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Defective brain glucose utilization is a hallmark of Alzheimer’s disease (AD) while Type II diabetes and elevated blood glucose escalate the risk for AD in later life. Isolating contributions of normal aging from coincident metabolic or brain diseases could lead to refined approaches to manage specific health risks and optimize treatments targeted to susceptible older individuals. We evaluated metabolic, neuroendocrine, and neurobiological differences between young adult (6 months) and aged (24 months) male rats. Compared to young adults, blood glucose was significantly greater in aged rats at the start of the dark phase of the day but not during the light phase. When challenged with physical restraint, a potent stressor, aged rats effected no change in blood glucose whereas blood glucose increased in young adults. Tissues were evaluated for markers of oxidative phosphorylation (OXPHOS), neuronal glucose transport, and synapses. Outright differences in protein levels between age groups were not evident, but circadian blood glucose was inversely related to OXPHOS proteins in hippocampal synaptosomes, independent of age. The neuronal glucose transporter, GLUT3, was positively associated with circadian blood glucose in young adults whereas aged rats tended to show the opposite trend. Our data demonstrate aging increases daily fluctuations in blood glucose and, at the level of individual differences, negatively associates with proteins related to synaptic OXPHOS. Our findings imply that glucose dyshomeostasis may exacerbate metabolic aspects of synaptic dysfunction that contribute to risk for age-related brain disorders.

Although gray matter atrophy is commonly observed with aging, it is highly variable, even among healthy people of the same age. This raises the question of what other factors may contribute to gray matter atrophy. Previous studies have reported that risk factors for cardiometabolic diseases are associated with accelerated brain aging. However, these studies were primarily based on standard correlation analyses, which do not unveil a causal relationship. While randomized controlled trials are typically required to investigate true causality, in this work, we investigated an alternative method by exploring data-driven causal discovery and inference techniques on observational data. Accordingly, this feasibility study used clinical and quantified gray matter volume data from 22,793 subjects from the UK biobank cohort without any known neurological disease. Our method identified that age, sex, body mass index (BMI), body fat percentage (BFP), and smoking exhibit a causal relationship with gray matter volume. Interventions on the causal network revealed that higher BMI and BFP values significantly increased the chance of gray matter atrophy in males, whereas this was not the case in females.

The effects of normal aging on functional connectivity (FC) within various brain networks of gray matter (GM) have been well-documented. However, the age effects on the networks of FC between white matter (WM) and GM, namely WM-GM FC, remains unclear. Evaluating crucial properties, such as global efficiency (GE), for a WM-GM FC network poses a challenge due to the absence of closed triangle paths which are essential for assessing network properties in traditional graph models. In this study, we propose a bipartite graph model to characterize the WM-GM FC network and quantify these challenging network properties. Leveraging this model, we assessed the WM-GM FC network properties at multiple scales across 1,462 cognitively normal subjects aged 22–96 years from three repositories (ADNI, BLSA and OASIS-3) and investigated the age effects on these properties throughout adulthood and during late adulthood (age ≥70 years). Our findings reveal that (1) heterogeneous alterations occurred in region-specific WM-GM FC over the adulthood and decline predominated during late adulthood; (2) the FC density of WM bundles engaged in memory, executive function and processing speed declined with age over adulthood, particularly in later years; and (3) the GE of attention, default, somatomotor, frontoparietal and limbic networks reduced with age over adulthood, and GE of visual network declined during late adulthood. These findings provide unpresented insights into multi-scale alterations in networks of WM-GM functional synchronizations during normal aging. Furthermore, our bipartite graph model offers an extendable framework for quantifying WM-engaged networks, which may contribute to a wide range of neuroscience research.

