bluuebunny/crossref_metadata_2025_split huggingface dataset:
Correlation analysis between magnetic susceptibility in MRI and amyloid β in PET
Authors: Sato Ryota , Kudo Kohsuke , Yamaguchi Akinori , Udo Niki , Matsushima Masaaki , Yabe Ichiro , Sasaki Makoto , Harada Masafumi , Matsukawa Noriyuki , Amemiya Tomoki , Kawata Yasuo , Bito Yoshitaka , Ochi Hisaaki , Shirai Toru 
Published: December 2020

AbstractBackgroundStudies on quantitative susceptibility mapping (QSM) have reported increased susceptibility in the brain of Alzheimer’s disease patients, reflecting the pathological accumulation of iron in Aβ plaques. Previously, we revealed moderate correlation between increased magnetic susceptibility in QSM and Aβ deposition in PET by using a region of interest (ROI) analysis in a relatively small cohort (26 patients) (Kudo K., et al. AAIC 2019). In this study, we examine the correlation in a larger sample size by using the ROI analysis and a whole‐brain voxel‐based analysis.MethodForty‐two patients were prospectively recruited in four centers. The clinical diagnoses were as follows: 23 dementia cases, 18 mild cognitive impairment cases, and one cognitively normal case. Magnetic resonance imaging was performed using 3‐T scanners (Hitachi, Ltd.). Amyloid PET imaging was performed using 18F‐flutemetamol. Both QSM and PET images were spatially normalized, and the ROI and voxel‐based analyses were performed to examine correlation between these two images. In the ROI analysis, the correlations were analyzed for 47 regions (defined by an automated anatomical labeling atlas) by using Pearson’s correlation coefficient. In the voxel‐based analysis, the correlation coefficients were calculated between spatially smoothed QSM and PET images on a voxel by voxel basis. This research was supported by AMED under Grant Number JP18he1402002.ResultBased on amyloid PET, 20 patients were Aβ positive and 22 were Aβ negative. In the ROI analysis, positive correlations were noted in 24 of the 47 regions, and moderate correlations (r>0.30) were noted in four regions: the supramarginal gyrus (r=0.35), anterior cingulate gyrus (r=0.32), rectal gyrus (r=0.31), and medial orbitofrontal cortex (r=0.30). When averaged for these four regions, the correlation was moderate (r=0.59), and receiver operator characteristic analysis to predict Aβ positivity revealed that the area under the curve was 0.79. In the voxel‐based analysis, three clusters were found as positively correlated regions (r>0.30) in the parietal and frontal cortices. When averaged for these three clusters, the correlation was high (r=0.80).ConclusionThe ROI‐based and voxel‐based analysis results suggest that the increased susceptibility of QSM was correlated with amyloid PET.
Effective interventions for potentially modifiable dementia risk factors: Their costs and cost‐effectiveness
Authors: Mukadam Naaheed , Anderson Robert , Knapp Martin Richard John , Wittenberg Raphael , Karagiannidou Maria , Gonzales Sergi Costafreda , Tutton Madison , Alessi Charles , Livingston Gill 
Published: December 2020

AbstractBackgroundThe potential economic value of interventions to prevent dementia is unknown. We modelled this for potentially modifiable dementia risk factors.MethodWe searched PubMed and Web of Science from inception to July 2018 and included interventions that (a) successfully targeted any of nine pre‐specified potentially modifiable risk factors (hypertension, diabetes, hearing loss, obesity, physical inactivity, social isolation, depression, cigarette smoking and less childhood education), (b) had robust evidence that the intervention improved risk or risk behaviour and (c) are feasible in an adult population. We established when in the life‐course each intervention would be delivered. We calculated dementia incidence reduction from: annual incidence of dementia in people with each risk factor; population attributable fraction for each risk, corrected for risk factor clustering, and how effectively the intervention controls the risk factor. We calculated the discounted value of lifetime health gain (including reduced dementia mortality) and impact on cost (including NHS, social care and carer costs) per person eligible for treatment. We estimated annual total expenditure on the fully operational intervention programme in England.ResultWe found effective treatments for hypertension, stopping smoking, diabetes prevention and hearing loss. Treatments for stopping smoking and provision of hearing aids reduced cost. Treatment of hypertension was cost‐effective by reference to standard UK thresholds. The three interventions when fully implemented would save £1·863 billion annually in England, reduce dementia prevalence by 8·5% and produce QALY gains. The intervention for diabetes was unlikely to be cost‐effective in terms of impact on dementia alone.ConclusionThere is a strong case for implementing the three effective interventions on grounds of cost‐effectiveness and quality of life gains, as well as for improvements in general health. While some people will decline or discontinue interventions, there is considerable room for the interventions to remain cost‐saving or cost‐effective even if adherence is lower.
Cognitive reserve, brain reserve, and cognitive performance in old age: A population‐based study
Authors: Li Yuanjing , Wang Xiang , Hou Tingting , Song Lin , Wang Mingqi , Zhang Jingwen , Ren Yifei , Shi Lin , Wang Yongxiang , Du Yifeng , Qiu Chengxuan 
Published: December 2020

