Higher Cognitive Reserve Research Articles

Dysregulation of RNA modification systems in clinical populations with neurocognitive disorders.

The study of modified RNA known as epitranscriptomics has become increasingly relevant in our understanding of disease-modifying mechanisms. Methylation of N6 adenosine (m6A) and C5 cytosine (m5C) bases occur on mRNAs, tRNA, mt-tRNA, and rRNA species as well as non-coding RNAs. With emerging knowledge of RNA binding proteins that act as writer, reader, and eraser effector proteins, comes a new understanding of physiological processes controlled by these systems. Such processes when spatiotemporally disrupted within cellular nanodomains in highly specialized tissues such as the brain, give rise to different forms of disease. In this review, we discuss accumulating evidence that changes in the m6A and m5C methylation systems contribute to neurocognitive disorders. Early studies first identified mutations within FMR1 to cause intellectual disability Fragile X syndromes several years before FMR1 was identified as an m6A RNA reader protein. Subsequently, familial mutations within the m6A writer gene METTL5, m5C writer genes NSUN2, NSUN3, NSUN5, and NSUN6, as well as THOC2 and THOC6 that form a protein complex with the m5C reader protein ALYREF, were recognized to cause intellectual development disorders. Similarly, differences in expression of the m5C writer and reader effector proteins, NSUN6, NSUN7, and ALYREF in brain tissue are indicated in individuals with Alzheimer's disease, individuals with a high neuropathological load or have suffered traumatic brain injury. Likewise, an abundance of m6A reader and anti-reader proteins are reported to change across brain regions in Lewy bodies diseases, Alzheimer's disease, and individuals with high cognitive reserve. m6A-modified RNAs are also reported significantly more abundant in dementia with Lewy bodies brain tissue but significantly reduced in Parkinson's disease tissue, whilst modified RNAs are misplaced within diseased cells, particularly where synapses are located. In parahippocampal brain tissue, m6A modification is enriched in transcripts associated with psychiatric disorders including conditions with clear cognitive deficits. These findings indicate a diverse set of molecular mechanisms are influenced by RNA methylation systems that can cause neuronal and synaptic dysfunction underlying neurocognitive disorders. Targeting these RNA modification systems brings new prospects for neural regenerative therapies.

Using Cognitive Reserve to Create Norms for the TMA-93 (Relational Binding of Images).

TMA-93 examines relational binding using images. Biomarker validation has demonstrated that it is discriminative for diagnosing early AD. The effect of cognitive reserve on TMA-93 performance remains unexplored and could improve the interpretative framework for using the test. To study the effect of cognitive reserve on TMA-93 performance and to provide new norms for the test that include its measurement. Cognitively unimpaired people aged 55 and over were systematically recruited for this cross-sectional normative study in southern Spain. Age, sex, and scores on the Cognitive Reserve Questionnaire (CRQ; maximum score: 25 points) were collected, and the TMA-93 was administered (maximum score: 30 points). Percentile-based reference data that captured combinations of socio-demographics variables with significant effect on TMA-93 performance were calculated. 902 participants (62.5% female; age: median = 68, IQR = 61-75, range = 55-90) were included. CRQ total scores were globally low (median = 8, IQR = 5-13, range = 0-24). Cognitive reserve, including modifiable items as reading activity and intellectual gaming activity, and age mainly supported the TMA-93 total score variance. Sex seemed to have some influence in the elderly. TMA-93 total scores medians began to drop from 70-75 years old. Higher total score on the CRQ and, possibly, female sex determined a gentler slope. New norms based on these variables showed wide variations in scores for the 5th and 10th percentiles. Visual relational binding ability depends on cognitive reserve, including modifiable items. The age-related binding deficit is buffered by higher cognitive reserve and, at older ages, by female sex.

Resting-state functional connectivity is modulated by cognitive reserve in early Parkinson's disease.

