Association of Cognitive Reserve Indicator with Cognitive Decline and Structural Brain Differences in Middle and Older Age: Findings from the UK Biobank.

BACKGROUND: Cognitive reserve (CR) contributes to preserving cognition when facing brain aging and damage. CR has been linked to dementia risk in late life. However, the association between CR and cognitive changes and brain imaging measures, especially in midlife, is unclear. OBJECTIVE: We aimed to explore the association of CR with cognitive decline and structural brain differences in middle and older age. DESIGN: This longitudinal study was from the UK Biobank project where participants completed baseline surveys between 2006 to 2010 and were followed (mean follow-up: 9 years). SETTING: A population-based study. PARTICIPANTS: A total of 42,301 dementia-free participants aged 40-70 were followed-up to detect cognitive changes. A subsample (n=34,041) underwent brain magnetic resonance imaging scans. MEASUREMENTS: We used latent class analysis to generate a CR indicator (categorized as high, moderate, and low) based on education, occupation, and multiple cognitively stimulating activities. Cognitive tests for global and domain-specific cognition were administrated at baseline and follow-up. Total brain, white matter, grey matter, hippocampal, and white matter hyperintensity volumes (TBV, WMV, GMV, HV, and WMHV) were assessed at the follow-up examination. Data were analyzed using mixed-effects models and analysis of covariance. RESULTS: At baseline, 16,032 (37.9%), 10,709 (25.3%), and 15,560 (36.8%) participants had low, moderate, and high levels of CR, respectively. Compared with low CR, high CR was associated with slower declines in global cognition (ß [95% confidence interval]: 0.10 [0.08, 0.11]), prospective memory (0.10 [0.06, 0.15]), fluid intelligence (0.07 [0.04, 0.10]), and reaction time (0.04 [0.02, 0.06]). Participants with high CR had lower TBV, WMV, GMV, and WMHV, but higher HV when controlling for global cognition (corrected P <0.01 for all). The significant relationships between CR and cognition and TBV were present among both middle-aged (<60 years) and older (≥60 years) participants. The CR-cognition association remained significant despite reductions in brain structural properties. CONCLUSIONS: Higher CR is associated with slower cognitive decline, higher HV, and lower microvascular burden, especially in middle age. Individuals with high CR could tolerate smaller brain volumes while maintaining cognition. The benefit of CR for cognition is independent of structural brain differences. Our findings highlight the contribution of enhancing CR to helping compensate for neuroimaging alterations and ultimately prevent cognitive decline.

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.

Longitudinal validation of cognitive reserve proxy measures: a cohort study in a rural Chinese community.

BACKGROUND: While evidence supports cognitive reserve (CR) in preserving cognitive function, longitudinal validation of CR proxies, including later-life factors, remains scarce. This study aims to validate CR's stability over time and its relation to cognitive function in rural Chinese older adults. METHODS: Within the project on the health status of rural older adults (HSRO), the survey included baseline assessment (2019) and follow-up assessment (2022). 792 older adults (mean age: 70.23 years) were followed up. The confirmatory factor analysis (CFA) was constructed using cognitive reserve proxies that included years of formal education, social support, hobbies, and exercise. We examined the longitudinal validity of the CR factor using confirmatory factor analyses and measurement invariance and explored the association of CR with cognition using Spearman's correlation and Generalized Estimating Equations (GEE). RESULTS: The results showed that CR's CFA structure was stable over time (T0, χ2/df: 3.21/2; RMSEA: 0.02, and T1, χ2/df: 7.47/2; RMSEA: 0.05) and that it accepted both configural and metric invariance (Δχ2/df = 2.28/3, P = 0.52). In addition, it was found that CR had a stable positive relationship with cognitive function across time (T0, r = 0.54; T1, r = 0.49). Furthermore, longitudinal CR were associated with MMSE (ß = 2.25; 95%CI = 2.01 ~ 2.49). CONCLUSIONS: This study provided valuable evidence on the stability and validity of cognitive reserve proxy measures in rural Chinese older adults. Our findings suggested that cognitive reserve is associated with cognitive function over time and highlighted the importance of accumulating cognitive reserve in later life.

Influence of cognitive reserve on cognitive and motor function in α-synucleinopathies: A systematic review and multilevel meta-analysis.

