Journal of Alzheimer's disease : JAD最新文献

{"title":"The 5HT2b Receptor in Alzheimer's Disease: Increased Levels in Patient Brains and Antagonist Attenuation of Amyloid and Tau Induced Dysfunction.","authors":"E. Acquarone, Elentina K. Argyrousi, O. Arancio, D. M. Watterson, Saktimayee M Roy","doi":"10.3233/JAD-240063","DOIUrl":"https://doi.org/10.3233/JAD-240063","url":null,"abstract":"BACKGROUND\u0000Background: Neurodegenerative diseases manifest behavioral dysfunction with disease progression. Intervention with neuropsychiatric drugs is part of most multi-drug treatment paradigms. However, only a fraction of patients responds to the treatments and those responding must deal with drug-drug interactions and tolerance issues generally attributed to off-target activities. Recent efforts have focused on the identification of underexplored targets and exploration of improved outcomes by treatment with selective molecular probes.\u0000\u0000\u0000Objective\u0000As part of ongoing efforts to identify and validate additional targets amenable to therapeutic intervention, we examined levels of the serotonin 5-HT2b receptor (5-HT2bR) in Alzheimer's disease (AD) brains and the potential of a selective 5-HT2bR antagonist to counteract synaptic plasticity and memory damage induced by AD-related proteins, amyloid-β, and tau.\u0000\u0000\u0000Methods\u0000This work used a combination of biochemical, chemical biology, electrophysiological, and behavioral techniques. Biochemical methods included analysis of protein levels. Chemical biology methods included the use of an in vivo molecular probe MW071, a selective antagonist for the 5HT2bR. Electrophysiological methods included assessment of long-term potentiation (LTP), a type of synaptic plasticity thought to underlie memory formation. Behavioral studies investigated spatial memory and associative memory.\u0000\u0000\u0000Results\u00005HT2bR levels are increased in brain specimens of AD patients compared to controls. 5HT2bR antagonist treatment rescued amyloid-β and tau oligomer-induced impairment of synaptic plasticity and memory.\u0000\u0000\u0000Conclusions\u0000The increased levels of 5HT-2bR in AD patient brains and the attenuation of disease-related synaptic and behavioral dysfunctions by MW071 treatment suggest that the 5HT-2bR is a molecular target worth pursuing as a potential therapeutic target.","PeriodicalId":219895,"journal":{"name":"Journal of Alzheimer's disease : JAD","volume":"92 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140746833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Contactin 5 and Apolipoproteins Interplay in Alzheimer's Disease.","authors":"M. Dauar, C. Picard, A. Labonté, John C S Breitner, P. Rosa-Neto, S. Villeneuve, Judes Poirier","doi":"10.3233/JAD-231003","DOIUrl":"https://doi.org/10.3233/JAD-231003","url":null,"abstract":"Background\u0000Apolipoproteins and contactin 5 are proteins associated with Alzheimer's disease (AD) pathophysiology. Apolipoproteins act on transport and clearance of cholesterol and phospholipids during synaptic turnover and terminal proliferation. Contactin 5 is a neuronal membrane protein involved in key processes of neurodevelopment.\u0000\u0000\u0000Objective\u0000To investigate the interactions between contactin 5 and apolipoproteins in AD, and the role of these proteins in response to neuronal damage.\u0000\u0000\u0000Methods\u0000Apolipoproteins (measured by Luminex), contactin 5 (measured by Olink's proximity extension assay), and cholesterol (measured by liquid chromatography mass spectrometry) were assessed in the cerebrospinal fluid (CSF) and plasma of cognitively unimpaired participants (n = 93). Gene expression was measured using polymerase chain reaction in the frontal cortex of autopsied-confirmed AD (n = 57) and control subjects (n = 31) and in the hippocampi of mice following entorhinal cortex lesions.