bluuebunny/crossref_metadata_2025_split huggingface dataset:
Informing policy development regarding the hospital management of people with dementia: A multi‐faceted approach
Authors: Batchelor Frances , Parker Amy , Garratt Stephanie , Williams Sue 
Published: December 2023

AbstractBackgroundIn Australia approximately 30% of older people are from culturally and linguistically diverse (CALD) backgrounds. Hospitals are difficult places for people with dementia and even more difficult for those from CALD backgrounds. 75‐90% of patients with dementia experience behavioural and psychological symptoms of dementia (BPSD) during a hospital stay, with agitation and aggression most common1,2. The factors associated with being acutely unwell, combined with unfamiliar environments, heightened by difficulties in communication, can exacerbate BPSD resulting in increased morbidity/mortality and distress. Our aim was to identify the current state regarding BPSD management, compare this with best practice, and inform policy development particularly in relation to those most vulnerable such as people from CALD backgrounds.MethodRetrospective and prospective observational mixed‐methods design in Victorian hospitals. Six studies were conducted: 1) literature review regarding management of patients with dementia; 2) state‐wide population‐level analysis regarding patients with dementia; 3) inpatient‐ward point prevalence of BPSD; 4) hospital‐wide audit regarding the severity/impact of dementia; 5) gap analysis regarding models‐of‐care for patients with dementia; 6) interviews exploring the experiences of staff and family members of patients with dementia.ResultThe synthesised results will be presented. We will outline how these will contribute to a best practice model‐of‐care for people with dementia in hospital. The challenges in establishing and obtaining relevant data related to dementia, delirium and BPSD in hospitals impacting on evidence‐informed policy will also be highlighted.ConclusionPolicy development for hospital management of people with dementia, particularly minority groups, is a challenge. This is due to the diversity of the population, the diversity in which the condition presents, the speed/severity of disease progression and the multi‐component interventions required. It is further complicated by the complexity of hospital systems and difficulties associated with obtaining meaningful and accurate qualitative and quantitative data. Comprehensive and collaborative approaches are urgently needed.
References:1. Sampson EL, et al. Behavioural and psychiatric symptoms in people with dementia admitted to the acute hospital. British J Psych. 2014;205(3):189‐96.2. White N, et al. The management of behavioural and psychological symptoms of dementia in the acute general medical hospital. Int J Geri Psych. 2017;32(3):297‐305.
Tele‐supervised home‐based transcranial alternating current stimulation (tACS) for Alzheimer’s disease
Authors: Fox Rachel , den Boer Tim , Yu Wanting , LaGanke Nicole , Cattaneo Gabriele , Perellón‐Alfonso Ruben , Bartrés‐Faz David , Manor Bradley , Pascual‐Leone Alvaro , Cappon Davide 
Published: December 2023

AbstractBackgroundOver 55 million people worldwide are currently diagnosed with Alzheimer’s disease (AD) and live with debilitating episodic memory deficits (World Health Organization, 2022). Current pharmacological treatments have limited efficacy. Recently, transcranial alternating current stimulation (tACS) has shown memory improvement in AD by normalizing high‐frequency neuronal activity (Benussi et al., 2022). Our goal was to assess the safety, feasibility, and preliminary effects on episodic memory of a caregiver‐led home‐based tACS approach (HB‐tACS).Method8 participants diagnosed with AD (Table 1) underwent high‐definition HB‐tACS (40 Hz, 20‐minutes) targeting the left angular gyrus (AG), a key node of the memory network. The Acute Phase comprised 14‐weeks of HB‐tACS with at least five weekly sessions. Three participants underwent resting‐state electroencephalography (EEG) before and after. Subsequently, participants completed a 2–3‐month Hiatus Phase not receiving tACS. In the Taper Phase, participants received 2‐3 sessions per week over 3‐months. Primary outcomes were memory and global cognition, measured with the Memory Index Score (MIS) and Montreal Cognitive Assessment (MoCA), respectively, and EEG theta/gamma ratio. Results reported as mean±SD.ResultAll participants completed the study with, on average, 97 HB‐tACS sessions; reporting mild side effects during 25% of sessions, moderate during 5%, and severe during 1%. Acute Phase adherence was 98±6.8% and Taper Phase was 125±22.3% (from minimum of 2/week). After the Acute Phase, all participants showed memory improvement, MIS of 7.25±3.77, sustained during Hiatus 7.00±4.90 and Taper 4.63±2.39 Phases (Table 2), and decreased theta/gamma ratio in AG (Figure 1A). Conversely, participants did not show improvement in the MoCA, 1.13±3.80 after the Acute Phase, and there was modest decrease during the Hiatus ‐0.64± 3.28 and Taper ‐2.56±5.03 phases. These results suggest the specificity of the intervention for memory functioning (Figure 1B) and relate improvement to decreased theta/gamma ratio.ConclusionThis pilot study shows the feasibility of a novel, remotely supervised, caregiver‐led HB‐tACS intervention for AD. Targeting the left AG, memory was noticeably improved while global cognition was relatively stable, indicating that future interventions might benefit from multifocal neuromodulation targeting multiple cognitive domains. These results are encouraging for the prospect of safe and feasible treatment within patients’ homes.
Pathological associations with parkinsonism in chronic traumatic encephalopathy
Authors: Adams Jason W , Kirsch Daniel A , Calderazzo Samantha M , Tuz‐Zahra Fatima , Aytan Nurgul , McKee Ann C. , Tripodis Yorghos , Mez Jesse B. , Alosco Michael L , Stein Thor D. 
Published: December 2023

