Engagement in social, physical, and cognitive activities is beneficial for maintaining cognitive health in later life by providing cognitive reserves against cognitive and neurodegenerative decline.

Insight is needed to understand how different activities combine to provide cognitive protection before and after the beginning of decline.

The current work used a cross-sectional data set of older adults who were cognitively unimpaired (CU), live with subjective cognitive impairment (SCI), live with mild cognitive impairment (MCI), or live with Alzheimer’s disease. Beneficial behaviors included easily modifiable risk factors for dementia in late life: engagement in social, creative, and physical activities. The study explored individual and combined effects on the relationships between hippocampal volume and memory.

Greater engagement in beneficial behaviors minimized the neural–cognitive relationship in the SCI group. Once disease progression continued to MCI, risk factors no longer modified the brain-cognition relationship.

Understanding how individual behaviors combine provides guidance when developing intervention trials or public policy procedures.

Cognitive impairment is a common feature of multiple sclerosis (MS), and its severity may be influenced by several factors, such as biological sex and levels of cognitive reserve (CR). The relationship between sex, CR, and cognition has not yet been fully investigated. Therefore, the present study aimed to explore sex differences in CR building and the effect of sex and CR on cognitive performance in MS.

233 participants underwent the Brief Repeatable Battery of Neuropsychological Tests (BRB-N), the Stroop test, and the Cognitive Reserve Scale. The t-test was performed to compare sociodemographic variables, Italian adaptation of the Cognitive Reserve Scale, and cognitive test scores between sexes. To evaluate the effect of CR and sex and their interaction on cognitive performance several models of multivariate analyses of covariance were performed (dependent variables: all subtests of Brief Repeatable Battery of Neuropsychological Tests and Stroop scores; independent variables: sex and CR). Covariates included age, Expanded Disability Status Scale, and BDI-II scores.

Women showed higher levels of CR, particularly in daily activities (t = −5.848, p<.001), hobbies (t = −2.591, p = .010), and social life (t = −2.362, p = .011). Sex differences were noted in verbal memory and fluency (with women outperforming men) and processing speed (with men performing better than women). Multivariate analyses revealed a nonsignificant interaction between CR and sex on cognition (Λ=.950, F(10,260)=.813, p = .617, ηp2 = .050).

CR and sex seemed to affect cognitive performance independently in pwMS. This highlights the importance of considering both factors in cognitive assessment, and that both sexes may benefit from specific psychoeducational training aimed at increasing CR levels.

To evaluate the impact of receptive vocabulary versus years of education on neuropsychological performance of Black and White older adults.

A community-based prospectively enrolled cohort (n = 1,007; 130 Black, 877 White) in the Emory Healthy Brain Study were administered the NIH Toolbox Picture Vocabulary Test and neuropsychological measures. Group differences were evaluated with age, sex, and education or age, sex, and Toolbox Vocabulary scores as covariates to determine whether performance differences between Black versus White participants were attenuated or eliminated.

With vocabulary as a covariate, the main effect of race was no longer significant for the MoCA, Phonemic Fluency, Rey Auditory Verbal Learning Test, and Rey Complex Figure Test immediate and delayed recall. Although still significantly different between groups, the effect sizes for Animal Fluency, Trails B-A, Symbol Digit Modalities Test, and Rey Copy were attenuated, with the greatest reductions occurring for the Multilingual Naming Test and Judgment of Line Orientation.

Findings support the value of using receptive vocabulary as a proxy for premorbid ability level when comparing the cognitive performance of Black and White older adults. The results extend investigations using measures of single word reading to encompass measures assessing word meaning.

Higher white matter hyperintensity (WMH) volume is a marker of cardiovascular disease (CVD) risk. CVD risk factors increase risk for Alzheimer’s disease and related dementias (ADRD). Mexican Americans (MA) and individuals of other Hispanic/Latino heritages have higher risk for CVD and ADRD. However, knowledge of associations between WMH volume and cognition in these groups remains limited.

