Foyzul Rahman , Kamen A. Tsvetanov , Jack Feron , Karen Mullinger , Kelsey Joyce , Ahmed Gilani , Eunice G. Fernandes , Allison Wetterlin , Linda Wheeldon , Samuel J.E. Lucas , Katrien Segaert
{"title":"Explaining tip-of-the-tongue experiences in older adults: The role of brain-based and cardiorespiratory fitness factors","authors":"Foyzul Rahman , Kamen A. Tsvetanov , Jack Feron , Karen Mullinger , Kelsey Joyce , Ahmed Gilani , Eunice G. Fernandes , Allison Wetterlin , Linda Wheeldon , Samuel J.E. Lucas , Katrien Segaert","doi":"10.1016/j.neurobiolaging.2025.06.008","DOIUrl":"10.1016/j.neurobiolaging.2025.06.008","url":null,"abstract":"<div><div>Cognitive decline associated with healthy ageing is multifactorial: brain-based and lifestyle factors uniquely and jointly contribute to distinct neurocognitive trajectories of ageing. To evaluate existing models of neurocognitive ageing such as compensation, maintenance, or reserve, we explore how various known brain-based and cardiorespiratory fitness factors intersect to better understand cognitive decline. In a pre-registered study (<span><span>https://osf.io/6fqg7</span><svg><path></path></svg></span>), we tested 73 healthy older adults aged 60—81 (<em>M</em> = 65.51, <em>SD</em> = 4.94) and collected neuroimaging (functional, structural, and perfusion MRI), cardiorespiratory fitness, and cognitive data to investigate a prominent challenge for older adults: word-finding failures. fMRI signal was recorded while participants responded to a definition-based tip-of-the-tongue task, T1-weighted imaging estimated grey matter volume, and cerebral blood flow was indexed using multi-delay pseudo-continuous arterial spin labelling. Commonality analyses were used to analyse these multi-domain data (neuroimaging, cardiorespiratory fitness, language skills, demographic characteristics) and uncover associations between predictors in explaining age-related tip-of-the-tongue rates. Commonality analyses revealed that functional activation of language networks associated with tip-of-the-tongue states is in part linked with age and, interestingly, cardiorespiratory fitness: the combination of higher cardiorespiratory fitness and functional recruitment in some older adults offsets part of the age-related variance in tip-of-the-tongues. Moreover, age-associated atrophy and perfusion in regions other than those showing functional differences accounted for variance in tip-of-the-tongues. Our findings can be interpreted in the context of the classic models of neurocognitive ageing, suggesting compensation. Brain health indices in concordance with cardiorespiratory fitness can provide a more holistic explanation of individual differences in age-related cognitive decline.</div></div>","PeriodicalId":19110,"journal":{"name":"Neurobiology of Aging","volume":"154 ","pages":"Pages 25-36"},"PeriodicalIF":3.7,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144502415","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}
Ummatul Siddique , Ashlyn K. Frazer , Jamie Tallent , Oliver Hayman , Justin Andrushko , Juha P. Ahtiainen , Janne Avela , Yonas Akalu , Mohamad Rostami , Sergio Uribe , Simon Walker , Dawson J. Kidgell
{"title":"Acute corticospinal and reticulospinal responses to strength training in ageing","authors":"Ummatul Siddique , Ashlyn K. Frazer , Jamie Tallent , Oliver Hayman , Justin Andrushko , Juha P. Ahtiainen , Janne Avela , Yonas Akalu , Mohamad Rostami , Sergio Uribe , Simon Walker , Dawson J. Kidgell","doi":"10.1016/j.neurobiolaging.2025.06.007","DOIUrl":"10.1016/j.neurobiolaging.2025.06.007","url":null,"abstract":"<div><div>Ageing is associated with declines in neuromuscular function, yet the neural mechanisms underlying strength adaptations in older adults remain unclear. While the corticospinal tract (CST) is the primary pathway for voluntary movement, the reticulospinal tract (RST) may play a compensatory role with age. This study investigated CST and RST responses following a single session of high-intensity metronome-paced strength training (MPST) in young and older adults. Thirty-five participants (17 young, 18 older) performed unilateral biceps curls at 70–75 % of their one-repetition maximum (1-RM). Cortical and subcortical excitability were assessed pre- and post-exercise using transcranial magnetic stimulation (TMS) and the StartReact paradigm. Young adults showed significant increases in