bluuebunny/crossref_metadata_2025_split huggingface dataset:
Aging and Alzheimer’s Disease Have Dissociable Effects on Local and Regional Medial Temporal Lobe Connectivity
Authors: Hrybouski Stanislau , Das Sandhitsu R. , Xie Long , Wisse Laura EM , Kelley Melissa , Lane Jacqueline , Sherin Monica , DiCalogero Michael , Nasrallah Ilya M. , Detre John A. , Yushkevich Paul A. , Wolk David A. 
Published: December 2023

AbstractBackgroundThe extent to which pathological processes in aging and Alzheimer’s disease (AD) relate to functional disruption of the medial temporal lobe (MTL)‐dependent brain networks is poorly understood. To address this knowledge gap, we examined functional connectivity (FC) alterations between anterior and posterior regions of the MTL and in MTL‐associated functional communities – the Anterior‐Temporal (AT) and Posterior‐Medial (PM) networks – in normal agers, individuals with preclinical AD, and patients with Mild Cognitive Impairment or mild dementia due to AD.MethodIn this cross‐sectional study, we analyzed data from 179 individuals from the Aging Brain Cohort study of the Penn ADRC. Detailed information about participants is provided in Table 1. For intra‐MTL FC comparisons, the MTL subregions were segmented using the automated segmentation of hippocampal subfields‐T1 (ASHS‐T1) pipeline (Fig. 1a). When modeling the MTL’s interactions with the rest of the cortex, we employed four MTL ROIs (left/right × anterior/posterior) derived from an ex vivo atlas of tau accumulation in the MTL. Our functional datasets were preprocessed using a customized fMRIprep pipeline. Sparse network estimations and modularity‐based consensus clustering were used to reconstruct the AT and PM network systems (Fig. 1b). Age effect analyses and group comparisons along the AD continuum were performed using the General Linear Model within the network‐based statistical framework.ResultsThe preclinical stage of AD was characterized by increased FC between the perirhinal cortex and other regions of the MTL, as well as between the anterior MTL and its direct neighbors in the AT network (Fig. 1c‐d). This effect was not present in symptomatic AD. Instead, symptomatic patients displayed reduced hippocampal and intra‐PM connectivity. For normal aging, our results led to three main conclusions (for visuals, see Fig. 2). First, intra‐network connectivity of both the AT and PM networks decreases with age. Second, FC between the anterior and posterior segments of the MTL declines with age. Finally, within the MTL, we observed greater vulnerability of the posterior MTL subregions, particularly the parahippocampal cortex, to age‐associated FC decline.ConclusionTogether, the current results provide evidence for aberrant connectivity in the preclinical stage of AD that may have implications for early AD pathophysiology.
Caregivers journey through experiences of people living with dementia and history of wandering behaviour
Authors: N Anu K , Thirumoorthy A , Antony Sojan , Vasanthra Cicil R , Issac Thomas Gregor , Sivakumar Palanimuthu Thangaraju 
Published: December 2023

AbstractIntroductionWandering is one of the major behavioural symptoms of dementia. It leads to the high level of caregiver burden. Understanding the caregivers’ difficulties and management strategies will help the mental health professionals to gain knowledge on feasible care techniques in India.AimAim of this study was to explore the experience of caregivers in the management of wandering among persons with dementia.MethodologyThree case studies were selected from the family caregiver population and who reported wandering behaviour and associated distress. Interview method was used to understand the experience of caregivers.ResultsAll caregivers used supervision and locking the doors of their houses as key strategies to prevent the wandering behaviour among the persons with dementia. Other prominent strategies were seeking community support and listing out the destinations in which the person is found commonly. Keeping an identity card, planned activities of daily living, restricted movement, safety planning and division of caregiving responsibility were also applied in management of wandering by family caregivers.ConclusionEarly identification of wandering behaviour and caregiver education can prevent the frequency of wandering and the associated burden. Low‐middle‐income countries are yet to develop a comprehensive case management services for the families affected by the wandering secondary to dementia.
Reducing Risk of ADRDs: Innovative Framework to Inform Behavior Change
Authors: Kurzman Alissa , Londono Mary , Truong Vivian , Morales‐Haro Omar , Lam Amy , Kaleem Hiba , Ritt‐Olson Anamara , Boden‐Albala Bernadette 
Published: December 2023

