Neurobiology of Aging最新文献

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Editorial Advisory Board 编辑顾问委员会

IF 3.7 3区医学 Q2 GERIATRICS & GERONTOLOGY

Neurobiology of Aging

Pub Date : 2025-04-06 DOI: 10.1016/S0197-4580(25)00064-8

引用次数: 0

Gene age gap estimate (GAGE) for major depressive disorder: A penalized biological age model using gene expression

IF 3.7 3区医学 Q2 GERIATRICS & GERONTOLOGY

Neurobiology of Aging

Pub Date : 2025-04-01 DOI: 10.1016/j.neurobiolaging.2025.01.012

Yijie (Jamie) Li , Rayus Kuplicki , Bart N. Ford , Elizabeth Kresock , Leandra Figueroa-Hall , Jonathan Savitz , Brett A. McKinney

Recent associations between Major Depressive Disorder (MDD) and measures of premature aging suggest accelerated biological aging as a potential biomarker for MDD susceptibility or MDD as a risk factor for age-related diseases. Residuals or “gaps” between the predicted biological age and chronological age have been used for statistical inference, such as testing whether an increased age gap is associated with a given disease state. Recently, a gene expression-based model of biological age showed a higher age gap for individuals with MDD compared to healthy controls (HC). In the current study, we propose an approach that simplifies gene selection using a least absolute shrinkage and selection operator (LASSO) penalty to construct an expression-based Gene Age Gap Estimate (GAGE) model. We train a LASSO gene age model on an RNA-Seq study of 78 unmedicated individuals with MDD and 79 HC, resulting in a model with 21 genes. The L-GAGE shows higher biological aging in MDD participants than HC, but the elevation is not statistically significant. However, when we dichotomize chronological age, the interaction between MDD status and age has a significant association with L-GAGE. This effect remains statistically significant even after adjusting for chronological age and sex. Using the 21 age genes, we find a statistically significant elevated biological age in MDD in an independent microarray gene expression dataset. We find functional enrichment of infectious disease and SARS-COV pathways using a broader feature selection of age related genes.

{"title":"Gene age gap estimate (GAGE) for major depressive disorder: A penalized biological age model using gene expression","authors":"Yijie (Jamie) Li , Rayus Kuplicki , Bart N. Ford , Elizabeth Kresock , Leandra Figueroa-Hall , Jonathan Savitz , Brett A. McKinney","doi":"10.1016/j.neurobiolaging.2025.01.012","DOIUrl":"10.1016/j.neurobiolaging.2025.01.012","url":null,"abstract":"<div><div>Recent associations between Major Depressive Disorder (MDD) and measures of premature aging suggest accelerated biological aging as a potential biomarker for MDD susceptibility or MDD as a risk factor for age-related diseases. Residuals or “gaps” between the predicted biological age and chronological age have been used for statistical inference, such as testing whether an increased age gap is associated with a given disease state. Recently, a gene expression-based model of biological age showed a higher age gap for individuals with MDD compared to healthy controls (HC). In the current study, we propose an approach that simplifies gene selection using a least absolute shrinkage and selection operator (LASSO) penalty to construct an expression-based Gene Age Gap Estimate (GAGE) model. We train a LASSO gene age model on an RNA-Seq study of 78 unmedicated individuals with MDD and 79 HC, resulting in a model with 21 genes. The L-GAGE shows higher biological aging in MDD participants than HC, but the elevation is not statistically significant. However, when we dichotomize chronological age, the interaction between MDD status and age has a significant association with L-GAGE. This effect remains statistically significant even after adjusting for chronological age and sex. Using the 21 age genes, we find a statistically significant elevated biological age in MDD in an independent microarray gene expression dataset. We find functional enrichment of infectious disease and SARS-COV pathways using a broader feature selection of age related genes.</div></div>","PeriodicalId":19110,"journal":{"name":"Neurobiology of Aging","volume":"151 ","pages":"Pages 13-21"},"PeriodicalIF":3.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143767827","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}

引用次数: 0

A more irregular shape of white matter hyperintensities is associated with cognitive decline over five years in community-dwelling older adults

