bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of APOE ε4 allele on associations between sub‐threshold, positive Amyloid‐β retention, brain function, and cognitive performances in cognitively normal older adults
Authors: Kang Dong Woo , Lim Hyun Kook , Lee Chang Uk 
Published: June 2023

AbstractBackgroundA growing body of evidence suggests a deteriorating effect of sub‐threshold amyloid‐beta (Aβ) accumulation on cognition before the onset of clinical symptoms of Alzheimer’s disease. Despite the association between the Aβ‐dependent pathway and the APOE ε4 allele, the impact of this allele on the progression from the sub‐threshold Aβ deposits to cognitive function impairment is unclear. Furthermore, the comparative analysis of positive Aβ accumulation in the preclinical phase is lacking. This study aimed to explore the differential effect of the APOE ε4 allele on the association between Aβ retention, brain function, and cognitive performance in cognitively healthy older adults, depending on the Aβ burden status.MethodOne hundred and eighty‐two older adults with normal cognition who underwent resting‐state functional magnetic resonance imaging were enrolled. They were dichotomized using [18F]‐labeled flutemetamol positron emission tomography into subjects with sub‐threshold (cognitively normal [CN] sub‐Aβ, n = 110; [APOE ε4 carrier, n = 30; non‐carrier, n = 80] and positive Aβ deposits [CN Aβ+ group, n = 72; APOE ε4 carrier, n = 34; non‐carrier, n = 38]).ResultWe found (i) distinct effects of the APOE ε4 allele and relationships with cognitive function in the preclinical phase; (ii) differences in local functional connectivity (FC) of the brain regions in networks vulnerable to Alzheimer’s disease according to the APOE ε4 allele, which was associated with higher executive and memory function; (iii) a differential association between regional Aβ retention and local FC according to the APOE ε4 allele; and (iv) a significant interaction between APOE ε4 allele and local FC for the remote inter‐network FC between the default‐mode and central‐executive network in the CN sub‐Aβ group, contributing a compensatory role for cognitive performance. Finally, these results were modulated according to Aβ positivity.ConclusionThis study is the first attempt to thoroughly examine the mechanism at play in the earliest phase of Alzheimer’s disease, focusing on the influence of the APOE ε4 allele from the sub‐threshold to positive Aβ retention during the preclinical phase.
Effect of APOE e4 allele on age‐related brain FDG‐PET uptake in older individuals at risk of dementia
Authors: Khalifa Khadija Nasralla 
Published: June 2023

AbstractBackgroundIn Alzheimer’s Disease (AD) patients, accumulating evidence suggests that the APOE‐e4 allele drives amyloid and tau pathology and decreases brain glucose metabolism. Similarly, in older healthy subjects, APOE‐e4 has been linked to brain hypometabolism. However, there are scarce clinical studies concerning the effect of APOE e4 and the age‐related cerebral glucose metabolism patterns of older individuals at‐risk for dementia.ObjectiveThis exploratory analysis aims to study the impact of carriage of the APOE‐e4 allele on age‐related brain glucose metabolism patterns of older individuals at‐risk for dementia.Method54 community‐dwelling older adults aged 60‐80 years with increased risk for AD due to cardiometabolic disorders (CMD, n = 32) or mild cognitive impairment (MCI, n = 22) who participated in a clinical trial. APOE genotyping was performed to identify carriers of the APOE‐e4 allele. 18F‐Fluoro‐2‐deoxy‐D‐glucose‐positron emission tomography/computed tomography (18F‐FDG PET/CT) was conducted and mean 18F‐FDG uptakes in brain regions of interest (ROI) from the atlas of anatomical labeling were obtained.Group differences by diagnosis (CMD,MCI) and APOE‐e4 status were examined using independent samples T‐tests. Linear regression models were conducted to evaluate the effect of age over mean 18F‐FDG uptake in each ROI. Age*APOE‐e4 interactions were examined, and the models were adjusted for diagnosis subgroup and gender effects. Adjusted models were corrected for multiple testing using the False Discovery Ratio (FDR).ResultMean 18F‐FDG uptake at each ROI was comparable between diagnosis and APOE‐e4 allele status groups. After correcting adjusted models for multiple testing, significant Age*APOE‐e4 interactions were found at the right inferior occipital gyrus (β ‐0.13, 95% CI ‐0.25 – 0.02, p = 0.035, FDR = 0.039), right paracentral lobule (β ‐0.14, 95% CI ‐0.25 – ‐0.03, p = 0.016, FDR = 0.024), and left superior parietal gyrus (β ‐0.11, 95% CI ‐0.20 – ‐0.02, p = 0.014, FDR = 0.021).ConclusionIn older individuals at risk of dementia, carriage of the APOE‐e4 allele was associated with an increased age‐related reduction in mean 18F‐FDG uptake in the right inferior occipital gyrus, right paracentral lobule, and left superior parietal gyrus. Knowledge of age‐ and APOE‐e4 allele‐related cerebral metabolic changes is critical to correctly interpreting brain 18F‐FDG PET/CT findings.
Phonemic Fluency in pathologically confirmed Alzheimer’s disease (AD) versus AD with Lewy Bodies
Authors: Johnson Jordan , Fernandez Kayri K , Barker Megan S , Hernandez Michelle , Soto Elizabeth , Gu Yian , Stern Yaakov , Cosentino Stephanie 
Published: June 2023

