Cognitive reserve moderates the association between cerebral blood flow and language performance in older adults with mild cognitive impairment.

Higher cognitive reserve (CR) may offer protection from cognitive changes associated with reduced cerebral blood flow (CBF). We investigated CR as a moderator of the effect of CBF on cognition in older adults with mild cognitive impairment (MCI; N = 46) and those who are cognitively unimpaired (CU; N = 101). Participants underwent arterial spin labeling MRI, which was used to quantify CBF in 4 a priori regions. Estimated verbal intelligence quotient (VIQ) served as a proxy for CR. Multiple linear regressions examined whether VIQ moderated associations between CBF and cognition and whether this differed by cognitive status. Outcomes included memory and language performance. There were 3-way interactions (CBF*VIQ*cognitive status) on category fluency when examining hippocampal, superior frontal, and inferior frontal CBF. Follow-up analyses revealed that, within the MCI but not CU group, there were CBF*VIQ interactions on fluency in all a priori regions examined, where there were stronger, positive associations between CBF and fluency at higher VIQ. Conclusion: In MCI, higher CR plays a role in strengthening CBF-fluency associations.

Brain reserve contributes to distinguishing preclinical Alzheimer's stages 1 and 2.

BACKGROUND: In preclinical Alzheimer's disease, it is unclear why some individuals with amyloid pathologic change are asymptomatic (stage 1), whereas others experience subjective cognitive decline (SCD, stage 2). Here, we examined the association of stage 1 vs. stage 2 with structural brain reserve in memory-related brain regions. METHODS: We tested whether the volumes of hippocampal subfields and parahippocampal regions were larger in individuals at stage 1 compared to asymptomatic amyloid-negative older adults (healthy controls, HCs). We also tested whether individuals with stage 2 would show the opposite pattern, namely smaller brain volumes than in amyloid-negative individuals with SCD. Participants with cerebrospinal fluid (CSF) biomarker data and bilateral volumetric MRI data from the observational, multi-centric DZNE-Longitudinal Cognitive Impairment and Dementia Study (DELCODE) study were included. The sample comprised 95 amyloid-negative and 26 amyloid-positive asymptomatic participants as well as 104 amyloid-negative and 47 amyloid-positive individuals with SCD. Volumes were based on high-resolution T2-weighted images and automatic segmentation with manual correction according to a recently established high-resolution segmentation protocol. RESULTS: In asymptomatic individuals, brain volumes of hippocampal subfields and of the parahippocampal cortex were numerically larger in stage 1 compared to HCs, whereas the opposite was the case in individuals with SCD. MANOVAs with volumes as dependent data and age, sex, years of education, and DELCODE site as covariates showed a significant interaction between diagnosis (asymptomatic versus SCD) and amyloid status (Aß42/40 negative versus positive) for hippocampal subfields. Post hoc paired comparisons taking into account the same covariates showed that dentate gyrus and CA1 volumes in SCD were significantly smaller in amyloid-positive than negative individuals. In contrast, CA1 volumes were significantly (p = 0.014) larger in stage 1 compared with HCs. CONCLUSIONS: These data indicate that HCs and stages 1 and 2 do not correspond to linear brain volume reduction. Instead, stage 1 is associated with larger than expected volumes of hippocampal subfields in the face of amyloid pathology. This indicates a brain reserve mechanism in stage 1 that enables individuals with amyloid pathologic change to be cognitively normal and asymptomatic without subjective cognitive decline.

Gray Matter Volume as Evidence for Cognitive Reserve in Bilinguals With Mild Cognitive Impairment.

