bluuebunny/crossref_metadata_2025_split huggingface dataset:
Utilization of a novel digital neuropsychological assessment Suite in patients with Alzheimer’s disease and cognitive healthy controls: A preliminary investigation
Authors: Myers Jennifer Rae , Ozaki Satoshi , Madero Erica N. , Harrison John E , Mak‐McCully Rachel , Onguchi Kaori , Gray Michelle , Glenn Jordan M. 
Published: December 2021

AbstractBackgroundGlobally, the prevalence of Alzheimer’s disease is expected to triple by 2050. Additionally, as COVID‐19 has accelerated the urgency for remote neuropsychological assessment, the development of easily accessible and valid remote methods of assessments are critical for continued monitoring of cognitive health. In response to this clinical and scientific need, we investigate the use of the Neurotrack assessment suite as a remote digital cognitive assessment platform.MethodAs part of an ongoing study, 9 patients diagnosed with AD (Mean age = 75.6, 55% female) and 9 cognitively healthy controls (Mean age = 75.6, 44% female) were assessed using three exams from the Neurotrack assessment suite which were designed to assess 1) processing speed, 2) associative learning and 3) associative and recognition memory. Independent samples t‐tests were conducted to examine differences in exams scores between the two groups.ResultsThere were significant differences observed in processing speed (p=.004), associative learning (p=.001), and associative memory performance (p=.03) between patients with AD and cognitive healthy controls. There was no difference in recognition memory (p=.47).ConclusionThe Neurotrack Assessment Suite appears to be a promising method for remote cognitive testing. Further investigation of the efficacy of this platform as a valid and easily accessible assessment tool is currently underway.
Lipid peroxidation mediates the relationship between cardiopulmonary fitness and depressive symptoms in people with coronary artery disease
Authors: Feng Vivian , Tumati Shankar , Wang RuoDing , Bawa Kritleen Kaur , Gallagher Damien , Herrmann Nathan , Andreazza Ana C. , Swardfager Walter , Marzolini Susan , Oh Paul I. , Lanctôt Krista L. 
Published: December 2021

AbstractBackgroundEmerging evidence suggests that poor cardiorespiratory fitness levels are related to greater depressive symptoms. In those with coronary artery disease (CAD) depressive symptoms are common and are associated with an increased risk of mortality. Exercise intervention is suggested to have positive effects on depressive symptoms and counteract oxidative stress (OS) in the body. However, a mechanistic link between cardiorespiratory fitness (CRF) and depressive symptoms has not been identified in CAD individuals. We aim to investigate if OS explains the relationship between poor cardiorespiratory fitness and higher depressive symptoms in CAD individuals.MethodCAD participants were recruited and OS was measured via serum lipid peroxidation marker 8‐isoprostane (8‐ISO), lipid hydroperoxides (LPH), and 4‐hydroxyneoneal (4‐HNE). CRF was assessed by peak oxygen uptake (VO2peak) and depressive symptoms measured via Center for Epidemiological Studies‐Depression (CES‐D) scale. Analyses were controlled for age, hypertension, hypercholesterolemia, and antidepressant use. Mediation effects of OS markers on the relationship between CRF and depressive symptoms were tested. A bias‐corrected inferential bootstrapping with 10,000 permutations was used to obtain a 95% confidence interval (CI) for the indirect effect.ResultAmong CAD individuals (n=224), lower VO2peak was associated with higher 8‐ISO (β=0.31, p<0.001) and greater depressive symptoms (β=‐0.143, p=0.038). LPH (B=‐0.172 p=0.017) was associated with greater CES‐D score, but not VO2peak levels (B=‐0.122, p=0.109), when controlling for the same covariates. 4‐HNE was not a significant predictor of CES‐D scores (B=0.059, p=0.372) or VO2peak levels (B=‐0.052, p=0.440). 8‐ISO mediated the relationship between VO2peak (β=0.02, p=0.01) and CES‐D (β=7.13, p=0.001), and LPH did not (‐0.0098, 95% CI [‐0.0314, 0.0042]). Bootstrapping produced a significant unstandardized indirect effect for 8‐ISO (β=‐0.20, SE=0.05, 95% CI=‐0.32, ‐0.01).ConclusionIn those with CAD, poor CRF and greater OS levels were associated with higher depressive symptoms, and this relationship was mediated by 8‐ISO, but not LPH or 4‐HNE. These findings provide greater understanding of the mechanistic reasoning for the link between poor CRF and depressive symptoms.
Reporting amyloid beta levels via bioluminescence imaging with amyloid reservoirs
Authors: Yang Jing , Ding Weihua , Zhu Biyue , Shen Shiqian , Ran Chongzhao 
Published: December 2021

