bluuebunny/crossref_metadata_2025_split huggingface dataset:
Healthy subjects with abnormal levels of amyloid‐B and tau have lower cortical volumes in the mesial temporal region
Authors: Huang Kun , Dore Vincent , Li Shenpeng , Krishnadas Natasha , Bourgeat Pierrick , Burnham Samantha C. , Fripp Jurgen , Villemagne Victor L.L. , Rowe Christopher C. 
Published: December 2020

AbstractBackgroundPost‐mortem studies on Alzheimer's disease (AD) have shown that the stereotypical pattern and density of tau deposition is strongly associated with cortical loss. In this study, we investigate if cognitively healthy elderly subjects with abnormal level of tau in the mesial temporal lobe and/or of Ab in the brain as measure with PET have lower cortical volumes in parahippocampal, entorhinal, inferiortemporal, fusiform, hippocampus and amygdala which are the early region of atrophy.Method232 healthy cognitively normal control (CN) participants from the AIBL cohort underwent an Ab PET scan (18F‐NAV6240) and a tau scan (18F‐MK6240), . Ab and MK6240 scans were spatially normalized and scaled to the cerebellar cortex using CapAIBL. Threshold for Ab abnormality was 20CL, and two standard deviations above the SUVR mean in the mesial temporal region on Ab‐ CN subjects for tau. Three groups were then defined A‐T‐ (n = 180, 74.5 ± 5 yrs), A+T‐(n = 32, 77 ± 6 yrs) and A+T+(n = 16, 78 ± 7 yrs). From T1w MRI, cortical volumes in the parahippocampus, hippocampus, entorhinal, amygdala, inferior temporal and fusiform were computed. Volumes were controlled for intracranial volumes and normal aging and compared between the different group using standard T‐tests.ResultThere were no significant differences in age between 3 groups. However, A+T+ cohort had lower MMSE scores than A‐T‐. In addition, the CDR scores for A+T+ were significantly higher than in the other two groups. A+T+ had a significant lower cortical volume in all examined regions compared to A‐T‐ and A+T‐, (p < 0.05). There were no significant difference in cortical volumes between A‐T‐ and A+T‐.ConclusionIn CN, Ab pathology alone is not associated with lower cortical volumes. However, Ab and tau deposition in the mesial temporal lobe is associated with GM loss, even at the presymptomatic stages.
CAIDE dementia risk score and cognitive correlates among Filipinos with mild cognitive impairment
Authors: Cano Jemellee , Guzman Ma Fe P , Phung Thien Kieu Thi , Dominguez Jacqueline C 
Published: December 2020

AbstractBackgroundThe Cardiovascular Risk Factors, Aging and Dementia (CAIDE) dementia risk score is a validated tool predicting the risk of dementia.1,2 It includes age, sex, education, blood pressure, cholesterol, body mass index (BMI), and physical inactivity, with higher scores indicating increased risk of subsequent dementia.1,2 Mild Cognitive Impairment (MCI) is a The objective is to compare the cognitive profiles of Mild Cognitive Impairment (MCI) participants with significant modifiable risk factors (CAIDE > 6) in a Filipino cohort.MethodA total of 60 participants with MCI from the Filipino Multicomponent Intervention to Maintain Cognitive Performance among High Risks Population (FINOMAIN) study were included. Data on age, sex, educational level, blood pressure, cholesterol, body mass index (BMI), and physical activity were obtained. Mini Mental Status Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scores were obtained. Participants were administered the Mini‐Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and Alzheimer’s Disease Assessment Scale Cognitive Subscale (ADAS‐Cog).ResultForty‐four participants (73%) have significant modifiable risk factors (CAIDE > 6). Compared to participants without significant risk factors, participants with significant modifiable risk factors (CAIDE > 6) have more impaired cognition with lower MoCA scores (16 + 4 vs 19 + 3, p=0.02). MMSE was noted to be lower (25 + 3 vs 27 + 2, p=0.06); and ADAS‐Cog scores higher (13.6 + 6 vs 11.8 + 5, p=0.2), however, it was not significant.ConclusionThis study shows that MCI participants with significant modifiable risk factors (CAIDE > 6) have more cognitive impairment suggesting the utility of CAIDE in the community to screen individuals at risk for dementia. Findings support the need to address modifiable risk factors to prevent cognitive deterioration. Further trials that investigate the effects of multi‐domain intervention and treatment for risk factors in improving cognition, delaying cognitive deterioration and dementia conversion.
Subjective memory decline and neuropsychological performance
Authors: Xu Ying , Peters Ruth , Eramudugolla Ranmalee , Anstey Kaarin J 
Published: December 2020