BACKGROUND: Compared with monolinguals, bilinguals have a later onset of mild cognitive impairment (MCI) and Alzheimer disease symptoms and greater neuropathology at similar cognitive and clinical levels. The present study follows a previous report showing the faster conversion from MCI to Alzheimer disease for bilingual patients than comparable monolinguals, as predicted by a cognitive reserve (CR). PURPOSE: Identify whether the increased CR found for bilinguals in the previous study was accompanied by greater gray matter (GM) atrophy than was present for the monolinguals. METHODS: A novel deep-learning technique based on convolutional neural networks was used to enhance clinical scans into 1 mm MPRAGEs and analyze the GM volume at the time of MCI diagnosis in the earlier study. PATIENTS: Twenty-four bilingual and 24 monolingual patients were diagnosed with MCI at a hospital memory clinic. RESULTS: Bilingual patients had more GM loss than monolingual patients in areas related to language processing, attention, decision-making, motor function, and episodic memory retrieval. Bilingualism and age were the strongest predictors of atrophy after other variables such as immigration and education were included in a multivariate model. DISCUSSION: CR from bilingualism is evident in the initial stages of neurodegeneration after MCI has been diagnosed.

Big Five personality factors predict self-rated cognitive reserve: a two-wave online study in a Mexican sample.

Introduction: One of the main contributors to cognitive reserve (CR) is the involvement in cognitively stimulating activities (CSAs), including education, work, leisure, social and physical activities. Personality traits are plausible determinants of CR, influencing the tendency to engage in CSAs. The goal of this study was to evaluate the association between personality and CR, operationalised as self-rated involvement in CSAs, in a sample of individuals aged 18-50 or more. Method: We collected two-wave non-probabilistic online data throughout Mexico. The instruments were the Big Five Inventory-2 for the baseline, its extra-short form for the follow-up and the Self-Rating of Cognitive Reserve (SRCR). Confirmatory factor analyses (CFAs) were performed to test the unifactorial structure of the SRCR, and multiple regressions were conducted with personality factors as predictors of CR. Results: For the baseline, 2025 participants were recruited, and 610 for the follow-up, most of them female and aged 18-40. CFAs showed excellent goodness-of-fit, and the regression analyses proved Negative Emotionality and Extraversion to be the main predictors of CR. Conclusions: Our study highlights the need to identify personality profiles at high risk of underdevelopment of CR in ages where it is still feasible to promote engagement in CSAs.

Effect of Cognitive Reserve on Physiological Measures of Cognitive Workload in Older Adults with Cognitive Impairments.

BACKGROUND: Cognitive reserve may protect against cognitive decline. OBJECTIVE: This cross-sectional study investigated the association between cognitive reserve and physiological measures of cognitive workload in older adults with cognitive impairment. METHODS: 29 older adults with cognitive impairment (age: 75±6, 11 (38%) women, MoCA: 20±7) and 19 with normal cognition (age: 74±6; 11 (58%) women; MoCA: 28±2) completed a working memory test of increasing task demand (0-, 1-, 2-back). Cognitive workload was indexed using amplitude and latency of the P3 event-related potential (ERP) at electrode sites Fz, Cz, and Pz, and changes in pupillary size, converted to an index of cognitive activity (ICA). The Cognitive Reserve Index questionnaire (CRIq) evaluated Education, Work Activity, and Leisure Time as a proxy of cognitive reserve. Linear mixed models evaluated the main effects of cognitive status, CRIq, and the interaction effect of CRIq by cognitive status on ERP and ICA. RESULTS: The interaction effect of CRIq total score by cognitive status on P3 ERP and ICA was not significant. However, higher CRIq total scores were associated with lower ICA (p = 0.03). The interaction effects of CRIq subscores showed that Work Activity affected P3 amplitude (p = 0.03) and ICA (p = 0.03) differently between older adults with and without cognitive impairments. Similarly, Education affected ICA (p = 0.02) differently between the two groups. No associations were observed between CRIq and P3 latency. CONCLUSION: Specific components of cognitive reserve affect cognitive workload and neural efficiency differently in older adults with and without cognitive impairments.

A framework for concepts of reserve and resilience in aging.