AbstractBackgroundBioluminescence imaging has changed daily practice in preclinical research of cancers and other diseases in the last decades; however, it has been rarely applied in preclinical research of Alzheimer’s disease (AD).MethodIn this report, we demonstrated that bioluminescence imaging could be used to report the levels of amyloid beta (Ab) species in vivo. We hypothesized that AkaLumine, a newly discovered substrate for luciferase, could bind to Ab aggregates and plaques. We further speculated that the Ab species have the reservoir capacity to sequester and release AkaLumine to control the bioluminescence intensity, which could be used to report the levels of Abs.ResultsOur hypotheses have been validated via in vitro tests, mimic phantom imaging, and in vivo imaging using transgenic AD mice that were virally transduced with aka Luciferase (AkaLuc), a new luciferase that generates bioluminescence in the near infrared window. As expected, compared to the control group, we observed that the Ab group showed lower bioluminescence intensity due to AkaLumine sequestering at early time points, while higher intensity due to AkaLumine releasing at later time points. Lastly, we demonstrated that this method could be used to monitor AD progression and therapeutic effectiveness of avagacestat, a well‐studied gamma‐secretase inhibitor.ConclusionOur approach can be easily implanted into daily imaging experiments. We believe that our method has tremendous potential to change daily practice of preclinical AD research.
Hearing loss in older adults interacts with sex and APOE4 to lower resting‐state functional connectivity
Authors: Fitzhugh Megan C , Pa Judy 
Published: December 2021

AbstractBackgroundHearing loss was recently identified as a modifiable risk factor for dementia. However, investigations have yet to evaluate whether hearing loss may interact with other risk factors of dementia, such as female sex and APOE4 allele. The goal of this study was to explore the associations between hearing loss, female sex, and APOE4 on functional connectivity.MethodResting‐state fMRI functional connectivity in 1,000 participants (61.98±7.41 years, 50% female, 50% APOE4 carriers) from the UK Biobank was computed between bilateral planum temporale ROIs (auditory seed regions) and the 1) default mode (DMN), 2) frontoparietal (FPN), and 3) cingulo‐opercular (CON) network ROIs (target regions). Hearing was measured with a speech in noise reception task, which was used to split participants into better performing ear groups (better left ear (56%): ‐5.97±1.50dB; better right ear (44%): ‐6.07±.1.55dB), in which higher scores indicate poorer hearing. ANCOVA models with FDR corrections were used to examine associations of functional connectivity and left and right ear hearing measures, controlling for age. Interactions with sex and APOE4 status were examined, followed by stratified models for sex and APOE4.ResultLeft ear hearing was poorer in females compared to males; this sex difference was also observed within APOE4 carriers. Right ear hearing did not differ between groups. Main effects of sex on functional connectivity showed that females generally have lower connectivity than males; no main effects of APOE4 were observed. Stratified analyses showed that female APOE4 carriers with poorer left ear hearing showed lower functional connectivity between left planum temporale and ROIs of the DMN and CON. Similar results were found for functional connectivity from right planum temporale. No significant associations were found for female noncarriers, male carriers and noncarriers, nor for right ear hearing.ConclusionHearing loss is associated with lower functional connectivity in females who are APOE4 carriers. Lower functional connectivity was observed between auditory processing areas and networks associated with episodic memory, working memory, and attention. These results support that a possible mechanistic underpinning for why hearing loss increases risk for dementia may be due to altered connectivity to higher‐order cognitive networks, particularly for females who are APOE4 carriers.
Microglia activation predicts tau positivity beyond Aβ in Alzheimer’s disease
Authors: Ottoy Julie , Bezgin Gleb , Savard Mélissa , Mathotaarachchi Sulantha , Pascoal Tharick A. , Chamoun Mira , Soucy Jean‐Paul , Gauthier Serge , Rosa‐Neto Pedro 
Published: December 2021

