bluuebunny/crossref_metadata_2025_split huggingface dataset:
Apolipoprotein E polymorphism in Kazakhstani population with Alzheimer’s disease
Authors: Kaiyrlykyzy Aiym , Baibulatova Aida , Olzhayev Farkhad , Tsoy Andrey , Davletov Kairat , Askarova Sholpan 
Published: December 2021

AbstractBackgroundAdvanced age, apolipoprotein E ε4 (APOE) and gender are well‐known risk factors for Alzheimer's disease (AD). At least one copy of APOE‐ε4 is present in around 60% of AD cases (1). However, there are worldwide variations of APOE‐ε4 carriers by region and by ethnicity (2). There is no available data on distribution of APOE polymorphism among Alzheimer’s patients in Kazakhstan. Thus, we assessed the apolipoprotein E allele and genotype frequencies in patients with Alzheimer’s disease and compared them to normal controls.MethodWe included 53 AD patients and 99 people with normal cognition recruited from city hospital in Astana, Kazakhstan. APOE genotypes were determined by Real Time PCR using TaqMan® SNP Genotyping Assays.ResultThe APOE‐ε4 allele frequencies were found to be 82.7% for ε3, 1.9% for ε2, 41.5% for ε4 in AD group, and 92.9% for ε3, 8.1% for ε2 and 25.2% for ε4 in the control group. Genotype ε4/ε4 was found in 9.4% of AD patients compared to 1% in controls (p<0.005) Genotypic distribution of APOE polymorphism did not differ between gender in study group, however, APOE‐ε4 carrying status was significantly different by ethnic groups (p=0.04), where Kazakhs had 34.3% of APOE‐ε4 carriers, Russian and other ethnic groups 16.6% and 17.6% respectively.ConclusionThis is the first study of APOE polymorphism distribution in AD patients in Kazakhstan. APOE ε4 carrier frequency was similar to other Asian and Central European populations. Our findings are consistent with previous literature on the significance of the subjects' geographical region and ethnic context in the study of APOE genotypes in association with AD. Reference: 1. Riedel BC, Thompson PM, Brinton RD. Age, APOE and sex: Triad of risk of Alzheimer's disease. J Steroid Biochem Mol Biol. 2016 Jun;160:134‐47. doi: 10.1016/j.jsbmb.2016.03.012. Epub 2016 Mar 8. PMID: 26969397; PMCID: PMC4905558. 2. Crean S, Ward A, Mercaldi CJ, Collins JM, Cook MN, Baker NL, Arrighi HM. Apolipoprotein E ε4 prevalence in Alzheimer's disease patients varies across global populations: a systematic literature review and meta‐analysis. Dement Geriatr Cogn Disord. 2011;31(1):20‐30. doi: 10.1159/000321984. Epub 2010 Dec 1. PMID: 21124030.
Ophthalmic pathology in patients with primary neurodegenerative diseases
Authors: Makhnovich Ekaterina Vladimirovna , Bogolepova Anna Nicolaevna 
Published: December 2021

AbstractBackgroundThe priority problem of modern healthcare is irreversible dementia due to the steady increase in morbidity, which leads to disability and complete dependence of the patient on others. Among irreversible dementias, Alzheimer's disease takes the first place. Most often, only with sufficiently pronounced cognitive disorders, the doctor can diagnose Alzheimer's disease, although it is obvious that the neurodegenerative process begins even before the clinical manifestations of the disease. Due to the common origin of the eye and the brain, we can say that the eye is a "window to the brain". Many scientists note the similarities between gerontophthalmological diseases and Alzheimer's disease.MethodThe study examined 60 patients who were divided into 2 groups: the first group included patients with Alzheimer's disease who met the criteria of NINCDS ADRDA, the second group included patients with vascular dementia who met the criteria of NINDS‐AIREN. These groups are fully comparable by gender and age. Each group included 9 men and 21 women, with an average age of 65.5 years. All patients underwent a comprehensive neuropsychological examination, using the short Mental Status Assessment Scale (MMSE), the Montreal Cognitive Function Assessment Scale (MoCA), the battery of tests for assessing frontal dysfunction (FAB), the clock drawing test. Also, all patients underwent ophthalmological examination of the visometry, measurement of intraocular pressure, examination of the anterior segment of the eye and fundus, and spectral optical coherence tomography.ResultIn the course of the study, significant ophthalmic pathology was detected in the group with neurodegenerative changes ‐ age‐related macular degeneration was found in 16.7%, pseudoexfoliative syndrome‐20%, primary open‐angle glaucoma‐46.7%. This means that the risk of developing gerontophthalmological diseases increases in patients with neurodegenerative disorders. Therefore, we can assume that the retina is a mirror of neurodegenerative changes in the brain, which will allow to diagnose the disease at early stages and with the help of drug therapy to delay further development of the disease, resulting in reduced disability for patients and socio‐economic costs of society.ConclusionThe results obtained are promising for the early diagnosis of primary neurodegenerative diseases and indicate the need for further research on this topic.
A population‐based study on awareness of young adults regarding the role of physical exercise in improving brain health in Turkey
Authors: Menengiç Kübra Nur , Güngör Feray , Ovacık Uğur 
Published: December 2021