corticospinal excitability (CSE; p < 0.05) and early-phase motor evoked potentials (MEPs) following exercise, whereas no changes were observed in older adults. Both groups exhibited reductions in silent period duration (SP; p < 0.01) and short-interval intracortical inhibition (SICI; p < 0.05), suggesting a general release of inhibition. However, no significant changes in reaction time or evidence of enhanced RST drive were observed in either group. These findings highlight age-related differences in the modulation of descending pathways, with older adults showing reduced CSE plasticity following acute MPST, possibly reflecting delayed potentiation due to ageing. Although MPST effectively reduced inhibition, it may be insufficient to engage the RST in older adults. Future research should explore alternative training modalities that more directly target subcortical circuits to optimise functional outcomes in ageing populations.</div></div>","PeriodicalId":19110,"journal":{"name":"Neurobiology of Aging","volume":"153 ","pages":"Pages 49-62"},"PeriodicalIF":3.7,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144492005","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}
Mohammad Akradi , Tara Farzane-Daghigh , Amir Ebneabbasi , Hanwen Bi , Alexander Drzezga , Bryce A. Mander , Simon B. Eickhoff , Masoud Tahmasian , for the Alzheimer’s Disease Neuroimaging Initiative
{"title":"How is self-reported sleep-disordered breathing linked with biomarkers of Alzheimer’s disease?","authors":"Mohammad Akradi , Tara Farzane-Daghigh , Amir Ebneabbasi , Hanwen Bi , Alexander Drzezga , Bryce A. Mander , Simon B. Eickhoff , Masoud Tahmasian , for the Alzheimer’s Disease Neuroimaging Initiative","doi":"10.1016/j.neurobiolaging.2025.06.006","DOIUrl":"10.1016/j.neurobiolaging.2025.06.006","url":null,"abstract":"<div><div>Sleep-disordered breathing (SDB) is prevalent in Alzheimer’s disease (AD). Here, we assessed how self-reported SDB is linked with AD biomarkers, including amyloid-beta plaque burden (Aβ), regional fluorodeoxyglucose uptake (rFDG-PET), grey matter volume (GMV), cognitive scores, and cerebrospinal fluid (CSF) biomarkers. We selected 757 individuals, including AD, mild cognitive impairment (MCI), and cognitively unimpaired (CU) groups, and divided them according to self-reported SDB condition. Using a stratified subsampling approach, we selected 512 matched subsamples, and effect sizes (ES) of the group-SDB interaction were computed for each biomarker and cognitive score across subsamples. Linear regression assessed associations between the ES of Aβ, rFDG, and GMV with the ES of cognitive scores and CSF biomarkers. The group-SDB interaction had a medium-sized effect on Aβ, rFDG, and GMV biomarkers in several brain areas. Participants with SDB exhibited reduced Aβ burden and increased rFDG uptake in the CU and MCI groups, whereas the AD group showed elevated Aβ burden and decreased rFDG. Additionally, SDB+ individuals demonstrated GMV alterations across all groups. The ES of group-SDB interaction on Aβ in the precuneus, middle temporal gyrus, and fusiform gyrus was associated with the ES of cognitive scores. Taken together, we observed a robust association of SDB with Aβ pathology in PET and CSF relative to rFDG and GMV in the AD group, which was also associated with cognitive decline.</div></div>","PeriodicalId":19110,"journal":{"name":"Neurobiology of Aging","volume":"154 ","pages":"Pages 16-24"},"PeriodicalIF":3.7,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144502413","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}
Alison R. Weiss , Anahit Grigorian , Steven Dash , Christopher D. Kroenke , Henryk F. Urbanski , Steven G. Kohama
{"title":"Age-related differences in cerebral morphology and microstructure in rhesus macaques","authors":"Alison R. Weiss , Anahit Grigorian , Steven Dash , Christopher D. Kroenke , Henryk F. Urbanski , Steven G. Kohama","doi":"10.1016/j.neurobiolaging.2025.06.004","DOIUrl":"10.1016/j.neurobiolaging.2025.06.004","url":null,"abstract":"<div><div>The rhesus macaque presents a promising model for translational research into human brain aging due to this species’ long lifespan and close phylogenic relationship. We conducted a cross-sectional study identifying microstructural and morphological biomarkers of aging in a cohort of 37 healthy animals (18F/19M, aged 5–28 years), using high-resolution