Fronto-striatal disconnection is thought to be at the basis of dysexecutive symptoms in patients with Parkinson's disease (PD). Multiple reserve-related processes may offer resilience against functional decline. Among these, cognitive reserve (CR) refers to the adaptability of cognitive processes. To test the hypothesis that functional connectivity of pathways associated with executive dysfunction in PD is modulated by CR. Twenty-six PD patients and 24 controls underwent resting-state functional magnetic resonance imaging. Functional connectivity was explored with independent component analysis and seed-based approaches. The following networks were selected from the outcome of the independent component analysis: default-mode (DMN), left and right fronto-parietal (l/rFPN), salience (SalN), sensorimotor (SMN), and occipital visual (OVN). Seed regions were selected in the substantia nigra and in the dorsolateral and ventromedial prefrontal cortex for the assessment of seed-based functional connectivity maps. Educational and occupational attainments were used as CR proxies. Compared with their counterparts with high CR, PD individuals with low CR had reduced posterior DMN functional connectivity in the anterior cingulate and basal ganglia, and bilaterally reduced connectivity in fronto-parietal regions within the networks defined by the dorsolateral and ventrolateral prefrontal seeds. Hyper-connectivity was detected within medial prefrontal regions when comparing low-CR PD with low-CR controls. CR may exert a modulatory effect on functional connectivity in basal ganglia and executive-attentional fronto-parietal networks. In PD patients with low CR, attentional control networks seem to be downregulated, whereas higher recruitment of medial frontal regions suggests compensation via an upregulation mechanism. This upregulation might contribute to maintaining efficient cognitive functioning when posterior cortical function is progressively reduced.

Association of Lifelong Cognitive Reserve with Dementia and Mild Cognitive Impairment among Older Adults with Limited Formal Education: A Population-Based Cohort Study

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.

Sex differences in cognitive reserve among first episode of psychosis patients.

Cognitive reserve (CR) has recently been considered a key factor in the onset of a first episode of psychosis (FEP). However, the differences in CR in FEP patients according to sex have not yet been investigated. CR was estimated among 443 FEP patients (246 men and 197 women) and 156 healthy controls (96 men and 60 women) by using the proxies premorbid IQ, years of education and employment status. A neuropsychological battery was administrated to measure neurocognitive specific domains. Analyses of variance were used to make comparisons between groups. FEP women had greater CR than FEP men. This circumstance was not observed in healthy controls. Among the group of patients with low CR, FEP women outperformed FEP men in the cognitive domains verbal memory and processing speed. Meanwhile, among the FEP patients with high CR, men showed better performance in attention than women. Differences in CR observed between FEP men and women could be related to a number of specific factors, such as, age at illness onset, education level, and variability in performance in verbal memory, processing speed, and attention domains. These results provide background information about CR in FEP patients that will be useful in the design of sex specific cognitive remediation interventions.

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.

Cognitive Reserve Moderates the Effects of Fatigue and Depressive Symptoms in Multiple Sclerosis.

To investigate cognitive reserve as a possible moderator in the relationship between fatigue and depressive symptoms in persons with multiple sclerosis (PwMS). Fifty-three PwMS (37 female; mean age, 52.66; mean education, 14.81) completed comprehensive neuropsychological testing and psychosocial questionnaires assessing the perceived effects of fatigue (Fatigue Impact Scale) and depressive symptoms (Beck Depression Inventory-Fast Screen). Cognitive reserve (CR) was operationalized as Fixed CR and Malleable CR. Fixed CR was quantified as the standardized mean of years of education and a vocabulary-based estimate of premorbid intelligence. Malleable CR was quantified as the standardized mean of cognitive exertion, exercise, and socializing items from the Cognitive Health Questionnaire. Regressions on depressive symptoms examining fatigue, both conceptualizations of CR, and their interactions were explored. A Bonferroni correction was used; results were considered significant at an alpha level of p < .01. The interactions between fatigue and both conceptualizations of CR were significant, p = .005 (Fixed CR); p = .004 (Malleable CR). Simple effects tests revealed that fatigue only predicted depressive symptoms in PwMS with low Fixed CR or low Malleable CR (p's < .001), and not in those with high Fixed or high Malleable CR (p > .01). Cognitive reserve moderated the relationship between fatigue and depressive symptoms in PwMS. Specifically, fatigue does not appear to influence depression in PwMS with high cognitive reserve. Having higher cognitive reserve (either Fixed or Malleable) may reduce the likelihood that fatigue will lead to depressive symptoms in MS.

