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Introduction: Early-life educational attainment contributes to cognitive reserve (CR). We investigated the associations of lifelong CR with dementia and mild cognitive impairment (MCI) among older people with limited formal education. Methods: This population-based cohort study included 2,127 dementia-free participants (≥60 years; 59.4% women; 81.5% with no or elementary school) who were examined at baseline (August-December 2014) and follow-up (March-September 2018). Lifelong CR score at baseline was generated from six lifespan intellectual factors. Dementia, MCI, and their subtypes were defined according to the international criteria. Data were analyzed using Cox proportional-hazards models. Results: During the total of 8,330.6 person-years of follow-up, 101 persons were diagnosed with dementia, including 74 with Alzheimer's disease (AD) and 26 with vascular dementia (VaD). The high (vs. low) tertile of lifelong CR score was associated with multivariable-adjusted hazards ratios (95% confidence interval) of 0.28 (0.14–0.55) for dementia and 0.18 (0.07–0.48) for AD. The association between higher CR and reduced AD risk was significant in people aged 60–74 but not in those aged ≥75 years (p for interaction = 0.011). Similarly, among MCI-free people at baseline (n = 1,635), the high (vs. low) tertile of lifelong CR score was associated with multivariable-adjusted hazard ratios of 0.51 (0.38–0.69) for MCI and 0.46 (0.33–0.64) for amnestic MCI. Lifelong CR was not related to VaD or non-amnestic MCI. Discussion: High lifelong CR is associated with reduced risks of dementia and MCI, especially AD and amnestic MCI. It highlights the importance of lifelong CR in maintaining late-life cognitive health even among people with no or limited education. [ABSTRACT FROM AUTHOR]

Background: Adverse childhood experiences (ACEs) are associated with later cognitive decline. However, the mechanisms underlying the effects of different types of ACEs are unclear. This study examined how ACEs impact cognitive function, specifically deprivation-related ACEs (DrACEs) and threat-related ACEs (TrACEs). Additionally, we explored the potential role of cognitive reserve (CR) and depression in these relationships., Methods: Data were taken from the China Health and Retirement Longitudinal Study (CHARLS) of 2014 and 2020. CR, depressive symptoms and cognitive function measures were collected from 2020. ACEs were assessed at the 2014 Life Course Survey. The main analyses included 7113 participants aged 45 years or older. To explore potential associations, linear regression and SPSS Macro PROCESS were employed., Results: Among middle-aged and older adults, only exposure to DrACEs was associated with cognitive function ((β = -0.101 [95%CI: -0.150, -0.052]) for DrACEs = 1; (β = -0.250 [95%CI: -0.333, -0.167]) for DrACEs ≥ 2). The indirect effects mediated by CR and depressive symptoms were statistically significant., Limitations: The use of retrospective self-reported data for ACEs may introduce recall bias., Conclusions: Chinese middle-aged and older adults who have experienced DrACEs exhibit poorer cognitive function, while the association between TrACEs and cognitive function was not significant. And the impact of DrACEs on cognitive function was mediated by CR and depressive symptoms. Further research is necessary to validate our findings, establish causal links, and uncover the underlying mechanisms involved., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024. Published by Elsevier B.V.)