T2-weighted (T2w) and diffusion-weighted (DW) images. Using Tensor Based Morphometry, significant age-associated regional brain atrophy was observed in some areas of the frontal and parietal cortex, as well as the striatum. Additionally, age-associated differences in white matter diffusion were observed in several brain regions, including frontal and temporal white matter areas, and regions of the internal capsule and corpus callosum. Taken together, the results demonstrate that morphological and microstructural age-related differences can be disclosed in cortical, striatal, and thalamic regions, as well as in the white matter fiber pathways connecting these areas, using high-resolution DTI and MRI.</div></div>","PeriodicalId":19110,"journal":{"name":"Neurobiology of Aging","volume":"154 ","pages":"Pages 37-46"},"PeriodicalIF":3.7,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144502414","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}
Marianne de Chastelaine , Sabina Srokova , Sarah Monier , Joshua M. Olivier , Michael D. Rugg
{"title":"Effects of age on the strategic control of recollected content as reflected by modulation of neural correlates of scene retrieval","authors":"Marianne de Chastelaine , Sabina Srokova , Sarah Monier , Joshua M. Olivier , Michael D. Rugg","doi":"10.1016/j.neurobiolaging.2025.06.005","DOIUrl":"10.1016/j.neurobiolaging.2025.06.005","url":null,"abstract":"<div><div>A previous study employing fMRI measures of retrieval-related neural selectivity reported that young, but not older, adults employ ‘retrieval gating’ to attenuate aspects of an episodic memory that are irrelevant to the retrieval goal. We examined whether the weak memories of the older adults in that study rendered goal-irrelevant memories insufficiently intrusive to motivate retrieval gating. Young and older participants studied words superimposed on rural or urban scenes, or on scrambled backgrounds. To strengthen memory for background information, word-image pairs were studied twice, initially centrally, and then in one of three locations. During scanning, one retrieval test probed memory for the test words’ studied backgrounds and another test assessed memory for their location. Background memory performance was markedly higher than in the prior study. Retrieval gating was examined in two scene-selective regions of interest, the parahippocampal place area (PPA) and the medial place area (MPA). In the background task, robust scene-specific retrieval effects were identified in both age groups in both ROIs. These effects were attenuated (‘gated’) in the location task in the young age group only, replicating the prior finding. The results did not differ when the two groups were sub-sampled to match strength of scene-specific retrieval effects when scene information was goal relevant. The findings indicate that older adults’ failure to gate goal-irrelevant scene information does not reflect age differences in memory strength and may instead reflect an age-related decline in top-down inhibitory control.</div></div>","PeriodicalId":19110,"journal":{"name":"Neurobiology of Aging","volume":"154 ","pages":"Pages 1-15"},"PeriodicalIF":3.7,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144502408","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}
Alexa Wawrzyniak , Justine Busby , Alice Dalo , Syllissa Duncan , Laila S. Almassri , Dakota Z. Smallridge , Andrew P. Ohl , Amir M. Mafi , Nick J. Tokar , Jesse W. Young , Jeffrey G. Mellott
{"title":"Age-related differences in GABAergic synapses across the central inferior colliculus in the Fischer Brown Norway rat","authors":"Alexa Wawrzyniak , Justine Busby , Alice Dalo , Syllissa Duncan , Laila S. Almassri , Dakota Z. Smallridge , Andrew P. Ohl , Amir M. Mafi , Nick J. Tokar , Jesse W. Young , Jeffrey G. Mellott","doi":"10.1016/j.neurobiolaging.2025.06.002","DOIUrl":"10.1016/j.neurobiolaging.2025.06.002","url":null,"abstract":"<div><div>Presbycusis, one of the most widespread disorders, is in part associated with the loss of temporal precision within the central auditory system. A contributor to the dysfunctional temporal precision during aging is the substantial downregulation of GABA in the central inferior colliculus (ICc), the hub of ascending and descending inputs of the auditory midbrain. However, how GABAergic inputs across the tonotopic axis of the ICc change with age has not been well