AbstractBackgroundParkinsonism has been shown to be more frequent in those with a history of traumatic brain injury, repetitive head impacts (RHI), and chronic traumatic encephalopathy (CTE), a disease characterized by tau pathology. However, the underlying pathological associations with parkinsonism in this context are not well known.MethodsAutopsy participants with a history of RHI exposure through contact sports participation and neuropathologically diagnosed with CTE (n = 481) were examined for pathology in the substantia nigra. Based on review of next‐of‐kin interviews and medical records, expert clinicians judged whether symptoms of parkinsonism, including bradykinesia, resting tremor, rigidity, micrographia, and shuffling gait, were present. The total number of consecutive years of contact sports play was used as a proxy for RHI exposure. Neuropathological diagnoses were made using established criteria. Pathology in the substantia nigra was quantified for alpha‐synuclein‐positive Lewy bodies, neurofibrillary tangles (NFTs), and neuronal loss.ResultsOf a total of 481 male CTE participants, 119 (24.7%) had symptoms of parkinsonism during life. Comparison of clinical characteristics of CTE participants with (n = 119) and without (n = 362) parkinsonism showed those with parkinsonism had an older age of death, and a larger proportion had symptoms of dementia, probable REM sleep behavior disorder, and visual hallucinations than participants without parkinsonism (p’s <0.00001). Of those with CTE and parkinsonism, the majority (70%) did not have Lewy bodies within the substantia nigra, suggesting other pathologies may also contribute to motor symptoms. In fact, those with parkinsonism were more likely to have nigral NFTs and neuronal loss (Figure), adjusting for age as well as when restricting to those age >65 (p’s<0.001). Years of contact sports play was associated with NFTs (p = 0.03) and neuronal loss (p = 0.016), but not Lewy bodies in the substantia nigra. Both nigral NFTs (p = 0.001) and Lewy bodies (p<0.001) were associated with nigral neuronal loss. Parkinsonism was associated with neuronal loss (p<0.001) and Lewy bodies (p = 0.027) in the substantia nigra.ConclusionOverall, these findings suggest that RHI contributes to tau pathology and neuronal loss in the substantia nigra. Those susceptible to Lewy body pathology may be further at risk for parkinsonism in CTE.
Implementation of Home Infusions in a Multinational Preclinical Alzheimer’s Disease Study
Authors: Velona Isabella , Yaari Roy , Holdridge Karen C. , Brown Cheryl Ann , Cohen Paula , Shaffer‐Bacareza Elizabeth , Arampatzidou Maria , Lizzul Nancy , Weiss Ellen 
Published: December 2023

