bluuebunny/crossref_metadata_2025_split huggingface dataset:
New insight for early detection of Alzheimer's disease
Authors: Dey Sharmistha 
Published: January 2025

AbstractBackgroundRecent research on Alzheimer’s disease (AD) has highlighted that the oxidative damage is the earliest event of disease. These oxidative modifications are closely associated with inflammatory molecules. It is necessary to explore these two pathways with AD pathophysiology and targeted for therapeutic intervention. At present, the most validated AD biomarker is Aβ levels in the cerebrospinal fluid (CSF) and tau PET scan. None of the techniques can be used to monitor the disease with the response of treatment. The present study focussed on novel molecules in these two pathways for establishing blood‐based biomarker and therapeutic interventions.MethodBlood samples were collected from 46 AD patients, 37 mild cognitive impairment (MCI) patients and 35 geriatric‐control (GC). The levels of inflammatory molecules (LOX‐5, LOX‐12, GSK‐3β, p53, NFkb) and antioxidant molecules (FOXO, Sestrin, Sirtuins) were measured by using surface plasmon resonance and verified using Western blot in serum from AD, MCI, and GC. Statistical analysis, including Receiver Operating Characteristic (ROC), was done for further affirmation with all demographic data and clinical assessment score. The Alzheimer’s disease model neurotoxic SH‐SY5Y cell line was treated with antioxidant plant extract for rescue effect on SH‐SY5Y to see the effect on expression level of above mentioned proteins.ResultThe significant alteration of some of these proteins were observed in the blood of AD patients compare to MCI and geriatric control. These proteins also showed positive correlation with the known hallmark Tau, pTau and ab‐amyloid in the study group. A significant (p<0.0001) downhill correlation was found between Tau as well as p‐Tau181 levels with HMSE and MoCA score. The treatment with antioxidant plant extract showed rescue effect of neurotoxicity by enhancing antioxidant enzymes thereby decreased reactive oxygen species (ROS).ConclusionThese proteins can serve as potential blood markers for the diagnosis of AD and supplementary antioxidant molecules can regulate and suppress their level by rescuing the neurotoxicity. This work has translational value and clinical utility in the future.
Meta‐Analysis & Review of Blood Neurofilament Light Performance in Diagnosis of All‐Cause Dementia
Authors: Schmidt Remington E , Shah Yogesh , Center Broadlawns Medical 
Published: January 2025

AbstractBackgroundNfL is a non‐specific biomarker that elevates in the presence of axonal damage. In the blood, it has recently been explored as a potential test in evaluating the presence or absence of dementia.MethodA systematic review and meta‐analysis of 58 studies examining plasma or serum NfL levels as measured on a single molecule array (SIMOA) platform was used to determine the discriminatory capacity of using NfL to distinguish between healthy controls and patients with dementia.ResultNfL provides reasonable discriminatory capacity between healthy controls and patients with all‐cause dementia (serum AUC=0.85, plasma AUC=0.75). For a reasonable range of cutoffs, NfL is more specific than it is sensitive. The meta‐analysis demonstrated a roughly 2‐fold increase in NfL levels in dementia patients from cognitively healthy controls (1.84‐fold change plasma, 2.77‐fold change serum).ConclusionIn the setting of memory care, NfL is likely to be most useful in detecting early dementia in patients presenting with subjective or mild cognitive impairment. As baseline NfL levels significantly change across a person’s lifetime, all NfL levels should be compared to population normals during their interpretation.
MicroRNA biomarkers in cerebrospinal fluid and plasma are associated with reduced cognitive decline in Alzheimer's Disease
Authors: Jiao Yang , Ding Yanfei , Niu Mengyue , Luo Ningdi , Zhong Min , Liu Jun , Zhao Aonan , Li Yuanyuan 
Published: January 2025