IF 3.7 3区医学 Q2 GERIATRICS & GERONTOLOGY

Neurobiology of Aging

Pub Date : 2025-04-01 DOI: 10.1016/j.neurobiolaging.2025.03.011

Jasmin Annica Kuhn-Keller , Sigurdur Sigurdsson , Lenore J. Launer , Mark A. van Buchem , Matthias J.P. van Osch , Vilmundur Gudnason , Jeroen de Bresser

WMH shape is associated with long-term risk for dementia after 10 years in community-dwelling older adults. The current study aimed to investigate the association of WMH shape and decline in three cognitive domains over five years’ time in community-dwelling older adults. The association of baseline WMH shape (solidity, convexity, concavity index, fractal dimension, and eccentricity) and cognitive decline over 5.2 ± 0.3 years (domains: memory, executive function, and processing speed) was investigated using linear regression models in the Age, Gene/Environment Susceptibility-Reykjavik (AGES) study (n = 2493). A more irregular shape of periventricular/confluent WMH was related to cognitive decline in the memory domain, the executive function domain, and the processing speed domain over five years (p < 0.05). No associations were found between deep WMH shape and decline in the cognitive domains. These findings show that WMH shape patterns may be indicative of relatively short-term cognitive decline in community-dwelling older adults. This supports the evidence of WMH shape being a valuable marker that may be used to assess and predict cognitive outcome related to cerebrovascular disease progression.

{"title":"A more irregular shape of white matter hyperintensities is associated with cognitive decline over five years in community-dwelling older adults","authors":"Jasmin Annica Kuhn-Keller , Sigurdur Sigurdsson , Lenore J. Launer , Mark A. van Buchem , Matthias J.P. van Osch , Vilmundur Gudnason , Jeroen de Bresser","doi":"10.1016/j.neurobiolaging.2025.03.011","DOIUrl":"10.1016/j.neurobiolaging.2025.03.011","url":null,"abstract":"<div><div>WMH shape is associated with long-term risk for dementia after 10 years in community-dwelling older adults. The current study aimed to investigate the association of WMH shape and decline in three cognitive domains over five years’ time in community-dwelling older adults. The association of baseline WMH shape (solidity, convexity, concavity index, fractal dimension, and eccentricity) and cognitive decline over 5.2 ± 0.3 years (domains: memory, executive function, and processing speed) was investigated using linear regression models in the Age, Gene/Environment Susceptibility-Reykjavik (AGES) study (n = 2493). A more irregular shape of periventricular/confluent WMH was related to cognitive decline in the memory domain, the executive function domain, and the processing speed domain over five years (p < 0.05). No associations were found between deep WMH shape and decline in the cognitive domains. These findings show that WMH shape patterns may be indicative of relatively short-term cognitive decline in community-dwelling older adults. This supports the evidence of WMH shape being a valuable marker that may be used to assess and predict cognitive outcome related to cerebrovascular disease progression.</div></div>","PeriodicalId":19110,"journal":{"name":"Neurobiology of Aging","volume":"151 ","pages":"Pages 22-28"},"PeriodicalIF":3.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143785933","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}

引用次数: 0

Sex-specific decline in prefrontal cortex mitochondrial bioenergetics in aging baboons correlates with walking speed

IF 3.7 3区医学 Q2 GERIATRICS & GERONTOLOGY

Neurobiology of Aging

Pub Date : 2025-03-24 DOI: 10.1016/j.neurobiolaging.2025.03.010

Daniel A. Adekunbi , Hillary F. Huber , Gloria A. Benavides , Ran Tian , Cun Li , Peter W. Nathanielsz , Jianhua Zhang , Victor Darley-Usmar , Laura A. Cox , Adam B. Salmon

