Cognitive and neuroscientific perspectives of healthy ageing.

With dementia incidence projected to escalate significantly within the next 25 years, the United Nations declared 2021-2030 the Decade of Healthy Ageing, emphasising cognition as a crucial element. As a leading discipline in cognition and ageing research, psychology is well-equipped to offer insights for translational research, clinical practice, and policy-making. In this comprehensive review, we discuss the current state of knowledge on age-related changes in cognition and psychological health. We discuss cognitive changes during ageing, including (a) heterogeneity in the rate, trajectory, and characteristics of decline experienced by older adults, (b) the role of cognitive reserve in age-related cognitive decline, and (c) the potential for cognitive training to slow this decline. We also examine ageing and cognition through multiple theoretical perspectives. We highlight critical unresolved issues, such as the disparate implications of subjective versus objective measures of cognitive decline and the insufficient evaluation of cognitive training programs. We suggest future research directions, and emphasise interdisciplinary collaboration to create a more comprehensive understanding of the factors that modulate cognitive ageing.

When I am sixty-four evaluating language markers of well-being in healthy aging narratives.

Natural language use is a promising candidate for the development of innovative measures of well-being to complement self-report measures. The type of words individuals use can reveal important psychological processes that underlie well-being across the lifespan. In this preregistered, cross-sectional study, we propose a conceptual model of language markers of well-being and use written narratives about healthy aging (N = 701) and computerized text analysis (LIWC) to empirically validate the model. As hypothesized, we identified a model with three groups of language markers (reflecting affective, evaluative, and social processes). Initial validation with established self-report scales (N = 30 subscales) showed that these language markers reliably predict core components of well-being and underlying processes. Our results support the concurrent validity of the conceptual language model and allude to the added benefits of language-based measures, which are thought to reflect less conscious processes of well-being. Future research is needed to continue validating language markers of well-being across the lifespan in a theoretically informed and contextualized way, which will lay the foundation for inferring people's well-being from their natural language use.

Functionally annotated electrophysiological neuromarkers of healthy ageing and memory function.

The unprecedented increase in life expectancy presents a unique opportunity and the necessity to explore both healthy and pathological aspects of ageing. Electroencephalography (EEG) has been widely used to identify neuromarkers of cognitive ageing due to its affordability and richness in information. However, despite the growing volume of data and methodological advancements, the abundance of contradictory and non-reproducible findings has hindered clinical translation. To address these challenges, our study introduces a comprehensive workflow expanding on previous EEG studies and investigates various static and dynamic power and connectivity estimates as potential neuromarkers of cognitive ageing in a large dataset. We also assess the robustness of our findings by testing their susceptibility to band specification. Finally, we characterise our findings using functionally annotated brain networks to improve their interpretability and multi-modal integration. Our analysis demonstrates the effect of methodological choices on findings and that dynamic rather than static neuromarkers are not only more sensitive but also more robust. Consequently, they emerge as strong candidates for cognitive ageing neuromarkers. Moreover, we were able to replicate the most established EEG findings in cognitive ageing, such as alpha oscillation slowing, increased beta power, reduced reactivity across multiple bands, and decreased delta connectivity. Additionally, when considering individual variations in the alpha band, we clarified that alpha power is characteristic of memory performance rather than ageing, highlighting its potential as a neuromarker for cognitive ageing. Finally, our approach using functionally annotated source reconstruction allowed us to provide insights into domain-specific electrophysiological mechanisms underlying memory performance and ageing. HIGHLIGHTS: We provide an open and reproducible pipeline with a comprehensive workflow to investigate static and dynamic EEG neuromarkers. Neuromarkers related to neural dynamics are sensitive and robust. Individualised alpha power characterises cognitive performance rather than ageing. Functional annotation allows cross-modal interpretation of EEG findings.

An Investigation of the Sled-Push Exercise Using a Resisted Sled Machine in Apparently Healthy Older Adults: An Exploratory Study.

