bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lower levels of episodic memory associated with long‐term air pollution exposures in older women: Differences in midlife versus late‐life exposures and effect modification by hormone treatment
Authors: Wang Xinhui , Younan Diana , Petkus Andrew J , Beavers Daniel P , Espeland Mark A , Chui Helena C , Resnick Susan M , Gatz Margaret , Kaufman Joel D , Wellenius Gregory , Whitsel Eric A , Manson JoAnn E , Chen Jiu‐Chiuan 
Published: December 2020

AbstractBackgroundLate‐life exposure to ambient air pollutants may accelerate episodic memory (EM) declines in older women, but very little is known about the midlife exposure effects. Animal data suggests that hormone therapy (HT) may protect female brain from neurotoxic insult. We examined the EM trajectories associated with air pollutants and whether the associations varied by HT, exposure time‐window or pollution sources.MethodWe studied 916 women from the Women’s Health Initiative Memory Study in Younger (WHIMS‐Y) Women. At age of 50‐54, postmenopausal women were randomly assigned to an average of 5 years of conjugated equine estrogen alone (E‐alone) if they had hysterectomy, its combination with medroxyprogesterone acetate (E+P) if without hysterectomy or matching placebos. From the WHIMS‐Y inception age of 62‐71, EM was assessed annually (2008‐16) using the telephone‐based California Verbal Learning Test. Three‐year average exposures at midlife (aged 50‐59) and late‐life (at inception) were derived from yearly exposures estimated by regionalized universal kriging models for PM2.5 (particulate matter <2.5μm) and NO2 (a proxy of traffic‐related air pollutants). We used linear mixed‐effect models to estimate the associations, adjusting for social‐demographic variables, lifestyles, HT, hysterectomy, cardiovascular risk factors and other clinical covariates.ResultEM performance improved (0.60/year, p<0.001) over the study period. Higher PM2.5 exposures in midlife, but not in late‐life, were associated with lower EM levels (β=‐0.49, per inter‐quartile‐range [IQR]=3.44 µg/m3, p=0.045). NO2 exposures in midlife or late‐life were not associated with EM levels. Compared to the women assigned to placebo group, the observed association between midlife PM2.5 and EM level differed by HT (interaction p=0.005). The putative adverse PM2.5 effect was greater (β=‐1.29 per IQR; p=0.03) in the E‐alone group, with no statistically significant difference in the E+P group (p=0.16). A similar pattern of effect modification was found for NO2 exposure (interaction p=0.09) in midlife, but not in late‐life. The slope of EM trajectory was not associated with either exposure, HT, or their interactions.ConclusionHigher midlife PM2.5 exposure decrease the EM levels of older women, with stronger associations in those randomly assigned to E‐alone treatment, which did not support the protection of HT against air pollution neurotoxicity.
Plasma Aβ in cerebral microbleeds‐positive subjects with cognitive impairment
Authors: Liu Shan , Ito Hitomi , Ogawa Norihiro , Akatsu Hiroyasu , Uchida Kazuhiko 
Published: December 2020

AbstractBackgroundCerebral amyloid angiopathy (CAA) is strongly related to Alzheimer’s disease (AD). Accumulation of amyloid affects pathophysiology of parenchyma and vessels in amyloidosis. Continuum of amyloid pathology may result in complicated clinical symptoms due to overlap of vascular and neurodegenerative factors during amyloidosis. MRI can detect hemosiderin deposits as cerebral microbleeds (CMBs) and cortical superficial siderosis. CMBs may be involved in amyloid pathology in AD and mixed dementia. Here, we analyzed relationship of these cerebrovascular changes to plasma Aβ42 and Aβ40 levels.MethodAge‐matched subjects with cognitive impairment were classified into CMBs‐positive, ‐suspective and ‐negative groups by MRI. Plasma Aβ42, Aβ40, BACE1 levels were determined by ELISA (ADx, Euroimun).ResultThere is no significant changes of MMSE score and hippocampal atrophy among the CMBs groups. CMBs‐positive subjects showed lower Aβ42 levels and higher Aβ40/42 ratio in plasma. Plasma BACE1 levels showed no significant change in CMBs‐positive subjects.ConclusionCMBs, plasma Aβ42 and Aβ40/42 ratio may be potential biomarkers for amyloid pathology in cognitive impairment.
Development of the Computer and Technology Attitude Questionnaire (CaTAQ) to inform performance on computerised cognitive testing in older adults in the CogSCAN Study
Authors: Croot Karen , Allison Karen C. , Sachdev Perminder S. , Brodaty Henry , Crawford John D. , Lam Ben C.P. , Lee Teresa , Henry Julie D. , Draper Brian , Close Jacqueline , Ong Min Yee , Rossie Matilda , Kochan Nicole A. 
Published: December 2020