High lifelong cognitive reserve prolongs disability‐free survival: Role of cognitive function

AbstractBackgroundHigh cognitive reserve (CR) has been related to a decreased dementia risk, but the association between CR and survival with independence is unknown. We examined whether lifelong CR accumulation is associated with disability‐free survival and explored the extent to which cognitive function mediates this association.MethodWithin the Rush Memory and Aging Project, 1,633 dementia‐ and disability‐free participants (mean age: 79.3 years) were followed annually for up to 22 years to detect disability and deaths. A lifelong CR indicator was derived based on information about education, early‐life, mid‐life, and late‐life cognitive activities, and late‐life social activity, and categorized into tertiles (low, moderate, and high). Disability was assessed annually in terms of participants’ ability to conduct activities of daily living and survival status was observed during the follow‐up period. Global cognitive function was assessed annually with a battery of 19 tests. Data were analyzed using Cox models, Laplace regression, and generalized structural equation models.ResultDuring the follow‐up (median: 4.35 years, interquartile range: 2.01 to 7.98 years), 1,079 (64.6%) participants died or developed disability. In multi‐adjusted Cox models, CR score was does‐dependently associated with disability/death (hazard ratio [HR] 0.96, confidence interval [CI] 0.93–0.99). Compared to low CR, the multi‐adjusted HR (95% CI) of high CR was 0.82 (0.70–0.95) for disability/death. In Laplace regression, the median disability‐free survival time was prolonged by 0.17 (95% CI 0.05–0.30) years per unit higher CR score, and 0.99 (95% CI 0.28–1.71) years for participants with high CR compared to low CR. In mediation analysis, cognitive function mediated 35.7% of the association between CR and disability‐free survival.ConclusionHigh lifelong CR is associated with prolonged disability‐free survival, and cognitive function mediates about one‐third of this association.

Associations of lifespan cognitive reserve with mild cognitive impairment and dementia among older adults with low literacy: A population‐based cohort study

AbstractBackgroundEducational attainment in early life represents a major contributor to cognitive reserve (CR). High CR capacity derived from lifespan enriching factors could delay cognitive decline. We sought to investigate the longitudinal associations of CR capacity with mild cognitive impairment (MCI) and dementia among older adults with no or low literacy.MethodThis population‐based cohort study included 2141 rural participants (age≥60 years; 59.5% women; 84.8% illiteracy or elementary school) in the Shandong Yanggu Study of Aging and Dementia who were free of dementia at baseline (August‐December 2014) and who undertook follow‐up examinations in March‐September 2018. CR capacity was estimated by integrating early‐life education attainment, adulthood occupation and marital status, and late‐life physical activity and social support, and categorized into low, intermediate, and high levels using tertiles. MCI and amnestic MCI were defined according to the Petersen’s criteria that integrated clinical assessment with neuropsychological tests. Dementia and Alzheimer’s disease (AD) were diagnosed according to the DSM‐IV and NIA‐AA criteria, respectively. Data were analyzed using the structural equation and Cox proportional‐hazards models.ResultDuring an average of 3.7 (SD = 0.4) years of follow‐up, 102 of the 2141 dementia‐free participants were diagnosed with dementia, including 75 with AD. Compared to the low CR level, intermediate and high CR levels were associated with multi‐adjusted hazards ratios (HRs) (95% confidence intervals [CIs]) of 0.59 (0.37–0.94) and 0.47 (0.26–0.85) for dementia and 0.53 (0.31–0.92) and 0.38 (0.17–0.83) for AD, respectively. In addition, out of the 1727 MCI‐free participants at baseline, 330 developed MCI at follow‐up, including 270 with aMCI. Intermediate and high CR levels (vs. low) were associated with multi‐adjusted HRs (95% CIs) of 0.70 (0.53–0.92) and 0.60 (0.45–0.81) for MCI and 0.65 (0.48–0.87) and 0.58 (0.42–0.79) for amnestic MCI, respectively.ConclusionIn Chinese rural elderly, high CR capacity is associated with reduced risks of MCI, amnestic MCI, dementia, and AD. This suggests that the effect of CR capacity in delaying the onset of MCI and dementia exists even among rural older adults with no or very low literacy.