AbstractBackgroundThe A4 Study is a Phase 3 clinical trial investigating solanezumab in preclinical Alzheimer’s disease. The COVID‐19 pandemic impacted the delivery of elective health services worldwide and social distancing restrictions created challenges for clinical trial participants to continue monthly infusions. In an effort to retain A4 participants, decentralized clinical trial methods were implemented, including deployment of mobile research nurses to conduct home visits.MethodThe A4 Study is a 4.5 year double‐blind trial, followed by an optional 4 year open‐label treatment period. The study launched in 2014 and 1163 males and females between the ages of 65 and 85 years old have been dosed. Home visits were not originally included in the study protocol, but were implemented in 2020 to mitigate the COVID‐19 pandemic impact on study conduct. PCM Trials offered home visits as an option to allow participants to continue to receive investigational product. Mobile research nurses traveled to participant homes and administered the 30‐ to 60‐minute intravenous infusions every 4 weeks.ResultTo date, more than 1,400 home infusions visits have been conducted in the A4 Study. 124 participants were enrolled in home infusions (99 in the United States; 1 in Canada and 24 in Australia) from 18 sites.ConclusionImplementation of home visits led to several positive outcomes, including reduced participant burden (particularly for participants living in rural/remote locations), study continuity and maintenance of treatment regimen, and retention of participants. Considering the length of the study, the infusion frequency, and the age of the participants, home visits have been a valuable option to help study completion and compliance. Data integrity and participant safety were ensured and maintained with the use of home visits in the A4 study.
Personalized nutritional ketosis through a whole‐food low‐carb diet, medium chain triglycerides, and other ketogenic strategies for people with mild cognitive impairment and Alzheimer’s disease
Authors: Newport Mary T 
Published: December 2023

AbstractInsulin resistance with abnormal brain glucose uptake, a brain‐energy gap, and neuroinflammation are common in the aging brain and are exaggerated in people with Alzheimer’s disease (AD) and in some people with MCI (Cunnane Nature Reviews Drug Discovery 2020). Ketones are an alternative fuel for the brain and ketone uptake is normal in brain regions affected by abnormal glucose uptake in AD (Castellano J Alzheim Dis 2015). Ketones are anti‐inflammatory (Kim Frontiers Immunol 2022) and lessen beta amyloid plaques, tau tangles, and anxiety in animal models (Kashiwaya PNAS 2000; Wu FASEB 2020). Increased brain energy from ketones has been demonstrated using PET imaging in clinical trials of MCT oil (Fortier Alz Dementia 2021), ketogenic diet (KD) (Neth Neurobiol Aging 2020), and exercise (Vandenberghe Appl Physiol Nutr Metab 2019). Recent studies report cognitive and/or other clinical improvements in MCI and/or AD with KD (Brandt J Alzheimers Dis 2019), modified Mediterranean KD (Neth Neurobiol Aging 2020), KD with MCT oil (Taylor Alzheimers Dement 2017), KD with coconut oil in keto study diet recipes (Phillips Alz Research & Therapy 2021), MCT oil with habitual diet (Reger Neurobio Ageing 2004; Constantini Nutri Metab 2009; Maynard Neuropsych Disease Treat 2013; Abe J Nutr Sci Vitaminol 2017; Abe J Nutr 2016; Xu et al. Clin Nutr 2020; Fortier Alz & Dementia 2021), and coconut oil with habitual diet (De la Rubia Orti Nutr Hosp 2017). Case reports of people with AD consuming KD, MCTs, and/or ketone ester also report cognitive improvement (Maynard Neuropsych Disease Treat 2013; Newport Alz Dementia 2015; Stoykovich Alz Dementia 2019; Morrill Diab Metab Syndr:Clin Res & Rev 2019). Ketone esters can rapidly and substantially increase blood ketone levels. Given the lack of any FDA‐approved drug that results in meaningful improvement for people with AD, accumulating evidence suggests that adopting a personalized program for people with AD, aiming for mild to moderate ketosis (blood betahydroxybutyrate levels 0.5‐2 mmol/L), could provide a safe and reasonable therapeutic approach to improve cognitive impairment and other symptoms and could offer a strategy to delay or prevent AD in persons at risk.
Plasma TDP‐43 Levels are Associated with Neuroimaging Measures of Temporal Lobe Structure
Authors: Gold Brian T. , Bauer Christopher E. , Zachariou Valentinos , Sudduth Tiffany L , Van Eldik Linda J. J. , Nelson Peter T , Jicha Gregory A , Wilcock Donna M. , Bauer Christopher 
Published: December 2023

