Age-related Cognitive Changes Research Articles

Unveiling the molecular landscape of cognitive aging: insights from polygenic risk scores, DNA methylation, and gene expression

BackgroundAging represents a significant risk factor for the occurrence of cerebral small vessel disease, associated with white matter (WM) lesions, and to age-related cognitive alterations, though the precise mechanisms remain largely unknown. This study aimed to investigate the impact of polygenic risk scores (PRS) for WM integrity, together with age-related DNA methylation, and gene expression alterations, on cognitive aging in a cross-sectional healthy aging cohort. The PRSs were calculated using genome-wide association study (GWAS) summary statistics for magnetic resonance imaging (MRI) markers of WM integrity, including WM hyperintensities, fractional anisotropy (FA), and mean diffusivity (MD). These scores were utilized to predict age-related cognitive changes and evaluate their correlation with structural brain changes, which distinguish individuals with higher and lower cognitive scores. To reduce the dimensionality of the data and identify age-related DNA methylation and transcriptomic alterations, Sparse Partial Least Squares-Discriminant Analysis (sPLS-DA) was used. Subsequently, a canonical correlation algorithm was used to integrate the three types of omics data (PRS, DNA methylation, and gene expression data) and identify an individual “omics” signature that distinguishes subjects with varying cognitive profiles.ResultsWe found a positive association between MD-PRS and long-term memory, as well as a correlation between MD-PRS and structural brain changes, effectively discriminating between individuals with lower and higher memory scores. Furthermore, we observed an enrichment of polygenic signals in genes related to both vascular and non-vascular factors. Age-related alterations in DNA methylation and gene expression indicated dysregulation of critical molecular features and signaling pathways involved in aging and lifespan regulation. The integration of multi-omics data underscored the involvement of synaptic dysfunction, axonal degeneration, microtubule organization, and glycosylation in the process of cognitive aging.ConclusionsThese findings provide valuable insights into the biological mechanisms underlying the association between WM coherence and cognitive aging. Additionally, they highlight how age-associated DNA methylation and gene expression changes contribute to cognitive aging.

Effect of Fitness-To-Drive and Metacognition on Road Traffic Injury Among Older Taxi Drivers: Hierarchical Modeling.

Age-related cognitive and somatic motor skills changes have been linked to impaired driving abilities. Taxi drivers play an important role in providing public transportation services and security. This study aimed to examine the level of fitness-to-drive (FTD) and identify the predictors of self-reported traffic injury among the older taxi drivers. Taxi drivers 60years and older in Bangkok and the metropolitan area were enrolled. Hierarchical regression models were carried out to examine the effects of demographics, FTD, and metacognition towards self-reported road traffic injury. Totally, 46.1% of the respondents were classified as at-risk drivers. Drivers with alcohol consumption and low risk perception toward road safety were more likely to experience road traffic injury. Regular assessment of physical and psychometric capacity among older taxi drivers could provide another empirical basis to improve public safety transport.

Turkish dichotic sentence mobile scan test results in young and elderly people

BackgroundThis study investigated the impact of age on dichotic listening performance by comparing results from the Turkish Dichotic Sentence Mobile Screening Test in young and elderly individuals with normal hearing. A total of 60 adults (30 young, 30 old) underwent otoscopic examination, audiological tests, and, for the elderly group, a mini-mental test. The Turkish Dichotic Sentence Mobile Screening Test was administered, and directed and undirected scores for the right and left ears were compared between age groups.ResultsIn the young group, the directed left ear mean (96.67% ± 8.02%), directed right ear mean (98.33% ± 3.79%), undirected left ear mean (97.67% ± 6.26%), and undirected right ear mean (98.67% ± 5.71%) were obtained. In the elderly group, corresponding values were lower: directed left ear mean (49.00% ± 36.33%), directed right ear mean (54.67% ± 40.66%), undirected left ear mean (64.00% ± 32.86%), and undirected right ear mean (65.00% ± 30.82%). Statistically significant differences were found between the young and elderly groups (p < 0.001), with the young group consistently outperforming the elderly group.ConclusionsThese results align with existing literature on dichotic listening tests, highlighting age-related declines in performance. The study contributes valuable insights into age-related changes in auditory processing and cognition, emphasizing the importance of considering dichotic listening as a marker of cognitive aging. Future research should explore potential interventions to mitigate age-related declines in dichotic listening performance.