AbstractBackgroundThe reserve theory has been proposed to account for the discrepancies between the load of brain pathologies and cognitive phenotypes in aging. We sought to explore the interplay of cognitive reserve and markers of brain reserve and brain lesions in determining cognitive performance in old age.MethodsThis population‐based cross‐sectional study included 215 people (age ≥65 years; 43.7% women; 28.4% illiterate) who were living in the rural communities of Yanggu County, Shandong Province, China. We used the Mini‐Mental State Examination to assess global cognitive function. We evaluated markers of brain reserve and brain lesions from the structural MRI scans, i.e., total intracranial volumes (ICV), deep white‐matter hyperintensity (DWMH) volumes, and cerebral microbleeds (CMBs). We used the structural equation modeling to generate a composite score of cognitive reserve capacity from multiple cognitive‐enhancing factors over the lifespan. We used the general linear regression model and the marginal effect model to disentangle the relations of cognitive reserve and brain reserve markers with MMSE score.ResultsThe composite cognitive reserve score ranged from 6.80 to 16.55. Overall, a higher cognitive reserve score was associated with multiple‐adjusted β‐coefficient of 0.04 (95% CI 0.03−0.76) for MMSE score. There was a stronger relationship between cognitive reserve score and MMSE score in people with lower ICV (β=1.16; 95% CI 0.99−2.24) than in those with larger ICV (β=0.44; ‐0.01−0.89, p=0.053). Furthermore, the association of cognitive reserve score with MMSE score was statistically significant in people with severe DWMH load (β=0.84; 95% CI 0.22−1.45) and CMBs (β=1.50; 0.60−2.40), but not in those with mild DWMH load or without CMBs. Compared to people with a higher cognitive reserve score, those with lower cognitive reserve capacity showed stronger correlations of MMSE score with ICV (β=2.66; 95% CI 0.08−5.25) and presence of CMBs (β=‐0.24; ‐0.43−‐0.04).ConclusionHigher cognitive reserve is associated with better cognitive performance among rural‐dwelling older adults with limited education, and such association is stronger in people with lower brain reserve. In addition, lower brain reserve is associated with poorer cognitive performance, and such association is stronger among people with lower cognitive reserve capacity.
Restoration of mental and cognitive functions in AD after transcatheter intracerebral photobiomodulation therapy
Authors: Maksimovich Ivan V. 
Published: December 2020

AbstractBackgroundThe study shows long‐term results of the dynamics of dementia and mental and cognitive disorders in AD treatment with transcatheter intracerebral photobiomadulation therapy (PBMT).MethodIn the long‐term period (2‐10 years), we examined 93 patients aged 34‐80 (average age 67.5), men 32 (34.40%), women 61 (65.59%), who had previously undergone AD treatment.The examination included: determination of CDR, MMSE, cerebral CT, MRI with determination of dementia severity using the Tomography Dementia Rating scale (TDR), SG, rheoencephalography (REG), cerebral MUGA. Before treatment, patients were divided: Test Group ‐ 48 (51.61%) patients: preclinical AD stage (TDR‐0) – 4 patients, early AD stage (TDR‐1) ‐ 16, medium AD stage (TDR‐2) ‐ 21, severe AD stage (TDR‐ 3) ‐ 7 patients ‐ Transcatheter intracerebral PBMT was performed. Control Group ‐ 45 (48.39%) patients: preclinical AD stage (TDR‐0) ‐ 6 patients, early AD stage (TDR‐1) ‐ 13, medium AD stage (TDR‐2) ‐ 15, severe AD stage (TDR‐ 3) ‐ 11 patients ‐ conservative treatment (Memantine or Rivastigmine).ResultTest Group: all 48 (100%) patients, along with improved microcirculation, showed development of neurogenesis and cerebral regenerative processes, which, depending on AD stage, was accompanied by a 10‐20% increase in cerebral temporal lobes volume. The process was accompanied by dementia decline, cognitive and mental functions restoration. Consequently, the patients were transferred to the lighter stage TDR group. The obtained positive dynamics in patients with TDR‐0 and TDR‐1 stages was observed over 10 years, in TDR‐2 ‐ 4‐5 years, in TDR‐3 ‐ 2‐2.5 years. Control Group: along with the treatment, stabilization of the condition for a period of about 2 years was detected only in patients with early AD stages (TDR‐0, TDR‐1). Further, cerebral involutive changes, dementia, cognitive and mental impairment increased. Patients with later AD stages (TDR‐2, TDR‐3) showed a steady increase in involutive changes, dementia, cognitive and mental impairment.ConclusionTranscatheter intracerebral PBMT is an effective AD treatment. The method allows brain revascularization, stimulates neurogenesis and tissue structures restoration. The effect is preserved for long causing dementia regression, cognitive and mental functions restoration.
Synaptic stimulation protects against pathological tau by enhancing lysosomal degradation
Authors: Akwa Yvette , Gondard Elise , Malta Chiara Di , Capetillo‐Zarate Estibaliz , Boiret Anne , Matute Carlos , Vaccari Thomas , Settembre Carmine , Lozano Andres M. , Baulieu Etienne E. , Tampellini Davide 
Published: December 2020

