bluuebunny/crossref_metadata_2025_split huggingface dataset:
Could intelligency be a proxy for cognitive resilience in the elderly?
Authors: Pires Lívia Rabelo , Ávila Rafaela , Costa Mônica Vieira , Dias Bruna Fugêncio , Bertola Laiss , Bicalho Maria Aparecida 
Published: December 2020

AbstractBackgroundResilience is a concept related to individual diferences between functionality/cognition and clinical situations associated to aging. In Brazil, elderlies commonly have low educational level and, years of schooling , is not necessarily associated to learning. In this context, we hypothesize that inteligency could be a potencial proxy of cognitive resilience. The aim of this study was to evaluate if inteligency could act as a measure of cognitive resilience, explaining individual variation between expected cognitive profile and its performance.MethodWe conducted a cross sectional study, enrolling 60 elderlies, 29 without functional and Cognitive Impairment (CG) and 31 with Mild Cognitive Impairment (MCI). To evaluate inteligency we applied WASI, Mattis scale for general cognition and, Frontal Assessment Battery (FAB) for executive functions. Participants were submitted to the same study protocol, including a geriatrician evaluation and neuropsychological assessment. We applied Mann‐Whitney and chi‐square to compare the groups. Pearson correlation coefficient and multivariate analysis were employed to compare samples. Linear regression analysis with control of independent variables age, sex and years of schooling and, the outcomes Mattis and FAB were applied to verify cognitive discrepancy. The intelligency quociente (IQ) was analyzed as a cognitive discrepancy predictor by regression analysis.Result60 individuals were selected, aged 76.8 ± 5.80 years, 75% female and 4.6 ± 3.42 years of schooling. There were no diferences between groups considering age, schooling and IQ, Mattis and FAB. In CG, we observed correlation between age and IQ and Mattis; and, schooling and IQ and Mattis. For MCI, there were correlation between age and Mattis; schooling and Mattis; IQ and FAB; and, Mattis and FAB. The regression model showed the higher the intelligence level, the greater the positive discrepancy in general cognition (Mattis) (Figure 1). The result of analysis carried out between IQ and discrepancy in executive functions (FAB) showed the higher the IQ, the greater the positive discrepancy in executive functions (Figure 2).ConclusionOur results suggest IQ can be measure of discrepancy in general cognition and executive functions. It can be a good proxy of cognitive reserve.
Plasma phospholipid fatty acids, cognitive function, and risk of dementia among older adults
Authors: Koch Manja , Furtado Jeremy D. , DeKosky Steven T. , Fitzpatrick Annette L. , Lopez Oscar L. , Kuller Lewis H. , Mukamal Kenneth J. , Jensen Majken K. 
Published: December 2020

AbstractBackgroundPlasma phospholipids are biomarkers of dietary fat intake and metabolism which have been linked to several cardiometabolic disorders. Few prospective studies have assessed plasma phospholipids in relation to adjudicated dementia risk and cognitive decline.MethodWe measured plasma phospholipids in a case‐cohort study nested within the Ginkgo Evaluation of Memory Study. We included 911 randomly selected participants and 498 participants who developed dementia during a mean [SD] of 5.0 [1.8] years of follow‐up. We measured individual plasma phospholipids (as a percentage of total plasma phospholipid fatty acids) by gas chromatography with flame ionization detection. These were evaluated in association with the Modified Mini‐Mental State Examination (3MSE) scores at baseline and neurologist‐adjudicated risks of all‐cause dementia and Alzheimer’s disease (AD), adjusting for sociodemographic and clinical characteristics.ResultWhen compared with saturated fatty acids (SFA), we found no associations of total mono‐unsaturated (MUFA), polyunsaturated (PUFA), or trans‐fatty acids (TFA) with risk of dementia or AD. However, higher docosahexaenoic acid was associated with a lower risk of dementia (hazard ratio 0.80 per 1% of docosahexaenoic acid instead of SFA; 95% confidence interval: 0.71‐0.91). Similarly, higher PUFA was associated with 0.04 point higher 3MSE score at baseline (per 1% PUFA instead of SFA; 95% confidence interval: 0.01, 0.08) signifying better cognitive function.ConclusionsAlthough we did not find strong associations of mono‐unsaturated or TFA with risk of dementia or AD when compared with SFA, replacement with PUFA was associated with better baseline cognitive function, and replacement with the marine n‐3 fatty acid docosahexaenoic acid was associated with lower risk of dementia. This prospective study highlights the potential of dietary improvement to prevent dementia.
Sex differences in the association between education in adulthood and late‐life cognition in the Kaiser Health Aging and Diverse Life Experiences (KHANDLE) Study
Authors: Gilsanz Paola , Mayeda Elizabeth Rose , Eng Chloe W , Glymour M Maria , Peterson Rachel , George Kristen M , Quesenberry Charles P , Mungas Dan M , DeCarli Charles , Whitmer Rachel A 
Published: December 2020