Purpose: We evaluate the impact of test target location in assessing rod-mediated dark adaptation (RMDA) along the transition from normal aging to intermediate age-related macular degeneration (AMD). We consider whether RMDA slows because the test locations are near mechanisms leading to or resulting from high-risk extracellular deposits. Soft drusen cluster under the fovea and extend to the inner ring of the ETDRS grid where rods are sparse. Subretinal drusenoid deposits (SDDs) appear first in the outer superior subfield of the ETDRS grid where rod photoreceptors are maximal and spread toward the fovea without covering it. Design: Cross-sectional. Participants: Adults ≥ 60 years with normal older maculas, early AMD, or intermediate AMD as defined by the Age-Related Eye Disease Study (AREDS) 9-step and Beckman grading systems. Methods: In 1 eye per participant, RMDA was assessed at 5° and at 12° in the superior retina. Subretinal drusenoid deposit presence was identified with multi-modal imaging. Main Outcome Measures: Rod intercept time (RIT) as a measure of RMDA rate at 5° and 12°. Results: In 438 eyes of 438 persons, RIT was significantly longer (i.e., RMDA is slower) at 5° than at 12° for each AMD severity group. Differences among groups were bigger at 5° than at 12°. At 5°, SDD presence was associated with longer RIT as compared to SDD absence at early and intermediate AMD but not in normal eyes. At 12°, SDD presence was associated with longer RIT in intermediate AMD only, and not in normal or early AMD eyes. Findings were similar in eyes stratified by AREDS 9-step and Beckman systems. Conclusions: We probed RMDA in relation to current models of deposit-driven AMD progression organized around photoreceptor topography. In eyes with SDD, slowed RMDA occurs at 5° where these deposits typically do not appear until later in AMD. Even in eyes lacking detectable SDD, RMDA at 5° is slower than at 12°. The effect at 5° may be attributed to mechanisms associated with the accumulation of soft drusen and precursors under the macula lutea throughout adulthood. These data will facilitate the design of efficient clinical trials for interventions that aim to delay AMD progression. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.

Diffusion tensor magnetic resonance imaging (DTI) is a widely adopted neuroimaging method for the in vivo mapping of brain tissue microstructure and white matter tracts. Nonetheless, the noise in the diffusion-weighted images (DWIs) decreases the accuracy and precision of DTI derived microstructural parameters and leads to prolonged acquisition time for achieving improved signal-to-noise ratio (SNR). Deep learning-based image denoising using convolutional neural networks (CNNs) has superior performance but often requires additional high-SNR data for supervising the training of CNNs, which reduces the feasibility of supervised learning-based denoising in practice. In this work, we develop a self-supervised deep learning-based method entitled “SDnDTI” for denoising DTI data, which does not require additional high-SNR data for training. Specifically, SDnDTI divides multi-directional DTI data into many subsets of six DWI volumes and transforms DWIs from each subset to along the same diffusion-encoding directions through the diffusion tensor model, generating multiple repetitions of DWIs with identical image contrasts but different noise observations. SDnDTI removes noise by first denoising each repetition of DWIs using a deep 3-dimensional CNN with the average of all repetitions with higher SNR as the training target, following the same approach as normal supervised learning based denoising methods, and then averaging CNN-denoised images for achieving higher SNR. The denoising efficacy of SDnDTI is demonstrated in terms of the similarity of output images and resultant DTI metrics compared to the ground truth generated using substantially more DWI volumes on two datasets with different spatial resolutions, b-values and numbers of input DWI volumes provided by the Human Connectome Project (HCP) and the Lifespan HCP in Aging. The SDnDTI results preserve image sharpness and textural details and substantially improve upon those from the raw data. The results of SDnDTI are comparable to those from supervised learning-based denoising and outperform those from state-of-the-art conventional denoising algorithms including BM4D, AONLM and MPPCA. By leveraging domain knowledge of diffusion MRI physics, SDnDTI makes it easier to use CNN-based denoising methods in practice and has the potential to benefit a wider range of research and clinical applications that require accelerated DTI acquisition and high-quality DTI data for mapping of tissue microstructure, fiber tracts and structural connectivity in the living human brain.

