bluuebunny/crossref_metadata_2025_split huggingface dataset:
Associations of plasma neurofilament light protein levels with cognitive functions and brain structure parameters
Authors: Coors Annabell , Boenniger Meta M. , Santos Marina , Koch Alexandra , Zeng Weiyi , Ettinger Ulrich , Aziz N. Ahmad , Breteler Monique M.B. 
Published: December 2021

AbstractBackgroundNeurofilament light (NfL) protein level is considered a non‐specific marker of neurodegeneration. NfL levels have been associated with established, non‐blood based neurodegenerative markers, including cognitive performance and reduced brain volume. However, most studies were small (N<300), and compared levels in patients (MCI, Alzheimer’s disease) with those in healthy controls. We investigated to what extent NfL levels are associated with cognitive performance and MRI measures of brain volume and microstructure, in a large non‐demented population‐based sample.MethodThe analyses were based on 4,578 participants (30‐95 years) of the Rhineland Study, a community‐based cohort study in Bonn, Germany. Plasma NfL levels were measured on the SIMOA platform. We assessed cognitive performance with tests for memory, processing speed, executive function and crystallized intelligence and an eye movement (EM) test battery. 3,206 persons underwent structural and diffusion weighted MR imaging. Imaging outcomes included volumetric measures (total brain, grey matter, white matter, hippocampus); diffusion tensor measures (fractional anisotropy; mean, radial, and axial diffusivity); and neurite orientation dispersion and density imaging (NODDI) measures. We used multivariable regression models to assess the relation between NfL levels and cognitive performance and MRI measures with adjustment for possible confounders.ResultAcross all participants, we found only negligibly small associations between NfL levels and cognitive performance, brain volumetric and diffusion tensor measures. However, age‐stratified analyses revealed that in age 40‐49 and from age 60 onwards higher NfL levels were associated with lower orientation dispersion index (ODI). In the 70‐ to 79‐year‐olds, higher NfL levels were additionally associated with higher prosaccade accuracy, higher mean, axial and radial diffusivity, higher extracellular and lower intracellular volume fraction and a lower neurite density index. In the 80+‐year‐olds, NfL levels were negatively associated with hippocampal and white matter volume and positively associated with fractional anisotropy and radial diffusivity.ConclusionHigher NfL levels were associated with smaller hippocampal volume and diffusion tensor and NODDI measures in older subjects. In younger persons (up to age 70 years), NfL levels were only associated with ODI. This suggests that NfL level is a sensitive marker of subtle changes in brain microstructure, especially in old age.
Like psychosis, like dementia: Nigella sativa oil enhanced olfactory and amygdalic phenotypes in socially isolated BALB/c mice model of schizophrenia
Authors: Folarin Royhaan , Bakare Falilat , Onamusi Barnabas 
Published: December 2021

AbstractBackgroundSocial isolation rearing (SIR) is a developmental schizophrenia model with characteristic behavioral symptoms like anxiety and olfactory deficits influenced by the amygdala and olfactory bulbs respectively. Psychiatric disorders and dementias are often comorbid, with neuropsychiatric disturbances constituting inherent component of Alzheimer’s. As long‐term side effects mar available antipsychotics, novel natural psycho‐dementia drugs are urgently needed. This study thus investigated Nigella sativa (NS) for its impacts on olfactory bulb and amygdalic phenotypes in socially isolated BALB/c mice.MethodFifty (50) male BALB/c mice weaned after 21 days of birth were grouped equally into five. CTRL and NS were reared socially and administered normal saline (1ml/kgbw) and Nigella sativa (1ml/kgbw) respectively. SIR‐NS, NS‐SIR and SIR were socially isolated and administered Nigella sativa (1ml/kgbw) post‐isolation, Nigella sativa pre‐isolation (through maternal exposure) and normal saline respectively. Respective administrations lasted 10 days while social isolation lasted 4 weeks. Amygdalic and olfactory bulb glutamate, GPX and dopamine levels as well as histo‐architecture were investigated in addition to body weights, relative brain weight, temperature, food and water consumption. Olfactory acuity was assayed with olfactory sensitivity and discrimination tests while anxiety levels were assayed with elevated plus maze. Statistical analysis was carried out using one‐way ANOVA at 95% CI.ResultIn addition to increased brain‐body weight ratios, Nigella sativa increased the glutamate and dopamine levels in the amygdala and olfactory bulb of socially isolated mice which were maternally exposed to Nigella sativa (NS‐SIR mice) compared to the untreated but isolated mice. GPX also increased in the amygdala of the NS‐SIR but not in the olfactory bulb. Maternal Nigella sativa exposure prevented olfactory insensitivity in the SIR mice but with no ameliorative effect on the open arm exploration time in the pre‐ or post‐treated mice compared with the untreated isolated mice. NS‐SIR animals exhibited better histoarchitecture than SIR mice, as evidenced by increased neuronal sizes, densities and neuro‐piliary staining.ConclusionSocial isolation modelled olfactory and partial emotional deficits in BALB/c mice similar to schizophrenics. Maternal exposure to Nigella sativa showed significant prophylactic potentials against these deficits especially in olfaction. However, farther isolation distance between the animals is recommended for better results.
Event related delta and theta oscillations are reduced in severe obstructive sleep apnea as a possible electrophysiologial evidence of subtle cognitive changes
Authors: Yerlikaya Deniz , Bircan Behice , Öztura İbrahim , Yener Gorsev 
Published: December 2021