Executive function may underlie cognitive reserve: A 3‐year follow‐up study

AbstractBackgroundThe hypothetical concept of cognitive reserve (CR) has been proposed to explain why someone can manage to function normally even in the presence of brain pathology. However, it still remains to be determined what components constitute such resilience against Alzheimer’s disease (AD) pathology. In the current study we investigated the characteristics of cognitively normal (CN) elders with high CR.MethodWe included CN participants from the Gwangju Alzheimer’s Disease and Related Dementia Cohort in Korea. We selected a group of CN individuals who showed a significant amyloid‐beta (aß) deposition at baseline and stayed CN over the follow‐up period. They were defined as high CR group. For comparison purpose, individuals with a significant aß deposition at baseline but converted to MCI at follow‐up were also included. In the final analysis, 94 high CR group and 24 control group were included. Group comparisons in socio‐demographic, clinical and cognitive variables were performed using χ2 tests and ANOVA controlling for age, education, gender, and follow‐up month.ResultMean follow‐up month were 43.37. There were no group differences in education, gender, socio‐economic status, family history of dementia or stroke, medical conditions, body mass index, subjective memory complaints, and instrumental activities of daily living. However, high CR group was younger and had shorter follow‐up period, therefore such variables were controlled when cognitive tests were compared. High CR group was more religious (p &lt; 0.001), showed higher complexity in former job (p = 0.009), and higher level of executive functoning (Digit Dpan Backward, p = 0.012; Fluency test, p = 0.008; Boston Naming Test, p = 0.014; Trail Making Test part B, p = 0.017) than control group. There were no group differences in episodic memory tests and visuospatial abilities.ConclusionIndividuals with high CR could cope better with AD pathology. Many factors have been suggested to be associated with CR. Regarding cognitive process involved, our findings suggest that executive function plays an important role in constituting high CR. Preserved executive function may, at least in part, underlie CR.

Cognitive dispersion as a function of cognitive reserve: influence on cognition and functional connectivity in a healthy middle‐aged population

AbstractBackgroundCognitive dispersion index (CDI), a measure of intraindividual variability across neuropsychological tests, is considered a sensitive marker of prodromic stages of Alzheimer’s Disease (Halliday et al. J. Intell 2018;6(1):12). CDI has been negatively associated with cognitive reserve (CR), another factor that influences the risk of dementia (Stern et al. Alzh&amp;Dement 2020;16(9):1305‐1311). Nevertheless, how these two elements interact with each other and are linked with cognition and brain state (e.g., functional connectivity), remains unclear. Our aim was to investigate whether CDI has a differential influence on cognitive performance (CP) and on resting‐state functional connectivity (rsFC) as a function of CR level, in a healthy middle‐aged sample.MethodFive hundred forty‐four healthy volunteers (aged 53.11±7.10 years; 269 female) from the Barcelona Brain Health Initiative cohort (BBHI, https://bbhi.cat/en), were stratified by CR (median = 14) into High CR (HCR, N = 230) and Low CR (LCR, N = 314) using the cognitive reserve questionnaire (CRQ; Rami et al. Rev Neurol 2011;52(4):195‐201). CDI was extracted by intraindividual standard deviation method (Costa et al. Clinic Neuropsychol 2019;33(2):369‐389) and CP was calculated as a global cognition composite score including episodic memory, speed of processing and executive function tests. Functional magnetic resonance imaging (fMRI) was acquired, and measures of rsFC within networks were computed through Shirer atlas (Shirer et al. Cerebral Cortex 2012;22(1):158‐165). Statistical analyses were based on univariate ANCOVA GLMs, and partial correlations adjusted by age and gender.ResultThough no significant group interaction was found, a negative correlation between CDI and CP was identified for the HCR group (r = ‐0.170,p = 0.010; Fig.1A). On fMRI there was a significant group difference (HCR vs. LCR) in the association between CDI and rsFC in anterior salience network (aSN: F = 5.005,p = 0.026), where only HCR participants showed a significant negative association between CDI and aSN rsFC values (r = ‐0.187,p = 0.010; Fig.1B&amp;C).ConclusionOur findings suggested that CDI has a clearly measurable effect on HCR participants, both in terms of its effect on CP and on rsFC. These results highlight the value of considering CDI measurements when performing neuropsychological assessments in middle‐aged individuals, particularly in those with high CR estimates.