Mitochondria play a crucial role in brain homeostasis and changes in mitochondrial bioenergetics are linked to age-related neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease. We investigated changes in the activities of the electron transport chain (ETC) complexes in normally aging baboon brains and determined how these changes relate to donor sex, morning cortisol levels, and walking speed. We assessed mitochondrial bioenergetics from archived prefrontal cortex (PFC) tissues from a large cohort (60 individuals) of well-characterized aging baboons (6.6–22.8 years, approximately equivalent to 26.4–91.2 human years). Aging was associated with a decline in mitochondrial ETC complexes in the PFC, which was more pronounced when normalized for citrate synthase activity, suggesting that the decline is predominantly driven by changes in the specific activity of individual complexes rather than global changes in mitochondrial content. When donor sex was used as a covariate, we found that ETC activity was preserved with age in females and declined in males. Males had higher activities of each individual ETC complex and greater lactate dehydrogenase activity at a given age relative to females. Circulating cortisol negatively correlated with walking speed when male and female data were combined. We also observed a robust positive predictive relationship between walking speed and respiration linked to complexes I, III, and IV in males but not in females. This data reveals a link between frailty and PFC bioenergetic function and highlights a potential molecular mechanism for sexual dimorphism in brain resilience.

{"title":"Sex-specific decline in prefrontal cortex mitochondrial bioenergetics in aging baboons correlates with walking speed","authors":"Daniel A. Adekunbi , Hillary F. Huber , Gloria A. Benavides , Ran Tian , Cun Li , Peter W. Nathanielsz , Jianhua Zhang , Victor Darley-Usmar , Laura A. Cox , Adam B. Salmon","doi":"10.1016/j.neurobiolaging.2025.03.010","DOIUrl":"10.1016/j.neurobiolaging.2025.03.010","url":null,"abstract":"<div><div>Mitochondria play a crucial role in brain homeostasis and changes in mitochondrial bioenergetics are linked to age-related neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease. We investigated changes in the activities of the electron transport chain (ETC) complexes in normally aging baboon brains and determined how these changes relate to donor sex, morning cortisol levels, and walking speed. We assessed mitochondrial bioenergetics from archived prefrontal cortex (PFC) tissues from a large cohort (60 individuals) of well-characterized aging baboons (6.6–22.8 years, approximately equivalent to 26.4–91.2 human years). Aging was associated with a decline in mitochondrial ETC complexes in the PFC, which was more pronounced when normalized for citrate synthase activity, suggesting that the decline is predominantly driven by changes in the specific activity of individual complexes rather than global changes in mitochondrial content. When donor sex was used as a covariate, we found that ETC activity was preserved with age in females and declined in males. Males had higher activities of each individual ETC complex and greater lactate dehydrogenase activity at a given age relative to females. Circulating cortisol negatively correlated with walking speed when male and female data were combined. We also observed a robust positive predictive relationship between walking speed and respiration linked to complexes I, III, and IV in males but not in females. This data reveals a link between frailty and PFC bioenergetic function and highlights a potential molecular mechanism for sexual dimorphism in brain resilience.</div></div>","PeriodicalId":19110,"journal":{"name":"Neurobiology of Aging","volume":"151 ","pages":"Pages 1-12"},"PeriodicalIF":3.7,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143724866","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}

引用次数: 0

Long-term nucleus basalis cholinergic lesions alter the structure of cortical vasculature, astrocytic density and microglial activity in Wistar rats

IF 3.7 3区医学 Q2 GERIATRICS & GERONTOLOGY

Neurobiology of Aging

Pub Date : 2025-03-18 DOI: 10.1016/j.neurobiolaging.2025.03.006

Chiara Orciani , Morgan K. Foret , A. Claudio Cuello , Sonia Do Carmo

Basal forebrain cholinergic neurons (BFCNs) are the sole source of cholinergic innervation to the cerebral cortex and hippocampus in humans and the primary source in rodents. This system undergoes early degeneration in Alzheimer's disease. BFCNs terminal synapses are involved in the regulation of the cerebral blood flow by making classical synaptic contacts with other neurons. Additionally, they are located in proximity to cortical cerebral blood vessels, forming connections with various cell types of the neurovascular unit (NVU), including vascular smooth muscle cells, endothelial cells, and astrocytic end-feet. However, the effects of the BFCNs input on NVU components remain unresolved. To address this issue, we immunolesioned the nucleus basalis by administering bilateral stereotaxic injections of the cholinergic immunotoxin 192-IgG-Saporin in 2.5-month-old Wistar rats. Seven months post-lesion, we observed a significant reduction in cortical vesicular acetylcholine transporter-immunoreactive synapses. This was accompanied by changes in the diameter of cortical capillaries and precapillary arterioles, as well as lower levels of vascular endothelial growth factor A (VEGF-A). Additionally, the cholinergic immunolesion increased the density of cortical astrocytes and microglia in the cortex. At these post-BFCN-lesion stages, astrocytic end-feet exhibited an increased co-localization with arterioles. The number of microglia in the parietal cortex correlated with cholinergic loss and exhibited morphological changes indicative of an intermediate activation state. This was supported by decreased levels of proinflammatory mediators IFN-γ, IL-1β, and KC/GRO (CXCL1), and by increased expression of M2 markers SOCS3, IL4Rα, YM1, ARG1, and Fizz1. Our findings offer a novel insight: that the loss of nucleus basalis cholinergic input negatively impacts cortical blood vessels, NVU components, and microglia phenotype.