The study of factors, across species, that allow some individuals to age more successfully than others has important implications for individual wellbeing as well as health education, policy and intervention. Design of studies and communication across investigators in this area has been hampered by a diversity of terminology. The Collaboratory on Research Definitions for Reserve and Resilience in Cognitive Aging and Dementia was funded by the National Institute on Aging and established in 2019 as a 3-year process of developing consensus definitions and research guidelines. The proposed Framework is based on an iterative process including 3 annual Workshops, focused workgroups, and input from numerous international investigators. It suggests the overarching term: resilience, and presents operational definitions for 3 concepts: cognitive reserve, brain maintenance, and brain reserve. Twelve pilot studies that integrate these definitions are presented. The use of a common vocabulary and operational definitions will facilitate even greater progress in understanding the factors that are associated with successful aging.

Psychometric properties of the Chinese version of the Cognitive Reserve Assessment Scale in Health in patients with cancer.

BACKGROUND: Cognitive reserve is a modifiable factor that could prevent cognitive decline in patients with cancer. The Cognitive Reserve Assessment Scale in Health (CRASH) is an instrument used to assess cognitive reserve. This study aims to develop and examine the psychometric properties of the Chinese version of the CRASH for patients with cancer. METHODS: A cross-sectional survey was conducted with 167 cancer patients from four wards of two hospitals in China. Thirty-one patients were re-assessed to examine the test-retest reliability. Four translators and three reviewers developed the Chinese version of the scale. We assessed its structural validity, concurrent validity, internal consistency, test-retest reliability, measurement error, and floor/ceiling effects. RESULTS: Confirmatory factor analysis showed a good model fit with the four-factor structure of the original CRASH. The CRASH scores were statistically significantly associated with neuropsychological test scores, indicating sufficient concurrent validity. The internal consistency was acceptable, except for leisure activities, with standardized Cronbach's alphas (0.64-0.94) and standardized Omega (0.66-0.95). There was excellent test-retest reliability, with a high intraclass correlation coefficient (0.914-0.993) of total scores and scores for each domain. The measurement error was acceptable, and no floor or ceiling effects were observed. CONCLUSIONS: The Chinese version of the CRASH is a valid and reliable instrument to assess cognitive reserve in patients with cancer. Moreover, cognitive reserve measured by the CRASH was associated with low cognitive performance in cancer patients.

Cognitive reserve in patients with mood disorders: Validation study of the Chinese version of the cognitive reserve assessment scale in health.

BACKGROUND: Cognitive reserve (CR) is closely associated with cognitive and functional outcome, disease severity, progression and prognosis in psychiatric patients; however, it has not been extensively tested in mood disorders. This study examined the psychometric properties of the Cognitive Reserve Assessment Scale in Health (CRASH) in mood disorder patients. METHODS: Altogether 166 subjects were recruited, 44 with major depressive disorder (MDD), 64 with bipolar disorder (BD), and 58 healthy controls. CR was assessed using the CRASH and the Cognitive Reserve Questionnaire (CRQ). RESULTS: Internal consistency (Cronbach's alpha) was 0.779 for the CRASH. The Receiver Operating Characteristic (ROC) curve analysis revealed an area under the ROC curve (AUC) value of 0.73 (95 % CI: 0.647-0.809). The optimal cut-off score of 51 generated the best combination of sensitivity (0.78) and specificity (0.43) for discriminating between patients with mood disorders and healthy controls. The CRASH score was highly correlated with the CRQ score in both mood disorder patients (rs = 0.586, P < 0.001) and healthy controls (rs = 0.627, P < 0.001), indicating acceptable convergent validity for the CRASH. Within the mood disorder sample, the CRASH score was associated with functional outcomes (FAST: rs = -0.243, P = 0.011). CONCLUSIONS: The CRASH is a useful tool to measure CR in mood disorder with acceptable psychometric properties and could be used in both research and clinical practice.

Cognitive reserve as a moderating factor between EDSS and cognition in multiple sclerosis.