explored. We sought to determine age-related changes to GABAergic synapses in the lemniscal ICc, and if changes are uniform across the ICc axis. Using immuno-electron microscopy across four age groups of Fisher Brown Norway rats, a model that acquires low frequency presbycusis, our results demonstrate several nonuniform ultrastructural changes to GABAergic synapses in the ICc. There was a significant (∼29–33 %) downregulation of GABAergic synapses in the high and middle frequency regions of old rats, but a loss (∼22 %) in the old low frequency region was not as robust and did not reach statistical significance. Interestingly, in the high and middle frequency regions, GABAergic presynaptic area increased with age, while there was an ultimately decline in the old low frequency region. Also unique to the high and middle frequencies was the increasing proportion of GABAergic synapses onto larger GABAergic dendrites. These changes demonstrate that aging differentially affects the GABAergic ultrastructure of the ICc tonotopic axis.</div></div>","PeriodicalId":19110,"journal":{"name":"Neurobiology of Aging","volume":"153 ","pages":"Pages 30-48"},"PeriodicalIF":3.7,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144263129","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}
Lasya P. Sreepada , Christopher A. Brown , Sandhitsu R. Das , Paul A. Yushkevich , David A. Wolk , Corey T. McMillan , on behalf of the Alzheimer’s Disease Neuroimaging Initiative
{"title":"Biological age acceleration in Alzheimer’s disease modulates relative cortical to medial temporal lobe neurodegeneration","authors":"Lasya P. Sreepada , Christopher A. Brown , Sandhitsu R. Das , Paul A. Yushkevich , David A. Wolk , Corey T. McMillan , on behalf of the Alzheimer’s Disease Neuroimaging Initiative","doi":"10.1016/j.neurobiolaging.2025.06.003","DOIUrl":"10.1016/j.neurobiolaging.2025.06.003","url":null,"abstract":"<div><div>Alzheimer’s disease (AD) is highly associated with aging, typically presenting with amnestic, multi-domain cognitive impairment and greater medial temporal lobe (MTL) atrophy relative to cortex. However, approximately 15 % of AD cases present atypically, often at younger ages and with greater cortical involvement relative to MTL. This association between age and AD presentation is imperfect: some younger-onset cases are typical, amnestic presentations while some older-onset cases present less typically. We hypothesize that this discordance may be partially modulated by discordance between chronological age and biological age, defined epigenetically. Participants from the Alzheimer’s Disease Neuroimaging Initiative with MRI and known amyloid status were selected (<em>n</em> = 1011, 44.4 % female, 75.33 ± 7.28 years) and classified as amyloid-negative, cognitively unimpaired (<em>n</em> = 329) or amyloid-positive, symptomatic individuals with mild cognitive impairment or dementia (<em>n</em> = 682). Biological age was estimated in individuals with DNA methylation (<em>n</em> = 448) using established epigenetic clocks. Biological age gap (BAG) was calculated to categorize individuals into “accelerated” (biological age > chronological age) or “decelerated” (biological age < chronological age) groups. We define the Cortico-Medial Temporal index (CoMeT), derived from MRI, to quantify age-adjusted relative differences between cortical and MTL structures. Lower CoMeT scores indicate relatively greater cortical involvement. BAG and CoMeT were significantly correlated (Pearson <em>R</em>=0.13, <em>p</em> = 0.023). Symptomatic individuals with decelerated BAG exhibited significantly lower CoMeT scores than individuals with accelerated BAG, with a large effect size, reflecting greater cortical involvement relative to MTL (Wilcoxon <em>p</em> = 0.023, rank-biserial correlation=−0.98). We conclude that biological aging modulates AD presentation beyond chronological age, providing novel insights into mechanisms underlying AD heterogeneity.</div></div>","PeriodicalId":19110,"journal":{"name":"Neurobiology of Aging","volume":"153 ","pages":"Pages 21-29"},"PeriodicalIF":3.7,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144254247","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}
