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The hypothalamus regulates homeostasis across the lifespan and is emerging as a regulator of aging. In murine models, aging-related changes in the hypothalamus, including microinflammation and gliosis, promote accelerated neurocognitive decline. We investigated relationships between hypothalamic microstructure and features of neurocognitive aging, including cortical thickness and cognition, in a cohort of community-dwelling older adults (age range 65–97 years, n=124). Hypothalamic microstructure was evaluated with two magnetic resonance imaging diffusion metrics: mean diffusivity (MD) and fractional anisotropy (FA), using a novel image processing pipeline. Hypothalamic MD was cross-sectionally positively associated with age and it was negatively associated with cortical thickness. Hypothalamic FA, independent of cortical thickness, was cross-sectionally positively associated with neurocognitive scores. An exploratory analysis of longitudinal neurocognitive performance suggested that lower hypothalamic FA may predict cognitive decline. No associations between hypothalamic MD, age, and cortical thickness were identified in a younger control cohort (age range 18–63 years, n=99). To our knowledge, this is the first study to demonstrate that hypothalamic microstructure is associated with features of neurocognitive aging in humans. • In animal models, aging-related changes in the hypothalamus drive brain aging. • The role of the hypothalamus in neurocognitive aging in humans is unknown. • We show that hypothalamic microstructure is altered with aging in older adults. • Hypothalamic microstructure is associated with cortical thickness and cognition. [ABSTRACT FROM AUTHOR]

Women have a higher incidence of Alzheimer's disease (AD), even after adjusting for increased longevity. Thus, there is an urgent need to identify genes that underpin sex-associated risk of AD. PIN1 is a key regulator of the tau phosphorylation signaling pathway; however, potential differences in PIN1 expression, in males and females, are still unknown. We analyzed brain transcriptomic datasets focusing on sex differences in PIN1 mRNA levels in an aging and AD cohort, which revealed reduced PIN1 levels primarily within females. We validated this observation in an independent dataset (ROS/MAP), which also revealed that PIN1 is negatively correlated with multiregional neurofibrillary tangle density and global cognitive function in females only. Additional analysis revealed a decrease in PIN1 in subjects with mild cognitive impairment (MCI) compared with aged individuals, again driven predominantly by female subjects. Histochemical analysis of PIN1 in AD and control male and female neocortex revealed an overall decrease in axonal PIN1 protein levels in females. These findings emphasize the importance of considering sex differences in AD research. • Reduced PIN1 levels are driven by females in aging and Alzheimer's disease. • PIN1 is negatively correlated with neurofibrillary tangle density in females. • PIN1 levels are negatively correlated with global cognitive function in females. • PIN1 levels are decreased in subjects with mild cognitive impairment. [ABSTRACT FROM AUTHOR]

Growing evidence suggests that aging is associated with impaired endogenous pain modulation, and that this likely underlies the increased transition from acute to chronic pain in older individuals. Resting-state functional connectivity (rsFC) offers a valuable tool to examine the neural mechanisms behind these age-related changes in pain modulation. RsFC studies generally observe decreased within-network connectivity due to aging, but its relevance for pain modulation remains unknown. We compared rsFC within a set of brain regions involved in pain modulation between young and older adults and explored the relationship with the efficacy of distraction from pain. This revealed several age-related increases and decreases in connectivity strength. Importantly, we found a significant association between lower pain relief and decreased strength of three connections in older adults, namely between the periaqueductal gray and right insula, between the anterior cingulate cortex (ACC) and right insula, and between the ACC and left amygdala. These findings suggest that the functional integrity of the pain control system is critical for effective pain modulation, and that its function is compromised by aging. • Older adults showed decreased rsFC within the descending pain control system. • This decrease was associated with lower distraction-related pain relief. • rsFC markers for pain modulation efficacy in aging have clear clinical benefits. [ABSTRACT FROM AUTHOR]

The aging population suffers from memory impairments. Slow-wave activity (SWA) is composed of slow (0.5–1 Hz) and delta (1–4 Hz) oscillations, which play important roles in long-term memory and working memory function respectively. SWA disruptions might lead to memory disturbances often experienced by older adults. We conducted behavioral tests in young and older C57BL/6 J mice. SWA was monitored using wide-field imaging with voltage sensors. Cell-specific calcium imaging was used to monitor the activity of excitatory and inhibitory neurons in these mice. Older mice exhibited impairments in working memory but not memory consolidation. Voltage-sensor imaging revealed aberrant synchronization of neuronal activity in older mice. Notably, we found older mice exhibited no significant alterations in slow oscillations, whereas there was a significant increase in delta power compared to young mice. Calcium imaging revealed hypoactivity in inhibitory neurons of older mice. Combined, these results suggest that neural activity disruptions might correlate with aberrant memory performance in older mice. • Slow wave activity disruptions lead to memory disturbances in older adults. • Older mice show impairments in working memory, but not memory consolidation. • Older mice showed abnormal synchronization of neuronal activity across the cortex. • Older mice exhibited aberrant activity of inhibitory neurons within the circuit. • The neural activity disruptions may be related to memory impairments in Older mice. [ABSTRACT FROM AUTHOR]

Sequence memory is subject to age-related decline, but the underlying processes are not yet fully understood. We analyzed electroencephalography (EEG) in 21 healthy older (60–80 years) and 26 young participants (20–30 years) and compared time-frequency spectra and theta-gamma phase-amplitude-coupling (PAC) during encoding of the order of visually presented items. In older adults, desynchronization in theta (4–8 Hz) and synchronization in gamma (30–45 Hz) power did not distinguish between subsequently correctly and incorrectly remembered trials, while there was a subsequent memory effect for young adults. Theta-gamma PAC was modulated by item position within a sequence for older but not young adults. Specifically, position within a sequence was coded by higher gamma amplitude for successive theta phases for later correctly remembered trials. Thus, deficient differentiation in theta desynchronization and gamma oscillations during sequence encoding in older adults may reflect neurophysiological correlates of age-related memory decline. Furthermore, our results indicate that sequences are coded by theta-gamma PAC in older adults, but that this mechanism might lose precision in aging. • Sequence memory, an important aspect of episodic memory, declines in healthy aging. • Lower theta and higher gamma activity in encoding of correct trials in young adults. • No subsequent memory effect in oscillatory brain activity in healthy older adults. • Theta phase modulates gamma amplitude to code for item position in older adults. [ABSTRACT FROM AUTHOR]

Some research has shown that older adults benefit more from multisensory information than do young adults. However, more recent evidence has shown that the multisensory age benefit varies considerably across tasks. In the current study, older (65 – 80) and young (18 – 30) adults (N = 191) completed a speeded perceptual discrimination task either online or face-to-face to assess task response speed. We examined whether presenting stimuli in multiple sensory modalities (audio-visual) instead of one (audio-only or visual-only) benefits older adults more than young adults. Across all three experiments, a consistent speeding of response was found in the multisensory condition compared to the unisensory conditions for both young and older adults. Furthermore, race model analysis showed a significant multisensory benefit across a broad temporal interval. Critically, there were no significant differences between young and older adults. Taken together, these findings provide strong evidence in favour of a multisensory benefit that does not differ across age groups, contrasting with prior research. • Multisensory information is responded to faster than unisensory information. • Both young and older adults benefit similarly from multisensory information. • An age-specific multisensory benefit was not replicated from prior research. [ABSTRACT FROM AUTHOR]