AbstractBackgroundAlthough Alzheimer’s Disease (AD) and Lewy Body Disease (LBD) have distinct underlying pathologies, the clinical differentiation of these disorders remains challenging, particularly AD versus mixed AD/LBD. Previous studies have shown that patients with mixed AD/DLB can have lower total output phonemic fluency than patients with AD. Examining the qualitative features of fluency performance may offer an even more sensitive approach to detecting group differences. One potentially useful measure is the ability to sustain generation of words over time; that is, whether a participant continues producing words across the full 60 seconds, or whether their responses “drop off”. A “drop off” in verbal generation on fluency tasks has previously been reported in Mild Cognitive Impairment due to AD. We assessed whether this qualitative phonemic fluency score would differ between autopsy confirmed AD versus mixed AD/DLB or DLB.MethodParticipants with postmortem pathological diagnoses of AD (n = 15) and DLB (mixed or pure DLB; n = 8) were included in the present study. Participants completed phonemic fluency task at their baseline visit as part of a neuropsychological battery of tests. Participants were asked to generate as many words as possible that start with a given letter in one minute across three trials (i.e., C, F, L). The drop off in phonemic fluency over time was calculated by dividing the number of words produced in the second half of the test (i.e. second 30‐second interval) by the total number of words generated across 60 seconds. Group differences were analyzed using a one‐way analysis of variance (ANOVA).ResultWhereas total CFL score did not differ in this sample (p = .21), patients with DLB produced a significantly higher proportion of words in the second half of the CFL test (M = 0.40; SD = 0.14), compared to patients with pure AD (M = 0.27, SD = 0.10), p = 0.016.ConclusionNovel scoring of the CFL test may help to differentiate cases with pure AD and cases with DLB pathology. In the current study, pure AD patients had more difficulty in sustaining word generation over 60 seconds. Future research should continue to look at different ways to score and analyze neuropsychological assessments to improve early differential diagnosis.
The Covid‐19 pandemic, depression, and cognitive decline: Insights from the Srinivaspura Aging, Neuro Senescence, and COGnition (SANSCOG) study
Authors: Stezin Albert , Sundarakumar Jonas S. , Lingegodwa Abhishek Mensegere , Ravindranath Vijayalakshmi 
Published: June 2023

