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PubMed2025

Protective Effects of Genetic Proxies of Cognitive Reserve in Parkinson's Disease: A Longitudinal Multi-Cohort Study.

BACKGROUND: Resilience factors are crucial in the progression of neurodegenerative diseases. However, it remains unclear whether a genetic predisposition to cognitive reserve influences clinical heterogeneity in the prognosis of Parkinson's disease (PD). OBJECTIVES: The aim is to evaluate the utility of polygenic scores (PGSs) for cognitive reserve proxies, including intelligence (INT), educational attainment (EA), and occupational attainment (OA), in predicting the clinical progression of PD. METHODS: Genetic and clinical data for progression of PD (progression to Hoehn and Yahr stage ≥3, progression to a Montreal Cognitive Assessment score ≤24, and occurrence of psychosis) were obtained from the Accelerating Medicine Partnership Parkinson's Disease database. We conducted multivariate Cox regression analysis, adjusting for relevant covariates, including years of education, variants in APOE, GBA1, LRRK2, and other cognitive reserve-related PGSs. RESULTS: All cognitive reserve-related PGSs significantly reduced the risk of cognitive decline, and EA-PGS (hazard ratio [HR], 0.550; 95% confidence interval [CI], 0.447-0.676; P < 0.001) remained significant after controlling for INT-PGS and OA-PGS. EA-PGS (HR, 0.805; 95% CI, 0.672-0.964; P = 0.019) was significantly associated with better motor prognosis after controlling for other PGSs. OA-PGS was linked to a decreased risk of developing psychosis in PD and remained significant after adjusting for others (HR, 0.784; 95% CI, 0.631-0.975; P = 0.029). CONCLUSIONS: Genetic proxies of cognitive reserve are associated with a reduced risk of cognitive decline, motor progression, and development of psychosis in PD. These findings may enhance our understanding of individual differences in resilience in progression of PD. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Humans↗

PubMed2003

The effect of education on cognitive performances and its implication for the constitution of the cognitive reserve.

Some studies have suggested that people with a high educational level have a lower risk of developing dementia compared to people with a low educational level. This protective effect of education has been explained by the constitution of a cognitive reserve which might delay the cognitive and functional expression of neurodegenerative illnesses. The aim of this study is, on the one hand, to evaluate the impact of education on cognitive functioning, which is thought to support the cognitive reserve capacity, and on the other, to determine the extent to which cognitive functioning is affected by other explanatory variables. The analysis was conducted on 1022 individuals without physical or neurological disorders in the Personnes Ages Quid study. These participants were aged 66 and over and had completed a neuropsychological battery. The effect of some demographic and socioeconomic variables on cognitive performance was also analyzed. Multivariate analysis showed a significant effect of education on most neuropsychological performances, independently of the other variables, and more particularly, in the high-attention-demanding tests. A principal component analysis demonstrated that education specifically increases 2 cognitive components: controlled processes and conceptualization ability. More-over, mental stimulation occurring after the education years, such as high-complex-activity occupations, seems to increase the controlled component. All these results suggest that the effect of education on cognitive reserve may be explained by an in-crease in controlled processes and conceptualization abilities. These 2 cognitive components might delay the clinical expression of neurodegenerative illnesses by maintaining global cognitive efficiency. Of these 2 components, controlled processes were also influenced by high attention-demanding occupations.

Aged↗

PubMed2006

The effects of acute alcohol consumption, cognitive reserve, partner risk, and gender on sexual decision making.

OBJECTIVE: In past alcohol administration studies, intoxicated college students have been more willing to have unprotected sex with a hypothetical new partner than sober or placebo students. The objective of the present research was to extend past work by examining the effects of gender, cognitive reserve, and partner risk on intoxicated sexual decision making. METHOD: Before assigning participants (60 women and 60 men) to a drink condition, cognitive reserve was assessed with the reading subtest of the Wide Range Achievement Test 3 (WRAT3). After drinking, participants watched a video of a male and female college student in a sexual situation. There were two versions of the video that were identical, except for information that suggested the opposite-gender character had many past sexual partners or only a few. RESULTS: There was a significant interaction between drink condition and cognitive reserve such that intoxicated participants with lower WRAT3 scores were more likely than other participants to indicate that they would have unprotected sex if they were in this situation. Partner risk did not influence participants' willingness to have unprotected sex; however, they were less interested in dating the high-risk partner. CONCLUSIONS: As expected, participants with less cognitive reserve made riskier decisions when intoxicated. Unexpectedly, although participants clearly perceived the high- and low-risk partners differently, this did not affect their willingness to have unprotected sex with this hypothetical partner. These findings demonstrate the need for sexually transmitted disease/ HIV prevention programs that go beyond factual presentations and provide students with the skills they need to assess risk realistically and the need for programs with messages tailored for individuals with low cognitive skills.

