiu Adrian 
Published: December 2021

AbstractBackgroundThe integrity of face identity recognition (FIR) in prodromal Alzheimer’s disease (prAD) is inconsistent in the literature, and the cognitive processes underpinning a potential impairment remain elusive. The concepts of pattern separation (PS) and pattern completion (PC) offer an interesting insight in this respect, since efficient FIR implies that facial identities are stored in at least partly distinct representations (corresponding to a PS process) and to fill‐in the currently perceived facial pattern based on these mnemonic representations (corresponding to the PC process). The goal of our study was therefore to investigate FIR in prAD patients with a PC and PS paradigm. In addition, we aimed to verify that prAD patients were able to individuate faces in a task that does not involve any long‐term memory component.MethodThirty‐two healthy older participants and 17 prAD patients were familiarized with 40 facial identities, through a picture‐matching task (Fig. 1.A). Participants then performed a forced‐choice recognition task aiming at assessing and strengthening the memory encoding of these 40 faces (Fig. 1.B). They then underwent separate yes/no recognition tasks involving parametrically controlled blurred or morphed faces (Fig. 2), designed to solicit PC and PS processes respectively (Fig. 1.C‐D). Finally, in two separate discrimination tasks (Fig. 1.E‐F), participants were instructed to determine whether two simultaneously displayed faces were identical or not. These discrimination tasks included the blurred and morphed faces displayed in the PC and PS recognition tasks respectively.ResultsprAD patients showed significantly lower performance than controls in both the PC and PS recognition tasks (Fig. 3). However, this group difference was not significant when the recognition accuracy index for the non‐manipulated faces (not blurred nor morphed) displayed in these tasks was included as a covariate. In addition, group differences were unexpectedly found for the familiarization and discrimination tasks.ConclusionOur study failed to highlight specific PC or PS deficits in prAD patients. However, it showed that prAD patients performed poorly on tasks that required comparing and matching simultaneously presented facial patterns, in the absence of any long‐term memory component. Future research should investigate whether this impairment could represent an early cognitive marker of AD that could be easily assessed in clinical practice.
Reduction of risk of development of Alzheimer’s disease and related dementias in patients with type 2 diabetes by drugs to treat hyperglycemia
Authors: Rodgers Kathleen E , Torrandell‐Haro Georgina , Branigan Gregory L , Brinton Roberta Diaz 
Published: December 2021

AbstractBackgroundAlzheimer’s Disease and Related Dementias (ADRD) are progressive neurodegenerative disorders that manifest in reduced cognition, executive function and memory impairments. Type 2 Diabetes (T2D) is suggested to be a risk factor for the development of ADRD. In this study, we evaluated the effects of anti‐hyperglycemic medications (HM) to treat hyperglycemia in T2D patients on the incidence of newly diagnosed ADRD.MethodUsing a retrospective analysis of healthcare claims dataset (Mariner 30), patients receiving HM for T2D treatment were identified and survival analysis, stratified by individual therapeutics, was used to determine the association between HM exposure and diagnosis of ADRD. A propensity score approach was used to minimize measured and unmeasured selection bias.ResultIn this cohort study of propensity score matched T2D patients over the age of 45, HM exposure was associated with decrease in diagnosis of ADRD, most specifically AD (RR, 0.61; 95% CI, 0.59‐0.62; P <0.001), Vascular Dementia (RR, 0.72; 95% CI, 0.69‐0.74; P < 0.001) and Dementia (RR, 0.65; 95% CI, 0.64‐0.66; P < 0.001). Patients that did not use HM were more likely to develop an ADRD. The protection by the use of HM was more pronounced after propensity score matching comorbidities significantly correlated with the assignment to HM treatment. Metformin was the most protective and insulin was the least protective compared to patients not taking any HM. The differences between these therapies was not due to age, gender or Charleston Comorbidity Index.ConclusionAfter controlling for age, gender and comorbidities, the use of HM in patients with T2D protected against the development of ADRD.
Ranking qualitative and timing‐based verbal fluency scores as predictors of incident cognitive impairment
Authors: Bushnell Justin , Svaldi Diana , Ayers Matthew , Gao Sujuan , Unverzagt Fredrick , Gaizo John Del , Wadley Virginia G , Kennedy Richard E , Goñi Joaquín , Clark David G. 
Published: December 2021