AbstractBackgroundChanges in synaptic excitability and reduced brain metabolism are among the earliest alterations associated with the development of Alzheimer’s disease (AD) (Reiman et al., 2004; Sperling et al., 2009). Among different approaches for therapeutics, the stimulation of synaptic activity has been shown to be protective in models of AD, and deep brain stimulation (DBS) provides amelioration in AD patients (Sankar et al., 2015; Swaab and Bao, 2010; Tampellini, 2015). Such positive effects might reflect changes occurring at cellular levels when activity is induced, indicating that brain stimulation might promote cellular mechanisms correcting neuronal and synaptic dysfunctions. We have demonstrated that synaptic stimulation, via DBS or other methods, exerts protection in mouse models of AD and frontotemporal dementia (FTD) by enhancing autophagy, lysosomal degradation of pathologic tau, and protecting synapses (Akwa et al., 2018; Mann et al., 2018). Ongoing investigations are revealing the involvement of TFEB and its downstream genes in the enhancement of lysosomal activity upon stimulation.MethodSynaptic activity was induced by electrode implantation in the entorhinal cortex of 3xTg mice (Mann et al., 2018). Cultured neurons were prepared from E15 PS19 mouse embryos (Akwa et al., 2018) and stimulated at 14 days in vitro (Ehlers, 2003). RT‐qPCR was performed as described (Napolitano et al., 2018). Confocal immunofluorescence, Western blot and statistical analyses were performed as described (Akwa et al., 2018).ResultDBS was able to reduce levels of hyperphosphorylated and oligomeric (but not total) tau restoring levels of synaptic proteins back to wild‐type in 3xTg mice. Pathological tau clearance required lysosmal activity, which was enhanced by synaptic stimulation. Trascription factor EB (TFEB) (Sardiello et al., 2009) plays a pivotal role in regulating lysosomal biogenesis and autophagy, and is involved in activity‐driven tau degradation. Indeed, our recent RT‐qPCR data analyses revealed increase expressions of TFEB downstream genes, including ATP6‐V1H and ATP6‐V0D1, in neurons during synaptic stimulation.ConclusionThe enhancement of lysosomal degradation by the involvement TFEB and related genes demonstrated positive effects of DBS/synaptic stimulation at cellular and molecular level against pathological tau.
Impaired lung function as a risk factor for accelerated brain ageing
Authors: Frenzel Stefan , Bülow Robin , Ewert Ralf , Habes Mohamad , Stubbe Beate , Voelzke Henry , Katharina Wittfeld , Seshadri Sudha , Grabe Hans J. 
Published: December 2020

