The Effect of Cognitive Reserve on the Cognitive Status of Persons With Multiple Sclerosis

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Validation of the cognitive reserve theory in patients with traumatic brain injury

White matter hyperintensities and cognition: Testing the reserve hypothesis

Cognitive Reserve and the Relationship Between Depressive Symptoms and Awareness of Deficits in Dementia

Elucidating the mechanisms by which late-life neurodegeneration causes cognitive decline requires understanding why some individuals are more resilient than others to the effects of brain change on cognition (cognitive reserve). Currently, there is no way of measuring cognitive reserve that is valid (e.g. capable of moderating brain-cognition associations), widely accessible (e.g. does not require neuroimaging and large sample sizes), and able to provide insight into resilience-promoting mechanisms. To address these limitations, this study sought to determine whether a machine learning approach to combining standard clinical variables could (i) predict a residual-based cognitive reserve criterion standard and (ii) prospectively moderate brain-cognition associations. In a training sample combining data from the University of California (UC) Davis and the Alzheimer's Disease Neuroimaging Initiative-2 (ADNI-2) cohort (N = 1665), we operationalized cognitive reserve using an MRI-based residual approach. An eXtreme Gradient Boosting machine learning algorithm was trained to predict this residual reserve index (RRI) using three models: Minimal (basic clinical data, such as age, education, anthropometrics, and blood pressure), Extended (Minimal model plus cognitive screening, word reading, and depression measures), and Full [Extended model plus Clinical Dementia Rating (CDR) and Everyday Cognition (ECog) scale]. External validation was performed in an independent sample of ADNI 1/3/GO participants (N = 1640), which examined whether the effects of brain change on cognitive change were moderated by the machine learning models’ cognitive reserve estimates. The three machine learning models differed in their accuracy and validity. The Minimal model did not correlate strongly with the criterion standard (r = 0.23) and did not moderate the effects of brain change on cognitive change. In contrast, the Extended and Full models were modestly correlated with the criterion standard (r = 0.49 and 0.54, respectively) and prospectively moderated longitudinal brain-cognition associations, outperforming other cognitive reserve proxies (education, word reading). The primary difference between the Minimal model—which did not perform well as a measure of cognitive reserve—and the Extended and Full models—which demonstrated good accuracy and validity—is the lack of cognitive performance and informant-report data in the Minimal model. This suggests that basic clinical variables like anthropometrics, vital signs, and demographics are not sufficient for estimating cognitive reserve. Rather, the most accurate and valid estimates of cognitive reserve were obtained when cognitive performance data—ideally augmented by informant-reported functioning—was used. These results indicate that a dynamic and accessible proxy for cognitive reserve can be generated for individuals without neuroimaging data and gives some insight into factors that may promote resilience.

P79. The effect of cognitive reserve in a subcohort of the EMPIR project NeuroMet ‘Innovative measurements for improved diagnosis and management of neurodegenerative diseases’

Previous studies showed inconsistent results for the correlation between cognitive reserve (CR) and cognitive function in Parkinson's disease (PD). Additionally, conflicting results were obtained for the association between CR and risk of longitudinal cognitive decline, longitudinal progression to mild cognitive impairment (MCI), and longitudinal progression to dementia in PD patients. Thus, a meta-analysis is essential to summary these inconsistent results. Articles published before November 2021 were searched in databases as follows: PubMed, Web of Science, Medline, EMBASE, and Google Scholar. We computed Fisher's z score and standard error (SE) of each transformation value of correlation coefficient for the correlation between educational level and cognitive function. Additionally, odds ratios (ORs) or hazard ratios (HRs) and their 95% confidence intervals (CIs) were computed as effect sizes for the correlation between educational level and risk of longitudinal progression to MCI. The present study showed that higher educational levels were related to better general cognitive function, executive function, memory, and information processing speed in PD patients, whereas no significant association was showed between educational levels and visuospatial function, language in PD patients. Additionally, included studies reported a negative association between educational level and risk of longitudinal progression to MCI in PD patients. In conclusion, the study demonstrated that higher CR might be correlated with better cognitive function and lower risk of longitudinal progression to MCI in PD. In addition, large-scale prospective studies are necessary to explore the effect of CR on cognitive function in PD.