OBJECTIVES: It is now well recognized that brain damage and/or atrophy apparent on MRI is only moderately correlated to cognitive functioning. The cognitive reserve (CR) hypothesis has been proposed to explain this functional heterogeneity, but it has only been addressed recently in the MS literature and has not yet been thoroughly investigated. The objective of this study is to examine the protective role of CR in cognition using a standardized CR tool in a population with a wide age range. METHODS: A neuropsychological evaluation was performed on 84 pwMS aged between 27 and 78 years old and the CR Index questionnaire (CRIq) was used to estimate CR. The EDSS scale was used to assess the degree of neurologic impairment and estimate the disease burden. RESULTS: A moderating effect of CR was observed in the relationship between EDSS score and specific cognitive domains: processing efficiency, visuospatial learning and memory, as well as a tendency for verbal memory. In pwMS with a high level of CR, there was no negative relationship between these cognitive domains and EDSS. CONCLUSION: The results support the protective role of CR in a sample of pwMS with a wide age range. This role seems to be limited to specific cognitive tasks that pose a greater challenge and therefore require greater adaptability.

Lifelong Cognitive Reserve, Imaging Markers of Brain Aging, and Cognitive Function in Dementia-Free Rural Older Adults: A Population-Based Study.

BACKGROUND: Cognitive reserve (CR) partly explains cognitive variability in the presence of pathological brain aging. OBJECTIVE: We investigated the interplay of lifelong CR with age, sex, and brain aging markers in cognitive phenotypes among older adults with very limited education. METHODS: This population-based cross-sectional study included 179 dementia-free participants (age ≥65 years; 39.7% women; 67.0% had no or elementary education) examined in 2014-2016. We assessed lacunes and volumes of hippocampus, ventricles, grey matter, white matter (WM), and white matter hyperintensities. Lifelong CR score was generated from six lifespan intellectual factors (e.g., education and social support). We used Mini-Mental State Examination (MMSE) score to assess cognition and Petersen's criteria to define mild cognitive impairment (MCI). Data were analyzed using general linear and logistic models. RESULTS: The association of higher lifelong CR score (range: -4.0-5.0) with higher MMSE score was stronger in women (multivariable-adjusted ß-coefficient and 95% CI: 1.75;0.99-2.51) than in men (0.68;0.33-1.03) (pinteraction = 0.006). The association of higher CR with MCI (multivariable-adjusted odds ratio and 95% CI: 0.77;0.60-0.99) did not vary by age or sex. Among participants with low CR (<1.4[median]), greater hippocampal and WM volumes were related to higher MMSE scores with multivariable-adjusted ß-coefficients being 1.77(0.41-3.13) and 0.44(0.15-0.74); the corresponding figures in those with high CR were 0.15(-0.76-1.07) and -0.17(-0.41-0.07) (pinteraction <0.01). There was no statistical interaction of CR with MRI markers on MCI. CONCLUSION: Greater lifelong CR capacity is associated with better late-life cognition among people with limited education, possibly by compensating for impact of neurodegeneration.

Connectome-based predictive modelling of cognitive reserve using task-based functional connectivity.

Cognitive reserve supports cognitive function in the presence of pathology or atrophy. Functional neuroimaging may enable direct and accurate measurement of cognitive reserve which could have considerable clinical potential. The present study aimed to develop and validate a measure of cognitive reserve using task-based fMRI data that could then be applied to independent resting-state data. Connectome-based predictive modelling with leave-one-out cross-validation was applied to predict a residual measure of cognitive reserve using task-based functional connectivity from the Cognitive Reserve/Reference Ability Neural Network studies (n = 220, mean age = 51.91 years, SD = 17.04 years). This model generated summary measures of connectivity strength that accurately predicted a residual measure of cognitive reserve in unseen participants. The theoretical validity of these measures was established via a positive correlation with a socio-behavioural proxy of cognitive reserve (verbal intelligence) and a positive correlation with global cognition, independent of brain structure. This fitted model was then applied to external test data: resting-state functional connectivity data from The Irish Longitudinal Study on Ageing (TILDA, n = 294, mean age = 68.3 years, SD = 7.18 years). The network-strength predicted measures were not positively associated with a residual measure of cognitive reserve nor with measures of verbal intelligence and global cognition. The present study demonstrated that task-based functional connectivity data can be used to generate theoretically valid measures of cognitive reserve. Further work is needed to establish if, and how, measures of cognitive reserve derived from task-based functional connectivity can be applied to independent resting-state data.