AbstractBackgroundPoor pulmonary health is increasingly recognized as an important risk factor for accelerated brain ageing and the development of dementia. We report on associations of spirometry with MRI‐based volumetry of the brain in the large community‐based Study of Health in Pomerania Trend (SHIP‐Trend).MethodN=1651 participants of SHIP‐Trend underwent both spirometry and MRI scans of the head. Measurements of forced expiratory volume during first second (FEV1), forced vital capacity (FVC) and relative FEV1 were standardized with respect to age, sex, and body height using the GLI 2012 reference equations. T1‐weighted MRI scans were processed with FreeSurfer 5.3 and total brain volumes (TBV), total gray matter volumes (TGM), total hippocampal volumes (HV) were determined. In addition, we considered the total volume of white matter hyperintensities (WMHV) estimated from T2‐FLAIR images and a recently proposed MRI‐based Alzheimer’s disease index (FSAD). Linear regressions of MRI parameters on standardized FEV1, FVC, and relative FEV1, respectively, were performed. Age, sex, intracranial volume, height, smoking status, and presence of diabetes were added as covariates to each model. Effect sizes were assessed by Cohen’s f2. Analyses were performed using data from young‐aged (≤ 60y), old‐aged (>60y), and all participants, respectively.ResultFEV1, FVC, and relative FEV1 were significantly positively associated with greater TBV, TGM, and HV in the whole sample. WMHV was significantly negatively associated with FVC and positively associated with relative FEV1. The FSAD index was significantly negatively associated with FEV1, and FVC. Associations with FEV1 and FVC were consistently stronger in old‐aged compared to young‐aged participants. For TBV, HV, WMHV, and FSAD, effect sizes were f2≈0.01. For TGM, effect sizes were f2≈0.05, significantly larger than those of diabetes. No significant associations with relative FEV1 were found in the group of old‐aged participants.ConclusionOur results suggest that impaired lung function is a risk factor for atrophy of brain tissue. In old‐aged individuals, this seems to be specifically related to restrictive spirometry patterns (i.e. reductions in FEV1 and FVC but not relative FEV1) but not obstructive ones (i.e. reductions in relative FEV1). This work was supported by the Cognitively Healthy Nonagenarians in the Cross‐Cohort Collaboration Consortium (CCC) grant AG059421.
Chronic exposure to mild therapeutic hypothermia prevents cognitive deterioration and neurodegeneration in a rat model of AD‐like pathology
Authors: Millon Maria Beatriz Bistue , Avila Ramiro , Bruno Martin Alejandro 
Published: December 2020

AbstractBackgroundMechanisms of epigenetic regulation modulate gene expression without alterations in the genomic sequence and play important roles in brain development1, synaptic plasticity and memory2. Epigenetic regulation of gene transcription would be an appropriate mechanism for cells to flexibly adapt to the environmental changes. In this context, lysine specific demethylase 1 (LSD1) is an important enzyme that modifies gene transcription3. Recently, it was reported that LSD1 is essential for the regulation of neuronal gene transcriptional programs involved in synaptic plasticity and cognition2–4. Despite, the well‐known function of LSD1 in early development1,4–6, there is some controversy about the specific role of LSD1 in aging. Upon cold exposure LSD1 regulates Brown adipose tissue function and mediates beige adipogenesis to increase thermogenic capacity and prevent changes in body temperature by inducing non‐shivering thermogenesis7. However, the role of repeat cold exposures on brain LSD1 function has never been studied. We investigated whether chronic repeat cold exposures could modulate the hippocampal expression of LSD1 and its potential impact on neurodegeneration and cognitive functions, using non‐transgenic (non‐tg) and transgenic (tg) AD‐like rat model.MethodMcGill‐R‐Thy1‐APP‐tg rats exhibited accumulation of intraneuronal Aβ peptide, display cognitive deficits and reproduce an AD‐like amyloid pathology. Thus,17 months tg and non‐tg rats were expose under therapeutic hypothermia for 2 hours at 4°C daily during 1 month.ResultOur results demonstrated how progressive intraneuronal Aβ accumulation correlates with upregulation of LSD1 at early stages (prior plaques formation) of the AD‐like amyloid pathology, which impact on the alteration of cognitive functions. We showed that chronic mild therapeutic hypothermia modulates hippocampal LSD1 levels, improving synaptic plasticity and preventing cognitive dysfunction.ConclusionTaken together our work suggests that modulating brain LSD1 levels through repeat cold exposures constitute a novel non‐pharmacological therapeutic strategy to prevent neurodegeneration and preserve cognitive functions. (1) Toffolo E, et al. J Neurochem. 2014; (2) Wang J, et al. Nat Neurosci. 2016; (3) Lim CS, Nam HJ, et al. Sci Rep. 201 7; (4) Rusconi F, et al. Trends Neurosci. 2017; (5) Maes T, et al. Epigenomics. 2015; (6) Ciceri F, et al. Curr Pharm Des. 2017; (7) Marcher AB, et al. Cell Rep. 2015.
Perspectives on dementia and family caregiving among the Oneida Nation of Wisconsin
Authors: Lambrou Nickolas H , Wyman Mary F , Miller Debra A , Thomas Lauren , Strong Lois , Summers Marlene , Lassila Patricia , Petri Florence , Miller Donald , Wheelock Sunshine , Williams Betty , Gleason Carey E , Edwards Dorothy Farrar 
Published: December 2020