AbstractBackgroundComputer‐administered neuropsychological assessment batteries (CNAs) have the potential to allow large‐scale cognitive screening and monitoring, increasing older adults’ access to cognitive assessment, and earlier diagnosis of and intervention for cognitive impairment. There is, however, little research on whether experience with and attitudes to computers and technology affect the validity, reliability and acceptability of CNAs in older adults. Here, we report the development and validation of an instrument to measure computer attitudes and computer experience in an older adult cohort from the CogSCAN study.MethodThe Computer and Technology Attitude Questionnaire (CaTAQ) is a new 27‐item self‐report questionnaire comprising five subscales (computer anxiety, comfort with computers, positive and negative attitudes to computers and computer learning self‐efficacy) that have been individually validated in diverse populations (young, predominantly Hispanic Los Angeles adults; Canadian business employees; older Pennsylvanian Caucasian adults), as well as items measuring experience with computers and related technologies. Responses from 196 community‐living older adults without dementia in Sydney, Australia (67% female, mean age 72.1 years, range 60‐91 years, mean years’ education 14.7, limited/no computer experience 9.2%) have been analysed to date.ResultConfirmatory factor analysis supported a three‐factor model (anxiety/discomfort, positive about technology, negative about technology) with good fit to items from the first four subscales (Figure 1), and four computer learning efficacy items formed a single factor with good fit in a subsample of 79 participants who reported not knowing how to use a computer (Figure 2). Our measurement models for this older Australian sample therefore replicate previous validation of these subscales. Analyses in progress will further clarify the factor structure of the questionnaire and remove redundant items.ConclusionResults suggest the CaTAQ can provide nuanced information about older adults’ attitudes to computers and technology that have the potential to influence CNA performance and acceptability. The results will need to be confirmed in a less‐educated sample with less computer experience, and in people with Mild Cognitive Impairment or mild dementia. This new instrument has the potential to inform decisions about suitability of computerised cognitive testing for older adults in research and clinical settings.
MRI investigations of white matter hyperintensity and structural abnormalities of brain in urban and rural cohorts of India
Authors: Tiwari Vivek , Kallur Kumar , Rao Naren P , Sivakumar Palanimuthu T , Balakrishnan Aditi , Ravindranath Vijayalakshmi ,   SANSCOG and TLSA Investigators
Published: December 2020

AbstractBackgroundWhite‐matter degeneration appears as white‐matter‐hyperintensities (WMHs) on T2‐weighted FLAIR (T2w‐FLAIR) MRI. WMH load and alterations in hippocampal volume may serve as an imaging‐marker to identify brain‐health in aging and associated disorders. Here, we have investigated periventricular‐white‐matter‐hyperintensities (PVWMHs) and deep‐white‐matter‐hyperintensities (DWMHs) together with brain volumetric‐measurements in an urban‐cohort TATA longitudinal study on aging (TLSA) and a rural‐cohort Srinivaspura Aging, Neuro Senescence and COGnition study (SANSCOG) at the baseline visit of the longitudinal‐study. These study cohorts have distinct population characteristics: SANSCOG participants are recruited from the rural area Srinivaspura, whereas, those in TLSA are recruited from urban Bangalore. The study cohorts comprise of cognitively healthy individuals aged ≥45 years.MethodMRI experiments were conducted on 3T whole‐body scanner. T2w‐FLAIR, 3D‐MPRAGE and DWI MR‐images were obtained. WMHs volume‐burden was measured using Fazekas grading on T2w‐FLAIR images. WMHs load and volumetric‐measures were stratified across three age‐groups, early (45‐54 years), intermediate (55‐64 years) and late (>65 years), for both cohorts.ResultMRI analysis was performed across 117 subjects in the urban‐cohort (TLSA) and 84 from the rural‐cohort (SANSCOG) from the ongoing study. Prevalence of PVWMHs in the SANSCOG‐cohort was significantly higher (p<0.001) at the early age‐group (45‐54 years) compared to that of TLSA‐cohort. PVWMHs in SANSCOG was significantly higher across all the age‐groups, although PVWMHs in TLSA closely catched‐up at the late‐age group. This suggests that rural cohort had severe vascular abnormality at much earlier age while vascular health deteriorated with increasing age for the urban cohort. Prevalence of PVWMHs in SANSCOG‐cohort did not significantly change across age‐groups, while TLSA‐cohort showed significant increase with increasing age. Similarly, DWMH prevalence was also higher in the SANSCOG at the early age‐group but did not increase significantly with age. However, WMH‐load (Fazekas grading) with aging showed significant positive correlation, indicating that WMH volume‐burden increases with age for both cohorts. Gender based segregation showed that WMH‐prevalence was significantly higher for males (>55%) in both cohorts.ConclusionIncreased WMHs prevalence at the early‐age in the rural‐cohort indicates occurrence of small vessel pathology of brain at much earlier age compared to the urban‐cohort. This may predispose the rural population towards aging associated disorders.
Plasma biomarkers Aβ42, Aβ40, and tau in Down syndrome dementia
Authors: Honig Lawrence S , Kang Min Suk , Lee Joseph H. , Silverman Wayne , Lott Ira T. , Lai Florence , Rosas H. Diana , Petersen Melissa , O'Bryant Sid , Andrews Howard , Pang Deborah , Krinsky‐McHale Sharon J. , Schupf Nicole 
Published: December 2020

