bluuebunny/crossref_metadata_2025_split huggingface dataset:
Status report on palliative care in Alzhiermers patients : Dark reality in resource poor nations
Authors: Rohan S P , Patil Y , Verma N 
Published: December 2023

AbstractBackgroundSocial stigma, Fatigue, sexual dysfunction, Sleeplessness, depression commonly seen in Alzhiermers patients . Palliative inaccessible in rural/tribal areas. Hence our NGO nurses took initiatives to help alleviate suffering of women with Alzhiermers patients since October 2018.MethodWe surveyed 110 subjects through QOL‐questionnaires. After 22 weeks therapy with psychosocial support. Counseling & palliative care with anti‐depressants/pain‐killers/nutrition, QOL improved to statistically significant level. Requirement of palliative care evaluated by Palliative Care Problem Severity Scale (PCPSS). Traditional faith‐healers involved for more psychological impact on patients community. Community leaders involved to reduce social stigma/discrimination among community.n = 110. Of these statistically over 90% express sexual‐dysfunction, 68% experience loneliness; 70% suffer social neglect/humiliation, 64% had depression. Importance of spirituality/religion in coping with terminal‐illness is increasingly recognized Hence Our NGO‐nurses involved community‐leaders to make more women involved in our spiritual healing.Resultcurrently 210 specialist palliative care beds required for our Rural/tribal population of 16,00,000. But only 80 available. 60% expressed that religious/community support/faith was most important factor that helped them to cope with Alzhiermers. higher scores of QOL (ANOVA p < 0.001) correlated with lack of sexual dysfunction/pain. Our NGO‐initiative suggests that over 70% patients will need well trained specialist for home‐based‐care.ConclusionLife‐span/QOL of Alzhiermers patients‐sufferers depends on social acceptance & appropriate‐palliative‐care. NGO‐personals should be trained in Palliative‐care‐services. Field of Spiritual/psycho‐social/community support is fertile ground for further investigations. We need focused platform like AAIC to discuss our project ideas/concerns/difficulties with senior researchers.
Structural Correlates of Speech Biomarkers in Alzheimer’s Disease and Mild Cognitive Impairment
Authors: Bae Minju , Ham Hyunsun , Lee Dasom , Kim Keun You , Lee Jun‐Young 
Published: December 2023

AbstractBackgroundIn the present study, we aimed to confirm the association between speech characteristics of individuals with Alzheimer’s disease (AD) and amnestic mild cognitive impairment (MCI) and brain regions, and to investigate the neurobiological basis of speech‐based AD detection.MethodIndividuals with MCI (n = 13, age = 78.3), mild‐to‐moderate AD (n = 12, age = 77.8) underwent a structural MRI scan and engaged in three speech tasks: an interview, sentence repetition, and paragraph recall. From the speech samples, we extracted frequency‐related, intensity‐related, and temporal features which were found to be altered in the course of AD and MCI pathology. We selected nine regions of interest (ROI) which were found to be involved in speech production and reduced in MCI and AD pathology; the Inferior Frontal Gyrus (IFG), the Medial Frontal Gyrus (MFG), the Precuneus, the Inferior Parietal Lobe (IPL), Inferior Temporal Gyrus (ITG), Medial Temporal Gyrus (MTG), the Superior Temporal Gyrus (STG), the Fusiform Gyrus (FFG), and the Cerebellum. The linear mixed‐effect analysis was used to identify the associations between speech features and regional brain volumes.ResultThe Left IPL (χ2 (1) = 7.69, corrected P = 0.033), the Right ITG (χ2 (1) = 11.5, corrected P = 0.0128) the Right FFG (χ2 (1) = 9.35, corrected P = 0.0198) reduced the pitch of voice by about 0.887 ± 0.292, 1.368 ± 0.329, and 1.69 ± 0.429 respectively. The associations between the Right FFG (χ2 (1) = 4.58, corrected P = 0.0900), Left FFG (χ2 (1) = 5.87, corrected P = 0.0675) and loudness were marginally significant, with the reduction of volumes in the Right FFG and Left FFG decreasing the loudness by 0.096 ± 0.041, and 0.1165 ± 0.0454. The marginally significant associations were observed between the Right IPL (χ2 (1) = 4.75, corrected P = 0.0900), the Left FFG (χ2 (1) = 0.39, corrected P = 0.53) and the speech rate, and the atrophy of brain regions decreased the speech rate by 0.0824 ± 0.0363, 0.0535 ± 0.0079.ConclusionThe present study identified the associations between speech biomarkers and regional brain volumes providing clinical validity for the speech‐based Alzheimer’s disease detection.
The nebulous association between cognitive impairment and falls in older adults : a systematic review of the literature
Authors: Leroy Victoire , Martinet Valérie , Nunkessore Oumashankar , Dentel Christel , Durand Hélène , Mockler David , PUISIEUX François , Fougere Bertrand , Chen Yaohua Sophie 
Published: December 2023