Acute Disease↗

PubMed2003

Exploring the neural basis of cognitive reserve.

There is epidemiologic and imaging evidence for the presence of cognitive reserve, but the neurophysiologic substrate of CR has not been established. In order to test the hypothesis that CR is related to aspects of neural processing, we used fMRI to image 19 healthy young adults while they performed a nonverbal recognition test. There were two task conditions. A low demand condition required encoding and recognition of single items and a titrated demand condition required the subject to encode and then recognize a larger list of items, with the study list size for each subject adjusted prior to scanning such that recognition accuracy was 75%. We hypothesized that individual differences in cognitive reserve are related to changes in neural activity as subjects moved from the low to the titrated demand task. To test this, we examined the correlation between subjects' fMRI activation and NART scores. This analysis was implemented voxel-wise in a whole brain fMRI dataset. During both the study and test phases of the recognition memory task we noted areas where, across subjects, there were significant positive and negative correlations between change in activation from low to titrated demand and the NART score. These correlations support our hypothesis that neural processing differs across individuals as a function of CR. This differential processing may help explain individual differences in capacity, and may underlie reserve against age-related or other pathologic changes.

Adaptation, Physiological↗

PubMed2003

Cognitive reserve and lifestyle.

The concept of cognitive reserve (CR) suggests that innate intelligence or aspects of life experience like educational or occupational attainments may supply reserve, in the form of a set of skills or repertoires that allows some people to cope with progressing Alzheimer's disease (AD) pathology better than others. There is epidemiological evidence that lifestyle characterized by engagement in leisure activities of intellectual and social nature is associated with slower cognitive decline in healthy elderly and may reduce the risk of incident dementia. There is also evidence from functional imaging studies that subjects engaging in such leisure activities can clinically tolerate more AD pathology. It is possible that aspects of life experience like engagement in leisure activities may result in functionally more efficient cognitive networks and therefore provide a CR that delays the onset of clinical manifestations of dementia.

Adaptation, Physiological↗

PubMed1992

Testing for limits of cognitive reserve capacity: a promising strategy for early diagnosis of dementia?

Examination of the range and limits of cognitive reserve capacity (plasticity) by means of cognitive training is proffered as a promising diagnostic strategy for the early (premorbid) identification of dementia, particularly Alzheimer's disease, in nonclinical populations. First data are presented from a sample of elderly independent-living people classified as healthy or at risk (beginning dementia) on the basis of a standardized psychiatric interview. Randomly assigned groups participated in a cognitive training program based on figural relations, a component of fluid intelligence. Stepwise regression analyses demonstrated that only healthy elderly profited from training and that only post-training scores predicted the psychiatric "at risk" diagnosis. The results hold promise for further development of testing-the-limits of individual differences in cognitive reserve capacity to identify premorbid states of dementia in nonclinical samples.

Aged↗

PubMed2003

The influence of cognitive reserve on memory following electroconvulsive therapy.

Cognitive reserve (CR) theory proposes that certain genetic and nonacquired variables, such as larger head size and greater neuronal density, and some life experiences, such as higher educational and occupational attainment, provide a buffer against brain dysfunction in the face of acquired central nervous system (CNS) dysfunction. This study examined CR in the pseudoexperimental paradigm of electroconvulsive therapy (ECT). Subjects included fifty (N = 50) depressed patients treated with bilateral ECT. Subjects were placed in high (n = 27) or low (n = 23) CR groups based on years of education and occupational attainment. At baseline, no significant differences were observed between the groups in the amount of information forgotten on a verbal memory measure (Randt stories) after a 30-minute delay. Following three ECT treatments, however, the high CR group forgot significantly less information after a 30-minute delay, as compared to the low CR group (p < 0.01). These data provide further support for CR theory and suggest that CR may be an underlying factor in differential memory loss in ECT.