Background: Cognitive abilities serves as a critical indicator of healthy aging. As China progresses into a stage of advanced population aging, there has been a significant increase in the number of elderly individuals experiencing age-related cognitive decline. Despite this demographic shift, there is a paucity of longitudinal research examining cognitive abilities among older Chinese adults over extended time periods. This study aims to investigate changes in cognitive abilities and explore group differences among older Chinese adults aged 65 to 110 years, employing a multidimensional temporal approach that encompasses age, period, and birth cohort effects., Methods: This study utilizes data from eight waves of the Chinese Longitudinal Healthy Longevity Survey (CLHLS), spanning from 1998 to 2018. The dataset comprises 94,116 observations from 36,157 unique participants. Cognitive abilities are assessed using Mini-Mental State Examination (MMSE) scores as a proxy measure. To address the issue of perfect collinearity in the temporal dimension, the study employs the Hierarchical Age-Period-Cohort Cross-Classified Random Effects Model (HAPC-CCREM). This model allows for the examination of age effects, period effects, and cohort effects on cognitive abilities among older Chinese adults. In the model specification, age is treated as a fixed effect, while period and birth cohort are incorporated as random effects. Drawing upon the cognitive reserve hypothesis, the study investigates significant factors influencing cognitive abilities in this population., Results: At the fixed-effect level, demographic factors, health behaviors, self-rated health, subjective well-being, and childhood adversity significantly influence cognitive abilities among older Chinese adults. The age effects are significant, with cognitive abilities exhibiting an inverted U-shaped curve across the lifespan. At the random-effect level, period effects are significant, revealing a gradual annual increase in overall cognitive levels among older Chinese adults since 2008. Cohort effects are also significant, demonstrating an increasing trend in overall cognitive levels for the earlier-born cohorts in the first six groups. Conversely, later-born cohorts in the latter five groups show a declining trend in overall cognitive levels. Notably, period effects significantly enhance cohort effects., Conclusions: The cognitive reserve hypothesis supports the significance of the majority of identified influencing factors. Cognitive abilities demonstrate an accelerating decline with increasing age, following an evolutionary trajectory consistent with physiological principles among older Chinese adults. Since 2008, cognitive abilities have shown a monotonic increasing trend annually, further validating the Flynn effect in this population. The cognitive abilities of the six earlier-born cohorts exhibit an increasing trend, supporting the compression of morbidity hypothesis. Conversely, the cognitive abilities of the five later-born cohorts show a declining trend, supporting the expansion of morbidity hypothesis. These findings collectively contribute to our understanding of cognitive aging patterns and their underlying mechanisms among older Chinese adults., Competing Interests: Declarations. Ethics approval and consent to participate: This study is a secondary analysis using CLHLS databases. This study Ethics Committees of Peking University and Duke University approved the ethics of the study (IRB00001052–13074). All methods were carried out in accordance with The Declaration of Helsinki. All included participants or their legal representatives provided written consent forms in the surveys. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Objective: We aimed to identify the effect of lifespan cognitive reserve and (pre)frailty on mild cognitive impairment (MCI) among older adults., Materials and Methods: A total of 4420 older adults aged above 60 with intact cognition recruited in 2011/2012 were followed up in 2015 from the China Health and Retirement Longitudinal Study (CHARLS). The assessment of MCI was based on executive function, episodic memory, and visual-spatial ability. (Pre)frailty was assessed by the validated version of the Fried physical frailty phenotype scale. The lifespan cognitive reserve consisted of the highest educational level, occupational complexity, and participation in leisure activities. Modified Poisson regression models were used to identify the risk of MCI in relation to (pre)frailty and lifespan cognitive reserve index. We examined the interactions of (pre)frailty and lifespan cognitive reserve index on both additive and multiplicative scales., Results: Baseline (pre)frailty significantly increased the risk of MCI after 3-4 years of follow-up, and high cognitive reserve protected individuals from the risk of MCI. There was an additive interaction between (pre)frailty and the low lifespan cognitive reserve (the relative excess interaction risk=1.08, 95 % CI= 0.25-1,91), but no multiplicative interaction (RR=0.95, 95 % CI= 0.67-1.37). The risk of MCI was larger among older adults with comorbid (pre)frailty and low cognitive reserve than those with each condition alone., Conclusion: Cognitive reserve attenuates the risk of MCI associated with (pre)frailty. This finding implicates the urgency for identifying and managing MCI among frail older adults who accumulate low cognitive reserve in the life course., Competing Interests: Declaration of competing interest The authors claim that there is no conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