AbstractBackgroundIn older people, dementia is a well‐established risk factor for falls. However, the association and the causal relationship between falls and earlier stage of cognitive impairment remains unclear. The purpose of the study was to review the literature data on the association between falls and cognitive impairment, no dementia, including Mild Cognitive Impairment.MethodAccording to PRISMA guidelines, we searched five electronic databases (EMBASE, Web of Science, Medline, CINAHL, and PsychINFO) for articles published between January 2011 and August 2022 on observational studies of older people with a cognitive assessment and/or cognitive impairment diagnosis and recording of falls. Their quality was reviewed according to STROBE checklist.ResultWe selected 42 of the 4934 initially retrieved publications. In 22 retrospective studies, a statistically significant association between falls and cognitive status was found in only 15 of the 37 comparisons (38%). Of the 27 cross‐sectional analyses in prospective studies, only 8 (30%) were positive and significant. We counted 4 longitudinal analyses, half of which suggested a causal relationship between falls and cognitive impairment. The investigational methods varied markedly from one study to another.ConclusionIt is still not clear whether falls are associated with cognitive imapirment, no dementia. Data in favor of a causal relationship are scarce. Further studies are needed to clarify their relationship.
Novel Multimodal Imaging Framework for Synaptic Integrity Characterization in Alzheimer’s Disease
Authors: Kim Woo Sik , Kim Sung‐Woo , Sohn Jun Young , Lee Wha‐Jin , Seong Joon‐Kyung 
Published: December 2023

AbstractBackgroundDynamic loss of synapses is well understood to be a crucial endpoint in many neurodegenerative diseases especially that of Alzheimer’s Disease (AD). Hence, successful in vivo characterization of synaptic integrity (SI) provides huge potential for opportunities in therapeutics targeting synaptic damage restoration. Though recent studies using synaptic glycoprotein 2A (SV2A) PET imaging remains as the most direct measure of SI, such methods are not readily available for clinical applications. Here, we examine a new framework for in vivo characterization of SI in the AD continuum by incorporating widely available imaging parameters such as atrophy, connectivity, and neuronal metabolism.Method53 amyloid‐negative cognitively normal (CN‐), 92 amyloid‐positive mild cognitive impairment (MCI+), and 50 amyloid‐positive AD (AD+) subjects with T1‐weighted MRI, diffusion‐weighted MRI and 18F‐fluorodeoxyglucose (FDG) PET images were collected from ADNI. Selected imaging modalities were each theorized to portray distinct parts of SI such as pre‐synaptic disruption, synaptic connectivity, and synaptic dysfunction. Hence, using an exogenous common factor analysis model, with each modality measures as primary manifestation variables, an amalgamated regional SI score was calculated. Using regional values, factor analysis was implemented again to produce global SI scores for each subject. Regional scores were normalized and adjusted for age, sex, and education for groupwise comparison.ResultRegional SI W‐scores showed progressive decline along the AD continuum in the entorhinal, lateral temporal, lateral parietal, and isthmus cingulate cortices, showing significant differences among most regions between CN‐ and AD+ groups. Bilateral entorhinal and isthmus cingulate cortices and left inferior temporal region showed strong significant differences between CN‐ and MCI+ groups, suggesting early synaptic loss in these areas, which agree well with previous results from SV2A PET studies. Global scores also declined significantly through disease progression and showed associations with decreased cognitive performance as measured by MMSE and CDR‐SOB.ConclusionVarious neuroimaging biomarkers have been extensively verified to observe different traits of AD, yet successful characterization of SI without SV2A PET is first to our knowledge. Our model has shown that synaptic change can be indirectly visualized using widely available imaging modalities, providing immense opportunities for applications in both clinical and research contexts.
CAM therapy initiative for Alzheimer’s patients : Asian perspectives
Authors: Rohan S P , Patil Y , Verma N 
Published: December 2023