{"title":"Long-term nucleus basalis cholinergic lesions alter the structure of cortical vasculature, astrocytic density and microglial activity in Wistar rats","authors":"Chiara Orciani , Morgan K. Foret , A. Claudio Cuello , Sonia Do Carmo","doi":"10.1016/j.neurobiolaging.2025.03.006","DOIUrl":"10.1016/j.neurobiolaging.2025.03.006","url":null,"abstract":"<div><div>Basal forebrain cholinergic neurons (BFCNs) are the sole source of cholinergic innervation to the cerebral cortex and hippocampus in humans and the primary source in rodents. This system undergoes early degeneration in Alzheimer's disease. BFCNs terminal synapses are involved in the regulation of the cerebral blood flow by making classical synaptic contacts with other neurons. Additionally, they are located in proximity to cortical cerebral blood vessels, forming connections with various cell types of the neurovascular unit (NVU), including vascular smooth muscle cells, endothelial cells, and astrocytic end-feet. However, the effects of the BFCNs input on NVU components remain unresolved. To address this issue, we immunolesioned the nucleus basalis by administering bilateral stereotaxic injections of the cholinergic immunotoxin 192-IgG-Saporin in 2.5-month-old Wistar rats. Seven months post-lesion, we observed a significant reduction in cortical vesicular acetylcholine transporter-immunoreactive synapses. This was accompanied by changes in the diameter of cortical capillaries and precapillary arterioles, as well as lower levels of vascular endothelial growth factor A (VEGF-A). Additionally, the cholinergic immunolesion increased the density of cortical astrocytes and microglia in the cortex. At these post-BFCN-lesion stages, astrocytic end-feet exhibited an increased co-localization with arterioles. The number of microglia in the parietal cortex correlated with cholinergic loss and exhibited morphological changes indicative of an intermediate activation state. This was supported by decreased levels of proinflammatory mediators IFN-γ, IL-1β, and KC/GRO (CXCL1), and by increased expression of M2 markers SOCS3, IL4Rα, YM1, ARG1, and Fizz1. Our findings offer a novel insight: that the loss of nucleus basalis cholinergic input negatively impacts cortical blood vessels, NVU components, and microglia phenotype.</div></div>","PeriodicalId":19110,"journal":{"name":"Neurobiology of Aging","volume":"150 ","pages":"Pages 132-145"},"PeriodicalIF":3.7,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143679923","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}

引用次数: 0

Age-related differences in resting glutamate levels and glutamate uptake in the hippocampus and frontal cortex of C57BL/6 mice

IF 3.7 3区医学 Q2 GERIATRICS & GERONTOLOGY

Neurobiology of Aging

Pub Date : 2025-03-18 DOI: 10.1016/j.neurobiolaging.2025.03.008

Francois Pomerleau , Brittany A. Sulkowski , Cocanut Suhail , Jorge E. Quintero , O. Meagan. Littrell , M. Paul. Murphy , Peter Huettl , Greg A. Gerhardt

