UNASSIGNED: Education, occupation, and cognitive activity are key indicators of cognitive reserve and are thought to influence cognitive impairment. However, the individual and combined impacts of these factors are not fully understood. This study aims to investigate the roles of education and occupation in cognitive impairment while controlling for brain reserve and cognitive activity.
UNASSIGNED: This cross-sectional study involved 369 participants aged 50 years or older from urban outpatient clinics in Jilin Province, China. Cognitive impairment was assessed using neuropsychological scales and brain imaging. Cognitive activity was evaluated with the Cognitive Reserve Scale (CRS). Covariance analysis and logistic regression models were used to analyze the associations, adjusting for age, sex, education, and occupation.
UNASSIGNED: Higher education was significantly associated with a lower risk of cognitive impairment (p < 0.001), regardless of occupation. In contrast, occupational complexity and cognitive activity did not show a significant relationship with cognitive impairment (p > 0.05).
UNASSIGNED: Education, rather than occupation or cognitive activities, is a significant predictor of cognitive impairment, highlighting the importance of educational attainment in cognitive health.

BACKGROUND: Cardiometabolic diseases (CMDs) including type 2 diabetes, heart disease, and stroke have been linked to a higher risk of dementia. We examined whether high levels of cognitive reserve (CR) can attenuate the increased dementia risk and brain pathologies associated with CMDs.
METHODS: Within the UK Biobank, 216,178 dementia-free participants aged ≥ 60 were followed for up to 15 years. Baseline CMDs and incident dementia were ascertained from medical records, medication use, and medical history. Latent class analysis was used to generate an indicator of CR (low, moderate, and high) based on education, occupational attainment, confiding in others, social contact, leisure activities, and television watching time. A subsample (n = 13,663) underwent brain MRI scans during follow-up. Volumes of total gray matter (GMV), hippocampus (HV), and white matter hyperintensities (WMHV) were ascertained, as well as mean diffusivity (MD) and fractional anisotropy (FA) in white matter tracts.
RESULTS: At baseline, 43,402 (20.1%) participants had at least one CMD. Over a mean follow-up of 11.7 years, 6,600 (3.1%) developed dementia. The presence of CMDs was associated with 57% increased risk of dementia (HR 1.57 [95% CI 1.48, 1.67]). In joint effect analysis, the HRs of dementia for people with CMDs and moderate-to-high CR and low CR were 1.78 [1.66, 1.91] and 2.13 [1.97, 2.30]), respectively (reference: CMD-free, moderate-to-high CR). Dementia risk was 17% lower (HR 0.83 [0.77, 0.91], p < 0.001) among people with CMDs and moderate-to-high compared to low CR. On brain MRI, CMDs were associated with smaller GMV (β -0.18 [-0.22, -0.13]) and HV (β -0.13 [-0.18, -0.08]) as well as significantly larger WMHV (β 0.06 [0.02, 0.11]) and MD (β 0.08 [0.02, 0.13]). People with CMDs and moderate-to-high compared to low CR had significantly larger GMV and HV, but no differences in WMHV, MD, or FA.
CONCLUSIONS: Among people with CMDs, having a higher level of CR was associated with lower dementia risk and larger gray matter and hippocampal volumes. The results highlight a mentally and socially active life as a modifiable factor that may support cognitive and brain health among people with CMDs.

UNASSIGNED: To develop a nomogram for mild cognitive impairment (MCI) in patients with subjective cognitive decline (SCD) undergoing physical examinations in China.
UNASSIGNED: We enrolled 370 patients undergoing physical examinations at the Medical Center of the First Hospital of Jilin University, Jilin Province, China, from October 2022 to March 2023. Of the participants, 256 were placed in the SCD group, and 74 were placed in the MCI group. The population was randomly divided into a training set and a validation set at a 7:3 ratio. A least absolute shrinkage and selection operator (LASSO) regression model was applied to optimize feature selection for the model. Multivariable logistic regression analysis was applied to construct a predictive model. The performance and clinical utility of the nomogram were determined using Harrell\'s concordance index, calibration curves, and decision curve analysis (DCA).
UNASSIGNED: Cognitive reserve (CR), age, and a family history of hypertension were associated with the occurrence of MCI. The predictive nomogram showed satisfactory performance, with a concordance index of 0.755 (95% CI: 0.681-0.830) in internal verification. The Hosmer-Lemeshow test results suggested that the model exhibited good fit (p = 0.824). In addition, DCA demonstrated that the predictive nomogram had a good clinical net benefit.
UNASSIGNED: We developed a simple nomogram that could help secondary preventive health care workers to identify elderly individuals with SCD at high risk of MCI during physical examinations to enable early intervention.