AbstractBackgroundIn resource‐poor‐settings, Unlike Western nations monitoring Alzheimer’s‐treatment‐Adherence is low priority due to lack of training modules/funds/expertise. drug‐toxicity, social stigma causes high‐incidence of withdrawal from therapy. Hence our we‐analyzed locally available Complementary‐Alternative Medicines [CAM] in Alzheimer’s‐casesFacilities for diagnosis/treatment located in major‐cities &are unaffordable to >75%. ADR’s & social stigma worsened situation. CAM must be incorporated along with standard DRUG’s to reduce ADR’s & control symptoms to get better treatment‐Adherence. Provide CAM to Traditional‐faith‐hearers. To assess CAM response to pain/fatigue/Myalgia/bed‐sores/wt‐loss, feeling of hopelessness, Dementia. Hence we combined CAM with standard‐drugs.Methodn = 72 cases aged 60‐70 years enrolled. 30% females, 70% males. self report questionnaire distributed in NGO clinic. Mud therapy 60%, Bach‐flower 40%, Accupressure/Accupuncture 80%, Hydrotherapy 10%, Hypnotherapy 70%, ayurvedic therapy 80%, 60% on Unani, 50% Homeopathic, 60% Herbal‐Oil‐TFH massage therapy, 30% Aromatherapy.Resultpatients treated in 7 CAM sessions. responses evaluated by feedback‐Performa periodically to modify treatment. Symptom relief 92%, Psycholocal mood elevation 52%, willingness to shift back to std‐drug thrapy 80%. CAM 80% cheaper compared to std drugsConclusion80% patients used & preferred CAMs. CAM effectively compliments Alzheimer’s treatment‐adherence. Community NGO’s must be part of such efforts to evolve newer concepts in Adherence. Realizing divergent versions of CAM multicentre study needed.
Assessing utility of imaging based biomarker to differentiate pathologically classified frontotemporal lobar degeneration syndromes
Authors: Hwang Yun Tae , Halliday Glenda M , Piguet Olivier , Burrell James R 
Published: December 2023

AbstractBackgroundFrontotemporal lobar degeneration (FTLD) comprises distinct neuropathological entities that present as several overlapping clinical syndromes. Two main pathological inclusions are identified in FTLD – TDP‐43, and tau itself further subdivided into 4 repeat (e.g., PSP‐tau and CBD‐tau) groups. Clinicopathological correlation is poor, at ∼60%. In vivo sensitive and specific biomarkers are needed to improve pathological diagnosis for clinical trials.The midbrain‐pons ratio (MP) is an imaging biomarker that has been shown to differentiate PSP‐tau from Parkinson’s disease and multisystems atrophy, as well as clinically defined progressive supranulclear palsy from other FTLD syndromes.We examined whether the MP at presentation could distinguish PSP‐tau from controls and Alzheimer’s disease (AD), as well as from other FTLD pathologies.MethodParticipants in a clinical cohort‐brain bank program based at Brain and Mind Centre, Sydney, Australia, with FTLD pathologies were included, as were matched healthy Controls and clinically diagnosed AD patients. The midbrain and pons were manually traced from the sagittal MRI slice at the midline at the initial clinical assessment of all the participants for comparison.ResultIn total, 65 participants were included in the study – 42 with FTLD (13 PSP‐tau, 6 CBD‐tau, 23 TDP‐43), 11 AD and 12 control participants; no patients with Pick’s disease were available for inclusion. Only 6/13 PSP‐tau patients, 1/6 CBD‐tau patients and 18/23 individuals with TDP‐43 were clinically diagnosed with PSP, CBS, and FTD respectively. The MP differed significantly in the PSP‐tau group compared to the control, AD, and other FTLD groups, including the CBD‐tau group. Using relevant cut off scores, positive predictive values of 90‐100% were achieved in distinguishing PSP‐tau from controls, AD, and other FTLD pathologies.ConclusionThe MP is a useful in vivo biomarker to identify individuals with PSP‐tau. It can distinguish PSP‐tau from controls, AD, and other FTLD pathologies with high PPVs, even CBD‐tau, another important tauopathy often causing a similar clinical presentation. The PPVs achieved in using the MP were similar to those achieved using CSF and PET biomarkers of amyloid to predict AD pathology. The MP should be considered for routine use in clinical practice and selection into trials of anti‐PSP‐tau therapies.
Association of cognitive reserve indicator with cognitive decline and structural brain differences in mid‐ and late life: a large population‐based cohort study
Authors: Yang Wenzhe , Wang Jiao , Guo Jie , Dove Abigail , Qi Xiuying , Xu Weili 
Published: December 2023