Adult↗

PubMed2003

Association of life activities with cerebral blood flow in Alzheimer disease: implications for the cognitive reserve hypothesis.

BACKGROUND: Regional cerebral blood flow (CBF), a good indirect index of cerebral pathologic changes in Alzheimer disease (AD), is more severely reduced in patients with higher educational attainment and IQ when controlling for clinical severity. This has been interpreted as suggesting that cognitive reserve allows these patients to cope better with the pathologic changes in AD. OBJECTIVE: To evaluate whether premorbid engagement in various activities may also provide cognitive reserve. DESIGN: We evaluated intellectual, social, and physical activities in 9 patients with early AD and 16 healthy elderly controls who underwent brain H(2)(15)O positron emission tomography. In voxelwise multiple regression analyses that controlled for age and clinical severity, we investigated the association between education, estimated premorbid IQ, and activities, and CBF. RESULTS: In accordance with previous findings, we replicated an inverse association between education and CBF and IQ and CBF in patients with AD. In addition, there was a negative correlation between previous reported activity score and CBF in patients with AD. When both education and IQ were added as covariates in the same model, a higher activity score was still associated with more prominent CBF deficits. No significant associations were detected in the controls. CONCLUSIONS: At any given level of clinical disease severity, there is a greater degree of brain pathologic involvement in patients with AD who have more engagement in activities, even when education and IQ are taken into account. This may suggest that interindividual differences in lifestyle may affect cognitive reserve by partially mediating the relationship between brain damage and the clinical manifestation of AD.

Aged↗

PubMed2003

Preliminary examination of cognitive reserve theory in closed head injury.

This investigation was designed to provide preliminary support for cognitive reserve theory in closed head injury (CHI), and demonstrate the effectiveness of using the Oklahoma premorbid intelligence estimate (OPIE) in research and clinical activities. Out of a possible 124 consecutive referrals, 26 patients (N=26) who underwent neuropsychological assessment following brain injury met study inclusion/exclusion criteria. Participants were included if they had exited post-traumatic amnesia (PTA), demonstrated uncompromised upper extremity use, displayed adequate verbal communication, and were judged capable of completing a full neuropsychological evaluation. Participants were divided into a closed head injury-negative premorbid history (CHI-) or closed head injury-positive premorbid history (CHI+) group based upon premorbid variables (e.g., history of alcoholism). Groups did not differ in terms of demographic variables or premorbid IQ. Despite having less severe head injuries, the CHI+ group had a greater pre-post difference for PIQ, and a significantly larger VIQ/PIQ discrepancy than the CHI- group. In conclusion, these findings suggest that the CHI+ group had diminished cognitive reserve secondary to the aggregate effects of premorbid insult, which resulted in greater cognitive decline following an additional stressor (i.e., CHI) than what might otherwise be expected from the head injury alone.

Adolescent↗

PubMed2004

Cognitive reserve and anosognosia in questionable and mild dementia.

Cognitive reserve (CR) theory posits that the clinical presentation of individuals with the same brain disease varies based upon premorbid variables (e.g., education, occupation, reading ability). Anosognosia (decreased insight regarding one's deficits) is common in dementia and has implications for safety, treatment, and caregiver burden. The current study examined the role of CR in anosognosia in individuals with mild dementia. Participants were individuals diagnosed with questionable or mild dementia (Clinical Dementia Rating 0.5 or 1) after neuropsychological evaluation. Anosognosia was measured by informant-patient discrepancy on the Cognitive Difficulties Scale. High and Low CR groups were created based upon reading performance. Low CR showed greater anosognosia than High CR. Anosognosia was associated with reduced reading performance, even after controlling for global cognitive decline. These findings suggest CR is related to anosognosia in questionable and mild dementia, and have clinical implications for the assessment of awareness in dementia.

Aged↗

PubMed2004

Cognitive reserve: implications for diagnosis and prevention of Alzheimer's disease.

Epidemiologic evidence suggests that higher occupational attainment and education, as well as increased participation in intellectual, social, and physical aspects of daily life, are associated with slower cognitive decline in healthy elderly and may reduce the risk of incident Alzheimer's disease (AD). There is also evidence from structural and functional imaging studies that patients with such life experiences can tolerate more AD pathology before showing signs of clinical dementia. It has been hypothesized that such aspects of life experience may result in functionally more efficient cognitive networks and, therefore, provide a cognitive reserve that delays the onset of clinical manifestations of dementia. In this article, we review some of the relevant literature of the noted associations between markers of cognitive reserve and AD and discuss the possible mechanisms that may explain these associations.