\u0000\u0000\u0000Results\u0000Contactin 5 positively correlated with apolipoproteins B (p = 5.4×10-8), D (p = 1.86×10-4), E (p = 2.92×10-9), J (p = 2.65×10-9), and with cholesterol (p = 0.0096) in the CSF, and with cholesterol (p = 0.02), HDL (p = 0.0143), and LDL (p = 0.0121) in the plasma. Negative correlations were seen between CNTN5, APOB (p = 0.034) and APOE (p = 0.015) mRNA levels in the brains of control subjects. In the mouse model, apoe and apoj gene expression increased during the reinnervation phase (p <  0.05), while apob (p = 0.023) and apod (p = 0.006) increased in the deafferentation stage.\u0000\u0000\u0000Conclusions\u0000Extensive interactions were observed between contactin 5 and apolipoproteins and cholesterol, possibly due to neuronal damage. The alterations in gene expression of apolipoproteins suggest a role in axonal, terminal, and synaptic remodeling in response to entorhinal cortex damage.","PeriodicalId":219895,"journal":{"name":"Journal of Alzheimer's disease : JAD","volume":"16 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140747781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Total Tau Protein Mediates the Association of Ischemic Cerebrovascular Disease with Cognitive Decline.","authors":"Shuang-Ling Han, Ya‐nan Ou, Bao-Lin Han, Hai-Hua Guo, Hao-Chen Chi, Yi-Ming Huang, Huifu Wang, Lan Tan","doi":"10.3233/jad-231093","DOIUrl":"https://doi.org/10.3233/jad-231093","url":null,"abstract":"Background\u0000Patients with transient ischemic attack (TIA) or ischemic stroke demonstrate an increased risk of cognitive dysfunction. Accumulating evidence indicates that ischemic cerebrovascular disease (ICVD) may interact with the amyloid/tau/neurodegeneration (AT[N]) biomarkers to promote dementia. However, the precise pathological mechanisms remain to be fully characterized.\u0000\u0000\u0000Objective\u0000To elucidate the interrelationships among ICVD, ATN biomarkers in cerebrospinal fluid (CSF), and cognition.\u0000\u0000\u0000Methods\u0000A total of 2524 participants were recruited from the CABLE study. ICVD referred to TIA/ischemic stroke. Cognitive performance was assessed by China Modified Mini-Mental State Examination (CM-MMSE) and Montreal Cognitive Assessment-b (MoCA-b). Multivariate linear regression analyses were performed to evaluate the associations of ICVD with CSF ATN biomarkers and cognition. Causal mediation analyses were used to identify whether the association was mediated by ATN biomarkers.\u0000\u0000\u0000Results\u0000ICVD was associated with higher total-tau (t-tau) (p = 2.828×10-2) and poorer cognition (CM-MMSE: p = 1.539×10-5, MoCA-b: p = 4.552×10-6). Additionally, no discernible correlation surfaced between ICVD and amyloid-β (Aβ) 42 (p = 6.910×10-1) or phosphorylated tau (p-tau) (p = 4.324×10-1). The influence of ICVD on cognitive function was partially mediated by CSF t-tau (CM-MMSE: proportion: 2.74%, MoCA-b: proportion: 2.51%). Subgroup analyses revealed the influences of t-tau were especially evident in male (CM-MMSE: proportion: 5.45%, MoCA-b: proportion: 5.38%) and mid-life group (CM-MMSE: proportion: 9.83%, MoCA-b: proportion: 5.31%).\u0000\u0000\u0000Conclusions\u0000These results delineated t-tau as a potential mediator for the influence of ICVD on cognition. Targeting brain ischemia and alleviating neuronal injury induced by ischemia may be a promising approach for preventing cognitive decline.","PeriodicalId":219895,"journal":{"name":"Journal of Alzheimer's disease : JAD","volume":"13 3","pages":"1133-1143"},"PeriodicalIF":0.0,"publicationDate":"2024-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140751709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardiorespiratory Fitness Attenuates the Deleterious Effects of Sleep Apnea on Cerebral Structure and Perfusion in the Wisconsin Sleep Cohort Study.","authors":"Kyle J Edmunds, I. Driscoll, E. Hagen, J. Barnet, L. Ravelo, D. Plante, J. M. Gaitan, Sarah R. Lose, Alice Motovylyak, B. Bendlin, O. Okonkwo, P. Peppard","doi":"10.2139/ssrn.4138281","DOIUrl":"https://doi.org/10.2139/ssrn.4138281","url":null,"abstract":"BACKGROUND\u0000Emerging evidence suggests that age-related changes in cerebral health may be sensitive to vascular risk modifiers, such as physical activity and sleep.