AbstractBackgroundAdults with Down syndrome (DS) develop Alzheimer’s disease (AD) brain changes, including excess Aβ42, Aβ40, and tau aggregates, generally by the fifth decade of life, and with time ultimately develop a dementia syndrome. Here we examine the relationship of baseline plasma biomarkers Aβ42, Aβ40, and tau, to dementia status, in adults with DS from a large DS cohort (ADDS funded by NIH grant U01AG051412).MethodsParticipants included 164 adults with DS who provided blood sample for plasma isolation at enrollment baseline, with mean age 50.9±6.9 yr (range 40 to 81), including 92 men (56%) and 72 women (44%), with ethnic distribution 87% white, 6% Hispanic, 4% Asian, 2% black, and 1% Native American. Dementia status was 18% with Dementia, 21% with Mild Cognitive Impairment (MCI), 58% without MCI or dementia, and 2% undetermined. Apolipoprotein E (APOE) status was available for N=157: 71% no e4, 29% ≥1 e4. Plasma Aβ42, Aβ40, and tau were determined using a SIMOA (Quanterix) SR‐X system with Neuroplex‐3 kits.ResultsMean levels (pg/ml) were Aβ42 20.3±5.8 (range 9.0‐47.0) , Aβ40 468±116 (163‐896), and tau 4.78±2.85 (1.52‐20.46), with derived ratios Aβ42/Aβ40 0.044±0.010 (0.018‐0.101) and tau/Aβ42 0.236±0.124 (0.065‐1.191). Neither AB42 nor AB40 levels, nor tau/AB42 ratio correlated with age, although the AB42/AB40 ratio did show some decline with age (r = .16; p = 0.04). Dementia status, adjusted for age, did not significantly relate to baseline Aβ42, Aβ40 or Aβ42/Aβ40 ratio, but did relate to tau/Aβ42 ratio. The group of individuals with DS and MCI or Dementia had significantly greater tau/Aβ42 ratios (p= 0.001), than the group without, as did the groups just with MCI (p = 0.012), or just with dementia (p = 0.008), when adjusted for age and sex. These relationships were preserved when additionally adjusting for ethnicity and presence of APOE e4 allele, which itself was significantly related to dementia status.ConclusionsWhile cerebrospinal fluid measures are the gold standard for assessing Alzheimer’ pathology, these results suggest that in persons with DS, plasma measurements of Aβ42 and tau using the SIMOA technique may allow biomarker confirmation of Alzheimer’s dementia.
Relation between CAIDE scores and cognition: Data from TATA Longitudinal Study of Ageing
Authors: M.L. Abhishek , Balakrishnan Aditi , Muralidhar Sneha Dhanvanthri , Rao Naren P. , Ravindranath Vijayalakshmi ,   TLSA Investigators
Published: December 2020