AbstractBackgroundObstructive Sleep Apnea Syndrome (OSAS) is a common sleep disorder that leads to widespread cognitive impairment when left untreated. OSAS is also reported as a risk factor for developing Alzheimer’s disease. Recent studies report a shared pathophysiology between OSAS and Alzheimer’s disease (Polsek et al., 2018; Baril et al., 2018). Working memory and attention related ERP P300 deficits were previously reported (for a review see, Raggi and Ferri, 2012). This study aims to investigate electrophysiological changes by using time‐frequency analysis to gain a better understanding on cognitive impairment in OSAS.Method56 severe OSAS patients and age, education and gender matched 33 healthy controls were participated to the study. Participants completed a classical auditory oddball task. A complex Morlet with Gabor normalization was applied and total power within four frequency bandwidths, delta (0.5‐3.5 Hz), theta (4‐7 Hz), alpha (8‐13 Hz), and beta (15‐30 Hz), was calculated using Event‐Related Spectral Perturbation (ERSP) analyses.ResultOSAS patients had reduced delta and theta ERPS to target stimuli compared to healthy controls in repeated measures ANOVA yielding a significant main GROUP effect (respectively, [F(1,87)=9.181, p=0.003] and [F(1,87)=5.083, p=0.027]). No differences were found on alpha and beta power.ConclusionWe found reduced delta and theta activity in severe OSAS patients. Delta EROs activity is associated with attention and decision making (Başar ve Stampfer, 1985; Stampfer ve Başar, 1985), whereas theta activity was associated with task induced activation of working memory (Yordanova et al. 2000). Reduced delta and theta EROs activity can be useful indices of subtle cognitive impairment in severe OSAS even before neuropsychological test. These results strengthen our understanding of the cognitive changes in OSAS by means of electrophysiological methodologies. This study was supported by Dokuz Eylul University Scientific Research Projects (Project Number: 2014.KB.SAG.058).
Abnormal event‐related EEG theta responses in patients with dementia with Lewy bodies and Parkinson's disease dementia
Authors: Yıldırım Ebru , Hanoğlu Lutfu , Güntekin Bahar 
Published: December 2021

