Can Fenerci , Roni Setton , Giulia Baracchini , Jamie Snytte , R. Nathan Spreng , Cam CAN , Signy Sheldon
{"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}
Camila de Ávila , Crystal Suazo , Jennifer Nolz , J. Nicholas Cochran , Qi Wang , Ramon Velazquez , Eric Dammer , Benjamin Readhead , Diego Mastroeni
{"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}
{"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}
{"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}
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
{"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}
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
{"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}
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
{"title":"Cerebrospinal fluid biomarkers and cognitive trajectories in patients with Alzheimer’s disease and a history of traumatic brain injury","authors":"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","doi":"10.1016/j.neurobiolaging.2024.06.001","DOIUrl":"10.1016/j.neurobiolaging.2024.06.001","url":null,"abstract":"<div><p>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 (AD<sup>TBI+,</sup> n=110), or without (AD<sup>TBI-</sup>, 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 AD<sup>TBI+</sup> and AD<sup>TBI-</sup> 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.</p></div>","PeriodicalId":19110,"journal":{"name":"Neurobiology of Aging","volume":"141 ","pages":"Pages 121-128"},"PeriodicalIF":3.7,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0197458024001192/pdfft?md5=0928a431c4d50a9745ff24f2e3b90e2f&pid=1-s2.0-S0197458024001192-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141391569","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}
Rikki Lissaman , Sricharana Rajagopal , Julia Kearley , Stamatoula Pasvanis , Maria Natasha Rajah
{"title":"Menopause status- and sex-related differences in age associations with spatial context memory and white matter microstructure at midlife","authors":"Rikki Lissaman , Sricharana Rajagopal , Julia Kearley , Stamatoula Pasvanis , Maria Natasha Rajah","doi":"10.1016/j.neurobiolaging.2024.05.017","DOIUrl":"https://doi.org/10.1016/j.neurobiolaging.2024.05.017","url":null,"abstract":"<div><p>Decline in spatial context memory emerges in midlife, the time when most females transition from pre- to post-menopause. Recent evidence suggests that, among post-menopausal females, advanced age is associated with functional brain alterations and lower spatial context memory. However, it is unknown whether similar effects are evident for white matter (WM) and, moreover, whether such effects contribute to sex differences at midlife. To address this, we conducted a study on 96 cognitively unimpaired middle-aged adults (30 males, 32 pre-menopausal females, 34 post-menopausal females). Spatial context memory was assessed using a face-location memory paradigm, while WM microstructure was assessed using diffusion tensor imaging. Behaviorally, advanced age was associated with lower spatial context memory in post-menopausal females but not pre-menopausal females or males. Additionally, advanced age was associated with microstructural variability in predominantly frontal WM (e.g., anterior corona radiata, genu of corpus callosum), which was related to lower spatial context memory among post-menopausal females. Our findings suggest that post-menopausal status enhances vulnerability to age effects on the brain’s WM and episodic memory.</p></div>","PeriodicalId":19110,"journal":{"name":"Neurobiology of Aging","volume":"141 ","pages":"Pages 151-159"},"PeriodicalIF":3.7,"publicationDate":"2024-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0197458024001155/pdfft?md5=ba0dbd9649fcb4efd3bf480369ec6cc7&pid=1-s2.0-S0197458024001155-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141482567","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}
Sandra Aleksic , Roman Fleysher , Erica F. Weiss , Noa Tal , Timothy Darby , Helena M. Blumen , Juan Vazquez , Kenny Q. Ye , Tina Gao , Shira M. Siegel , Nir Barzilai , Michael L. Lipton , Sofiya Milman
{"title":"Hypothalamic MRI-derived microstructure is associated with neurocognitive aging in humans","authors":"Sandra Aleksic , Roman Fleysher , Erica F. Weiss , Noa Tal , Timothy Darby , Helena M. Blumen , Juan Vazquez , Kenny Q. Ye , Tina Gao , Shira M. Siegel , Nir Barzilai , Michael L. Lipton , Sofiya Milman","doi":"10.1016/j.neurobiolaging.2024.05.018","DOIUrl":"10.1016/j.neurobiolaging.2024.05.018","url":null,"abstract":"<div><p>The hypothalamus regulates homeostasis across the lifespan and is emerging as a regulator of aging. In murine models, aging-related changes in the hypothalamus, including microinflammation and gliosis, promote accelerated neurocognitive decline. We investigated relationships between hypothalamic microstructure and features of neurocognitive aging, including cortical thickness and cognition, in a cohort of community-dwelling older adults (age range 65–97 years, n=124). Hypothalamic microstructure was evaluated with two magnetic resonance imaging diffusion metrics: mean diffusivity (MD) and fractional anisotropy (FA), using a novel image processing pipeline. Hypothalamic MD was cross-sectionally positively associated with age and it was negatively associated with cortical thickness. Hypothalamic FA, independent of cortical thickness, was cross-sectionally positively associated with neurocognitive scores. An exploratory analysis of longitudinal neurocognitive performance suggested that lower hypothalamic FA may predict cognitive decline. No associations between hypothalamic MD, age, and cortical thickness were identified in a younger control cohort (age range 18–63 years, n=99). To our knowledge, this is the first study to demonstrate that hypothalamic microstructure is associated with features of neurocognitive aging in humans.</p></div>","PeriodicalId":19110,"journal":{"name":"Neurobiology of Aging","volume":"141 ","pages":"Pages 102-112"},"PeriodicalIF":4.2,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141274954","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}