AbstractBackgroundExercise is known for many benefits such as cardiovascular fitness, muscle strength and endurance, and reduction of adipose tissue. It is known that exercise has many important health‐related effects, but it is a question mark whether there is awareness about its positive benefits on brain health and dementia, which has become one of the increasing problems of the developing world. The aim of this study was to determine the level of awareness about the effects of exercise on brain health.Method361 participants were included in the study. Informed consents of the participants were obtained. The socio‐demographic information of the participants was recorded and six questions were asked about exercise and brain health. The answers were evaluated over 3 options, “yes”, “no” and “not sure”. It was also questioned whether the participants exercised regularly or not.ResultDemographic characteristics of the participants are presented in Table 1 and the percentages of the answers given to the questions about the effects of exercise on brain health are shown in Table 2. The awareness of the role of exercise on brain health was found to be high. However, only 18.6% of the participants have been exercising regularly for more than 6 months.ConclusionParticipants are aware of the effects of exercise, but this is not enough to motivate them to perform exercise and physical activity regularly. It becomes important to identify the barriers and facilitating factors for exercise participation. In addition, most of the participants were not aware of the World Health Organization's recommendation of ≥150 minutes of moderate intensity or ≥75 minutes of high‐intensity aerobic physical activity throughout the week and muscle strengthening activities on ≥2 days a week. The content of awareness studies aimed at preventing or delaying the onset of dementia is important. It is necessary to increase the informative studies on the dose, intensity and frequency of exercise required for maintaining health and for diseases such as dementia.
Gait characteristics in preclinical Alzheimer’s disease: Preliminary results of the RADAR‐AD study
Authors: de Boer Casper , Muurling Marijn , Curcic Jelena , Kouzak Rouba , Verheij Herman , Nies Vera J.M. , Durudas Andre , Hannesdottir Kristin , Hinds Chris , Stavropoulos Thanos G. , Daskalova Yoanna , Owens Andrew P. , Wu Yuhao , Erdemli Gul , Stolk Pieter , Lucivero Federica , Narayan Vaibhav A. , Aarsland Dag , Visser Pieter Jelle ,   RADAR‐AD Consortium
Published: December 2021