We conducted a cross-sectional study of associations between WMH volume and neuropsychological performance (attention/executive functioning, memory) in MA (n = 851) and non-Hispanic White (NHW; n = 747) adults in the Health and Aging Brain Study: Health Disparities.

The MA group (mean age = 63.72 ± 7.90 years; 66.3% female) had higher rates of consensus diagnoses of hypertension and diabetes, whereas the NHW group (mean age = 69.18 ± 8.65 years; 55.2% female) had higher rates of diagnosed CVD (ps < .01). WMH volumes were higher among individuals with CVD risk factors/conditions (ps < .01). There were differential associations between WMH and neuropsychological performance across ethnoracial groups (ps < .001), wherein associations were steeper in the NHW group than in the MA group. Lower educational level was associated with higher WMH volume in the NHW group (p < .001), but no association was seen in the MA group (p > .05).

Negative effects of pathological changes in the form of WMH on cognition may be less robust or consistent for MA adults than NHW adults. Furthermore, the impact of WMH on cognition in NHW adults may be mitigated by cognitive reserve related to educational attainment.

Cognitive reserve (CR) has been linked to dementia, yet its influence on the risk of depression and related outcomes remains unknown. We aimed to examine the association of CR with depression and subsequent dementia or death, and to assess the extent to which CR is related to depression-free survival.

Within the UK Biobank, 436,232 participants free of depression and dementia were followed. A comprehensive CR indicator (low, moderate, and high) was created using latent class analysis based on information on education, occupation, mentally passive sedentary behavior, social connection, confiding with others, and leisure activities. Depression, dementia, and survival status were ascertained through self-reported medical history and/or linkages to medical records. Data were analyzed using multi-state Markov model and Laplace regression.

Over a median follow-up of 12.96 years, 16,560 individuals developed depression (including 617 with subsequent dementia) and 28,655 died. In multivariable multi-state models, compared with low CR, high CR was associated with lower risk of depression (hazard ratio 0.53 [95% confidence interval 0.51–0.56]) and lower risk of post-depression dementia (0.55 [0.34–0.88]) or death (0.69 [0.55–0.88]) in middle-aged adults (aged <60 years). In Laplace regression, the depression-free survival time was prolonged by 2.77 (2.58–2.96) years in participants with high compared to low CR.

High CR is associated with lower risks of depression and subsequent transitions to dementia and death, particularly in middle age. High CR may prolong depression-free survival. Our findings highlight the importance of enhancing CR in the prevention and prognosis of depression.

It remains unclear whether cognitive reserve can attenuate dementia risk among people with different genetic predispositions.

We aimed to examine the association between cognitive reserve and dementia, and further to explore whether and to what extent cognitive reserve may modify the risk effect of genetic factors on dementia.

Within the UK Biobank, 210 631 dementia-free participants aged ≥60 years were followed to detect incident dementia. Dementia was ascertained through medical and death records. A composite cognitive reserve indicator encompassing education, occupation and multiple cognitively loaded activities was created using latent class analysis, categorised as low, moderate and high level. Polygenic risk scores for Alzheimer's disease were constructed to evaluate genetic risk for dementia, categorised by tertiles (high, moderate and low). Data were analysed using Cox models and Laplace regression.

In multi-adjusted Cox models, the hazard ratio (HR) of dementia was 0.66 (95% confidence interval (CI) 0.61–0.70) for high cognitive reserve compared with low cognitive reserve. In Laplace regression, participants with high cognitive reserve developed dementia 1.62 (95% CI 1.35–1.88) years later than those with low cognitive reserve. In stratified analysis by genetic risk, high cognitive reserve was related to more than 30% lower dementia risk compared with low cognitive reserve in each stratum. There was an additive interaction between low cognitive reserve and high genetic risk on dementia (attributable proportion 0.24, 95% CI 0.17–0.31).