AbstractBackgroundThe COVID‐19 pandemic and the policies to contain it had a widespread impact on the life and livelihood of participants enrolled in the Srinivaspura Aging, Neuro Senescence, and COGnition (SANSCOG) study. We evaluated the prevalence of depression associated with the pandemic and its impact on cognition in our cohort.MethodWe used the geriatric depression scale (GDS) to objectively assess the depression scores of 400 participants before the first wave (March 2020; W1) and after the second (March 2021; W2) wave of the pandemic. We also assessed the cognitive profile of participants at these two timepoints using tests from the COGNITO battery.Based on the GDS score, the participants were classified into three groups‐ (a) Group A: participants with depression (GDS>4) at W1 and no depression W2 assessments (b) Group B: participants without depression at W1 and with depression at W2 assessments, and (c) Group C: participants with depression at W1 and W2. In each subgroup, the neuropsychological scores were compared using the Mann‐Whitney U test.ResultThe overall prevalence of depression was 26.5%. The prevalence of depression at W1 and W2 were 12.5% and 17.7%, respectively.The participants in group A (n = 55) had a significant increase in the reaction time between W1 and W2. In group B (n = 35), there was a significant increase in the reaction time and decrease in auditory attention, dual attention, Immediate and delayed recall scores of logical memory test, category fluency, letter fluency, and copying score in stick‐figure design test. In group C (n = 16), there was a significant increase in the reaction time and a decrease in auditory attention.ConclusionThere was a 5.2% increase in the prevalence of depression between W1 and W2 in our cohort. The cognitive decline was more evident in participants who developed depression during the intercurrent interval between the W1 and W2.
Baseline data from the Australian PITCH study: Characteristics of home care workers providing dementia care
Authors: Goh Anita M Y , Dang Christa , Savvas Steven , Doyle Colleen , Batchelor Frances , Tan Esther , Oglivy Veronica , Duckworth Tanya , Wise Erica , Low Lee‐Fay , Dow Briony 
Published: June 2023

AbstractBackgroundPeople living with dementia increasingly prefer to live in their own home as their care needs progress. Home care workers (HCWs) are essential for supporting independent living, and need training and support on how to deliver evidence‐based and best‐practice dementia care. The home care workforce is diverse, and in Australia, the number of workers who identify as culturally and linguistically diverse (CALD) in 2020 represented 21% of the total direct‐care workforce.The Promoting Independence Through quality Care at Home (PITCH) project aims to improve outcomes for people living with dementia and their paid and family carers by co‐designing and testing an evidence‐based specialist training program for dementia care. A pragmatic stepped‐wedge cluster RCT is being conducted to evaluate the program. To date, 227 HCWs from seven home care providers across Australia have completed baseline measures.MethodHCWs completed the Strain in Dementia Care Scale (SDCS), Sense of Competence In Dementia Care – Staff (SCIDS), Dementia Attitudes Scale (DAS) and Dementia Knowledge Assessment Scale (DKAS). Associations between these measures was assessed using Pearson correlations. HCWs were grouped into CALD/non‐CALD groups based on self‐reported cultural background. ANOVAs examined group differences by CALD status.ResultFor the whole sample, SCIDS was correlated with DAS (r = 0.599, p<0.005) and DKAS (r = 0.257, p<0.005). DAS and DKAS were moderately correlated (r = 0.334, p<0.005). Nearly 30% of HCWs in our sample identified as CALD. The CALD group showed lower DAS, DKAS and SCIDS compared to the non‐CALD group (p’s<0.001). No differences were observed on SDCS (p = 0.58).ConclusionHCWs who were more knowledgeable about dementia had more positive attitudes toward dementia and a higher sense of competence in dementia care. HCWs who did not identify as CALD showed greater dementia knowledge, more positive dementia attitudes, and higher sense of competence in dementia care. Findings suggest that better dementia literacy supports more positive attitudes to dementia and sense of competence, and highlights that more targeted and specialized support may be beneficial for staff from CALD backgrounds (who comprise a high proportion of the Australian aged care workforce). Findings have implications for clinicians, researchers, policy‐makers, educators, and providers of dementia services.
Kernel flow and the eye‐ brain connectome: Study design and objectives
Authors: DeBuc Delia Cabrera , Ramos Alberto R , Galor Anat , Mendoza‐Santiesteban Carlos , Sapahia Rishav , Hasalami Ardita , Fernandez Javier De Jesus , Habash Ranya 
Published: June 2023