AbstractBackgroundThe Remote Assessment of Disease and Relapse – Alzheimer’s Disease (RADAR‐AD) study is assessing functional decline in Alzheimer’s Disease (AD) using remote monitoring techniques (RMT’s). RMT’s allow for continuous and objective monitoring of function, potentially improving the sensitivity of assessment in AD. Gait is an important functional domain to maintain independent living. Yet, relatively little is known on gait impairments in the pre‐symptomatic stages of AD. Therefore, the aim of this study is to compare outcomes of in‐clinic gait assessments, using high frequency inertial measurement units, between healthy controls, preclinical AD patients, and cognitively impaired AD patients.MethodWe included early data from amyloid negative cognitively healthy participants (controls, n=9), amyloid positive cognitively healthy participants (preclinical AD, n=6) and amyloid positive cognitively impaired participants (n=3) participants (Table 1) from the RADAR‐AD study. Participants performed a one‐minute walking task, a one‐minute dual task (walking while counting backwards from 100) and timed up‐and‐go (TUG) task, while wearing GaitUp Physilog sensors1 on the left foot, right foot, and right hip. Metrics provided by the sensors include gait speed, steps per minute, double support time, and TUG task completion time.ResultRegression analyses with models corrected for age, sex, and education revealed no between‐group differences on the main outcomes. However, the preclinical AD group showed several interesting near‐significant trends that warrant further investigation (Figure 1). This included an apparent smaller difference in gait speed between the walking task and dual task compared to controls (β=‐10.78 (5.8), p=0.09), accompanied by a smaller difference in steps per minute (β=‐9.27 (5.05), p=0.09), and a larger difference in double support time (β=14.32 (7.28), p=0.07).ConclusionAlthough no between‐group differences in gait outcomes were found in this initial data, early near‐significant trends in the preclinical AD group appears to show altered gait patterns in particular during the dual task. These preliminary findings will be further investigated on possible pathological causality of such behavior as our dataset increases. Inclusion in the RADAR‐AD study is ongoing, and subsequent analyses will include larger sample sizes, more in‐depth analyses of gait behavior, and associations with rating scales of mobility. Reference: [1] https://research.gaitup.com/physilog/
Trajectories of daytime sleepiness and sleep duration before diagnosis of dementia: A 14‐year follow‐up study
Authors: Cavaillès Clémence , Carriere Isabelle , Wagner Maude , Berr Claudine , Dauvilliers Yves , Jaussent Isabelle 
Published: December 2021

AbstractBackgroundSleep problems have been associated with an increased risk of dementia. However, the period in which sleep begins to deteriorate in the natural history of dementia remains unknown. The aim was to model and compare trajectories of several sleep measurements in the 14 years prior to diagnosis of dementia in subjects with dementia and matched controls.MethodData were collected from a large community‐dwelling elderly cohort (3‐City‐Montpellier) at baseline and at each follow‐up. Incident cases of dementia were systematically diagnosed and validated. Repeated measures of total sleep time (TST), time in bed (TIB), wake‐up time, bedtime and, daytime sleepiness (DS) were assessed via self‐questionnaire. Based on a nested case‐control study, sleep trajectories between cases and controls were performed using latent‐process mixed models and a backward timescale.ResultAnalyses were conducted on 205 cases and 813 matched controls. TST and TIB were higher among cases during all the follow‐up with a significant faster increase in cases. For TST, mean predicted values were ‐14 years before diagnosis and at year 0 (matching visit): 6.9 [95%CI= 6.6‐7.1] and 7.2 [95%CI= 6.9‐7.4] for controls and 7.0 [95%CI= 6.6‐7.3] and 7.9 [95%CI= 7.5‐8.2] for cases. Trajectories between both groups differed from 0 to ‐8.5 years before diagnosis. Bedtime trajectories decrease significantly over time in the two groups, more strongly in cases (mean predicted values at ‐14 years before diagnosis and at year 0 were 22.8 [95%CI= 22.7‐22.9] and 22.6 [95%CI= 22.5‐22.7] for controls and 22.7 [95%CI= 22.6‐22.9] and 22.2 [95%CI= 22.0‐22.4] for cases). A significant case‐control difference from 0 to ‐8.2 years prior to diagnosis was reported. In contrast, trajectories of wake‐up time and DS remained stable over time in both groups. Still, wake‐up time trajectories crossed at about ‐5 years before diagnosis. There were no significant case‐control differences in trajectories for DS.ConclusionIn prodromal dementia, TST and TIB increased, whereas bedtime was getting earlier and, wake‐up time and DS remained stable. Results suggest that optimal period for the management of sleep health to prevent dementia begins at least 8 years before the diagnosis of dementia.
Prediction of future Alzheimer’s disease dementia using plasma phospho‐tau combined with other accessible measures
Authors: Palmqvist Sebastian , Tideman Pontus , Cullen Nicholas , Zetterberg Henrik , Blennow Kaj , Stomrud Erik , Janelidze Shorena , Mattsson‐Carlgren Niklas , Hansson Oskar ,   for the Alzheimer’s Disease Neuroimaging Initiative
Published: December 2021

