bluuebunny/crossref_metadata_2025_split huggingface dataset:
Degeneration of the cholinergic system in subjective cognitive decline: A systematic review
Authors: Alemany Iris , Rodriguez‐Hernandez Marta A. , Diaz‐Galvan Patricia , Nemy Milan , Westman Eric , Barroso Jose , Ferreira Daniel , Cedres Nira 
Published: June 2023

AbstractBackgroundSubjective cognitive decline (SCD) is topic of mayor interest when identifying individuals at risk for future cognitive impairment and dementia. The degeneration of the cholinergic system is linked to the onset of cognitive symptoms in mild cognitive impairment (MCI) and dementia. Yet, it is uncertain whether the neurodegeneration of the cholinergic system is already present in SCD individuals. This review is the first to synthetize the available data on the association of SCD with multiple markers of degeneration in the cholinergic system.MethodFollowing the PRISMA guidelines, original articles focused on the association of SCD and the cholinergic system were extracted from three databases: Pubmed, WOS and Scopus, in November 2021. Two researchers reviewed the studies independently in a 2‐stepwise approach. The quality of the studies and risk of bias were assessed using FLC 3.0, that allows to systematically evaluate the studies and summarize them easily.ResultAmong 119 studies found in our systematic search, 11 were included in the current review. Seven were cross‐sectional and 4 had a longitudinal design. Most of the studies operationalized SCD based on amnestic cognitive complaints (n = 9, 82%). The cholinergic system measures were based on neuroimaging markers for volume of the basal forebrain and/or functional connectivity, transcranial magnetic stimulation, or biofluid markers (i.e. cerebrospinal fluid (CSF) and plasma). The studies focused on association of SCD with basal brain atrophy, 75% reported reduce volumes in SCD; From those focused on functional connectivity of the cholinergic system, 33% reported poorer connectivity in SCD.ConclusionBased on scientific evidence, neurodegeneration of the cholinergic system is already evident during SCD. Using multiple cholinergic biomarkers, degeneration of cholinergic system in SCD seems to occur with significant structural and functional degeneration of cholinergic nuclei in the basal forebrain and their connections with other brain areas. These findings have implications on identifying individuals with increased vulnerability to cognitive impairment and for targeting individuals that might benefit from cholinergic‐target treatments. Further research is needed to elucidate potential contributors to the cholinergic degeneration in SCD and its impact on cognition and clinical progression.
The performance of connected speech is correlated with cognitive tests in very early Alzheimer disease
Authors: Liu Yi‐Chien , Chang Chih‐Ting , Lee Chia‐Ying , Chou Chia‐Ju 
Published: June 2023

AbstractBackgroundLanguage impairment is one of the most important clinical features of Alzheimer disease. However, it is very difficult to detect at a very early stage. In this study, we try to analyze the language performance via a set of language tests. At the same time, various biomarkers were also checked and compared.MethodFrom 2020 to 2021, we recruited 11 aMCI and 24 normal controls from the memory clinic of Cardinal Tian Hospital in Taiwan. The clinical diagnosis of aMCI is based on clinical history (with short‐term memory impairment over 6 months), brain MRI, amyloid PET, and various neuropsychological tests. All the participants received the Picture Description Test (PDT), Taiwanese Boston naming test (T‐BNT, 30 items) and semantic fluency test. In PDT, the participants were requested to describe three Taiwanese‐culture‐based pictures to evaluate their performance of connected speech. The responses were recorded, transcribed, and subsequently analyzed by the Chinese tokenize system. Linguistic variables such as the number of total words, content words, grammatically intact sentences, long‐pauses (more than 2s), and fillers were recorded and analyzed.ResultIn our cohort, their baseline MMSE scores are lower (24.1 ± 3.1 V.S. 28.9 ± 1.6, p<0.001). The amyloid positive rate is significantly higher in the aMCI group (54.8% V.S. 29.1%, p = 0.05). The scores of T‐BNT (19.9 ± 4.7 V.S. 24.9 ± 2.3, p<0.001) and semantic fluency test (9.7 ± 3.8 V.S. 17.3 ± 4.0, p<0.001) were significantly lower in the aMCI group. The multiple regression model showed that the variable of non‐repeated words and numbers of long‐pauses were significant in the final model and explained of 32% the total variance of the MMSE (R2 = 0.32; p<0.01).ConclusionEven in the MCI stage, the language‐based examinations can be very different from the normal controls. More non‐repeated words and less long‐pauses in connected speech predict better cognitive performance. Combining with biomarkers, these linguistic variables may detect AD at the earlier stage.
Blood DNA methylation biomarkers for cognitive decline in older adults with type 2 diabetes
Authors: Manzali Sigalit , Ravona‐Springer Ramit , Jacob‐Hirsch Jasmine , Heymann Anthony , Beeri Michal Schnaider , Greenbaum Lior 
Published: June 2023