Cognitive reserve has shown promise as a justification for neuropathologically unexplainable clinical outcomes in Alzheimer's disease. Recent evidence suggests this effect may be replicated in conditions like Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy. However, the relationships between cognitive reserve and different cognitive abilities, as well as motor outcomes, are still poorly understood in these conditions. Additionally, it is unclear whether the reported effects are confounded by medication. This review analysed studies investigating the relationship between cognitive reserve and clinical outcomes in these α-synucleinopathy cohorts, identified from MEDLINE, Scopus, psycINFO, CINAHL, and Web of Science. 85 records, containing 176 cognition and 31 motor function effect sizes, were pooled using multilevel meta-analysis. There was a significant, positive association between higher cognitive reserve and both better cognition and motor function. Cognition effect sizes differed by disease subtype, cognitive reserve measure, and outcome type; however, no moderators significantly impacted motor function. Review findings highlight the clinical implications of cognitive reserve and importance of engaging in reserve-building behaviours.

Cognitive resilience/reserve: Myth or reality? A review of definitions and measurement methods.

INTRODUCTION: This review examines the concept of cognitive reserve (CR) in relation to brain aging, particularly in the context of dementia and its early stages. CR refers to an individual's ability to maintain or regain cognitive function despite brain aging, damage, or disease. Various factors, including education, occupation complexity, leisure activities, and genetics are believed to influence CR. METHODS: We revised the literature in the context of CR. A total of 842 articles were identified, then we rigorously assessed the relevance of articles based on titles and abstracts, employing a systematic approach to eliminate studies that did not align with our research objectives. RESULTS: We evaluate-also in a critical way-the methods commonly used to define and measure CR, including sociobehavioral proxies, neuroimaging, and electrophysiological and genetic measures. The challenges and limitations of these measures are discussed, emphasizing the need for more targeted research to improve the understanding, definition, and measurement of CR. CONCLUSIONS: The review underscores the significance of comprehending CR in the context of both normal and pathological brain aging and emphasizes the importance of further research to identify and enhance this protective factor for cognitive preservation in both healthy and neurologically impaired older individuals. HIGHLIGHTS: This review examines the concept of cognitive reserve in brain aging, in the context of dementia and its early stages. We have evaluated the methods commonly used to define and measure cognitive reserve. Sociobehavioral proxies, neuroimaging, and electrophysiological and genetic measures are discussed. The review emphasizes the importance of further research to identify and enhance this protective factor for cognitive preservation.

Lower cognitive reserve is related to worse working memory performance in older adults after mTBI. An ERP study.

OBJECTIVE: Older adults (OA) after mild traumatic brain injury (mTBI) have a high risk of developing persistent post-injury cognitive impairments. Lower pre-morbid cognitive reserve (CR) is increasingly investigated as a risk factor for cognitive dysfunction in OA. However, how CR protects against effects of mTBI at the brain level remains largely understudied. METHODS: We examined 22 OA who sustained mTBI (mean 67.69 years, SD 5.11) in the sub-acute phase and 15 age- and CR-matched healthy OA (mean 68 years, SD 5.55) performing a three-level visual N-back task using electroencephalography. We calculated inverse efficiency scores of performance from accuracy and reaction times. Event-related potentials served as neurocognitive correlates of attentional (P2) and working memory (P3) processing. RESULTS: Overall, mTBI OA performed worse than healthy OA (p = 0.031). Lower CR generally decreased performance (p < 0.001). Furthermore, with increasing task difficulty, task performance was more affected by CR (p = 0.004). At the brain level, P2 amplitude was lower in mTBI OA than in healthy OA (p = 0.05). There was no clear effect of CR on P2 or P3 measures. CONCLUSION: As mTBI OA with lower CR performed worse on a working-memory task, lower CR may be a risk factor for worse recovery after mTBI in this group.

Brain reserve affects the expression of cognitive reserve networks.

Cognitive reserve (CR) explains differential susceptibility of cognitive performance to neuropathology. However, as brain pathologies progress, cognitive decline occurs even in individuals with initially high CR. The interplay between the structural brain health (= level of brain reserve) and CR-related brain networks therefore requires further research. Our sample included 142 individuals aged 60-70 years. National Adult Reading Test intelligence quotient (NART-IQ) was our CR proxy. On an in-scanner Letter Sternberg task, we used ordinal trend (OrT) analysis to extract a task-related brain activation pattern (OrT slope) for each participant that captures increased expression with task load (one, three, and six letters). We assessed whether OrT slope represents a neural mechanism underlying CR by associating it with task performance and NART-IQ. Additionally, we investigated how the following brain reserve measures affect the association between NART-IQ and OrT slope: mean cortical thickness, total gray matter volume, and brain volumes proximal to the areas contained in the OrT patterns. We found that higher OrT slope was associated with better task performance and higher NART-IQ. Further, the brain reserve measures were not directly associated with OrT slope, but they affected the relationship between NART-IQ and OrT slope: NART-IQ was associated with OrT slope only in individuals with high brain reserve. The degree of brain reserve has an impact on how (and perhaps whether) CR can be implemented in brain networks in older individuals.