OBJECTIVE: We aimed to identify the effect of lifespan cognitive reserve and (pre)frailty on mild cognitive impairment (MCI) among older adults.
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.
CONCLUSIONS: 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.

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.
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.
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.
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.
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.

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BACKGROUND: Cognitive reserve (CR) and the catechol-O-methyltransferase (COMT) Val/Met polymorphism are reportedly linked to negative symptoms in schizophrenia. However, the regulatory effect of the COMT genotype on the relationship between CR and negative symptoms is still unexamined.
OBJECTIVE: To investigate whether the relationship between CR and negative symptoms could be regulated by the COMT Val/Met polymorphism.
METHODS: In a cross-sectional study, 54 clinically stable patients with schizophrenia underwent assessments for the COMT genotype, CR, and negative symptoms. CR was estimated using scores in the information and similarities subtests of a short form of the Chinese version of the Wechsler Adult Intelligence Scale.
RESULTS: COMT Met-carriers exhibited fewer negative symptoms than Val homozygotes. In the total sample, significant negative correlations were found between negative symptoms and information, similarities. Associations between information, similarities and negative symptoms were observed in Val homozygotes only, with information and similarities showing interaction effects with the COMT genotype in relation to negative symptoms (information, β = -0.282, 95%CI: -0.552 to -0.011, P = 0.042; similarities, β = -0.250, 95%CI: -0.495 to -0.004, P = 0.046).
CONCLUSIONS: This study provides initial evidence that the association between negative symptoms and CR is under the regulation of the COMT genotype in schizophrenia.

UNASSIGNED: This research aims to investigate putative mechanisms between glymphatic activity and cognition in mild cognitive impairment (MCI) and analyzes whether the relationship between cognitive reserve (CR) and cognition was mediated by glymphatic activity.
UNASSIGNED: 54 MCI patients and 31 NCs were enrolled to evaluate the bilateral diffusivity along the perivascular spaces and to acquire an index for diffusivity along the perivascular space (ALPS-index) on diffusion tensor imaging (DTI). The year of education was used as a proxy for CR. The ALPS-index was compared between two groups and correlation analyses among the ALPS-index, cognitive function, and CR were conducted. Mediation analyses were applied to investigate the correlations among CR, glymphatic activity and cognition.
UNASSIGNED: MCI group had a significantly lower right ALPS-index and whole brain ALPS-index, but higher bilateral diffusivity along the y-axis in projection fiber area (Dyproj) than NCs. In MCI group, the left Dyproj was negatively related to cognitive test scores and CR, the whole brain ALPS-index was positively correlated with cognitive test scores and CR. Mediation analysis demonstrated that glymphatic activity partially mediated the correlations between CR and cognitive function.
UNASSIGNED: MCI exhibited decreased glymphatic activity compared to NCs. CR has a protective effect against cognitive decline in MCI, and this effect may be partially mediated by changes in glymphatic activity.

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.
METHODS: 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).
METHODS: A population-based study.
METHODS: 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.
METHODS: 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 (β [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.

UNASSIGNED: The number of people with dementia is soaring. Cognitive reserve has been thought to be associated with dementia risk. It is not clear at which period in the life course and which cognitive reserve proxies contribute to the reduced risk of dementia.
UNASSIGNED: By scanning four databases (PubMed, Embase, Web of Science, and MEDLINE) up to Jun 3, 2023, longitudinal studies of life-course cognitive reserve and risk of dementia were found. The HRs and 95% CIs for each study were summarized using random effects models. Subgroup analyses and sensitivity analyses were conducted. Utilizing funnel plots, Begg and Egger tests, publication bias was investigated.
UNASSIGNED: A total of 27 studies were included, containing 10 in early-life, 10 in middle-life, and 13 in late-life. All studies used validated questionnaires to measure cognitive reserve, and dementia diagnosis followed recognized worldwide guidelines. All included studies were of medium or low risk. Cognitive reserve in early-life (Hazard ratio (HR): 0.82; 95% confidence interval (CI): 0.79-0.86), middle-life (HR: 0.91; 95% CI: 0.84-0.98) and late-life (HR: 0.81; 95% CI: 0.75-0.88) all have protective effects on dementia risk. Multiple sensitivity analyses showed consistent results.
UNASSIGNED: Dementia risk is reduced by the buildup of cognitive reserves during life-course. Accumulation of proxies for cognitive reserve in early and late life had the greatest effect on dementia risk reduction. Social connection may be an effective approach to lower dementia risk.