Physical function is regarded as the cornerstone of healthy aging, and exercise is an important determinant of healthy aging. This study examined the feasibility and physiological (heart rate, blood pressure, blood lactate, and rate of perceived exertion) and psychological (enjoyment) response resulting from an acute progressive sled-push (SLP) exercise session using the novel XPO Sled Trainer in older adults and compared that with walking (WKC) condition. The exercise session comprised six exercise bouts at 75%, 85%, 100% (2×), and 125% (2×) of normal velocity with a 2-min rest between bouts. Thirty-six older adults were randomly allocated into either the SLP or WKC conditions. No adverse events were observed during the exercise session, and all participants completed the exercise protocol as prescribed. One-third of the participants in the SLP group reported minimal body discomfort. Significantly higher responses were observed for all physiological variables as the intensity of the exercise increased in the SLP group compared with the WKC group (p < .001). The SLP group presented a decline in enjoyment as the intensity of the exercise increased (during), but similar enjoyment level than the WKC group for the overall exercise session (p = .711). Our findings support the viability and safety of SLP exercise using the XPO Sled Trainer in older adults. Such exercise demonstrated an intensity-driven modality that may have potential to elucidate positive adaptations in the cardiovascular system of older adults with acceptable levels of enjoyment.

Normative data beyond the total scores: a process score analysis of the Rey's 15 word test in healthy aging and Alzheimer's Disease.

BACKGROUND: The Rey's 15 words test is currently the most frequently used task in Italy to detect memory deficits in AD. The current standardised version is however quite outdated and lacks some cognitive indexes which may highlight problems in recall or encoding processes. The aim of the study was to update the normative data of the test and to consider some variables which were not accounted for in the original study, that is, recognition, learning rate and forgetfulness. We also adopted the process scores approach to ascertain the effects of serial position (primacy and recency). METHODS: Three hundred ninety-six healthy participants were recruited. To detect any variables useful for intercepting the early stages of dementia, a group of 208 patients in the very early stage of AD was also recruited. Linear models were used to calculate the corrections scores for age, education, and gender, and ROCs were used to calculate cut-offs based on the maximum sum of sensitivity and specificity and the positive and negative predictive values. RESULTS: All main indexes showed excellent Area Under the Curve (0.90-1), strong sensitivity and PPVs for distinguishing between the HCs and AD participants. However, the Intrusions index performed poorly in all parameters. CONCLUSION: The study provides updated, normative data which may be reliably used as a cognitive marker to detect early AD. The strength of the study is the large sample size and the number of indexes which make it possible to explore the utility of memory test process scores.

Increased hyaluronan by naked mole-rat Has2 improves healthspan in mice.

Abundant high-molecular-mass hyaluronic acid (HMM-HA) contributes to cancer resistance and possibly to the longevity of the longest-lived rodent-the naked mole-rat1,2. To study whether the benefits of HMM-HA could be transferred to other animal species, we generated a transgenic mouse overexpressing naked mole-rat hyaluronic acid synthase 2 gene (nmrHas2). nmrHas2 mice showed an increase in hyaluronan levels in several tissues, and a lower incidence of spontaneous and induced cancer, extended lifespan and improved healthspan. The transcriptome signature of nmrHas2 mice shifted towards that of longer-lived species. The most notable change observed in nmrHas2 mice was attenuated inflammation across multiple tissues. HMM-HA reduced inflammation through several pathways, including a direct immunoregulatory effect on immune cells, protection from oxidative stress and improved gut barrier function during ageing. These beneficial effects were conferred by HMM-HA and were not specific to the nmrHas2 gene. These findings demonstrate that the longevity mechanism that evolved in the naked mole-rat can be exported to other species, and open new paths for using HMM-HA to improve lifespan and healthspan.

Sense of purpose in life and allostatic load in two longitudinal cohorts.