AbstractBackgroundThe clinical and cognitive characteristics of people at increased risk of dementia may help provide insights into preclinical stage of dementia. The Cardiovascular Risk Factors, Aging and Dementia (CAIDE) study risk score is a reliable tool to estimate the individual risk of future dementia. Associations of CAIDE with performance in different cognitive domains are not fully clear in Indian population. Hence we studied the relation of CAIDE scores with cognitive performance in healthy middle aged elderly individuals from India.MethodData from 215 volunteers participated in TATA longitudinal study of aging was analyzed. All participants underwent cognitive tests such as Hindi mental state examination (HMSE), Digit symbol substitution test (DSST), Stroop test, Logical memory test and Addenbrooke Cognitive Examination‐III (ACE III). CAIDE scores are calculated by assigning scores to participants risk factors [age(<47 years = 0, 47–53 years=3, >53 years = 4); education (>/= 10 years = 0, 7–9 years = 2, 0–6 years = 3); sex (female = 0, male = 1); systolic blood pressure (</= 140 mmHg = 0, >140 mmHg = 2); body mass index (</= 30 kg/m2 = 0, >30 mg/m2 = 2); total cholesterol (</= 6.5 mmol/L = 0, >6.5 mmol/L = 2); physical activity (active = 0, inactive = 1)] and then totaling it. Spearman’s rank correlation analysis was conducted to examine the relation between CAIDE scores and cognitive tests.ResultThere was a significant negative correlation between CAIDE score and ACE III total score (rs = −.265, P < 0.001). DSST time and Stroop C time correlated positively with CAIDE score (rs = .241, P < 0.001 & rs = .283, P = 0.01). There was no significant correlation with HMSE.ConclusionOur findings indicate an inverse relation between CAIDE scores and global cognitive performance (ACE III), attention (DSST) and executive functioning (Stroop) but not with memory (Logical memory test). No relation was found with HMSE probably due to ceiling effect. If these findings are replicated then it could give insights in to clinical manifestations of preclinical stage of dementia.
Clinical utility of transcranial direct current stimulation and online language training in semantic dementia
Authors: Rangarajan Subhashini K. , Mukku Shiva Shanker Reddy , Gorthi Naga V.S.S. , Jagtap Namrata , Shetty Preetie A. , Girimaji Akhila , Sreeraj Vanteemar S. , Selvaraj Sowmya , Sivakumar Palanimuthu T. , B.K. Yamini , Shivashankar N. , Venkatasubramanian Ganesan 
Published: December 2020

AbstractBackgroundSemantic dementia (SD) is a variant of primary progressive aphasia (PPA) which is characterised by impaired confrontation naming, single word comprehension and object recognition with preserved fluency and syntax. Similar to many other neurodegenerative dementias, there is currently no effective treatment for semantic dementia. Neuromodulatory interventions like transcranial direct current stimulation(tDCS) and repetitive transcranial magnetic stimulation(rTMS) along with language training is emerging as a potential treatment strategy for Primary progressive aphasia. Aim: Four patients with semantic dementia were administered concomitant online language training with tDCS to study the feasibility and clinical outcome.MethodFour patients (2 males) aged between 50‐63 years, diagnosed with semantic dementia after a comprehensive clinical assessment and Addenbrooke’s cognitive examination and Clinical Dementia Rating(CDR) scale by an experienced geriatric Psychiatrist were included in the case series. Detailed assessment of neurolinguistic skills was done using Western Aphasia Battery (WAB‐Kannada/Hindi) before and after 5‐days of tDCS by qualified speech pathologist. Daily tDCS sessions were delivered using 2mA current with anode over the left dorsolateral prefrontal cortex and cathode over right supraorbital area for 30 minutes, except one female patient with moderate dementia who received 2 session daily at an interval of 3 hours. Online cognitive‐linguistic intervention was provided by the speech pathologist during tDCS sessions. Adverse effects were monitored using structured questionnaire.ResultThree Patients had mild dementia and one had moderate dementia as per CDR. tDCS was tolerated well except for burning sensation in two sessions in one patient and all were able to attend the linguistic training. All subjects improved in the domains of Spontaneous speech, Auditory verbal comprehension, repetition and naming on the WAB.ConclusiontDCS can be a potential therapeutic modality in semantic dementia. Randomized Sham Controlled Clinical trials are required to establish the efficacy of tDCS and language training in the treatment of semantic dementia.
High‐resolution postmortem MRI reveals TDP‐43 association with medial temporal lobe subregional atrophy
Authors: Wisse Laura , Ravikumar Sadhana , Ittyerah Ranjit , Lim Sydney A. , Lane Jacqueline , Lavery Madigan , Xie Long , Robinson John L. , Schuck Theresa , Grossman Murray , Lee Eddie B. , Tisdall Dylan M. , Prabhakaran Karthik , Detre John A. , Das Sandhitsu R. , Mizsei Gabor , Artacho‐Perula Emilio , Martin Maria Mercedes Iniguez de Onzono , Jimenez Maria del Mar Arroyo , Munoz Monica , Romero Francisco Javier Molina , Rabal Maria del Pilar Marcos , Sanchez Sandra Cebada , Gonzalez Jose Carlos Delgado , Prieto Carlos de la Rosa , Parada Marta Corcoles , Irwin David J. , Trojanowski John Q. , Wolk David A. , Insausti Ricardo , Yushkevich Paul A. 
Published: December 2020

