Alzheimer's disease and bilingualism

The Babylonian benefit: Neurological research shows that being bilingual enhances mental performance and may protect from Alzheimer's disease.

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

Linking cognitive and behavioral reserve: Evidence from the CAN‐PROTECT study

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

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Neural substrates of cognitive reserve in Alzheimer's disease spectrum and normal aging

In recent years, the concepts of cognitive reserve (CR) and brain reserve (BR) have been used to take account of the interindividual variability between cognitive impairment and degree of brain damage occurring in a variety of neurological disorders. These studies, however, have typically not addressed the critical issue of the clinical implications of this research for the clinical care of the patients. After an introduction to CR and BR theory, the present chapter will review studies exploring CR and BR in healthy aging and in a series of progressive and relatively common neurological conditions such as Alzheimer’s disease (AD), multiple sclerosis (MS), and Parkinson’s disease (PD). In the second part of the chapter, we will discuss the implications of CR and BR for clinical interventions based on mind-body medicine (in particular meditation), as possible approaches aimed at potentiating individuals’ reserve in the conditions of healthy aging, AD, MS, and PD.

BackgroundThe incidence and prevalence of Alzheimer’s disease (AD) continues to rise in the growing elderly population putting public health at increased economic, healthcare, and caregiving burdens. The effects of AD pathology on the brain are irreversible, making it hard to determine effective treatment after symptom onset. Primary prevention has been proven to reduce the risk of developing AD later in life. Past research found that cognitive reserve (CR), an individual’s ability to cope with brain changes, impacts AD risk. The buildup of CR over a life span has shown positive cognitive implications. However, the influence that CR has on the rate of AD progression remains to be explored. This study used a survey tool that accounts for all CR proxies to explore this gap.MethodTo quantify CR in the study population of 90 AD participants, the Cognitive Reserve Index questionnaire was used. The Clinical Dementia Rating scale was utilized to stage AD progression. One‐way ANOVA and Independent Samples T‐tests were used to test for differences between the mean CR scores of dementia groups. One‐way ANOVA was also used to test for differences between CR level groups and mean number of days it took to transition from one dementia stage to the next. Multivariable linear regression was utilized to determine the unit change in time associated with an increase in CR score.ResultThere was not a significant difference in mean CR score by dementia group (F = 1.96, p = 0.15). After collapsing the moderate and severe dementia groups to compare to the mild dementia group, there was a significant difference in mean CR score (mild mean (SD) = 131(15.0), moderate/severe mean (SD) = 123(20.6), p = 0.05). After controlling for physical activity, for every unit increase in CR score, the number of days for transitioning from mild to severe dementia increased by 34 days (β = 33.94, 95% CI: 8.07, 59.81, p = 0.01).ConclusionHigher CR was associated with slower AD progression. This indicates that consistent engagement in activities that promote CR buildup over a life span are methods for improving AD and dementia health outcomes.

BackgroundEvidence has emerged that cognitive reserve (CR) could mitigate the genetic risk of APOE ε4 allele for dementia and Alzheimer’s disease (AD) in Caucasian and Black populations. Whether CR counteracts dementia risk attributable to TOMM40 variants is unknown. We examined whether lifelong CR might modify the risk of dementia and AD from APOE and TOMM40 variants among Chinese older adults.MethodThis population‐based cohort study included 2052 dementia‐free participants from the Shandong Yanggu Study of Aging and Dementia, who were free of dementia at baseline (2014‐2015) and underwent follow‐up examinations in March‐September 2018. APOE (rs429358 and rs7412) and TOMM40 (rs2075650) were defined using multiple polymerase chain reaction amplification. A lifelong composite CR score was generated from six lifespan intellectual factors and then dichotomized into high and low levels according to the median CR score. Dementia and AD were clinically diagnosed following the international criteria. Data were analyzed using Cox proportional‐hazards models. The interaction between CR and APOE or TOMM40 variants was assessed on multiplicative and additive scales.ResultDuring an average of 3.72 years (range, 2.98‐4.46) of follow‐up, dementia was diagnosed in 94 persons, including 70 with AD. Overall, carrying APOE e4 allele (vs. non‐carriers) was associated with multivariable‐adjusted hazard ratio of 1.50 (95%CI: 0.91‐2.50) for dementia and 1.71 (0.97‐3.01) for AD; the corresponding figures were 1.76 (1.09‐2.85) and 1.81 (1.04‐3.15) for carrying TOMM40 G allele (vs. AA), and 0.47 (0.27‐0.80) and 0.52 (0.27‐0.996) for high CR, respectively. There was a significant additive interaction of APOE or TOMM40 variants with CR on risks of dementia and AD. Compared to low CR, having high lifelong CR was associated with a lower risk of developing dementia and AD in APOE e4 carriers, with multivariable‐adjusted hazard ratios being 0.17 (95%CI: 0.04‐0.73) and 0.13 (0.02‐1.02); the corresponding figures were 0.23 (0.07‐0.81) and 0.13 (0.02‐1.02) in TOMM40 G carriers, and 0.22(0.06‐0.74) and 0.12(0.02‐0.91) in APOE‐e4 or TOMM40 G carriers, respectively.ConclusionCarrying TOMM40 G or APOE e4 allele is associated with increased risks of dementia and AD in Chinese older adults, and the genetic risk could be counteracted by high lifelong CR capacity.