AbstractBackgroundIn the United States alone, more than six million individuals are living with Alzheimer’s disease and related dementias (ADRDs), with minority groups disproportionately impacted. An estimated one‐third of ADRD cases is associated with eight modifiable risk factors: physical inactivity, smoking, depression, low education, diabetes, midlife obesity, midlife hypertension, and hearing loss. With the ADRD pandemic fast approaching, there is greater urgency to identify and adopt risk reduction behavior changes. Lifestyle interventions have shown efficacy in reducing risk for ADRDs and delaying the onset of symptoms. These interventions are often grounded in traditional theories of health behavior change; however, few intervention frameworks exist that combine constructs from multiple discrete theories, or incorporate concept of stigma, a powerful influence in setting the foundation of risk reduction behavior change.MethodsA review of the literature identified health behavior models from which risk reduction interventions are developed. Insights from these studies informed the development of a new framework to inform ADRD risk reduction interventions. This new framework seeks to leverage constructs from the Social Ecological Model (SEM), Health Belief Model (HBM), Transtheoretical Model (TTM), and the Health Stigma and Discrimination Framework (HSDF) to better inform and understand the factors that influence ADRD risk reduction behaviors.ResultThis framework contains several concepts that predict why individuals will take action to reduce risk of ADRDs: individual factors, social‐environmental factors, self and public stigma, and perceptions. Our model also includes stages of change to integrate processes and principles of change, offering a temporal dimension for understanding behavior change. This novel framework can be utilized to inform both individual and community‐level interventions.ConclusionThis new framework provides an innovative and alternative foundation for new ADRD risk reduction interventions. Applicable across a range of risk reduction behaviors, the model highlights the domains and pathways common across ADRD research and intervention implementation. This crosscutting approach will support a more efficient and effective response to addressing preventable risk factors for ADRDs, with the goal of application and realization. Further research is needed to assess the strengths and limitations of this framework in real‐world settings.
Changes in saccade parameters during non‐visual cognitive tasks in younger and older adults
Authors: Yang Hee Won , Kim Jeong Lan , Kim Ki Woong 
Published: December 2023

AbstractBackgroundAlthough eye movements such as saccades are related to internal cognitive processes and are independent of visual processing, few studies have investigated whether non‐visual cognitive tasks simultaneously affect horizontal and vertical saccades in younger and older adults.MethodWe included 28 younger adults aged 20‐29 years and 26 older adults aged > 60 years through advertisements in community settings. All participants were free from major psychiatric, neurological, or ocular diseases. In the investigation, all participants performed the mental arithmetic task (MAT) and verbal fluency task (VFT). The primary measures were saccade parameters, including frequency, amplitude, and velocity.ResultDuring the MAT and VFT phases, the frequencies of horizontal and vertical saccades increased (p = 0.0005 for horizontal saccade in MAT; p < 0.0001 for horizontal saccade in VFT; p = 0.012 for vertical saccade in MAT; p = 0.001 for vertical saccade in VFT), but were comparable between the MAT and VFT phases. The old group showed a slower vertical saccade than the young group during the task phase (p = 0.011 in the MAT phase; p = 0.006 in the VFT phase). The amplitude of the horizontal saccade decreased in both groups during the MAT phase compared with the resting phase (p = 0.013), but did not change significantly during the VFT phase.ConclusionSaccade parameters can change during non‐visual cognitive tasks. Saccades should be examined as a potential non‐invasive biomarker of cognitive disorders in future studies.
Plasma neurofilament light and brain volumetric outcomes among middle‐aged urban adults
Authors: Beydoun May A , Hooten Nicole Noren , Beydoun Hind A. , Weiss Jordan , Maldonado Ana I. , Katzel Leslie , Davatzikos Christos , Gullapalli Rao , Seliger Stephen , Erus Guray , Evans Michele K , Zonderman Alan B , Waldstein Shari R. 
Published: December 2023