AbstractBackgroundVerbal fluency tasks are a valuable tool for neuropsychological assessment of cognitive impairment. In recent decades, researchers have proposed qualitative scores, such as clustering and switching, to index cognitive processes underlying fluency. However, the best approach to computing these scores is not clear, and no study addresses the handling of erroneous utterances.MethodWe transcribed animals and letter F fluency recordings on 703 cases of ICI and matched controls from the REGARDS study, amending each transcription with word timings. We then calculated clustering and switching scores with three methods described in the literature and new scores indexing speed of switch and edge transitions. After fitting a base model with only counts of valid words, perseverations, and intrusions, we fit a series of logistic regression models adding either clustering and switching scores or switch and edge speed scores, ranking the models with Watanabe‐Akaike Information Criterion.ResultsFor animal fluency, we found that a model with switch‐edge speeds dominated the other models. Clustering and switching, when defined by the slope difference algorithm, offered a slim improvement over the base model. For letter fluency, none of the novel scores we computed yielded an improvement over the base model. A model with animal and letter fluency variables offered further improvement.ConclusionSwitch‐edge speed scores improve on a base model predicting ICI from animal fluency. Animals and letter F fluency provide complementary prognostic information.
Associations between different FDG PET indices and clinical ratings in cognitively unimpaired older adults
Authors: Protas Hillary D. , Chen Kewei , Chen Yinghua , Luo Ji , Raichle Marcus E. , Morris John C. , Benzinger Tammie L.S. , Goyal Manu S. , Vlassenko Andrei G. , Reiman Eric M. , Su Yi 
Published: December 2021

AbstractBackgroundFDG PET measurements of cerebral glucose hypometabolism in brain regions that are preferentially affected by Alzheimer’s disease (AD) are known to be associated with clinical decline. However, commonly used FDG PET indices such as the standard uptake value ratio (SUVR) lack the sensitivity to detect early metabolic changes associated with cognitive decline. In this study we examine whether the full quantitative FDG net uptake rate (Ki) can track metabolic change in cognitive unimpaired elderly (CU) and compare that with indices that do not require full dynamic acquisition including the AD‐related hypometabolic convergence index (HCI), the AD‐related statistical region of interest (sROI), and regional SUVRs from known AD affected brain regions, e.g. precuneus (SUVRpre), posterior cingulate (SUVRpc) and hippocampus(SUVRhipp).MethodDynamic FDG PET images were acquired between 0 and 60 min after intravenous radiotracer administration in 75 subjects (all with CDR=0, age 67±7 years) from Washington University cohort. Full quantification of FDG PET was achieved using an image‐derived arterial input function to estimate hippocampal Ki. A Patlak model with reference region was used to estimate the hippocampal relative uptake rate Ri. HCI, sROI, SUVRpre, SUVRpc, SUVRhipp were also estimated using the last 30 minutes of data from each dynamic scan. Using Pearson correlation (r), we examined MMSE association with Ki, Ri, SUVRpre, SUVRpc, SUVRhipp, HCI and sROI each separately. Using statistical Steiger test, we compared the difference of these correlation strengths.ResultLower hippocampal Ki and AD‐related sROI FDG measurements were significantly correlated with lower MMSE in CU older adults (r=0.31, p=0.007, r=0.27, p=0.019), but not Ri, HCI, SUVRpre ,SUVRpc, and SUVRhipp (r=0.09,‐0.06,0.13,0.12,0.03, p>0.28). MMSE correlations with hippocampal Ki and AD‐related sROI measurements were not significantly different (p=0.74, Steiger test). Among the FDG indices that did not require full dynamic scan, sROI also had the strongest correlation with Ki (r=0.39, p<0.001).ConclusionAmong the tested FDG PET indicators of AD, lower Hippocampal Ki and AD‐related sROI measurements were associated with lower clinical ratings in CU older adults. Additional studies are needed to clarify the extent to which they predict subsequent cognitive decline.
White matter neuroinflammation correlates cognition in preclinical Alzheimer disease
Authors: Wang Qing , Schindler Suzanne E. , Chen Gengsheng , McKay Nicole S. , Liu Jingxia , Flores Shaney E. , Wang Sicheng , Hassenstab Jason , Morris John C. , Wang Yong , Benzinger Tammie L.S. 
Published: December 2021