Online Mindful Movement Approach for Older Adults: Two Case Studies

ABSTRACT The COVID-19 pandemic had a devastating impact, especially on many older individuals. Outbreaks significantly affected accessibility and community engagement, making it challenging to maintain social connections with family, friends, and society. Social distancing measures and lockdown restrictions have been linked to challenges in physical and mental health, highlighting the urgent need for comprehensive strategies that can alleviate the pandemic’s impact and foster meaningful social connections, particularly for older adults experiencing age-related cognitive changes (ACC). In response, an online mindful movement approach (MMA) targeting loneliness and psychological wellbeing in older adults experiencing ACC (n = 16) was implemented. This paper presents a comparative analysis highlighting two case studies derived from the parent study, examining the impact of the online MMA for older adults experiencing ACC. Thematic analysis was employed to analyze the two cases. The participants reported a decrease in loneliness along with notable improvements in self-awareness, mood, and social connectedness. Additionally, they experienced an enhancement in their mindfulness practice and discovered new ways to use movement to enhance their well-being. The findings suggested that online MMA offered an alternative platform that can provide physical and psychosocial health benefits to older adults experiencing ACC during the COVID-19 pandemic.

Audiovisual speech perception in noise in younger and older bilinguals.

Speech perception in noise becomes increasingly difficult with age. Similarly, bilinguals often have difficulty with speech perception in noise in their second language (L2) due to less developed language knowledge in L2. Little is known about older bilinguals, who experience age-related sensory and cognitive changes but have extensive L2 experience. Furthermore, while audiovisual (AV) speech cues and supportive sentence context facilitate speech perception in noise in native listeners, much less is known for bilingual listeners, particularly older bilinguals. This study investigated how much young (n = 30) and older (n = 31) French-English/English-French bilinguals benefit from AV speech cues and sentence context in their first (L1) and second language during speech perception in noise. Participants completed the task in L1 and L2. Importantly, the level of background noise was individually calibrated for each participant to equate performance during the baseline task. The results suggest that there were no age differences in overall performance during the speech perception in noise task. However, older adults showed smaller language effects and smaller modality effects (i.e., comparing auditory-only speech perception to audiovisual speech perception) compared to younger adults. Furthermore, both young and older bilinguals benefited from AV speech cues and sentence context in both of their languages. However, during L2 speech perception in noise, visual speech cues were particularly important for young adults. In contrast, older adults show equal benefit from visual speech cues in L1 and L2. Taken together, these findings extend current models of AV speech perception to a second language in both younger and older adults. Furthermore, the findings suggest that bilinguals are likely to benefit from visual speech cues and supportive sentence context, although this benefit may differ slightly between younger and older bilinguals. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Exploring age-related changes in saccades during cognitive tasks in healthy adults.

Although eye movements such as saccades are related to internal cognitive processes and are independent of visual processing, few studies have investigated whether non-visual cognitive tasks simultaneously affect horizontal and vertical saccades in younger and older adults. We recruited 28 younger adults aged 20-29 years and 26 older adults aged >60 years through advertisements in community settings. All participants were free of major psychiatric, neurological, or ocular diseases. All participants performed the mental arithmetic task (MAT) and verbal fluency task (VFT). The primary measures were saccade parameters, including frequency, mean amplitude, and mean velocity. During MAT and VFT, the frequencies of horizontal and vertical saccades increased (p = 0.0005 for horizontal saccade in MAT; p < 0.0001 for horizontal saccade in VFT; p = 0.012 for vertical saccade in MAT; p = 0.001 for vertical saccade in VFT), but were comparable between MAT and VFT. The old group showed a slower vertical saccade than the young group during the tasks (p = 0.011 in the MAT phase; p = 0.006 in the VFT phase). The amplitude of the horizontal saccade decreased in both groups during MAT compared to the resting period (p = 0.013), but did not change significantly during VFT. Saccade parameters can change during non-visual cognitive tasks with differences between age groups and saccade directions. This study significantly contributes to our understanding of the distinct dynamics of horizontal and vertical saccades across various age group in cognitive aging, despite its restricted focus on specific saccade parameters and cognitive tasks, and inclusion solely of cognitively normal individuals. This study highlights the importance of saccade analysis in elucidating age-related cognitive changes. In conclusion, saccades should be examined in future studies as a potential non-invasive biomarker for early detection of cognitive decline and neurodegenerative diseases.