Cognitive reserve proxies for individuals with intellectual developmental disability: A scoping review.

BACKGROUND: Cognitive reserve (CR) has not been studied in people with Intellectual Developmental Disability, a population with a high incidence of dementia. Commonly adopted CR proxies should be adapted to reflect more specifically the experiences of people with Intellectual Developmental Disability. METHOD: This scoping review intended to identify CR proxies relevant to people with this condition. RESULTS: Some of these were the same already detected in a population without intellectual disabilities (education, occupation, physical activity, leisure, community and social activities); others were found to be specifically relevant for this population: type of schooling, parental educational level, environmental stimulation and living place. CONCLUSIONS: These proxies need to be considered in studies on CR and Intellectual Developmental Disability and in clinical practice. Research on the protective effect of CR aims to encourage policies promoting lifestyle-based educational and preventive interventions and overcome participation barriers for people with Intellectual Developmental Disability.

Cognition and Cognitive Reserve.

Cognition is a mental process that provides the ability to think, know, and learn. Though cognitive skills are necessary to do daily tasks and activities, cognitive aging causes changes in various cognitive functions. Cognitive abilities that are preserved and strengthened by experience can be kept as a reserve and utilized when necessary. The concept of reserving cognition was found when people with Alzheimer's disease had differences in clinical manifestations and cognitive functions. The cognitive reserve builds resilience against cognitive decline and improves the quality of life. Also, several lines of studies have found that the plasticity between neurons has a significant impact on cognitive reserve and acts against cognitive decline. To extend the findings, the present study provides a comprehensive understanding of cognitive reserve and the variables that are involved in maintaining cognition. The study also considers reading as one of the cognitive proxies that develops and maintains cognitive reserve.

Systematic review of cognitive reserve in multiple sclerosis: Accounting for physical disability, fatigue, depression, and anxiety.

BACKGROUND: Cognitive reserve (CR) describes an individual's ability to adapt cognitive processes in response to brain atrophy, and has been reported to explain some of the discrepancy between brain atrophy and cognitive functioning outcomes in multiple sclerosis (MS). CR in MS is typically investigated by assessing an individual's pre- and/or post-diagnosis enrichment, which includes premorbid intellectual abilities, educational level, occupational attainment, and engagement in cognitively enriching leisure activities. Common MS symptoms (e.g., physical disability, fatigue, depression, anxiety) may impact an individual's ability to engage in various CR-enhancing activities post-diagnosis. It is unknown to what extent these MS symptoms have been taken into account in MS research on CR. As such, we identified whether studies assessed CR using measures of premorbid or continuous (including post-diagnosis) enrichment. For studies investigating continuous enrichment, we identified whether studies accounted for MS-impact, which MS symptoms were accounted for, and how, and whether studies acknowledged MS symptoms as potential CR-confounds. METHODS: Three electronic databases (PsycINFO, PubMed, Scopus) were searched. Eligible studies investigated CR proxies (e.g., estimated premorbid intellectual abilities, vocabulary knowledge, educational level, occupational attainment, cognitively enriching leisure activities, or a combination thereof) in relation to cognitive, brain atrophy or connectivity, or daily functioning outcomes in adult participants with MS. We extracted data on methods and measures used, including any MS symptoms taken into account. Objectives were addressed using frequency analyses and narrative synthesis. RESULTS: 115 studies were included in this review. 47.8% of all studies investigated continuous enrichment. Approximately half of the studies investigating continuous enrichment accounted for potential MS-impact in their analyses, with only 31.0% clearly identifying that they treated MS symptoms as potential confounds for CR-enhancement. A narrative synthesis of studies which investigated CR with and without controlling statistically for MS-impact indicated that accounting for MS symptoms may impact findings concerning the protective nature of CR. CONCLUSION: Fewer than half of the studies investigating CR proxies in MS involved continuous enrichment. Just over half of these studies accounted for potential MS-impact in their analyses. To achieve a more complete and accurate understanding of CR in MS, future research should investigate both pre-MS and continuous enrichment. In doing so, MS symptoms and their potential impact should be considered. Establishing greater consistency and rigour across CR research in MS will be crucial to produce an evidence base for the development of interventions aimed at improving quality of care and life for pwMS.

