bluuebunny/crossref_metadata_2025_split huggingface dataset:
The AGED Triad: Opportunities for delaying dementia
Authors: Pieruccini‐Faria Frederico , Finger Elizabeth , Hachinski Vladimir , Montero‐Odasso Manuel 
Published: December 2023

AbstractBackgroundApathy, gait impairment, and executive dysfunction (AGED) commonly occur jointly in the elderly, sometimes masked by the generic description of “late life depression.” The recognition of the triad is clinically useful because it often results from hypertension, which is treatable and preventable. Vascular risk factors, especially hypertension, can insidiously cause brain damage which may increase the risk of dementia in older adults. Hence the AGED triad can be a behavioral marker of cerebrovascular damaging which may lead to cognitive disability. It is unclear, however, whether individuals diagnosed with the AGED triad phenotype are at higher risk of earlier conversion to dementia compared with non‐AGED triad phenotype. We also tested the hypothesis that AGED triad would have better predictive capability than each of the three components separately.MethodAfter baseline assessments 275 community‐dwelling older individuals (72.15±6.68 years of age; 58% women) from the Gait and Brain Study underwent face‐to‐face interviews every 6 months for up to 7 years (22.93±20.33 months; 6∼105). Gait performance was assessed electronically; apathy was assessed through the Geriatric Depression Scale‐3A; dysexecutive function was assessed trough the Trail Making test‐part B; dementia was diagnosed through the clinical dementia rating scale. Adjusted Cox‐regression models were used to determine early dementia risk in each exposure group.ResultA greater percentage of AGED triad individuals at baseline had more than 2 vascular risk factors (p<.01) including hypertension, diabetes, hypercholesterolemia, obesity and smoking history. Incidence of dementia in the AGED triad was 16.8% vs. 6% in the non‐AGED triad. AGED triad significantly increased the risk of earlier conversion to dementia compared with non‐AGED triad by 323% independently of the number of vascular risk factors at baseline. AGED triad predicted earlier conversion to dementia more than the three components separately (HR = 6.60 95%CI 1.48 to 29.46; p = .01; see figure 1).ConclusionAGED triad phenotype predicts earlier conversion to dementia compared with non‐AGED triad; and earlier than slow gait, apathy and dysexecutive function separately. AGED triad may be a behavioral marker of severe insidious brain damage over of an individual’s life course likely caused by unmanaged modifiable vascular risk factors.
Exercise‐induced alterations to glial activation in the 5xFAD mouse model of Alzheimer’s Disease
Authors: Birnbaum Allison , Rorrer Shelby , Wilson Anna , Cortes Constanza J 
Published: December 2023

AbstractBackgroundGlial activation and subsequent inflammation are well‐described characteristics of Alzheimer’s disease (AD) and have been demonstrated to contribute to disease progression. Exercise contributes to structural and functional changes in the brain, including in models of AD by improving neuronal plasticity and reducing glial activation. The exact glial pathways altered by exercise have not been well‐described, making it difficult to develop therapeutic interventions that can provide similar benefits as physical activity.MethodWe selected to use the 5xFAD model based on the early amyloid plaque development (1.5‐2 months) and neuroinflammation onset (5‐6 months) time points. Two‐month‐old hemizygous 5xFAD and B6SJLF1 control female mice were given free access to running wheels for 16 weeks. All running activity was tracked over 12‐hour cycles. Locked wheels were used for both genotypes as sedentary controls. Hippocampal RNA from all 4 groups was isolated and analyzed using the Nanostring mouse AD and mouse neuroinflammation nCounter panels. We will also examine changes to amyloid plaque burden and morphological differences in astrocytes and microglia in the hippocampus via histological approaches.Result5xFAD runners had significantly higher weights compared to their sedentary littermate controls, suggesting endurance exercise provides metabolic maintenance in this model. In agreement with this, no such weight gain was observed in the B6SJLF1 age‐ and sex‐matched control runners. Surprisingly, we found control mice ran faster and more often per interval than their 5XFAD counterparts. Using Nanostring nCounter, we observed little to no difference between B6SJLF1 running and sedentary groups, however runner 5XFAD mice were closer to control values compared to their sedentary 5XFAD counterparts for many pathways including lipid metabolism and neural connectivity. We are currently investigating the genes in these pathways and other inflammatory genes not included in the two nCounter panels, as well as histological analysis of amyloid plaque burden.ConclusionWe have observed significant physical changes between running and sedentary 5xFAD mice, supporting the hypothesis that physical activity provides beneficial effects against AD. Data acquired from this study will also aid in our understanding of exercise alterations to signaling pathways, and highlight potential therapeutic targets to reduces neurodegenerative disease‐associated neuroinflammation.
The DECIDE‐initiative: A multi‐dimensional project aiming to reduce sedative drugs of patients with dementia in long term care
Authors: Diehl‐Schmid Janine , Kohl Sarah , Trojan Monika 
Published: December 2023