AbstractBackgroundAlthough neuroinflammation plays a critical role in the progression of Alzheimer disease (AD), the exact mechanism underlying neuroinflammation remains largely unclear. Neuro‐inflammation imaging (NII), a diffusion‐based MRI method for neuroinflammation, has been used to quantify white matter (WM) neuroinflammation in the sporadic AD. This study aims to evaluate WM neuroinflammation in reference to the A/T/N framework of AD and assess its associations with cognition.Method266 participants enrolled in ongoing studies at the Knight ADRC at Washington University underwent NII measures, CSF biomarker measures, and a test battery of cognitive tasks. The CSF levels of Aβ42/Aβ40, ptau181, and total‐tau were measured with the automated Lumipulse platform and used to classify the participants into the following groups – A‐T‐N‐ (n=145), A+T‐N‐ (n=71), and A+T+N+(n=50) (Table 1). The preclinical Alzheimer Cognitive Composite (PACC) and Global Composite scores for each individual were derived from a subset of the Knight ADRC cognitive battery to assess cognitive performance. NII was acquired with a multi‐b value scheme (bmax =1400s/mm2 and 25 directions). The whole WM neuroinflammation (unit, mm2/ms) was quantified using the Tract Based Spatial Statistics (http://www.fmrib.ox.ac.uk/fsl) based WM skeleton. All statistical tests were conducted in R (R Core Team, 2020). Continuous and categorical variables in characteristics across all the three groups were compared using the Kruskal‐Wallis test and the Chi‐square tests where appropriate. The correlation between the NII WM neuroinflammation and cognition was determined by Spearman correlation. Analyses were adjusted for covariates, including age, sex, education, and APOE ε4 carrier status.ResultNII WM neuroinflammation was significantly correlated with the PACC (Figure 1A) and Global Composite score (Figure 1B) in all participants. Significant correlations between NII WM neuroinflammation and cognition composite scores were found in the A‐T‐N‐ and the A+T+N+ groups (Figure 1).ConclusionOur findings suggest that NII WM neuroinflammation is associated with cognitive performance both in individuals with no evidence of brain amyloidosis and in individuals with biomarkers consistent with Alzheimer disease. Given that this measure is acquired without using a contrast agent or radioactive tracer, NII holds great promise as an accessible measure for quantifying neuroinflammation in AD pathogenesis.
Metabolic syndrome in relation to cognitive function and white matter integrity in midlife: The CARDIA study
Authors: Dintica Christina S , Allen Norrina , Sidney Stephen , Yaffe Kristine 
Published: December 2021

AbstractBackgroundMetabolic syndrome (MetS) has been associated with poorer cognition in old age, however this association has yet to be defined in midlife. We aimed to investigate the relationship of early adulthood to midlife MetS in relation to cognition and white matter integrity in midlife.MethodsWithin the prospective study of Coronary Artery Risk Development in Young Adults, 2882 participants were identified with follow‐up of 30 years (age 18–30 years at baseline). MetS was defined using National Cholesterol Education Program guidelines and assessed across 9 follow‐ups over 25 years. Cognitive function was assessed at Year 30 using the Rey Auditory Verbal Learning Test (verbal memory), Digit Symbol Substitution Test (processing speed), Stroop test (executive function) and Verbal Fluency. Using logistic regression, we examined the association of MetS at Year 25, and persistent MetS (at least two assessments over the follow‐up) with poor mid‐life cognition, defined as ≥1 standard deviation below the mean in each domain. In a sub‐sample (n=453), brain MRI measures of total and region‐specific white matter integrity (fractional anisotropy [FA] and mean diffusivity [MD]) were assessed at Year 30 (mean age of 55±3.5 years) and converted to standardized z‐scores.ResultsMetS at Year 25 (n=534, 18.54%) was associated with poor cognitive function five years later in verbal memory (OR: 1.32, 95% CI: 1.04; 1.67) and processing speed (OR: 1.59, 95% CI: 1.23; 2.05), adjusting for age, sex, education, race, income, and smoking. Similarly, participants with persistent MetS over 25 years had lower cognitive performance in verbal memory (OR: 1.38, 95% CI: 1.10;1.73) and processing speed (OR: 1.72, 95% CI: 1.34; 2.22). In the MRI sub‐sample, MetS at Year 25 (n=60, 13.3%) was associated with lower total FA (β: ‐0.31, 95% CI: ‐0.57; ‐0.05). Persistent and non‐persistent MetS was associated with lower frontal FA (β: ‐0.36, 95% CI: ‐0.62; ‐0.09, β: ‐0.21, 95% CI: ‐0.62; ‐0.08, respectively) and higher total MD (β: 0.30, 95% CI: 0.03; 0.56, β: 0.26, 95% CI: 0.01; 0.51, respectively).ConclusionMetS from early adulthood to midlife may be a risk factor for poor cognitive function in midlife and is associated with microstructural white matter differences.
Successful cognitive aging definitions and associated demographic, biomarker profiles and lifestyles in the 80+ MCSA population
Authors: Arenaza‐Urquijo Eider M , Castillo Anna , Przybelski Scott A. , Lesnick Timothy G. , Pillai Sheela Kumari Raghavan , Mielke Michelle M. , Machulda Mary M. , Knopman David S. , Radford Jonathan Graff , Jack Clifford R. , Petersen Ronald C. , Vemuri Prashanthi 
Published: December 2021