High cognitive reserve is associated with reduced risk of dementia and may delay dementia onset. Genetic risk for dementia may be mitigated by high cognitive reserve. Our findings underscore the importance of enhancing cognitive reserve in dementia prevention.

Cognitive Reserve (CR) developed from observation that several individuals show fewer cognitive impairment compared to others with the same brain injuries or neuropathology. Cognitive reserve is a potentially modifiable characteristic. Most of studies on cognitive reserve were conducted on chronic progressive diseases such as dementia. This study aims to define the role of cognitive reserve in geriatric delirium cases.

This case-control study was conducted in the acute geriatric inpatient of Cipto Mangunkusumo Hospital, Jakarta, Indonesia on June to September 2019 that consisted of 33 subjects with delirium and 33 controls. The measurement of cognitive reserve was done using the Indonesian adaptation of Cognitive Reserve Index questionnaire (CRIq) with 3 subscales, i.e. Education, Work Activity and Leisure Time.

We found that the CRIq scores of delirium patients were lower compared to the non-delirium controls both on total and each subscores, with a statistically significant mean difference (p<0,01). Patients with low-medium cognitive reserve also more likely to develop delirium compared to those with medium-high cognitive reserve (OR 9; 95% CI 2.86 to 28.22).

Low cognitive reserve may serve as a risk factor for delirium in the elderly. The measure of CRI in the geriatric inpatients unit can be used to determine those at risk of developing delirium. Further research are warranted to elaborate potentially modifiable variables of cognitive reserve to minimize the risk of delirium.

Polygenic risk scores for educational attainment (PRSEA), cognitive reserve (CR), and clinical symptoms are associated with functioning in first-episode psychosis (FEP). Nevertheless, the mechanisms underlying their complex interaction are yet to be explored. This study assessed the mediating role of CR and clinical symptoms, both negative (NS) and positive (PS), on the interrelationship between PRSEA and functionality, one year after a FEP.

A total of 162 FEP patients underwent clinical, functional, and genetic assessments. Using genome-wide association study summary results, PRSEA were constructed for each individual. Two mediation models were performed. The parallel mediation model explored the relationship of PRSEA with functionality through CR and clinical symptoms. The serial mediation model tested a causal chain of the three mediators: CR, NS, and PS. Mediation analysis was performed using the PROCESS function V.4.1 in SPSS V.22.

A serial mediation model revealed a causal chain for PRSEA > CR > NS > Functionality (β = −0.35, 95%CI [−0.85, −0.04], p < 0.05). The model fit the data satisfactorily (CFI = 1.00; RMSEA = 0.00; SRMR = 7.2 × 10−7). Conversely, no parallel mediation was found between the three mediators, PRSEA and functionality and the model poorly fit the data (CFI = 0.30; RMSEA = 0.25; SRMR = 0.11).

Both CR and NS mediate the relationship between PRSEA and functionality at one-year follow-up, using serial mediation analysis. This may be relevant for prevention and personalized early intervention to reduce illness impact and improve functional outcomes in FEP patients.

Amyotrophic Lateral Sclerosis (ALS) is a devastating neurodegenerative disease that results in progressive decline in motor function in all patients and cognitive impairment in a subset of patients. Evidence suggests that cognitive reserve (CR) may protect against cognitive and motor decline in ALS, but less is known about the impact of specific occupational skills and requirements on clinical outcomes in ALS. We expected that a history of working jobs with more complex cognitive demands would protect against cognitive decline, while jobs that require fine and complex motor skills would protect against motor dysfunction.