AbstractBackgroundDespite the promising prospects of using microRNAs in Alzheimer's disease (AD) research, several challenges remain unresolved.MethodOur study analyzed the changes in microRNA expression levels in cerebrospinal fluid (CSF) and plasma samples and their association with concurrent cognitive decline and hippocampal volume changes in patients with AD using the Alzheimer's Disease Neuroimaging Initiative database.ResultWe observed a significant decrease in plasma hsa‐mir‐125b‐5p levels (P=0.018), significant increase in plasma hsa‐mir‐26a‐5p levels (P=0.017), and significant decrease in mir‐185b‐5p levels in CSF (P=0.017). However, these microRNAs showed no significant differences between the control and AD groups across various ATN subtypes. Lower plasma hsa‐mir‐125b‐5p and hsa‐mir‐26a‐5p concentrations and CSF mir‐185b‐5p concentrations were associated with a faster increase in Alzheimer’s Disease Assessment Scale Cognition 13‐item scale scores (P= 0.011, P=0.009, P=0.018, respectively) and a decline in hippocampal volume (P=0.25, P=0.052, P=0.044, respectively), suggesting a potentially detrimental influence on cognitive and memory impairment in AD progression. CSF mir‐185b‐5p concentrations were positive for amyloid deposition (P= 0.0451, r=0.1754) and negative for fibrillar amyloid levels (P= 0.0392, r=‐0.1647), indicating their potential relevance in AD pathology and the development of AD.ConclusionThese results highlight the role of CSF and plasma microRNA biomarkers in predicting cognitive and clinical decline in patients with AD.
CSF α‐synuclein reflects neurodegeneration in Alzhiemer's disease
Authors: Igarashi Kazuya , Kasuga Kensaku , Tsukie Tamao , Kikuchi Masataka , Miyashita Akinori , Iwatsubo Takeshi , Ikeuchi Takeshi 
Published: January 2025

AbstractBackgroundThe aim of this study is to investigate the clinical significance of cerebrospinal fluid (CSF) α‐synuclein (αSyn), a presynaptic protein, in Alzheimer's disease (AD) continuum.MethodWe analyzed 177 CSF samples obtained from participants of Japanese Alzheimer’s Disease Neuroimaging Initiative (J‐ADNI). To investigate the clinical utility of CSF αSyn, subjects were divided into cognitively unimpaired (CU) group (n = 46), mild cognitive impairment (MCI) group (n = 76), and AD dementia (ADD) group (n = 43). We measured CSF αSyn, amyloid β (Aβ)42, phosphorylated tau (pTau), total tau (tTau), Neurofilament Light chain (NfL), hemoglobin (Hb). Because high CSF Hb levels affect αSyn levels due to red blood cell contamination, 12 patients with CSF Hb levels of 1000 ng/mL or higher were excluded. We analyzed the correlation between CSF αSyn and age, gender differences, cognitive function, brain volume (entorhinal cortex, hippocampus, ventricle, cortex, white matter, gray matter, white matter hyperintensities), and each biomarker.ResultCSF αSyn were significantly higher in the MCI and ADD groups than in the CU group, and significantly negatively correlated with the MMSE score. The hazard ratio for conversion to dementia was significantly higher in the CSF αSyn high and middle tertile groups compared to the low tertile group. CSF αSyn was also associated with baseline and 24‐month score change of MMSE, ADAS, CDR‐SB, and FAQ. CSF αSyn were significantly positively correlated with CSF pTau181, tTau, and NfL and hippocampal volume, but not with CSF Aβ42.ConclusionOur results suggests CSF αSyn is a biomarker reflecting neurodegeneration in the Alzheimer's continuum.
Diagnosis of Alzheimer's disease using highly specific amyloid and tau positron emission tomography
Authors: Matsuda Hiroshi , Hanyu Haruo , Kaneko Chikako , Yamao Tensho 
Published: January 2025