MAINTENANCE OF HEALTH BEHAVIOR CHANGE: RECOMMENDATIONS FOR FUTURE RESEARCH

Abstract Modifying poor health behaviors can enhance function, improve quality-of-life, and reduce morbidity and mortality among older adults. However, achieving and sustaining behavior change can be difficult. A growing body of research suggest that initiation and maintenance are unique constructs within health behavior change; each requiring unique skills and each associated with unique outcomes. Although some leading health behavior change models (e.g., Transtheoretical Model of Change) include maintenance as a construct, maintenance is often overlooked in the scientific literature. As part of a NIA Research Centers Collaborative Network (RCCN) pilot award, this project utilized a series of qualitative activities to explore the concept of maintenance and identify future recommendations for advancing the field. Three unique listening sessions were conducted with clinician-researchers (1 group) and community-based service organizations (2 groups). An interdisciplinary expert think tank was then convened to reflect on key findings. All sessions were conducted virtually; transcripts were reviewed using a priori themes with additional themes generated by an open coding approach. Major themes included the following: (1) To date, there is no consensus definition of maintenance nor is there agreement on maintenance across behaviors. (2) Few behavior change models consider how health behaviors must shift to accommodate for age-related changes in cognition and/or physical function. (3) Existing funding mechanisms and timelines may not allow sufficient follow-up periods to examine maintenance over time. (4) Although the terms maintenance and sustainment are used interchangeably, community leaders emphasized the importance of sustaining health promotion programs in order to enable maintenance to occur.

EVALUATION OF AN OFF-THE-SHELF, WEARABLE ACTIGRAPH SYSTEM FOR USE BY OLDER COUPLES

Abstract There are many off-the-shelf wearable devices that provide the user with information regarding their physical activity and sleep patterns. Little is known about how easy it is for older individuals to use these devices. We tested a wrist-worn actigraph on couples both of whom were at least 70 years old. The aim was to evaluate the usability of the device, and to share data within the couples. Mixed methods were used to collect data. Over the three-week trial, 14 couples, nine of which had one member with mild cognitive impairment, used the system. Each person wore a Garmin Vivofit 4 continuously and used the Garmin application installed on an iPad mini to compare and review results over time. At the end of weeks one and three, participants completed the positively scored System Usability Scale (SUS), and each week met with the researcher to discuss the data and system usability. All couples were able to work together to use the system after being trained. Scores on the SUS indicated the system was moderately easy to use. Qualitative findings were that most participants (88%) liked being able to wear the device continuously, without breaks for charging. They compared information about their activity and sleep patterns within the dyad. There were several age-specific usability challenges, but use of off-the-shelf actigraphs by older individuals holds promise if age-related physical and cognitive changes are considered during selection of the device.