AbstractBackgroundThe association between subjective memory decline (SMD) and different domains of cognition is not well understood.MethodFour waves (4‐year intervals between waves) of data from 2,551 participants (aged 62.5 ±1.5 years, 52% male) of the Personality and Total Health (PATH) study were used. SMD was defined as a response of ‘no’ to one question: ‘Do you feel you can remember things as well as you used to?’ (w1 and w2), and categorized as ‘consistent’ (SMD both waves), ‘fluctuate’ (either wave) and ‘neither’. The more comprehensive Memory Assessment Clinic‐Q (MAC‐Q) was also available at w4, and includes remembering names, phone numbers, postcodes, where objects are, newspaper reports and shopping‐list items. Neuropsychological tests (w2 to w4) included immediate and delayed recall, digit span backwards, spot the word, symbol digit modalities (SMDT), Trails A and B and Purdue pegboard. We used random‐effect linear mixed models (LMMs) to examine temporal and prospective associations between SMD categories and neuropsychological performance, and linear regression models to investigate cross‐sectional associations between SMD and neuropsychological performance at w4.ResultFifty‐one percent, 27% and 22% of participants had ‘neither’, ‘fluctuate’ and ‘consistent’ SMD. SMD categories were not associated with steeper decline in any neuropsychological performance, but were associated with lower z transformed SDMT and purdue pegboard (both hands and dominant hand) scores at w2 in all LMMs (adjusted for age, sex, education [model 1], plus anxiety, depression [model 2], smoking, hypertension, diabetes and high cholesterol [model 3], and effect sizes were ‐0.07 (‐0.13, ‐0.01), ‐0.20 (‐0.32, ‐0.08) and ‐0.13 (‐0.24, ‐0.02) in model 3 (all P ≤ 0.03). In sensitivity analyses, similar results were found when using SMD at w1 or w2, separately, as the ‘exposure’. Nineteen percent of participants had MAC‐Q assessed SMD, which was cross‐sectionally associated with all neuropsychological tests except for digit span backwards (all P<0.02).ConclusionPresence of MAC‐Q assessed SMD was cross‐sectionally associated with verbal memory, executive function, processing speed, manual dexterity and bimanual coordination. To be useful in healthcare settings, while ensuring simplicity, SMD measurement may need to contain specific memory items, and its value in predicting cognitive decline needs confirmation.
Collaborative co‐design of an active and healthy ageing program using mobile technology to reduce dementia risk in older Aboriginal Australians
Authors: Radford Kylie , Nichols Madeleine , Timbery Alison , Wettasinghe Pam , Allan Wendy , Daylight Gail , Lavrencic Louise , Broe Gerald A , Garvey Gail , Delbaere Kim 
Published: December 2020

AbstractBackgroundHigh rates of dementia have been observed in Aboriginal Australians and dementia risk reduction is a priority in this population. The Koori Active and Healthy Ageing Project aimed to develop new, effective, culturally appropriate healthy brain ageing approaches in collaboration with older Aboriginal people and partner communities in regional and urban Australia.MethodInitially, 34 semi‐structured interviews and 2 yarning (focus) groups were conducted with older Aboriginal participants to understand perceptions regarding community health priorities, preferences for healthy ageing programs and acceptability of technology as a platform for program delivery. Following consultation and development, a pilot randomised control trial (RCT) was conducted over 16 weeks, to evaluate the feasibility of a new program versus a health education control condition in 30 Aboriginal people aged 45+ years. The primary outcome included dual‐task walking. Trial registration ID: ACTRN12619001130156.ResultQualitative interviews identified key health concerns including memory loss, mobility, depression, and access to healthcare services. Using self‐directed technology for healthy ageing was widely supported, however, the importance of maintaining social group connections was emphasised. StandingTall is an unsupervised balance exercise program delivered using mobile technology for older people and was the preferred option selected in yarning groups. With further consultation, this program was redeveloped to provide a culturally inclusive interface, and incorporate cognitive‐motor (dual‐task) activities to boost potential benefits for healthy brain ageing and maintaining functional independence. Eighteen participants were enrolled and completed the RCT (8 intervention, 10 control). Users rated the StandingTall program as easy and enjoyable to use. There was no significant effect of intervention observed on dual‐task walking in intention to treat analysis (F(1,16)=0.14, p=0.71). However, adherence was highly variable and likely affected outcomes; three participants did not engage with the program and five reached a median of 33.4 minutes per week (max=130.7).ConclusionBy implementing a technological platform, this program has strong potential to improve access to dementia prevention strategies, enable low‐cost individualised program tailoring and facilitate transferability across diverse community settings. Understanding the factors related to program adherence is critical and a larger trial is needed to examine the effectiveness of the program in this population.
Comparing conventional wet EEG vs dry‐sensor wireless EEG to probe sensory processing and neuronal function in the aging brain
Authors: Nolan Hugh , Barbey Florentine , Buick Alison R , Dyer John , Murphy Brian 
Published: December 2020