OBJECTIVE: Sense of purpose in life has been linked with better physical health, longevity, and reduced risk for disability and dementia, but the mechanisms linking sense of purpose with diverse health outcomes are unclear. Sense of purpose may promote better physiological regulation in response to stressors and health challenges, leading to lower allostatic load and disease risk over time. The current study examined the association between sense of purpose in life and allostatic load over time in adults over age 50. METHODS: Data from the nationally representative US Health and Retirement Study (HRS) and English Longitudinal Study of Ageing (ELSA) were used to examine associations between sense of purpose and allostatic load across 8 and 12 years of follow-up, respectively. Blood-based and anthropometric biomarkers were collected at four-year intervals and used to compute allostatic load scores based on clinical cut-off values representing low, moderate, and high risk. RESULTS: Population-weighted multilevel models revealed that sense of purpose in life was associated with lower overall levels of allostatic load in HRS, but not in ELSA after adjusting for relevant covariates. Sense of purpose in life did not predict rate of change in allostatic load in either sample. CONCLUSIONS: The present investigation supports sense of purpose predicting preserved differentiation of allostatic regulation, with more purposeful individuals demonstrating consistently lower allostatic load over time. Persistent differences in allostatic burden may account for divergent health trajectories between individuals low and high in sense of purpose.

Identifying subtle functional change in individuals with mild cognitive impairment: development and validation of the Healthy Brain Ageing - Functional Assessment Questionnaire.

Accumulating research suggests that individuals with Mild Cognitive Impairment (MCI) experience subtle functional changes, but that available functional assessment tools are insensitive to this. To address this gap, we describe the development and validation of the self-report, "Healthy Brain Ageing Functional Assessment Questionnaire" (HBA-FAQ). We examined the factor structure and psychometric properties of the HBA-FAQ in 503 participants with normal cognition, subjective cognitive decline (SCD), MCI or dementia. Our results found the HBA-FAQ to have good reliability, validity and stronger discriminative ability between healthy control participants and those with SCD (0.734, p = .001), MCI (0.666, p = .012) and dementia (0.798, p < .001) compared to a widely-used instrumental activities of daily living screener. In conclusion, the HBA-FAQ is a valid, reliable self-report tool, providing an efficient and sensitive approach to identifying subtle changes in daily functioning in older people at risk of dementia.

Establishment of Clinical Construct of Intrinsic Capacity in Older Adults and Its Prediction of Functional Decline.

Background: The World Health Organization has conceptualised the health and healthcare of older adults around the concept of healthy ageing. Healthy ageing is defined as "the process of developing and maintaining the functional ability that enables well-being in older age". This functional ability is the sum of two key factors: intrinsic capacity and interacting environment. This concept of intrinsic capacity encompasses a wide spectrum of health characteristics including the physiological and psychological changes associated with the ageing process. In general, IC declines from a high and stable state to an impaired status as people age. Monitoring individuals for changes in intrinsic capacity in the context of their environment will provide a holistic method of tracking the functioning of older adults at both a population and individual level, providing an opportunity to address any reversible factors of decline. However, this would require a clear and objective conceptualisation of the concept of intrinsic capacity. Methodology: One hundred subjects were recruited via invitation by advertisement on the institute campus. Study participants underwent detailed physical examination and measurement of various physical and chemical biomarkers which were likely to represent intrinsic capacity as evidenced by the literature review. Outcomes measured were a decline in ADL, IADL, mortality and hospitalisation over a follow-up period of six months. Exploratory factor analysis (EFA) was done to obtain a clinical construct of the proposed entity of intrinsic capacity. Unpaired t-test and univariate logistic regression were used to check for the association between the composite score (IC) and its domains with the decline in ADL, IADL, mortality and hospitalisation. Results: One composite score (composite IC score) and eight subfactors emerged. The composite score and subfactor domains showed good construct validity. Composite intrinsic capacity score and subdomains of strength and cognition were significantly different among subjects with and without ADL and IADL decline. Univariate logistic regression showed that composite intrinsic capacity score was a predictor of decline in ADL and IADL even after adjusting for age, sex, comorbidity status and education level of the subject with an adjusted odds ratio of 0.99 and 0.98, respectively. Subdomains of strength and cognition also predicted a decline in ADL and IADL independently. Conclusion: The development of an objective construct of the concept of intrinsic capacity, using commonly measured clinical and biochemical parameters, is feasible and predictive of the subsequent functionality of an individual.