Prior studies have reported inconsistent results regarding the relationships between the integrity of the fornix and parahippocampal cingulum and both memory performance and longitudinal change in performance. In the present study, we examined associations in a sample of cognitively healthy older adults between free water-corrected fractional anisotropy (FA) metrics derived from the fornix and cingulum, baseline memory performance, and 3-year memory change. Neither fornix nor cingulum FA correlated with memory performance at baseline. By contrast, FA of each tract was predictive of memory change, such that greater FA was associated with less longitudinal decline. These associations remained significant after controlling for FA of other white matter tracts and for performance in other cognitive domains. Furthermore, fornix and cingulum FA explained unique variance in memory change. These results suggest that free water-corrected measures of fornix and parahippocampal cingulum integrity are reliable predictors of future memory change in cognitively healthy older adults. The findings for the fornix in particular highlight the utility of correcting for free water when estimating diffusion tensor imaging metrics of white matter integrity. • Free water-corrected fornix and cingulum FA were unrelated to memory performance. • FA of both fornix and cingulum demonstrated a specific association with memory change. • Fornix and cingulum FA explained unique variance in memory change. [ABSTRACT FROM AUTHOR]

Aging affects the scalp-to-cortex distance (SCD) and the comprising tissues. This is crucial for noninvasive neuroimaging and brain stimulation modalities as they rely on traversing from the scalp to the cortex or vice versa. The specific relationship between aging and these tissues has not been comprehensively investigated. We conducted a study on 250 younger and older adults to examine age-related differences in SCD and its constituent tissues. We identified region-specific differences in tissue thicknesses related to age and sex. Older adults exhibit larger SCD in the frontocentral regions compared to younger adults. Men exhibit greater SCD in the inferior scalp regions, while women show similar-to-greater SCD values in regions closer to the vertex compared to men. Younger adults and men have thicker soft tissue layers, whereas women and older adults exhibit thicker compact bone layers. CSF is considerably thicker in older adults, particularly in men. These findings emphasize the need to consider age, sex, and regional differences when interpreting SCD and its implications for noninvasive neuroimaging and brain stimulation. [Display omitted] • Scalp-to-cortex distance (SCD) and the comprising tissues are different across age groups. • Across 19 regions, we examined age and sex effects on the SCD tissues in 250 adults. • Older adults have larger SCD values in frontal and central regions than younger adults. • The comprising tissues show unique age and sex differences, depending on the region. • Considering tissue changes is key for scalp-based neuroimaging and brain stimulation. [ABSTRACT FROM AUTHOR]

We explored neural processing differences associated with aging across four cognitive functions. In addition to ERP analysis, we included task-related microstate analyses, which identified stable states of neural activity across the scalp over time, to explore whole-head neural activation differences. Younger and older adults (YA, OA) completed face perception (N170), word-pair judgment (N400), visual oddball (P3), and flanker (ERN) tasks. Age-related effects differed across tasks. Despite age-related delayed latencies, N170 ERP and microstate analyses indicated no age-related differences in amplitudes or microstates. However, age-related condition differences were found for P3 and N00 amplitudes and scalp topographies: smaller condition differences were found for in OAs as well as broader centroparietal scalp distributions. Age group comparisons for the ERN revealed similar focal frontocentral activation loci, but differential activation patterns. Our findings of differential age effects across tasks are most consistent with the STAC-r framework which proposes that age-related effects differ depending on the resources available and the kinds of processing and cognitive load required of various tasks. • ERP and microstate analyses showed that age effects differed across four tasks. • Microstates with ERPs help distinguish among current theories of neural aging. • Spatial distributions of neural processing phases differ by age across time and task. • Different age-related effects across tasks were most consistent with STAC-r. [ABSTRACT FROM AUTHOR]

Enlarged perivascular spaces (ePVS) may adversely affect cognition. Little is known about how basal ganglia ePVS interact with apolipoprotein (APOE)-ε4 status. Vanderbilt Memory and Aging Project participants (n = 326, 73 ± 7, 59% male) underwent 3 T brain MRI at baseline to assess ePVS and longitudinal neuropsychological assessments. The interaction between ePVS volume and APOE -ε4 carrier status was related to baseline outcomes using ordinary least squares regressions and longitudinal cognition using linear mixed-effects regressions. ePVS volume interacted with APOE -ε4 status on cross-sectional naming performance (β = −0.002, p = 0.002), and executive function excluding outliers (β = 0.001, p = 0.009). There were no significant longitudinal interactions (p-values>0.10) except for Coding excluding outliers (β = 0.002, p = 0.05). While cross-sectional models stratified by APOE -ε4 status indicated greater ePVS related to worse cognition mostly in APOE -ε4 carriers, longitudinal models stratified by APOE -ε4 status showed greater ePVS volume related to worse cognition among APOE -ε4 non-carriers only. Results indicated that greater ePVS volume interacts with APOE- ε4 status on cognition cross-sectionally. Longitudinally, the association of greater ePVS volume and worse cognition appears stronger in APOE -ε4 non-carriers, possibly due to the deleterious effects of APOE -ε4 on cognition across the lifespan. • ePVS volume interacts with APOE- ε4 status on cognition cross-sectionally. • Greater ePVS relates to worse cognition in APOE -ε4 carriers cross-sectionally. • No interaction between ePVS volume and APOE- ε4 status on cognition longitudinally. [ABSTRACT FROM AUTHOR]

Neural tracking of spoken speech is considered a potential clinical biomarker for speech-processing difficulties, but the reliability of neural speech tracking is unclear. Here, younger and older adults listened to stories in two sessions while electroencephalography was recorded to investigate the reliability and generalizability of neural speech tracking. Speech tracking amplitude was larger for older than younger adults, consistent with an age-related loss of inhibition. The reliability of neural speech tracking was moderate (ICC ∼0.5–0.75) and tended to be higher for older adults. However, reliability was lower for speech tracking than for neural responses to noise bursts (ICC >0.8), which we used as a benchmark for maximum reliability. Neural speech tracking generalized moderately across different stories (ICC ∼0.5–0.6), which appeared greatest for audiobook-like stories spoken by the same person. Hence, a variety of stories could possibly be used for clinical assessments. Overall, the current data are important for developing a biomarker of speech processing but suggest that further work is needed to increase the reliability to meet clinical standards. • Neural speech tracking is a potential EEG biomarker for impaired speech processing. • However, reliability and generalizability of neural speech tracking are unclear. • Younger and older adults show moderate reliability of neural speech tracking. • Neural tracking also moderately generalized across speech materials. • Current results are critical for the development of a biomarker of speech processing. [ABSTRACT FROM AUTHOR]

