Pub Date : 2024-08-13DOI: 10.1016/j.neurobiolaging.2024.08.001
George M. Opie , James M. Hughes , Rohan Puri
While the shape of cortical oscillations is increasingly recognised to be physiologically and functionally informative, its relevance to the aging motor system has not been established. We therefore examined the shape of alpha and beta band oscillations recorded at rest, as well as during performance of simple and go/no-go reaction time tasks, in 33 young (23.3 ± 2.9 years, 27 females) and 27 older (60.0 ± 5.2 years, 23 females) adults. The shape of individual oscillatory cycles was characterised using a recently developed pipeline involving empirical mode decomposition, before being decomposed into waveform motifs using principal component analysis. This revealed four principal components that were uniquely influenced by task and/or age. These described specific dimensions of shape and tended to be modulated during the reaction phase of each task. Our results suggest that although oscillation shape is task-dependent, the nature of this effect is altered by advancing age, possibly reflecting alterations in cortical activity. These outcomes demonstrate the utility of this approach for understanding the neurophysiological effects of ageing.
{"title":"Age-related differences in how the shape of alpha and beta oscillations change during reaction time tasks","authors":"George M. Opie , James M. Hughes , Rohan Puri","doi":"10.1016/j.neurobiolaging.2024.08.001","DOIUrl":"10.1016/j.neurobiolaging.2024.08.001","url":null,"abstract":"<div><p>While the <em>shape</em> of cortical oscillations is increasingly recognised to be physiologically and functionally informative, its relevance to the aging motor system has not been established. We therefore examined the shape of alpha and beta band oscillations recorded at rest, as well as during performance of simple and go/no-go reaction time tasks, in 33 young (23.3 ± 2.9 years, 27 females) and 27 older (60.0 ± 5.2 years, 23 females) adults. The shape of individual oscillatory cycles was characterised using a recently developed pipeline involving empirical mode decomposition, before being decomposed into waveform motifs using principal component analysis. This revealed four principal components that were uniquely influenced by task and/or age. These described specific dimensions of shape and tended to be modulated during the reaction phase of each task. Our results suggest that although oscillation shape is task-dependent, the nature of this effect is altered by advancing age, possibly reflecting alterations in cortical activity. These outcomes demonstrate the utility of this approach for understanding the neurophysiological effects of ageing.</p></div>","PeriodicalId":19110,"journal":{"name":"Neurobiology of Aging","volume":"142 ","pages":"Pages 52-64"},"PeriodicalIF":3.7,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0197458024001325/pdfft?md5=70b87d1e5a245772f9470cc43494761b&pid=1-s2.0-S0197458024001325-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141993355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-10DOI: 10.1016/j.neurobiolaging.2024.08.002
Simone Beer , David Elmenhorst , Gerard N. Bischof , Alfredo Ramirez , Andreas Bauer , Alexander Drzezga , for the Alzheimer’s Disease Neuroimaging Initiative
Aquaporin-4 (AQP4) is hypothesized to be a component of the glymphatic system, a pathway for removing brain interstitial solutes like amyloid-β (Aβ). Evidence exists that genetic variation of AQP4 impacts Aβ clearance, clinical outcome in Alzheimer’s disease as well as sleep measures. We examined whether a risk score calculated from several AQP4 single-nucleotide polymorphisms (SNPs) is related to Aβ neuropathology in older cognitively unimpaired white individuals. We used a machine learning approach and explainable artificial intelligence to extract information on synergistic effects of AQP4 SNPs on brain amyloid burden from the ADNI cohort. From this information, we formulated a sex-specific AQP4 SNP-based risk score and evaluated it using data from the screening process of the A4 study. We found in both cohorts significant associations of the risk score with brain amyloid burden. The results support the hypothesis of an involvement of the glymphatic system, and particularly AQP4, in brain amyloid aggregation pathology. They suggest also that different AQP4 SNPs exert a synergistic effect on the build-up of brain amyloid burden.