AbstractBackgroundNeurodegenerative conditions such as AD, PD and MS can develop slowly, making early detection and on‐going characterisation a challenge. Current methods rely primarily on clinical opinion/self‐reports, or on burdensome and expensive clinic‐based methods. Visual and other sensory evoked potential tasks, particularly with steady‐state stimulation, have been used to probe neuronal function in healthy aging (Sridhar & Manian 2019), and neurodegeneration (Jacob et al 2002, Viallate et al 2010), in pre‐clinical and symptomatic stages (Shahmiri et al 2017) – but using conventional lab/clinic based wired wet EEG systems. In this proof‐of‐concept study, we evaluate wireless dry EEG as a less burdensome alternative. If feasible this could provide an easy‐to‐use, scalable and objective measure of neuronal function, for use in larger longitudinal studies of these conditions.MethodsWe compare signals recorded from a wireless dry‐EEG headset (BrainWaveBank Ltd – Murphy 2018, 2019), and state‐of‐the‐art conventional wet‐EEG hardware (Biosemi ActiveTwo). Informed consent was obtained from 8 healthy adult males for this methodological study. Each attended 2 separate in‐lab sessions, one week apart, in which both dry and wet recordings were made. Static and flickering steady state (14Hz) visual stimulus conditions were presented. Grand average VEPs were calculated for each recording and stimulus condition. Signal stability was quantified using a Monte Carlo process to estimate 95% confidence intervals. From the steady state VEP, scalp topographies of spectral power were also computed.ResultsAfter band‐pass and notch filtering, a grand average of a simple visual‐evoked potential (Figure 1) recorded at posterior recording sites with the wireless dry‐EEG headset has similar waveform morphology and noise levels to that from conventional wet‐EEG equipment – as does the steady state VEP (Figure 2). Topographies of spectral power at 14 and 28Hz (Figure 3) show a similar central/posterior scalp distribution.ConclusionsIn controlled environments, a wireless dry‐sensor EEG headset can yield aggregate data of comparable quality to a state‐of‐the‐art wet‐EEG, making much larger scale studies of sensory processing and broader neuronal function possible for the first time.
Perception of fragmented letters differentiates pathologically confirmed dementia with Lewy bodies from Alzheimer’s disease
Authors: Salmon David P. , Smirnov Denis S. , Hamilton Joanne M. , Hansen Lawrence A. , Galasko Doug R. 
Published: December 2020