Episodic memory performance declines with increasing age, and older adults typically show reduced activation of inferior temporo-parietal cortices in functional magnetic resonance imaging (fMRI) studies of episodic memory formation. Given the age-related cortical volume loss, it is conceivable that age-related reduction of memory-related fMRI activity may be partially attributable to reduced grey matter volume (GMV). We performed a voxel-wise multimodal neuroimaging analysis of fMRI correlates of successful memory encoding, using regional GMV as covariate. In a large cohort of healthy adults (106 young, 111 older), older adults showed reduced GMV across the entire neocortex and reduced encoding-related activation of inferior temporal and parieto-occipital cortices compared to young adults. Importantly, these reduced fMRI activations during successful encoding could in part be attributed to lower regional GMV. Our results highlight the importance of controlling for structural MRI differences in fMRI studies in older adults but also demonstrate that age-related differences in memory-related fMRI activity cannot be attributed to structural variability alone. [Display omitted] • Structural differences in distinct age groups may in part explain fMRI differences. • We included voxel-wise GMV into models of the fMRI subsequent memory effect. • Reduced encoding-related activations could in part be attributed to lower local GMV. • Care is advised when modelling fMRI effects for groups with structural differences. • Structural modalities may in part explain alleged differences in function. [ABSTRACT FROM AUTHOR]

Healthy aging is typically accompanied by cognitive decline. Previous work has shown that engaging in multiple, non-work activities during midlife can have a protective effect on cognition several decades later, rendering it less dependent on brain structural health; the definition of "cognitive reserve". Other work has shown that increasing age is associated with reduced segregation of large-scale brain functional networks. Here we tested the hypothesis that functional segregation (SyS) mediates this effect of middle-aged lifestyle on late-life cognition. We used fMRI data from three tasks in the CamCAN dataset, together with cognitive data on fluid intelligence, episodic memory, and retrospective lifestyle data from the Lifetime of Experiences Questionnaire (LEQ). In all three tasks, we showed that SyS related to fluid intelligence even after adjusting for the (nonlinear) age effects. However, we found no evidence that SyS in late-life mediated the relationship between non-specific (non-occupation) midlife activities and either measure of cognition in late-life. Thus, the brain correlates of cognitive reserve arising from mid-life activities remain to be discovered. • System segregation (SyS) is stable across different brain states. • SyS is negatively associated with age. • Fluid intelligence, but not episodic memory, was robustly predicted by SyS. • Late life SyS was not associated with midlife outside of work activities. [ABSTRACT FROM AUTHOR]

While capacity for motor skill acquisition changes with healthy aging, there has been little consideration of how age-related changes in brain function or baseline brain structure support motor skill acquisition. We examined: (1) age-dependent changes in functional reorganization related to frontoparietal regions during motor skill acquisition, and (2) whether capacity for motor skill acquisition relates to baseline white matter microstructure in frontoparietal tracts. Healthy older and younger adults engaged in 4 weeks of skilled motor practice. Resting-state functional connectivity (rsFC) assessed functional reorganization before and after practice. Diffusion tensor imaging indexed microstructure of a frontoparietal tract at baseline, generated by rsFC seeds. Motor skill acquisition was associated with decreases in rsFC in healthy older adults and increases in rsFC in healthy younger adults. Frontoparietal tract microstructure was lower in healthy older versus younger adults, yet it was negatively associated with rate of skill acquisition regardless of group. Findings indicate that age-dependent alterations in frontoparietal function and baseline structure of a frontoparietal tract reflect capacity for motor skill acquisition. [ABSTRACT FROM AUTHOR]

The relationship between tau deposition and cognitive decline in cognitively healthy older adults is still unclear. The tau PET tracer 18F-MK-6240 has shown favorable imaging characteristics to identify early tau deposition in aging. We evaluated the relationship between in vivo tau levels (18F-MK-6240) and retrospective cognitive change over 5 years in episodic memory, processing speed, and reasoning. For tau quantification, a set of regions of interest (ROIs) was selected a priori based on previous literature: (1) total-ROI comprising selected areas, (2) medial temporal lobe-ROI, and (3) lateral temporal lobe-ROI and cingulate/parietal lobe-ROI. Higher tau burden in most ROIs was associated with a steeper decline in memory and speed. There were no associations between tau and reasoning change. The novelty of this finding is that tau burden may affect not only episodic memory, a well-established finding but also processing speed. Our finding reinforces the notion that early tau deposition in areas related to Alzheimer's disease is associated with cognitive decline in cognitively unimpaired individuals, even in a sample with low amyloid-β pathology. [ABSTRACT FROM AUTHOR]

Dysfunction of the cholinergic basal forebrain (BF) system and amyloid-β (Aβ) deposition are early pathological features in Alzheimer's disease (AD). However, their association in early AD is not well-established. This study investigated the nature and magnitude of volume loss in the BF, over an extended period, in 516 older adults who completed Aβ-PET and serial magnetic resonance imaging scans. Individuals were grouped at baseline according to the presence of cognitive impairment (CU, CI) and Aβ status (Aβ−, Aβ+). Longitudinal volumetric changes in the BF and hippocampus were assessed across groups. The results indicated that high Aβ levels correlated with faster volume loss in the BF and hippocampus, and the effect of Aβ varied within BF subregions. Compared to CU Aβ+ individuals, Aβ-related loss among CI Aβ+ adults was much greater in the predominantly cholinergic subregion of Ch4p, whereas no difference was observed for the Ch1/Ch2 region. The findings support early and substantial vulnerability of the BF and further reveal distinctive degeneration of BF subregions during early AD. [ABSTRACT FROM AUTHOR]

Aging is associated with decreased cognitive function. One theory posits that this decline is in part due to multiple neural systems becoming dedifferentiated in older adults. Exercise is known to improve cognition in older adults, even after only a single session. We hypothesized that one mechanism of improvement is a redifferentiation of neural systems. We used a within-participant, cross-over design involving 2 sessions: either 30 minutes of aerobic exercise or 30 minutes of seated rest (n = 32; ages 55–81 years). Both functional Magnetic Resonance Imaging (fMRI) and Stroop performance were acquired soon after exercise and rest. We quantified neural differentiation via general heterogeneity regression. There were 3 prominent findings following the exercise. First, participants were better at reducing Stroop interference. Second, while there was greater neural differentiation within the hippocampal formation and cerebellum, there was lower neural differentiation within frontal cortices. Third, this greater neural differentiation in the cerebellum and temporal lobe was more pronounced in the older ages. These data suggest that exercise can induce greater neural differentiation in healthy aging. [ABSTRACT FROM AUTHOR]

Using data from a clinical trial, we tested the hypothesis that daily sessions modulating heart rate oscillations affect older adults' volume of a region-of-interest (ROI) comprised of adjacent hippocampal subregions with relatively strong locus coeruleus (LC) noradrenergic input. Younger and older adults were randomly assigned to one of two daily biofeedback practices for 5 weeks: (1) engage in slow-paced breathing to increase the amplitude of oscillations in heart rate at their breathing frequency (Osc+); (2) engage in self-selected strategies to decrease heart rate oscillations (Osc-). The interventions did not significantly affect younger adults' hippocampal volume. Among older adults, the two conditions affected volume in the LC-targeted hippocampal ROI differentially as reflected in a significant condition × time-point interaction on ROI volume. These condition differences were driven by opposing changes in the two conditions (increased volume in Osc+ and decreased volume in Osc-) and were mediated by the degree of heart rate oscillation during training sessions. [ABSTRACT FROM AUTHOR]