AbstractBackgroundThere have been no standard definitions of successful cognitive aging (SA). Our goal was to apply different SA definitions to the 80+ population in the Mayo Clinic Study of Aging (MCSA) on the basis of (i) cross‐sectional vs longitudinal cognition (“Exceptionality” vs “Maintenance”) and (ii) memory vs global cognitive scores and explore the participant characteristics for each SA definition on the basis of baseline imaging markers and mid/late‐life health.MethodWe included 2157 participants from the MCSA, all ≥80 years at baseline and classified them into two SA definitions using memory z‐scores or global z‐scores: “Exceptionality” when high cognitive performance was observed (z‐scores ≥ 1 SD), “Maintenance” when cognitive function was preserved over time (Slope ≥ ‐0.1/year using mixed‐effect models). Our imaging markers were: PET‐based amyloid positivity (A+), MRI‐based neurodegeneration positivity (N+), WMH, FDG‐PET SUVR markers of resilience (anterior cingulate, ACC) and AD‐related areas (posterior cingulate). We also examined APOE4 status and other health characteristics. Group comparison was performed within each definition (e.g. exceptional vs non‐exceptional memory) using ANCOVA and binary logistic regressions with adjustments for age, sex, and education.ResultA lower number of participants met the “Exceptionality” criteria (10%: memory and 4%: global). A greater number met the “Maintenance” criteria (53%: memory and 32%: global). Less than 7% showed both “Exceptional” cognition and “Maintenance” over time. Participants across SA definitions were in general younger, more often women, with a higher education/occupation and less often APOE4 carriers. All SA groups showed higher ACC metabolism and lower N+ compared to the corresponding non‐SA group. More than 50% of the participants in the “Exceptional” groups were A+ (57%: memory, 50%: global). A+ frequency was significantly lower in the “Maintainers” (<42%). Better mid/late‐life health indicators were observed in the SA groups, including lower cardio‐metabolic conditions, higher mid‐life cognitive activities, lower depressive symptomatology, lower hypersomnolence and better self‐perception of health.ConclusionDifferent SA definitions identified mainly non‐overlapping 80+ groups that showed several common features including higher education/occupation, percent of women, better lifestyles, lower N+ frequency, and higher ACC metabolism. Lower A+ frequency was a key distinct feature of “Maintenance”.
Super‐agers in memory are not necessarily super‐agers in other cognitive domains
Authors: Corrada Maria M. , Melikyan Zarui A. , Dominguez Elena N. , Ho ChuChing , Sajjadi S. Ahmad , Kawas Claudia H. 
Published: December 2021

AbstractBackgroundSuperAgers are individuals who, despite their advanced age, retain superior cognitive performance. Although there is no consensus on how to define SuperAgers, identifying such individuals remains an important research question as they may help us identify protective factors against cognitive impairment that may be amenable to intervention strategies. Here we explore whether ‘SuperAgers’ who are the best performers in a test of memory, show equally exceptional performance in other cognitive domains.MethodParticipants are from The 90+ Study, a longitudinal study of aging and dementia in people 90 and older. Out of 1,134 participants in the study, the 349 with normal cognition at baseline were included in these analyses. Cognitive diagnosis was based on clinical examination and mental status exam independent of the tests investigated here. We evaluated performance in tests of verbal memory (9‐item California Verbal Learning Test‐long delay [CVLT]), executive function (Trails B), language (15‐item Boston naming test [BNT]), and attention (Digit Span backward [DSB]). For each test, we determined whether participants were in the top quartile of performance (SuperAgers). We investigated whether SuperAgers according to memory were also SuperAgers in other domains. We also tested whether being a SuperAger was related to age, sex, or education.Result47 participants were in the top quartile of CVLT with a perfect score of 9 and were classified as memory‐SuperAgers. Of these 47 participants, 8 (17%) were also in the top quartile for Trails B, 14 (30%) in the top quartile for BNT, and 12 (26%) in the top quartile of DSB (Figure). None of the 349 participants were in the top quartile for all four tests and only 13 participants (4%) were in the top quartile for three tests (Figure). Younger age was associated with being a SuperAger for CVLT, Trails B, & BNT and female sex was associated with being a memory‐SuperAger (CVLT) (Table). Education was not associated with being a SuperAger for any test.ConclusionIn this oldest‐old cohort, those who perform exceptionally well in a memory test do not perform equally well in other cognitive tests suggesting that the biological and sociodemographic determinants of superior performance will vary by cognitive domain.