Relapse, cognitive reserve, and their relationship with cognition in first episode schizophrenia: a 3-year follow-up study.

Schizophrenia is frequently characterized by the presence of multiple relapses. Cognitive impairments are core features of schizophrenia. Cognitive reserve (CR) is the ability of the brain to compensate for damage caused by pathologies such as psychotic illness. As cognition is related to CR, the study of the relationship between relapse, cognition and CR may broaden our understanding of the course of the disease. We aimed to determine whether relapse was associated with cognitive impairment, controlling for the effects of CR. Ninety-nine patients with a remitted first episode of schizophrenia or schizophreniform disorder were administered a set of neuropsychological tests to assess premorbid IQ, attention, processing speed, working memory, verbal and visual memory, executive functions and social cognition. They were followed up for 3 years (n=53) or until they relapsed (n=46). Personal and familial CR was estimated from a principal component analysis of the premorbid information gathered. Linear mixed-effects models were applied to analyse the effect of time and relapse on cognitive function, with CR as covariate. Patients who relapsed and had higher personal CR showed less deterioration in attention, whereas those with higher CR (personal and familial CR) who did not relapse showed better performance in processing speed and visual memory. Taken together, CR seems to ameliorate the negative effects of relapse on attention performance and shows a positive effect on processing speed and visual memory in those patients who did not relapse. Our results add evidence for the protective effect of CR over the course of the illness.

Brain Reserve, Resilience, and Cognitive Stimulation Across the Lifespan: How Do These Factors Influence Risk of Cognitive Impairment and the Dementias?

In the absence of effective treatments for dementia, maintaining cognitive health in old age is one of the major challenges facing aging societies. Interventions for cognitive health that are tailored to the person are more likely to bring the best benefits with a minimum burden. We review the existing literature on this topic and discuss the role of the primary care physician.

The association between low cognitive reserve and subjective memory complaints in functionally independent older women.

BACKGROUND: Several factors have been found to defend against pathologic cognitive decline in aging (i.e., cognitive reserve [CR]); however, other factors, including subjective memory complaints (SMC) and decreased functionality are considered early indicators of underlying neurocognitive dysfunction. Despite these known associations, the relationship between the presence of CR and SMC remains equivocal. This study sought to determine the relationship between objectively measured CR and SMC in a sample of functionally independent older women. METHODS: This cross-sectional study recruited women aged ≥60 years who attended fitness or continuing education programs at the University for Seniors in Mexico City. Participants underwent a battery of physical and cognitive evaluations, including the Cognitive Reserve Questionnaire (CRQ), and were asked probing questions used to identify the presence of SMC. RESULTS: The 269 participants had a median age of 69 years; most were single (40.5 %), lived alone (32.7 %), retired (58.2 %), well-educated (≥12 years of education), and functionally independent (89.2 %). 62 % scored "high" on the CRQ, while 9.3 % scored "low". After adjusting for multiple covariates, an independent association between CRQ score and the probability to have SMC was found (adjusted OR = 0.87, 95% CI 0.80-0.95, p-value = 0.002). CONCLUSIONS: This study identified a relationship between low CR and the presence of SMC, independently of the cognitive function and motoric marker of muscle strength (i.e., low gait speed and handgrip strength) in functionally independent older women over 60y. This relationship remains independent of other variables such as age, symptoms of depression and instrumented activities of daily living.

Activation changes induced by cognitive training are consistent with improved cognitive reserve in older adults with subjective cognitive decline.

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.