Facilitating communication between generations has become increasingly important. However, individuals often demonstrate a preference for their own age group, which can impact social interactions, and such bias in young adults even extends to inhibitory control. To assess whether older adults also experience this phenomenon, a group of younger and older adults completed a Go/NoGo task incorporating young and old faces, while undergoing functional magnetic resonance imaging. Within the networks subserving successful and unsuccessful response inhibition, patterns of activity demonstrated distinct neural age bias effects in each age group. During successful inhibition, the older adult group demonstrated significantly increased activity to other-age faces, whereas unsuccessful inhibition in the younger group produced significantly enhanced activity to other-age faces. Consequently, the findings of the study confirm that neural responses to successful and unsuccessful inhibition can be contingent on the stimulus-specific attribute of age in both younger and older adults. These findings have important implications in regard to minimizing the emergence of negative consequences, such as ageism, as a result of related implicit biases. [ABSTRACT FROM AUTHOR]

We investigated how resting electroencephalography (EEG) measures are associated with risk factors for late-life cognitive impairment and dementia, including age, apolipoprotein E ɛ4 (APOE-ɛ4) carriage, and cardiometabolic burden. Resting EEG was recorded from 86 adults (50–80 years of age). Participants additionally completed the Addenbrooke's Cognitive Examination (ACE) III and had blood drawn to assess APOE-ɛ4 carriage status and cardiometabolic burden. EEG power spectra were decomposed into sources of periodic and aperiodic activity to derive measures of aperiodic component slope and alpha (7–14 Hz) and beta (15–30 Hz) peak power and peak frequency. Alpha and beta peak power measures were corrected for aperiodic activity. The aperiodic component slope was correlated with ACE-III scores but not age. Alpha peak frequency decreased with age. Individuals with higher cardiometabolic burden had lower alpha peak frequencies and lower beta peak power. APOE-ɛ4 carriers had lower beta peak frequencies. Our findings suggest that the slope of the aperiodic component of resting EEG power spectra is more closely associated with measures of cognitive performance rather than chronological age in older adults. [ABSTRACT FROM AUTHOR]

Socioeconomic status (SES) is associated with white matter hyperintensities (WMHs) and contributes to racial and ethnic health disparities. However, traditional measures of SES may not accurately represent individual financial circumstances among non-Latinx Black and Latinx older adults due to longstanding structural inequities. This study examined associations between multiple SES indicators (education, income, subjective financial worry) and WMHs across non-Latinx Black, Latinx, and non-Latinx White older adults in the Washington Heights-Inwood Columbia Aging Project (N = 662). Latinx participants reported the lowest SES and greatest financial worry, while Black participants evidenced the most WMHs. Greater financial worry was associated with higher WMHs volume above and beyond education and income, which were not associated with WMHs. However, this association was only evident among Latinx older adults. These results provide evidence for the minority poverty hypothesis and highlight the need for systemic socioeconomic interventions to alleviate brain health disparities in older adulthood. [ABSTRACT FROM AUTHOR]

Brain-derived estrogen is an endogenous neuroprotective agent, whether and how might this protective function with aging, especially postmenopausal drops in circulating estrogen, remain unclear. We herein subjected 6, 14, and 18 Mon female rats to mimic natural aging, and found that estrogen synthesis is more active in the healthy aged brain, as evidenced by the highest levels of mRNA and protein expression of aromatase, the key enzyme of E2 biosynthesis, among the three groups. Aromatase knockout in forebrain neurons (FBN-Aro-/-) impaired hippocampal and cortical neurons, and cognitive function in 18 Mon rats, compared to wild-type controls. Furthermore, estrogen nuclear receptors (ERα/β) displayed opposite changes, with a significant ERα decrease and ERβ increase, while membrane receptor GPR30 expressed stably in hippocampus during aging. Intriguingly, GPR30, but not ERα and ERβ, was decreased by FBN-Aro-/-. The results indicate that GPR30 is more sensitive to brain local E2 synthesis. Our findings provide evidence of a critical role for brain-derived estrogen in maintaining healthy brain function in older individuals, possibly involving GPR30. [ABSTRACT FROM AUTHOR]

Topographic maps form a critical feature of cortical organization, yet are poorly described with respect to their microstructure in the living aging brain. We acquired quantitative structural and functional 7T-MRI data from younger and older adults to characterize layer-wise topographic maps of the primary motor cortex (M1). Using parcellation-inspired techniques, we show that quantitative T1 and Quantitative Susceptibility Maps values of the hand, face, and foot areas differ significantly, revealing microstructurally distinct cortical fields in M1. We show that these fields are distinct in older adults and that myelin borders between them do not degenerate. We further show that the output layer 5 of M1 shows a particular vulnerability to age-related increased iron, while layer 5 and the superficial layer show increased diamagnetic substance, likely reflecting calcifications. Taken together, we provide a novel 3D model of M1 microstructure, where body parts form distinct structural units, but layers show specific vulnerability toward increased iron and calcium in older adults. Our findings have implications for understanding sensorimotor organization and aging, in addition to topographic disease spread. [ABSTRACT FROM AUTHOR]

Deficits in physical function that occur with aging contribute to declines in quality of life and increased mortality. There has been a growing interest in examining associations between physical function and neurobiology. Whereas high levels of white matter disease have been found in individuals with mobility impairments in structural brain studies, much less is known about the relationship between physical function and functional brain networks. Even less is known about the association between modifiable risk factors such as body mass index (BMI) and functional brain networks. The current study examined baseline functional brain networks in 192 individuals from the Brain Networks and mobility (B-NET) study, an ongoing longitudinal, observational study in community-dwelling adults aged 70 and older. Physical function and BMI were found to be associated with sensorimotor and dorsal attention network connectivity. There was a synergistic interaction such that high physical function and low BMI were associated with the highest network integrity. White matter disease did not modify these relationships. Future work is needed to understand the causal direction of these relationships. [ABSTRACT FROM AUTHOR]

Obesity and sarcopenia are associated with cognitive impairments at older age. Current research suggests that blood biomarkers may mediate this body-brain crosstalk, altering neurometabolism and brain structure eventually resulting in cognitive performance changes. Seventy-four older adults (60–85 years old) underwent bio-impedance body composition analysis, handgrip strength measurements, 8-Foot Up-and-Go (8UG) test, Montreal Cognitive Assessment (MoCA), blood analysis of interleukin-6 (IL-6), kynurenine, and insulin-like growth factor-1 (IGF-1), as well as brain magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy (1H-MRS), estimating neurodegeneration and neuroinflammation. Normal fat% or overweight was associated with larger total gray matter volume compared to underweight or obesity in older adults and obesity was associated with higher N-acetylaspartate/Creatine levels in the sensorimotor and dorsolateral prefrontal cortex. Muscle strength, not muscle mass/physical performance, corresponded to lower kynurenine and higher N-acetylaspartate/Creatine levels in the dorsal posterior cingulate and dorsolateral prefrontal cortex. The inflammatory and neurotrophic blood biomarkers did not significantly mediate these body-brain associations. This study used a multimodal approach to comprehensively assess the proposed mechanism of body-brain crosstalk. [ABSTRACT FROM AUTHOR]