AbstractPrescription prevalence of sedative drugs – mostly used for the treatment of neuropsychiatric symptoms ‐ in patients with dementia in Germany is approximately 40%. Since sedative drugs cause a variety of adverse effects and might reduce quality of life significantly, the aim must be to use sedative drugs only as much as necessary and as little as possible.The DECIDE initiative was founded at the Department of Psychiatry at the Technical University of Munich and funded by the Bavarian State Ministry of Health. DECIDE uses a multidimensional approach to raise awareness among all stakeholders in the health care system for a more conscious and responsible use of sedative medication in people with dementia and thus to sustainably reduce the frequency of prescriptions.The DECIDE initiative includes a webpage (www.decide.bayern) with thorough and comprehensive information for informal and formal caregivers, legal guardians, nursing staff and doctors; a telephone hotline for patients and caregivers; network building; awareness campaigns; and continuing education.A particular important component of the DECIDE‐initiative is the DECIDE LTC‐visits. So far, 30 randomly chosen LTC facilities in Bavaria have been visited by a medical specialist for gerontopsychiatry. In each facility the gerontopsychiatrist offered a training event for the nursing home staff in order to explain behavioral symptoms, non‐pharmacological interventions, and the effects and side effects of sedative drugs, as well as the potential for deprescribing. In each attending LTC facility the prescription prevalence of sedative drugs was assessed. Medical and nursing records were checked in order to find out, if deprescribing – according to a deprescribing algorithm that was recently developed within the DECIDE project (Roßmeier et al., 2022, Nervenarzt) ‐ could be recommended. The prescribing prevalence as assessed in 1492 residents with dementia was 51%. In 70 out of 202 residents describing could be recommended and was discussed with the treating physician.One year follow‐up visits will show if the DECIDE initiative is able to sensitize physicians and nursing homes to the problem of sedating psychopharmacotherapy and the potential for deprescribing, reflected then in a lower prescription prevalence.
Update on [18F]ACI‐12589: a novel and promising PET tracer for a‐synuclein
Authors: Capotosti Francesca , Smith Ruben , Vokali Efthymia , Molette Jerome , Ohlsson Tomas , Schain Martin , Ravache Myriam , Dimitrakopoulos Ioannis K , Delgado Christophe , Kocher Jacqueline , Pittet Laure , Vallet Coralie , Luthi‐Carter Ruth , Hliva Valerie , Pfeifer Andrea , Kosco‐Vilbois Marie , Streffer Johannes , Hansson Oskar 
Published: December 2023

AbstractBackgroundParkinson’s disease (PD) and other synucleinopathies, such as Multiple System Atrophy (MSA), involve a progressive accumulation of a‐synuclein (a‐syn) inclusions which correlate well with clinical manifestations. A PET agent capable of imaging specifically and selectively a‐syn inclusions could significantly improve differential diagnosis and clinical trials for drug candidates targeting a‐syn. Here, we report the preclinical and initial clinical characterization of [18F]ACI‐12589 in patients with different synucleinopathies.MethodLeveraging AC Immune’s proprietary small molecule Morphomer® library, compounds were optimized for affinity and specificity for pathological a‐syn as well as for selectivity versus frequent co‐pathologies, using autoradiography and radiobinding techniques. Based on these results [18F]ACI‐12589, was selected for initial clinical evaluation. PET scans were acquired for approximately 50 participants including idiopathic and genetic PD, MSA, Dementia with Lewy bodies (DLB) in addition to controls and cases from other neurodegenerative disorders (NDDs). Initial participants underwent 0‐90 min dynamic scans with arterial blood sampling allowing full kinetic modeling, while following scans were acquired as 60‐90 min static scans.ResultWhen tested on tissue sections, ACI‐12589 demonstrated a specific signal matching the distribution of pathological a‐syn. This target engagement was observed across a range of cases with different synucleinopathy diagnoses, but also in tissues from other NDDs, when a‐syn inclusions were present as co‐pathology. ACI‐12589 is selective in vitro versus frequent co‐pathologies such as amyloid‐b and Tau and has a clean off‐target profile, including for MAO‐A and B. Initial clinical data indicate that [18F]ACI‐12589 displayed substantial retention in MSA cases in expected disease‐affected brain areas based on clinical manifestations. When quantified, the signal in the cerebellar peduncles was clearly discriminating the MSA group from controls, synucleinopathy cases and other NDDs. In addition, this signal could not be blocked in vivo by the MAO‐B inhibitor Selegiline. Although to a lower level than in MSA cases, some signal retention was observed in different NDDs.Conclusion[18F]ACI‐12589 displays the preclinical and clinical characteristics deemed necessary to become a reliable and accurate PET radiotracer for the detection of a‐syn pathology in MSA. Additional evaluations of this tracer will focus on the longitudinal and early disease stage assessments.
Synaptic proteins in pre‐symptomatic Alzheimer’s disease: biomarkers for early detection of Cognitive Decline
Authors: Ao Jiarui , Labonté Anne , Brinkmalm Ann , Blennow Kaj , Zetterberg Henrik , Breitner John C.S. , Villeneuve Sylvia , Poirier Judes ,   the PREVENT‐AD Research Group
Published: December 2023