\u0000\u0000\u0000OBJECTIVE\u0000We examine whether cardiorespiratory fitness modifies the association of obstructive sleep apnea (OSA) severity with MRI-assessed measures of cerebral structure and perfusion.\u0000\u0000\u0000METHODS\u0000Using data from a cross-sectional sample of participants (n = 129, 51% female, age range 49.6-85.3 years) in the Wisconsin Sleep Cohort study, we estimated linear models of MRI-assessed total and regional gray matter (GM) and white matter (WM) volumes, WM hyperintensity (WMH:ICV ratio), total lesion volume, and arterial spin labeling (ASL) cerebral blood flow (CBF), using an estimated measure of cardiorespiratory fitness (CRF) and OSA severity as predictors. Participants' sleep was assessed using overnight in-laboratory polysomnography, and OSA severity was measured using the apnea-hypopnea index (AHI), or the mean number of recorded apnea and hypopnea events per hour of sleep. The mean±SD time difference between PSG data collection and MRI data collection was 1.7±1.5 years (range: [0, 4.9 years]).\u0000\u0000\u0000RESULTS\u0000OSA severity was associated with reduced total GM volume (β=-0.064; SE = 0.023; p = 0.007), greater total WM lesion volume (interaction p = 0.023), and greater WMHs (interaction p = 0.017) in less-fit subjects. Perfusion models revealed significant differences in the association of AHI and regional CBF between fitness groups (interaction ps <  0.05).\u0000\u0000\u0000CONCLUSION\u0000This work provides new evidence for the protective role of cardiorespiratory fitness against the deleterious effects of OSA on brain aging in late-middle age to older adults.","PeriodicalId":219895,"journal":{"name":"Journal of Alzheimer's disease : JAD","volume":"2 9 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"133046849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of Alcohol Consumption with Cognition in Older Population: The A4 Study.","authors":"B. Nallapu, Kellen K. Petersen, R. Lipton, E. Grober, R. Sperling, A. Ezzati","doi":"10.2139/ssrn.4199077","DOIUrl":"https://doi.org/10.2139/ssrn.4199077","url":null,"abstract":"BACKGROUND\u0000Alcohol use disorders have been categorized as a 'strongly modifiable' risk factor for dementia.\u0000\u0000\u0000OBJECTIVE\u0000To investigate the cross-sectional association between alcohol consumption and cognition in older adults and if it is different across sexes or depends on amyloid-β (Aβ) accumulation in the brain.\u0000\u0000\u0000METHODS\u0000Cognitively unimpaired older adults (N = 4387) with objective and subjective cognitive assessments and amyloid positron emission tomography (PET) imaging were classified into four categories based on their average daily alcohol use. Multivariable linear regression was then used to test the main effects and interactions with sex and Aβ levels.\u0000\u0000\u0000RESULTS\u0000Individuals who reported no alcohol consumption had lower scores on the Preclinical Alzheimer Cognitive Composite (PACC) compared to those consuming one or two drinks/day. In sex-stratified analysis, the association between alcohol consumption and cognition was more prominent in females. Female participants who consumed two drinks/day had better performance on PACC and Cognitive Function Index (CFI) than those who reported no alcohol consumption. In an Aβ-stratified sample, the association between alcohol consumption and cognition was present only in the Aβ- subgroup. The interaction between Aβ status and alcohol consumption on cognition was not significant.