AbstractBackgroundPlasma phospho‐tau (P‐tau) has shown a high diagnostic accuracy for Alzheimer’s disease (AD), but its performance in predicting development of AD dementia and what other measures to combine it with for an optimal predictive accuracy is less known. We examined this using plasma P‐tau combined with other easily accessible measures and compared the results to the clinical diagnostic prediction and to results obtained using cerebrospinal fluid (CSF) biomarkers.MethodWe included patients with subjective cognitive decline (SCD) and mild cognitive impairment (MCI) who were consecutively recruited in the BioFINDER study (n=340). The results were validated in SCD and MCI participants in the ADNI study (n=543). Plasma P‐tau, plasma Aβ42/Aβ40, plasma neurofilament light, APOE genotype, brief cognitive tests and MRI (cortical thickness in AD‐specific regions) were examined as predictors of progression to AD dementia within 4 years (2 and 6 years were secondary outcomes). The accuracy was determined using the area under the ROC curve (AUC) from logistic regression models.ResultWithin 4 years, plasma P‐tau217 predicted AD dementia accurately (AUC 0.83) in BioFINDER. A model consisting of plasma P‐tau217, memory, executive function, and APOE had higher accuracy (AUC 0.91, p<0.001). In ADNI, this model produced a similar AUC (0.90) using plasma P‐tau181 instead of P‐tau217. A cross‐validated version of this model using binary plasma P‐tau data (normal/abnormal) was implemented online for the prediction of the individual probability of progressing to AD dementia. Parsimonious models had similar accuracies for predicting AD dementia within 2 and 6 years (AUCs 0.90‐0.91 in both cohorts). Using CSF P‐tau, Aβ42/Aβ40 and neurofilament light instead of plasma biomarkers did not improve the accuracy. In BioFINDER, the clinical diagnostic prediction by memory clinic physicians blinded to fluid biomarker data had significantly lower accuracy than all models (4‐year AUC 0.71).ConclusionPlasma P‐tau in combination with brief cognitive tests and APOE genotyping improves the predictive accuracy of whether a patient will progress to AD dementia or remain stable/progress to other dementias, compared to using just plasma P‐tau or to the clinical prediction. Plasma P‐tau combined with these measures may also facilitate recruitment for AD trials.
Repetitive transcranial magnetic stimulation ameliorates the pathology and cognitive dysfunction in a mouse model of Alzheimer's disease through increased drainage efficiency of meningeal lymphatic system
Authors: Jin Jian , Wang Yuling , Ye Xiaojing , Lv Rongke , Dai Weiping , Li Wenchang , Lin Wei Jye , Lin Yangyang 
Published: December 2021

AbstractBackgroundAlzheimer’s disease (AD) is a progressive neurodegenerative disease with high prevalence rate among elderly population. Given numerous studies that have shown promising outcomes in delaying or reversing the disease at preclinical stage, however, successful translation into clinical applications has been rare. Repetitive transcranial magnetic stimulation (rTMS) is a non‐invasive, painless technique that has been clinically proven to improve cognitive function in AD patients, but the underlying cellular and molecular mechanisms remain largely uninvestigated.Method5xFAD mice, an AD mouse model that overexpresses human familiar APP and presenilin 1 mutations under regulated expression of mouse neuronal‐specific Thy1 promotor, were stimulated by rTMS for 2 weeks. The stimulation contained a total of 4000 magnetic stimulation pulses given daily, which consisted of 100 burst trains and 40 pulses of each train at 20 Hz with a 5 sec intertrain interval. At the end of rTMS treatment, mice underwent memory tests including Y‐maze, novel object recognition and novel location recognition. A 10kD Dextran‐AlexaFluo647 tracer was injected into the cisterna magna compartment and mice were perfused 30 minutes later. Brains, meninges and deep cervical lymph nodes were resected for subsequent immunofluorescent analysis.Result5xFAD mice treated with high frequency rTMS for two weeks showed improved long‐term object and spatial memory, increased neuronal activity as revealed by the elevation of c‐fos‐positive neurons in the prefrontal cortex and the hippocampus, and reduced pathological features of AD, which included enhanced clearance of β‐amyloid deposit and reduced glial activation. Importantly, rTMS significantly enhanced the drainage of the intra‐cisterna magna injected tracer in 5xFAD mice, as revealed by tracer penetration and clearance in the brain parenchyma, dura mater, and deep cervical lymph nodes.ConclusionOur findings provide the novel mechanistic insight of the regulatory role of rTMS in the drainage efficiency of brain lymphatic system and the clearance of β‐amyloid in the 5xFAD mouse model, suggesting rTMS as a potential tool for the intervention of neurodegenerative and other disorders related to meningeal lymphatic dysfunction.
Social functioning and cognitive impairment among the oldest old
Authors: Lisko Inna , Ngandu Tiia , Solomon Alina , Kivipelto Miia , Kulmala Jenni 
Published: December 2021