In normal aging, little is known in human and animal models about functional changes to glutamate neuronal systems that may contribute to age-related cognitive differences. The present studies investigated glutamate neuronal signaling in the hippocampus (dentate gyrus) and frontal cortex (infralimbic) of young adult (3–8 months), middle-aged (10–13 months), and aged (15–27 months) male and female C57BL/6 mice using microelectrode electrode array (MEA) recording technology to measure second-by-second resting levels of glutamate in anesthetized mice. Glutamate regulation was investigated in vivo by inhibiting the uptake of glutamate by local application of the competitive non-transportable blocker of excitatory amino acid transporters DL-threo-beta-benzyloxyaspartate (TBOA). Resting levels of glutamate and TBOA-induced changes in extracellular glutamate concentration were reliably measured in the hippocampus and frontal cortex of young adult, middle-aged, and aged mice and were seen to significantly increase in aging in the hippocampus. In the frontal cortex we observed an increase only in the middle-aged animals. TBOA produced robust changes in extracellular glutamate in the hippocampus and frontal cortex which showed significant changes in the kinetics of the signals in the middle-aged mice. Interestingly, the variance of the resting glutamate levels in the hippocampus of aged female mice was greater than in aged male mice, supporting a possible age-related gender difference in glutamate function. Taken together, these data support that glutamate signaling in the hippocampus and frontal cortex of aged mice is affected in normal aging with changes in glial regulation of glutamate uptake observed from the TBOA effects in the middle-aged mice.

{"title":"Age-related differences in resting glutamate levels and glutamate uptake in the hippocampus and frontal cortex of C57BL/6 mice","authors":"Francois Pomerleau , Brittany A. Sulkowski , Cocanut Suhail , Jorge E. Quintero , O. Meagan. Littrell , M. Paul. Murphy , Peter Huettl , Greg A. Gerhardt","doi":"10.1016/j.neurobiolaging.2025.03.008","DOIUrl":"10.1016/j.neurobiolaging.2025.03.008","url":null,"abstract":"<div><div>In normal aging, little is known in human and animal models about functional changes to glutamate neuronal systems that may contribute to age-related cognitive differences. The present studies investigated glutamate neuronal signaling in the hippocampus (dentate gyrus) and frontal cortex (infralimbic) of young adult (3–8 months), middle-aged (10–13 months), and aged (15–27 months) male and female C57BL/6 mice using microelectrode electrode array (MEA) recording technology to measure second-by-second resting levels of glutamate in anesthetized mice. Glutamate regulation was investigated <em>in vivo</em> by inhibiting the uptake of glutamate by local application of the competitive non-transportable blocker of excitatory amino acid transporters DL-threo-beta-benzyloxyaspartate (TBOA). Resting levels of glutamate and TBOA-induced changes in extracellular glutamate concentration were reliably measured in the hippocampus and frontal cortex of young adult, middle-aged, and aged mice and were seen to significantly increase in aging in the hippocampus. In the frontal cortex we observed an increase only in the middle-aged animals. TBOA produced robust changes in extracellular glutamate in the hippocampus and frontal cortex which showed significant changes in the kinetics of the signals in the middle-aged mice. Interestingly, the variance of the resting glutamate levels in the hippocampus of aged female mice was greater than in aged male mice, supporting a possible age-related gender difference in glutamate function. Taken together, these data support that glutamate signaling in the hippocampus and frontal cortex of aged mice is affected in normal aging with changes in glial regulation of glutamate uptake observed from the TBOA effects in the middle-aged mice.</div></div>","PeriodicalId":19110,"journal":{"name":"Neurobiology of Aging","volume":"150 ","pages":"Pages 146-156"},"PeriodicalIF":3.7,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143679924","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}

引用次数: 0

Chronic pain and its association with cognitive decline and brain function abnormalities in older adults: Insights from EEG and neuropsychological assessment

IF 3.7 3区医学 Q2 GERIATRICS & GERONTOLOGY

Neurobiology of Aging

Pub Date : 2025-03-18 DOI: 10.1016/j.neurobiolaging.2025.03.009

A.M. González-Roldán, M. Delgado-Bitata, A. Dorado, I. Costa da Silva, P. Montoya

Studies examining the interplay between chronic pain, cognitive function, and functional brain abnormalities in older adults are scarce. To address this gap, we administered a series of neuropsychological tests and recorded electroencephalography (EEG) data during resting-state conditions in 26 older adults with chronic pain (CPOA), 30 pain-free older adults (OA), and 31 younger adults (YA). CPOA demonstrated poorer performance compared to OA on the Stroop test, the Wisconsin Card Sorting Test (WCST) and Digit Span. Both groups of older adults exhibited higher beta activity compared to younger adults, with CPOA displaying particularly elevated beta-2 activity localized in the posterior cingulate cortex compared to OA. Correlational analyses indicated that in CPOA participants, heightened beta activity was linked to decreased performance on the WCST. Conversely, in OA, we observed a positive correlation between beta activity and performance on the WCST. Overall, our findings suggest that the cumulative impact of pain in aging would diminish the effectiveness of the functional compensatory mechanisms that occur during healthy aging, exacerbating cognitive decline.