AbstractBackgroundParkinson's disease with dementia (PDD) and dementia with Lewy bodies (DLB) are characterized by intracellular Lewy bodies in the brain neurons and clinical symptoms including cognitive impairment and flucations, motor symptoms, and hallucinations with some differences, namely non‐motor symptoms appear earlier in DLB over PDD patients (McKeith et al., 2017). An unmet need in the actual diagnostic criteria is the availability of biomarkers probing working brain cognitive systems. A promising biomarker may be derived from the frequency analysis of electroencephalographic oscillatory responses (EROs) during cognitive demands, as a decrease of frontal‐central EROs at theta (4‐7 Hz) frequencies was reapatedly demonstrated in Alzheimer’s disease patients with mild cognitive impairment and dementia over cognitively unimpaired (CU) persons (Yener et al., 2007; Guntekin et al., 2008). In this line, the present study tested the hypothesis of abnormal event‐related EROs at theta frequencies in PDD and DLB patients.MethodElectroencephalographic activity was recorded during a visual oddball paradigm (i.e., 30% of target stimuli requiring mental counting intermingled with 70% of stimuli to be ignored) in 15 PDD, 12 DLB, and 15 CU persons. EROs at theta power and phase‐locking were computed for the oddball target stimuli and compared among the groups (ANOVA, p < 0.05).ResultAs compared to the CU group, both PDD and DLB groups showed a strong topographically widespread reduction in ERO theta power (p < 0.005) (Figure 1). They also showed a strong reduction in ERO theta phase‐locking, especially in frontal‐central locations (p < 0.0001)( Figure 2).ConclusionThe present study showed that ERO theta power and phase‐locking during a standard visual oddball paradigm probing visual focused attention and short‐term memory may be suitable biomarkers to investigate working cognitive brain systems in both PDD and LBD patients. References: 1) McKeith et al. (2017). 10.1212/WNL.0000000000004058 2) Yener et al. (2007). https://doi.org/10.1016/j.ijpsycho.2006.07.006. 3) Güntekin et al.(2008). 10.1016/j.brainres.2008.06.028
Improving research recruitment through participant input
Authors: Large Stephanie E , Munoz Haydee Izurieta , Davila Marcela , Hall James R , O'Bryant Sid , Johnson Leigh Ann 
Published: December 2021

AbstractBackgroundRecruitment of older adults into aging research is a challenge. Several research studies and clinical trials have failed due to low participant enrollment. Older adults face many barriers to study participation (mistrust of research, lack of transportation, health status, etc.), so special efforts must be made to recruit them into research. We created a recruitment questionnaire with the goal of understanding how to better promote the study and to obtain participant suggestions of groups and locations where the study team could recruit new participants.MethodThe Health and Aging Brain Study: Health Disparities (HABS‐HD) is a community based research study of cognitive aging in diverse communities. We designed a voluntary exit questionnaire for current study participants regarding their recruitment preferences. The questionnaire included the following questions: 1) How did you find out about the study? 2) How can we promote the study to someone similar to you? 3)Which of the following advertising methods do you prefer? 4) Do you know any organization/group that would benefit from the study information? Questionnaire data was compiled and analyzed to assess recruitment preferences and suggestions.ResultThe total number of participants who responded to the questionnaire was 413. 26.9% of respondents stated that they would prefer TV as their main advertising method, followed by the internet (23%) and postal service (mail) (22.7%). Word of mouth was listed as the best way to promote the study (26.9%) followed by community engagement (16.2%) and church (8.2%). When asked for names of organizations, participants recommended tradition groups such as churches, senior centers, and retirement homes. Participants also recommended groups such as rotary clubs, veterans associations, libraries, and the community college senior education program.ConclusionParticipants can assist in recruitment efforts through suggesting organizations that study personnel may not have reached out to. The input allows for assessment of recruitment and the suggestions can broaden the study’s reach.
A smartphone‐based self‐administered test of verbal episodic memory: Development and initial validation
Authors: Valentine Sophie , Hall John , Gagnon Julien , Binning Emily , Narayan Vaibhav A , Wittenberg Gayle , Jaeger Judith , Mosca Kenneth 
Published: December 2021