1 Detection of Cognitive Subtypes Within Cognitively Normal Older Adults Using Hierarchical Community Detection

Objective:Identifying individuals at the earliest stages of Alzheimer’s Disease (AD) would enable development and study of interventions prior to onset of symptoms. However, differentiating age-related cognitive changes from subtle pathological changes remains a challenge in the field. Methods that would enable earlier detection of AD in elders with no subjective or objective cognitive concerns (i.e., individuals in the preclinical stage) would be of great interest. Community detection, a metric founded in graph theory, offers an alternative approach for characterizing subtle heterogeneity within aging samples and has the potential to inform cognitive variability in aging.Participants and Methods:Using a hierarchical community detection, we examined whether cognitive subtypes could be identified in 226 cognitively normal older adults (from the Alzheimer’s Disease Neuroimaging Initiative [ADNI] study). Cognitive profiles of each community were characterized first using MANOVAs to examine the relationship between community membership and 12 age-, gender-, and education-corrected neuropsychological variables. Pair-wise comparisons were examined for significant main effects. We then examined whether these subtypes were related to biomarkers (cortical volumes, fluorodeoxyglucose (FDG)-positron emission tomography (PET) hypometabolism) or clinical progression. All p values were corrected for multiple comparisons.Results:Three communities (i.e., cognitive subtypes) were identified within the healthy aging sample. The first and largest community identified (N = 106) was characterized by a relative weakness on a single measure visuospatial executive function. Both the second (N = 76) and third community (N = 44) scored significantly lower on immediate, delayed, and recognition memory relative to the first community. The third community was characterized by a relative weakness in category fluency and speeded visual sequencing as well (p &lt; .000). The three communities did not differ on age, gender, education, race, or ethnicity. Community membership was associated with entorhinal volume (with the second and third communities having significantly smaller entorhinal volumes than the first community), though community membership was not significantly associated with other biomarkers examined. Conversion rate reached trend level significance at 12 month follow up (more converters in the third community).Conclusions:Hierarchical community detection is an alternative method for characterizing neuropsychological variation and it appears sensitive to relatively small differences that may be observed in a normal aging sample. While the sample size was relatively small, this approach shows promise for potentially leading to earlier detection of cognitive decline among individuals classified to be aging normally (e.g., community 3).

Cognitive correlates of reduced driving performance in healthy older adults: A meta-analytic review

Aims / ObjectivesThis meta-analytic review examines the evidence for the relationship between cognitive function and driving performance in older adults. The primary aims of this review were: (a) to identify cognitive correlates of reduced driving performance in older adults and (b) to determine whether such measures reliably predict reductions in driving performance over time. MethodsThis review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Peer reviewed studies that examined the (cross-sectional or longitudinal) relationship between standardised neuropsychological test performance measures and driving performance (e.g., via an on-road test, in-vehicle monitoring system, hazard perception test or driving simulator) in healthy adults aged 60 years and older, were included. Results/DiscussionEighteen studies were eligible for inclusion, of which 12 met requirements for meta-analysis. The results indicated that reaction time and Trail Making Test (TMT) A scores exhibited small-to-moderate correlations with driving performance, with moderate effects identified for block design, TMT B, Useful Field of View (UFOV) 2 and 3 tests. Further, no significant relationships were observed between the Mini-Mental State Examination and UFOV 1 with driving performance. Due to a paucity of data, the longitudinal relationship between such measures and driving could not be identified. The findings highlight (a) the potential of cognitive assessments to identify older adults at risk of driving impairment (as part of a larger diagnostic assessment), and (b) the urgent need for prospective longitudinal studies in investigating the impact of age-related changes in cognition on driving performance over time.

The integrity of dopaminergic and noradrenergic brain regions is associated with different aspects of late-life memory performance

Changes in dopaminergic neuromodulation play a key role in adult memory decline. Recent research has also implicated noradrenaline in shaping late-life memory. However, it is unclear whether these two neuromodulators have distinct roles in age-related cognitive changes. Here, combining longitudinal MRI of the dopaminergic substantia nigra–ventral tegmental area (SN-VTA) and noradrenergic locus coeruleus (LC) in younger (n = 69) and older (n = 251) adults, we found that dopaminergic and noradrenergic integrity are differentially associated with memory performance. While LC integrity was related to better episodic memory across several tasks, SN-VTA integrity was linked to working memory. Longitudinally, we found that older age was associated with more negative change in SN-VTA and LC integrity. Notably, changes in LC integrity reliably predicted future episodic memory. These differential associations of dopaminergic and noradrenergic nuclei with late-life cognitive decline have potential clinical utility, given their degeneration in several age-associated diseases.