Cardiovascular health is associated with the epigenetic clock in the Berlin Aging Study II (BASE-II).

The epigenetic clock parameter DNAm age acceleration is a promising biomarker of aging. We have recently described an epigenetic clock based on only seven cytosine-phosphate-guanine sites, which is highly associated with chronological age. The aim of this study was to examine this epigenetic clock with respect to its relationship with cardiovascular health (CVH) in older adults. We used data from the Berlin Aging Study II (BASE-II; 1,671 participants; 68.8 ± 3.7 years old). CVH was operationalized using two different CVH scores, the Framingham Risk Score (FRS), and the Life's simple 7 (LS7). To adjust for potential confounding, e.g. by sex, we performed regression analyses. The LS7 score was higher, i.e. more favorable, in woman than in men (8.8 ± 2 vs. 8.2 ± 2, p < 0.001). DNAm age acceleration was associated with the FRS (ß = 0.122, p = 0.028) and with the LS7 (ß = -0.804, p = 0.032). In more detail, physical activity (ß = -0.461, p = 0.05), HDL-cholesterol (ß = 0.343, p = 0.03) and total cholesterol (ß = -0.364, p = 0.002) were associated with epigenetic age acceleration. We present evidence suggesting that better CVH is associated with decelerated biological aging measured by the epigenetic clock.

Building memories on prior knowledge: behavioral and fMRI evidence of impairment in early Alzheimer's disease.

Impaired memory is a hallmark of prodromal Alzheimer's disease (AD). Prior knowledge associated with the memoranda improves memory in healthy individuals, but we ignore whether the same occurs in early AD. We used functional MRI to investigate whether prior knowledge enhances memory encoding in early AD, and whether the nature of this prior knowledge matters. Patients with early AD and Controls underwent a task-based fMRI experiment where they learned face-scene associations. Famous faces carried pre-experimental knowledge (PEK), while unknown faces with which participants were familiarized prior to learning carried experimental knowledge (EK). Surprisingly, PEK strongly enhanced subsequent memory in healthy controls, but importantly not in patients. Partly nonoverlapping brain networks supported PEK vs. EK associative encoding in healthy controls. No such networks were identified in patients. In addition, patients displayed impaired activation in a right sub hippocampal region where activity predicted successful associative memory formation for PEK stimuli. Despite the limited sample sizes of this study, these findings suggest that the role prior knowledge in new learning might have been so far overlooked and underestimated in AD patients. Prior knowledge may drive critical differences in the way healthy elderly and early AD patients learn novel associations.

Influence of tDCS over right inferior frontal gyrus and pre-supplementary motor area on perceptual decision-making and response inhibition: A healthy ageing perspective.

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.

Healthy Diet for Healthy Aging.

Extending healthspan is a major public health challenge. Diet is one of the modifiable factors for preventing age-related diseases and preserving overall good health status during aging. Optimizing individuals' intrinsic capacity, including domains in cognition, psychological, sensory function, vitality, and locomotion, has been proposed as a model of healthy aging by the World Health Organization. To better understand the relationships between a healthy diet and healthy aging, this review summarizes the recent epidemiologic and clinical data for dietary patterns that have been shown to play a role in (domains of) healthy aging. Regardless of priori or posteriori dietary patterns, it appears that dietary patterns centered on plant-based foods have a beneficial role in (domains of) healthy aging. Our review identified a knowledge gap in dietary patterns and multidimensional concepts of healthy aging. More epidemiological studies should consider intrinsic capacity as an outcome measure to further our understanding of a healthy diet and multidimensional concepts of healthy aging. When a sufficient number of epidemiological studies is available, evidence can be synthesized and clinical trials can be designed to evaluate a healthy diet as a strategy for healthy aging to further our progress in translating evidence to practice and promoting healthy aging.

Healthy memory aging - the benefits of regular daily activities increase with age.