{"title":"Explainable artificial intelligence identifies an AQP4 polymorphism-based risk score associated with brain amyloid burden","authors":"Simone Beer , David Elmenhorst , Gerard N. Bischof , Alfredo Ramirez , Andreas Bauer , Alexander Drzezga , for the Alzheimer’s Disease Neuroimaging Initiative","doi":"10.1016/j.neurobiolaging.2024.08.002","DOIUrl":"10.1016/j.neurobiolaging.2024.08.002","url":null,"abstract":"<div><p>Aquaporin-4 (AQP4) is hypothesized to be a component of the glymphatic system, a pathway for removing brain interstitial solutes like amyloid-β (Aβ). Evidence exists that genetic variation of AQP4 impacts Aβ clearance, clinical outcome in Alzheimer’s disease as well as sleep measures. We examined whether a risk score calculated from several AQP4 single-nucleotide polymorphisms (SNPs) is related to Aβ neuropathology in older cognitively unimpaired white individuals. We used a machine learning approach and explainable artificial intelligence to extract information on synergistic effects of AQP4 SNPs on brain amyloid burden from the ADNI cohort. From this information, we formulated a sex-specific AQP4 SNP-based risk score and evaluated it using data from the screening process of the A4 study. We found in both cohorts significant associations of the risk score with brain amyloid burden. The results support the hypothesis of an involvement of the glymphatic system, and particularly AQP4, in brain amyloid aggregation pathology. They suggest also that different AQP4 SNPs exert a synergistic effect on the build-up of brain amyloid burden.</p></div>","PeriodicalId":19110,"journal":{"name":"Neurobiology of Aging","volume":"143 ","pages":"Pages 19-29"},"PeriodicalIF":3.7,"publicationDate":"2024-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0197458024001337/pdfft?md5=c5699bac2cc221af526e85186f349a58&pid=1-s2.0-S0197458024001337-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142087225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-30DOI: 10.1016/j.neurobiolaging.2024.06.006
Can Fenerci , Roni Setton , Giulia Baracchini , Jamie Snytte , R. Nathan Spreng , Cam CAN , Signy Sheldon
Age-related episodic memory decline is attributed to functional alternations in the hippocampus. Less clear is how aging affects the functional connections of the hippocampus to the rest of the brain during episodic memory processing. We examined fMRI data from the CamCAN dataset, in which a large cohort of participants watched a movie (N = 643; 18–88 years), a proxy for naturalistic episodic memory encoding. We examined connectivity profiles across the lifespan both within the hippocampus (anterior, posterior), and between the hippocampal subregions and cortical networks. Aging was associated with reductions in contralateral (left, right) but not ipsilateral (anterior, posterior) hippocampal subregion connectivity. Aging was primarily associated with increased coupling between the anterior hippocampus and regions affiliated with Control, Dorsal Attention and Default Mode networks, yet decreased coupling between the posterior hippocampus and a selection of these regions. Differences in age-related hippocampal-cortical, but not within-hippocampus circuitry selectively predicted worse memory performance. Our findings comprehensively characterize hippocampal functional topography in relation to cognition in older age, suggesting that shifts in cortico-hippocampal connectivity may be sensitive markers of age-related episodic memory decline.