AbstractBackgroundWhile education is strongly associated with late‐life cognitive level, it is unclear how education after young adulthood is associated with late‐life cognition. This study examines the association between adult education and overall and domain specific cognition in a diverse sample allowing for possible differences in associations by sex. This is important to consider given recent increases in educational opportunities for women.MethodThe Kaiser Healthy Aging and Diverse Life Experiences Study (KHANDLE) enrolled Kaiser Permanente Northern California members age 65+ who completed a Multiphasic Health Checkup (MHC) conducted from 1964‐1996. Among 1,363 KHANDLE participants who reported education attainment at an MHC before age 25, education in adulthood was a binary variable reflecting reporting higher levels of education during KHANDLE interviews than at their first MHC visit after age 25. Executive function, semantic memory and verbal episodic memory were captured through the Spanish and English Neuropsychological Assessment Scales (SENAS) during KHANDLE baseline interviews and z‐standardized. Linear regressions estimated the association between education in adulthood and domain‐specific late‐life cognition adjusting for age at MHC, age at KHANDLE, sex, race/ethnicity, and educational attainment at MHC. Stratified models and interaction terms tested for possible sex differences in associations.ResultWomen were more likely than men to have ≤ HS at their MCH (33% vs 20%; chi‐square p‐value=<0.0001) and to receive additional education during adulthood (37% vs 27%; chi‐square p‐value=<0.0001). Among recipients of adult education, 50% had ≤ HS at their MCH and at the KHANDLE interview 25% completed HS or trade school, 18% completed college, and 24% completed graduate school. Education during adulthood was associated with executive function (β=0.18, 95% CI: 0.07, 0.28) but not semantic memory (β=0.09, 95% CI: ‐0.02, 0.19) nor verbal episodic memory (β=0.06, 95% CI: ‐0.05, 0.18). The association between adulthood education and executive function was stronger among women than men (women: β=0.19, 95% CI: 0.06, 0.32; men β=0.12, 95% CI: ‐0.07, 0.32; executive function*female interaction term p‐value=0.04).ConclusionEducation during adulthood was associated with better executive function among women. Additional research is needed to assess if education during adulthood is associated with cognition and cognitive decline in late‐life.
High frequency of progranulin mutations in Caribbean Hispanic families with dementia
Authors: Vardarajan Badri N. , Reyes‐Dumeyer Dolly , Piriz Angel , Medrano Martin , Lantigua Rafael , Mayeux Richard 
Published: December 2020

AbstractBackgroundProgranulin (GRN) mutations cause frontotemporal dementia (FTD) and have been implicated in causing a variety of clinical neuro‐degenerative syndromes, including Alzheimer’s disease (AD) but it is hypothesized that these presentations all result from TDP‐43 pathology. We estimated the frequency of GRN mutations in multiplex families with dementia in the Dominican Republic and in New York.MethodsWe analyzed GRN mutations from whole genome sequencing data in 1941 individuals from 307 multiplex Caribbean Hispanic families with dementia. We prioritized rare (MAF<0.05 in GnomAD exomes and genomes) GRN variants annotated as having moderate‐high functional effect. Identified variants were cross‐referenced with FTD mutations found in Orphanet, MedGen, SNOMED and OMIM databases. GRN mutation carriers further were assessed for clinical and behavioral symptoms.ResultsWe identified 27 rare, moderate‐high impact variants in GRN in the Caribbean Hispanic families. Six mutations (rs63750723, rs368705304, rs63750479, rs63750412, rs63751294, rs25647) were previously reported as associated with FTD and were found with MAF<0.05 in the GnomAD genomes. 92 individuals (4.7%) from 45 families carried at least one of the six previously reported GRN variants. Of these 47 (51 %) were initially thought to have Alzheimer’s Disease with an average age at onset of 77.8 (±8.93) and the remaining 46 were unaffected (average age of last healthy exam= 65.05 (±8.4)). Aggression and psychosis were frequently observed behavioral symptoms in the demented patients consistent with FTD phenotype.ConclusionsIn this study we observed a higher than expected frequency of damaging GRN mutations in families multiply affected by dementia. The majority of demented individuals were thought to have Alzheimer’s disease initially. Further analyses of phenotype‐genotype correlations should provide insight into impact of GRN mutations among Caribbean Hispanics.
Vascular cognitive impairment due to dilated perivascular spaces in putamen: Connections with the ventrolateral prefrontal cortex and neurological deficits
Authors: Canella Marcelo , de Oliveira Souza Natalia Vasconcellos , Bertolucci Paulo Henrique Ferreira , de Oliveira Fabricio Ferreira 
Published: December 2020

