Neuroimaging and fluid biomarkers are used to differentiate frontotemporal dementia (FTD) from Alzheimer\'s disease (AD). We implemented a machine learning algorithm that provides individual probabilistic scores based on magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) data. We investigated whether combining MRI and CSF levels could improve the diagnosis confidence. 215 AD patients, 103 FTD patients, and 173 healthy controls (CTR) were studied. With MRI data, we obtained an accuracy of 82 % for AD vs. FTD. A total of 74 % of FTD and 73 % of AD participants have a high probability of accurate diagnosis. Adding CSF-NfL and 14-3-3 levels improved the accuracy and the number of patients in the confidence group for differentiating FTD from AD. We obtain individual diagnostic probabilities with high precision to address the problem of confidence in the diagnosis. We suggest when MRI, CSF, or the combination are necessary to improve the FTD and AD diagnosis. This algorithm holds promise towards clinical applications as support to clinical findings or in settings with limited access to expert diagnoses.

Idiopathic normal-pressure hydrocephalus (iNPH) is a clinic-radiological neurological syndrome presenting with cognitive deficits, gait disturbances and urinary incontinence. It often coexists with Alzheimer\'s disease (AD). Due to the reversible nature of iNPH when promptly treated, a lot of studies have focused on possible biomarkers, among which are cerebrospinal fluid (CSF) biomarkers. The aim of the present study was to determine the rate of beta-amyloid pathology and AD co-pathology by measuring AD CSF biomarkers, namely, amyloid beta with 42 and 40 amino acids (Aβ42), the Aβ42/Aβ40 ratio, total Tau protein (t-Tau) and phosphorylated Tau protein at threonine 181 (p-Tau), in a cohort of iNPH patients, as well as to investigate the possible associations among CSF biomarkers and iNPH neuropsychological profiles. Fifty-three patients with iNPH were included in the present study. CSF Aβ42, Aβ40, t-Tau and p-Tau were measured in duplicate with double-sandwich ELISA assays. The neuropsychological evaluation consisted of the Mini-Mental State Examination, Frontal Assessment Battery, Five-Word Test and CLOX drawing tests 1 and 2. After statistical analysis, we found that amyloid pathology and AD co-pathology are rather common in iNPH patients and that higher values of t-Tau and p-Tau CSF levels, as well as the existence of the AD CSF profile, are associated with more severe memory impairment in the study patients. In conclusion, our study has confirmed that amyloid pathology and AD-co-pathology are rather common in iNPH patients and that CSF markers of AD pathology and t-Tau are associated with a worse memory decline in these patients.

BACKGROUND: We investigated the link between habitual caffeine intake with memory impairments and cerebrospinal fluid (CSF) biomarkers in mild cognitive impairment (MCI) and Alzheimer\'s disease (AD) patients.
METHODS: MCI (N = 147) and AD (N = 116) patients of the Biomarker of AmyLoid pepTide and AlZheimer\'s diseAse Risk (BALTAZAR) cohort reported their caffeine intake at inclusion using a dedicated survey. Associations of caffeine consumption with memory impairments and CSF biomarkers (tau, p-tau181, amyloid beta 1-42 [Aβ1-42], Aβ1-40) were analyzed using logistic and analysis of covariance models.
RESULTS: Adjusted on Apolipoprotein E (APOE ε4), age, sex, education level, and tobacco, lower caffeine consumption was associated with higher risk to be amnestic (OR: 2.49 [95% CI: 1.13 to 5.46]; p = 0.023) and lower CSF Aβ1-42 (p = 0.047), Aβ1-42/Aβ1-40 (p = 0.040), and Aβ1-42/p-tau181 (p = 0.020) in the whole cohort.
CONCLUSIONS: Data support the beneficial effect of caffeine consumption to memory impairments and CSF amyloid markers in MCI and AD patients.
CONCLUSIONS: We studied the impact of caffeine consumption in the BALTAZAR cohort. Low caffeine intake is associated with higher risk of being amnestic in MCI/AD patients. Caffeine intake is associated with CSF biomarkers in AD patients.

