bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cognition differentiates gait speed among older adults
Authors: Paulson Sally , Gray Michelle , Glenn Jordan M. , Madero Erica N. , Myers Jennifer , Gills Joshua L. , Jones Megan , Campitelli Anthony , Vincenzo Jennifer , Walter Christopher 
Published: December 2021

AbstractBackgroundThe ability to perform a motor and cognitive dual‐task (DT) becomes more challenging as one ages and shows a greater deficit, if one has a cognitive impairment (CI). CI has also been shown to predict a decline in physical functioning. Therefore, the purpose was to examine differences between cognitively healthy (CN) and cognitively impaired (CI) older adults on gait speed (GS) during habitual (HAB) and fast (FAST) walking trials with and without a DT.Method83 older adults (80.66±5.36) completed a digital Visual Paired Comparison (VPC) cognitive assessment, which measured working memory, and a Digital Symbol (DS) cognitive assessment, which measured processing speed. Participants were grouped into CN or CI based on their results for each assessment. Subjects performed two trials of each walking test: HAB, FAST, HAB‐DT, and FAST‐DT. The DT trials were performed using a working memory task. GS was calculated using the time to cover 10m. One‐way ANOVA was used to assess for differences in GS between VPC and DS cognitive groups.ResultWhile HAB GS (p=.10) was not significantly different between the VPC cognitive groups, the CN group walked significantly faster than the CI group during the FAST, HAB DT, and FAST DT trials (p<.05). There was not a significant difference in HAB GS (p=.10) or HAB DT GS (p=.08) between the CI and CN DS groups. However, the DS CI group walked significantly slower during the FAST (p=.03) and FAST DT (p=.05) assessments.ConclusionIndividuals with CI showed no statistical difference in habitual walking speed. However, this was clinically meaningful as the individuals with an average or above average working memory and processing speed walked faster than individuals with CI by 8.4% and 6.5%, respectively. While GS declined during the DT trials, individuals with a working memory impairment showed a greater decline, and it was even larger during the fast DT trials and for individuals with a working memory (19.5%) or processing speed (17.6%) impairment. Previous research has suggested DT walking involves activation of the prefrontal cortex, which may partially explain the greater decline in DT GS for those with working memory impairment.
Steeper basal cortisol slopes are associated with elevated risk of pathological amyloid‐beta accumulation
Authors: Saelzler Ursula G. , Moffat Scott D. , Panizzon Matthew S. 
Published: December 2021

AbstractBackgroundThe accumulation of amyloid‐beta (Aβ) plaques, the hallmark neuropathology of Alzheimer’s disease (AD), begins several decades prior to the onset of cognitive symptoms. The progression of the disease is believed to be driven by this accumulation; therefore, there is interest in identifying factors which trigger or accelerate the aggregation of Aβ. We examined whether changes or elevations in basal cortisol levels predicted the transition to a state of Aβ‐positivity, as determined by Pittsburgh Compound B (PIB) thresholds.MethodData were utilized from the neuroimaging subset of the Baltimore Longitudinal Study of Aging. One‐hundred and fifteen middle‐aged to older adults (mean age 58.39 at baseline) with at least two 24‐hour urinary free cortisol measures collected prior to reaching the threshold for Aβ‐positivity were included.ResultA Cox regression model showed that after controlling for age, the slope of basal cortisol levels over time was significantly associated with the risk of becoming Aβ‐positive, such that each standard deviation unit increase in slope was associated with a 38% increase in Aβ‐positivity risk. Conversely, the average cortisol level during this same period was not significantly associated with Aβ‐positivity risk (HR = 1.03, p = 0.14).ConclusionThese results suggest that increases in basal cortisol levels, regardless of the average level, are associated with increased likelihood of pathological Aβ accumulation. Further investigation is warranted to determine whether basal cortisol increases directly contribute to increased Aβ accumulation and whether this mechanism can be targeted by therapeutic intervention.
Racial‐ethnic differences in baseline and longitudinal change in neuropsychological test scores in the NACC Uniform Data Set 3.0
Authors: Chan Kwun Chuen Gary , Barnes Lisa L. , Saykin Andrew J. , Sano Mary , Au Rhoda , Craft Suzanne , Teylan Merilee A. , Levey Allan I , Weintraub Sandra , Kukull Walter A. , Dodge Hiroko H 
Published: December 2021