The hippocampus is a small but complex grey matter structure that plays an important role in spatial and episodic memory and can be affected by a wide range of pathologies including vascular abnormalities. In this work, we introduce the use of Ferumoxytol, an ultra-small superparamagnetic iron oxide (USPIO) agent, to induce susceptibility in the arteries (as well as increase the susceptibility in the veins) to map the hippocampal micro-vasculature and to evaluate the quantitative change in tissue fractional vascular density (FVD), in each of its subfields. A total of 39 healthy subjects (aged 35.4 ± 14.2 years, from 18 to 81 years old) were scanned with a high-resolution (0.22×0.44×1 mm3) dual-echo SWI sequence acquired at four time points during a gradual increase in Ferumoxytol dose (final dose = 4 mg/kg). The volumes of each subfield were obtained automatically from the pre-contrast T1-weighted data. The dynamically acquired SWI data were co-registered and adaptively combined to reduce the blooming artifacts from large vessels, preserving the contrast from smaller vessels. The resultant SWI data were used to segment the hippocampal vasculature and to measure the FVD ((volume occupied by vessels)/(total volume)) for each subfield. The hippocampal fissure, along with the fimbria, granular cell layer of the dentate gyrus and cornu ammonis layers (except for CA1), showed higher micro-vascular FVD than the other parts of hippocampus. The CA1 region exhibited a significant correlation with age (R = −0.37, p 0.05) of the CA1 subfield, which would suggest that vascular degeneration may precede tissue atrophy.

We provide functional connectivity matrices generated during functional magnetic resonance imaging (fMRI) during different tasks of cognitive control in healthy aging adults. These data can be used to replicate the primary results from the related manuscript: Reconfiguration and dedifferentiation of functional networks during cognitive control across the adult lifespan (Rieck et al., 2021). One-hundred-forty-four participants (ages 20–86) were scanned on a Siemens 3T MRI scanner while they were completing tasks to measure functional activity during inhibition, initiation, shifting, and working memory. Estimates of functional connectivity (quantified with timeseries correlations) between different brain regions were computed using three different brain atlases: Schaefer 100 parcel 17 network atlas (Schaefer et al., 2018; Yeo et al., 2011), Power 229 node 10 network atlas (Power et al., 2011), and Schaefer 200 parcel 17 network atlas (Schaefer et al., 2018; Yeo et al., 2011). The resulting functional connectivity correlation matrices are provided as text files with this article. Cov-STATIS (Abdi et al., 2012; a multi-table multivariate statistical technique; https://github.com/HerveAbdi/DistatisR) was used to examine similarity between functional connectivity during the different domains of cognitive control. The effect of aging on these functional connectivity patterns was also examined by computing measures of “task differentiation” and “network segregation.” This dataset also provides supplemental analyses from the related manuscript (Rieck et al., 2021) to replicate the primary age findings with additional brain atlases. Cognitive neuroscience researchers can benefit from these data by further investigating the age effects on functional connectivity during tasks of cognitive control, in addition to examining the impact of different brain atlases on functional connectivity estimates. These data can also be used for the development of other multi-table and network-based statistical methods in functional neuroimaging.

An 11–25% increase in total ventricular volume has been documented in astronauts following spaceflight on the ISS. Given the approximately 2-year time interval between pre- and post-flight MRI, it is unknown if ventricular enlargement simply reflects normal aging or is unique to spaceflight exposure. Therefore, we compared percent ventricular volume change per year (PVVC/yr) documented on pre- to post-flight MRI in a group of NASA ISS astronauts (n = 18, 16.7% women, mean age (SD) 48.43 (4.35) years) with two groups who underwent longitudinal MRI: (1.) healthy age- and sex-matched adults (n = 18, 16.7% women, mean age (SD) 51.26 (3.88) years), and (2.) healthy older adults (n = 79, 16.5% women, mean age (SD) 73.26 (5.34) years). The astronauts, who underwent a mean (SD) 173.4 (51.3) days in spaceflight, showed a greater increase in PVVC/yr than the control (6.86 vs 2.23%, respectively, p