AbstractBackgroundIndividuals with type 2 diabetes (T2D) are at particularly high risk for cognitive decline and dementia. Finding early, pre‐clinical biomarkers for detecting and tracking cognitive impairment and dementia in this population is important for personalized medicine approach. Our study aims to find blood DNA methylation biomarkers for cognitive decline among elderly T2D patients.MethodTwo groups of 30 T2D subjects each, from the Israel Diabetes and Cognitive Decline (IDCD) cohort, were included. One group (converters) was cognitively normal at baseline, yet at 36‐54 months follow‐up deteriorated from a Clinical Dementia Rating scale CDR = 0 (no dementia) to CDR≥0.5 (questionable dementia or frank dementia). The control group (non‐converters) was cognitively normal at baseline and maintained normal cognition during the follow‐up period (CDR = 0). We performed an epigenome‐wide association study, using the Illumina Infinium MethylationEPIC microarray, and searched for differentially methylated positions (DMPs) with significant methylation alterations (≥ 2 fold and FDR corrected p value <0.05) between the baseline and the follow‐up time points for each of the two groups.ResultParticipants were 65‐83 years of age (mean‐73.6 ± 4.1), 72% were men. The mean hemoglobin A1C value was 6.9 ± 0.8%, and T2D duration was 9.4 ± 4.7 years. Converters and non‐converters did not differ in any of these characteristics. Results show significant changes in multiple DMPs among the converters, but only in a few DMPs in the non‐converters. Gene ontology analyses indicates primarily involvement of central nervous system‐related pathways, mainly neurodevelopmental disorders.ConclusionThese preliminary results, employing a high‐throughput approach for methylation profile in blood, suggest methylomic alterations as a potential biomarker for cognitive decline in T2D elderly. A priori identification of patients at risk for cognitive decline may lead to early intervention in modifiable risk factors in this population, which is highly susceptible to dementia.
Atypical mixed logopenic and semantic progressive primary aphasia (PPA) in Arabic with white matter abnormalities
Authors: Taiebine Mohamed , Faris Mustapha El Alaoui 
Published: June 2023

AbstractBackgroundThe concept of primary progressive aphasia (PPA) or Mesulam syndrome (Mesulam, 2014) is an isolated and progressive deterioration of language, usually due to progressive focal atrophy of the left perisylvian regions (of the dominant hemisphere). Four types of PPA have been already identified: Non‐fluent variant or Nfv‐PPA; Logopenic variant or Lv‐PPA; Semantic variant or Sv‐PPA and Mixed variant M‐PPA (Gorno‐Tempini et al., 2011; Mesulam et al., 2014).MethodWe report MH who displayed a Mixed‐variant of PPA (M‐PPA) in Arabic. Her daily activities were preserved. Neuroimaging using MRI coronal cut (FLAIR) showed a bi‐hippocampal atrophy, an increase in the sylvian valley and ventricular dilation; signs of cortical and subcortical vascular leukoencephalopathy. While the axial T2 cut showed a peri‐ventricular leukoencephalopathy. In FDG‐PET, there was a hypometabolism in the left anterior and the upper temporal gyrus. A neuropsychological battery was administered to the patient as well as a neurolinguistic assessment using an adapted and validated version of Moroccan Mini‐Linguistic State Examination (MLSE). It has been developed in English and Italian (Catricalà et al, 2017; Patel et al, 2020).ResultThe clinical profile of MH clearly showed an atypical overlap of neuropsychological, neurolinguistic and neuroradiological features which objectified a mixed variant of PPA predominantly logopenic and semantic with a slight syntactic impairment. These linguistic disturbances included some elements of Lv‐PPA (impaired sentence repetition and dysnomia) and some features of Sv‐PPA (dysnomia, impaired word comprehension, semantic association and sentence comprehension).ConclusionThe findings of this case study were mainly based on clinical and semiological criterias which are consistent with Mesulam’s descriptions (2014). It is possible that the presence of multi‐domain linguistic deficits may be linked eventually to a mixed underlying neuropathology which might be both neurodegenerative and vascular. This study is a call for a cross‐cultural neuropsychological, neuro‐anatomical and neurolinguistic characterization of PPA and Mixed‐PPA in non‐European languages
Incidence trends of dementia in Czechia: A national registry‐based study over 15 years
Authors: Kučera Matěj 
Published: June 2023