AbstractBackgroundRacial/ethnic differences in cross‐sectional assessment of cognitive test performance are well known. However, longitudinal studies of differences in cognitive decline have been mixed. The purpose of this study was to examine racial/ethnic differences in baseline and longitudinal change on the Uniform Data Set (UDS) version 3 of the NIA Alzheimer’s Disease Research Centers program.MethodLongitudinal data from 2,806 participants (2336 non‐Hispanic White, 350 non‐Hispanic Black, 120 Hispanics tested in Spanish) were acquired from the National Alzheimer’s Coordinating Center (NACC), and included baseline and at least two follow‐up visits. We used marginal linear regression models to examine racial/ethnic differences in standardized test scores, by including racial group indicators, time (in years) since initial visit and their interaction, controlling for baseline age, sex, education and changes in global CDR scores during the follow‐up. Additional models examining longitudinal change also controlled for baseline score. The outcome variables included the Montreal Cognitive Assessment (MoCA, Number Span (Forward/Backward), Craft Story 21 Recall (Immediate/Delayed), Multilingual Naming Test (MINT), Category Naming (animals and vegetables), Trail Making A and B, and Benson Figure (Copy/Recall). Estimates were obtained from generalized estimating equations with an exchangeable working correlation, and robust standard errors were used to construct confidence intervals and compute p‐values.ResultBlack and Hispanic participants had lower baseline scores on all tests (difference in standard deviation units: ‐0.029 to ‐0.858 for blacks, and ‐0.014 to ‐1.214 for Hispanics), but showed attenuated decline on all tests (difference in standard deviation units per year: 0.002 to 0.102 for blacks, 0.022 to 0.296 for Hispanics) compared to non‐Hispanic Whites. When baseline test scores were controlled, the differences in longitudinal changes became mostly statistically non‐significant.ConclusionDespite large racial/ethnic differences in baseline test scores, there were no racial/ethnic differences in longitudinal change over time once baseline differences were controlled. Further, results suggest that the utility of baseline test scores in UDS version 3 to predict longitudinal change may not be compromised in racially diverse populations.
A phase 1 study of AL002 in healthy volunteers
Authors: Ward Michael , Long Hua , Schwabe Tina , Rhinn Herve , Tassi Ilaria , Salazar Santiago Viveros , Rychkova Anna , Tu GuangHuan , Barner Cheryl , Yeh Felix L , Spencer Madeline , Paul Robert 
Published: December 2021

AbstractBackgroundTriggering receptor expressed on myeloid cells ‐2 (TREM2) is a prominent Alzheimer’s disease (AD) risk gene that is expressed by microglia in the brain; reduced function of TREM2 is associated with a 3‐fold increase in AD risk. AL002 is a humanized monoclonal IgG1 antibody. The proposed mechanism of action is that it binds to TREM2 and activates the TREM2 signaling pathway to increase the ability of microglia to clear pathology and protect neurons with the goal of treating patients suffering from AD. INVOKE was a first‐in‐human Phase 1 study designed to investigate the safety, tolerability, pharmacokinetics and pharmacodynamics of intravenously administered AL002 in healthy volunteers (HV).MethodINVOKE was a randomized, placebo‐controlled, double‐blind investigation of AL002 in healthy volunteers (HV). The SAD portion of the study, which included a total of 64 HV receiving a single dose of 0.003 to 60 mg/kg AL002 or matching placebo is complete. Blood and CSF biomarkers were measured before dosing and at multiple timepoints after dosing.ResultIn the SAD portion of the INVOKE study, AL002 was generally well tolerated in HV. AL002 decreased sTREM2 in cerebral spinal fluid (CSF), in a dose‐dependent manner, demonstrating proof of target engagement in the brain. Microglia biomarkers of TREM2 activation, such as CSF1R, SPP1 and IL1RN, were identified with in vitro and in vivo non‐clinical experiments. Consistent with these findings, treatment of HV with AL002 caused an increase in CSF levels of CSF1R, SPP1 and IL1RN in a dose‐dependent manner, suggesting proof of microglia activity through the TREM2 pathway.ConclusionAL002 treatment resulted in TREM2 target engagement and proof of activity in the CSF of HVs. These results have supported progressing AL002 to an ongoing Phase 2 study (INVOKE‐2) to investigate its effects on cognitive decline and neurodegeneration in subjects with early AD.
Smartphone ownership and usage in Chinese‐ and English‐speaking older adults
Authors: Li Clara , Zeng Xiaoyi , Wang Kun , Neugroschl Judith A. , Aloysi Amy , Cai Dongming , Martin Jane , Sewell Margaret , Greenberg Jonathan , Xu Mengfei , Evans Kirsten , Pun Kelly , Tocco Carly , Ardolino Allison , Meuser Caroline , Sheppard Faye , Gamino Juliana , Velasco Nelly , Sano Mary , Loizos Maria , Zhu Carolyn W 
Published: December 2021