{"title":"Chronic pain and its association with cognitive decline and brain function abnormalities in older adults: Insights from EEG and neuropsychological assessment","authors":"A.M. González-Roldán, M. Delgado-Bitata, A. Dorado, I. Costa da Silva, P. Montoya","doi":"10.1016/j.neurobiolaging.2025.03.009","DOIUrl":"10.1016/j.neurobiolaging.2025.03.009","url":null,"abstract":"<div><div>Studies examining the interplay between chronic pain, cognitive function, and functional brain abnormalities in older adults are scarce. To address this gap, we administered a series of neuropsychological tests and recorded electroencephalography (EEG) data during resting-state conditions in 26 older adults with chronic pain (CPOA), 30 pain-free older adults (OA), and 31 younger adults (YA). CPOA demonstrated poorer performance compared to OA on the Stroop test, the Wisconsin Card Sorting Test (WCST) and Digit Span. Both groups of older adults exhibited higher beta activity compared to younger adults, with CPOA displaying particularly elevated beta-2 activity localized in the posterior cingulate cortex compared to OA. Correlational analyses indicated that in CPOA participants, heightened beta activity was linked to decreased performance on the WCST. Conversely, in OA, we observed a positive correlation between beta activity and performance on the WCST. Overall, our findings suggest that the cumulative impact of pain in aging would diminish the effectiveness of the functional compensatory mechanisms that occur during healthy aging, exacerbating cognitive decline.</div></div>","PeriodicalId":19110,"journal":{"name":"Neurobiology of Aging","volume":"150 ","pages":"Pages 172-181"},"PeriodicalIF":3.7,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143697976","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}

引用次数: 0

BOLD amplitude correlates of preclinical Alzheimer’s disease

IF 3.7 3区医学 Q2 GERIATRICS & GERONTOLOGY

Neurobiology of Aging

Pub Date : 2025-03-17 DOI: 10.1016/j.neurobiolaging.2025.03.007

Stanislau Hrybouski , Sandhitsu R. Das , Long Xie , Christopher A. Brown , Melissa Flamporis , Jacqueline Lane , Ilya M. Nasrallah , John A. Detre , Paul A. Yushkevich , David A. Wolk

Alzheimer’s disease (AD) is characterized by a long preclinical stage during which molecular markers of amyloid beta and tau pathology rise, but there is minimal neurodegeneration or cognitive decline. Previous literature suggests that measures of brain function might be more sensitive to neuropathologic burden during the preclinical stage of AD than conventional measures of macrostructure, such as cortical thickness. Among studies that used resting-state functional Magnetic Resonance Imaging (fMRI) acquisitions with Blood Oxygenation Level Dependent (BOLD) contrast, most employed connectivity-based analytic approaches. Consequently, little is known about the effects of amyloid and tau pathology on amplitude of intrinsic BOLD signal fluctuations. To address this knowledge gap, we characterized the effects of preclinical and prodromal AD on the amplitude of low-frequency fluctuations (ALFF) of the BOLD signal both at the whole-brain level and at a more granular level focused on subregions of the medial temporal lobe. We observed reduced ALFF in both preclinical and prodromal AD. In preclinical AD, amyloid positivity was associated with a spatially diffuse ALFF reduction in the frontal, medial parietal, and lateral temporal association cortices. In contrast, tau pathology was negatively associated with ALFF in the entorhinal cortex. These ALFF effects were observed in the absence of observable macrostructural changes in preclinical AD and remained after adjusting for structural atrophy in prodromal AD, indicating that ALFF offers additional sensitivity to early disease processes beyond what is provided by traditional structural imaging biomarkers of neurodegeneration. We conclude that ALFF may be a promising imaging-based biomarker in preclinical AD.