AbstractBackgroundDeposition of amyloid‐beta (Aβ) plaques and hyperphosphorylated tau are known hallmarks of Alzheimer’s disease (AD). In addition, neuroinflammation or microglia activation plays a role in Alzheimer’s pathophysiology and may be a potential driver of abnormal tau deposition. This study demonstrated the important brain regions where microglia activation, in addition to Aβ, is driving tau positivity in AD.Method120 participants from the TRIAD cohort underwent 18F‐AZD4694 amyloid‐PET, 18F‐MK620 tau‐PET, and 11C‐PBR28 neuroinflammation‐PET. All images were normalized to the ADNI template and quantified as SUVR in 35 regions‐of‐interest using cerebellar gray as the reference region. ANCOVA was used to assess the differences in levels of microglia activation between tau‐positive (T+; n=38) vs. tau‐negative (T‐; n=82), corrected for age, sex, APOE‐e4, education, and global Aβ. Tau status was based on both visual rating with elevated uptake in Braak1and2 and quantitative cut‐off of 1.22. In addition, step‐wise logistic regression was conducted to predict T+ in three steps: 1) the covariates, i.e. age, sex, APOEε4, and education, 2) covariates + global Aβ, and 3) covariates + global Aβ + activated microglia in each of the 35 ROIs, corrected for multiple comparisons using FDR. Our prediction model was trained based on a randomly selected 70%/30% training/test set. In order to investigate the stability of our model, this procedure was repeated 500 times.ResultLevels of microglia activation were significantly increased in T+ compared to T‐ in the posterior cingulate (p=0.0001), middle (p=0.02) and inferior (p=0.0005) temporal, fusiform (p=0.0004), and orbitofrontal cortex (p=0.005). Based on logistic regression and a likelihood‐ratio test between each step, we found that the ‘covariates + global Aβ model’ performed significantly better in predicting T+ than the ‘covariates‐only’ model (χ2(1)=72.64, p<0.0001). In the 3‐step model, the addition of activated microglia showed a significantly improvement of the model’s performance to predict T+, particularly the activated microglia in the hippocampus (p=0.001), middle (p=0.006) and inferior (p=0.001) temporal, and fusiform (p=0.001) cortex. Receiver operating characteristic curves (ROC) and AUCs are shown in Fig 1.ConclusionOur study demonstrated that activated microglia in the Braak2 to Braak4 regions play an important role in predicting tau positivity in addition to Aβ.
The link between blood‐based biomarkers and mild cognitive impairment and Alzheimer's disease in a Panamanian sample
Authors: Oviedo Diana C. , Villarreal Alcibiades E. , Rangel Giselle , Carreira Maria B. , Perez‐Lao Ambar R. , Rodriguez Sofía A. , Posada Camilo , Britton Gabrielle B. 
Published: December 2021

AbstractBackgroundStudies on blood‐based biomarkers associated with age‐related cognitive impairment are key to improve intervention mechanisms and delay the expression of symptoms. The objective of this study was to assess the relationship between blood‐based biomarkers and mild cognitive impairment (MCI) and AD in a sample of elderly Panamanians enrolled from an outpatient geriatric service.MethodA descriptive, cross‐sectional, observational study was conducted. Participants were 84 Panamanians (controls, n=41; MCI=32; and AD=11). They were assessed with MMSE and Clock Test. Non‐fasting blood samples were collected to genotype for ApoE4 and to determine a blood‐based biomarker profile.ResultCRP levels among AD participants were significantly increased relative to MCI participants (p < 0.05). A2M levels in AD participants were significantly increased compared to normal controls (p < 0.05). SAA levels in AD participants were significantly increased when compared to MCI participants (p < 0.05).ConclusionThese results show that in the AD group CRP, A2M and SAA are significantly increased. The link between MCI and AD and inflammatory markers can produce an accurate tool that can aid in early diagnosis of AD.
Semantic clustering and memory in the everyday problem‐solving of mild cognitive impairment subtypes
Authors: Nayares Claudia , Bailey Makayla , Jimenez Celine , Balakid Jannine , Lent David D , Alving Loren , Woo Ellen 
Published: December 2021