\u0000\u0000\u0000CONCLUSION\u0000Low or moderate consumption of alcohol was associated with better objective cognitive performance and better subjective report of daily functioning in cognitively unimpaired individuals. The association was present only in Aβ- individuals, suggesting that the pathophysiologic mechanism underlying the effect of alcohol on cognition is independent of Aβ pathology. Further investigation is required with larger samples consuming three or more drinks/day.","PeriodicalId":219895,"journal":{"name":"Journal of Alzheimer's disease : JAD","volume":"14 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"132317619","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cerebrovascular miRNAs Track Early Development of Alzheimer's Disease and Target Molecular Markers of Angiogenesis and Blood Flow Regulation.","authors":"Phoebe P Chum, Mary Bishara, Summer Solis, Erik J Behringer","doi":"10.1152/physiol.2023.38.s1.5732898","DOIUrl":"https://doi.org/10.1152/physiol.2023.38.s1.5732898","url":null,"abstract":"BACKGROUND\u0000Alzheimer's disease (AD) is associated with impaired cerebral circulation which underscores diminished delivery of blood oxygen and nutrients to and throughout the brain. In the 3xTg-AD mouse model, we have recently found that > 10 cerebrovascular miRNAs pertaining to vascular permeability, angiogenesis, and inflammation (e.g., let-7d, miR-99a, miR-132, miR-133a, miR-151-5p, and miR-181a) track early development of AD. Further, endothelial-specific miRNAs (miR-126-3p, miR-23a/b, miR-27a) alter with onset of overall AD pathology relative to stability of smooth muscle/pericyte-specific miRNAs (miR-143, miR-145).\u0000\u0000\u0000OBJECTIVE\u0000We tested the hypothesis that cerebrovascular miRNAs indicating AD pathology share mRNA targets that regulate key endothelial cell functions such as angiogenesis, vascular permeability, and blood flow regulation.\u0000\u0000\u0000METHODS\u0000As detected by NanoString nCounter miRNA Expression panel for 3xTg-AD mice, 61 cerebrovascular miRNAs and respective mRNA targets were examined using Ingenuity Pathway Analysis for canonical Cardiovascular (Cardio) and Nervous System (Neuro) Signaling.\u0000\u0000\u0000RESULTS\u0000The number of targets regulated per miRNA were 21±2 and 33±3 for the Cardio and Neuro pathways respectively, whereby 14±2 targets overlap among pathways. Endothelial miRNAs primarily target members of the PDE, PDGF, SMAD, and VEGF families. Individual candidates regulated by≥4 miRNAs that best mark AD pathology presence in 3xTg-AD mice include CFL2, GRIN2B, PDGFB, SLC6A1, SMAD3, SYT3, and TNFRSF11B.\u0000\u0000\u0000CONCLUSION\u0000miRNAs selective for regulation of endothelial function and respective downstream mRNA targets support a molecular basis for dysregulated cerebral blood flow regulation coupled with enhanced cell growth, proliferation, and inflammation.","PeriodicalId":219895,"journal":{"name":"Journal of Alzheimer's disease : JAD","volume":"21 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"117298549","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Surface-Based Federated Chow Test Model for Integrating APOE Status, Tau Deposition Measure, and Hippocampal Surface Morphometry","authors":"Jianfeng Wu, Yindan Su, Yanxi Chen, Wenjie Zhu, E. Reiman, R. Caselli, Kewei Chen, P. Thompson, Junwen Wang, Yalin Wang","doi":"10.48550/arXiv.2304.00134","DOIUrl":"https://doi.org/10.48550/arXiv.2304.00134","url":null,"abstract":"BACKGROUND\u0000Alzheimer's disease (AD) is the most common type of age-related dementia, affecting 6.2 million people aged 65 or older according to CDC data. It is commonly agreed that discovering an effective AD diagnosis biomarker could have enormous public health benefits, potentially preventing or delaying up to 40% of dementia cases. Tau neurofibrillary tangles are the primary driver of downstream neurodegeneration and subsequent cognitive impairment in AD, resulting in structural deformations such as hippocampal atrophy that can be observed in magnetic resonance imaging (MRI) scans.\u0000\u0000\u0000OBJECTIVE\u0000To build a surface-based model to 1) detect differences between APOE subgroups in patterns of tau deposition and hippocampal atrophy, and 2) use the extracted surface-based features to predict cognitive decline.