The mainstay behind Alzheimer\'s disease (AD) remains unknown due to the elusive pathophysiology of the disease. Beta-amyloid and phosphorylated Tau is still widely incorporated in various research studies while studying AD. However, they are not sufficient. Therefore, many scientists and researchers have dug into AD studies to deliver many innovations in this field. Many novel biomarkers, such as phosphoglycerate-dehydrogenase, clusterin, microRNA, and a new peptide ratio (Aβ37/Aβ42) in cerebral-spinal fluid, plasma glial-fibrillary-acidic-protein, and lipid peroxidation biomarkers, are mushrooming. They are helping scientists find breakthroughs and substantiating their research on the early detection of AD. Neurovascular unit dysfunction in AD is a significant discovery that can help us understand the relationship between neuronal activity and cerebral blood flow. These new biomarkers are promising and can take these AD studies to another level. There have also been big steps forward in diagnosing and finding AD. One example is self-administered-gerocognitive-examination, which is less expensive and better at finding AD early on than mini-mental-state-examination. Quantum brain sensors and electrochemical biosensors are innovations in the detection field that must be explored and incorporated into the studies. Finally, novel innovations in AD studies like nanotheranostics are the future of AD treatment, which can not only diagnose and detect AD but also offer treatment. Non-pharmacological strategies to treat AD have also yielded interesting results. Our literature review spans from 1957 to 2022, capturing research and trends in the field over six decades. This review article is an update not only on the recent advances in the search for credible biomarkers but also on the newer detection techniques and therapeutic approaches targeting AD.

Plasma phosphorylated-tau 217 (p-tau217) is currently the most promising biomarkers for reliable detection of Alzheimer\'s disease (AD) pathology. Various p-tau217 assays have been developed, but their relative performance is unclear. We compared key plasma p-tau217 tests using cross-sectional and longitudinal measures of amyloid-β (Aβ)-PET, tau-PET, and cognition as outcomes, and benchmarked them against cerebrospinal fluid (CSF) biomarker tests. Samples from 998 individuals (mean[range] age 68.5[20.0-92.5], 53% female) from the Swedish BioFINDER-2 cohort were analyzed. Plasma p-tau217 was measured with mass spectrometry (MS) assays (the ratio between phosphorylated and non-phosphorylated [%p-tau217WashU]and ptau217WashU) as well as with immunoassays (p-tau217Lilly, p-tau217Janssen, p-tau217ALZpath). CSF biomarkers included p-tau217Lilly, and the FDA-approved p-tau181/Aβ42Elecsys and p-tau181Elecsys. All plasma p-tau217 tests exhibited high ability to detect abnormal Aβ-PET (AUC range: 0.91-0.96) and tau-PET (AUC range: 0.94-0.97). Plasma %p-tau217WashU had the highest performance, with significantly higher AUCs than all the immunoassays (P diff<0.007). For detecting Aβ-PET status, %p-tau217WashU had an accuracy of 0.93 (immunoassays: 0.83-0.88), sensitivity of 91% (immunoassays: 84-87%), and a specificity of 94% (immunoassays: 85-89%). Among immunoassays, p-tau217Lilly and plasma p-tau217ALZpath had higher AUCs than plasma p-tau217Janssen for Aβ-PET status (P diff<0.006), and p-tau217Lilly outperformed plasma p-tau217ALZpath for tau-PET status (P diff=0.025). Plasma %p-tau217WashU exhibited higher associations with all PET load outcomes compared to immunoassays; baseline Aβ-PET load (R2: 0.72; immunoassays: 0.47-0.58; Pdiff<0.001), baseline tau-PET load (R2: 0.51; immunoassays: 0.38-0.45; Pdiff<0.001), longitudinal Aβ-PET load (R2: 0.53; immunoassays: 0.31-0.38; Pdiff<0.001) and longitudinal tau-PET load (R2: 0.50; immunoassays: 0.35-0.43; Pdiff<0.014). Among immunoassays, plasma p-tau217Lilly was more strongly associated with Aβ-PET load than plasma p-tau217Janssen (P diff<0.020) and with tau-PET load than both plasma p-tau217Janssen and plasma p-tau217ALZpath (all P diff<0.010). Plasma %p-tau217 also correlated more strongly with baseline cognition (Mini-Mental State Examination[MMSE]) than all immunoassays (R2 %p-tau217WashU: 0.33; immunoassays: 0.27-0.30; P diff<0.024). The main results were replicated in an external cohort from Washington University in St Louis (n =219). Finally, p-tau217Nulisa showed similar performance to other immunoassays in subsets of both cohorts. In summary, both MS- and immunoassay-based p-tau217 tests generally perform well in identifying Aβ-PET, tau-PET, and cognitive abnormalities, but %p-tau217WashU performed significantly better than all the examined immunoassays. Plasma %p-tau217 may be considered as a stand-alone confirmatory test for AD pathology, while some immunoassays might be better suited as triage tests where positive results are confirmed with a second test.