Activities of Daily Living↗

PubMed1997

Association of premorbid intellectual function with cerebral metabolism in Alzheimer's disease: implications for the cognitive reserve hypothesis.

OBJECTIVE: Clinical heterogeneity in Alzheimer's disease has been widely observed. One factor that may influence the expression of dementia in Alzheimer's disease is premorbid intellectual ability. It has been hypothesized that premorbid ability, as measured by educational experience, reflects a cognitive reserve that can affect the clinical expression of Alzheimer's disease. The authors investigated the relation between estimates of premorbid intellectual function and cerebral glucose metabolism in patients with Alzheimer's disease to test the effect of differing levels of premorbid ability on neurophysiological dysfunction. METHOD: In a resting state with eyes closed and ears occluded, 46 patients with Alzheimer's disease were evaluated with positron emission tomography and [18F]-2-fluoro-2-deoxy-D-glucose to determine cerebral metabolism. Premorbid intellectual ability was assessed by a demographics-based IQ estimate and performance on a measure of word-reading ability. RESULTS: After the authors controlled for demographic characteristics and dementia severity, both estimates of premorbid intellectual ability were inversely correlated with cerebral metabolism in the prefrontal, pre-motor, and left superior parietal association regions. In addition, the performance-based estimate (i.e., reading ability) was inversely correlated with metabolism in the anterior cingulate, paracentral, right orbitofrontal, and left thalamic regions, after demographic and clinical variables were controlled for. CONCLUSIONS: The results suggest that higher levels of premorbid ability are associated with greater pathophysiological effects of Alzheimer's disease among patients of similar dementia severity levels. These findings provide support for a cognitive reserve that can alter the clinical expression of dementia and influence the neurophysiological heterogeneity observed in Alzheimer's disease.

Aged↗

PubMed2003

The influence of cognitive reserve on seizure-induced injury.

Status epilepticus (SE) is associated with a significant risk of cognitive impairment. While many factors likely determine cognitive outcome following SE, there is evidence that cognitive ability prior to a neurological insult may be an important determinant of outcome. Patients with greater cognitive abilities or so-called cognitive reserve may be less vulnerable to injury than patients with limited cognitive ability. Here we tested the hypothesis that cognitive abilities prior to SE would be predictive of cognitive outcome. Immature rats were tested in the water maze, a test of visual-spatial memory, and divided into fast and slow learners. Animals were then subjected to SE and retested in the water maze 23 days later. Control rats were tested in the same manner but not subjected to SE. SE resulted in marked impairment in water maze performance. However, no statistical difference was noted in performance between slow and fast learners in either the SE or control group. Likewise, no differences were seen in the histopathology of the slow and fast learners. This study demonstrates that SE adversely effects visual-spatial memory equally in both fast and slow learners and does not support the theory that cerebral reserve plays a major role in cognitive function following a cerebral insult.

Animals↗

PubMed2003

Cognitive reserve modulates functional brain responses during memory tasks: a PET study in healthy young and elderly subjects.

Cognitive reserve (CR) is the ability of an individual to cope with advancing brain pathology so that he remains free of symptomatology. Epidemiological evidence and in vivo neurometabolic data suggest that CR may be mediated through education or IQ. The goal of this study was to investigate CR-mediated differential brain activation in 17 healthy young adults and 19 healthy elders. Using nonquantitative H(2)(15)O PET scanning, we assessed relative regional cerebral blood flow while subjects performed a serial recognition memory task under two conditions: nonmemory control (NMC), in which one shape was presented in each study trial; and titrated demand (TD), in which study list length was adjusted so that each subject recognized shapes at approximately 75% accuracy. A factor score that summarized years of education and scores on two IQ indices was used as an index of CR. Voxel-wise, multiple regression analyses were performed with TD minus NMC difference PET counts as the dependent variable and the CR variable as the independent variable of interest. We identified brain regions where regression slopes were different from zero in each separate group, and also those where regression slopes differed between the two age groups. The slopes were significantly more positive in the young in the right inferior temporal gyrus, right postcentral gyrus, and cingulate, while the elderly had a significantly more positive slope in left cuneus. Brain regions where systematic relationships between CR and brain activation differ as a function of aging are loci where compensation for aging has occurred. They may mediate differential ability to cope with brain changes in aging.