• Examined associations of prior sleep patterns with late-life brain microstructure. • Poor sleep quality predicted abnormal brain microstructure, more strongly for men. • Short and long sleep durations in midlife predicted abnormal microstructure for women. • Associations were not observed for volume or accounted for by health or lifestyle. • Maintaining sleep quality throughout life may help to optimize healthy brain aging. Although poor sleep quality and extreme sleep durations have been associated with brain atrophy and dementia, it is unclear whether sleep disturbances contribute to neural injury in the absence of neurodegeneration and cognitive impairment. In 146 dementia-free older adults of the Rancho Bernardo Study of Healthy Aging (76.7 ± 7.8 years at MRI), we examined associations of restriction spectrum imaging metrics of brain microstructure with self-reported sleep quality 6.3 ± 0.7 years prior, and with sleep duration reported 25, 15 and 9 years prior. Worse sleep quality predicted lower white matter restricted isotropic diffusion and neurite density and higher amygdala free water, with stronger associations between poor sleep quality and abnormal microstructure for men. Among women only, short or long sleep duration 25 and 15 years before MRI predicted lower white matter restricted isotropic diffusion and increased free water. Associations persisted after accounting for associated health and lifestyle factors. Sleep patterns were not related to brain volume or cortical thickness. Optimizing sleep behaviors throughout the life-course may help to preserve healthy brain aging. [ABSTRACT FROM AUTHOR]

• Older adults learn to trust differently than younger adults. • Age-related differences in trust not due to differences in feedback learning. • Prediction error signals observed in striatal, insular, and frontal regions. • Older learners display greater activity in memory brain regions during decisions. • Older adults display learning-related overactivation of many cortical regions. Trust is a key component of social interaction. Older adults, however, often exhibit excessive trust relative to younger adults. One explanation is that older adults may learn to trust differently than younger adults. Here, we examine how younger (N = 33) and older adults (N = 30) learn to trust over time. Participants completed a classic iterative trust game with 3 partners. Younger and older adults shared similar amounts but differed in how they shared money. Compared to younger adults, older adults invested more with untrustworthy partners and less with trustworthy partners. As a group, older adults displayed less learning than younger adults. However, computational modeling suggests that this is not because older adults learn differently from positive and negative feedback than younger adults. Model-based fMRI analyses revealed several age- and learning-related differences in neural processing. Specifically, we found that older learners (N = 19), relative to older non-learners (N = 11), had greater reputation-related activity in metalizing/memory areas while making their decisions. Collectively, these findings suggest that older adult learners use social cues differently from non-learners. [ABSTRACT FROM AUTHOR]

• Data were collected from 26 younger, 25 middle-aged and 28 older adults. • At a younger age, theta power increased in curved, relative to straight segments. • In older adults, this midfrontal theta power upregulation was absent. • With aging, mental resources might be depleted when driving in challenging settings. Motor control, a ubiquitous part of driving, requires increased cognitive controlled processing in older adults relative to younger adults. However, the influence of aging on motor-related neural mechanisms in the context of driving has rarely been studied. The present study aimed to identify age-related changes in cognitive control and attention allocation during a simulated steering task, using electroencephalography. Midfrontal theta, a marker for cognitive control, and posterior alpha power, a marker for attention allocation, were measured in a total of 26 young, 25 middle-aged, and 28 older adults. By adapting driving speed, the difficulty level of this steering task was individualized for each participant. Results show age-related changes in midfrontal theta power, but not in posterior alpha power, despite similar steering accuracy across age groups. Specifically, only younger and, to a lesser extent, middle-aged adults exhibited increased theta power while driving through more demanding curved segments relative to straight segments. In contrast, theta power upregulation was absent in older adults, suggesting a saturation of cognitive resources while driving, possibly due to a limitation in resource capacity, or less automatic motor-related neural processing. [ABSTRACT FROM AUTHOR]

• Older adults were more risk-taking than younger adults in lottery choice decisions. • Younger adults had higher earlier choice ERPs and parsed value monotonically. • Older adults showed non-monotonic value-modulation in later choice ERPs. • Younger and older feedback FRN (RPE) and LPP (salience integration) were similar. • Older expectancy violation modulation of feedback P3 reflected more subjectivity. This study evaluates age-related differences in the temporal dynamics underlying neural processing of value for decision-making in younger and older adults. We applied a lottery-choice task with event-related potentials to determine how and when brain activity during choice and outcome processing diverge between younger and older adults. Behaviorally, older adults accepted more losing stakes than younger adults. During choice, younger adults evinced higher P2 ERP-response positivity with a later P3 positivity that monotonically increased with low to middle to high win probability. Older adults evinced lower P2 responses and P3 amplitudes with more positivity for high and low relative to middle win probability. Both age groups showed similar feedback-related negativity and late parietal positivity, indicating intact reward prediction error representations and salience integration. Feedback-P3 showed more complex sensitivity to expectancy violations in older than younger adults, suggesting subjective uncertainty about reward expectations. Reduced early general neural processing of objective stimulus value with greater contribution of downstream subjective processes might underlie older adult risk-taking behaviors. [ABSTRACT FROM AUTHOR]

Age-related positivity preferences are represented as greater memory benefits for positive and/or reduced benefits for negative material with age. It is unknown if positivity preferences are limited to older adults without depressive symptoms. In this fMRI study, adults across the lifespan with a range of depressive symptoms were scanned as they rated emotional intensity of images and subsequently completed a recognition memory task. Behavioral, univariate, and functional connectivity analyses provided evidence for interactive effects between age and depressive symptoms. With low depressive symptoms, typical age-related emotional preferences emerged: younger age was associated with better memory for negative images, and this benefit was reduced with older age. With increasing depressive symptoms in older age, positivity preferences were reduced, manifesting as improvements in negative memory. The neural data highlighted potential underlying mechanisms, including reductions in prefrontal cortex connectivity reflecting diminished ability to engage regulatory processes to reduce negative affect in older participants with higher depressive symptoms. These findings suggest that depressive symptoms in older adulthood reduce positivity preferences through alterations in neural networks underlying emotion regulation. [ABSTRACT FROM AUTHOR]

• Lower education was associated with reduced activation of the right temporal lobe. • Memory training increased left inferior pre-frontal activation during encoding. • Memory training reduced bilateral frontostriatal activation during retrieval. • Memory training increased temporal lobe activation in people with lower education. • Education differences in temporal activation were no longer present after training. Functional magnetic resonance imaging (fMRI) was used to assess the effect of cognitive training on brain activation as a function of the learning phase and level of education. Forty older adults with subjective cognitive decline (SCD) received 6 1-hour memory training sessions with the method of loci. Brain imaging (N = 29) was measured during word list encoding and retrieval before training (PRE), after 3 training sessions (POST3), and after 6 training sessions (POST6). Participants showed increased activation of the left inferior pre-frontal gyrus from PRE to POST6 during encoding and reduced bilateral frontostriatal activation from PRE to POST3 during retrieval, regardless of education. Activation changes from PRE to POST3 varied as a function of education in 2 regions of the right temporal lobe: participants with lower education showed increased activation, while those with higher education showed decreased activation. These regions were initially less active in people with lower education. Results suggest a strategic shift in people with lower education and expertise building in those with higher education, along with a restoration of initial education-related differences. [ABSTRACT FROM AUTHOR]