AbstractBackgroundTar DNA binding protein of 43kDa (TDP‐43) proteinopathy is a pathological hallmark of limbic‐predominant age‐related TDP‐43 encephalopathy (LATE), with or without comorbid Alzheimer’s disease neuropathologic change (AD‐NC). At present, the diagnosis of LATE neuropathologic change (LATE‐NC) can only be made at autopsy. There is thus an urgent need for a clinical biomarker for LATE and a blood‐based method would be optimal for clinical and economic reasons. Here, we assessed the relationship between plasma TDP‐43 levels with imaging measures of neurodegeneration (volume and cortical thickness).MethodParticipants were 72 nondemented older adults (47 women, age range 60‐94 years). Immunoassays for TDP‐43, phosphorylated threonine‐181 tau (p‐tau181), total tau (t‐tau), amyloid beta‐42 (Aβ42), and amyloid beta‐40 (Aβ40) were quantified (pg/mL) in duplicate for each participant using the Quanterix Simoa HD‐X instrument. Neuroimaging was conducted using a 3 Tesla MRI Siemens Prisma scanner with a 64‐channel head coil. A T1‐weighted MPRAGE sequence with 1 cubic mm voxels covering the entire brain was acquired. FreeSurfer software was used to estimate intracranial volume (ICV) and volumes of the entorhinal cortex (ERC), amygdala, and subiculum of the hippocampus, regions known to harbor TDP‐43 pathology in early stages of LATE‐NC. Multivariate linear regression models controlling for age, sex, and ICV were conducted in SPSS using plasma TDP‐43 as the predictor and volumetric or cortical thickness measurements as dependent variables.ResultThere was a negative association between plasma TDP‐43 concentration and ERC volume, a relationship that remained significant after controlling for plasma markers of AD‐NC (the Aβ42/Aβ40 ratio, p‐tau181/Aβ40 ratio or t‐tau/Aβ40 ratio). Results from subsequent exploratory analyses indicated a negative association between TDP‐43 and cortical thickness in the inferior temporal lobe, a finding which also remained significant after controlling for AD‐NC plasma biomarkers.ConclusionHigh plasma TDP‐43 levels were associated with in vivo imaging measures of neurodegeneration in multiple temporal lobe structures. Plasma TDP‐43 assays may prove useful in clinical trials seeking to enroll individuals at risk for LATE‐NC.
Unlocking cognition with pulsatile GnRH in Down Syndrome: implications for Alzheimer’s disease
Authors: Prevot Vincent 
Published: December 2023

AbstractBackgroundThere is currently no viable treatment for the cognitive and olfactory deficits of Trisomy 21 and Alzheimer’s disease.MethodPhysiological characterization and epigenetic, cellular, chemogenetic, and pharmacological interventions in male and female Ts65Dn mice (P9‐P360), a mouse model of Down syndrome, and 12‐month‐old THY::TAU22 male mice, a mouse model of Alzheimer’s disease, and their wild‐type littermates. Seven men with Down syndrome (20‐50 years of age) were enrolled in an open‐label pilot study to assess the effect of 6‐month pulsatile GnRH therapy on cognitive and olfactory function.ResultWe show in Ts65Dn mice that olfactory and cognitive neurological symptoms are closely related to a post‐pubertal decrease in hypothalamic and extra‐hypothalamic expression of a master molecule controlling reproduction ‐ gonadotropin‐releasing hormone (GnRH) ‐ and appear to be linked to an imbalance in a microRNA‐gene network known to regulate the maturation of GnRH neurons as well as to an alteration in hippocampal synaptic transmission. Restoring physiological GnRH levels abolishes olfactory and cognitive deficits in Ts65Dn and THY::TAU22 mice, while pulsatile GnRH treatment improves cognition and brain connectivity in adult T21 patients.ConclusionWe have discovered that GnRH plays a crucial role in olfaction and cognition, and pulsatile GnRH treatment holds promise for improving cognitive deficits in patients with Down syndrome. Such treatment could potentially also be beneficial for mobilizing cognitive reserve in pathological brain aging such as that found in Alzheimer’s disease.
Frequency of social isolation among older adults in Nepal
Authors: Shrestha Prabha , Baral Dikshya 
Published: December 2023