AbstractBackgroundThere is evidence that disproportionate impairment of visuoperceptual abilities can help distinguish Dementia with Lewy Bodies (DLB) from Alzheimer’s Disease (AD), but the reliability of this effect has not been established in patients with autopsy confirmed disease, and the impact of co‐occurring Lewy body and Alzheimer pathology has not been examined.MethodA relatively pure test of visuoperceptual ability, the Fragmented Letters Task of the Visual Object and Space Perception (VSOP) battery was administered to 19 patients with pathologically confirmed DLB (17 Neocortical, 2 Limbic) with various levels of concomitant AD and 23 patients with pathologically confirmed AD only. Groups were matched for a mild level of dementia (MMSE >15, AD mean=24.7+3.6 and DLB mean=25.7+3.4) and were compared to 45 healthy elderly controls. In the Fragmented Letters Task individuals must identify 20 letters that are visually degraded by 70%. Performances on more complex visuospatial (Block Design) and memory (California Verbal Learning Test; CVLT) tests were also compared.ResultDLB patients performed worse than AD patients (B=‐2.29±0.64, p = 6x10‐4) and controls (B=‐2.73±0.62, p=3.8x10‐5) on the Fragmented Letters Task even after adjustment for demographics, MMSE, and ability to identify intact letters. AD patients did not differ from controls (B=‐0.53±0.62, p=0.34). Results were similar when DLB with (n=8, B=‐2.31±0.81, p = 0.006) or without (n=11, B=‐2.15±0.77, p = 0.006) concomitant AD pathology (Braak stage < 4 vs. 5‐6) were separately compared to pure AD. ROC analyses to distinguish DLB from AD showed that the Fragmented Letter Test (AUC 0.86) outperformed Block Design (AUC 0.71) and CVLT Immediate Recall (AUC 0.48).ConclusionIn contrast to complex visuospatial and memory tasks, a relatively pure test of visuoperceptual ability, the Fragmented Letters Task, was uniquely impaired in DLB (vis a vis AD) and effective at distinguishing DLB from AD. Because impairment was not associated with concomitant AD pathology in DLB patients, and patients with AD were unimpaired, the deficit appears to be driven primarily by Lewy body pathology. Results suggest the quick and easily administered Fragmented Letters Task has excellent clinical utility for differentiating DLB from AD in mild to moderate stages of dementia.
Role of white matter hyperintensities, hemoglobin and vitamin B‐12 on cognitive decline: Two‐year follow‐up data from the Tata Longitudinal Study of Ageing (TLSA)
Authors: Balakrishnan Aditi , Tiwari Vivek , Abhishek M.L. , Rao Naren P. , Ravindranath Vijayalakshmi ,   TLSA Investigators
Published: December 2020

AbstractBackgroundThe presence of white matter hyperintensities is commonly seen in elderly individuals and many studies have identified its relation to cognitive decline, however the effect size of this relationship has been seen to be relatively small. Evidence also suggests that among older individuals, low levels of hemoglobin and Vitamin B‐12 are indicators of cognitive decline. This study seeks to identify the role of white matter hyperintensities, hemoglobin and Vitamin B‐12 on cognitive change among an urban elderly population in Bangalore, India.MethodA subset of 87 individuals (49 Males and 38 Females, mean age=65.9 years) from TLSA Cohort above the age of 45 participated in the TATA longitudinal Study of Ageing, conducted in Bangalore, India. All participants underwent the Addenbrooke’s Cognitive Examination III (ACE‐III), blood investigations and Magnetic Resonance Imaging (MRI) scans as per the Alzheimer's Disease Neuroimaging Initiative (ADNI‐II) protocol at baseline. Brain images were acquired with a 3T Siemens Skyra MR Scanner. MRI scans were then visually rated on Fazeka’s scale for white matter lesions. Cognitive assessments were repeated two years later, on all participants. Change in cognition was calculated by subtracting followup scores from baseline scores. Regression analysis was conducted in order to examine the relation between White matter hyperintensities, vitamin b‐12 and hemoglobin at baseline with change in cognitive scores over time.ResultThe results indicate that Fazeka’s deep white matter scores, hemoglobin and vitamin B‐12 are significant predictors of changes in ACE‐III Memory scores at a 2 year follow up. A significant regression equation was found (F(3,38)=6.73, p<0.001), with an R2 of 0.347.ConclusionThe findings of the study suggest that an individual’s deep white matter hyperintensity, along with hemoglobin levels and Vitamin B12 at baseline are potential indicator of cognitive change during follow up. Future longitudinal studies with larger sample size are required to examine whether this model is a significant predictor of cognitive decline and dementia.
Cognitive decline and conversion to MCI and dementia in heart failure: A 12‐year follow‐up study
Authors: Jung Miyeon J , Apostolova Liana G. , Gao Sujuan , Burney Heather , Saykin Andrew J. , Pressler Susan J 
Published: December 2020