Most magnetic resonance imaging (MRI) studies investigating the relationship between regional brain myelination or axonal density and aging have relied upon nonspecific methods to probe myelin and axonal content, including diffusion tensor imaging and relaxation time mapping. While these studies have provided pivotal insights into changes in cerebral architecture with aging and pathology, details of the underlying microstructural alterations have not been fully elucidated. In the current study, we used the BMC-mcDESPOT analysis, a direct and specific multicomponent relaxometry method for imaging of myelin water fraction (MWF), a marker of myelin content, and NODDI, an emerging multicomponent diffusion technique, for neurite density index (NDI) imaging, a proxy of axonal density. We investigated age-related differences in MWF and NDI in several white matter brain regions in a cohort of cognitively unimpaired participants over a wide age range. Our results indicate a quadratic, inverted U-shape, relationship between MWF and age in all brain regions investigated, suggesting that myelination continues until middle age followed by a decrease at older ages, in agreement with previous work. We found a similarly complex regional association between NDI and age, with several cerebral structures also exhibiting a quadratic, inverted U-shape, relationship. This novel observation suggests an increase in axonal density until the fourth decade of age followed by a rapid loss at older ages. We also observed that these age-related differences in MWF and NDI vary across different brain regions, as expected. Finally, our study indicates no significant association between MWF and NDI in most cerebral structures investigated, although this association approached significance in a limited number of brain regions, indicating the complementary nature of their information and encouraging further investigation. Overall, we find evidence of nonlinear associations between age and myelin or axonal density in a sample of well-characterized adults, using direct myelin and axonal content imaging methods.

Defective brain glucose utilization is a hallmark of Alzheimer's disease (AD) while Type II diabetes and elevated blood glucose escalate the risk for AD in later life. Isolating contributions of normal aging from coincident metabolic or brain diseases could lead to refined approaches to manage specific health risks and optimize treatments targeted to susceptible older individuals. We evaluated metabolic, neuroendocrine, and neurobiological differences between young adult (6 months) and aged (24 months) male rats. Compared to young adults, blood glucose was significantly greater in aged rats at the start of the dark phase of the day but not during the light phase. When challenged with physical restraint, a potent stressor, aged rats effected no change in blood glucose whereas blood glucose increased in young adults. Tissues were evaluated for markers of oxidative phosphorylation (OXPHOS), neuronal glucose transport, and synapses. Outright differences in protein levels between age groups were not evident, but circadian blood glucose was inversely related to OXPHOS proteins in hippocampal synaptosomes, independent of age. The neuronal glucose transporter, GLUT3, was positively associated with circadian blood glucose in young adults whereas aged rats tended to show the opposite trend. Our data demonstrate aging increases daily fluctuations in blood glucose and, at the level of individual differences, negatively associates with proteins related to synaptic OXPHOS. Our findings imply that glucose dyshomeostasis may exacerbate metabolic aspects of synaptic dysfunction that contribute to risk for age-related brain disorders., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Multiple cognitive domains, including learning, memory, and psychomotor speed, show significant reductions with age. Likewise, several cerebrospinal fluid (CSF) neurodegenerative biomarkers, including total tau (t-tau, a marker of neuronal body injury) and neurofilament light chain (NfL, a marker of axonal injury) show age-related increases in normal aging. In the current study, we aimed to investigate whether the age-effect within different cognitive domains was mediated by age-associated CSF markers for neurodegenerative changes. We fitted 10 mediation models using structural equation modeling to investigate this in a cohort of 137 healthy adults, aged 40-80 years, from the Norwegian Dementia Disease Initiation (DDI) study. Here, t-tau and NfL were defined as mediators between age and different cognitive tests. The models showed that NfL mediated the age-effect for CERAD learning and memory recall (learning: β = -0.395, p < 0.05; recall: β = -0.261, p < 0.01). No such effect was found in the other models. Our findings suggest that the age-related lower performance in verbal learning and memory may be linked to NfL-associated neurodegenerative changes in cognitively healthy adults., Competing Interests: Declaration of Competing Interest BEK has served as a consultant for Biogen. TF has served as a consultant and at the advisory boards for Biogen, Novo Nordisk, Eli Lilly and Roche. MSH, LJC, MHB, BG, GRG, AN, and AR report no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Some cross-sectional studies suggest reduced cerebellar volumes with aging, but there have been few longitudinal studies of age changes in cerebellar subregions in cognitively healthy older adults. In this work, 2,023 magnetic resonance (MR) images of 822 cognitively normal participants from the Baltimore Longitudinal Study of Aging (BLSA) were analyzed. Participants ranged in age from 50 to 95 years (mean 70.7 years) at the baseline assessment. Follow-up intervals were 1–9 years (mean 3.7 years) for participants with two or more visits. We used a recently developed cerebellum parcellation algorithm based on convolutional neural networks to divide the cerebellum into 28 subregions. Linear mixed effects models were applied to the volume of each cerebellar subregion to investigate cross-sectional and longitudinal age effects, as well as effects of sex and their interactions, after adjusting for intracranial volume. Our findings suggest spatially varying atrophy patterns across the cerebellum with respect to age and sex both cross-sectionally and longitudinally.