Background: Despite existing studies showing that physical exercise improves cognitive function in older adults either concurrently or in a delayed manner, studies examining these associations simultaneously are rare. Additionally, the underlying mechanisms in these associations remain incompletely understood., Objective: This study explores the concurrent and delayed (two years later) associations between physical exercise and older adults' cognitive function. This study also investigates the mediating roles of three negative physical, psychological, and social resources: limitations in daily abilities, depressive mood, and isolation from friends, as well as the moderating roles of cognitive reserve on these associations., Design: A cohort sample of 6646 Chinese older adults (Mean age = 69.28, SD = 7.03) is obtained from the 2016 and 2018 waves of the China Longitudinal Aging Social Survey. Regression analysis was employed to test the concurrent and delayed associations between physical exercise and cognitive function. The bootstrap method was utilized to examine the mediating roles of limitations in daily activities, depression mood, and isolation from friends. Interaction terms were generated to investigate the moderating roles of cognitive reserve., Results: Physical exercise presents concurrent and delayed positive associations with cognitive function. Limitations in daily activities, depressive mood and isolation from friends mediate the above associations. Moreover, cognitive reserve plays a significant role in buffering the concurrent and delayed negative links between depressive mood, isolation from friends, and cognitive function, with larger negative relationships observed for older adults with lower rather than higher levels of cognitive reserve., Conclusions: This study validates the concurrent and delayed benefits of physical exercise on older adults' cognitive function while elucidating the underlying mechanisms. These findings offer practical implications for health policies and intervention programs aimed at enhancing older adults' cognitive function., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Cognitive reserve (CR) could partly explain the individual heterogeneity in cognitive decline. No study measured CR from a life course perspective and investigated the association between CR and trajectories of cognitive decline in older Chinese adults.Methods: Data of 6795 Chinese adults aged 60+ from China Health and Retirement Longitudinal Study were used. Global cognition score (0-32) was assessed in all four waves. A life-course CR score was constructed using markers of childhood circumstance, education, highest occupational class, and leisure activities in later life. Latent growth curve modelling (LGCM) was applied to assess the association between CR and trajectories of cognitive decline.Results: For the life-course CR, factor loadings of markers in adulthood and later life were larger than that of markers in childhood. The life-course CR score (ranged between - 2.727 and 6.537, SD: 1.74) was higher in urban Chinese adults (0.75, SD: 1.90) than in rural Chinese adults (- 0.50, SD: 1.43). The unconditional LGCM results showed that urban older Chinese adults had better global cognition at baseline (intercept: 15.010, 95% CI: 14.783, 15.237) and a slower rate of cognitive decline per year (linear slope: -0.394, 95% CI: - 0.508, - 0.281) than their rural counterparts (intercept: 12.144, 95% CI: 11.960, 12.329; linear slope: -0.498, 95% CI: - 0.588, - 0.408). After controlling for all covariates, one-unit higher CR score was associated with 1.615 (95% CI: 1.521, 1.709) and 1.768 (95% CI: 1.659, 1.876) unit higher global cognition at baseline for urban and rural older Chinese adults, respectively. The slower rate of cognitive decline associated with higher CR was more evident in rural residents (slope: 0.083, 95% CI: 0.057, 0.108) than in their urban counterparts (0.054, 95% CI: 0.031, 0.077).Conclusions: CR was associated with better baseline cognition and slower cognitive decline in Chinese older adults. Although rural residents were disadvantaged in both CR and cognition, the protective effect of CR against cognitive decline was stronger for them than in those who live in urban area. [ABSTRACT FROM AUTHOR]

Background: Mounting evidence suggests that sex differences exist in cognitive reserve (CR) for cognitively unimpaired (CU) elderly individuals. Global left frontal connectivity (gLFC connectivity) is a reliable neural substrate of CR.Objective: The purpose of this study was to explore sex differences in gLFC connectivity among CU elderly individuals.Methods: One hundred thirteen normal controls (NCs) (women = 66) and 132 individuals with subjective cognitive decline (SCD) (women = 92) were recruited from the Sino Longitudinal Study on Cognitive Decline (SILCODE) (data 1). Among them, 88 subjects underwent amyloid-β (Aβ) imaging, including 32 Aβ+ and 56 Aβ-subjects. Forty-six subjects underwent another rs-fMRI examination (data 2) to validate the repeatability of the calculation of gLFC connectivity, which was determined through seed-based functional connectivity between the LFC and voxels throughout the whole brain. Independent-sample t-tests were used to evaluate the sex differences in gLFC connectivity across different subgroups (NC versus SCD, Aβ+ versus Aβ-). Partial correlation analysis was used to calculate the correlations between gLFC connectivity and cognitive assessments.Results: Women exhibited lower gLFC connectivity in both the NC (p = 0.001) and SCD (p = 0.020) subgroups than men. Women also exhibited lower gLFC connectivity in both the Aβ-(p = 0.006) and Aβ+ (p = 0.025) groups. However, the significant difference disappeared in the Aβ+ group when considering the covariates of age, education, total intracranial volume, and APOE4-carrying status. In addition, gLFC connectivity values were negatively correlated with Geriatric Depression Scale scores in the SCD group (r = -0.176, p = 0.047).Conclusion: Women showed lower gLFC connectivity among CU elderly individuals. [ABSTRACT FROM AUTHOR]

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, χ 2 /df: 3.21/2; RMSEA: 0.02, and T1, χ 2 /df: 7.47/2; RMSEA: 0.05) and that it accepted both configural and metric invariance (Δχ 2 /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 (β = 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., (© 2024. The Author(s).)