{"title":"Lifespan differences in hippocampal subregion connectivity patterns during movie watching","authors":"Can Fenerci , Roni Setton , Giulia Baracchini , Jamie Snytte , R. Nathan Spreng , Cam CAN , Signy Sheldon","doi":"10.1016/j.neurobiolaging.2024.06.006","DOIUrl":"10.1016/j.neurobiolaging.2024.06.006","url":null,"abstract":"<div><p>Age-related episodic memory decline is attributed to functional alternations in the hippocampus. Less clear is how aging affects the functional connections of the hippocampus to the rest of the brain during episodic memory processing. We examined fMRI data from the CamCAN dataset, in which a large cohort of participants watched a movie (N = 643; 18–88 years), a proxy for naturalistic episodic memory encoding. We examined connectivity profiles across the lifespan both within the hippocampus (anterior, posterior), and between the hippocampal subregions and cortical networks. Aging was associated with reductions in contralateral (left, right) but not ipsilateral (anterior, posterior) hippocampal subregion connectivity. Aging was primarily associated with increased coupling between the anterior hippocampus and regions affiliated with Control, Dorsal Attention and Default Mode networks, yet decreased coupling between the posterior hippocampus and a selection of these regions. Differences in age-related hippocampal-cortical, but not within-hippocampus circuitry selectively predicted worse memory performance. Our findings comprehensively characterize hippocampal functional topography in relation to cognition in older age, suggesting that shifts in cortico-hippocampal connectivity may be sensitive markers of age-related episodic memory decline.</p></div>","PeriodicalId":19110,"journal":{"name":"Neurobiology of Aging","volume":"141 ","pages":"Pages 182-193"},"PeriodicalIF":3.7,"publicationDate":"2024-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141538212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-29DOI: 10.1016/j.neurobiolaging.2024.06.007
Camila de Ávila , Crystal Suazo , Jennifer Nolz , J. Nicholas Cochran , Qi Wang , Ramon Velazquez , Eric Dammer , Benjamin Readhead , Diego Mastroeni
Women have a higher incidence of Alzheimer’s disease (AD), even after adjusting for increased longevity. Thus, there is an urgent need to identify genes that underpin sex-associated risk of AD. PIN1 is a key regulator of the tau phosphorylation signaling pathway; however, potential differences in PIN1 expression, in males and females, are still unknown. We analyzed brain transcriptomic datasets focusing on sex differences in PIN1 mRNA levels in an aging and AD cohort, which revealed reduced PIN1 levels primarily within females. We validated this observation in an independent dataset (ROS/MAP), which also revealed that PIN1 is negatively correlated with multiregional neurofibrillary tangle density and global cognitive function in females only. Additional analysis revealed a decrease in PIN1 in subjects with mild cognitive impairment (MCI) compared with aged individuals, again driven predominantly by female subjects. Histochemical analysis of PIN1 in AD and control male and female neocortex revealed an overall decrease in axonal PIN1 protein levels in females. These findings emphasize the importance of considering sex differences in AD research.
{"title":"Reduced PIN1 expression in neocortical and limbic brain regions in female Alzheimer’s patients correlates with cognitive and neuropathological phenotypes","authors":"Camila de Ávila , Crystal Suazo , Jennifer Nolz , J. Nicholas Cochran , Qi Wang , Ramon Velazquez , Eric Dammer , Benjamin Readhead , Diego Mastroeni","doi":"10.1016/j.neurobiolaging.2024.06.007","DOIUrl":"10.1016/j.neurobiolaging.2024.06.007","url":null,"abstract":"<div><p>Women have a higher incidence of Alzheimer’s disease (AD), even after adjusting for increased longevity. Thus, there is an urgent need to identify genes that underpin sex-associated risk of AD. PIN1 is a key regulator of the tau phosphorylation signaling pathway; however, potential differences in PIN1 expression, in males and females, are still unknown. We analyzed brain transcriptomic datasets focusing on sex differences in PIN1 mRNA levels in an aging and AD cohort, which revealed reduced PIN1 levels primarily within females. We validated this observation in an independent dataset (ROS/MAP), which also revealed that PIN1 is negatively correlated with multiregional neurofibrillary tangle density and global cognitive function in females only. Additional analysis revealed a decrease in PIN1 in subjects with mild cognitive impairment (MCI) compared with aged individuals, again driven predominantly by female subjects. Histochemical analysis of PIN1 in AD and control male and female neocortex revealed an overall decrease in axonal PIN1 protein levels in females. These findings emphasize the importance of considering sex differences in AD research.</p></div>","PeriodicalId":19110,"journal":{"name":"Neurobiology of Aging","volume":"141 ","pages":"Pages 160-170"},"PeriodicalIF":3.7,"publicationDate":"2024-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0197458024001258/pdfft?md5=c32858ca61f61acfd6886574acd18ff8&pid=1-s2.0-S0197458024001258-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141534891","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-26DOI: 10.1016/j.neurobiolaging.2024.06.005
Pei Ying Lee, Bang V. Bui
Age-related neuronal adaptations are known to help maintain function. This study aims to examine gross age-related in vivo retinal functional adaptations (using electroretinography) in young and middle aged C57BL/6J and Thy1-YFPh mice and to relate this to in vivo retinal structure (using optical coherence tomography). Electroretinography responses were generally larger in Thy1-YFPh mice than in C57BL/6J mice, with similar in vivo retinal layer thicknesses except for longer inner/outer photoreceptor segment in Thy1-YFPh mice. Relative to 3-month-old mice, 12-month-old mice showed reduced photoreceptor (C57BL/6J 84.0±2.5 %; Thy1-YFPh 80.2±5.2 %) and bipolar cell (C57BL/6J 75.6±2.3 %; Thy1-YFPh 68.1±5.5 %) function. There was relative preservation of ganglion cell function (C57BL/6J 79.7±3.7 %; Thy1-YFPh 91.7±5.0 %) with age, which was associated with increased b-wave (bipolar cell) sensitivities to light. Ganglion cell function was correlated with both b-wave amplitude and sensitivity. This study shows that there are normal age-related adaptations to preserve functional output. Different mouse strains may have varied age-related adaptation capacity and should be taken into consideration when examining age-related susceptibility to injury.