Cognitive reserve counteracts typical neural activity changes related to ageing.

Studies have shown that older adults with high Cognitive Reserve (HCR) exhibit better executive functioning than their low CR (LCR) counterparts. However, the neural processes linked to those differences are unclear. This study investigates (1) the neural processes underlying executive functions in older adults with HCR compared to older adults with LCR and (2) how executive control differences between HCR and LCR groups are modulated by increased task difficulty. We recruited 74 participants (37 in each group) with diverse CR levels, as determined by a standardised CR questionnaire. Participants performed two executive control tasks with lower and higher difficulty levels (i.e., Simon and spatial Stroop tasks, respectively) while recording the electroencephalogram. The accuracy on both tasks requiring inhibition of irrelevant information was better in the HCR than the LCR group. Also, in the task with higher difficulty level (i.e., the spatial Stroop task), event-related potential (ERP) latencies associated with inhibition (i.e., frontal N200) and updating of working memory (i.e., P300) were earlier in HCR than LCR. Moreover, the HCR, but not the LCR group, showed larger P300 amplitude in parietal than frontal regions and in the left than right hemisphere, suggesting a posterior to anterior shift of activity and loss of inter-hemispheric asymmetries in LCR participants. These results suggest that high CR counteracts neural activity changes related to ageing. Thus, high levels of CR may be related to maintenance of neural activity patterns typically observed in young adults rather than to deployment of neural compensatory mechanisms.

The relationship between cognitive reserve and the spontaneous use of emotion regulation strategies in older adults: a cross-sectional study.

BACKGROUND: Several studies reported cognitive reserve (CR) as an important factor in promoting healthy aging within a non-clinical aging population. AIMS: The main goal of the present study is to investigate the link between higher levels of CR and more effective emotion regulation. In more detail, we examine the association between a number of CR proxies and the habitual use of two emotion regulation strategies, cognitive reappraisal and emotional suppression. METHODS: Three hundred and ten older adults aged between 60 and 75 (mean = 64.45, SD = 4.37; 69.4% female) joined this cross-sectional study by filling out self-report measures of CR and emotion regulation.² RESULTS: Reappraisal and suppression use were correlated. Practicing different leisure activities constantly over many years, being more original and having a higher education promoted more frequent use of cognitive reappraisal. These CR proxies were also significantly related to suppression use, even though the percentage of variance explained was lower. DISCUSSION AND CONCLUSIONS: Exploring the role played by the cognitive reserve on different emotion regulation techniques can be useful in understanding which variables predict the use of antecedent-focused (reappraisal) or response-focused (suppression) emotion regulation strategies in aging individuals.

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.

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.

Issues and recommendations for the residual approach to quantifying cognitive resilience and reserve.

BACKGROUND: Cognitive reserve and resilience are terms used to explain interindividual variability in maintenance of cognitive health in response to adverse factors, such as brain pathology in the context of aging or neurodegenerative disorders. There is substantial interest in identifying tractable substrates of resilience to potentially leverage this phenomenon into intervention strategies. One way of operationalizing cognitive resilience that has gained popularity is the residual method: regressing cognition on an adverse factor and using the residual as a measure of resilience. This method is attractive because it provides a statistical approach that is an intuitive match to the reserve/resilience conceptual framework. However, due to statistical properties of the regression equation, the residual approach has qualities that complicate its interpretation as an index of resilience and make it statistically inappropriate in certain circumstances. METHODS AND RESULTS: We describe statistical properties of the regression equation to illustrate why the residual is highly correlated with the cognitive score from which it was derived. Using both simulations and real data, we model common applications of the approach by creating a residual score (global cognition residualized for hippocampal volume) in individuals along the AD spectrum. We demonstrate that in most real-life scenarios, the residual measure of cognitive resilience is highly correlated with cognition, and the degree of this correlation depends on the initial relationship between the adverse factor and cognition. Subsequently, any association between this resilience metric and an external variable may actually be driven by cognition, rather than by an operationalized measure of resilience. We then assess several strategies proposed as potential solutions to this problem, such as including both the residual and original cognitive measure in a model. However, we conclude these solutions may be insufficient, and we instead recommend against "pre-regression" strategies altogether in favor of using statistical moderation (e.g., interactions) to quantify resilience. CONCLUSIONS: Caution should be taken in the use and interpretation of the residual-based method of cognitive resilience. Rather than identifying resilient individuals, we encourage building more complete models of cognition to better identify the specific adverse and protective factors that influence cognitive decline.