AbstractBackgroundElevated plasma neurofilament light chain (NfL) is associated with dementia, but the specific underlying mechanisms are largely unknown. We examined cross‐sectional and longitudinal relationships of plasma NfL with selected brain structural magnetic resonance imaging (sMRI) prognostic markers of dementia, namely global and cortical brain, hippocampal and white matter lesion volumes (WMLV).MethodData were extracted from three prospective visits within the Healthy Aging in Neighborhoods of Diversity Across the Life Span (HANDLS) study, selecting participants with complete v1 (2004‐2009) and v2 (2009‐2013) plasma NfL exposure and ancillary sMRI data at vscan (2011‐2015, n = 179, mean v1 to vscan time: 5.4y). Multivariable‐adjusted linear regression models were conducted, overall, by sex, and by race, correcting for multiple testing with q‐values.ResultNfL(v1) (Loge transformed) had a moderately strong association with larger WMLV at follow‐up vscan visit, after a period of 5‐6 years of follow‐up, overall (β = +2.131±0.660, b = +0.29, p = 0.001, q = 0.0029). Moreover, a 1 unit increase in NfLv2 was linked to a left hippocampal volume that was lower by 125 mm3 (p = 0.004, q = 0.015), using minimally adjusted models and mainly among males. Associations were largely unaltered by further adjustment for downstream health‐related factors.ConclusionIn summary, plasma NfL may be an independent medium‐term (within 5 years) marker for increase in WMLV, and a short term (within 1 year) marker for smaller hippocampal volumes normalized to the intracranial volume, independently of other confounding factors. Therefore, plasma NfL holds promise as a blood‐based marker to predict future subclinical brain pathologies in middle‐aged adults.
An Examination of Reverse Causation in the Association between Serum Folate Deficiency and Dementia
Authors: Rotstein Anat , Kodesh Arad , Goldberg Yair , Reichenberg Abraham , Levine Stephen Z 
Published: December 2023

AbstractBackgroundEvidence suggests that serum folate deficiency increases the likelihood of deficits in cognitive performance and neurological functioning. This situates serum folate as a possible biomarker positioned to modify the risk of dementia. However, the few observational studies that have examined the association between serum folate deficiency and the risk of dementia have shown inconsistent results. Prior studies of the associations between serum concentrations of folate and the risks of incident dementia have been unable to directly exclude the possibility that such associations are a by‐product of reverse causation. Reverse causation has been demonstrated to be particularly relevant to studies of dementia, because the neuropathological processes of dementia may start decades before a formal diagnosis is given. Thus, plausibly, serum folate deficiency is a consequence of preclinical dementia rather than its cause.MethodA prospective cohort aged 60‐75 years (n = 27 188) without pre‐existing dementia for at least 10 years, was tested for serum concentrations of folate and followed up for dementia. Serum folate deficiency was classified as present (<4.4 ng/mL), otherwise absent. HRs and 95% CIs from competing risks Cox models were fitted to quantify the associations between serum folate deficiency and the risks of dementia. To examine reverse causation, the analysis was stratified by duration of follow‐up. Based on the median follow‐up cut point, the associations between serum folate deficiency and dementia were scrutinized in the first then second half of follow‐up. Serum folate deficiency was assumed to be little affected by preclinical dementia when the assessment was long before dementia onset and considerably affected when the assessment was nearer the diagnosis.ResultThe presence compared with the absence of serum folate deficiency was associated with higher risks of dementia (HR = 1.68; 95% CI 1.32 to 2.13; p<0.001). Evidence for reverse causation were moderate for dementia.ConclusionSerum concentrations of folate may function as a biomarker used to identify those at risk of dementia and mortality; however, reverse causation is likely. Further research is needed to examine the role of serum folate deficiency in dementia etiology.
Profiles of modifiable dementia risk factors in later midlife: a latent class analysis
Authors: Xiong Lisa Y. , Cogo‐Moreira Hugo , Wong Yuen Yan , Wu Che‐Yuan , Ruthirakuhan Myuri , Edwards Jodi D. , Rabin Jennifer S. , Lanctôt Krista L. , Black Sandra E. , Swardfager Walter 
Published: December 2023