Physical activity has been suggested as modifiable factor that might contribute to improving cognitive and brain function during aging. However, previous studies were mainly of cross-sectional design and did not consider effects of time or potential reverse causality. We aimed to investigate the bidirectional associations of physical activity with brain structure in middle-aged and older adults. Overall, 4365 participants (64.01 ± 10.82 years; 56% women) from the Rotterdam Study had physical activity and brain structure assessed on at least one of 2 timepoints ('baseline': 2006–2012 or 'follow-up': 2012-2017, median duration between visits: 5 years). Physical activity was assessed through the LASA Physical Activity Questionnaire. T1-weighted MRI and diffusion tensor imaging were used to quantify brain volumes and white matter microstructure, respectively. Cross-lagged panel models were performed to estimate bidirectional associations, and linear mixed-effects models to investigate the consistency of findings. Larger total brain volume (β = 0.067, 95%-confidence interval 0.035;0.099, p FDR = 0.001), gray matter volume (β = 0.063, 0.031;0.096, p FDR = 0.002), and white matter volume (β = 0.051, 0.020;0.083, p FDR = 0.013) at baseline were associated with higher levels of sports at follow-up. Lower global mean diffusivity at baseline was associated with higher levels of walking at follow-up (β = -0.074, -0.111;-0.037, p FDR = 0.001). No associations were found between physical activity levels at baseline and brain metrics at follow-up. In conclusion, larger brain volumes and white matter microstructure at baseline were associated with individuals remaining more physically active at follow-up. Overall, this study identified older adults with potentially advanced brain aging status as being at higher risk of physical inactivity over time, and therefore as potential target group for prevention and novel intervention strategies. [ABSTRACT FROM AUTHOR]

The locus coeruleus-noradrenergic system integrates signals about arousal states throughout the brain and helps coordinate cognitive selectivity. However, age-related changes in this system may impact how arousal coordinates selectivity in older adults. To examine this, we compared how increases in emotional arousal modulates cognitive selectivity for images differing in perceptual salience in young and older adults. Using functional magnetic resonance imaging, we found that relative to older adults, hearing an arousing sound enhanced young adults' bottom-up processing and incidental memory for high versus low salience category-selective body images. We also examined how arousing sounds impacted a top-down goal to detect dot-probes that appeared immediately after high or low salience images. We found that young adults were slower to detect probes appearing after high salience body images on arousing trials, whereas older adults showed this pattern on non-arousing trials. Taken together, our findings show that arousal's effect on selectivity changes with age and differs across bottom-up and top-down processing. [ABSTRACT FROM AUTHOR]

Aging changes autobiographical memory (AM), yet the neural correlates of these changes are poorly understood, likely due to methodological variability across studies. We conducted a quantitative meta-analysis using activation likelihood estimation (GingerALE 3.0.2) to identify regions AM retrieval engaged in younger and older adults across 45 studies (N younger = 24 studies, 357 participants, 349 foci; N older = 21 studies, 299 participants, 356 foci), considering methodological differences in cueing AMs (i.e., using generic vs. specific/personalized cues). Both age-groups commonly engaged a left-lateralized pattern of brain activity that included the hippocampus, retrosplenial/posterior cingulate cortex, and angular gyrus. Younger adults showed enhanced right posterior cingulate cortical activity, while older adults presented with bilateral activity in the hippocampus, and enhanced activity in left middle temporal gyrus, precuneus, and retrosplenial cortex. Exploratory analyses indicated that age-related commonalties and differences in brain activity depended on the method of AM cuing. These findings suggest that key regions of AM retrieval are preserved in older age, yet subtle changes exist, especially depending on how AMs are cued. [ABSTRACT FROM AUTHOR]

Nearly 75% of older adults in the US report balance problems. Although it is known that aging results in widespread brain atrophy, less is known about how brain structure relates to balance in aging. We collected T 1 - and diffusion-weighted MRI scans and measured postural sway of 36 young (18–34 years) and 22 older (66–84 years) adults during eyes open, eyes closed, eyes open-foam, and eyes closed-foam conditions. We calculated summary measures indicating visual, proprioceptive, and vestibular contributions to balance. Across both age groups, thinner cortex in multisensory integration regions was associated with greater reliance on visual inputs for balance. Greater gyrification within sensorimotor and parietal cortices was associated with greater reliance on proprioceptive inputs. Poorer vestibular function was correlated with thinner vestibular cortex, greater gyrification within sensorimotor, parietal, and frontal cortices, and lower free water-corrected axial diffusivity across the corona radiata and corpus callosum. These results expand scientific understanding of how individual differences in brain structure relate to balance and have implications for developing brain stimulation interventions to improve balance. [ABSTRACT FROM AUTHOR]

Aging is associated with cognitive changes, with strong variations across individuals. One way to characterize this individual variability is to use techniques such as magnetoencephalography (MEG) to measure the dynamics of neural synchronization between brain regions, and the variability of this connectivity over time. Indeed, few studies have focused on fluctuations in the dynamics of brain networks over time and their evolution with age. We therefore characterize aging effects on MEG phase synchrony in healthy young and older adults from the Cam-CAN database. Age-related changes were observed, with an increase in the variability of brain synchronization, as well as a reversal of the direction of information transfer in the default mode network (DMN), in the delta frequency band. These changes in functional connectivity were associated with cognitive decline. Results suggest that advancing age is accompanied by a functional disorganization of dynamic networks, with a loss of communication stability and a decrease in the information transmitted. [ABSTRACT FROM AUTHOR]

Vigor reflects how motivated people are to respond to stimuli. We previously showed that, on average, humans are more vigorous when a higher rate of reward is available, and that this relationship is modulated by the dopamine precursor levodopa. Dopamine signaling and probabilistic reward learning deteriorate across the adult life span, and thus, the relationship between vigor and reward may also change in aging. We tested this assertion and assessed whether it correlates with D1 dopamine receptor availability, measured using Positron Emission Tomography. We registered response times of 30 older and 30 younger participants during an oddball discrimination task where rewards varied systematically between trials. The average reward rate had a similar impact on vigor in both age groups. There was a weak positive association between ventral striatal dopamine receptor availability and the effect of average reward rate on response time. Overall, the effect of reward on response vigor was similar in younger and older adults, and weakly correlated with dopamine D1 receptor availability. [ABSTRACT FROM AUTHOR]

• Cognitive reserve (CR) modulates resting-state networks in healthy older adults. • High CR is associated to increased Frontal-Parietal Control Network connectivity and reduced Dorsal Attention Network connectivity. • High CR connectivity pattern are associated to better cognitive performance. Cognitive Reserve (CR) is considered a protective factor during the aging process. However, although CR is a multifactorial construct, it has been operationalized in a unitary way (years of formal education or IQ). In the present study, a validated measure to categorize CR holistically (Cognitive Reserve Index Questionnaire) was used to evaluate the resting-state functional connectivity in 77 cognitively unimpaired participants aged 50 years and over with high and low CR, and matched brain global atrophy levels. The connectivity of networks linked to attentional (Dorsal Attention Network -DAN-) and executive (Frontal-Parietal Control Network -FPCN-) processes were evaluated by the combination of Independent Component Analysis and seed-based approaches, since these networks have been proposed as candidates to underlie the protective effect of CR in the aging context. Participants with high CR showed an increase of the connectivity in the FPCN and a decrease in the DAN with respect to the low CR group, correlating with neuropsychological scores and supporting that high CR is related to a better neurocognitive preservation during aging. [ABSTRACT FROM AUTHOR]