Exposure factors associated with dementia among older adults in Iceland: the AGES-Reykjavik study.

The study aimed to assess whether factors related to cognitive performance were associated with the development of dementia. Additionally, the study aimed to establish whether cognitive performance at baseline or change in cognition between baseline and follow-up (five-year period) had a stronger association with whether an individual would fulfill a dementia criterion at follow-up. The data was collected from 2002 to 2011. Logistic regression was applied to the AGES-Reykjavik Study epidemiological data. The analysis, which builds upon previous data analyses of the same dataset, included 1,491 participants between the ages of 66 and 90. All those included were considered to have normal cognition at baseline; 8.2% (n = 123) of them fulfilled a dementia criterion at follow-up five years later. The study's results indicated that being high on cognitive reserve factors reduced the risk of developing dementia. Compared to other known dementia risk factors, cognitive reserve factors (education level, participation in leisure activities, and self-reported health) were more likely than others to have an association with dementia. Additionally, the study's findings showed that cognitive performance at baseline, rather than change in cognition between baseline and follow-up five years later, had a stronger association with dementia at the follow-up assessment. Together, these findings support the notion that promoting high cognitive reserve throughout the lifespan and reaching high cognitive performance is important in reducing dementia risk.

The Influence of Birth Cohorts on Future Cognitive Decline.

Slowed rates of cognitive decline have been reported in individuals with higher cognitive reserve (CR), but interindividual discrepancies remain unexplained. Few studies have reported a birth cohort effect, favoring later-born individuals, but these studies remain scarce. We aimed to predict cognitive decline in older adults using birth cohorts and CR. Within the Alzheimer's Disease Neuroimaging Initiative, 1,041 dementia-free participants were assessed on four cognitive domains (verbal episodic memory; language and semantic memory; attention; executive functions) at each follow-up visit up to 14 years. Four birth cohorts were formed according to the major historical events of the 20th century (1916-1928; 1929-1938; 1939-1945; 1946-1962). CR was operationalized by merging education, complexity of occupation, and verbal IQ. We used linear mixed-effect models to evaluate the effects of CR and birth cohorts on rate of performance change over time. Age at baseline, baseline structural brain health (total brain and total white matter hyperintensities volumes), and baseline vascular risk factors burden were used as covariates. CR was only associated with slower decline in verbal episodic memory. However, more recent birth cohorts predicted slower annual cognitive decline in all domains, except for executive functions. This effect increased as the birth cohort became more recent. We found that both CR and birth cohorts influence future cognitive decline, which has strong public policy implications.

Getting the brain into gear: An online study investigating cognitive reserve and word-finding abilities in healthy ageing.