AbstractBackgroundThe number of people living with dementia in Czechia reached 156 thousand in 2015. According to estimates, prevalence of dementia is supposed to reach 250 thousand by year 2050, but little is known about current trends of dementia incidence. In our study we aimed to identify trends in age‐ and sex‐specific incidence of dementia in the Czechia between years 1999 and 2017.MethodTo assess changes in the incidence of dementia in Czechia we examined linked data about the entire Czech population aged 65 year and over from national healthcare registers (National Register of Hospitalized Patients, National Register of Paid Health Services, Register of Deaths). We traced dementia based on a combination of information about the clinical diagnosis (Alzheimer’s disease, vascular dementia, unspecified dementia, dementia with Lewy bodies, Parkinson’s disease with dementia, frontotemporal dementia) and use of drugs for dementia (Donepezil, Rivastigmine, Galantamine, Memantine). Incidence rates (calculated for both genders in strata of five years) were measured with survival analysis techniques using Poisson regression analysis, testing the calendar year as a time‐dependent covariate.ResultThere were 30587776 person‐years during the follow‐up. Total crude incidence rates per 10000 person‐years between years 1999 and 2017 were higher in women with 118,62 to 89,46 in men and steeply increasing with age. The crude yearly incidence was increasing for men and women during the entire follow‐up period with rapid decline in the last two years of the follow up. The age‐ and sex‐stratified results indicate different trends in age groups with age between 65‐79 year being relatively stable compared to older age groups.ConclusionOur results provide evidence that number of new patients diagnosed with dementia may be currently declining and this trend may continue in future.
Can You Hear Me? Exploring the use of a sing‐along audio program as a method for creative community engagement in times of continued isolation
Authors: Mize Cheyenne M 
Published: June 2023

AbstractBackgroundLoneliness in older adults has been linked to accelerated cognitive and functional decline. Furthermore, lonely individuals are twice as likely to develop Alzheimer’s disease. This was before COVID‐19 and the isolation that older adults are experiencing disproportionately. Engagement in singing groups and other creative experiences has been shown to address the health and wellbeing of older adults, including their experience of connectedness, loneliness and isolation. Can You Hear Me? was developed as an alternative to in‐person singing groups in times of continued isolation due to the COVID‐19 pandemic.Method
Can You Hear Me? is a sing‐along audio program highlighting the voices and music of elders in Louisville, Kentucky, USA. Unlike typical receptive audio programs, Can You Hear Me? has participatory elements that give listeners the opportunity to sing along to familiar songs, learn about organizations in the area and how to get involved, and contribute to the show by sending in their responses to creative prompts. The program will also implement a repeat design 25‐item Listener Survey, which will be utilized to understand more about listeners’ wellbeing and perceptions of loneliness and aging, as well as for quality improvement.ResultNow in its second season, this podcast‐style audio program is exploring an alternative model for creative individual and community engagement. Strategic community partners are assisting in the development of the program as a resource for individuals living in the community with Alzheimer’s disease and their carers, as well as in care homes when group engagement is still not feasible or possible.ConclusionIn the absence of a cure for dementia, Alzheimer’s, or COVID‐19, it is imperative that we work to build ways for elders to be socially connected wherever they live and provide opportunities for them to engage actively and creatively. Can You Hear Me? provides just such an initiative, to be a model for arts‐driven community engagement through an audio program that not only addresses health inequities and stigmas of aging and dementia, but also has the capacity to enhance wellbeing and connect people, even in times of isolation.
Neuropsychiatric symptoms of Alzheimer’s dementia and their association with dorsolateral prefrontal cortex TMS evoked potentials
Authors: Asare Gifty , Joseph Shaylyn , Alhabbal Hiba , Zomorrodi Reza , Blumberger Daniel M. , Daskalakis Zafiris J. , Mulsant Benoit H. , Pollock Bruce G. , Rajji Tarek K. , Kumar Sanjeev 
Published: June 2023