UNASSIGNED: Alzheimer\'s disease (AD) is a progressive neurodegenerative disorder. Current core cerebrospinal fluid (CSF) AD biomarkers, widely employed for diagnosis, require a lumbar puncture to be performed, making them impractical as screening tools. Considering the role of sleep disturbances in AD, recent research suggests quantitative sleep electroencephalography features as potential non-invasive biomarkers of AD pathology. However, quantitative analysis of comprehensive polysomnography (PSG) signals remains relatively understudied. PSG is a non-invasive test enabling qualitative and quantitative analysis of a wide range of parameters, offering additional insights alongside other biomarkers. Machine Learning (ML) gained interest for its ability to discern intricate patterns within complex datasets, offering promise in AD neuropathology detection. Therefore, this study aims to evaluate the effectiveness of a multimodal ML approach in predicting core AD CSF biomarkers.
UNASSIGNED: Mild-moderate AD patients were prospectively recruited for PSG, followed by testing of CSF and blood samples for biomarkers. PSG signals underwent preprocessing to extract non-linear, time domain and frequency domain statistics quantitative features. Multiple ML algorithms were trained using four subsets of input features: clinical variables (CLINVAR), conventional PSG parameters (SLEEPVAR), quantitative PSG signal features (PSGVAR) and a combination of all subsets (ALL). Cross-validation techniques were employed to evaluate model performance and ensure generalizability. Regression models were developed to determine the most effective variable combinations for explaining variance in the biomarkers.
UNASSIGNED: On 49 subjects, Gradient Boosting Regressors achieved the best results in estimating biomarkers levels, using different loss functions for each biomarker: least absolute deviation (LAD) for the Aβ42, least squares (LS) for p-tau and Huber for t-tau. The ALL subset demonstrated the lowest training errors for all three biomarkers, albeit with varying test performance. Specifically, the SLEEPVAR subset yielded the best test performance in predicting Aβ42, while the ALL subset most accurately predicted p-tau and t-tau due to the lowest test errors.
UNASSIGNED: Multimodal ML can help predict the outcome of CSF biomarkers in early AD by utilizing non-invasive and economically feasible variables. The integration of computational models into medical practice offers a promising tool for the screening of patients at risk of AD, potentially guiding clinical decisions.

Considering the growing age of the world population, the incidence of epilepsy in older adults is expected to increase significantly. It has been suggested that late-onset temporal lobe epilepsy (LO-TLE) may be neurodegenerative in origin and overlap with Alzheimer\'s Disease (AD). Herein, we aimed to characterize the pattern of cortical atrophy and cerebrospinal fluid (CSF) biomarkers of AD (total and phosphorylated tau, and β-amyloid) in a selected population of LO-TLE of unknown origin. We prospectively enrolled individuals with temporal lobe epilepsy onset after the age of 50 and no cognitive impairment. They underwent a structural MRI scan and CSF biomarkers measurement. Imaging and biomarkers data were compared to three retrospectively collected groups: (i) age-sex-matched healthy controls, (ii) patients with Mild Cognitive Impairment (MCI) and abnormal CSF AD biomarkers (MCI-AD), and (iii) patients with MCI and normal CSF AD biomarkers (MCI-noAD). From a pool of 52 patients, twenty consecutive eligible LO-TLE patients with a mean disease duration of 1.8 years were recruited. As control populations, 25 patients with MCI-AD, 25 patients with MCI-noAD, and 25 healthy controls were enrolled. CSF biomarkers returned normal values in LO-TLE, significantly different from patients with MCI due to AD. There were no differences in cortico-subcortical atrophy between epilepsy patients and healthy controls, while patients with MCI demonstrated widespread injuries of cortico-subcortical structures. Individuals with a late-onset form of temporal lobe epilepsy, characterized by short disease duration and normal CSF β-amyloid and tau protein levels, showed patterns of cortical thickness and subcortical volumes not significantly different from healthy controls, but highly different from patients with MCI, either due to Alzheimer\'s Disease or not.