\u0000\u0000\u0000METHODS\u0000Using data obtained from different institutions, we develop a surface-based federated Chow test model to study the synergistic effects of APOE, a previously reported significant risk factor of AD, and tau on hippocampal surface morphometry.\u0000\u0000\u0000RESULTS\u0000We illustrate that the APOE-specific morphometry features correlate with AD progression and better predict future AD conversion than other MRI biomarkers. For example, a strong association between atrophy and abnormal tau was identified in hippocampal subregion cornu ammonis 1 (CA1 subfield) and subiculum in e4 homozygote cohort.\u0000\u0000\u0000CONCLUSION\u0000Our model allows for identifying MRI biomarkers for AD and cognitive decline prediction and may uncover a corner of the neural mechanism of the influence of APOE and tau deposition on hippocampal morphology.","PeriodicalId":219895,"journal":{"name":"Journal of Alzheimer's disease : JAD","volume":"14 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134349930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Automated Video Analysis of Audio-Visual Approaches to Predict and Detect Mild Cognitive Impairment and Dementia in Older Adults.","authors":"Che-Sheng Chu, Di Wang, C. Liang, M. Chou, Ying-Hsin Hsu, Yu-Chun Wang, M. Liao, W. Chu, Yu-Te Lin","doi":"10.2139/ssrn.4172084","DOIUrl":"https://doi.org/10.2139/ssrn.4172084","url":null,"abstract":"BACKGROUND\u0000Early identification of different stages of cognitive impairment is important to provide available intervention and timely care for the elderly.\u0000\u0000\u0000OBJECTIVE\u0000This study aimed to examine the ability of the artificial intelligence (AI) technology to distinguish participants with mild cognitive impairment (MCI) from those with mild to moderate dementia based on automated video analysis.\u0000\u0000\u0000METHODS\u0000A total of 95 participants were recruited (MCI, 41; mild to moderate dementia, 54). The videos were captured during the Short Portable Mental Status Questionnaire process; the visual and aural features were extracted using these videos. Deep learning models were subsequently constructed for the binary differentiation of MCI and mild to moderate dementia. Correlation analysis of the predicted Mini-Mental State Examination, Cognitive Abilities Screening Instrument scores, and ground truth was also performed.\u0000\u0000\u0000RESULTS\u0000Deep learning models combining both the visual and aural features discriminated MCI from mild to moderate dementia with an area under the curve (AUC) of 77.0% and accuracy of 76.0% . The AUC and accuracy increased to 93.0% and 88.0%, respectively, when depression and anxiety were excluded. Significant moderate correlations were observed between the predicted cognitive function and ground truth, and the correlation was strong excluding depression and anxiety. Interestingly, female, but not male, exhibited a correlation.\u0000\u0000\u0000CONCLUSION\u0000The study showed that video-based deep learning models can differentiate participants with MCI from those with mild to moderate dementia and can predict cognitive function. This approach may offer a cost-effective and easily applicable method for early detection of cognitive impairment.","PeriodicalId":219895,"journal":{"name":"Journal of Alzheimer's disease : JAD","volume":"202 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"131865236","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hierarchical Two-Stage Cost-Sensitive Clinical Decision Support System for Screening Prodromal Alzheimer's Disease and Related Dementias","authors":"M. Kleiman, T. Ariko, J. Galvin","doi":"10.1101/2022.09.06.22279650","DOIUrl":"https://doi.org/10.1101/2022.09.06.22279650","url":null,"abstract":"Background: The detection of subtle cognitive impairment in a clinical setting is difficult, and because time is a key factor in small clinics and research sites, the brief cognitive assessments that are relied upon often misclassify patients with very mild impairment as normal. In this study, we