Lifetime experiences and lifestyle, such as education and engaging in leisure activities, contribute to cognitive reserve (CR), which delays the onset of age-related cognitive decline. Word-finding difficulties have been identified as the most prominent cognitive problem in older age. Whether CR mitigates age-related word-finding difficulties is currently unknown. Using picture-naming and verbal fluency tasks, this online study aimed to investigate the effect of CR on word-finding ability in younger, middle-aged, and older adults. All participants were right-handed, monolingual speakers of British English. CR for both the period preceding and coinciding with the COVID-19 pandemic was measured through years of education and questionnaires concerning the frequency of engagement in cognitive, leisure, and physical activities. Linear mixed-effect models demonstrated that older adults were less accurate at action and object naming than middle-aged and younger adults. Higher CR in middle age predicted higher accuracies for action and object naming. Hence, high CR might not only be beneficial in older age, but also in middle age. This benefit will depend on multiple factors: the underlying cognitive processes, individual general cognitive processing abilities, and whether task demands are high. Moreover, younger and middle-aged adults displayed faster object naming compared to older adults. There were no differences between CR scores for the period preceding and coinciding with the pandemic. However, the effect of the COVID-19 pandemic on CR and, subsequently, on word-finding ability might only become apparent in the long term. This article discusses the implications of CR in healthy ageing as well as suggestions for conducting language production studies online.

Moderating effects of cognitive reserve on the relationship between brain structure and cognitive abilities in middle-aged and older adults

The cognitive reserve (CR) hypothesis is reinforced by negative moderating effects, suggesting that those with higher CR are less reliant on brain structure for cognitive function. Previous research on CR’s moderating effects yielded inconsistent results, motivating our 3 studies using UK Biobank data. Study I examined five CR proxies' moderating effects on global, lobar, and regional brain-cognition models; study II extended study I by using a larger sample size; and study III investigated age-related moderating effects on the hippocampal regions. In study I, most moderating effects were negative and none survived the multiple comparison correction, but study II identified 13 global-level models with significant negative moderating effects that survived correction. Study III showed age influenced CR proxies’ moderating effects in hippocampal regions. Our findings suggest that the effects of CR proxies on brain integrity and cognition varied depending on the proxy used, brain integrity indicators, cognitive domain, and age group. This study offers significant insights regarding the importance of CR for brain integrity and cognitive outcomes.

The influence of culture and cognitive reserve on the clinical presentation of behavioural-variant frontotemporal dementia

Characterisation of the clinical profile of behavioural-variant frontotemporal dementia (bvFTD) has predominantly been based on Western samples. Some small studies have suggested that the clinical profile may differ in culturally and linguistically diverse populations. Additionally, there is evidence that patients from non-English speaking backgrounds may have more cognitive reserve, allowing them to tolerate more disease pathology before clinical symptoms emerge. This study aims to characterise the clinical profiles of patients with bvFTD from culturally diverse backgrounds. BvFTD patients were classified as Australian-born (Australian) or Culturally and Linguistically Diverse-English-speaking (CALD-English) and Culturally and Linguistically Diverse-Language Other Than English (CALD-LOTE). Clinical features, cognitive test performance and cognitive reserve were compared between groups. Voxel-based morphometry was used to examine the neural correlates of cognitive reserve. 107 patients with bvFTD (53 Australian, 36 CALD-English, 18 CALD-LOTE) and 51 controls were included. Analysis of neuropsychiatric features revealed more elation in Australian patients compared to CALD-English patients, with trends for CALD-LOTE patients to report more irritability. CALD-LOTE patients also had higher cognitive reserve and showed relatively greater verbal than non-verbal cognitive impairment. Neuroimaging analyses revealed that higher cognitive reserve was associated with lower integrity in the frontal–temporal regions associated with typical disease pathology in bvFTD. Our findings support the hypothesis that cognitive reserve may delay early cognitive decline in culturally and linguistically diverse patients, although these patients may still show poor verbal performance due to cultural testing biases. Clinically, these results highlight the need to consider cultural and linguistic background to inform the assessment of dementia.