Alzheimer’s disease (AD) is the most common form of dementia, with no means of cure or prevention. The presence of abnormal disease-related proteins in the population is, in turn, much more common than the incidence of dementia. In this context, the cognitive reserve (CR) hypothesis has been proposed to explain the discontinuity between pathophysiological and clinical expression of AD, suggesting that CR mitigates the effects of pathology on clinical expression and cognition. fMRI studies of the human connectome have recently reported that AD patients present diminished functional efficiency in resting-state networks, leading to a loss in information flow and cognitive processing. No study has investigated, however, whether CR modifies the effects of the pathology in functional network efficiency in AD patients. We analyzed the relationship between CR, pathophysiology and network efficiency, and whether CR modifies the relationship between them. Fourteen mild AD, 28 amnestic mild cognitive impairment (aMCI) due to AD, and 28 controls were enrolled. We used education to measure CR, cerebrospinal fluid (CSF) biomarkers to evaluate pathophysiology, and graph metrics to measure network efficiency. We found no relationship between CR and CSF biomarkers; CR was related to higher network efficiency in all groups; and abnormal levels of CSF protein biomarkers were related to more efficient networks in the AD group. Education modified the effects of tau-related pathology in the aMCI and mild AD groups. Although higher CR might not protect individuals from developing AD pathophysiology, AD patients with higher CR are better able to cope with the effects of pathology—presenting more efficient networks despite pathology burden. The present study highlights that interventions focusing on cognitive stimulation might be useful to slow age-related cognitive decline or dementia and lengthen healthy aging.

BackgroundThe cognitive reserve (CR) theory posits that higher CR can delay Alzheimer's onset and influence disease progression. While this has been studied in late‐onset Alzheimer's disease (LOAD), its effects in young‐onset Alzheimer's disease (YOAD, onset before age 65) have not been extensively explored. This study aims to examine whether high CR in YOAD delays onset and leads to faster cognitive deterioration, as seen in LOAD.MethodsThis retrospective study included 72 patients (39 females, age range: 46‐64 years) diagnosed with YOAD, selected from a memory clinic database of 2,040 dementia patients. These patients were followed for three years, with cognitive function assessed using the Mini‐Mental State Examination (MMSE).ResultAge of diagnosis did not correlate significantly with CR variables, years of education or family size. However, education, family size, and gender predicted cognitive decline six months after diagnosis. Higher education was associated with greater decline, larger families with lower decline. Women showed higher decline rates than men.ConclusionIn contrast to studies among LOAD, there was no significant correlation between age and CR among YOAD, suggesting that other mechanisms might be more influential than CR parameters in younger individuals. However, similar to LOAD, YOAD patients with higher education and smaller families experienced faster disease progression, implying that diagnoses are frequently made when brain pathology is already severe. These findings highlight the urgent need for early detection tools and cognitive interventions to ease the challenges faced by these young patients.