Amyloid plaque aggregation is a pathologic hallmark of Alzheimer's disease (AD) that occurs early in the disease. However, little is known about its progression throughout the brain. Using Pittsburgh Compound B (PIB)-PET imaging, we investigated the progression of regional amyloid accumulation in cognitively normal older adults. We found that all examined regions reached their peak accumulation rates 24–28 years after an estimated initiation corresponding to the mean baseline PIB-PET signal in amyloid-negative older adults. We also investigated the effect of increased genetic risk conferred by the apolipoprotein-E ɛ4 allele on rates of amyloid accumulation, as well as the relationship between regional amyloid accumulation and regional tau pathology, another hallmark of AD, measured with Flortaucipir-PET. Carriers of the ɛ4 allele had faster amyloid accumulation in all brain regions. Furthermore, in all regions excluding the temporal lobe, faster amyloid accumulation was associated with greater tau burden. These results indicate that amyloid accumulates near-simultaneously throughout the brain and is associated with higher AD pathology, and that genetic risk of AD is associated with faster amyloid accumulation. [ABSTRACT FROM AUTHOR]

• Lower interference control in aging is associated with less white matter integrity • Increased interference in older age is associated with decreased Fornix integrity • White matter integrity mediates age-proactive interference relation in older age Proactive interference (PI) occurs when old information interferes with newly acquired information and has been suggested as a major cause of forgetting in working memory. In this study, we investigate cross-sectional (N = 267) and longitudinal (N = 148) associations between PI and white-matter integrity (WMI) using diffusion-weighted imaging in an adult life-span sample (25–80 years; Mage = 60.15; 138 female). Older age was related to higher PI and lower WMI. Cross-sectional analyses showed associations between PI and WMI spanning several white-matter tracts as well as globally, suggesting that the age-related decline in PI may be driven primarily by global changes in WMI. Furthermore, longitudinal changes in PI were shown to be negatively correlated with concurrent changes in WMI in the fornix. Mediation analyses showed that WMI mediated the relationship between age and PI only in older adults, indicating that WMI becomes increasingly connected to cognitive functioning with increasing age. This is the first demonstration of WMI decline contributing to the age-related decline in PI. [ABSTRACT FROM AUTHOR]

• Reserve is associated with more activation of the right caudate for high-load. • Caudate activation is linked to a reduced impact of age on working memory. • The activation is found in a region which is part of the fronto-striatal network. • Neural flexibility is a major substrate for cognitive reserve. The goal of this study was to identify the brain mechanisms underlying cognitive reserve using a parametric n-back working memory (WM) task in a sample of healthy older adults. We first identified the WM-related activations associated with years of education and then tested whether these activations mitigated the detrimental impact of age on cognition. Thirty-nine older adults received a magnetic resonance imaging examination while completing an n-back task with different levels of WM load (0-, 1- vs. 2-back). Results show that more education is associated with lower activation of the left medial superior frontal gyrus (BA8) in the 1-back condition and a greater activation of the right caudate nucleus in the 2-back condition. The caudate and frontal activations are task-positive and task-negative regions, respectively. Moderation analyses indicate that the effect of age on performance is less detrimental in participants with higher caudate activation in the 2-back condition. Overall, these results suggest that cognitive reserve is explained by a superior ability to flexibly engage greater or novel activation as cognitive demand increases. [ABSTRACT FROM AUTHOR]

Typical aging is associated with increases in false memory rates among older adults. Such errors are frequently associated with differential neural activity during encoding and retrieval in older compared to younger adults within visual cortices and the hippocampus. It remains unknown how pattern similarity reductions relate to false memories in healthy aging. Using encoding-retrieval similarity (ERS) analyses in a sample of younger and older adults, we examined how the similarity of neural patterns between memory phases associated with target and lure objects was impacted by age and contributed to false memory rates. Single-item ERS for targets and lures was reduced by age throughout much of the ventral visual stream and the posterior hippocampus. Furthermore, ERS associated with perceptual lures within the visual stream maintained differential relationships with false memory. Finally, a global ERS metric accounted for age deficits in single-item ERS, but did not contribute to false memory rates. These findings highlight the contribution of age-related reductions in ERS across multiple representational levels to false memories in healthy aging. [ABSTRACT FROM AUTHOR]

White matter hyperintensities (WMH) are among the most prominent structural changes observed in older adulthood. These changes coincide with functional changes to the intrinsic network organization of the aging brain. Yet little is known about how WMH are associated with changes to the whole-brain functional connectome in normal aging. We used a lesion prediction algorithm to quantify WMH as well as resting-state multiecho functional magnetic resonance imaging to characterize resting-state functional connectivity in a cross-sectional sample of healthy older adults (N = 105, 60–83 years of age). In a multivariate analysis, we found that higher lesion load was associated with a global pattern of network dedifferentiation, marked by lower within- and greater between- network connectivity. Network specific changes included greater visual network integration and greater posterior-anterior connectivity. The relationship between WMH and resting-state functional connectivity was negatively associated with fluid IQ as well as Blood Oxygen Level Dependent signal dimensionality. Reduced functional network segregation is a widely observed pattern of age-related change. Our findings show that these functional changes are associated with the accumulation of WMH in older adulthood. [ABSTRACT FROM AUTHOR]

One important factor contributing to age-related memory decline is the loss of distinctiveness with which information is represented in brain activity. This loss in neural selectivity may be driven by neural attenuation (i.e., reduced activation to target stimuli) or neural broadening (i.e., increased activation to nontarget stimuli). In this fMRI study, we assessed age differences in neural selectivity during first encoding, repeated encoding, and recognition, as well as the underlying pattern (broadening vs. attenuation). We found lower neural selectivity in older compared to younger adults during all memory stages. Crucially, while reduced selectivity in older adults was due to neural broadening during first encoding, it was driven by neural attenuation during recognition, but revealed no clear pattern during repeated encoding. Our findings suggest that intrinsic differences between memory stages may interact with neural activity to manifest as either neural broadening or attenuation. Moreover, despite these differential patterns, neural selectivity was highly correlated across memory stages, indicating that one common mechanism may underly distinct expressions of age-related neural dedifferentiation. [ABSTRACT FROM AUTHOR]

• A large sample of older adults (N = 907) with MRI and resting EEG were analyzed. • Voxel-wise white matter hyperintensities were linked to alpha oscillations. • Probability of voxel-wise white matter hyperintensities relates positively to occipital alpha power. • WMHs should be considered when investigating the aging effects on neural oscillations. Aging is associated with increased white matter hyperintensities (WMHs) and with alterations of alpha oscillations (7–13 Hz). However, a crucial question remains, whether changes in alpha oscillations relate to aging per se or whether this relationship is mediated by age-related neuropathology like WMHs. Using a large cohort of cognitively healthy older adults (N = 907, 60–80 years), we assessed relative alpha power, alpha peak frequency, and long-range temporal correlations from resting-state EEG. We further associated these parameters with voxel-wise WMHs from 3T MRI. We found that a higher prevalence of WMHs in the superior and posterior corona radiata as well as in the thalamic radiation was related to elevated alpha power, with the strongest association in the bilateral occipital cortex. In contrast, we observed no significant relation of the WMHs probability with alpha peak frequency and long-range temporal correlations. Finally, higher age was associated with elevated alpha power via total WMH volume. We suggest that an elevated alpha power is a consequence of WMHs affecting a spatial organization of alpha sources. [ABSTRACT FROM AUTHOR]