Background: Several studies have found that bilingualism can delay the age of onset of Alz­heimer disease (AD). The interpretation of these findings is that switching between two languages can enhance cognitive reserve. However, some studies have provided inconsistent results. Diverse language pairs used by the bilinguals in different studies may contribute to the discrepancies. Cantonese and Mandarin are widely used in southern China, and regarded as bilingualism. The present study aims to determine if Cantonese/Mandarin bilingualism can delay the onset of AD. Methods: The data of 129 patients diagnosed with probable AD, including 48 Cantonese monolinguals, 20 Mandarin monolinguals, and 61 Cantonese/Mandarin bilinguals were analyzed. Results: Cantonese/Mandarin bilinguals were found to have an older age at AD onset, and older age at the first clinic visit than Mandarin monolinguals and Cantonese monolinguals. Both Mandarin monolinguals and Cantonese/Mandarin bilinguals had a higher education level and higher occupation status than the Cantonese monolinguals. Mandarin monolinguals did not differ from Cantonese/Mandarin bilinguals significantly in years of education and occupation status. The multiple linear regression analyses indicated that Cantonese/Mandarin bilingualism can delay the onset of AD independently. Conclusion: Constantly speaking both Cantonese and Mandarin from at least early adulthood can delay the onset of AD. [ABSTRACT FROM AUTHOR]

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., (© 2022. The Author(s).)

Abstract: This paper explores whether educational attainment has a cognitive reserve capacity in elder life. Using pilot data from the China Health and Retirement Longitudinal Study (CHARLS), we examined the impact of education on cognitive abilities at old ages. OLS results showed that respondents who completed primary school obtained 18.2 percent higher scores on cognitive tests than those who did not. We then constructed an instrumental variable (IV) by leveraging China's Great Famine of 1959–1961 as a natural experiment to estimate the causal effect of education on cognition. Two-stage least squares (2SLS) results provided sound evidence that completing primary school significantly increases cognition scores, especially in episode memory, by almost 20 percent on average. Moreover, Regression Discontinuity (RD) analysis provides further evidence for the causal interpretation, and shows that the effects are different for the different measures of cognition we explored. Our results also show that the Great Famine can result in long-term health consequences through the pathway of losing educational opportunities other than through the pathway of nutrition deprivation. [Copyright &y& Elsevier]

Background and Objectives: To investigate the relationship between baseline structural measurements of brain reserve and clinical progression in Parkinson disease (PD). To further provide a possible underlying mechanism for structural measurements of brain reserve in PD, we combined functional and transcriptional data and investigated their relationship with progression-associated patterns derived from structural measurements and longitudinal clinical scores., Methods: This longitudinal study collected data from June 2010 to March 2019 from 2 datasets. The Parkinson's Progression Markers Initiative (PPMI) included controls and patients with newly diagnosed PD from 24 participating sites worldwide. Results were confirmed using data from the Huashan dataset (Shanghai, China), which included controls and patients with PD. Clinical symptoms were assessed with Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) scores and Schwab & England activities of daily living (ADL). Both datasets were followed up to 5 years. Linear mixed-effects (LME) models were performed to examine whether changes in clinical scores over time differed as a function of brain structural measurements at baseline., Results: A total of 389 patients with PD (n = 346, age 61.3 ± 10.03, 35% female, PPMI dataset; n = 43, age 59.4 ± 7.3, 38.7% female, Huashan dataset) with T1-MRI and follow-up clinical assessments were included in this study. Results of LME models revealed significant interactions between baseline structural measurements of subcortical regions and time on longitudinal deterioration of clinical scores (MDS-UPDRS Part II, absolute β > 0.27; total MDS-UPDRS scores, absolute β > 1.05; postural instability-gait difficulty (PIGD) score, absolute β > 0.03; Schwab & England ADL, absolute β > 0.59; all p < 0.05, false discovery rate corrected). The interaction of baseline structural measurements of subcortical regions and time on longitudinal deterioration of the PIGD score was replicated using data from Huashan Hospital. Furthermore, the β-coefficients of these interactions recapitulated the spatial distribution of dopaminergic, metabolic, and structural changes between patients with PD and normal controls and the spatial distribution of expression of the α-synuclein gene ( SNCA )., Discussion: Patients with PD with greater brain resources (that is, higher deformation-based morphometry values) had greater compensatory capacity, which was associated with slower rates of clinical progression. This knowledge could be used to stratify and monitor patients for clinical trials., (© 2022 American Academy of Neurology.)