AbstractBackgroundThe Alzheimer's disease (AD) research framework has advocated defining AD as a function of the presence or absence of amyloidopathy (A), tauopathy (T), and neurodegeneration/neuronal injury (N) biomarkers, as well as the clinical syndrome. Recent advances have made it possible to perform A/T/N classification in vivo using neuroimaging techniques such as amyloid positron emission tomography (PET), tau PET, and MRI or fluorodeoxyglucose PET. Under this new framework, AD is diagnosed when both A and T are positive, regardless of whether N is positive or negative. In this study, we investigated this classification by PET using 18F‐NAV4694, which has a high dynamic range with low nonspecific accumulation of amyloid, and 18F‐MK6240, which specifically accumulates 3R/4R tau seen in AD, in patients with cognitive impairment and suspected AD.MethodTwenty‐three patients with cognitive impairment and suspected AD (12 females, 11 males, 72.1 ± 6.6 years old, Mini‐Mental State Examination; MMSE score 25.3 ± 2.1) underwent both 18F‐NAV4694 (300MBq) and 18F‐MK6240 (185MBq) PET scans using semiconductor PET/CT (United Imaging Healthcare, uMI780). Structural MRI was analyzed using VSRAD (Voxel‐based Specific Regional analysis for Alzheimer's disease ) software for voxel‐based morphometry. In addition, amyloid and tau protein deposition were quantified using the Centiloid scale and standardized uptake value ratio (SUVR) with the whole cerebellum and cerebellar cortex as reference regions, respectively.ResultEleven patients were classified as A+T+N+ and one as A+T+N‐ and diagnosed with AD. The other classifications were A‐T‐N‐ in 5 patients, A‐T‐N+ in 2, and A+T‐N‐, A+T‐N+, A‐T+N‐, and A‐T+N+ in 1 each. The Centiloid scale of amyloid deposition did not significantly correlate with the MMSE score (r=‐0.368, p=0.083), but the composite SUVR of tau deposition did (r=‐0.463, p=0.025).ConclusionA/T/N classification by PET and MRI correctly diagnosed AD in 12 of 23 cases (52%). Tau PET with 18F‐MK6240 was found to be as important in the diagnosis of AD as amyloid PET, with 2 of 14 cases (14%) being 3R/4R tau negative despite being amyloid positive. These results suggest that highly specific amyloid and tau PET can be used to accurately diagnose AD, and that tau deposition correlates well with cognitive function.
Glymphatic System Efficiency, Choroid Plexus Volume, and Lateral Ventricle Volume Variations in Normal Individuals and Throughout the Progression of Alzheimer's Disease
Authors: Nakaya Moto , Kamagata Koji , Takabayashi Kaito , Uchida Wataru , Hagiwara Akifumi , Christina Andica , Wada Akihiko , Taoka Toshiaki , Naganawa Shinji , Abe Osamu , Aoki Shigeki 
Published: January 2025

AbstractBackgroundAlzheimer’s disease (AD) progression is often characterized by the accumulation of amyloid and tau proteins, which can be linked to impaired brain clearance mechanisms, including the glymphatic system. Our research evaluates noninvasive MRI‐based indicators of brain clearance functionality, such as choroid plexus volume (CPV), lateral ventricular volume (LVV), and the perivascular space diffusivity index (ALPS index), throughout various stages of AD.MethodWe analyzed MRI data measuring CPV, LVV, and ALPS index from participants categorized as amyloid‐beta (Aβ)‐ negative healthy controls (HC), Aβ‐positive HC, Aβ‐negative subjective cognitive decline (SCD), Aβ‐positive SCD, mild cognitive impairment (MCI), and AD, using the Alzheimer's Disease Neuroimaging Initiative database. A General Linear Model was used for cross‐group comparisons of MRI metrics. Additionally, partial Spearman's Rank Correlation tests were conducted to investigate associations between MRI measures, neuropsychological assessments, and CSF biomarker levels within each group.ResultThe participant pool comprised 21 Aβ‐negative cognitively healthy individuals, 10 Aβ‐positive HCs, 21 patients with Aβ‐negative SCD, 9 with Aβ‐positive SCD, 19 MCI patients, and 26 AD patients. We observed increased CPV and LVV and decreased ALPS index in advanced stages of the disease. Notably, the ALPS index was significantly reduced in Aβ‐positive HCs compared to Aβ‐negative ones. In SCD subjects and across the AD spectrum, correlations were found between these MRI indicators of brain clearance and both tau protein levels and cognitive performance metrics.ConclusionOur findings suggest that MRI‐detected alterations in brain clearance metrics are associated with Aβ deposition and can be identified early in SCD that is linked to AD pathology.
Associations of C‐reactive protein and homocysteine with neuropsychological outcomes in older adults at risk of dementia
Authors: Yu Rachael , Michaelian Johannes C , Kong Shawn Dexiao , Ireland Catriona , Bassett Kimberley , Naismith Sharon L 
Published: January 2025