Participants were 150 ALS patients recruited from the University of Pennsylvania’s Comprehensive ALS Center. Participants underwent clinical and neuropsychological evaluations within 1 year of ALS diagnosis. Cognitive performance was measured using the Edinburgh Cognitive and Behavioral ALS Screen (ECAS), which includes ALS-Specific (e.g., verbal fluency, executive functions, language, social cognition) and NonSpecific (e.g., memory, visuospatial functions) composite scores. Motor functioning was measured using the Penn Upper Motor Neuron (UMN) scale and the ALS Functional Rating Scale (ALS-FRS). Occupational skills and requirements for each participant were assessed using data from the Occupational Information Network (O*NET) Database. O*NET data were assessed using principal components analysis, and 17 factor scores were derived representing distinct worker characteristics (n=5), occupational requirements (n=7), and worker requirements (n=5). These scores were entered as independent variables in multiple linear regression models using ECAS, UMN, and ALS-FRS scores as dependent variables covarying for education.

Preserved ECAS ALS-Specific performance was associated with jobs that involve greater reasoning abilities (ß=2.03, S.E.=0.79, p<.05), analytic skills (ß=3.08, S.E.=0.91, p<.001), and humanities knowledge (ß=1.20, S.E.=0.58, p<.05), as well as less exposure to environmental hazards (ß=-2.42, S.E.=0.76, p<.01) and fewer demands on visualperceptual (ß=-1.75, S.E.=0.73, p<.05) and technical skills (ß=-1.62, S.E.=0.63, p<.05). Preserved ECAS Non-Specific performance was associated with jobs that involve greater exposure to conflict (ß=0.82, S.E.=0.33, p<.05) and social abilities (ß=0.65, S.E.=0.29, p<.05). Jobs involving greater precision skills (ß=1.92, S.E.=0.79, p<.05) and reasoning ability (ß=2.10, S.E.=0.95, p<.05) were associated with greater disease severity on the UMN, while jobs involving more health services knowledge were associated with worse motor functioning on the ALS-FRS (ß=-1.30, S.E.=0.60, p<.05).

Specific occupational skills and requirements show protective effects on cognitive functioning in ALS, while others confer risk for cognitive and motor dysfunction. Preserved cognitive functioning was linked to a history of employment in jobs requiring strong reasoning abilities, social skills, and humanities knowledge, while poorer cognitive functioning was linked to jobs involving a high risk of exposure to environmental hazards and high visuo-perceptual and technical demands. In contrast, we did not find evidence of motor reserve, as no protective effects of occupational skills and requirements were found for motor symptoms, and jobs involving greater precision skills, reasoning abilities, and health services knowledge were linked to worse motor functioning. Our findings offer new insights into how occupational history may protect against cognitive impairment or confer elevated risk for cognitive and motor dysfunction in ALS.

Cognitive reserve and health-related fitness are associated with favorable cognitive aging, but Black/African American older adults are underrepresented in extant research. Our objective was to explore the relative contributions and predictive value of cognitive reserve and health-related fitness metrics on cognitive performance at baseline and cognitive status at a 4-year follow up in a large sample of Black/African American older adults.

Participants aged 65 years and older from the Health and Retirement Study (HRS) who identified as Black/African American and completed baseline and follow-up interviews (including physical, health, and cognitive assessments) were included in the study. The final sample included 321 Black/African American older adults (mean age = 72.8; sd = 4.8; mean years of education = 12.3; sd = 2.9; mean body mass index (BMI) = 29.1; sd = 5.2; 60.4% identified as female). A cross-sectional analysis of relative importance – a measure of partitioned variance controlling for collinearity and model order – was first used to explore predictor variables and inform the hierarchical model order. Next, hierarchical multiple regression was used to examine cross-sectional relationships between cognitive reserve (years of education), health-related fitness variables (grip strength, lung capacity, gait speed, BMI), and global cognition. Multiple logistic regression was used to examine prospective relationships between predictors and longitudinal cognitive status (maintainers versus decliners). Control variables in all models included age, gender identity, and a chronic disease index score.

Cross-sectional relative importance analyses identified years of education and gait speed as important predictors of global cognition. The cross-sectional hierarchical regression model explained 33% of variance in baseline global cognition. Education was the strongest predictor of cognitive performance (β = 0.48, p < 0.001). Holding all other variables constant, gait speed was significantly associated with baseline cognitive performance and accounted for a significant additional amount of explained variance (ΔR = 0.01, p = 0.032). In a prospective analysis dividing the sample into cognitive maintainers and decliners, a single additional year of formal education increased chances of being classified as a cognitive maintainer (OR = 1.30, 95% CI = 1.17-1.45). There were no significant relationships between rate of change in health-related fitness and rate of change in cognition.