AbstractBackgroundSynaptic proteins in the cerebrospinal fluid (CSF) may reveal changes in the pre‐symptomatic stages of Alzheimer’s disease (AD), thus may be candidate biomarkers for early detection of the disease.MethodThe PREVENT‐AD cohort includes symptom‐free (upon enrolment) elderly participants who are at risk of developing AD from their family history. We used enzyme‐linked immunosorbent assay kits to assess CSF samples from 129 such participants for the “classical” AD biomarkers total tau, phosphorylated (181) tau and Aβ42. We also used neuroimaging data (MRI, PET) and neuropsychological assessments (MMSE, RBANS) as potential indicators disease progression. We then used in the CSF samples to measure the soluble synaptic biomarkers ADAM 22 (post‐synaptic), ADAM23 (pre‐synaptic). Immunoprecipitated SYT1 (pre‐synaptic) from CSF were analyyzed using high‐resolution selected ion monitoring analyses on a quadrupole–orbitrap mass spectrometer Q Exactive. Statistical analysis of the association of these markers with evidence of disease in analyses were done included sex and APOE e4 status as covariates.ResultAmong participants who remained cognitively unimpaired, we observed significant correlations between baseline CSF ADAM 22 levels and t‐tau (R2 = 0.22, p < 0.0001), p‐tau (R2 = 0.22, p < 0.0001), and Aβ42 (R2 = 0.06, p = 0.01488). We also found similarly suggestive correlations also between CSF ADAM 23, CSF SYT1 and the same disease markers. Covariate analyses suggested little or no variation in the associations between these synaptic proteins with t‐tau and p‐tau by sex, APOE e4 status, negative PET amyloid positivity (standardized uptake value ratio ≤ 1.37) and negative CSF total tau positivity (≤ 335pg/ul). PET amyloid positivity was significantly associated with ADAM22 and p‐tau interactions whereas SYT1 was significantly associated with t‐tau and p‐tau in CSF tau‐positive participants. In linear regression analyses, baseline CSF ADAM22 levels correlated with the language cognitive performance trajectory slopes estimated over the course of 5 to 8 years on the RBANS (R2 = 0.04, p = 0.03912). We found no significant interaction between other baseline CSF synaptic protein levels and other subscales of the RBANS.ConclusionCSF synaptic protein levels show promising correlation with landmark AD proteins and emerging cognitive deficits.
Effects of Acceptance and Commitment Therapy (ACT) group intervention for the treatment of anxiety in family carers of people with dementia: an exploratory randomised controlled trial
Authors: Ferreira Michele Gomes , Kishita Naoko , de Faria Renata Caetano Vieira , Plautino Maria Eduarda Almeida , Yonamine Gustavo Campos , Torres Suellen Caroline Ribeiro , Caramelli Paulo 
Published: December 2023