Brain Connectivity Correlates of Cognitive Dispersion in a Healthy Middle-Aged Population: Influence of Subjective Cognitive Complaints.

Cognitive dispersion, representing intraindividual fluctuations in cognitive performance, is associated with cognitive decline in advanced age. We sought to elucidate sociodemographic, neuropsychological, and brain connectivity correlates of cognitive dispersion in middle age, and further consider potential influences of the severity of subjective cognitive complaints (SCC). Five hundred and twenty healthy volunteers from the Barcelona Brain Health Initiative (aged 40-66 years; 49.6% females, 453 with magnetic resonance imaging acquisitions) were included and stratified into high and low SCC groups. Two analysis steps were undertaken: (1) for the whole sample and (2) by groups. Generalized linear models and analysis of covariance were implemented to study associations between cognitive dispersion and performance (episodic memory, speed of processing, and executive function), white matter integrity, and resting-state functional connectivity (rs-FC) of the default mode network (DMN) and dorsal attentional networks (DAN). Across-domain dispersion was negatively related to cognitive performance, rs-FC within the DMN, and between the DMN and the DAN, but not to white matter integrity. The rs-FC values were not explained by cognitive performance. When considering groups, the above findings were significant only for those with high SCC. In healthy middle-aged individuals, high cognitive dispersion was related to poorer cognition and DMN dysregulation, being these associations stronger among subjects with high SCC. The present results reinforce the interest in considering dispersion measures within neuropsychological evaluations, as they may be more sensitive to incipient age-related cognitive and functional brain changes than traditional measures of performance.

Investigating the effects of age and prior military service on fluid and crystallized cognitive functions using virtual morris water maze (vMWM) and NIH Toolbox tasks

Much of current knowledge of aging involves war veterans and research about age-related cognitive changes in veterans involves generalized or single function tests or health or neurological disorders. The current study examined military service within the context of comparisons of young and old humans involving generally healthy individuals to address normal age-associated cognitive changes. Adult participants included 11 young females (8 non-veterans; 3 veterans; 21–31 years), 5 young males (non-veterans, 21-24 years), 9 older females (non-veterans, 62–80 years), and 21 older males (11 non-veterans; 10 veterans; 60–86 years). They were tested in virtual Morris water maze (vMWM) tasks, which were designed to test spatial learning, cognitive flexibility and working memory, similar to rodent studies, and were validated by correlations with specific NIH Toolbox (NIH-TB) Cognitive Battery or Wechsler Memory Scale (WMS) Logical Memory I and II tests. Significant age-related deficits were seen on multiple vMWM tasks and NIH-TB fluid cognition tasks. Among older males, vMWM tasks appeared to be more sensitive, based on finding statistical differences, to prior military service than NIH Toolbox tasks. Compared with male non-veterans of comparable age and younger, older male veterans exhibited significant deficits in spatial learning, cognitive flexibility, and working memory on vMWM tasks. Our findings support continued development and characterization of vMWM tasks that are comparable between rodents and humans for translating aging interventions between species, and provide impetus for larger investigations examining the extent to which prior military service can serve as a “hidden” variable in normal biological declines of cognitive functions.

Mind the gap: trajectory of cognitive development in young individuals with sickle cell disease: a cross-sectional study.