BACKGROUNDThe need for scientific knowledge about aging is predicated on the demand of modern society to extend the active life of a person. To maintain intellectual longevity, it is necessary to take into account not only the pathological, but also compensatory mechanisms that arise during aging. The cerebral-cognitive reserve (CCR) influences the rate of transition from pre-phenomenological stages to the clinical stage of the disease, thereby changing the prognosis of Alzheimer’s disease (AD).AIMThe aim of this work was to review meta-analyses from studies that have examined the principles and functions of the CCR in people with AD.METHODSThe work included 83 scientific publications devoted to the issues of the CCR in neurodegenerative diseases such as AD. The Results and Discussion sections of this article provide reviews of the results of 12 meta-analyses published from 2012 to 2024 and selected from the PubMed and eLibrary databases using the following keywords in English and Russian: “cerebral reserve”, “cognitive “reserve”, and “Alzheimer’s disease”. The scope of the definition was not limited, since the goal here was to determine the terminological boundaries of the concepts of “cognitive reserve” and “single brain reserve”.RESULTSThe modern understanding of AD as a biological continuum covering the preclinical, prodromal, and clinical phases of the disease makes it possible to infer that insufficiency of protective factors underlies the progression of AD. The cognitive reserve is involved in the sanogenetic protective mechanism during neurodegeneration. The cognitive reserve is a theoretical concept that reflects modern research’s understanding of how the integrative functioning of the brain (cerebral) and cognitive reserves extend the period of active intellectual longevity through energy-saving mechanisms. It considers these mechanisms as central to healthy mental activity and in slowing the progression of neurodegenerative diseases. At some point, an increase in excess interneuronal activity that reflects the hypercompensatory function of the reserve would accelerate the depletion of brain structures and contribute to clinical and psychopathological manifestations of AD.CONCLUSIONThe concept of the CCR puts the spotlight on the need to determine the compensatory indicators of cognitive deficit in AD, assess the architecture and volume of the reserve, and develop and follow protocols for its maintenance. It appears just as crucial to adopt measures to prevent the Reserve’s depletion as early as at the preclinical stages of the disease. Elaborating protective and compensatory mechanisms that help to maintain the functional activity of the brain in conditions of neurodegeneration, that is, CCR, require further research and can form a conceptual basis for the prevention of AD, starting from the preclinical stages of the disease.

Adult hippocampal neurogenesis in Alzheimer's disease: A roadmap to clinical relevance.

Charting the shared genetic architecture of Alzheimer's disease, cognition, and educational attainment, and associations with brain development

BackgroundThe cognitive reserve (CR) has been associated with the extension/compensation of the mental functioning of individuals affected by a neurodegenerative disease in the early stages of the disease. Most of the analyses evaluating CR are in high‐income countries, while there is a lack of capturing the variability related to low‐middle‐income environments such as Colombia. Objective: to analyze the relationship between CR and the age of onset of MCI and/or dementia by Alzheimer’s disease (AD) in patients from Antioquia‐Colombia.MethodA retrospective cohort study of 194 individuals. Clinical and socioeconomic characteristics were described using absolute and relative frequencies, followed by a mixed principal component analysis to represent the CR. A Varimax rotation was used for its interpretation, generating Z scores for the CR and the resulting dimensions. CR was categorized according to the median as high or low. This categorization aims to assess differences in the onset time of MCI and dementia by AD for the survival analysis and Cox regression with multiple imputation models (m = 30). We also examined all data to estimate the raw effect and adjusted for age, sex, and area.Resultsfrom 194 patients, 151 informed the age of onset of MCI, and 165 were later diagnosed with dementia by AD. There were differences between 5 and 9 years in the median age of onset of MCI and dementia by AD, with a later onset for patients with high CR. The CR hazard ratios (HR) were 1.05 and 0.97 for MCI and dementia, respectively. The ratio for the total score tended to be null after adjustment with confounding variables. However, its dimensions remained significant. Specifically, the HRs for an academic position, growing environment, and family status increased the speed of onset of the outcomes for MCI: 1.43, 1.06, and 1,72 and dementia: 1.40, 1.12, and 1.68.Conclusionthe onset times of the MCI and dementia were five years later in subjects with higher CR. Thus, a high academic position, a protective growth environment, and a family status that favors social relationships were associated with the reduction in clinical symptoms of AD since the early stages.