AbstractBackgroundThe prevalence of anxiety symptoms is estimated to be equal to or higher than the prevalence of depressive symptoms in family carers of people with dementia. However, anxiety is currently somehow neglected in the carer literature. Previous studies demonstrated that Acceptance and Commitment Therapy (ACT) is effective for treating anxiety symptoms in family carers of people with dementia, but these studies were mainly conducted in developed countries. The current study explored the effectiveness of an ACT group intervention on the anxiety symptoms in Brazilian family carers of people with dementia.MethodA single‐centre, unblinded, double‐arm exploratory randomised trial was conducted. Fifty‐seven family carers of people with dementia presenting with mild to severe anxiety symptoms were randomised to the intervention group (n = 29) or waiting list group (n = 28). The intervention group received eight weekly sessions of Group ACT, delivered through videoconference. Participants completed the measure of anxiety and depressive symptoms, caregiver burden, psychological flexibility and quality of life at Week 0, Week 9 and Week 20. Multiple linear regression analyses were performed to evaluate whether there was a significant difference in scores between the intervention and control groups, at week 9 and week 20, while controlling for the baseline scores using both intention‐to‐treat and completers data analyses.ResultParticipants were mostly women, from low‐ to middle‐income socioeconomic levels, with a mean age of 52 years and median education of 15 years. Participants in the intervention group had lower scores of anxiety and depression symptoms compared to participants in the control condition at weeks 9 and 20 in both the intention‐to‐treat and completer analyses. Only participants who attended six or more sessions (i.e. completer sample) demonstrated reduced caregiver burden at both follow‐up points. The completer sample also showed improvement in quality of life at week 9. The results did not show any effect of the intervention on psychological flexibility.ConclusionThis study provides evidence supporting the use of group ACT, delivered through videoconference, with family carers of people with dementia to help them cope better with anxiety and depressive symptoms.
Decline in white matter volume and EEG delta oscillations in mild cognitive impairment
Authors: Özbek Yağmur 
Published: December 2023

AbstractBackgroundChanges in white matter (WM) may be associated with progression and risk of Alzheimer’s disease (AD) (Nasrabady et. al, 2018) along with conversion to Mild Cognitive Impairment (MCI) (Smith et. al, 2008). Total WM volume and its relation with EROs in MCI remain unclear. As a general notion, greater delta EROs occurring in the post‐stimulus time‐period indicate better cognitive responses in contrary to dynamics of resting state EEG. Surgical WM disruptions are associated with alterations more prominently in low frequency brain oscillations (EROs) (Hawasli et al, 2016). The current study aims to investigate WM volumes and EROs in cognitively unimpaired individuals (CU) and MCI.MethodSixteen individuals with MCI were compared with demographically matched 16 CU using EROs elicited by a visual classical‐oddball paradigm along with WM volumes obtained 3D T1‐weighted TFE‐sequence. WM volumes analyzed with univariate ANOVA. Repeated measures ANOVAs conducted for delta(0.5‐3.5Hz), theta(4‐7Hz), alpha(8‐13Hz), beta(15‐30Hz), and gamma(30‐48Hz) amplitudes. Binary logistic regression analyses conducted for significant WM volume variables and EROs. Correlations between WM and EROs were analyzed with Person correlation coefficient.ResultDelta ERO amplitudes were diminished [F(5,145) = 3.373,p = .035] in MCI at frontal (p = .011), central (p = .014) and parietal (p = .006) electrode locations. Furthermore, WM in right middle orbitofrontal [F(1,29) = 4.599,p = .041], left inferior temporal [F(1,29) = 4.198,p = .049] and left parahippocampal gyrus [F(51,29) = 5.182,p = .030] demonstrated less volume in MCI compared to CU. Binary logistic regression indicated that [X2(9) = 26.615,p = .002] combined WM volumes and delta EROs can classify MCI and CU with 87.1% accuracy. There were positive correlations between occipital delta and left (r = .501, p = .003) and right gyrus rectus (r = .374, p = .003) WM volumes.ConclusionThis study showed WM volumes and delta EROs were reduced in MCI. Decreased amplitudes of delta EROs seem to reflect volume loss of WM in MCI, possibly indicating an underlying demyelination or axonal loss. Delta EROs and WM changes may be helpful tools to monitor MCI focusing on axons and myelination/oligodendrocytes. Furthermore, their combined measurements can classify MCI from healthy individuals sufficiently.
Lobe‐specific changes in white matter volume and myelination following 6‐month 40 Hz gamma sensory stimulation in patients on the Alzheimer’s disease spectrum
Authors: Cimenser Aylin , Da Xiao , Hempel Evan , Malchano Zach , Vaughan Brent , Megerian Jonathan Thomas , Hajos Mihaly 
Published: December 2023