Compared to typically developing children and young adults (CYA-TD), those living with Sickle Cell Disease (CYA-SCD) experience more cognitive difficulties, particularly with executive function. Few studies have examined the relative importance of silent cerebral infarction (SCI), haemoglobin and arterial oxygen content on age-related cognitive changes using cross-sectional or longitudinal (developmental trajectory) data. This study presents cohort data from a single timepoint to inform studies with multiple timepoints. We compared cross-sectional raw and scaled scores as age-related changes in cognition (trajectories) in CYA-SCD and age-and ethnicity-matched CYA-TD. We also compared cross-sectional age-related changes in cognition (trajectories) in CYA-SCD with and without SCI to CYA-TD. General cognitive abilities were assessed using Wechsler Intelligence Scales, including the Verbal Comprehension Index (VCI) and Perceptual Reasoning Index (PRI) underpinning IQ. Executive function was evaluated using the Delis-Kaplan Executive Function System (D-KEFS) Tower subtest and the Behaviour Rating Inventory of Executive Function (BRIEF) questionnaire. SCI were identified from contemporaneous 3 T MRI; participants with overt stroke were excluded. Recent haemoglobin was available and oxygen saturation (SpO2) was measured on the day of the MRI. Data were available for 120 CYA-SCD [62 male; age = 16.78 ± 4.79 years; 42 (35%) with SCI] and 53 CYA-TD (23 male; age = 17.36 ± 5.16). Compared with CYA-TD, CYA-SCD experienced a delayed onset in VCI and slower rate of development for BRIEF Global Executive Composite, Metacognition Index (MI), and Behaviour Regulation Index. The rate of executive function development for the BRIEF MI differed significantly between CYA-TD and CYA-SCD, with those with SCI showing a 26% delay compared with CYA-TD. For CYA-SCD with SCI, arterial oxygen content explained 22% of the variance in VCI and 37% in PRI, while haemoglobin explained 29% of the variance in PRI. Age-related cognitive trajectories of CYA-SCD may not be impaired but may progress more slowly. Longitudinal studies are required, using tests unaffected by practice. In addition to initiation of medical treatment, including measures to improve arterial oxygen content, early cognitive intervention, educational support, and delivery of extracurricular activities could support cognitive development for CYA-SCD.Graphical Abstract.

The use of driver screening tools to predict self-reported crashes and incidents in older drivers

There is a clear need to identify older drivers at increased crash risk, without additional burden on the individual or licensing system. Brief off-road screening tools have been used to identify unsafe drivers and drivers at risk of losing their license. The aim of the current study was to evaluate and compare driver screening tools in predicting prospective self-reported crashes and incidents over 24 months in drivers aged 60 years and older. 525 drivers aged 63–96 years participated in the prospective Driving Aging Safety and Health (DASH) study, completing an on-road driving assessment and seven off-road screening tools (Multi-D battery, Useful Field of View, 14-Item Road Law, Drive Safe, Drive Safe Intersection, Maze Test, Hazard Perception Test (HPT)), along with monthly self-report diaries on crashes and incidents over a 24-month period. Over the 24 months, 22% of older drivers reported at least one crash, while 42% reported at least one significant incident (e.g., near miss). As expected, passing the on-road driving assessment was associated with a 55% [IRR 0.45, 95% CI 0.29–0.71] reduction in self-reported crashes adjusting for exposure (crash rate), but was not associated with reduced rate of a significant incident. For the off-road screening tools, poorer performance on the Multi-D test battery was associated with a 22% [IRR 1.22, 95% CI 1.08–1.37] increase in crash rate over 24 months. Meanwhile, all other off-road screening tools were not predictive of rates of crashes or incidents reported prospectively. The finding that only the Multi-D battery was predictive of increased crash rate, highlights the importance of accounting for age-related changes in vision, sensorimotor skills and cognition, as well as driving exposure, in older drivers when using off-road screening tools to assess future crash risk.

Source connectivity patterns in the default mode network differ between elderly golf-novices and non-golfers

Learning to play golf has high demands on attention and therefore may counteract age-related changes of functional brain networks. This cross-sectional study compared source connectivity in the Default Mode Network (DMN) between elderly golf novices and non-golfers. Four-minute resting-state electroencephalography (128 channels) from 22 elderly people (mean age 67 ± 4.3 years, 55% females) were recorded after completing a 22-week golf learning program or after having continued with normal life. Source connectivity was assessed after co-registration of EEG data with native MRI within pre-defined portions of the DMN in the beta band (14–25 Hz). Non-golfers had significantly higher source connectivity values in the anterior DMN compared to non-golfers. Exploratory correlation analyses did not indicate an association to cognitive performance in either group. Inverse correlations between a marker of external attention with source connectivity of the anterior DMN may suggest a trend in the golf group only, but have to be replicated in future studies. Clinical relevance of these findings remains to be elucidated, but the observed difference in the anterior DMN may provide a starting point to further investigate if and how learning golf may have an impact on physiological age-related cognitive changes.