AbstractBackgroundAnatomical studies in animals have described multiple striatal circuits and suggested that sub‐components of the striatum project to distinct cortical areas. Researchers that reconstructed tracts of the left and right putamen have shown ipsilateral projections to the primary motor area, primary somatosensory area, supplementary motor area, premotor area, cerebellum, thalamus and prefrontal cortex (specifically to the ventrolateral prefrontal cortex). The ventrolateral prefrontal cortex appears to have a specific role in spatial processing and memory retrieval.MethodCase report and analyses of MR Images (T1, T2 and Flair) of a patient presenting with vascular cognitive impairment due to dilated perivascular spaces in putamen bilaterally.ResultMale patient, 81 years‐old, right‐handed, with four years of formal education and high cerebrovascular risk. His cognitive complaints began twelve years ago, and worsened in the last two years (losing personal belongings inside his own house, sometimes forgetting names of well‐known persons, with word finding difficulties). He denied impairment in activities of daily living, was able to organize his home budget, take his medications and go to the market alone. Now, he is physically and intellectually active (walking, reading newspapers, and talking about Philosophy), and still drives cars. His CDR score is 0.5, and his MMSE score is 29 (with 3 points in evoked memory). Word List Memory Task (Immediate Recall):4/5/8 (intrusion of "vessel" in the first two lists); Evocation:6 (intrusion of "vessel"); Recognition:10; Verbal Fluency (Animals):20; Verbal Fluency (Fruits):9. MR (10/15/2018): mild supratentorial microangiopathy; encephalomalacia/gliosis in the vermis and the left cerebellar hemisphere; Fasekas = 1 / Scheltens = 1 (bilaterally); bilateral supratentorial dilated perivascular spaces, particularly in the putamen.ConclusionOur patient does not have dementia, regardless of more than ten years of cognitive impairment. Bilateral dilated perivascular spaces in the putamen may cause deficits in memory retrieval and spatial processing. Neuropsychological evaluations must consider specific areas of brain injury. Our patient has impaired memory retrieval (with false memories verified by constant intrusions in the Word List Memory Task), and the high occurrence of losing personal belongings inside his house can be due to difficulties in spatial processing (mental map of positions of items in space).
Association of late‐onset dementia risk scores and Alzheimer’s disease pathology status in preclinical older adults
Authors: Udeh‐Momoh Chinedu T. , Zheng Bang , Price Geraint J. , Watermeyer Tam J. , Jager Celeste A. , Su Bowen , Giannakopoulou Parthenia , Saad Ziad , Fogle Michael , Robb Catherine , Ford Jamie , Ritchie Craig W. , Baker David , Novak Gerald P. , Ahmadi‐Abhari Sara , Middleton Lefkos T. 
Published: December 2020