The role of cognitive and brain reserve in late-life depressive events: The Rotterdam Study.

BACKGROUND: Cognitive and brain reserve aim to explain individual differences in susceptibility to dementia and may also affect the risk of late-life depressive events. We assessed whether higher cognitive and brain reserve are associated with lower risk of a late-life depressive event. METHODS: This study included 4509 participants from the population-based Rotterdam Study (mean age: 63.4 ± 10.2 years, 55 % women) between 2005 and 2019. Participants completed cognitive testing and brain-MRI at baseline. Cognitive reserve was defined as the common variance across cognitive tests, while adjusting for demographic factors and brain MRI-markers. Brain reserve was defined as total brain volume divided by intracranial volume. Depressive events (depressive symptoms/depressive syndrome/major depressive disorder) were repeatedly measured (follow-up: 6.6 ± 3.9 years) with validated questionnaires, clinical interviews, and follow-up of medical records. Hazard ratios (HR) with 95 % confidence intervals (CI) were estimated using Cox-regressions. RESULTS: Higher cognitive (HR: 0.91/SD, 95%CI: 0.84; 1.00) and brain reserve (HR: 0.88/SD, 95%CI: 0.77; 1.00) were associated with a lower risk of a depressive event after adjustment for baseline depressive symptoms. These associations attenuated when participants with clinically relevant depressive symptoms at baseline were excluded (HR: 0.95/SD, 95%CI: 0.86; 1.05, HR: 0.89/SD, 95%CI: 0.76; 1.03, respectively). LIMITATIONS: No data was available on depression in early-life and the number of participants with major depressive disorder was relatively low (n = 105). CONCLUSIONS: Higher cognitive and brain reserve may be protective factors for late-life depressive events, particularly in those who have experienced clinical relevant depressive symptoms before. Further research is needed to determine whether cognitive and brain reserve could be used as targets for the prevention of late-life depression.

Lifelong experiences as a proxy of cognitive reserve moderate the association between connectivity and cognition in Alzheimer's disease.

Alzheimer's disease (AD) is associated with alterations in functional connectivity (FC) of the brain. The FC underpinnings of CR, that is, lifelong experiences, are largely unknown. Resting-state FC and structural MRI were performed in 76 CSF amyloid-ß (Aß) negative healthy controls and 152 Aß positive individuals as an AD spectrum cohort (ADS; 55 with subjective cognitive decline, SCD; 52 with mild cognitive impairment; 45 with AD dementia). Following a region-of-interest (ROI) FC analysis, intrinsic network connectivity within the default-mode network (INC-DMN) and anti-correlation in INC between the DMN and dorsal attention network (DMN:DAN) were obtained as composite scores. CR was estimated by education and Lifetime Experiences Questionnaire (LEQ). The association between INC-DMN and MEM was attenuated by higher LEQ scores in the entire ADS group, particularly in SCD. In ROI analyses, higher LEQ scores were associated with higher FC within the DMN in ADS group. INC-DMN remains relatively intact despite memory decline in individuals with higher lifetime activity estimates, supporting a role for functional networks in maintaining cognitive function in AD.

Neural similarity across task load relates to cognitive reserve and brain maintenance measures on the Letter Sternberg task: a longitudinal study.

The aging process is characterized by change across several measures that index cognitive status and brain integrity. In the present study, 54 cognitively-healthy younger and older adults, were analyzed, longitudinally, on a verbal working memory task to investigate the effect of brain maintenance (i.e., cortical thickness) and cognitive reserve (i.e., NART IQ as proxy) factors on a derived measure of neural efficiency. Participants were scanned using fMRI while presented with the Letter Sternberg task, a verbal working memory task consisting of encoding, maintenance and retrieval phases, where cognitive load is manipulated by varying the number of presented items (i.e., between one and six letters). Via correlation analysis, we looked at region-level and whole-brain relationships between load levels within each phase and then computed a global task measure, what we term phase specificity, to analyze how similar neural responses were across load levels within each phase compared to between each phase. We found that longitudinal change in phase specificity was positively related to longitudinal change in cortical thickness, at both the whole-brain and regional level. Additionally, baseline NART IQ was positively related to longitudinal change in phase specificity over time. Furthermore, we found a longitudinal effect of sex on change in phase specificity, such that females displayed higher phase specificity over time. Cross-sectional findings aligned with longitudinal findings, with the notable exception of behavioral performance being positively linked to phase specificity cross-sectionally at baseline. Taken together, our findings suggest that phase specificity positively relates to brain maintenance and reserve factors and should be better investigated as a measure of neural efficiency.