AbstractBackgroundSocial isolation is a recently documented modifiable risk factors for dementia but little is known about its prevalence in low and middle income countries (LMICs).1 Older adults in Nepal are increasingly at for risk for social isolation given trends of adult child migration to other communities. The resultant social isolation increases risk for depression, psychological distress, and dementia2‐3. This study aimed to estimate the prevalence of social isolation among older adults of Nepal and its associated factors.MethodsA quantitative cross‐sectional study in Dhulikhel municipality of Nepal. Two geographical regions within the city were randomly selected. Systematic random sampling was used for the selection of respondents. We employed the Lubben Social Network Scale (LSNS‐18), a brief tool validated in LMIC, to quantify social isolation.4 Data were analyzed with Statistical Package for Social Sciences (SPSS) v25.ResultsMore than half of respondents (52.3%) were age 60‐70 years, 56.1% were male, 55.1% were illiterate, and 59.8% were living in a nuclear family. More than one third (37.4%) met criteria for socially isolation. Social isolation associated with age (p = 0.026), being a widow (p = 0.002), living in a nuclear family (p = 0.001), and the presence of chronic diseases (p = 0.014). Whereas gender and education were not significantly associated with social isolation.ConclusionMore than one third of older adults in this representative community met criteria for social isolation despite the family‐based societal norms that are typical of Nepal. Addressing this issue may promote brain health among older adults. Further research is recommended to examine the cognitive health of this isolated population.References1. Livingston et al, Dementia prevention, intervention, and care. The Lancet. 20172. Xiang X, et al Trajectories of Social Isolation and Dementia in Older Adults J Aging Health. 20213. Taylor HO, et al. Social Isolation, Depression, and Psychological Distress Among Older Adults. J Aging Health. 20184. Bincy, K. et al. Validation of Expanded form of Lubben Social Network Scale among Community‐Dwelling Geriatric Population in India. Indian Journal of Community Medicine 2022.
Keywords:Older adults, Social isolation, Dementia
Proteomics Analysis Identifying New Markers Related to Alzheimer’s Disease Pathology In Vivo
Authors: Binette Alexa Pichet , Salvadó Gemma , Spotorno Nicola , Vogel Jacob W , Kumar Atul , Strandberg Olof , Janelidze Shorena , Hansson Oskar 
Published: December 2023

AbstractBackgroundTo better understand the pathophysiological processes in Alzheimer’s disease (AD), we need to broaden our knowledge on molecular pathways and discover molecular markers that co‐occur with, precipitate and follow the accumulation beta‐amyloid (Aβ) and tau pathology. Using high‐throughput proteomics, we investigated how a wide array of proteins relate to AD pathology in a large cohort spanning the AD continuum.MethodWe included 949 BioFINDER‐2 participants with cerebrospinal fluid (CSF) measurements of 2943 proteins (Olink Explore 3072 assay), and CSF and/or PET measurements of Aβ and tau. We compared CSF proteins between groups based on their Aβ (A) and tau (T) status, defined respectively from CSF Aβ42/40 ratio and tau‐PET RO948 in the temporal meta‐ROI (i.e. A‐T‐ vs. A+T‐ and A+T‐ vs. A+T+). We also compared A+T+ vs. non‐AD neurodegenerative diseases. Then, among the significant proteins identified across all three comparisons, we evaluated their associations with Aβ‐ (flutemetamol) and tau‐PET, both cross‐sectionally and longitudinally (based on rate of change). These latter analyses were restricted to cognitively unimpaired and patients with MCI, who all had Aβ‐ and tau‐PET available (n = 548).ResultAcross all AT comparisons, 85 proteins were significantly different between groups (pFDR<0.05; Fig.1). More advanced pathology was associated with higher protein levels, except ApoE levels that were decreased. The A+T‐ vs. A+T+ comparison revealed most protein differences (n = 74; Fig.1B), compared to A‐T‐ vs. A+T‐ or A+T+ vs. non‐AD neurodegenerative diseases. In cross‐sectional analyses, 32/85 proteins (38%) were significantly associated with Aβ‐ and tau‐PET load, with the strongest ones being microtubule‐associated protein tau (MAPT), neurogranin (NRGN), ITGAM, ITGB2 and SMOC1. When putting both pathologies in the same model, all proteins remained associated with Aβ only, except for ENO2 and GPI, which remained associated with tau only (Table 1). In longitudinal analyses, 19 proteins were associated with greater tau‐PET rate of change (the top five being MAPT, NRGN, ITGB2, FABP3 and CHIT1), whereas only SMOC1 and ITGAM were associated with greater Aβ‐PET rate of change (Table 1).ConclusionThrough comprehensive proteomics analysis, we identified novel proteins associated with AD pathology, many of which are involved innate immunity, intracellular transport and extracellular matrix binding.