AbstractBackgroundDementia risk scores (DRS) for the prediction of Alzheimer’s disease (AD) have the potential to identify at‐risk individuals for secondary prevention trials. To date, risk scores have focused primarily on predicting dementia symptoms rather than AD histopathology. Prediction of biological disease status could inform more precise targeting of at‐risk populations for prevention strategies.In this study, we compare the predictive value of three late‐life DRSs, namely the revised CAIDE (younger and older old) and the Reitz DRS (Reitz et al. 2010). Capacity for distinguishing pathogenic amyloid‐beta status and relation to multi‐domain cognitive performance was explored.Methods1378 cognitively‐unimpaired participants aged 60‐85 years from the UK Cognitive Health in Ageing Register: Investigational, Observational, and Trial Studies in Dementia Research: Prospective Readiness cOhort (CHARIOT‐PRO) Sub‐study had cerebral amyloid load dichotomized as positive vs negative. The predictive value of the Reitz and CAIDE risk scores for determining amyloid status were tested in separate logistic regression models. Associations of the risk scores with global and multi‐domain cognitive performance (assessed via the RBANS) were further evaluated. Finally, the contributions of individual components of the risk scores on amyloid status and cognitive performance were tested in multiple logistic and linear regression models.Results19.3% of the participants were amyloid‐positive. The Reitz and CAIDE young‐old (age<75) scores were higher in the amyloid positive versus negative group (median(IQR): 20 (10) vs 15 (11), 1 (2) vs 0 (2) respectively; P<0.05). Higher Reitz and CAIDE younger‐old scores were associated with increased risk of amyloid positivity (OR=1.05 (1.03‐1.08) and 1.17 (1.03‐1.34) respectively; P<0.05). Reitz score alone was negatively correlated with global cognition, memory and visuospatial indices (r ranges from ‐0.10 to ‐0.14; P<0.05). The potential contributing factors for predicting amyloid status were age, ApoE‐e4, and ethnicity; while diabetes and education predicted cognitive performance. In contrast, nil associations of CAIDE older‐old (age≥75) score with amyloid status or cognitive performance were noted (P>0.05).ConclusionsThe risk scores tested revealed differential predictive abilities in relation to amyloid pathology status and late‐life cognitive performance. Risk composites focusing on identified genetic and metabolic factors may be useful for more precise participant selection in targeted prevention and risk‐reduction trials.
Defining Alzheimer’s disease subtypes using polygenic risk scores integrated with genomic and brain transcriptomic profiles
Authors: Hu Junming , Chung Jaeyoon , Panitch Rebecca , Zhu Congcong , Beecham Gary W. , Mez Jesse , Farrer Lindsay A. , Stein Thor D. , Crane Paul K. , Jun Gyungah R. 
Published: December 2020

AbstractBackgroundIn light of the complex etiology of Alzheimer’s disease (AD), classifying AD patients into clinical subtypes is important for precision medicine. We tested whether polygenic risk scores (PRSs) combined with brain expression profiles in AD patients are correlated with clinically defined AD subtypes.MethodsWe generated 143 co‐expressed gene networks (modules) using RNA sequencing (RNA‐Seq) data derived from 64 autopsied AD brains from the Framingham Heart Study and Boston University Alzheimer’s Disease Center. These modules were validated using brain RNA‐seq data from participants with AD in the Religious Orders Study and Memory and Aging Project (n = 363) and the Mayo Clinic Study of Aging (n = 82). Fourteen AD‐related modules were selected by enrichment analysis using the significant genes (P < 0.001) identified in a genome‐wide association study for neuropathological traits (Beecham, 2015) and then characterized by brain cell‐type specific expression profiles. We computed polygenic risk scores of the AD‐associated genes within each module (module‐based PRSs) using the estimates from Beecham et al. in the 449 AD patients of the Alzheimer’s Disease Neuroimaging Initiative. Next, we examined correlations of the 14 module‐based PRSs with (1) scores for 9 different cognitive tests and six cognitively‐defined AD subtypes including memory, language, visuospatial, executive, multi, or no domains (Mukherjee, 2018).ResultsEleven of the 14 AD‐related modules were significantly enriched (P < 0.05) for specific brain cell types including four in neurons (best P = 6.8 × 10−104), four in astrocytes (best P = 5.2 × 10−76), two in endothelial cells (best P = 9.9 × 10−87), and one in microglia (P = 1.7 × 10−129). The most significant correlation between the PRSs from the 14 modules and clinical phenotypes was found with an astrocyte‐specific module and language‐related cognitive functions (correlation r2>0.2; P = 6.7 × 10−3), and this module contained 8 AD genes (best gene: DOCK1, P = 3.4 × 10−5). The individual PRSs of the astrocyte‐module were significantly higher in the language‐specific AD patients compared with in other five subtypes (best P = 0.01 from comparison with AD patients in the no domain group).ConclusionThese findings illustrate for the first time that genetic risk scores integrated with system biology may define clinical subtypes of AD. Our findings will facilitate genome‐guided precision medicine efforts in prevention and treatment of AD.
Arterial stiffness acts synergistically with APOE genotype and amyloid status to predict cognitive impairment in non‐demented elderly
Authors: Smirnov Denis S. , Bangen Katherine J. , Galasko Doug R. , Brewer James B. , Salmon David P. 
Published: December 2020