Cognitive and Physiologic Reserve Independently Relate to Superior Neurocognitive Abilities in Adults Aging With HIV.

BACKGROUND: To investigate joint contributions of cognitive and physiologic reserve to neurocognitive SuperAging in older persons with HIV (PWH). METHODS: Participants included 396 older PWH (age range: 50-69 years) who completed cross-sectional neuropsychological and neuromedical evaluations. Using published criteria, participants exhibiting global neurocognition within normative expectations of healthy 25-year-olds were classified as SuperAgers (SA; n = 57). Cognitively normal (CN; n = 172) and impaired (n = 167) participants were classified with chronological age-based norms. Cognitive reserve was operationalized with an estimate of premorbid verbal intelligence, and physiologic reserve was operationalized with a cumulative index of 39 general and HIV-specific health variables. Analysis of variance with confirmatory multinomial logistic regression examined linear and quadratic effects of cognitive and physiologic reserve on SA status, adjusting for chronological age, depression, and race/ethnicity. RESULTS: Univariably, SA exhibited significantly higher cognitive and physiologic reserve compared with CN and cognitively impaired ( d s ≥ 0.38, p s < 0.05). Both reserve factors independently predicted SA status in multinomial logistic regression; higher physiologic reserve predicted linear increases in odds of SA, and higher cognitive reserve predicted a quadratic "J-shaped" change in odds of SA compared with CN (ie, odds of SA > CN only above 35th percentile of cognitive reserve). CONCLUSIONS: Each reserve factor uniquely related to SA status, which supports the construct validity of our SA criteria and suggests cognitive and physiologic reserve reflect nonoverlapping pathways of neuroprotection in HIV. Incorporation of proxy markers of reserve in clinical practice may improve characterization of age-related cognitive risk and resilience among older PWH, even among PWH without overt neurocognitive impairment.

Social Networks and Cognitive Reserve: Network Structure Moderates the Association Between Amygdalar Volume and Cognitive Outcomes.

OBJECTIVES: The cognitive reserve hypothesis has been proposed as a key mechanism explaining the link between social networks and cognitive function but has rarely been empirically tested using neuroimaging data. This study examines whether social network attributes moderate the association between amygdalar volume and cognitive function. METHODS: Data were from the Social Networks in Alzheimer Disease study (N = 154) and Indiana Alzheimer's Disease Research Center. Social networks were measured using the PhenX Social Network Battery. Regional data from magnetic resonance imaging (amygdalar volume [AV]) were analyzed using FreeSurfer software. Cognitive function was measured using the Montreal Cognitive Assessment (MoCA) and consensus diagnosis. Linear regression analyses were conducted to test the moderating role of social networks on the association between AV and cognitive function. RESULTS: Participants with greater ability to span multiple social roles and subgroups within their networks scored higher on the MoCA after adjusting for sociodemographic variables, depression, frequency of contact, and AV. Social networks moderated the association between AV and cognitive function. DISCUSSION: Among participants who engaged in diverse and loosely connected social networks, the expected adverse cognitive effects of brain volume in regions implicated in socioemotional processing were attenuated. These findings suggest that cognitive stimulation achieved through social interaction with a diverse array of social relationships across multiple contexts may help promote cognitive reserve.

Gender differences in cognitive reserve: implication for subjective cognitive decline in women.