众所周知,与年龄相关的神经元适应有助于维持功能。本研究旨在检测年轻和中年C57BL/6J小鼠和Thy1-YFPh小鼠体内视网膜功能适应(使用视网膜电图)的粗略年龄相关性,并将其与体内视网膜结构(使用光学相干断层扫描)联系起来。Thy1-YFPh小鼠的视网膜电图反应一般比C57BL/6J小鼠大,体内视网膜层厚度相似,但Thy1-YFPh小鼠的内/外光感受器节段较长。与3月龄小鼠相比,12月龄小鼠的感光细胞(C57BL/6J 84.0±2.5%;Thy1-YFPh 80.2±5.2%)和双极细胞(C57BL/6J 75.6±2.3%;Thy1-YFPh 68.1±5.5%)功能降低。随着年龄的增长,神经节细胞功能相对保持不变(C57BL/6J 79.7±3.7%;Thy1-YFPh 91.7±5.0%),这与b波(双极细胞)对光的敏感性增加有关。神经节细胞功能与 b 波振幅和灵敏度相关。这项研究表明,存在与年龄相关的正常适应,以保持功能输出。不同的小鼠品系可能具有不同的与年龄相关的适应能力,在研究与年龄相关的损伤易感性时应加以考虑。
{"title":"Age-related differences in retinal function and structure in C57BL/6J and Thy1-YFPh mice","authors":"Pei Ying Lee, Bang V. Bui","doi":"10.1016/j.neurobiolaging.2024.06.005","DOIUrl":"10.1016/j.neurobiolaging.2024.06.005","url":null,"abstract":"<div><p>Age-related neuronal adaptations are known to help maintain function. This study aims to examine gross age-related <em>in vivo</em> retinal functional adaptations (using electroretinography) in young and middle aged C57BL/6J and Thy1-YFPh mice and to relate this to <em>in vivo</em> retinal structure (using optical coherence tomography). Electroretinography responses were generally larger in Thy1-YFPh mice than in C57BL/6J mice, with similar <em>in vivo</em> retinal layer thicknesses except for longer inner/outer photoreceptor segment in Thy1-YFPh mice. Relative to 3-month-old mice, 12-month-old mice showed reduced photoreceptor (C57BL/6J 84.0±2.5 %; Thy1-YFPh 80.2±5.2 %) and bipolar cell (C57BL/6J 75.6±2.3 %; Thy1-YFPh 68.1±5.5 %) function. There was relative preservation of ganglion cell function (C57BL/6J 79.7±3.7 %; Thy1-YFPh 91.7±5.0 %) with age, which was associated with increased b-wave (bipolar cell) sensitivities to light. Ganglion cell function was correlated with both b-wave amplitude and sensitivity. This study shows that there are normal age-related adaptations to preserve functional output. Different mouse strains may have varied age-related adaptation capacity and should be taken into consideration when examining age-related susceptibility to injury.</p></div>","PeriodicalId":19110,"journal":{"name":"Neurobiology of Aging","volume":"141 ","pages":"Pages 171-181"},"PeriodicalIF":3.7,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0197458024001234/pdfft?md5=02b1a963332ac9bdba26abf96e92e507&pid=1-s2.0-S0197458024001234-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141534890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
This study explores the impact of aging on reinforcement learning in mice, focusing on changes in learning rates and behavioral strategies. A 5-armed bandit task (5-ABT) and a computational Q-learning model were used to evaluate the positive and negative learning rates and the inverse temperature across three age groups (3, 12, and 18 months). Results showed a significant decline in the negative learning rate of 18-month-old mice, which was not observed for the positive learning rate. This suggests that older mice maintain the ability to learn from successful experiences while decreasing the ability to learn from negative outcomes. We also observed a significant age-dependent variation in inverse temperature, reflecting a shift in action selection policy. Middle-aged mice (12 months) exhibited higher inverse temperature, indicating a higher reliance on previous rewarding experiences and reduced exploratory behaviors, when compared to both younger and older mice. This study provides new insights into aging research by demonstrating that there are age-related differences in specific components of reinforcement learning, which exhibit a non-linear pattern.