AbstractBackgroundIn 2020, the Lancet Commission identified 12 modifiable risk factors that may increase dementia risk at the population level. At the individual level, these risk factors may co‐occur; therefore, this study aimed to identify profiles of dementia risk factors in later midlife, and to explore differences in biological markers associated with those profiles.MethodsParticipants aged 60‐64 without dementia at baseline and who identified as Caucasian were identified from the UK Biobank. Data for each risk factor (education, hearing loss, traumatic brain injury, hypertension, alcohol consumption, obesity, smoking, depression, social isolation, physical inactivity, air pollution, and diabetes) were collected using a standardized clinical assessment or through linkage of inpatient records. Latent class analysis was performed to identify latent classes of individuals; missing data were handled using full information maximum likelihood. A multigroup analysis was used to consider differences by self‐reported sex. Associations between the classes and a panel of 29 blood biomarkers across six broad categories (hormonal, inflammatory, kidney, liver, lipids, and metabolic) were explored using the Bolck, Croon, and Hagenaars (BCH) method, considering sex and controlling for age; pairwise comparisons between classes were made using z‐tests.ResultsAmong n = 117,275 participants (males: n = 53,426, females: n = 63,849), a 4‐class solution was identified based on model fit statistics. Invariance testing revealed significantly different class solutions between sexes (Δχ2 = 11,615, Δdf = 52, p < 0.001). In general, the following four groups were identified in both males and females: low risk, psychosocial risk, cardiometabolic risk, and risk related to substance use (Figure 1). These classes differed in their blood biomarkers in both males and females, with the greatest differences observed in females. Specifically, the largest differences were observed between the cardiometabolic risk class vs. other classes, and in biomarkers for inflammation and metabolism (e.g. c‐reactive protein, triglyceride:HDL cholesterol ratio).ConclusionIn both males and females in later midlife, four classes defined by modifiable dementia risk factors were identified. These profiles were associated with unique biomarker signatures. might further examine the effects of these risk factor profiles on dementia‐related pathophysiological changes.
A digital intervention to improve or maintain cognitive function in people at risk for cognitive decline
Authors: Marquard Inna A. 
Published: December 2023

AbstractBackgroundThe landmark FINGER study (Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability) demonstrated that a multidomain intervention, including diet, exercise, cognitive training, and vascular risk monitoring, can improve or maintain cognitive functioning in at‐risk older people. However, implementing a multidomain intervention is challenging since it requires significant resources from healthcare professionals and often poses a considerable burden for senior people regarding costs, transportation, and time commitment. We developed a digital multidomain intervention for people at risk for cognitive impairment or with mild cognitive impairment (MCI) with the overall aim to prevent or alter cognitive decline and to offer an easily accessible solution.MethodBased on the Finger study, we designed a multidomain intervention that was delivered daily (via a mobile app) over 90 days to 17 participants that were recruited online. Participants received assignments for activities related to body fitness, cognitive exercises, multisensory stimulation, and nutritional advice. They received educational material on metabolic risk factors for dementia. Participants were encouraged daily to participate in social activities. Outcomes were evaluated on days 0, 30, 60, and 90 using the Health‐Related Quality of Life Questionnaire (HRQOL) and the Subjective Cognitive Questionnaire.Result17 participants volunteered to participate. Participants between 41 and 80 years of age were included; 9 participants were 60 or younger and 8 participants were 61 or older. One‐third of the participants had a formal diagnosis of MCI. 15 participants completed the program (84% completion rate); After 90 days 71% of the participants indicated that their memory has improved, 50% reported improvements related to remembering recent conversations and, making plans and completing tasks. The number of reported healthy days increased from 13.6; 13.1 (mean, SD) to 21.4; 8.5 (mean, SD) and the days of limited activity dropped from 9.8; 10.1 (mean, SD) initially to 3.4; 3.5 (mean, SD) at the end.ConclusionThe digital delivery of a multidomain intervention was feasible and accepted by participants, shown by a high completion rate. A digital dementia prevention and neurorehabilitation program may help overcome implementation issues of cost and time‐intensive in‐person programs and may improve clinical outcomes.
Midlife Hearing, Vision, Olfactory, and Motor Function Improve the Long‐Term Prediction of Cognitive Decline and Onset of Cognitive Impairment
Authors: Merten Natascha , Pinto A Alex , Paulsen Adam J , Chappell Richard J , Chen Yanjun , Engelman Corinne D , Ferrucci Luigi , Hancock Laura M , Johnson Sterling C , Schubert Carla R 
Published: December 2023