AbstractBackgroundFindings from observational studies support the benefits of social activities on cognition. The ability to carry out social activities is described by social functioning. However, only little data exists on the associations between social functioning and cognition among the oldest old. The aim of this study is to explore if social functioning is associated with cognitive impairment among the oldest old.MethodThe study uses cross‐sectional data from a Finnish population‐based Cardiovascular Risk Factors, Aging and Dementia (CAIDE) 85+ study. Altogether 187 individuals aged 85+ provided data on health‐related quality of life, RAND‐36, from which the following question on social functioning was used: “During the past 4 weeks, how much of the time has your physical health or emotional problems interfered with your social activities (like visiting with friends, relatives, etc.)?“ Social functioning was divided into three categories: 1) Low (all the time or most of the time), 2) Moderate (some time), and 3) High (a little time or not at all). Cognitive impairment was defined as Mini‐Mental State Examination score < 25. Logistic regression model was used in the analyses which were adjusted for sex.ResultAccording to these preliminary results, individuals with low social functioning were 7 times more likely to have cognitive impairment as compared to individuals with high social functioning (Odds ratio [OR] 7.46, 95% Confidence Interval [CI] 2.16–25.75). No differences in cognitive impairment were found between individuals with moderate social functioning as compared to high social functioning (OR 0.68, 95% CI 0.26–1.84).ConclusionLower social functioning appears to be associated with cognitive impairment among the oldest old. These results need further exploration. Causality behind the found association should be examined and if supporting social activities particularly among cognitively impaired would carry health benefits.
Clinical experience with polygenic risk score in subjects with early cognitive concerns
Authors: Sauer Justin , Ballard Clive , Gibson Alex , Daunt Paula , Pither Richard 
Published: December 2021

AbstractBackgroundThere is mounting evidence that lifestyle interventions and behavioural changes play a significant role in maintaining cognition and function, as well as preventing dementia. Consequently, it is important that clinicians confronted with subjects with early cognitive concerns, have appropriate tools available to assist in diagnosis and to facilitate risks management appropriately. The application of polygenic risk score (PRS) tests has the potential to contribute towards management planning and to reduce the burden of testing in subjects with low overall risk.MethodsThis retrospective analysis considered the application of genoSCORETM in a small cohort of patients seen over a six month period in a London Memory Clinic. The test was offered to selected patients in the clinic with MCI not clinically attributable to dementia, or cognitively normal individuals concerned about their risks of dementia. The impact upon clinical management and lifestyle modification was reviewed. genoSCORE, a polygenic risk score algorithm, was developed by Cytox to assess genetic risk for the future development of Late‐Onset Alzheimer’s disease (LOAD).ResultsPatients receiving the genoSCORE test included those with early MCI, subjective memory complaints and a small number concerned about their risk of dementia. In each case, a medical history was taken and individuals assessed using the Addenbrooke’s Cognitive Examination, conducted either in clinic or remotely. genoSCORE polygenic risk score was easy to conduct and well received. The results stimulated individuals at risk of developing LOAD to make lifestyle adjustments and thereby potentially modifying their dementia risk.ConclusionsIn this study, the genoSCORE PRS test provided a valuable assessment of genetic risk of individuals most likely to decline cognitively decline towards AD and as such, contributed significantly to clinical management decisions. The ease and effectiveness of home sampling of saliva as source DNA for the PRS test was a major factor and well aligned with the continuing need for remote consultations in the light of COVID‐19 concerns. Further larger‐scale studies to determine the full clinical and associated economic impact of the genoSCORE PRS test are required.