{"title":"Nonlinear age-related differences in probabilistic learning in mice: A 5-armed bandit task study","authors":"Hiroyuki Ohta , Takashi Nozawa , Takashi Nakano , Yuji Morimoto , Toshiaki Ishizuka","doi":"10.1016/j.neurobiolaging.2024.06.004","DOIUrl":"10.1016/j.neurobiolaging.2024.06.004","url":null,"abstract":"<div><p>This study explores the impact of aging on reinforcement learning in mice, focusing on changes in learning rates and behavioral strategies. A 5-armed bandit task (5-ABT) and a computational Q-learning model were used to evaluate the positive and negative learning rates and the inverse temperature across three age groups (3, 12, and 18 months). Results showed a significant decline in the negative learning rate of 18-month-old mice, which was not observed for the positive learning rate. This suggests that older mice maintain the ability to learn from successful experiences while decreasing the ability to learn from negative outcomes. We also observed a significant age-dependent variation in inverse temperature, reflecting a shift in action selection policy. Middle-aged mice (12 months) exhibited higher inverse temperature, indicating a higher reliance on previous rewarding experiences and reduced exploratory behaviors, when compared to both younger and older mice. This study provides new insights into aging research by demonstrating that there are age-related differences in specific components of reinforcement learning, which exhibit a non-linear pattern.</p></div>","PeriodicalId":19110,"journal":{"name":"Neurobiology of Aging","volume":"142 ","pages":"Pages 8-16"},"PeriodicalIF":3.7,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141727584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-21DOI: 10.1016/j.neurobiolaging.2024.06.002
Ankita Chatterjee , Shannon Lee , Valentina Diaz , Rowan Saloner , Mark Sanderson-Cimino , Charles deCarli , Pauline Maillard , Jason Hinman , Keith Vossel , Kaitlin B. Casaletto , Adam M. Staffaroni , Emily W. Paolillo , Joel H. Kramer
Cerebrovascular disease (CVD) and Alzheimer’s disease (AD) often co-occur and may impact specific cognitive domains. This study’s goal was to determine effects of CVD and AD burden on cross-sectional and longitudinal executive function (EF) and memory in older adults.
Longitudinally followed participants from the National Alzheimer Coordinating Center database (n = 3342) were included. Cognitive outcomes were EF and memory composite scores. Baseline CVD presence was defined by moderate-to-severe white matter hyperintensities or lacunar infarct on MRI. Baseline AD pathology was defined by amyloid positivity via PET or CSF. Linear mixed models examined effects of CVD, AD, and time on cognitive outcomes, controlling for sex, education, baseline age, MoCA score, and total number of study visits.
At baseline, CVD associated with lower EF (p < 0.001), while AD associated with lower EF and memory (ps < 0.001). Longitudinally only AD associated with faster declines in memory and EF (ps < 0.001).
These results extend our understanding of CVD and AD pathology, highlighting that CVD does not necessarily indicate accelerated decline.