AbstractBackgroundThe medial temporal lobe (MTL) is a hotspot of different neurodegenerative pathologies, and recent studies have shown associations of severity of pathology with atrophy measured on antemortem MRI. However, these studies are limited by the interval between time of scan and death and the relatively low resolution of the commonly acquired in vivo MRI scans, limiting the granularity of the regions being measured. We investigate the association of different neurodegenerative pathologies, particularly TDP‐43, and the thickness of different MTL subregions measured on high‐resolution postmortem MRI. As prior work suggests an anterior‐to‐posterior gradient of atrophy for TDP‐43 in frontotemporal dementia spectrum disorders and Limbic‐predominant Age‐related TDP‐43 Encephalopathy (LATE), we also examined differences along the long axis of the MTL.MethodTau, TDP‐43, β‐amyloid and α‐synuclein pathology were rated (0‐absent – 3‐frequent) in the hippocampus and entorhinal cortex (ERC) of 35 individuals with and without neurodegenerative diseases (Table 1). Thickness measurements were obtained from 0.2x0.2x0.2 mm3 post‐mortem MRI scans of excised MTL specimens from the contralateral hemisphere (Figure 1) in the ERC, Brodmann Area 35 and 36, parahippocampal cortex, subiculum, cornu ammonis (CA)1 and the stratum radiatum lacunosum moleculare. For each region, thickness was measured at an anterior and posterior location using a semi‐automated approach (Figure 2). Spearman’s rank correlations were performed, correcting for age, sex and hemisphere, including all four proteinopathies in the model.ResultWe find strong negative associations of TDP‐43 with thickness in all cortical MTL regions (Table 2, Figure 3) and with CA1, averaged over the two locations. We repeated the analyses for the thickness measurements separately in the anterior and posterior locations, but did not find a clear difference along the longitudinal axis. This is potentially due to the severity of the TDP‐43 pathology.ConclusionIn this unique dataset with neurodegenerative pathologies and high‐resolution scans of the MTL, preliminary results show strong associations between TDP‐43 pathology and atrophy in several MTL subregions. As this dataset continues to grow, we will be able to tease apart the effects of multiple MTL pathologies at a subregional level.
Cognitive worry in cognitively normal older adults is associated with decreased memory binding, hippocampal volume and parahippocampal thickness
Authors: Markova Hana , Mazancova Adela Fendrych , Cechova Katerina , Nikolai Tomas , Matuskova Veronika , Nedelska Zuzana , Sheardova Katerina , Laczó Jan , Hort Jakub , Vyhnalek Martin 
Published: December 2020

AbstractBackgroundWorry associated with subjective cognitive decline (cognitive worry) in cognitively normal (CN) older adults has been established as a feature that increases the likelihood of preclinical Alzheimer´s disease (AD). Previously, it has been associated with a higher risk of progression to mild cognitive impairment and dementia. We aimed to examine whether presence of cognitive worry reflects poorer memory performance and decreased volumes or cortical thicknesses in AD‐related regions in CN older adults.MethodIn total, 85 CN older adults reporting cognitive complaints were recruited from the Czech Brain Aging Study and classified into two groups by subjective evaluation of presence/absence of cognitive worry (WORRY+/‐, n = 36 and n = 49, respectively). All participants underwent a comprehensive neuropsychological examination, including the Rey Auditory Verbal Learning Test (RAVLT), Logical Memory I (LM I) and the challenging Memory Binding Test (MBT). 1.5T MRI with T1‐weighted 3‐dimensional images and FreeSurfer 5.3. algorithm was used to measure left and right hippocampal volume (HVL, HVR), left and right entorhinal and parahippocampal thickness (ERCL, ERCR, PHCL, PHCR). Individuals with significant vascular‐related white matter hyperintensities were not included. A one‐way ANCOVA assessed the between‐groups differences, controlling for sex, age and education.ResultThe WORRY+ did not differ from the WORRY‐ group in the RAVLT or LM I scores, but performed significantly lower in the MBT scores evaluating both free and cued recall in immediate and delayed conditions (ps ≤ 0.012). Consistently, the WORRY+ group had significantly decreased adjusted HVR, decreased PHCL and PHCR (ps ≤ 0.019). No other between‐group differences were found in medial temporal lobe measures.ConclusionCognitive worry in CN older adults is associated with both poorer memory performance in the challenging test of memory binding and decreased hippocampal volume and parahippocampal thickness even cross‐sectionally. Given that cortical thinning and hippocampal atrophy on MRI, together with poor cognitive performance on challenging tests, are detectable in late stages of preclinical AD, cognitive worry may be a risk factor for imminent functional impairment and disease progression.