Adult↗

PubMed2006

The influence of cognitive reserve on neuropsychological functioning following coronary artery bypass grafting (CABG).

Neuropsychological impairment is common, yet variable, after coronary artery bypass grafting (CABG). Similar variability has been observed in other CNS-related diseases. Empirical findings in Alzheimer's disease and HIV, among other areas, suggest cognitive reserve (CR) may mediate the cognitive impact of these diseases. The present study examined whether CR mediates neuropsychological outcome after CABG. Participants were 42 (N=42) individuals who underwent elective, normothermic CABG. Each was placed in high (n=22) or low (n=20) CR groups based on estimated premorbid intelligence and occupational attainment. All were administered neuropsychological tests preoperatively and at discharge. The total incidence of neuropsychological decline (66.7%) was not significantly different between CR groups. However, on working memory and executive function tests, specifically, the high CR group demonstrated greater post-operative decline compared to the low CR group. These data are considered in the context of a threshold model of CR theory.

Aged↗

PubMed2003

Relation of cognitive reserve and task performance to expression of regional covariance networks in an event-related fMRI study of nonverbal memory.

Cognitive reserve (CR) has been established as a mechanism that can explain individual differences in the clinical manifestation of neural changes associated with aging or neurodegenerative diseases. CR may represent individual differences in how tasks are processed (i.e., differences in the component processes), or in the underlying neural circuitry (of the component processes). CR may be a function of innate differences or differential life experiences. To investigate to what extent CR can account for individual differences in brain activation and task performance, we used fMRI to image healthy young individuals while performing a nonverbal memory task. We used IQ estimates as a proxy for CR. During both study and test phase of the task, we identified regional covariance patterns whose change in subject expression across two task conditions correlated with performance and CR. Common brain regions in both activation patterns were suggestive of a brain network previously found to underlie overt and covert shifts of spatial attention. After partialing out the influence of task performance variables, this network still showed an association with the CR, i.e., there were reserve-related physiological differences that presumably would persist were there no subject differences in task performance. This suggests that this network may represent a neural correlate of CR.

Adult↗

PubMed2005

Cognitive reserve: a SPECT study of 132 Alzheimer's disease patients with an education range of 0-19 years.

This study examines the associations between education, cerebral perfusion, and cognitive test performance among 132 patients with Alzheimer's disease. The participants had had between 0 and 19 years of formal schooling, and had either mild or moderate dementia according to the Clinical Dementia Rating Scale. Cerebral perfusion was evaluated by the (99m)Tc-hexamethylpropylene amine oxime single photon emission computed tomography. The Mini-Mental State Examination and the Cognitive Abilities Screening Instrument were used to assess cognitive performance. For patients at each clinical dementia severity level, statistical parametric mapping was used to examine voxel by voxel the association between education and cerebral perfusion, and Pearson's correlation coefficients were calculated between education and cognitive test scores. Years of formal schooling had negative associations with cerebral perfusion and positive associations with cognitive test scores. The brain regions showing a significant education effect on perfusion involved bilateral posterior association areas in mild dementia, and bilateral parieto-temporo-frontal areas in moderate dementia. The present findings indicate that the cognitive reserve effect starts at the low end of the education range. They also suggest that the main effect of more education is a more facile use of alternative brain circuits instead of locally increased synaptic connections.

Aged↗

PubMedDate not supplied

Cognitive reserve and Alzheimer disease.

Epidemiologic evidence suggests that individuals with higher IQ, education, occupational attainment, or participation in leisure activities have a reduced risk of developing Alzheimer disease (AD). The concept of cognitive reserve (CR) posits that individual differences in how tasks are processed provide differential reserve against brain pathology or age-related changes. This may take 2 forms. In neural reserve, preexisting brain networks that are more efficient or have greater capacity may be less susceptible to disruption. In neural compensation, alternate networks may compensate for pathology's disruption of preexisting networks. Imaging studies have begun to identify the neural substrate of CR. Because CR may modulate the clinical expression of AD pathology, it is an important consideration in studies of "preclinical" AD and treatment studies. There is also the possibility that directly enhancing CR may help forestall the diagnosis of AD.

Alzheimer Disease↗