seek to identify a parsimonious screening tool in one stage, followed by additional assessments in an optional second stage if additional specificity is desired, tested using a machine learning algorithm capable of being integrated into a clinical decision support system. Methods: The best primary stage incorporated measures of short-term memory, executive and visuospatial functioning, and self-reported memory and daily living questions, with a total time of 5 minutes. The best secondary stage incorporated a measure of neurobiology as well as additional cognitive assessment and brief informant report questionnaires, totaling 30 minutes including delayed recall. Combined performance was evaluated using 25 sets of models, trained on 1181 ADNI participants and tested on 127 patients from a memory clinic. Results: The 5-minute primary stage was highly sensitive (96.5%) but lacked specificity (34.1%), with an AUC of 87.5% and DOR of 14.3. The optional secondary stage increased specificity to 58.6%, resulting in an overall AUC of 89.7% using the best model combination of logistic regression for stage 1 and gradient-boosted machine for stage 2. Conclusions: The primary stage is brief and effective at screening, with the optional two-stage technique further increasing specificity. The hierarchical two-stage technique exhibited similar accuracy but with reduced costs compared to the more common single-stage paradigm.","PeriodicalId":219895,"journal":{"name":"Journal of Alzheimer's disease : JAD","volume":"26 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"132367855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of cognitive reserve on physiological measures of cognitive workload in older adults with cognitive impairments","authors":"Hannes Devos, Kathleen Gustafson, Ke Liao, Pedram Ahmadnezhad, Emily Kuhlmann, Bradley J Estes, Laura E Martin, J. Mahnken, William M. Brooks, Jeffrey M. Burns","doi":"10.1101/2022.09.08.22279748","DOIUrl":"https://doi.org/10.1101/2022.09.08.22279748","url":null,"abstract":"Background: Cognitive reserve may protect against cognitive decline. However, its effect on physiological measures of cognitive workload in adults with cognitive impairments is unclear. Objective: The aim was to determine the association between cognitive reserve and physiological measures of cognitive workload in older adults with and without cognitive impairments. Methods: 29 older adults with cognitive impairment (age: 75 (6), 11 (38%) women, MOCA scores 20 (7)) and 19 with normal cognition (age: 74 (6); 11 (58%) women; MOCA 28 (2)) completed a working memory test of increasing task demand (0-, 1-, 2-back). Cognitive workload was indexed using amplitude and latency of the P3 event-related potential (ERP) at electrode sites Fz, Cz, and Pz, and changes in pupillary size, converted to an index of cognitive activity (ICA). The Cognitive Reserve Index questionnaire (CRIq) evaluated Education, Work Activity, and Leisure Time as a proxy of cognitive reserve. Results: Higher CRIq total scores were associated with larger P3 ERP amplitude (p=0.048), independent of cognitive status (p=0.80), task demand (p=0.003), and electrode site (p<0.0001). This relationship was mainly driven by Work Activity (p=0.0005). Higher CRIq total scores also correlated with higher mean ICA (p=0.002), regardless of cognitive status (p=0.29) and task demand (p=0.12). Both Work Activity (p=0.0002) and Leisure Time (p=0.045) impacted ICA. No relationship was found between CRIq and P3 latency. Conclusion: Cognitive reserve affects cognitive workload and neural efficiency, regardless of cognitive status. Future longitudinal studies should investigate the causal relationship between cognitive reserve and physiological processes of neural efficiency across cognitive aging.","PeriodicalId":219895,"journal":{"name":"Journal of Alzheimer's disease : JAD","volume":"35 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"124329312","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}