AbstractBackgroundRemote, self‐administered assessment of cognitive impairment offers immense value to all those impacted by Alzheimer’s disease: patients, carers, healthcare professionals, researchers and pharmaceutical companies alike. The high cost, slow pace and inaccessibility of traditional methods for evaluating novel assessment tools maintains a chasm between innovation and real‐world impact. Focusing on user‐centered design development and technical feature optimisation, we present the next generation of a digitisation of the examiner‐administered Rey Auditory Verbal Learning Test (RAVLT) (Morrison et al., 2018; Mackin et al., 2017) as a smartphone‐based self‐administered test of verbal episodic memory.MethodA smartphone‐based version of RAVLT was developed, integrating artificial intelligence (AI), psychometric assessment principles and user‐centric design. Key risks to user acceptability were identified with moderated and unmoderated testing of the user interface (UI) in 11 users (aged 50+). AI speech‐recognition solutions implemented to replace traditional human components of RAVLT were tested for accuracy, via comparison to a human listener, in a real‐world environment (N = 13).ResultAll testers were able to complete the assessment without additional assistance, indicating high UI acceptability. Qualitative outcomes highlighted potential patient anxiety, insights which were used to iterate the UI design. AI solutions, when implemented alongside data‐driven adjustment features, achieved speech‐recognition accuracy of over 92%.ConclusionWe present extrapolatable principles for developers of remote assessment tools. Thorough inclusion of patients in the development process is essential to ensure that technical and clinical accuracy can be mirrored by optimal adherence and patient experience. Novel technical solutions required to adapt clinic‐based tests for remote use must be validated in ecologically appropriate environments. A fully remote validation study is underway to assess user acceptability and speech‐recognition accuracy at scale in people with subjective memory complaints (SMC). These methods and results hold promise for the continued development of effective at‐home digital tools for remote assessment and reduction of time‐to‐market for innovations in Alzheimer’s disease and beyond. References: Morrison et al., 2018, Alzheimer’s Dement (Amst), 10, 647‐656. doi.org/10.1016/j.dadm.2018.08.010 Mackin et al., 2017, Alzheimer's & Dementia, 13, 598‐599. doi.org/10.1016/j.jalz.2017.07.239.
Parental education and delirium risk after surgery in older adults: A lifecourse analysis
Authors: Arias Franchesca , Chen Fan , Shiff Haley , Marcantonio Edward R , Jones Richard N , Travison Thomas G , Schmitt Eva M , Fong Tamara G , Inouye Sharon K 
Published: December 2021

AbstractBackgroundDelirium is common in older adults and is a risk factor for long‐term cognitive decline. Efforts to conceptualize risk factors for delirium have focused on the time period proximate to the episode, and the role of early‐life exposures on delirium risk is poorly understood. Social and historical factors interact with psychological and biological predispositions, particularly during critical and sensitive periods in childhood, to influence health across the lifespan. Understanding the association between early life exposures and acute conditions occurring after surgeries provides an innovative first step in applying cumulative lifecourse models to examine perioperative risks and outcomes.MethodPatients in the Successful Aging after Elective Surgery study, a cohort of adults 70+ scheduled for major non‐cardiac surgery, were interviewed prior to surgery to assess reading abilities. Cognitive functioning, neighborhood‐level characteristics, and medical co‐morbidities. Delirium incidence and severity were measured daily after surgery using the Confusion Assessment Method (CAM) and CAM‐severity (CAM‐S), respectively. Parental education and participation in cognitive stimulating activities were also assessed.ResultIn our sample of 547 patients, higher paternal education was associated with significantly lower incidence of delirium (odds ratio OR = 0.93, 95% CI [0.87, 0.98]) and inversely associated with delirium severity (Spearman’s rho = ‐.13, p < .001). Higher maternal education was associated with lower delirium incidence, but this association did not reach statistical significance. A multivariate model revealed that the effect of paternal education on delirium incidence was independent of the patient’s education, the patient’s verbal intelligence assessed pre‐operatively, medical comorbidities, neighborhood disadvantage, and participation in cognitively stimulating activities throughout the lifespan. Paternal education and general cognitive functioning at baseline explained about 10% of the variance in incidence of delirium (R2=.10, X2(7) =39.35, p<.001).ConclusionPaternal education is associated with delirium severity and predicts delirium incidence independent of other delirium risk factors. A life course perspective examining early‐life exposures may yield unique insights into the risks and pathogenesis of delirium. More broadly, this study represents a novel exploration in the field of delirium, and our results contribute to the growing body of literature on the early‐life exposures associated with health in adulthood and will into older age.
Sex differences in connectivity in the default mode network in healthy aging adults
Authors: Ficek Bronte , Horien Corey , Lacadie Cheryl , Shen Xilin , Scheinost Dustin , Constable Todd , Fredericks Carolyn A 
Published: December 2021