Education, a proxy for cognitive reserve, was a robust predictor of global cognition at baseline and was associated with increased odds of maintaining cognitive ability at 4-year follow up in Black/African American older adults. Of the physical performance metrics, gait speed was associated with cognitive performance at baseline. The lack of observed association between other fitness variables and cognition may be attributable to the brief assessment procedures implemented in this large-scale study.

Individuals with Parkinson's disease (PD) have varying trajectories of cognitive decline. One reason for this heterogeneity may be "cognitive reserve": where higher education/IQ/current mental engagement compensates for increasing brain burden (Stern et al., 2020). With few exceptions, most studies examining cognitive reserve in PD fail to include brain metrics. This study's goal was to examine whether cognitive reserve moderated the relationship between neuroimaging indices of brain burden (diffusion free water fraction and T2-weighted white matter changes) and two commonly impaired domains in PD: executive function and memory. We hypothesized cognitive reserve would mitigate the relationship between higher brain burden and worse cognitive performance.

Participants included 108 individuals with PD without dementia (age mean=67.9±6.3, education mean=16.6±2.5) who were prospectively recruited for two NIH-funded projects at the University of Florida. All received neuropsychological measures of executive function (Trails B, Stroop, Letter Fluency) and memory (delayed recall: Hopkin's Verbal Learning Test-Revised, WMS-III Logical Memory). Domain specific z-score composites were created using data from age/education matched non-PD peer controls (N=62). For the Cognitive Reserve (CR) proxy, a z-score composite included years of education, WASI-II Vocabulary, and Wechsler Test of Adult Reading. At the time of testing, participants completed multiple MRI scans (T1-weighted, diffusion, Fluid Attenuated Inversion Recovery) from which the following were extracted: 1) whole-brain free water within the white matter (a measure of microstructural integrity and neuroinflammation), 2) white matter hyperintensities/white matter total volume (WMH/WMV), and bilaterally-averaged edge weights of white matter connectivity between 3) dorsolateral prefrontal cortex and caudate and 4) entorhinal cortex and hippocampi. Separate linear regressions for each brain metric used executive function and memory composites as dependent variables; predictors were age, CR proxy, respective brain metric, and a residual centered interaction term (brain metric*CR proxy). Identical models were run in dichotomized short and long disease duration groups (median split=6 years).

In all models, a lower CR proxy significantly predicted worse executive function (WMH/WMV: beta=0.49, free water: beta=0.54, frontal edge weight: beta=0.49, p's<0.001) and memory (WMH/WMV: beta=0.42, free water: beta=0.35, temporal edge weight: beta=0.39, p's <0.01). For neuroimaging metrics, higher free water significantly predicted worse executive function (beta=-0.39, p=0.002) but not memory. No other brain metrics were significant predictors of either domain. Accounting for PD duration, higher free water predicted worse executive function for those with both short (beta=-0.49, p=0.04) and long disease duration (beta=-0.48, p=0.02). Specifically in those with long disease duration, higher free water (beta=-0.57 p=0.02) and lower edge weights between entorhinal cortex and hippocampi (beta=0.30, p=0.03) predicted worse memory. Overall, no models contained significant interactions between the CR proxy and any brain metric.

Results replicate previous work showing that a cognitive reserve proxy relates to cognition. However, cognitive reserve did not moderate brain burden's relationship to cognition. Across the sample, greater neuroinflammation was associated with worse executive function. For those with longer disease duration, higher neuroinflammation and lower medial temporal white matter connectivity related to worse memory. Future work should examine other brain burden metrics to determine whether/how cognitive reserve influences the cognitive trajectory of PD.