AbstractBackgroundMore evidence suggests how the eye health may be crucial in older adults at risk of developing cognitive impairment (CI) and Alzheimer’s disease (AD). Ocular conditions and AD share several common factors, including older age behavioral and cardiometabolic disease. Poor vision can lead to reduced activation of central sensory pathways, which is associated with higher cognitive load and brain structure damage. We showed that CI is not limited to the brain but also affects the retina. However, despite recent advances in neuroimaging biomarkers (e.g., PET diagnostics), there remains a need for more readily available and affordable diagnostic testing for AD risk. While blood flow within the optic nerve head can be quantified using advanced optical imaging technologies, it is essential to measure what is going on in the brain at the same time.MethodWe propose a cross‐sectional and longitudinal, observational study evaluating structural and functional biomarkers of the retina and brain associated with AD disease risk and/or progression. The study objective is to collect structural and functional data of the retina and brain to facilitate the discovery of reliable and sensitive multimodal biomarkers of AD disease risk and/or progression. We will examine participants (N = 200) aged 55‐80; 50 cognitively healthy (CH), 50 with preclinical AD, 50 with mild CI (MCI), and 50 with mild AD. Assessments will include neuropsychological testing, medical/functional assessment, retinal imaging, brain activity, electroretinography, pupillometry, and contrast sensitivity. We will use a wearable, whole‐head coverage time‐domain functional near‐infrared spectroscopy system (Kernel Inc) to measure local changes in blood oxygenation and electroencephalography.ResultThe eye‐brain connectome is integral in understanding pathology in neurodegenerative diseases. We aim to use the eye‐brain data to develop screening and monitoring tools to identify and track AD risk and severity.ConclusionThis study will overcome limitations for performing functional brain imaging due to the lack of portability and user‐friendliness of neuroimaging devices. Our eye‐brain multimodal biomarker study could also facilitate a novel application for diagnostic assessment and therapeutic intervention to target neuroanatomical sites compromised early in AD, leading to a more robust technique to identify high‐risk individuals before cognitive decline with sufficient sensitivity and specificity.
A comparative study of cardiovascular risk factors and its impact on cognitive function in rural and urban Indian cohorts
Authors: Jain Shubham , Lingegodwa Abhishek Mensegere , Stezin Albert , Ravindranath Vijayalakshmi 
Published: June 2023

AbstractBackgroundThe Cardiovascular Risk Factors, Aging, and Dementia (CAIDE) risk score is used to assess the future risk of developing dementia based on cardiovascular risk factors. In this study, we compared the cognitive functions of participants with higher and lower risk of dementia assessed using CAIDE score, in the rural and urban Indian populations. Data was obtained from participants enrolled in the TATA Longitudinal Study of Aging (TLSA) and Srinivaspura Aging, Neuro Senescence, and COGnition (SANSCOG) study, which are two large, harmonized studies from urban and rural India, respectively.MethodsThe clinical and blood biochemistry data from rural (n = 2005) and urban (n = 291) participants were used to estimate the CAIDE score and classify participants as high risk (score ≥ 9) and low risk of dementia (score < 9). The neuropsychological evaluation was performed using COGNITO battery, a computerized neuropsychometric platform that tests five cognitive domains. The cognitive scores of the high‐risk and the low‐risk groups were compared.ResultsThe rural cohort, compared to the urban cohort, had a lower proportion of people with formal education ≥10 years (17.0% vs. 99.3%), age above 54 years (63.5% vs. 90.8%), systolic BP > 140 mm Hg (10.1% vs. 33.7%) and BMI >30 kg/m2 (6.6% vs. 20.9%). The proportion of people with higher total cholesterol, gender distribution, and physical activity was comparable in both cohorts.On risk stratification, the high‐risk category comprised 26.34% of the rural and 9.46% of the urban cohort. The participants belonging to the high‐risk category from the rural cohort performed poorly in all cognitive domains, compared to the low‐risk category. In the urban cohort, there was no significant difference between both groups.ConclusionThe rural population had a higher proportion of people at high risk of dementia in the future, despite the younger age and lower proportion of participants with higher systolic BP and BMI. It seems that the lack of formal education may be primarily responsible for higher CAIDE scores in the rural population. Their baseline neuropsychological profile probably forecasts the possibility of cognitive dysfunction in the future. Interventions may help modify the cardiovascular risk factors and decrease the future burden of dementia.
Subjective and objective cognitive impairment in patients with obstructive sleep apnea
Authors: Rattanabannakit Chatchawan , Tungwacharapong Pecharut , Kuendee Sorawich , Pimolsri Chawanont , Senanarong Vorapun , Chotinaiwattarakul Wattanachai 
Published: June 2023