AbstractBackgroundInflammation is becoming increasingly recognised as a core feature of dementia and neurodegenerative processes. High‐sensitivity C‐reactive protein (hs‐CRP) and homocysteine are blood‐based markers of non‐specific inflammation used in clinical settings. This study aimed to 1) investigate the associations of hs‐CRP and homocysteine on neuropsychological performance (i.e. verbal memory, executive function, processing speed) in older adults attending a memory clinic; and 2) examine whether these associations differed for individuals at varying risk stages of dementia, i.e. with subjective cognitive decline (SCD) vs. mild cognitive impairment (MCI).MethodWe recruited older adults aged ≥ 50 years with new‐onset cognitive concerns without dementia. A fasting blood sample was used to obtain concentrations of serum hs‐CRP (mg/L) and plasma homocysteine (µmol/L). Hs‐CRP levels were grouped into low <1.0mg/L, moderate 1.0‐3.0mg/L, and high risk >3.0‐10.0 mg/L. A standardised neuropsychological assessment was conducted by a clinical neuropsychologist, and composite scores for each neuropsychological outcome were calculated as an average of z‐scores of all tests within the same domain. Classifications of MCI were determined by clinician consensus as having objective impairments in neuropsychological tests (≥1.5SDs below normative scores). Multiple regression analyses were conducted, adjusting for relevant demographic and clinical factors.ResultThe final sample consisted of 423 participants (Mean age = 67.37 years [SD = 8.15], 63.1% female, mean MMSE = 28.95 [SD = 1.35]), who were classified as either having SCD (n = 158) or MCI (n = 265). Hs‐CRP and homocysteine concentrations did not differ between SCD and MCI groups. In participants with SCD, high‐risk CRP concentrations were significantly associated with poorer executive function (β = ‐.226, 95% CI = [‐0.692, ‐0.059], p = .020) and processing speed (β = ‐.212, 95% CI = [‐0.584, ‐0.025], p = .033). There were no significant associations between CRP and neuropsychological outcomes in those with MCI, or in the total sample. Homocysteine was not associated with cognitive outcomes.ConclusionCRP may be involved in early disruptions to cerebral frontal‐subcortical pathways. Targeting inflammation in the earliest stages of cognitive decline, where subjective complains are paramount, may be a viable strategy for prevention.
The relationship between physiological biomarkers, physical function, and fall‐risk among people living with dementia
Authors: Hamill Sophia N , Dong Yanbin , Zhu Haidong , Huang Ying , Soares Andre , Waller Jennifer L , Young Lufei , Robinson‐Johnson Dawnchelle , Sams Richard , Hamrick Mark , Jehu Deborah A 
Published: January 2025

AbstractBackgroundPeople living with dementia (PWD) have upregulated inflammatory pathways, exaggerated metabolic aging, and cellular aging. They also have declines in physical function and heightened fall‐risk. Understanding the physiologic factors that influence physical decline and fall‐risk in PWD is vital to assess and prevent adverse health outcomes, such as future falls. The purpose of this study was to explore the association between physiological biomarkers, physical decline, and fall‐risk in PWD.MethodIn this cross‐sectional study, we used the baseline data of n=42 PWD in residential care facilities from our pilot randomized controlled trial [NCT05488951]. We assessed fall‐risk with the Morse Fall Scale and pulled fall history in the last 6 months from incident reports in medical charts. Participants completed two 4‐meter usual pace walking trials. We assessed two trials of maximum quadriceps strength on each leg with a portable dynamometer. We drew fasted blood and measured inflammatory biomarkers (Interleukin(IL)‐1b, IL‐6, IL‐8, IL‐10, IL‐12p70, IL‐17A, IL‐18, IL23, IL‐33, chemokine ligand 2, tumor necrosis factor‐a, human interferon (INF)‐a2, INFg), metabolic aging (kynurenine), and cellular aging (telomere length). Separate multiple linear regressions were performed for each biomarker, with gait speed, leg strength, fall history, and the Morse Fall Scale as variables of interest. We controlled for age, sex, and the Montreal Cognitive Assessment in each model.ResultFall history (β=5.61, p=0.03) and older age (β=0.49, p=0.005) were associated with greater INF‐a2 (R2=0.49, p=0.07). Fall history (β=4.93, p=0.07) showed a trend for a relationship with greater IL‐10 (R2=0.50, p=0.04). Older age (β=0.28, p=0.009) and lower MOCA scores (β=‐0.40, p=0.04) were related to greater IL‐12p70 (R2=0.64, p=0.003). Older age (β=9.26, p=0.01), fall history (β=74.42, p=0.04), and poorer leg strength (β=‐7.40, p=0.06) were related to greater kynurenine (R2=0.49, p=0.02).ConclusionOur exploratory findings suggest that there may be a relationship between certain physiological biomarkers (INF‐a2, IL‐10, kynurenine), physical function, and fall history. These inflammatory and metabolic aging biomarkers may play an important role for physical function and fall‐risk in PWD. This preliminary research may have implications for screening and monitoring of physical decline and fall‐risk among PWD.
A brain MRI estimate of whole‐body aging in midlife predicts late life risk for Alzheimer’s disease
Authors: Whitman Ethan T. , Elliott Maxwell L. , Knodt Annchen R. , Moffitt Terrie E. , Caspi Avshalom , Hariri Ahmad R. 
Published: January 2025