BACKGROUND: Subjective Cognitive Decline (SCD) is a self-experienced decline in cognitive capacity with normal performance on standardized cognitive tests, showing to increase risk of Alzheimer's Disease (AD). Cognitive reserve seems to influence the progression from SCD to Mild Cognitive Impairment (MCI) and to AD. The aim of our study was to investigate gender differences in cognitive reserve evaluating how sex might modulate the role of cognitive reserve on SCD. METHODS: We included 381 SCD patients who underwent clinical evaluation, neuropsychological assessment, evaluation of premorbid intelligence by the Test di Intelligenza Breve (TIB), cognitive complaints by the Memory Assessment Clinics Questionnaire (MAC-Q), and apolipoprotein E (APOE) genotyping. RESULTS: The proportion between women and men was significantly different (68.7% [95% CI 63.9-73.4 vs 31.4%, 95% CI 26.6-36.0]). Women were younger than men at onset of SCD and at the baseline visit (p = 0.021), had lower years of education (p = 0.007), lower TIB scores (p < 0.001), and higher MAC-Q scores (p = 0.012). TIB was directly associated with age at onset of SCD in both women and men, while years of education was inversely associated with age at onset only in women. Multivariate analysis showed that sex influences TIB independently from years of education. TIB was directly associated with MAC-Q in men. CONCLUSIONS: Sex interacts with premorbid intelligence and education level in influencing the age at onset and the severity of SCD. As the effect of education was different between men and women, we speculated that education might act as a minor contributor of cognitive reserve in women.

Effect of Cognitive Reserve on the Association of Vascular Brain Injury With Cognition: Analysis of the PURE and CAHHM Studies.

BACKGROUND AND OBJECTIVES: To determine whether cognitive reserve attenuates the association of vascular brain injury with cognition. METHODS: Cross-sectional data were analyzed from 2 harmonized studies: the Canadian Alliance for Healthy Hearts and Healthy Minds (CAHHM) and the Prospective Urban and Rural Epidemiology (PURE) study. Markers of cognitive reserve were education, involvement in social activities, marital status, height, and leisure physical activity, which were combined into a composite score. Vascular brain injury was defined as nonlacunar brain infarcts or high white matter hyperintensity (WMH) burden on MRI. Cognition was assessed using the Montreal Cognitive Assessment Tool (MoCA) and the Digit Symbol Substitution Test (DSST). RESULTS: There were 10,916 participants age 35-81. Mean age was 58.8 years (range 35-81) and 55.8% were female. Education, moderate leisure physical activity, being in a marital partnership, being taller, and participating in social groups were each independently associated with higher cognition, as was the composite cognitive reserve score. Vascular brain injury was associated with lower cognition (ß -0.35 [95% confidence interval [CI] -0.53 to -0.17] for MoCA and ß -2.19 [95% CI -3.22 to -1.15] for DSST) but the association was not modified by the composite cognitive reserve variable (interaction p = 0.59 for MoCA and p = 0.72 for DSST). CONCLUSIONS: Both vascular brain injury and markers of cognitive reserve are associated with cognition. However, the effects were independent such that the adverse effects of covert vascular brain injury were not attenuated by higher cognitive reserve. To improve cognitive brain health, interventions to both prevent cerebrovascular disease and promote positive lifestyles are needed.

Influence of Cognitive Reserve on Cognitive Trajectories: Role of Brain Pathologies.

BACKGROUND AND OBJECTIVES: Evidence on the association of cognitive reserve (CR) with the cognitive trajectories is limited. We aimed to examine the influence of CR indicator on domain-specific cognitive trajectories taking brain pathologies into account. METHODS: Within the Rush Memory and Aging Project, 1,697 participants without dementia (mean age 79.6 years) were followed up to 21 years. CR indicator encompassing education, early-life, mid-life, and late-life cognitive activities and late-life social activity was ascertained at baseline and categorized as tertiles (lowest, middle, and highest). Global cognition, episodic memory, semantic memory, working memory, visuospatial ability, and perceptual speed were assessed annually with 19 tests, from which composite scores were derived. During the follow-up, 648 participants died and underwent autopsies to evaluate brain pathologies. Data were analyzed using linear mixed-effect models. RESULTS: Among the participants, the score of the CR indicator ranged from -8.00 to 5.74 (mean 0.00 ± 2.23). In multi-adjusted mixed-effect models, compared to the lowest CR, the highest was related to a slower decline in global cognition (ß = 0.028, 95% confidence interval [CI] 0.012-0.043), episodic memory (ß = 0.028, 95% CI 0.010-0.047), and working memory (ß = 0.019, 95% CI 0.005-0.033) during the follow-up. In brain pathologic data analysis, the association of the highest CR with cognitive function changes remained significant among participants with high Alzheimer disease pathology or gross infarcts. DISCUSSION: High CR indicator is associated with preserved global cognitive function, episodic memory, and working memory, even in the presence of brain pathologies. Our findings highlight the important role of high CR accumulation in the prevention of cognitive decline.