{"title":"Associations of cerebrovascular disease and Alzheimer’s disease pathology with cognitive decline: Analysis of the National Alzheimer’s Coordinating Center Uniform Data Set","authors":"Ankita Chatterjee , Shannon Lee , Valentina Diaz , Rowan Saloner , Mark Sanderson-Cimino , Charles deCarli , Pauline Maillard , Jason Hinman , Keith Vossel , Kaitlin B. Casaletto , Adam M. Staffaroni , Emily W. Paolillo , Joel H. Kramer","doi":"10.1016/j.neurobiolaging.2024.06.002","DOIUrl":"10.1016/j.neurobiolaging.2024.06.002","url":null,"abstract":"<div><p>Cerebrovascular disease (CVD) and Alzheimer’s disease (AD) often co-occur and may impact specific cognitive domains. This study’s goal was to determine effects of CVD and AD burden on cross-sectional and longitudinal executive function (EF) and memory in older adults.</p><p>Longitudinally followed participants from the National Alzheimer Coordinating Center database (n = 3342) were included. Cognitive outcomes were EF and memory composite scores. Baseline CVD presence was defined by moderate-to-severe white matter hyperintensities or lacunar infarct on MRI. Baseline AD pathology was defined by amyloid positivity via PET or CSF. Linear mixed models examined effects of CVD, AD, and time on cognitive outcomes, controlling for sex, education, baseline age, MoCA score, and total number of study visits.</p><p>At baseline, CVD associated with lower EF (p < 0.001), while AD associated with lower EF and memory (ps < 0.001). Longitudinally only AD associated with faster declines in memory and EF (ps < 0.001).</p><p>These results extend our understanding of CVD and AD pathology, highlighting that CVD does not necessarily indicate accelerated decline.</p></div>","PeriodicalId":19110,"journal":{"name":"Neurobiology of Aging","volume":"142 ","pages":"Pages 1-7"},"PeriodicalIF":3.7,"publicationDate":"2024-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0197458024001209/pdfft?md5=8720dbfa497c4bc9ebf648ef72b4054b&pid=1-s2.0-S0197458024001209-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141638563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-20DOI: 10.1016/j.neurobiolaging.2024.06.003
Christopher W. Davies-Jenkins , Clifford I. Workman , Kathleen E. Hupfeld , Helge J. Zöllner , Jeannie-Marie Leoutsakos , Michael A. Kraut , Peter B. Barker , Gwenn S. Smith , Georg Oeltzschner
Positron emission tomography (PET) and magnetic resonance spectroscopy (1H-MRS) are complementary techniques that can be applied to study how proteinopathy and neurometabolism relate to cognitive deficits in preclinical stages of Alzheimer’s disease (AD)—mild cognitive impairment (MCI) and late-life depression (LLD). We acquired beta-amyloid (Aβ) PET and 7 T 1H-MRS measures of GABA, glutamate, glutathione, N-acetylaspartate, N-acetylaspartylglutamate, myo-inositol, choline, and lactate in the anterior and posterior cingulate cortices (ACC, PCC) in 13 MCI and 9 LLD patients, and 13 controls. We used linear regression to examine associations between metabolites, Aβ, and cognitive scores, and whether metabolites and Aβ explained cognitive scores better than Aβ alone. In the ACC, higher Aβ was associated with lower GABA in controls but not MCI or LLD patients, but results depended upon MRS data quality control criteria. Greater variance in California Verbal Learning Test scores was better explained by a model that combined ACC glutamate and Aβ deposition than by models that only included one of these variables. These findings identify preliminary associations between Aβ, neurometabolites, and cognition.