AbstractBackgroundAlzheimer’s Dementia (AD) is characterized by cognitive and neuropsychiatric symptoms (NPS). Recently, cognitive decline in AD has been linked to increased cortical excitability. However, the relationship between NPS and cortical excitability remains unclear. This study investigated the relationship between NPS and cortical excitability in the dorsolateral prefrontal cortex (DLPFC).Method24 participants with probable AD diagnosed using National Institute of Aging‐Alzheimer’s Association criteria (Mage (SD) = 74.1 (7.2) years) were recruited and followed for up to 6 months. Global cognition was assessed with the Montreal Cognitive Assessment (MoCA). NPS were assessed using the Neuropsychiatric Inventory Questionnaire (NPI‐Q) total score and subdomain scores. Single pulse transcranial magnetic stimulation (TMS) was applied at the DLPFC (localized using MRI‐based neuronavigation) at a frequency of 0.1 Hz, at sufficient intensity; and collected using 62 channel electroencephalography (EEG) recorded from the scalp. TMS‐evoked potential (TEP) peak amplitudes for individual TEP peaks (P30, N45 and P60) were calculated.ResultNPI‐Q severity score was positively correlated with DLPFC TEP peak P30 (r (19) = .64, p = .003) and negatively correlated with DLPFC TEP peak N45 (r (22) = ‐.46, p = .033). These associations remained significant after controlling for age, sex and cognition (DLPFC TEP peak P30 (ß = .93, p = .001) and N45 (ß = ‐.47, p = .031)). Further, NPI‐Q severity score at 6 month follow up negatively correlated with baseline DLPFC TEP peak N45 (r (16) = ‐.56, p = .025). Among NPI‐Q subdomains, apathy was positively correlated with DLPFC TEP peak P30 (r (19) = .64, p = .003) and negatively correlated with DLPFC TEP peak N45 (r (22) = ‐.42, p = .049).ConclusionNPS burden in AD was positively associated with excitatory activity (i.e., P30) and negatively associated with inhibitory activity (i.e., N45) using combined TMS‐EEG over the DLPFC. These associations were largely driven by the apathy domain. These findings may have implications for developing neurophysiological biomarkers and targeted treatment interventions for NPS in AD.
Comparative pathological study of Carbon‐11 labeled Pittsburgh compound‐B PET Centiloid Scale and amyloid beta deposition in postmortem brains
Authors: Matsubara Tomoyasu , Murayama Shigeo , Ihara Ryoko , Higashihara Mana , Nishina Yasushi , Kanemaru Kazutomi , Iwata Atsushi , Arai Tomio , Kameyama Masashi , Tokumaru Aya M. , Imabayashi Etsuko , Ishibashi Kenji , Toyohara Jun , Saito Yuko , Ishii Kenji 
Published: June 2023

AbstractBackgroundCentiloid Scale (CL) was developed to standardize the quantitative results of amyloid beta (Aβ) positron emission tomography (PET). CL can allow not only categorization of the binary results of amyloid PET as positive or negative, but also parametric weighting within each category. To date, several neuropathological studies evaluated the performance of CL, but further validation studies of the Asian population, elderly cohorts, and relatively short intervals between PET scanning and autopsy may be required.MethodTwenty‐two consecutive autopsy cases registered to the Brain Bank for Aging Research, who received Carbon‐11 labeled Pittsburgh compound‐B PET were included. Amyloid PET results of CL were compared with the final neuropathological diagnosis and the grading of Aβ deposition.ResultThe mean age of the 22 patients at death was 81.0 (SD: 8.4) years, seven of whom fulfilled pathological diagnosis of Alzheimer’s disease (AD). The mean interval from PET to autopsy was 17.5 (SD: 15.3) months. The mean CL was higher in the AD group (88.5 [SD: 30.9]) than in the non‐AD group (9.7 [SD: 25.6], p <0.001). Cutoff value of 50 could segregated seven AD and two non‐AD patients above and 13 non‐AD patients below. CL correlated with CERAD plaque score, Thal phase, and Braak amyloid stage with polyserial correlation coefficient of 0.93, 0.87, and 0.87, respectively. The lower limit of the CL value corresponding to moderate to frequent CERAD plaque score or equal to or more than Thal phase 4 was 17.31.ConclusionThe CL value is in good agreement with the extent of Aβ accumulation. The cutoff value for predicting moderate or greater accumulation of Aβ was 15‐20, and the cutoff value for predicting AD pathology was 50‐60. Further accumulation and integration of data will allow us to establish more appropriate cutoff value.
In vitro activity of polyphenol‐rich extract of sorghum relevant to treatment of Alzheimer’s disease
Authors: Rezaee Nasim , Fernando Binosha , Hone Eugene , Sohrabi Hamid R , Johnson Stuart K , Gunzburg Stuart , Martins Ralph N 
Published: June 2023