AbstractBackgroundAging is the strongest risk factor for Alzheimer’s disease (AD). Accordingly, identifying biomarkers of accelerated aging is a major focus of AD prevention research. Current MRI‐based “aging clocks” (i.e., brain age) derive from cross‐sectional associations with chronological age. However, chronological age differs fundamentally from biological aging. We introduce a novel brain MRI proxy for biological aging in midlife developed in the Dunedin Study, a population‐representative longitudinal birth cohort, and demonstrate its ability to differentiate and predict AD in the Alzheimer’s Disease Neuroimaging Initiative (ADNI).MethodThe pace of whole‐body aging was determined by tracking physiological decline of 6 organ systems over 20 years in Dunedin Study members. An elastic‐net regression model was trained to estimate this pace of aging using a single T1‐weighted scan collected at age 45 from 860 Study members. We call this measure the Dunedin Pace of Aging Calculated from NeuroImaging or “DunedinPACNI.” We exported DunedinPACNI to ADNI and tested its association with current and future AD. Lastly, we compared DunedinPACNI to “brain age” using brainageR.ResultDunedinPACNI estimated whole‐body aging with a cross‐validated accuracy of r=0.43 in Dunedin Study members. Derived in 6,199 T1‐weighted ADNI scans, DunedinPACNI was on average 0.40 standard deviations higher in MCI patients and 1.13 standard deviations higher in AD patients compared to healthy participants (MCI 95% CI:[0.36‐0.45]; AD 95% CI:[1.08‐1.19]). DunedinPACNI outperformed brainageR in differentiating MCI and AD patients from controls (MCI: b=.25; 95% CI:[.14‐.35]; AD: b=.68; 95% CI:[.56‐.80]). In 1,326 ADNI participants followed up to 16 years, baseline DunedinPACNI was associated with a higher probability of AD conversion (HR=1.58, 95% CI:[1.36‐1.84]) as was brainageR (HR=1.61; 95% CI:[1.42‐1.84]). DunedinPACNI and brainageR together predicted conversion more accurately than either measure alone (combined HR=2.10, 95% CI:[1.76‐2.51).ConclusionDunedinPACNI, a novel MRI proxy for longitudinal whole‐body aging during midlife, offers advantage over “brain age” in detecting neurodegenerative disease and predicting AD conversion in late life. DunedinPACNI can be applied to existing neuroimaging datasets to estimate whole‐body aging to better gauge early AD risk.
LOVOT: LOVE + ROBOT
Authors: Low Zheng Yi 
Published: January 2025

AbstractBackgroundSocial robots have been used in other countries for improvement of quality of life for persons with dementia.MethodLOVOT was introduced as an adjunct to regular therapy sessions (either Physiotherapy or Occupational Therapy) and as an interactive companion during the patient’s inpatient stay. The project was carried out over a span of 6 weeks (weekdays) for a maximum of 10‐15 mins on an ad‐hoc basis.ResultA total of 19 participants were recruited over this 6 weeks. These included 11 patients (age between 49 to 81 year old, 6 with formal diagnosis of dementia and 5 without one). The other 8 participants were staff members (age 29 to 57 year old, ranging from the medical doctors to nurses to allied health staff). We administered one common questionnaire on both groups of participants, this questionnaire is “Sociability of robot”. There is 3 components to this questionnaire and they are as follows:1. Perceived sociability. This component received 78% positive feedback from the participants2. Social influence, which received 74% positive feedback3. Social presence, which had 70% positive feedback. However it is worth noting that 54% of the participants felt that LOVOT was not a real pet during the interaction.We also administered a second questionnaire: Older People’s Quality of Life (QoL) for the group of patient participants. There is a total of 13 statements. Most statements received positive agreement and 2 statements that had higher disagreement (36%) were:• “I look forward to things.”• “I try to stay involved with things”It was noticed that 3 out of 11 patient participants gave more than 50% neutral or disagreement to the above statements.ConclusionDuring the trial, some patients and their caregivers started to ask about LOVOT and wanted to interact with LOVOT as well. Staff in SCH looked forward to spending time with LOVOT after a long day of work and are already anticipating for the next LOVOT visit. Most respondents had positive experience with LOVOT with patients reporting it as an interactive partner and staff respondents reporting positive well‐being and a good form of stress relief from the hectic work day.