AbstractBackgroundTwo‐thirds of individuals diagnosed with Alzheimer’s disease (AD) are women, but the reasons for women’s elevated risk are unknown, and sex differences in brain aging trajectories are poorly understood. Both symptomatic AD and aging are associated with decreased connectivity within the default mode network (DMN), which supports short‐term memory processing, while individuals with preclinical AD show increased connectivity in some DMN regions. We sought to identify sex‐based differences in DMN connectivity over the lifespan in a large cross‐sectional study of healthy adults.MethodWe examined functional MRI data from a cross‐sectional cohort of n=595 cognitively normal individuals (aged 36‐100 years; 249 females) drawn from the Human Connectome Project‐Aging (HCP‐A) dataset (Harms et al., 2018; Bookheimer et al., 2019). Preprocessing followed our previously described pipeline, with stringent motion thresholds applied. The four resting‐state scans for each individual were averaged and masked to a standard DMN parcellation (Yeo et al., 2011). We calculated within‐network connectivity of each DMN voxel using the intrinsic connectivity distribution (ICD) (Scheinost et al., 2012), a robust voxel‐based metric of functional connectivity, and used a general linear model to assess the main effect of sex on within‐network ICD with increasing age.ResultFemales showed relative hyperconnectivity in posterior DMN with age compared to males, but lower connectivity in anterior nodes (Fig 1). Specifically, z‐scores for female minus male contrasts for posterior clusters were 3.9 (posterior cingulate), 4.5 (R angular gyrus), and 4.7 (L), and for anterior clusters were ‐4.1 (R frontal pole) and ‐4.3 (L).ConclusionIn a large sample of healthy aging adults, women showed increased connectivity in posterior, and decreased connectivity in anterior, nodes of the DMN compared with their aging male counterparts. Interestingly, individuals with preclinical AD show a similar pattern of posterior hyperconnectivity, often interpreted as the compensatory response of a network under stress. These findings provide early clues to a potential role for network‐level sex differences in explaining women’s increased vulnerability to AD as they age.
Imagining the preventive city: How can urban environments support dementia prevention? A qualitative study
Authors: Roehr Susanne , Rodriguez Francisca S , Siemensmeyer Rosa , Mueller Felix , Romero‐Ortuno Roman , Riedel‐Heller Steffi G 
Published: December 2021

AbstractBackgroundInterventions for the risk reduction of cognitive decline and dementia are currently largely focused on individual‐level strategies. To maximize risk reduction, it is useful to consider how the environment we live in can support dementia prevention, i.e. promote healthy lifestyle behaviors known to attenuate dementia risk. As the majority of the ageing population will be living in cities in the future, we specifically explored how dementia prevention could be addressed in urban environments with the aim of generating transformative ideas for public health policy.MethodIn our trans‐ and multidisciplinary qualitative study, we conducted in‐depth problem‐centered, semi‐structured interviews with 10 community‐dwelling individuals at least 65 years of age and 10 experts (fields covered: architecture, cultural/arts education, environmental sciences, geriatrics, health policy, IT, philosophy, psychology, public health, and urban sociology), all living in the city of Leipzig, Germany. Interview guides were informed by the framework on modifiable risk factors for dementia of the Lancet Commission on Dementia Prevention, Intervention, and Care. Interviews were audio‐recorded and verbatim transcribed. Data were categorized and coded using computer‐assisted content analysis.ResultCommunity‐dwelling individuals were M = 73.7 (SD = 6.0) years old, 50% were women. Experts were aged 39 to 72 years, 70% were women. Across interviews, both older individuals and experts stressed three urban environmental aspects to promote dementia prevention in the city: social participation and inclusion (emphasizing intergenerationality, digital literacy, co‐creating, cultural/arts/community events and lifelong learning), proximity and accessibility (emphasizing neighborhoods, social housing, mobility, access to health care services, public toilets) and local recreation (emphasizing urban greenery, environmental protection, public gardening, outdoor physical activity, cleanliness and security, especially after dark).ConclusionUrban environments play a crucial, but yet too little recognized role for promoting comprehensive healthy lifestyle behaviors that attenuate dementia risk. Public policy should more involve older community members in defining and creating such environments. Moreover, urban environments that promote healthy lifestyle behaviors may be particularly beneficial for marginalized and deprived community groups, which are usually hard to reach by individual‐level interventions.