AbstractBackgroundData collection by smartphone is becoming more widespread in healthcare research. Previous studies reported racial/ethnical differences in the use of digital health technology. However, cross‐language group comparison (Chinese‐ and English‐speaking older adults) were not performed in these studies. This project will expand to smartphone technology use in diverse older populations with a focus on Chinese American older adults who are monolingual Chinese‐speakers.MethodThe Alzheimer’s Disease Research Center (ADRC) at Icahn School of Medicine at Mount Sinai (ISMMS) evaluates diverse older populations using National Alzheimer’s Coordinating Center’s Uniform Data Set (NACC UDS). The UDS has different language versions, including English and Chinese. The evaluation includes a medical examination, cognitive assessments, and a research blood draw. Smartphone ownership and usage were captured using a local questionnaire developed by our ADRC. The questionnaire, available in English and Chinese, was administered by our ADRC coordinators during the COVID‐19 pandemic. Multivariate analysis of variance (MANOVA) was used to examine differences in technology ownership and usages between the two language groups, while controlling for age, gender, education, and cognitive status (measured by Clinical Dementia Rating).Result33 Chinese‐ and 117 English‐speaking older adults who received a diagnosis of normal cognition or mild cognitive impairment at consensus were included in the data analysis. Results reveal a high prevalence of smartphone ownership in our Chinese‐ (100%) and English‐speaking older participants (86.3%). Participants in both language groups use mobile technology for a wide range of purposes, such as getting news and other information (Chinese=90.9%; English=87.2%), sending/receiving text (Chinese=97.0%; English=96.6%), watching videos/TV shows (Chinese=78.8%; English=69.2%), and taking classes (Chinese=57.5%; English=57.3%). However, Chinese‐speaking older adults were less likely than English‐speaking older adults to use mobile technology to post their own reviews or comments online (Chinese=9.1%; English=39.3%, p=0.001), download or purchase an app (Chinese=21.2%; English=70.9%, p<0.001), track health/ fitness via apps/website (Chinese=12.1%; English=47.9%, p<0.001) and manage/receive medical care (Chinese=15.2%; English=67.5%, p<0.001).ConclusionOur findings highlight potential barriers to smartphone usage in Chinese American older adults with limited English proficiency. The results have implications for how smartphone technology can be used in clinical practice and aging research.
On the use of saliency maps and convolutional neural networks for improved Alzheimer's disease assessment
Authors: Lopes Marilia Karla Soares , Cassani Raymundo , Falk Tiago H 
Published: December 2021