AbstractBackgroundDementia has a long preclinical phase with pathological changes starting decades before clinical symptoms. Early detection of high‐risk individuals in midlife has great potential for future targeted treatments and prevention but we currently lack non‐invasive, low‐cost screening tools. Sensory (hearing, vision, olfaction) and motor changes are common in aging adults and have been associated with cognitive impairment and dementia. We aimed to assess whether midlife sensory and motor function can improve risk prediction models of 10‐year cognitive decline and impairment in comparison to risk predictions using the CAIDE and Framingham Risk Score (FRS).MethodThis longitudinal study is based on N = 1529 (54% women, mean age 49 years, range = 22‐84) Beaver Dam Offspring Study participants with data from baseline, 5‐year, and 10‐year follow‐up that have undergone a neurocognitive review. We assessed hearing, vision, olfactory, motor, cardiovascular health, and health history, and calculated the CAIDE and FRS at baseline. We determined 10‐year cognitive decline (Trail‐Making Test B time;10% most decline) and cognitive impairment (neurocognitive case review by clinical expert panel). We tested whether including baseline sensory (hearing, vision, olfactory) impairment and motor function improves CAIDE or FRS risk prediction models of 10‐year incidence of cognitive decline or cognitive impairment. We used logistic regression models to calculate the area under the receiver operating characteristics curve (AUROC) for models using only CAIDE or FRS and for CAIDE‐sensory‐motor / FRS‐sensory‐motor models.ResultsOverall, 139 participants experienced cognitive decline and 240 developed a cognitive impairment. Adding sensory and motor measures improved AUROCs for cognitive decline models from 0.72[95% confidence interval 0.68–0.76] in CAIDE‐only to 0.77[0.73–0.81] in CAIDE‐sensory‐motor (p<.001) and from 0.71[0.67–0.76] in FRS‐only to 0.78[0.74–0.82] in FRS‐sensory‐motor (p<.001). Cognitive impairment AUROCs improved 0.59[0.55–0.63] to 0.65[0.61–0.68] (CAIDE;p<.001) and 0.59[0.55–0.63] to 0.65[0.61–0.69] (FRS;p<.01), after adding sensory and motor measures.ConclusionIncluding midlife hearing, vision, olfactory, and motor function improved risk prediction of long‐term cognitive decline and impairment in middle‐aged to older adults. Sensory and motor assessments could potentially become relevant cost‐effective and non‐invasive screening tools to identify those at high risk for neurodegeneration and cognitive decline early to target future prevention and intervention strategies.
Role of Neuroimaging in Suspected Dementia Patients: Utilization of Structural Imaging Algorithmic‐Based Diagnosis in Resource Limited Settings
Authors: Ayele Biniyam A. 
Published: December 2023

AbstractBackgroundIn 2050, it is estimated that the number of dementia patients in the sub Saharan Africa is expected to reach 5.05 million, an increase of 136% from the previous estimate of 2.14 million. The objectives of the present study were to assess the neuroimaging findings and associated factors in dementia suspected patients.MethodA retrospective survey of the medical records of 121 suspected dementia patients whom presented to the Yehuleshet Specialty Clinic with subjective forgetfulness were reviewed. The study duration was between January 1, 2020 and December 31, 2021. Both descriptive and analytical statistics were used to analyze the data.ResultThe mean age was 70.4 (1SD = 10.3) years. Sixty four (52.9%) participants were age below 70. Male accounted for 57.9%. Hyperlipidemia was the commonest (38%) identified vascular risk factor followed by prevalence of hypertension (32.2%) and diabetes mellitus (22.3%). HIV infection was observed in 3.3%. Low mean serum vitamin D level (below 20ng/mL) was observed in individuals with focal & global cortical atrophy and those with white matter hyperintensity. Fifty two (43%) participants fulfilled the clinical and imaging criteria of vascular cognitive impairment (VCI). Nearly quarter of the patients had imaging evidences of focal or global cortical atrophy. Eleven (9.1%) had imaging evidences of surgical causes of dementia. the presences of comorbid hypertension, previous stroke, and Parkinsonism were independent predictors of vascular dementia.ConclusionThe present study shows high burden of vascular cognitive impairment among individuals suspected of dementia.Furthermore, the presences of comorbid hypertension, previous stroke, and Parkinsonism were independent predictors of vascular dementia.