AbstractBackgroundCognitive reserve (CR) contributes to preserving cognition when facing brain aging and damage. CR has been linked to reduced dementia risk in late life. However, the association between CR and brain imaging measures, especially in mid‐life, is unclear. We aimed to explore the association of CR with cognitive decline and structural brain differences in mid‐ and late life.MethodWithin the UK Biobank, 42,301 dementia‐free participants aged 40‐70 were followed for a median of 9 (interquartile range: 8 to 10) years. Latent class analysis was used to generate an indicator of CR (categorized as high, moderate, and low) based on education, occupation, and multiple cognitively stimulating activities at baseline. Cognitive tests for global and domain‐specific cognitive function were administrated at baseline and follow‐up. A subsample (n = 34,041) underwent brain magnetic resonance imaging (MRI) scans at the follow‐up examination. Volumes of total brain, white matter, grey matter, hippocampus, and white matter hyperintensities (TBV, WMV, GMV, HV, and WMHV) were assessed. Data were analyzed using mixed‐effects models and linear regression.ResultAt baseline, 16,032 (37.90%), 10,709 (25.32%), and 15,560 (36.78%) participants had low, moderate, and high levels of CR, respectively. In multi‐adjusted mixed‐effects models, compared to low CR, high CR was associated with a slower decline in global cognitive function (β [95% confidence interval, CI]: 0.10 [0.08, 0.11]), prospective memory (0.10 [0.06, 0.15]), fluid intelligence (0.07 [0.04, 0.10]), and reaction time (0.04 [0.02, 0.06]). In MRI data analysis, high CR was related to lesser TBV (‐0.03 [‐0.04, ‐0.02]), WMV (‐0.03 [‐0.04, ‐0.02], GMV (‐0.02 [‐0.04, ‐0.01]), and WMHV (‐0.03 [‐0.05, ‐0.002]), but greater HV (0.04 [0.02, 0.06]) compared to low CR. In analyses stratified by baseline age, the significant associations between high CR and global cognition and TBV were present among both mid‐life (<60 years) and late‐life (≥60 years) participants. The CR‐cognitive decline association remained significant after additional adjustment for MRI measures.ConclusionHigher CR is associated with slower cognitive decline, lesser TBV, greater HV, and lower microvascular burden, especially in mid‐life. The protective role of high CR on cognition is independent of structural brain differences.
Age‐equivalent induced neurons from patients reveal neuronal fate loss and metabolic transformation underlying neurodegeneration in sporadic Alzheimer’s disease
Authors: Mertens Jerome 
Published: December 2023

AbstractBackgroundOld age is the dominating risk factor for Alzheimer’s Disease (AD), which exclusively affects people at older ages. Sporadic AD represents the overwhelming majority of all cases, but most research on AD has been performed on genetic causes and their directly related pathways, also because we were in lack of models that can reflect complex human genetics and age in a neuronal context.MethodPatient‐specific iPSC models represent an attractive solution, but iPSC reprogramming results in cellular rejuvenation and thus yields phenotypically young neurons mirroring fetal development. By contrast, direct conversion of old patient fibroblasts into induced neurons (iNs) preserves endogenous signatures of aging and produces neurons that resemble the adult human brain on an epigenome‐ and transcriptome‐wide scale. To control for the involvement of aging in AD, we generated age‐equivalent fibroblast‐derived iNs and rejuvenated iPSC‐derived neurons from a cohort of AD patients and controls.ResultPatient‐derived AD iNs reflect a hypo‐mature neuronal identity characterized by markers of stress, cell cycle, glycolytic reprogramming, and de‐differentiation, which share similarities with malignant cancer transformation and age‐dependent epigenetic erosion. We identified an isoform switch of pyruvate kinase M (PKM) to the PKM2 isoform as a trigger of a Warburg effect‐like metabolic switch, and further as a key transcriptional regulator leading to cell fate instability. Metabolomics, glucose tracing, and acetylome analysis confirmed a hyper‐acetylated state of AD iNs. This affects several splicing factors, triggering an isoform switch to PKM that ultimately leads to a loss of neuronal fate and maturity. Inhibition of the resulting citrate shunt to acetylCoA modulates the isoform switch in favor of PKM1, and re‐instates a mature and more resilient neuronal state.ConclusionWe conclude that age‐equivalent adult‐like iNs from patients are a useful model to study age‐dependent pathological signatures of AD. This iN model identifies AD‐related neuronal changes as part of an active cellular program that impairs neuronal cell identity and neuronal resilience by utilizing cancer‐related signaling cascades. We further reason that the AD‐specific metabolic switch and fate loss in neurons regulates, and is reinforced by, alternative splicing of PKM.
ASO‐mediated downregulation of Amyloid Precursor Protein: a new avenue for AD treatment?
Authors: Gabriele Rebcca M C , Arber Charles , Zetterberg Henrik , Abel Emily , Fox Nick C , Jolly Sarah , Whiting Paul , Zhao Hien , Wray Selina 
Published: December 2023