AbstractBackgroundCognitive decline and development of mild cognitive impairment (MCI) and dementia over time in heart failure (HF) have not been fully examined. The purpose of this study was to compare (1) cognitive decline and (2) time to convert to MCI or dementia between people with and without HF.MethodData were retrieved from the National Alzheimer’s Coordinating Center database in September 2017. People with baseline dementia were excluded. Cognitive decline was assessed using changes in age, education, and gender‐adjusted z‐scores of verbal memory (Logical Memory Test delayed recall), attention (Digit Span Forward, Trail Making Test A), executive function (Trail Making B, Digit Symbol Test), and language (Category Fluency, Boston Naming Test) over 12 years. Time to convert was assessed using diagnosis of cognitive status by neurologists at each visit. Statistical analyses were conducted using multivariable Cox Proportional Hazards Models after adjusting for covariates (e.g., comorbidity, APOE carrier status).ResultAmong 4,149 participants, 87 had HF (66 with normal cognition, 21 with MCI) at baseline Median years of follow‐up was 6 (SD=2; range = 1‐12). At baseline, compared with non‐HF participants, HF participants were significantly older, had less education and more comorbidities, and were more likely to have MCI. Compared with non‐HF participants, HF participants had faster decline in attention (time by group interaction b=‐0.059, p=.0007), executive function (b=‐0.095, p=.0006) and language (b=‐0.051, p=.0137) but not memory (b=‐0.055, p=.0595) over 12 years after controlling for covariates and baseline cognitive status. Time to convert from normal cognition to MCI was not significantly different between participants with and without HF. Similarly, time to convert from MCI to dementia did not differ between the groups. The small number of HF participants may have limited the ability to detect 50% survival probability.ConclusionParticipants with HF had accelerated cognitive decline, especially in the domains of attention, executive function, and language compared with people without HF. The effect of HF on time to convert needs to be tested in larger samples.
Combining MRI and genetic data in the Tohoku Medical Megabank Organization cohort study for innovative Alzheimer’s disease research
Authors: Taira Makiko , Fuse Nobuo , Mugikura Shunji , Kinoshita Kengo , Yamamoto Masayuki 
Published: December 2020

AbstractBackgroundThe Tohoku Medical Megabank Organization (ToMMo) is a prospective genome cohort study and biobank established in 2012 in Northern Japan’s Miyagi Prefecture following the Great East Japan Earthquake and Tsunami. ToMMo has enrolled 120,000 healthy male and female adults aged over 20, plus 30,000 children in a longitudinal study designed to identify diverse biological, psychological, and lifestyle characteristics associated with mainly common diseases and support additional innovative research. Baseline information includes brain MRI, genetic data, physiological measurements, several cognitive and psychological screening tests, and health/lifestyle assessments. Alzheimer’s disease (AD) is a key research focus; goals include using MRI, genomic and other data in combination to identify predictive biomarkers. This communication reports initial progress.MethodMRI: MP‐RAGE, PCASL, FLAIR and DTI sequences were performed. Following quality checks and pre‐processing, Freesurfer (2.1.0) was used with the Destrieux or Desikan‐Killiany atlas to parcellate multiple anatomical brain regions and derive cortical thickness data. The digitized data were archived; raw data was preserved. Genetics: whole genome sequencing (WGS) and/or DNA array data were obtained for participants; apolipoprotein E (APOE) genotype was identified. Blood, urine, stool, saliva and dental plaque samples were collected and stored for biomarker identification and other studies.ResultUsable MRI data exist for >12,000 participants (4,000 for FLAIR); approximately half the scans are of participants aged ≥50 (see Table). The quality exclusion rate was <5%. WGS and DNA array data have so far been prepared for 800 participants who had MRI scans; APOE genotype information exists for all participants with MRI scans. The MRI and genetic data, plus demographic, cognitive screening and relevant health data are currently being readied for use in combination to identify valuable biomarkers, e.g., those predicting incipient cognitive impairment in preclinical AD. The frequency of major known AD risk alleles in the ToMMo sample will also be determined and compared to that in external GWAS studies.ConclusionToMMo’s MRI, WGS/DNA array, biospecimen repository and other data represent a powerful resource for AD research. Specifically, the combination of MRI and genetic data will support unique disease progression analyses and investigations to elucidate AD pathophysiology.