The integrity of the cholinergic system plays a central role in cognitive decline both in normal aging and neurological disorders including Alzheimer’s disease and vascular cognitive impairment. Most of the previous neuroimaging research has focused on the integrity of the cholinergic basal forebrain, or its sub-region the nucleus basalis of Meynert (NBM). Tractography using diffusion tensor imaging data may enable modelling of the NBM white matter projections. We investigated the contribution of NBM volume, NBM white matter projections, small vessel disease (SVD), and age to performance in attention and memory in 262 cognitively normal individuals (39–77 years of age, 53% female). We developed a multimodal MRI pipeline for NBM segmentation and diffusion-based tracking of NBM white matter projections, and computed white matter hypointensities (WM-hypo) as a marker of SVD. We successfully tracked pathways that closely resemble the spatial layout of the cholinergic system as seen in previous post-mortem and DTI tractography studies. We found that high WM-hypo load was associated with older age, male sex, and lower performance in attention and memory. A high WM-hypo load was also associated with lower integrity of the cholinergic system above and beyond the effect of age. In a multivariate model, age and integrity of NBM white matter projections were stronger contributors than WM-hypo load and NBM volume to performance in attention and memory. We conclude that the integrity of NBM white matter projections plays a fundamental role in cognitive aging. This and other modern neuroimaging methods offer new opportunities to re-evaluate the cholinergic hypothesis of cognitive aging.

Previous in-vivo magnetic resonance imaging (MRI)-based studies of age-related differences in the human brainstem have focused on volumetric morphometry. These investigations have provided pivotal insights into regional brainstem atrophy but have not addressed microstructural age differences. However, growing evidence indicates the sensitivity of quantitative MRI to microstructural tissue changes in the brain. These studies have largely focused on the cerebrum, with very few MR investigations addressing age-dependent differences in the brainstem, in spite of its central role in the regulation of vital functions. Several studies indicate early brainstem alterations in a myriad of neurodegenerative diseases and dementias. The paucity of MR-focused investigations is likely due in part to the challenges imposed by the small structural scale of the brainstem itself as well as of substructures within, requiring accurate high spatial resolution imaging studies. In this work, we applied our recently developed approach to high-resolution myelin water fraction (MWF) mapping, a proxy for myelin content, to investigate myelin differences with normal aging within the brainstem. In this cross-sectional investigation, we studied a large cohort (n = 125) of cognitively unimpaired participants spanning a wide age range (21–94 years) and found a decrease in myelination with age in most brainstem regions studied, with several regions exhibiting a quadratic association between myelin and age. We believe that this study is the first investigation of MWF differences with normative aging in the adult brainstem. Further, our results provide reference MWF values.

This article contains a spreadsheet computing estimates of the expected subcortical regional volumes of an individual based on its characteristics and the scanner characteristics, in addition to supplementary results related to the article “Normative data for subcortical regional volumes over the lifetime of the adult human brain” (O. Potvin, A. Mouiha, L. Dieumegarde, S. Duchesne, 2016) [1] on normative data for subcortical volumes. Data used to produce normative values was obtained by anatomical magnetic resonance imaging from 2790 healthy individuals aged 18–94 years using 23 samples provided by 21 independent research groups. The segmentation was conducted using FreeSurfer. The spreadsheet includes formulas in order to compute for a new individual, significance test for volume abnormality, effect size and estimated percentage of the normative population with a smaller volume while taking into account age, sex, estimated intracranial volume (eTIV), and scanner characteristics. Detailed R-squares of each predictor for all formula are also reported as well as the difference of subcortical volumes segmented by FreeSurfer on two different computer hardware setups.