AbstractBackgroundMutations in the APP, PSEN1 and PSEN2 genes are causative of familial AD (fAD) and lead to accelerated cerebral amyloid beta (Aβ) accumulation. This finding led to the development of the amyloid cascade hypothesis which proposed that the aberrant production of Aβ peptides triggers a cascade of events that ultimately leads to neurodegeneration and clinical Alzheimer’s disease. Synthetic antisense oligonucleotides (ASOs) are small molecules that modify gene expression at the RNA level. We investigated the effect of ASO‐mediated APP downregulation in induced pluripotent stem cell derived neurons from individuals with fAD mutations in APP and PSEN1 to determine whether this approach can rescue disease‐associated phenotypes or Aβ processing defects.MethodiPSC with PSEN1 Int4del and R278I mutations, and APP duplication were differentiated into cortical neurons before treatment with ASOs targeting APP or non‐targeting controls. APP downregulation was assessed at the RNA level using qPCR and protein level by western blot. The impact of APP downregulation was assessed utilising a triplex ELISA to measure Ab38/40/42 and immunocytochemistry with antibodies against Rab5 and LAMP1 to assess the endolysosomal system.ResultASO treatment led to a dose‐dependent downregulation of APP, both at the RNA and protein levels. Downregulation was stable over 3 weeks following ASO administration. This resulted in a significant reduction in the absolute levels of each Aβ species measured, although the Ab42/40 ratio was unchanged.ConclusionConsidering the central role of Aβ in AD pathology, it is reasonable to believe that the downregulation of APP could be a successful therapeutic approach. ASO‐mediated APP downregulation was efficient and stable, highlighting the potential of this approach. Although the Aβ ratio was unchanged following APP downregulation, the absolute value of each Aβ species was significantly reduced, and so we hypothesise that lower levels of total Ab may reduce its harmful effects. Future work will determine the impact of reducing Ab levels on downstream cellular dysfunction, including endosome/lysosome defects.
Association between Anemia and Dementia in Korea older adults: A national cohort study
Authors: Cho Yong Hyuk , Roh Hyun Woong , Hong Chang Hyung , Son Sang Joon , Nam You Jin , Hong Sunhwa , Park Sunghong , Back Joung Hwan 
Published: December 2023

AbstractBackgroundAs the global elderly population increases, the prevalence of dementia is also increasing. Korea is one of the rapidly aging countries in the world, and 10.33% of elderly people aged 65 and older are receiving treatment for dementia as reported in 2021. Since disease modifying drugs have not yet been developed for dementia, the importance of modifiable risk factors that can lower the risk of dementia is being emphasized, and one of them is anemia in the elderly. We analyze national cohort data of approximately 20 years to disclose the relationship between anemia and dementia in Korean elderly, and suggest that anemia is a modifiable risk factor for dementia needed active intervention.MethodWe analyzed a large population‐based cohort study of aged ³65 years who participated in the national health screening program including blood tests and cognitive function tests from 2007 to 2008 in Korean National Health Insurance Service database 2006‐2020. The risk of AD according to the presence and severity of anemia was evaluated using a multivariable Cox regression model, after adjustments for sex, BMI, HTN, DM, LDL, TG, SCr, GFR and past medical history (depression, HTN, DM, cardiovascular disease, cerebrovascular disease).ResultAs a result of the analysis, dementia occurred in 27.9% of the total subjects (316,881 persons) during the follow‐up period until 2020. Also, dementia occurred in 27.5% of the normal group, but 30.1% of the anemia group. As a result of survival analysis, even after adjusting for sex, there was a statistically significant difference between the presence of anemia and the prevalence of dementia (HR 1.07, 95% CI 1.05‐1.09). In addition, even after adjusting for sex, BMI, HTN, DM, LDL, SCr, GFR, and past medical history, there was a statistically significant association between anemia and dementia (HR 1.05, 95% CI 1.03‐1.07).ConclusionWe reported that the presence of anemia statue and the severity of anemia in the elderly were related to the occurrence of dementia through a national date of Korea. We suggest that anemia is a modifiable risk factor for dementia and requires intensive intervention in the elderly.