AbstractBackgroundObstructive sleep apnea (OSA) is associated with cognitive impairment (CI). We aimed to study subjective cognitive complaint (SCC) and objective cognitive scores, and its relation to polysomnography (PSG) parameters, in patients suspected of OSA.MethodPatients suspected of OSA who were scheduled for PSG were recruited. Cognition was assessed by the Montreal Cognitive Assessment (MoCA) and the Color Trails Test (CTT). The Memory index score (MIS) was also calculated from the MoCA. The presence of SCC was assessed by asking patients directly and using the Cognitive Change Index rated by self (CCI‐S) or informants (CCI‐I). Patients with severe dementia were excluded.ResultAmong 258 patients with an age of 61.46±7.05 years, 51.2% are female. The mean MoCA was 23.89±3.89. Based on PSG, patients were classified as having no OSA to mild OSA (20.1%), moderate (28.3%), and severe OSA (51.6%). Based on cognitive tests, patients with moderate to severe OSA had a higher proportion of objective cognitive impairment (64.1%) but less SCC (38.3%) than patients with no OSA or mild OSA. CCI‐S and CCI‐I scores were significantly correlated with each other (r = 0.238, p = 0.019) but not with MoCA score nor CTT‐time. Objective cognitive tests scores were associated with the number of comorbidities and several PSG parameters, i.e., total sleep time, sleep onset latency, wake after sleep onset, sleep stages, mean O2 saturation, and time spent of SaO2 under 90% (all p<0.05). Meanwhile, subjective cognitive scores were not associated with any PSG parameters. However, the self‐report (CCI‐S) was significantly correlated with the Thai‐Geriatric Depression Scale and the Epworth Sleepiness Scale (r = 0.388 and 0.262, respectively, p <0.001). Thirty patients with severe OSA and CI were followed‐up after CPAP treatment for the mean of 12.2 months and showed a significant improvement on MoCA and MIS scores, but not the CTT and CCI scores.ConclusionMost patients with OSA had objective cognitive impairment, but SCC was found less in a more severe stage of OSA. Several PSG parameters were associated with cognitive scores but not subjective cognitive scores. Patients with severe OSA could have a cognitive benefit after CPAP treatment.
Hydroxy‐docosahexaenoic acid (DHA‐H) and its immediate metabolite Heneicosapentaenoic acid (HPA) exert neuroprotection and prevent amyloidogenic APP processing
Authors: Cabot Joan , Parets Sebastià , Miralles Marc , Fernández‐García Paula , Lladó Victoria , Busquets Xavier , Escriba Pablo V. , Torres Manuel 
Published: June 2023

AbstractBackgroundDHA‐H (Hydroxy‐docosahexaenoic acid) is a molecule in development for Alzheimer’s disease (AD) treatment based on the concept of membrane lipid therapy (melitherapy). Once entered the cell, DHA‐H is metabolized via α‐oxidation to the fatty acid HPA (Heneicosapentaenoic acid). DHA‐H has been shown to reduce the amyloidogenic processing of Amyloid Precursor Protein (APP), as well as having a neuroprotective effect in cellular models. Although the mechanism of action of DHA‐H is not yet fully understood, results obtained in excitotoxicity models and lipid profile analysis suggest that HPA could be a DHA‐H effector.Methods: APP processing was assessed in cell cultures of HEK293 and N2a neuroblastoma cell lines and analyzed by western blot. Neuroprotective effect of DHA‐H and HPA was tested in neuron cells differentiated from SH‐SY5Y neuroblastoma cells that were stimulated with NMDA (N‐Methyl‐D‐Aspartate)/Ca to induce excitotoxicity. Lipid samples for lipid profile analysis were obtained from the same cultured cells by addition of chloroform/methanol. Fatty acids were transformed into methyl esters and analyzed by GC‐FID (Gas Chromatography‐Flame ionization detector).Results: DHA‐H administration decreases the levels of derivatives from the APP amyloidogenic processing. DHA‐H and HPA showed a neuroprotective effect in a neuronal model of NMDA‐induced excitotoxicity. DHA‐H administration does not significantly alter the main fatty acids but clearly increases HPA levels in the cells.ConclusionAll these results together demonstrate that DHA‐H exerts neuroprotection and prevents amyloidogenic processing possibly through its metabolic intermediate HPA. Therefore, HPA appears as a new promising molecule for Alzheimer’s therapy.