The prefrontal cortex (PFC) has been implicated as a key brain region responsible for age-related cognitive decline. Little is known about aging-related molecular changes in PFC that may mediate these effects. To date, no studies have used untargeted discovery methods with integrated analyses to determine PFC molecular changes in healthy female primates. We quantified PFC changes associated with healthy aging in female baboons by integrating multiple omics data types (transcriptomics, proteomics, metabolomics) from samples across the adult age span. Our integrated omics approach using unbiased weighted gene co-expression network analysis to integrate data and treat age as a continuous variable, revealed highly interconnected known and novel pathways associated with PFC aging. We found Gamma-aminobutyric acid (GABA) tissue content associated with these signaling pathways, providing 1 potential biomarker to assess PFC changes with age. These highly coordinated pathway changes during aging may represent early steps for aging-related decline in PFC functions, such as learning and memory, and provide potential biomarkers to assess cognitive status in humans., Competing Interests: Declaration of Competing Interest The authors report no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Data from human studies suggest that immune dysregulation is associated with Alzheimer's disease (AD) pathology and cognitive decline and that neurites may be affected early in the disease trajectory. Data from animal studies further indicate that dysfunction in astrocytes and inflammation may have a pivotal role in facilitating dendritic damage, which has been linked with negative cognitive outcomes. To elucidate these relationships further, we have examined the relationship between astrocyte and immune dysregulation, AD-related pathology, and neuritic microstructure in AD-vulnerable regions in late life., Methods: We evaluated panels of immune, vascular, and AD-related protein markers in blood and conducted in vivo multi-shell neuroimaging using Neurite Orientation Dispersion and Density Imaging (NODDI) to assess indices of neuritic density (NDI) and dispersion (ODI) in brain regions vulnerable to AD in a cohort of older adults (n = 109)., Results: When examining all markers in tandem, higher plasma GFAP levels were strongly related to lower neurite dispersion (ODI) in grey matter. No biomarker associations were found with higher neuritic density. Associations between GFAP and neuritic microstructure were not significantly impacted by symptom status, APOE status, or plasma Aβ42/40 ratio; however, there was a large sex effect observed for neurite dispersion, wherein negative associations between GFAP and ODI were only observed in females., Discussion: This study provides a comprehensive, concurrent appraisal of immune, vascular, and AD-related biomarkers in the context of advanced grey matter neurite orientation and dispersion methodology. Sex may be an important modifier of the complex associations between astrogliosis, immune dysregulation, and brain microstructure in older adults., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Sleep is a key determinant of healthy and cognitive aging. Sleep patterns change with aging, independent of other factors, and include advanced sleep timing, shortened nocturnal sleep duration, increased frequency of daytime naps, increased number of nocturnal awakenings and time spent awake during the night, and decreased slow-wave sleep. The sleep-related hormone secretion changes with aging. Most changes seem to occur between young and middle adulthood; sleep parameters remain largely unchanged among healthy older adults. The circadian system and sleep homeostatic mechanisms become less robust with normal aging. The causes of sleep disturbances in older adults are multifactorial., Competing Interests: Disclosure This work is supported by National Institute of Nursing Research R00NR016484., (Copyright © 2022 Elsevier Inc. All rights reserved.)

BOLD variability, which measures moment-to-moment fluctuations in brain signal, is sensitive to age differences in cognitive performance. However, the effect of aging on BOLD variability in the context of different cognitive demands is still unclear. The current study examined how aging affects brain variability across cognitive loads and the contribution of BOLD variability to working memory abilities. Participants (N = 149, ages 20‒86) completed an fMRI n-back paradigm with 3 loads and 10-minute resting state scan. We found that BOLD variability was greater during rest compared to task and decreased even further as n-back load increased. Older age was associated with smaller load-related modulations of BOLD variability in default mode and fronto-parietal control networks. Increased variability in default mode, fronto-parietal control, and limbic regions and decreased variability in sensori-motor regions during the n-back task was associated with better working memory performance, regardless of age. Our findings suggest that working memory reductions in older ages are related to failure of core cognitive control and default mode regions to modulate dynamic range of activity in the face of increased demands., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Brain atrophy occurs in aging even in the absence of dementia, but it is unclear to what extent this is due to undetected preclinical Alzheimer disease. Here we examine a cross-sectional cohort (ages 18-88) free from confounding influence of preclinical Alzheimer disease, as determined by amyloid PET scans and three years of clinical evaluation post-imaging. We determine the regional strength of age-related atrophy using linear modeling of brain volumes and cortical thicknesses with age. Age-related atrophy was seen in nearly all regions, with greatest effects in the temporal lobe and subcortical regions. When modeling age with the estimated derivative of smoothed aging curves, we found that the temporal lobe declined linearly with age, subcortical regions declined faster at later ages, and frontal regions declined slower at later ages than during midlife. This age-derivative pattern was distinct from the linear measure of age-related atrophy and significantly associated with a measure of myelin. Atrophy did not detectably differ from a preclinical Alzheimer disease cohort when age ranges were matched., (Copyright © 2021. Published by Elsevier Inc.)