AbstractBackgroundSemantic clustering, which involves grouping words into categories, is an efficient memory strategy that enhances the recall of older adults. Changes in the semantic network are a hallmark of Alzheimer’s disease (AD). The associated decline in semantic clustering that has been observed, even in mild cognitive impairment (MCI), can affect the ability to compensate for memory difficulties. In this study, we investigated the roles of semantic clustering and memory in the everyday problem solving of MCI and its subtypes.MethodParticipants included 56 healthy older controls and 52 persons with MCI (n=26 amnestic MCI; n=36 non‐amnestic MCI). All participants were administered the California Verbal Learning Test‐II to assess semantic clustering and memory. The Everyday Problems Test (EPT) was also administered to assess problem‐solving skills involved in activities of daily living (ADLS; i.e., telephone use, shopping, meal preparation, housekeeping, transportation, health/medication use, and finances).ResultRegression analyses indicated that immediate and delayed free recall predicted EPT scores in the control group, while only immediate free recall predicted EPT scores in the non‐amnestic MCI group. Semantic clustering was not predictive of EPT scores in any group. Further, memory and semantic clustering did not predict EPT scores in the amnestic MCI group.ConclusionOverall, we found that memory performance predicted everyday problem solving, while semantic clustering, an efficient memory strategy, did not. More specifically, memory predicted everyday problem solving only in those who did not exhibit objective memory deficits (i.e., healthy older controls and non‐amnestic MCI). This suggests that older adults engage intact memory skills to perform problem‐solving based ADLs. In contrast, those with memory deficits do not employ memory or memory strategies to perform these ADLs. This indicates that possibly training persons with MCI in compensatory strategies may benefit them in their everyday lives.
SoUth Korean study to PrEvent cognitive impaiRment and protect BRAIN (SUPERBRAIN) showed improvement in cognitive function mostly in individuals with nutritional improvement: Sub‐analysis of SUPERBRAIN results
Authors: Park Yoo Kyoung , Song Jae Eun , Hong Chang Hyung , Moon So Young , Jeong Jee Hyang , Park Hee Kyung , Na Hae Ri , Choi Seong Hye 
Published: December 2021

AbstractBackgroundThe MIND diet (Mediterranean‐DASH Intervention for Neurodegenerative Delay) is reported to be effective in preventing dementia. As the number of older adults with dementia in Korea increases, intervention programs suitable for older adults with dementia are needed. Therefore, we developed a Korean multi‐domain dementia prevention program including nutrition, exercise, cognitive training, vascular disease prevention and motivation.MethodOne‐hundred fifty three participants aged 60‐79 years with at least 1 dementia risk factor were randomly assigned in a 1:1:1 ratio to the FMI (Facility‐based intervention), HMI (Home‐based intervention) and the control group. The nutrition education program consisted of 10 classes during 24 weeks: the FMI received 7 group sessions and 3 1:1 sessions, the HMI received 4 group sessions and 3 1:1 sessions with 3 times homework sessions. The NQ‐E (Nutrition Quotient for Elderly) and the MNA (Mini Nutritional Assessment) were used to evaluate nutritional status. The RBANS (Repeatable Battery for Neuropsychological Status) and the CCI (Cognitive Complaint Interview) were used to evaluate cognitive function.ResultA total of 136 people (36 males and 100 females) completed the program with an 11.1% dropout rate. The NQ‐E score (p=0.009) and the RBANS score (p=0.001) were significantly increased in the FMI (N=45) and HMI (N=49) compared to the control group (N=42) after the study. The changes in the MNA score and the CCI score did not differ significantly among groups. As a result of sub‐analysis with the changes in the NQ‐E score before and after the study, there was no significant difference in cognitive function indicators among three groups when there was no change or improvement in the NQ‐E score. On the other hand, for those whose NQ‐E score was improved, the RBANS scores of the FMI (N=32) and the HMI (N=37) were significantly increased compared to the control group (N=25) (FMI: 0wk 496.69 points, 24wk 510.41 points; HMI: 0wk 502.86 points, 24wk 519.86 points, p=0.024).ConclusionIn conclusion, nutritional intervention focused on the MIND diet as a part of a multi‐domain intervention had an effect on improving the nutritional status and cognitive function score in the high‐risk group of dementia.
Cognitive health mediates the effect of hippocampal volume on COVID‐19‒related knowledge or anxiety change during the COVID‐19 pandemic
Authors: Kang Min Su , Ottoy Julie , Servaes Stijn , Lussier Firoza Z , Bezgin Gleb , Chamoun Mira , Stevenson Jenna , Bzdok Danilo , King Suzanne , Gauthier Serge , Rosa‐Neto Pedro 
Published: December 2021