An Overview of Cognitive Reserve in Aging Based on Keyword Network Analysis.

Many studies have reported that Cognitive reserve is a critical mechanism affecting cognitive statuses, such as dementia. The purposes of this study were to identify the knowledge structure and the research trend on cognitive reserve by conducting keyword analysis on research papers ranging from the earliest to the most recent studies done on the topic and to suggest directions for future research. The Web of Science (WOS) database was used to search for articles on cognitive reserve in aging from 2001 to 2020. NetMiner version 4 (cyram, KOREA), a social network analysis program, was used for keyword network analysis. Data analysis showed keywords that could be categorized as cognitive reserve related keywords (cognitive reserve related concepts, cognitive reserve related factor, cognitive reserve diagnosis and measurement, cognitive reserve outcomes) and cognitive reserve research keywords (research subject/disease, research method, intervention, research field). Through trend analysis, we found that various keywords appeared, indicating that the research has gradually developed conceptually and methodically. Based on these findings, future CR studies require the development of multimodal interface-based tools by applying modern digital technology that can be used to more accurately diagnose and monitor CR; remotely, in real time. In addition, to improve CR, it is suggested that the development of cognitive stimulation interventions utilizing VR which fuses AI based interaction technology with the subjects. Finally, CR could develop further through a cooperation of multidisciplinary professionals such as psychology, medicine and nursing.

Contributions of early-life cognitive reserve and late-life leisure activity to successful and pathological cognitive aging.

BACKGROUND: The identification of factors that specifically influence pathological and successful cognitive aging is a prerequisite for implementing disease prevention and promoting successful aging. However, multi-domain behavioral factors that characterize the difference between successful and pathological cognitive aging are not clear yet. METHODS: A group of community-dwelling older adults (N = 1347, aged 70-88 years) in Beijing was recruited in this cross-sectional study, and a sub-cohort was further divided into successful cognitive aging (SCA, N = 154), mild cognitive impairment (MCI, N = 256), and cognitively normal control (CNC, N = 173) groups. Analyses of variance, regression models with the Shapley value algorithm, and structural equation model (SEM) analyses were conducted to determine specific influencing factors and to evaluate their relative importance and interacting relationships in altering cognitive performance. RESULTS: We found that abundant early-life cognitive reserve (ECR, including the level of education and occupational attainment) and reduced late-life leisure activity (LLA, including mental, physical, and social activities) were distinct characteristics of SCA and MCI, respectively. The level of education, age, mental activity, and occupational attainment were the top four important factors that explained 31.6% of cognitive variability. By SEM analyses, we firstly found that LLA partially mediated the relationship between ECR and cognition; and further multi-group SEM analyses showed ECR played a more direct role in the SCA group than in the MCI group: in the SCA group, only the direct effect of ECR on cognition was significant, and in the MCI group, direct effects between ECR, LLA and cognition were all significant. CONCLUSIONS: Results of this large-sample community-based study suggest it is important for older adults to have an abundant ECR for SCA, and to keep a high level of LLA to prevent cognitive impairment. This study clarifies the important rankings of behavioral characteristics of cognitive aging, and the relationship that ECR has a long-lasting effect on LLA and finally on cognition, providing efficient guidance for older adults to improve their cognitive function and new evidence to explain the heterogeneity of cognitive aging.