Healthy aging is accompanied by reduced cognitive control and widespread alterations in the underlying brain networks; but the extent to which large-scale functional networks in older age show reduced specificity across different domains of cognitive control is unclear. Here we use cov-STATIS (a multi-table multivariate technique) to examine similarity of functional connectivity during different domains of cognitive control-inhibition, initiation, shifting, and working memory-across the adult lifespan. We report two major findings: (1) Functional connectivity patterns during initiation, inhibition, and shifting were more similar in older ages, particularly for control and default networks, a pattern consistent with dedifferentiation of the neural correlates associated with cognitive control; and (2) Networks exhibited age-related reconfiguration such that frontal, default, and dorsal attention networks were more integrated whereas sub-networks of somato-motor system were more segregated in older age. Together these findings offer new evidence for dedifferentiation and reconfiguration of functional connectivity underlying different aspects of cognitive control in normal aging., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Growing evidence has linked cardiorespiratory fitness (CRF) to more conserved white matter (WM) microstructure. Additional research is needed to determine which WM tracts are most strongly related to CRF and if the neuroprotective effects of CRF are age-dependent. Participants were community-dwelling adults (N = 499; ages 20-85) from the open-access Nathan Kline Institute - Rockland Sample (NKI-RS) with CRF (bike test) and diffusion tensor imaging (DTI) data. Mixed-effect modeling tested the interaction between CRF and age on global (main effect across 9 tracts) and local (individual tract effects) WM microstructure. Among older participants (age ≥ 60), CRF was significantly related to whole-brain (z-score slope = 0.11) and local WM microstructure within several tracts (| z-score slope | range = 0.13 - 0.27). Significant interactions with age indicated that the CRF-WM relationship was weaker (z-score slope ≤ 0.11) and more limited (one WM tract) in younger adults. The findings highlight the importance of aerobic exercise to maintain brain health into senescence. CRF may preferentially preserve a collection of anterior and posterior WM connections related to visuomotor function., (Copyright © 2021. Published by Elsevier Inc.)

An 11-25% increase in total ventricular volume has been documented in astronauts following spaceflight on the ISS. Given the approximately 2-year time interval between pre- and post-flight MRI, it is unknown if ventricular enlargement simply reflects normal aging or is unique to spaceflight exposure. Therefore, we compared percent ventricular volume change per year (PVVC/yr) documented on pre- to post-flight MRI in a group of NASA ISS astronauts (n = 18, 16.7% women, mean age (SD) 48.43 (4.35) years) with two groups who underwent longitudinal MRI: (1.) healthy age- and sex-matched adults (n = 18, 16.7% women, mean age (SD) 51.26 (3.88) years), and (2.) healthy older adults (n = 79, 16.5% women, mean age (SD) 73.26 (5.34) years). The astronauts, who underwent a mean (SD) 173.4 (51.3) days in spaceflight, showed a greater increase in PVVC/yr than the control (6.86 vs 2.23%, respectively, p  < .001) and older adult (4.18%, p  = 0.04) groups. These results highlight that on top of physiologically ventricular volume changes due to normal aging, NASA astronauts undergoing ISS missions experience an additional 4.63% PVVC/yr and underscore the need to perform post-flight follow-up scans to determine the time course of PVVC in astronauts over time back on Earth along with monitoring to determine if the PVVC is ultimately clinically relevant., One Sentence Summary: NASA astronauts who were exposed to prolonged spaceflight experienced an annual rate of ventricular expansion more than three times that expected from normal aging., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Author(s).)