AbstractBackgroundIndividuals with cognitive/memory impairments may be more vulnerable to COVID19 due to having poor knowledge of COVID19 and how to protect themselves under current policies. Here, we aimed to show cognitive/memory impairment is associated with less knowledge or less anxiety change related to COVID19. We hypothesized that the effect of hippocampal volume on COVID19‐related knowledge or anxiety change during the pandemic is mediated by cognitive health.MethodA total of 247 participants (162 cognitively normal (CN) and 85 cognitively impaired (CI)) from the Montreal TRIAD cohort underwent a structural MRI and cognition and anxiety assessments using CDRSOB and GAD score, respectively before the COVID19 pandemic. During the first wave of COVID19, the participants were assessed for anxiety using GAD score and knowledge related to COVID19. Hippocampal volume was measured using Freesurfer, and the anxiety was evaluated as the rate of change in the GAD score: (follow‐up – baseline)/time difference. Then, the effect of hippocampal volume on the rate of change in the anxiety or knowledge on COVID19 was evaluated based on a mediation analysis with CDRSOB as a mediator, 2000 bootstrapping, and age, sex, education, and APOEe4 as covariates.ResultThe CI group showed significantly less knowledge of COVID19, or less anxiety change compared to the CN group, while hippocampal volume showed a significant association with knowledge of COVID19 or the rate of change in anxiety. Upon further examination, we revealed that the effect of hippocampal volume on COVID19 knowledge or the rate of change in anxiety was significantly mediated by cognitive health, indicated by CDRSOB (Figure 1).ConclusionOur finding highlights the poorer knowledge of COVID19 and related risks in individuals with cognitive/memory impairments; the CDRSOB, indicative of cognitive health, significantly mediated the effect of hippocampal volume on the rate of change in anxiety or knowledge on COVID19 in our cohort. This study urges for a more effective strategy and policy about informing and educating the individual with cognitive/memory impairment on COVID19 and related risks.
Behavioral and psychological symptoms of Alzheimer’s disease during the COVID‐19 pandemic in underserved settings
Authors: Castro‐Suarez Sheila , Failoc‐Rojas Virgilio E , del Castillo Rossana Cruz , Montesinos Rosa , Herrera‐Perez Eder , Custodio Nilton 
Published: December 2021

AbstractBackgroundThe behavioral and psychological symptoms of dementia (BPSD) are characterized by disturbances in perceptions, thought contents, moods, and behaviors. The causes for these symptoms are connected to factors related to the people with dementia (PWD), his/her caregivers, and environmental factors as well as the interrelationship between these three. Disruptions of routine due to confinements during the COVID‐19 pandemic has led to the onset/worsening of BPSD, thereby increasing distress levels in caregivers, and risks of self‐injury, hospitalization, and death for PWD. Our aim is to describe the onset/ worsening of BPSD during COVID‐19 pandemic confinement.MethodThis is a longitudinal study in patients and caregivers of people with Alzheimer’s disease from the Instituto Peruano de Neurociencias in Lima, Perú. A structured confinement interview was delivered to caregivers exploring how the caregiver's activities have been affected or modified by the confinement measures. All patients have neuropsychological, neuropsychiatric, and functional assessments performed six months before the onset of the confinement. BPSD was assessed using the neuropsychiatric inventory questionnaire (NPI).ResultA total of 91 patients with Alzheimer’s disease and caregivers participated in the study. The average age of the patients was 73.4 years. Most patients had a CDR score of 0.5‐1. Caregivers reported that the pandemic affected their mood by 74%. Percentage of time spent caring increased from 15% to 25% (p<0.001).Worsening and new onset of behavioral and psychological symptoms were reported. The NPI (Fig 1.) and ADCS_ADL scores increased significantly during quarantine from baseline (6.6 and 10, respectively) (p<0.001). Delusions (75%), sleep disorder (71.7%), and hallucinations were the most frequently reported worsening symptoms. Sleep disorder (71.1%), agitation (68.6%) and depression (53.3%) were the most frequently reported new symptoms (p<0.001) (Table 1). Profile of BPSD did not vary according to the CDR score.ConclusionQuarantine induces increases in behavioral and psychological symptoms in patients with early stages of Alzheimer’s disease. Caregivers spent more time with the patient with AD and their emotions were affected by the pandemic. We need to plan for strategies in order to address these needs.