As the number of older adults increases, so does the pressure on health care systems due to age-related disorders. Attempts to reduce cognitive decline have focused on individual interventions such as exercise or diet, with limited success. This study adopted a different approach by investigating the impact of combined daily activities on memory decline. We used data from the National Institute of Aging's Health and Retirement Study to explore two new questions: does combining activities affect memory decline, and if yes, does this impact change across the lifespan? We created a new machine learning model using 33 daily activities and involving 3210 participants. Our results showed that the effect of combined activities on memory decline was stronger than any individual activity's impact. Moreover, this effect increased with age, whereas the importance of historical factors such as education, and baseline memory decreased. The present findings point out the importance of selecting multiple, diverse activities for older adults as they age. These results could have a significant impact on aging health policies promoting new programs such as social prescribing.

Microbiome and Human Aging: Probiotic and Prebiotic Potentials in Longevity, Skin Health and Cellular Senescence.

The role of the microbiome in human aging is important: the microbiome directly impacts aging through the gastrointestinal system. However, the microbial impact on skin has yet to be fully understood. For example, cellular senescence is an intrinsic aging process that has been recently associated with microbial imbalance. With age, cells become senescent in response to stress wherein they undergo irreversible growth arrest while maintaining high metabolic activity. An accumulation of senescent cells has been linked to various aging and chronic pathologies due to an overexpression of the senescence-associated secretory phenotype (SASP) comprised of proinflammatory cytokines, chemokines, growth factors, proteases, lipids and extracellular matrix components. In particular, dermatological disorders may be promoted by senescence as the skin is a common site of accumulation. The gut microbiota influences cellular senescence and skin disruption through the gut-skin axis and secretion of microbial metabolites. Metabolomics can be used to identify and quantify metabolites involved in senescence. Moreover, novel anti-senescent therapeutics are warranted given the poor safety profiles of current pharmaceutical drugs. Probiotics and prebiotics may be effective alternatives, considering the relationship between the microbiome and healthy aging. However, further research on gut composition under a senescent status is needed to develop immunomodulatory therapies.

Active Aging through Volunteerism: A Longitudinal Assessment of Perceived Neighborhood Safety as a Predictor among Older Adults, 2008-2018.

Volunteering can play an important role in active aging. The resource theory of volunteering posits that volunteerism depends on human, social, and cultural capital. Benefits of volunteering have been documented at the micro-, meso-, and macrolevels, positively affecting individual older people as well as their local communities and society at large. Taking a process-oriented theoretical approach, this study focused on the mesolevel factor of the environment with the purpose of determining the relationship between perceived neighborhood safety and volunteerism over the course of a decade and the extent to which this relationship differs by gender and race. Longitudinal data from the Health and Retirement Study in the United States of America between 2008 and 2018 were used (N = 72,319 adults 60 years and older). Generalized estimating equations (GEE) with robust standard errors were employed while controlling for a number of covariates. A third of the sample volunteered in the past year (33%). The probability of volunteering among older adults who rated their perceived neighborhood safety as excellent was greater compared with those who rated their perceived neighborhood safety as fair/poor after controlling for all other model covariates (ME: 0.03, 95% CI: 0.02, 0.05). Among males rating their perceived neighborhood safety as excellent, the probability of volunteering was higher (ME: 0.04, 95% CI: 0.02, 0.07). Among females, the probability of volunteering was higher among those who perceived their neighborhood safety to be excellent (ME: 0.03, 95% CI: 0.01, 0.05) or very good (ME: 0.02, 95% CI: 0.00, 0.04). White respondents who rated their neighborhood safety as excellent (ME: 0.05, 95% CI: 0.03, 0.07) or very good (ME: 0.04, 95% CI: 0.02, 0.06) had a higher probability of volunteerism. Results were not significant among Black respondents and those who described their race as "other." This study's process-oriented theoretical approach indicates that initiatives aimed at improving neighborhood safety and older adults' perceptions of neighborhood safety could increase social capital and lead older adults to engage in more volunteering, providing benefits at micro-, meso-, and macrolevels-to older individuals, their local communities, and society at large.