Journal Digest: CBT With Cardiac Rehab, PMDD Neurochemistry, and More

Journal Digest: CBT With Cardiac Rehab, PMDD Neurochemistry, and More

Age-Related Trajectories of General Fluid Cognition and Functional Decline in the Health and Retirement Study: A Bivariate Latent Growth Analysis.

There have been few studies on associations between age-related declines in fluid cognition and functional ability in population-representative samples of middle-aged and older adults. We used a two-stage process (longitudinal factor analysis followed by structural growth modeling) to estimate bivariate trajectories of age-related changes in general fluid cognition (numeracy, category fluency, executive functioning, and recall memory) and functional limitation (difficulties in daily activities, instrumental activities, and mobility). Data came from the Health and Retirement Study (Waves 2010-2016; N = 14,489; ages 50-85 years). Cognitive ability declined on average by -0.05 SD between ages 50-70 years, then -0.28 SD from 70-85 years. Functional limitation increased on average by +0.22 SD between ages 50-70 years, then +0.68 SD from 70-85 years. Significant individual variation in cognitive and functional changes was observed across age windows. Importantly, cognitive decline in middle age (pre-age 70 years) was strongly correlated with increasing functional limitation (r = -.49, p < .001). After middle age, cognition declined independently of change in functional limitation. To our knowledge, this is the first study to estimate age-related changes in fluid cognitive measures introduced in the HRS between 2010-2016.

CCR3 plays a role in murine age-related cognitive changes and T-cell infiltration into the brain

Targeting immune-mediated, age-related, biology has the potential to be a transformative therapeutic strategy. However, the redundant nature of the multiple cytokines that change with aging requires identification of a master downstream regulator to successfully exert therapeutic efficacy. Here, we discovered CCR3 as a prime candidate, and inhibition of CCR3 has pro-cognitive benefits in mice, but these benefits are not driven by an obvious direct action on central nervous system (CNS)-resident cells. Instead, CCR3-expressing T cells in the periphery that are modulated in aging inhibit infiltration of these T cells across the blood-brain barrier and reduce neuroinflammation. The axis of CCR3-expressing T cells influencing crosstalk from periphery to brain provides a therapeutically tractable link. These findings indicate the broad therapeutic potential of CCR3 inhibition in a spectrum of neuroinflammatory diseases of aging.

Effects of Brain Maintenance and Cognitive Reserve on Age-Related Decline in Three Cognitive Abilities.

Age-related cognitive changes can be influenced by both brain maintenance (BM), which refers to the relative absence over time of changes in neural resources or neuropathologic changes, and cognitive reserve (CR), which encompasses brain processes that allow for better-than-expected behavioral performance given the degree of life-course-related brain changes. This study evaluated the effects of age, BM, and CR on longitudinal changes over 2 visits, 5 years apart, in 3 cognitive abilities that capture most of age-related variability. Participants included 254 healthy adults aged 20-80 years at recruitment. Potential BM was estimated using whole-brain cortical thickness and white matter mean diffusivity at both visits. Education and intelligence quotient (IQ; estimated with American National Adult Reading Test) were tested as moderating factors for cognitive changes in the 3 cognitive abilities. Consistent with BM-after accounting for age, sex, and baseline performance-individual differences in the preservation of mean diffusivity and cortical thickness were independently associated with relative preservation in the 3 abilities. Consistent with CR-after accounting for age, sex, baseline performance, and structural brain changes-higher IQ, but not education, was associated with reduced 5-year decline in reasoning (β = 0.387, p = .002), and education was associated with reduced decline in speed (β = 0.237, p = .039). These results demonstrate that both CR and BM can moderate cognitive changes in healthy aging and that the 2 mechanisms can make differential contributions to preserved cognition.