AbstractBackgroundAlzheimer’s disease (AD) is a progressive neurodegenerative disease accounting for 60–80∖% of dementia cases worldwide[2]. Early diagnosis can decrease the severity of the disorder in addition to improving the quality of life of patients. Biomarkers based on electroencephalography (EEG) have emerged as a promising tool in the study of AD, with the advantage of being non‐invasive, less expensive, and potentially portable when compared to other biomarkers. One such biomarker has been the so‐called "modulation‐spectral‐patch‐feature" proposed in [1]. Such features were found based on visual inspection of modulation spectra from healthy‐controls and age‐matched AD patients. Over the last few years, however, innovations in machine learning, in particular in deep‐neural‐networks, have revolutionized many biomedical image and signal processing applications[4,5,6]. In this paper, we explore their use in building better biomarkers for AD assessment. In particular, we explore the use of saliency‐maps(SM)[3] obtained from classification using convolutional‐neural‐networks(CNN) to extract optimal feature patches in a data‐driven sense.MethodThe study collected data from fifty‐four participants, including 20‐healthy‐controls, 19‐Mild‐Cognitive‐Impairment, and 15‐moderate‐to‐severe‐AD, all age‐matched. Twenty‐channel EEG signals were acquired during eyes‐closed‐resting‐state sessions of eight minutes. The EEG recordings were pre‐processed to remove artifacts. The model performance was evaluated using 5‐fold‐cross‐validation(CV). The average SM was extracted from the validation‐set in order to highlight the relevant modulation "patches" in a data‐driven manner. The CNN model has two convolutional‐layers and three fully‐connected‐layers.ResultThe tested CNN resulted in the following figures‐of‐merit over the 5‐fold‐CV: 89.4%+/‐2.3% for accuracy and 89.3%+/‐2.3% for f1. From the average SM of each fold, it can be seen that theta‐modulated‐by‐delta and beta‐modulated‐by‐theta were important modulation regions . Others regions such as beta‐modulated‐by‐alpha, alpha‐modulated‐by‐delta, and gamma‐modulated‐by‐beta were also important. While some of these regions match those found visually in[1], other provide more insights into AD assessment.ConclusionIn this paper, we show the efficacy of EEG modulation‐spectrograms coupled CNNs saliency‐maps to extract data specific features useful for Alzheimer's disease diagnosis. In particular, several main regions of interest were identified, thus building on previous work that relied on visual inspection. As future work, we will also explore the importance of each EEG channel, thus potentially leading to a more low‐cost and portable solution.
MRI and CSF markers of mild behavioural impairment: Findings from the MEMENTO cohort study
Authors: Chen Hung‐Yu , Robert Philippe , Nathan Santhosh , Smith Eric E. , Ismail Zahinoor 
Published: December 2021

AbstractBackgroundMild behavioural impairment (MBI) is characterized by late‐life emergent and persistent neuropsychiatric symptoms (NPS). It is as an at‐risk state for incident cognitive decline and dementia. For some, MBI may be the first observable manifestation of a neurodegenerative process such as Alzheimer’s disease (AD).MethodsWe examined associations between MBI and established dementia imaging and CSF markers, in 789 participants with mild cognitive impairment (MCI). Study data were obtained from the French MEMENTO cohort study.Neuropsychiatric Inventory (NPI) scores were used to determine MBI scores using a published algorithm. NPI data at baseline and 6‐month visits were used to categorize patients into MBI+ (persistent NPS i.e., NPS at both time points) and MBI‐ (no NPS or NPS at either but not both time points). MRI and CSF measurements were completed at baseline. Linear regressions were fitted to assess if MBI status at 6 months was associated with reduced thickness or volume in each of the a priori selected regions associated with Braak stages 1‐5: entorhinal cortex, hippocampus, fusiform gyrus, inferior temporal cortex and frontal pole. To assess if MBI status was associated with CSF biomarkers (Aβ42, Aβ40, t‐tau, p‐tau, Aβ42/Aβ40, p‐tau/Aβ42 and t‐tau/Aβ42), seven linear regressions were conducted. All models controlled for age, sex, education, and mini‐mental state examination scores. Volume and thickness analysis further controlled for total intracranial volume.ResultsMBI+ (persistent NPS) status was associated with decreased entorhinal thickness and smaller hippocampal volume compared to MBI‐ (Table 1). There were no differences between MBI+ and MBI‐ groups in thickness of the Braak stage 3‐5 regions (Table 1). In the subset of MCI participants with CSF data (n=155), compared to MBI‐, MBI+ had lower CSF Aβ42 levels, higher CSF p‐tau/Aβ42 and t‐tau/Aβ42 ratios (Table 2).ConclusionIn a memory clinic sample of older adults with MCI, MBI was associated with AD markers and served as a proxy marker to capture AD changes in a non‐demented sample. These findings extend the literature linking MBI with known dementia biomarkers and emphasize the importance of appropriately ascertained NPS, in this case with respect to symptom persistence, in dementia detection and prognostication.
Effects of novel Cognitive Stimulating Activities (CSAs) on cognition and depression: A 5‐year pragmatic and naturalistic study
Authors: Ng Ted Kheng Siang , Chua Rhu Yuan , Feng Lei , Goh Lee Gan , Kua Ee‐Heok , Mahendran Rathi 
Published: December 2021