{"title":"Multimodal investigation of neuropathology and neurometabolites in mild cognitive impairment and late-life depression with 11C-PiB beta-amyloid PET and 7T magnetic resonance spectroscopy","authors":"Christopher W. Davies-Jenkins , Clifford I. Workman , Kathleen E. Hupfeld , Helge J. Zöllner , Jeannie-Marie Leoutsakos , Michael A. Kraut , Peter B. Barker , Gwenn S. Smith , Georg Oeltzschner","doi":"10.1016/j.neurobiolaging.2024.06.003","DOIUrl":"10.1016/j.neurobiolaging.2024.06.003","url":null,"abstract":"<div><p>Positron emission tomography (PET) and magnetic resonance spectroscopy (<sup>1</sup>H-MRS) are complementary techniques that can be applied to study how proteinopathy and neurometabolism relate to cognitive deficits in preclinical stages of Alzheimer’s disease (AD)—mild cognitive impairment (MCI) and late-life depression (LLD). We acquired beta-amyloid (Aβ) PET and 7 T <sup>1</sup>H-MRS measures of GABA, glutamate, glutathione, N-acetylaspartate, N-acetylaspartylglutamate, myo-inositol, choline, and lactate in the anterior and posterior cingulate cortices (ACC, PCC) in 13 MCI and 9 LLD patients, and 13 controls. We used linear regression to examine associations between metabolites, Aβ, and cognitive scores, and whether metabolites and Aβ explained cognitive scores better than Aβ alone. In the ACC, higher Aβ was associated with lower GABA in controls but not MCI or LLD patients, but results depended upon MRS data quality control criteria. Greater variance in California Verbal Learning Test scores was better explained by a model that combined ACC glutamate and Aβ deposition than by models that only included one of these variables. These findings identify preliminary associations between Aβ, neurometabolites, and cognition.</p></div>","PeriodicalId":19110,"journal":{"name":"Neurobiology of Aging","volume":"142 ","pages":"Pages 27-40"},"PeriodicalIF":3.7,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141902477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-14DOI: 10.1016/j.neurobiolaging.2024.06.001
Suzan van Amerongen , Shreyasee Das , Suzie Kamps , Julie Goossens , Bram Bongers , Yolande A.L. Pijnenburg , Eugeen Vanmechelen , Everard G.B. Vijverberg , Charlotte E. Teunissen , Inge M.W. Verberk
Traumatic brain injury (TBI) and Alzheimer’s disease (AD) have overlapping mechanisms but it remains unknown if pathophysiological characteristics and cognitive trajectories in AD patients are influenced by TBI history. Here, we studied AD patients (stage MCI or dementia) with TBI history (ADTBI+, n=110), or without (ADTBI-, n=110) and compared baseline CSF concentrations of amyloid beta 1–42 (Aβ42), phosphorylated tau181 (pTau181), total tau, neurofilament light chain (NfL), synaptosomal associated protein-25kDa (SNAP25), neurogranin (Ng), neuronal pentraxin-2 (NPTX2) and glutamate receptor-4 (GluR4), as well as differences in cognitive trajectories using linear mixed models. Explorative, analyses were repeated within stratified TBI groups by TBI characteristics (timing, severity, number). We found no differences in baseline CSF biomarker concentrations nor in cognitive trajectories between ADTBI+ and ADTBI- patients. TBI >5 years ago was associated with higher NPTX2 and a tendency for higher SNAP25 concentrations compared to TBI ≤ 5 years ago, suggesting that TBI may be associated with long-term synaptic dysfunction only when occurring before onset or in a pre-clinical disease stage of AD.
创伤性脑损伤(TBI)和阿尔茨海默病(AD)的发病机制有重叠之处,但 AD 患者的病理生理学特征和认知轨迹是否受 TBI 史的影响仍是未知数。在此,我们研究了有 TBI 史(ADTBI+,n=110)或无 TBI 史(ADTBI-,n=110)的 AD 患者(MCI 或痴呆期),并比较了淀粉样 beta 1-42 (Aβ42)、磷酸化 tau181 (pTau181)、总 tau、神经纤维轻链(NfL)、突触体相关蛋白-25kDa(SNAP25)、神经粒蛋白(Ng)、神经元五肽-2(NPTX2)和谷氨酸受体-4(GluR4)的浓度,以及认知轨迹的差异。在按创伤性脑损伤特征(时间、严重程度、次数)分层的创伤性脑损伤组中,我们重复进行了探索性分析。我们发现ADTBI+和ADTBI-患者的基线CSF生物标志物浓度和认知轨迹均无差异。与≤5年前的创伤性脑损伤相比,5年前的创伤性脑损伤与较高的NPTX2和较高的SNAP25浓度有关,这表明创伤性脑损伤只有在AD发病前或临床前疾病阶段发生时才可能与长期突触功能障碍有关。
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