Background: Education could offer a protective effect on cognition in individuals with Subjective Cognitive Decline (SCD), which is considered to be the early stage of Alzheimer's Disease (AD). However, the effect of education on cognition in SCD individuals with SCD-plus features is not clear., Objective: The aim of the study was to explore the effect of education on cognition in SCD individuals with SCD-plus features., Methods: A total of 234 individuals with SCD were included from the Sino Longitudinal Study on Cognitive Decline (SILCODE). Cognition was assessed across 4 domains (memory, executive, language, and general cognitive functions). Multiple linear regression models were constructed to examine the effect of education on cognitive scores in individuals without worry (n=91) and with worry (n=143). Furthermore, we assessed differences in effects between APOE ε4 noncarriers and APOE ε4 carriers in both groups., Results: Multiple linear regression analysis showed a positive effect of education on memory, executive, and language cognition in individuals without worry and all cognitive domains in individuals with worry. Furthermore, we found a positive effect of education on executive cognition in APOE ε4 noncarriers without worry and language and general cognition in APOE ε4 carriers without worry. Meanwhile, education had a positive effect on all cognitive domains in APOE ε4 noncarriers with worry and executive, language, and general cognition in APOE ε4 carriers with worry., Conclusion: This study indicates that education has the potential to delay or reduce cognitive decline in SCD individuals with SCD-plus features., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Subjective cognitive decline (SCD) is the preclinical stage of Alzheimer's disease (AD). Abnormal brain glucose metabolism and Aβ depositions can be observed in SCD subjects. Nevertheless, there was not cognitive impaired performance in standardized neuropsychological in these subjects. Cognitive reserve (CR) could be the reason to explain this phenomenon. However, correspondence between CR and SCD was still uncleared. In this study, we attained 74 subjects underwent 18FFDG PET scans (SCD1 group) and 38 patients underwent 18FAV45 PET scans (SCD2 group) from Xuanwu Hospital, Beijing, China. First, SCD1 group was divided into SCD1H (high CR, n=33, educational years>12) and SCD1L (low CR, n=41, educational years<=12) groups. The SCD2 group was divided into SCD2H (high CR, n=17, educational years>12) and SCD2L (low CR, n=21, educational years<=12) groups. Second, we calculated standardized uptake value rate (SUVR) values of 18 FFDG PET and 18 F-AV45 PET images in voxel-wise level. Third, the two-sample t-test between low and high CR groups was used to investigate the effects of CR. As a result, the SUVR values of FDG-PET images in SCD1H (0.89±0.11) were significant lower than SCD1L (0.96±0.13, p=0.017). The SUVR values of AV45PET images in SCD2H (0.63±0.11) were significant lower than SCD2L (0.78±0.15, p=0.001). In addition, the frontal lobe was found as the main area of hypometabolism and reduced AB depositions. As a conclusion, there are differential glucose metabolism and Aβ deposition patterns in SCD subjects between low and high CR groups.

Background: Cognitive reserve (CR) can prevent the risk of incident cognitive impairment in the elderly. However, the moderator effects of CR on the link between hearing difficulties (HDs) and the risk of incident cognitive impairment are not well understood., Methods: This cohort study obtained data from the Chinese Longitudinal Healthy Longevity Survey from 2008 to 2014. The baseline samples included 6309 participants aged 65 years and older at baseline. Cognitive impairment was assessed using the Chinese version of the Mini Mental State Examination. A composite measure of CR was calculated based on education, occupational complexity, and leisure activities of the participants. The marginal structural model was utilized to investigate whether CR moderates the association between HD and incident cognitive impairment. Odds ratios (ORs) and accompanying 95% confidence intervals (CIs) were calculated., Results: Of the 6309 participants at baseline, 1936 (30.7%) developed cognitive impairment during the 6-year follow-up period and 2562 (40.6%) reported HD. The risk of incident cognitive impairment was 1.90-fold (95% CI 1.69-2.14) for participants developing HD compared to those without. Those with middle CR had lower OR (0.72, 95% CI 0.62-0.82) that further decreased to 0.58 (95% CI 0.49-0.69) for those with high CR. Participants with HD with low CR showed the highest OR (4.32, 95% CI 3.42-5.47). In addition, individuals with HD with low education levels or low complex occupations had the highest risk of incident cognitive impairment., Conclusions: CR moderates the negative association between HD and cognitive function. Education and occupation complexity may be more sensitive proxies for CR.

Introduction: An important index of brain reserve is the maximal attained brain size, which can be estimated by measuring the head circumference (HC). We investigated the association of HC and education with incident dementia in a population-based study of Chinese older adults., Methods: We conducted a prospective follow-up study of 1,659 non-demented participants with a mean age of 71.5 years. Characteristics and anthropometry of the participants were collected at baseline. Consensus diagnoses for dementia were made using DSM-IV criteria based on functional, neurological, and neuropsychological assessments., Results: We identified 168 new-onset dementia cases after a mean of 5.2 years of follow-up. Participants with smaller HC combined with low educational attainment had a significantly higher risk of incident dementia than those with larger HC who had completed more than 12 years of education (adjusted hazard ratio 4.48, 95% CI 2.47-8.12)., Discussion/conclusion: Our results suggest that smaller HC in combination with low education leads to a markedly increased risk of dementia., (© 2019 S. Karger AG, Basel.)