AbstractBackgroundAccumulating epidemiological evidence suggest that cognitive stimulating activities (CSAs) improve cognition in older adults. However, there is a lack of longitudinal naturalistic follow‐up studies supporting the effectiveness of CSAs, particularly in a real‐world setting. Whether baseline cognitive status affects cognitive outcomes, and whether a higher involvement in CSAs elicits greater improvements are unknown. We aimed to investigate a novel multimodal CSA intervention to prevent cognitive decline amongst community‐dwelling older adults.MethodFrom the Singapore Longitudinal Diet and Healthy Aging (DaHA) study (n=991, aged ≥60), 264 subjects were assigned to the novel multimodal CSAs controlled trials (mindfulness intervention, horticultural therapy, arts and music reminiscence therapy, and choral singing). The other participants not involved in the CSAs (n=727) served as the control group. At the DaHA cohort’s 5‐year follow‐up, we examined the effects of CSAs on cognitive function. The primary outcomes were changes in global cognition measured by the mini‐mental state examination (MMSE) and its domain scores. Intention‐to‐treat analysis was performed utilizing a linear mixed model. We also conducted sub‐group analyses stratified by baseline cognitive status and the number of CSAs involved.ResultCompared to the control group, although non‐significant, there was an improvement in the CSA group after five years based on the total MMSE score (β =0.108, 95% CI= ‐0.022 to 0.239, P =0.104). Notably, there was a significant improvement in MMSE‐immediate recall score domain (β = 0.199, 95% CI = 0.048 to 0.351, P = 0.010). Sub‐group analyses showed that older adults with MCI and those involved in more CSAs had greater improvements in total MMSE and selective domain scores after 5 years, with effect sizes of Cohen’s D=0.42.ConclusionAlthough global cognition was not significantly improved, the multimodal CSA intervention showed significant improvements in the scores of working memory domain, possibly, highlighting the high malleability of this cognitive domain. Furthermore, moderate effect sizes of improvements observed in the MCI sub‐group and those involved in more CSAs suggesting that these individuals could gain greater long‐term benefits participating in CSAs. From a public health perspective, these sustained improvements in cognitive functions over five years’ time could potentially delay or prevent dementia.
Risk factors of oral health related quality of life: An evidence from Australian Longitudinal Study of Ageing
Authors: Bindal Priyadarshni , Barnett Anthony , Hoang Ha , Mishra Vijay Kumar 
Published: December 2021

AbstractBackgroundOral disease and tooth loss have a significant negative impact on the quality of life and well‐being of older adults. As OHRQoL is a major feature of the daily experiences of older adults, alongside decreased general health and functioning, and shrinking social networks and activities, it is particularly important to examine whether a relationship between OHRQoL and amongst socioeconomic and psychological factors exists. Socioeconomic disparities in oral health have been consistently demonstrated for various indicators, mostly clinical and disease related but also subjective measures of oral health and quality of life. The key risk factors include poor general health, depression, anxiety, loneliness and low social participation and social support.MethodWe utilized secondary data from the seventh wave of Australian longitudinal study of Ageing (ALSA). ALSA was coordinated by the research teams of Flinders University, Australia. The data analysis included a sample of 257 (98‐male, 159‐female) participants from rural Australia. Chi‐square and Wilcoxon’s tests were applied on categorical variables to under the association between outcome and predictors. We created depression scale based on 20 indicators of depression among older people. The multinomial logistic regression model was used to study the strengths of relationships between oral health related quality of life (OHRQoL) and its possible risk factors.ResultThe study found a clear and significant association between OHRQoL and depression, loneliness, anxiety including socio‐economic factors such as age, sex, income and family structure. The older people who faced a little or no difficulty in performing the activities such as eating food, speaking clearly, smiling, laughing and showing teeth without embarrassment are more likely to live better life. Females are less likely to have good oral health related quality of life than men.ConclusionThis findings of this study would lead future work and will be beneficial to understand healthy ageing through oral health related quality of life (OHRQoL) and its risk factors as well as providing policy and practice recommendations improve overall quality of life in old age, and achieve targets laid out in Sustainable Development Goals for Health (SDG‐3).