AbstractBackgroundVascular disease is a known contributor to cognitive impairment in the elderly, often associated with impairments in Executive Functions. Aortic‐femoral Pulse Wave Velocity (PWV) measures have been proposed as a non‐invasive measure of vascular risk. However, the predictive value for cognitive decline and interactions with amyloid biomarkers have received limited study.MethodsPWV was assessed in 129 non‐demented participants (108 cognitively normal and 21 mild cognitive impairment [MCI]) who underwent comprehensive medical and neuropsychological evaluation at the Shiley‐Marcos UCSD ADRC. PCA‐derived Domain Z‐Scores (relative to robust normal controls) were generated, representing Memory, Language, Visuospatial, Executive Functions, and Attention. Linear models examined if PWV significantly predicted each Domain Score and global cognition (the Mattis Dementia Rating Scale (DRS) total score), adjusting for age, sex, and education. In a subanalysis, history of hypertension, hypercholesterolemia, diabetes, stoke/TIA, CVD, atrial fibrillation, and current smoking status were each added to the model. Next, presence of an APOE ε4 allele was added and allowed to interact with PWV. Amyloid status was determined using CSF AB42/40 ratios in a subset of participants (n = 93), and its interaction with PWV was similarly tested.ResultsAfter adjusting for demographics, PWV predicted DRS scores (B=‐0.47, p=0.01), Memory Domain Scores (B=‐0.11, p=0.02), and Executive Domain Scores (B=‐0.10, p = 0.04, Figure 1). The pattern of results did not change when history of vascular risk factors was added to the models. When restricting to only cognitively normal participants, PWV significantly predicted only Executive Domain Scores (B=‐0.08, p = 0.03). Presence of an APOE e4 allele showed a significant interaction with PWV in predicting Memory (B=‐0.18, p=0.03, Figure 2). In the subsample with CSF data, the Memory Domain Score was predicted by the interaction of PWV with amyloid status (B = ‐0.30, p = 4.2x10‐4, Figure 3).ConclusionsArterial Stiffness measured through aortic‐femoral PWV is a predictor of cognitive impairment, especially in the Memory and Executive Function domains, and interacts with markers of Alzheimer’s disease (APOE and amyloid status), such that a stronger relationship is found in the amyloid/ε4 positive population.
Longitudinal change in CSF biomarkers, especially NPTX2, in non‐demented elderly predicts cognitive decline and conversion to dementia
Authors: Galasko Doug R. , Smirnov Denis S. , Salmon David P. ,   Alzheimer's Disease Neuroimaging Initiative (ADNI)
Published: December 2020

AbstractBackgroundWe have previously shown that markers of synaptic dysfunction (e.g. NPTX2) measured cross‐sectionally in CSF improve prediction of current cognitive status and future cognitive decline above and beyond amyloid (i.e., Aβ1‐42) alone (Galasko et al, 2019). Here we assess if longitudinal change in these and other candidate CSF biomarkers (NPTX2, VGF, SCG2, CMGA, FAPBH), with total tau (T‐Tau), correlate with cognitive decline and predict conversion to dementia.MethodsLongitudinal CSF samples collected over 4 years from 193 non‐demented elderly from ADNI (81 NC, 45 EMCI, 67 MCI, age = 72.6±7, 45% Female, MMSE = 28.4±1.7) were analyzed by mass spectrometry for absolute concentration of NPTX2, VGF, SCG2, CMGA, and FAPBH. Elecsys data for Aβ1‐42 and T‐Tau were also available. All biomarker values were log transformed. Rates of change (Δ) were calculated from regression on age. Linear mixed effects models assessed the ability of the slope of each marker over the same time period to predict the rate of longitudinal cognitive decline on the cognitive tests of the ADNI cognitive battery, adjusted for age, sex, education, baseline cognitive performance, and baseline CSF Aβ1‐42 levels. Cox Proportional Hazard models were fit for progression to dementia (CDR >= 1.0), adjusting for the same covariates.ResultsAlthough the candidate markers were all highly intercorrelated (r= .42‐.95), their change over time was differentially associated with amyloid status (Figure 1) and to longitudinal decline on cognitive test score and functional measures (Table 1, e.g. Figure 2). Slopes of NPTX2 (p=0.0008), SCG2 (p=0.03), CMGA (p=0.04) and VGF (p=0.01) each predicted conversion to dementia (Table 2, e.g. Figure 3) and MMSE decline. Change in T‐tau only predicted MMSE decline.ConclusionsLongitudinal change of candidate markers, especially NPTX2, has utility for predicting degree of prodromal/early cognitive decline and transition to dementia, beyond the ability of amyloid alone or change in CSF T‐tau. Thus, these candidate CSF biomarkers may have utility as indicators of cognitive impairment and predictors of cognitive decline.