To examine cross-sectional effects of cognitive reserve (CR) and brain reserve (BR) on cognition across the spectrum of Alzheimer disease (AD). We included 663 AD biomarker-positive participants with dementia (probable AD, n = 462) or in the predementia stages (preclinical/prodromal AD, n = 201). Education was used as a proxy of CR and intracranial volume as a proxy of BR. Cognition was assessed across 5 domains (memory, attention, language, visuospatial, and executive functions). We performed multiple linear regression models to examine effects of CR and BR on cognitive domain Z scores, adjusted for cerebral atrophy. Furthermore, we assessed differences in effects according to disease stage and across degrees of total reserve using a 4-level variable (high CR/high BR, high CR/low BR, low CR/high BR, and low CR/low BR). We found positive, independent effects of both CR and BR across multiple cognitive domains. Stratification for disease stage showed that effects of CR on attention and executive functioning were greater in predementia than in dementia (β = 0.39 vs β = 0.21 [Welch t = 2.40, p < 0.01] and β = 0.46 vs β = 0.26 [t = 2.83, p < 0.01]). Furthermore, we found a linear trend for better cognitive performance in all domains in the high CR/high BR group, followed by high CR/low BR, low CR/high BR, and then low CR/low BR (p for trend <0.05). CR and BR both independently mitigate cognitive symptoms in AD. The positive effect of CR is most strongly expressed in the predementia stages and the additive effects of high CR and BR are most beneficial.

Effect of cognitive reserve on cognitive function and cognitive deterioration in Parkinson's disease: a longitudinal cohort study.

Cognitive Impairment in Dialysis Patients: Focus on the Blood Vessels?

The aim of the paper is to determine the effects of the cognitive reserve on brain tumour patients' cognitive functions and, specifically, if cognitive reserve helps patients cope with the negative effects of brain tumours on their cognitive functions. We retrospectively studied a large sample of around 700 patients, diagnosed with a brain tumour. Each received an MRI brain examination and performed a battery of tests measuring their cognitive abilities before they underwent neurosurgery. To account for the complexity of cognitive reserve, we construct our cognitive reserve proxy by combining three predictors of patients' cognitive performance, namely, patients' education, occupation, and the environment where they live. Our statistical analysis controls for the type, side, site, and size of the lesion, for fluid intelligence quotient, and for age and gender, in order to tease out the effect of cognitive reserve on each of these tests. Clinical neurological variables have the expected effects on cognitive functions. We find a robust positive effect of cognitive reserve on patients' cognitive performance. Moreover, we find that cognitive reserve modulates the effects of the volume of the lesion: the additional negative impact of an increase in the tumour size on patients' performance is less severe for patients with higher cognitive reserve. We also find substantial differences in these effects depending on the cerebral hemisphere where the lesion occurred and on the cognitive function considered. For several of these functions, the positive effect of cognitive reserve is stronger for patients with lesions in the left hemisphere than for patients whose lesions are in the right hemisphere. The development of prevention strategies and personalized rehabilitation interventions will benefit from our contribution to understanding the role of cognitive reserve, in addition to that of neurological variables, as one of the factors determining the patients' individual differences in cognitive performance caused by brain tumours.

Cognitive reserve moderates the association between hippocampal volume and episodic memory in middle age

This study mainly intended to disentangle the role played by physical reserve as a mediator of the relationship between cognitive reserve and global cognitive functioning in older people aging well. A sample of 120 67-101-year-old community-dwellers was recruited in the Sardinian Blue Zone, an area characterized by the extreme longevity of its inhabitants. Each respondent completed a battery of tests examining cognitive functioning, perceived physical health, cognitive reserve, and physical reserve (objectively assessed through accelerometric-derived measures). Significant associations were found among measures of cognitive reserve, physical reserve, perceived physical health, and cognition. Besides, two mediational analyses pointed out that physical reserve and distinct indexes of cognitive reserve explained 18% and 32% of the variance associated with global cognitive functioning. In conclusion, the combination of high cognitive reserve and more preserved motor functioning seems to contribute to the maintenance of healthy cognition in older people aging well.

Vulnerable Neural Systems and the Borderland of Brain Aging and Neurodegeneration

Openness to experience and cognitive functioning and decline in older adults: The mediating role of cognitive reserve