{"title":"BOLD amplitude correlates of preclinical Alzheimer’s disease","authors":"Stanislau Hrybouski , Sandhitsu R. Das , Long Xie , Christopher A. Brown , Melissa Flamporis , Jacqueline Lane , Ilya M. Nasrallah , John A. Detre , Paul A. Yushkevich , David A. Wolk","doi":"10.1016/j.neurobiolaging.2025.03.007","DOIUrl":"10.1016/j.neurobiolaging.2025.03.007","url":null,"abstract":"<div><div>Alzheimer’s disease (AD) is characterized by a long preclinical stage during which molecular markers of amyloid beta and tau pathology rise, but there is minimal neurodegeneration or cognitive decline. Previous literature suggests that measures of brain function might be more sensitive to neuropathologic burden during the preclinical stage of AD than conventional measures of macrostructure, such as cortical thickness. Among studies that used resting-state functional Magnetic Resonance Imaging (fMRI) acquisitions with Blood Oxygenation Level Dependent (BOLD) contrast, most employed connectivity-based analytic approaches. Consequently, little is known about the effects of amyloid and tau pathology on amplitude of intrinsic BOLD signal fluctuations. To address this knowledge gap, we characterized the effects of preclinical and prodromal AD on the amplitude of low-frequency fluctuations (ALFF) of the BOLD signal both at the whole-brain level and at a more granular level focused on subregions of the medial temporal lobe. We observed reduced ALFF in both preclinical and prodromal AD. In preclinical AD, amyloid positivity was associated with a spatially diffuse ALFF reduction in the frontal, medial parietal, and lateral temporal association cortices. In contrast, tau pathology was negatively associated with ALFF in the entorhinal cortex. These ALFF effects were observed in the absence of observable macrostructural changes in preclinical AD and remained after adjusting for structural atrophy in prodromal AD, indicating that ALFF offers additional sensitivity to early disease processes beyond what is provided by traditional structural imaging biomarkers of neurodegeneration. We conclude that ALFF may be a promising imaging-based biomarker in preclinical AD.</div></div>","PeriodicalId":19110,"journal":{"name":"Neurobiology of Aging","volume":"150 ","pages":"Pages 157-171"},"PeriodicalIF":3.7,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143697975","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}

引用次数: 0

Age-related differences in locus coeruleus intensity across a demographically diverse sample

IF 3.7 3区医学 Q2 GERIATRICS & GERONTOLOGY

Neurobiology of Aging

Pub Date : 2025-03-13 DOI: 10.1016/j.neurobiolaging.2025.03.005

Elizabeth Riley, Nicholas Cicero, Senegal Alfred Mabry, Khena M Swallow, Adam K Anderson, Eve De Rosa

Understanding the trajectory of in vivo locus coeruleus (LC) signal intensity across the adult lifespan and among various demographic groups, particularly during middle age, may be crucial for early detection of neurodegenerative diseases, which begin in the LC decades before symptom onset. Even though pathological changes in the LC are thought to begin in middle age, its characteristics across the adult lifespan, and its consistency and variation across demographic groups, remain not well understood. Using T1-weighted turbo spin echo magnetic resonance (MRI) scans to characterize the LC, we measured LC signal intensity in 134 participants aged 19–86 years, with an effort to recruit a more racially diverse sample (41 % non-White). LC signal intensity was lowest in early adulthood, peaked around age 60, and then decreased again in the oldest adults, particularly in the caudal portion of the LC, which exhibited the greatest overall signal intensity; education, income, and history of early trauma did not alter this general pattern. Rostral LC signal intensity was further heightened in women and Black participants. In higher-performing older adults, increased rostral LC signal intensity was positively associated with higher fluid cognition. The potential accumulation of LC signal intensity across the adult lifespan and its possible dissipation in later life as well as its modification by demographic factors, may be associated with differential susceptibility to neurocognitive aging.

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Editorial Advisory Board

IF 3.7 3区医学 Q2 GERIATRICS & GERONTOLOGY

Neurobiology of Aging

Pub Date : 2025-03-11 DOI: 10.1016/S0197-4580(25)00046-6

引用次数: 0

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