AbstractBackgroundAlzheimer’s disease (AD) is a progressive neurodegenerative disorder that accounts for most dementia cases. It has become a serious international health and economic concern as there is no effective treatment. Naturally derived products, particularly polyphenols (PP), have become very popular for developing effective therapeutic strategies for AD. PP apply their neuroprotective actions through targeting various pathological hallmarks of the disease, such as Aβ and/or aggregation, oxidative stress and mitochondrial dysfunction. Aβ aggregation is majorly implicated in the pathogenesis of AD. Therefore, finding a way to attenuate Aβ‐induced toxicity could be a potential approach for disease‐modifying treatments of AD. In the current study, the effect of polyphenolic extract from different sorghum varieties was assessed against Aβ42‐induced cytotoxicity.MethodA cell viability assay (MTS) was utilized to assess the protective effect of the extracts on Aβ‐induced cytotoxicity in human neuroblastoma BE (2)‐M17 cells. Following that, a thioflavin T (Th‐T) assay was performed to assess the anti‐Aβ aggregation effect of the extracts.ResultThe sorghum extracts significantly increased the cell viability. Of the six different tested extracts, QL33(2000 µg/ml) and B923296(1000 µg/ml) demonstrated the strongest and weakest protective effect in decreasing Aβ‐induced cell death (p < 0.01), respectively. In addition, the sorghum extracts were effective at inhibiting the Aβ aggregation.ConclusionSorghum polyphenolic extracts demonstrated a promising neuroprotective effect against Aβ‐induced cytotoxicity and therefore can be considered as a potential naturally derived agent for AD treatment. However, further studies are required to confirm the anti‐AD effects of these sorghum extracts.
Fused multi‐modal similarity network as prior in guiding brain imaging genetic association
Authors: He Bing , Xie Linhui , Varathan Pradeep , Nho Kwangsik , Risacher Shannon L. , Saykin Andrew J. , Yan Jingwen 
Published: June 2023

AbstractBackgroundBrain imaging genetics aims to explore the genetic architecture underlying brain structure and functions. Recent studies showed that incorporation of prior knowledge, such as subject diagnosis information and brain regional correlation, can help identify significantly stronger imaging genetic associations. However, sometimes such information may be incomplete or even unavailable. In this project, we explore a new data‐driven prior knowledge that captures the subject‐level similarity matrix derived from fusion of multi‐modal similarity networks. It was built into the sparse canonical correlation analysis model, which is expected to identify brain imaging and genetic markers that contribute to the fused similarity matrix.MethodThe Amyloid and Tau imaging data were downloaded from the ADNI database. We have 800 and 291 subjects for amyloid and tau imaging respectively (Table. 1). SNPs with p<5×10−6 (n = 1080) were extracted from the large‐scale GWAS summary statistics from the IGAP. We built similarity networks for imaging and genetic data individually using normalized mutual information and then fused these network following (Fig. 1). Fused network was then applied as a prior knowledge in the discriminative sparse canonical correlation analysis (DSCCA) model. We also tested other prior knowledge in SCCA model for comparison including diagnosis group network and transcriptomic brain network. All methods were evaluated using ADNI genotype, amyloid and tau imaging data, where nested 5‐fold cross validation with the same set of training and test data was applied for fair comparison.ResultSCCA with fused network and diagnosis group showed better performances over others in both training and testing data set (Table. 2,3). In Fig. 2 are top 10 ROIs identified by SCCA with fused network, whose amyloid deposition are strongly associated with APOE SNP (rs429358). For tau, we identified left and right amygdala with tau accumulation strongly and consistently associated with rs429358 (fig.3).ConclusionAs prior knowledge incorporated into SCCA algorithm, fused similarity network can help improve the performance of imaging genetic association over traditional SCCA and that guided by the brain co‐expression network. It showed comparable performance as diagnosis information and thus could be a potential prior knowledge to consider when lack of diagnosis information.