• Choice in reward task better modeled by gain-loss frequency than average reward • Older adults maintain suboptimal choices based on reward frequency • Younger adults show greater activation in OFC related to average reward • Older adults show greater frequency-based activation in DLPFC • Similar brain regions sensitive to average and frequency-based prediction error Research on the biological basis of reinforcement-learning has focused on how brain regions track expected value based on average reward. However, recent work suggests that humans are more attuned to reward frequency. Furthermore, older adults are less likely to use expected values to guide choice than younger adults. This raises the question of whether brain regions assumed to be sensitive to average reward, like the medial and lateral PFC, also track reward frequency, and whether there are age-based differences. Older (60-81 years) and younger (18-30 years) adults performed the Soochow Gambling task, which separates reward frequency from average reward, while undergoing fMRI. Overall, participants preferred options that provided negative net payoffs, but frequent gains. Older adults improved less over time, were more reactive to recent negative outcomes, and showed greater frequency-related activation in several regions, including DLPFC. We also found broader recruitment of prefrontal and parietal regions associated with frequency value and reward prediction errors in older adults, which may indicate compensation. The results suggest greater reliance on average reward for younger adults than older adults. [ABSTRACT FROM AUTHOR]

• Stimulation affected hippocampal network connectivity and memory in young adults. • Stimulation effects were rhythm-specific for theta-burst versus beta rhythms. • Theta-burst also increased connectivity in older adults, but non-selectively. • Stimulation did not affect memory in older adults. • Direct evidence that hippocampal network de-differentiation in aging is functional. Episodic memory is supported by hippocampal interactions with a distributed network. Aging is associated with memory decline and network de-differentiation. However, the role of de-differentiation in memory decline has not been directly tested. We reasoned that hippocampal network-targeted stimulation could test these theories, as age-related changes in the network response to stimulation would indicate network reorganization, and corresponding changes in memory would suggest that this reorganization is functional. We compared effects of stimulation on fMRI connectivity and memory in younger versus older adults. Theta-burst network-targeted stimulation of left lateral parietal cortex selectively increased hippocampal network connectivity and modulated memory in younger adults. In contrast, stimulation in older adults increased connectivity throughout the brain, without network selectivity, and did not influence memory. These findings provide evidence that network responses to stimulation are de-differentiated in aging and suggest that age-related de-differentiation is relevant for memory. This manuscript is part of the Special Issue entitled "Cognitive Neuroscience of Healthy and Pathological Aging" edited by Drs. M. N. Rajah, S. Belleville, and R. Cabeza. This article is part of the Virtual Special Issue titled COGNITIVE NEUROSCIENCE OF HEALTHY AND PATHOLOGICAL AGING. The full issue can be found on ScienceDirect at https://www.sciencedirect.com/journal/neurobiology-of-aging/special-issue/105379XPWJP. [ABSTRACT FROM AUTHOR]

• Age-related atrophy patterns indicated increased atrophy in early Braak regions • Phospho-tau levels were associated with hippocampal atrophy • Phospho-tau levels partially mediate age effects on the hippocampus • Primary age-related tauopathy may drive age-related medial temporal lobe changes Hippocampal atrophy is endemic in 'normal aging' but it is unclear what factors drive age-related changes in medial temporal lobe (MTL) structural measures. We investigated cross-sectional (n = 191) and longitudinal (n = 164) MTL atrophy patterns in cognitively normal older adults from ADNI-GO/2 with no to low cerebral β-amyloid and assessed whether white matter hyperintensities (WMHs) and cerebrospinal fluid (CSF) phospho tau (p-tau) levels can explain age-related changes in the MTL. Age was significantly associated with hippocampal volumes and Brodmann Area (BA) 35 thickness, regions affected early by neurofibrillary tangle pathology, in the cross-sectional analysis and with anterior and/or posterior hippocampus, entorhinal cortex and BA35 in the longitudinal analysis. CSF p-tau was significantly associated with hippocampal volumes and atrophy rates. Mediation analyses showed that CSF p-tau levels partially mediated age effects on hippocampal atrophy rates. No significant associations were observed for WMHs. These findings point toward a role of tau pathology, potentially reflecting Primary Age-Related Tauopathy, in age-related MTL structural changes and suggests a potential role for tau-targeted interventions in age-associated neurodegeneration and memory decline. [ABSTRACT FROM AUTHOR]

Elevated expression of β-amyloid (Aβ 1-42) and tau are considered risk-factors for Alzheimer's disease in healthy older adults. We investigated the effect of aging and cerebrospinal fluid levels of Aβ 1-42 and tau on 1) frontal metabolites measured with proton magnetic resonance spectroscopy (MRS) and 2) cognition in cognitively normal older adults (n = 144; age range 50-85). Levels of frontal gamma aminobutyric acid (GABA+) and myo-inositol relative to creatine (mI/tCr) were predicted by age. Levels of GABA+ predicted cognitive performance better than mI/tCr. Additionally, we found that frontal levels of n-acetylaspartate relative to creatine (tNAA/tCr) were predicted by levels of t-tau. In cognitively normal older adults, levels of frontal GABA+ and mI/tCr are predicted by aging, with levels of GABA+ decreasing with age and the opposite for mI/tCr. These results suggest that age- and biomarker-related changes in brain metabolites are not only located in the posterior cortex as suggested by previous studies and further demonstrate that MRS is a viable tool in the study of aging and biomarkers associated with pathological aging and Alzheimer's disease. [ABSTRACT FROM AUTHOR]

• tDCS over the preSMA improves inhibitory control performance in older adults. • Perceptual decision-making speed can be improved by preSMA tDCS, irrespective of age. • rIFG tDCS improved decision-making speed and inhibitory control in young adults. A wide body of literature suggests that transcranial direct current stimulation (tDCS) administered over the prefrontal cortex can improve executive function – including decision-making and inhibitory control – in healthy young adults. However, the effects of tDCS in older adults are largely unknown. Here, using a double-blind, sham-controlled approach, changes in a combined perceptual decision-making and inhibitory control task were assessed before and after the application of tDCS (1 mA, 20 minute) targeting the right inferior frontal gyrus (rIFG) or pre-supplementary motor area (preSMA) in 42 young (18–34 years) and 41 older (60–80 years) healthy adults. Compared to sham stimulation, anodal tDCS over the preSMA improved decision-making speed for both age groups. Furthermore, the inhibitory control performance of older and younger adults was improved by preSMA and rIFG stimulation, respectively. This study provides evidence that tDCS can improve both perceptual decision-making and inhibitory control in healthy older adults, with the causal role of the preSMA and rIFG regions in cognitive control appearing to vary as a function of healthy ageing. [ABSTRACT FROM AUTHOR]