BACKGROUND: VGF and neuroserpin are neurosecretory proteins involved in the pathophysiology of neurodegenerative diseases. We aimed to evaluate their cerebrospinal fluid (CSF) concentrations in patients with Alzheimer\'s disease (AD) and Lewy body disease (LBD).
METHODS: We measured CSF VGF [AQEE] peptide and neuroserpin levels in 108 LBD patients, 76 AD patients and 37 controls, and tested their associations with clinical scores and CSF AD markers.
RESULTS: We found decreased CSF levels of VGF [AQEE] in patients with LBD and dementia compared to controls (p = 0.016) and patients with AD-dementia (p = 0.011), but with significant influence of age and sex distribution. Moreover, we observed, on the one hand, a significant associations between lower VGF [AQEE] and neuroserpin levels and poorer cognitive performance (i.e., lower Mini-Mental State Examination scores). On the other hand, higher levels of CSF tau proteins, especially pTau181, were significantly associated with higher concentrations of VGF [AQEE] and neuroserpin. Indeed, LBD patients with AD-like CSF profiles, especially T+ profiles, had higher levels of VGF [AQEE] and neuroserpin compared to controls and LBD/T- cases.
CONCLUSIONS: CSF VGF [AQEE] and neuroserpin may show a complex relationship with cognitive decline when the levels are reduced, and with AD pathology when levels are increased. They may represent novel markers of neurosecretory impairment in neurodegenerative disorders.

UNASSIGNED: Postoperative delirium (POD) often occurs in elderly patients after surgery. We conducted two clinical studies to determine whether COVID-19 vaccination has a protective effect on POD and to explore the role of CSF biomarkers in this process.
UNASSIGNED: We conducted two clinical studies, Perioperative Neurocognitive Disorder Risk Factor and Prognosis (PNDRFAP) and Perioperative Neurocognitive Disorder and Biomarker Lifestyle (PNDABLE), in which patients more than or equal to 65 years old who have had elective non-cardiac surgery were enrolled. The preoperative cognitive status of patients were evaluated by Mini-Mental State Examination (MMSE) one day preoperatively. Confusion Assessment Method (CAM) was used to diagnose POD. We used the mediation model to analyze the relationship between CSF biomarkers, COVID-19 vaccination and POD, as well as Dynamic Nomogram to calculate the incidence of Non-Postoperative Delirium (NPOD). The main outcome of these studies was the incidence of POD during seven days postoperatively or before discharge, which was assessed by CAM.
UNASSIGNED: In the final, 705 participants were enrolled in the PNDRFAP study, and 638 patients in the PNDABLE. In both studies, we found that the occurrence of POD was lower in patients who had injected COVID-19 vaccination before surgery compared with those without vaccination (PNDRFAP: 10.20 % [21/205] vs 25.80 % [129/500], P < 0.001; PNDABLE: 2.40 % [4/164] vs 34.60 % [164/474], P < 0.001). Mediation analysis showed that the protective effect of preoperative COVID-19 vaccine on POD was significantly mediated by CSF Aβ42 (proportion = 17.56 %), T-tau (proportion = 19.64 %), Aβ42/T-tau (proportion = 29.67 %), and Aβ42/P-tau (proportion = 12.26 %).
UNASSIGNED: COVID-19 vaccine is a protective factor for POD in old patients, which is associated with CSF biomarkers.

BACKGROUND: Spinal cord ischemia is one of the complications that can occur after open and endovascular thoracoabdominal aortic repair. This occurs despite various perioperative approaches, including distal aortic perfusion, hybrid procedures with extra anatomical bypasses, motor-evoked potential, and cerebrospinal fluid drainage. The inability to recognize spinal ischemia in a timely manner remains a devastating complication after thoracoabdominal aortic repair.This review aims to look at novel technologies that are designed for continuous monitoring to detect early changes that signal the development of spinal cord ischemia and to discuss their benefits and limitations.
METHODS: We conducted a systematic review of the technologies available for continuous monitoring in the intensive care unit for early detection of spinal cord ischemia. Studies were eligible for inclusion if they used different technologies for monitoring spinal ischemia during the postoperative period. All articles that were not available in English were excluded. To ensure that all relevant articles were included, no other significant restrictions were imposed.
RESULTS: We identified 59 studies from the outset to December 2022 to be included in our study. New techniques have been studied as potentially useful monitoring tools that could provide simple and effective monitoring of the spinal cord. These include near-infrared spectroscopy, contrast-enhanced ultrasound, magnetic resonance imaging, fiber optic monitoring of the spinal cord, and cerebrospinal fluid biomarkers.
CONCLUSIONS: Despite the development of new techniques to monitor for postoperative spinal cord ischemia, their use remains limited. We recommend more future research to ensure rapid intervention for our patients.