AbstractBackgroundAlthough morphometric changes in Alzheimer’s Disease (AD) occur both in gray and white matter, gray matter changes had been the primary focus of previous work. Recent studies have highlighted the importance of pathological changes in white matter and myelination in AD patients, including early changes to oligodendrocytes and transcription of myelin protein genes in the white matter prior to symptoms of cognitive decline, even in subjects with AD but without other neurological comorbidities (Ferrer et al., 2020). Since neuronal activities, particularly network oscillations have been shown to promote myelination, the present study examined how 40Hz gamma stimulation affected white matter volume and myelination in different cortical lobes in patients with AD.MethodData were obtained from the Overture trial (NCT03555281) in which treatment participants received daily, at‐home, 40Hz gamma sensory stimulation for six months, while placebo participants received sham stimulation (treatment‐to‐placebo ratio 2:1). Magnetic resonance imaging (MRI) data were collected at 1.5 Tesla at baseline, month 3, and month 6. MRI T1 images and T1w/T2w ratios were used to estimate volume (N = 38) and myelination (N = 36), respectively. Using Bayesian linear mixed effects modeling, we estimated white matter volume and myelination percent changes with respect to baseline. Treatment group results were reported in relation to the placebo group.ResultWith respect to the placebo group: In the left hemisphere, the treatment group exhibited reduced white matter atrophy in the frontal lobe (‐3.27±1.4, p = 0.0225), in the temporal lobe (‐3.9±1.76, p = 0.0306), in the parietal lobe (‐3.32±1.43, p = 0.0236), in the occipital lobe (‐4.1±1.72, p = 0.0195) and reduced demyelination in the frontal lobe (‐5.13±2.12, p = 0.0186), in the temporal lobe (‐5.33±2.42, p = 0.0321), in the parietal lobe (‐5.7±2.07 (p = 0.0079), in the occipital lobe (‐5.65±2.52, p = 0.0296). In the right hemisphere, the treatment group trended towards reduced white matter volume loss and demyelination in all lobes, however, demyelination was significantly reduced in the parietal lobe (‐4.48±2.09, p = 0.037), and in the occipital lobe (‐5.5±2.22, p = 0.0165).ConclusionWhite matter atrophy and demyelination were statistically significantly reduced in all lobes of the left hemisphere and trended towards reduction in the right hemisphere, demonstrating that 40Hz sensory stimulation can reduce the neurodegeneration associated with AD.
Gestational Diabetes Mellitus Triggers Maternal Premature Brain Aging and Brain Pathologies
Authors: Huang Huatuo , Oo Thura Tun , Apaijai Nattayaporn , Suntornsaratoon Panan , Charoenphandhu Narattaphol , Chattipakorn Nipon , Chattipakorn Siriporn C 
Published: December 2023

AbstractBackgroundIt has been well‐documented that diabetes mellitus (DM) causes brain pathologies and premature brain aging. Previous studies showed that women with gestational diabetes mellitus (GDM) are at a high risk to develop depression. It is unclear whether GDM can lead to brain pathologies and premature brain aging, thus contributing to cognitive behavior changes as observed in human and animal studies.MethodFemale Sprague‐Dawley rats were fed either a normal diet (ND, 5% kcal from fat) or a high‐fat diet (HFD, 45% kcal from fat) throughout the entire study. At week 4, rats were mated overnight with ND‐fed male rats, and successful pregnancy was denoted as pregnancy day 0 (P0). At P0, HFD‐treated rats were intraperitoneally injected with a single‐dose streptozotocin (STZ, 35 mg/kg) to induce DM or the same amount of vehicle as HFD‐control. The ND‐treated rats received the same amount of vehicle as the ND‐control. Oral glucose tolerance test and plasma insulin levels were assessed at pregnancy day 16 to confirm the GDM model. At postpartum day 21, maternal rats were sacrificed, and brains were rapidly removed to determine brain pathologies and premature brain aging in the prefrontal cortex and hippocampus.ResultRats treated with HFD and HFD+STZ developed prediabetes and diabetes conditions, respectively. GDM induced brain inflammation and brain cell senescence, as indicated by increases in nuclear factor kappa‐light‐chain‐enhancer of activated B, senescence‐associated beta‐galactosidase, and p16 expression in the prefrontal cortex and hippocampus (Figure 1). Furthermore, mitochondrial fusion was enhanced, while brain apoptosis was attenuated in the prefrontal cortex and hippocampus of GDM rats (Figure 1).ConclusionGDM triggers maternal brain pathologies as well as premature brain aging in both prefrontal cortex and hippocampus. Our findings highlight that the brain may have compensatory mechanisms that can help guard against the negative effects of GDM.