{"title":"Age-related differences in the impact of background noise on neural speech tracking","authors":"Björn Herrmann","doi":"10.1016/j.neurobiolaging.2025.06.001","DOIUrl":"10.1016/j.neurobiolaging.2025.06.001","url":null,"abstract":"<div><div>Tracking the envelope of speech in the brain is important for speech comprehension. Recent research suggests that acoustic background noise can enhance neural speech tracking, enabling the auditory system to robustly encode speech even under unfavorable conditions. Aging and hearing loss are associated with internal, neural noise in the auditory system, raising the question whether additional acoustic background noise enhances neural speech tracking in older adults. In the current electroencephalography study, younger (∼25.5 years) and older adults (∼68.5 years) listened to spoken stories in quiet (clear) or in the presence of background noise at a wide range of different signal-to-noise ratios. In younger adults, early neural speech tracking responses (<0.15 s) were enhanced by minimal background noise, indicating response facilitation through noise. In contrast, older adults, compared to younger adults, showed enhanced neural speech tracking for clear speech and speech masked by minimal background noise, but the acoustic noise led to little enhancement of the early neural tracking response in older people. The data demonstrate different sensitivity of the auditory cortex to speech masked by noise between younger and older adults. The results are consistent with the idea that the auditory cortex of older people exhibits more internal, neural noise that enhances neural speech tracking but that additional acoustic noise does not further support speech encoding. The work points to a highly non-linear auditory system that differs between younger and older adults.</div></div>","PeriodicalId":19110,"journal":{"name":"Neurobiology of Aging","volume":"153 ","pages":"Pages 10-20"},"PeriodicalIF":3.7,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144212768","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}
David Villarroel-Campos , Elena R. Rhymes , Andrew P. Tosolini , Bilal Malik , Alessio Vagnoni , Giampietro Schiavo , James N. Sleigh
{"title":"Processivity and BDNF-dependent modulation of signalling endosome axonal transport are impaired in mice with advanced age","authors":"David Villarroel-Campos , Elena R. Rhymes , Andrew P. Tosolini , Bilal Malik , Alessio Vagnoni , Giampietro Schiavo , James N. Sleigh","doi":"10.1016/j.neurobiolaging.2025.05.002","DOIUrl":"10.1016/j.neurobiolaging.2025.05.002","url":null,"abstract":"<div><div>A healthy nervous system is reliant upon an efficient transport network to deliver essential cargoes throughout the extensive and polarised architecture of neurons. The trafficking of cargoes, such as organelles and proteins, is particularly challenging within the long projections of neurons, which, in the case of axons, can be more than four orders of magnitude longer than cell bodies. It is therefore unsurprising that disruptions in axonal transport have been reported across neurological diseases. A decline in this essential process has also been identified in many aging models, perhaps compounding age-related neurodegeneration. Via intravital imaging, we recently determined that, despite a reduction in overall motility, the run speed and displacement of anterograde mitochondrial transport were unexpectedly enhanced in 19–22 month-old mouse peripheral nerves. Here, to determine how aging impacts a different axonal cargo, we evaluated <em>in vivo</em> trafficking of signalling endosomes in motor axons of mouse sciatic nerves from 3 to 22 months. Contrasting with mitochondria, we did not detect alterations in signalling endosome speed, but found a consistent rise in pausing that manifested after 18 months. We then treated muscles with brain-derived neurotrophic factor (BDNF), which regulates axonal transport of signalling endosomes in motor neurons; however, we observed no change in the processivity defect at 22 months, consistent with downregulation of the BDNF receptor TrkB at the neuromuscular junction. Together, these findings indicate that aging negatively impacts signalling endosome trafficking in motor axons, likely through dampened BDNF signalling at the motor neuron-muscle interface.</div></div>","PeriodicalId":19110,"journal":{"name":"Neurobiology of Aging","volume":"153 ","pages":"Pages 1-9"},"PeriodicalIF":3.7,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144178635","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}