Genetic propensity for cerebral amyloidosis and risk of mild cognitive impairment and Alzheimer's disease within a cognitive reserve framework.

We constructed a polygenic risk score (PRS) for β-amyloid (PRSAβ42) to proxy AD pathology and investigated its association with incident Alzheimer's disease (AD)/amnestic mild cognitive impairment (aMCI) and the influence of cognitive reserve (CR), proxied by educational years, on the relationship between PRSAβ42 and AD/aMCI risk. A total of 618 cognitive-normal participants were followed-up for 2.92 years. The association of PRSAβ42 and CR with AD/aMCI incidence was examined with COX models. Then we examined the additive interaction between PRSAβ42 and CR and the CR effect across participants with different PRSAβ42 levels. Higher PRSAβ42 and CR were associated with a 33.9% higher risk and 8.3% less risk for AD/aMCI, respectively. An additive interaction between PRSAβ42 and CR was observed. High CR was associated with 62.6% less risk of AD/aMCI incidence only in the high-PRSAβ42 group. A super-additive effect of PRSAβ42 and CR on AD/aMCI risk was observed. CR influence was evident in participants with high PRSAβ42.

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

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

Assessing Flexibility of Solution Strategy: Strategy Shifting as a Measure of Cognitive Reserve.

This series of experiments explores whether flexibility in strategy shifting might function as an expression of cognitive reserve (CR). A reasoning task was designed using matrix reasoning stimuli that each required 1 of 2 specific solution strategies: logicoanalytic and visuospatial. It was formatted as a task-switching paradigm, assessing the ability to switch between solution strategies as measured by switch costs. Study 1 was done on Amazon Mechanical Turk and included an assessment of CR proxies. Study 2 used participants who had been studied extensively with neuropsychological assessments and structural neuroimaging. Study 1 found that switch costs increased with aging. In addition, a relationship between switch costs and CR proxies was noted, suggesting a relationship between the flexibility of strategy shifting and CR. The results of Study 2 again indicated that age negatively affected strategy-shifting flexibility, but that individuals with higher CR as measured with standard proxies performed better. The flexibility measure accounted for additional variance in cognitive performance over that explained by cortical thickness, suggesting that it may contribute to CR. Overall, the results are consistent with the idea that flexibility in strategy shifting might be 1 cognitive process that underlies cognitive reserve.

Education reduces cognitive dysfunction in Alzheimer's disease by changing regional cerebral perfusion: An in-vivo arterial spin labeling study.

Formal education and other cognitive challenges influence brain structure and improve function. It is believed that cognitive activities create a cognitive reserve (CR) that can slow the decline due to aging and neurodegenerative diseases. This study investigated alterations of regional cerebral blood flow (rCBF) associated with high and low CR in different stages of Alzheimer's disease (AD) and examined whether rCBF alteration mediates the relationship between education and cognitive performance. Patients with AD or amnestic mild cognitive impairment (aMCI) and healthy controls were divided into low cognitive reserve (LCR) and high cognitive reserve (HCR) subgroups according to median of education years (≤ 9 vs. > 9 years). The final study population included 89 AD patients (67 LCR, 22 HCR), 74 aMCI patients (44 LCR, 30 HCR), and 66 healthy controls (29 LCR, 37 HCR). All subjects were examined by arterial spin labeling magnetic resonance imaging and a neurocognitive test battery. rCBF was compared among groups by two-way analysis of variance. Mediation analyses were used to explore the relationships among education, rCBF, and cognitive test scores. There were significant interaction effects of disease state (AD, aMCI, HC) and education level (LCR, HCR) on CBF in right hippocampus, posterior cingulate cortex, and right inferior parietal cortex (R_IPC). Education regulated episodic memory score by influencing right hippocampal CBF in HC_HCR and aMCI_HCR subgroups. Our results indicate that the protective effect of education against cognitive dysfunction in early-stage AD is mediated at least partially by altered CBF in right hippocampus.