AbstractBackgroundRecent research indicates that prevalence of dementia amongst American Indian/Alaska Natives (AI/AN) is > 40% higher compared to Asian Americans and ∼18% higher than Whites. Yet, little is known about how AI/AN people conceptualize dementia, caregiving, and dementia care services. This study aimed to deepen understanding and highlight how the Oneida Nation of Wisconsin experiences and makes meaning of dementia, the family caregiver role, and home and community‐based service use.MethodTenets of Community‐Based Participatory Research (CBPR) guided study design, recruitment, data collection and analysis. The study team conducted semi‐structured interviews with 22 Oneida Nation of Wisconsin participants. Audio recorded interviews were transcribed to text and coded thematically within and across participant narratives. A mixed‐methods approach was used to identify themes and to quantify participants’ awareness of community dementia services.ResultParticipants were a community sample of 22 Oneida Nation people in Northeastern Wisconsin. Mean participant age was 70.5 years; 16 participants identified as female and 6 as male. Of the entire sample, 77.3% of participants knew someone in the Oneida community with dementia, and 63.6% of participants identified as a caregiver (past or present) for a loved one with dementia, 82% were aware of monthly memory cafes, 43% were familiar with services provided by the dementia care specialist, and 75% were aware of the caregiver support group. Thematic analysis revealed commonalities in experiences of dementia and caregiving, including the value of family and community in caring for elders. Qualitative domains surrounding dementia diagnosis included: (1) Meaning making and stigma around “dementia” (2) The family caregiver experience, and (3) Awareness of and need for home and community based‐services.ConclusionExploratory qualitative and quantitative analysis revealed the nuances of how the Oneida Nation of Wisconsin conceptualizes dementia, the family caregiving role, and community‐based dementia care services. As participants shared their lived experiences with dementia, caregiving, and care resources, themes around community and cultural values emerged. Implications for Native communities, health care practitioners, and future research directions are discussed.
Prevalence of alexithymia and its association with geriatric depression in a sample of elderly persons living in Buenos Aires, Argentina
Authors: Tartaglini María Florencia , Hermida Paula , Feldberg Carolina , Somale Maria Veronica , Caruso Diego , Stefani Dorina 
Published: December 2020

AbstractBackgroundAlexithymia has been considered a personality trait characterized by difficulties of identifying and describing feelings, and an externally oriented thinking style. Furthermore, has been descripted as a multidimensional concept sensitive at stressful environment. Moreover, the ageing is a period characterized by physical, affective and economics loses, where alexithymia seems to be a common feature of neurological disease. Objetive: To evaluate the prevalence of Alexithymia and its possible association with geriatric depression in elderly people self‐sufficient.MethodA simple retrospective, cross sectional, correlational study was conducted. A non‐probability, purposive sampling strategy was used. The sample was comprised of 300 older adults over sixty years old, living in Buenos Aires, Argentina. They were evaluated in individual interviews using the following measures: a socio‐demographic questionnaire (ad hoc), Latin American Consensual Toronto Alexithymia Scale LAC TAS‐20 and Geriatric Depression Scale (V‐15). Measures of central tendency and of dispersion were obtained to describe alexithymia and the Pearson’s “r” correlation coefficient was used to measure the degree of association between alexithymia and geriatric depression. An error probability minor or equal to 0.05 was established. Data were analyzed by SPSS statistical software version 21.0.ResultThe mean age was 71.71 year old (+ 7.34 years) and 76,2% of the participants were women. The prevalence of Alexithymia was 53.1%, and the mean of total score was 45.41 (sd 17.55). The subscales scores were: DIF 14.55 (sd + 7.3), DDF 11.40 (sd + 6.0), EOT 19.45 (sd + 7.3). Furthermore, a moderate positive correlation was found between the alexithymia and geriatric depression (“r”: .369, p: .000).ConclusionDetecting alexithymia could be relevant for preserving the wellbeing of elderly people and diagnose diagnosticate affective disorders and neurological diseases.