GBA moderates cognitive reserve's effect on cognitive function in patients with Parkinson's disease.

BACKGROUND: Cognitive reserve (CR) involves an individual's ability to maintain cognitive vitality over their lifespan. Glucocerebrosidase (GBA) gene mutations contribute to additional effects on cognitive function in Parkinson's disease (PD) patients, but the interplay between GBA mutations and CR remains unclear. We investigated the interactions among CR, GBA, and diseases, aiming to examine whether the CR established at different stages interacts with specific genotypes to affect cognitive function. METHODS: Three hundred and eighteen participants' CR indicators (i.e., education, occupation, and social function) and comprehensive neuropsychological function (i.e., tests for executive function, attention/working memory, visuospatial function, memory, and language) were evaluated. RESULTS: We found that CR established in a specific life stage influences the individual's cognitive function, particularly in PD, based on their distinct GBA rs9628662 genotypes. Attention/working memory and memory performance are affected by occupational complexity in midlife in PD patients with the GG genotype (q < 0.0001; q < 0.0001) and healthy adults with the T genotype (q = 0.0440; q < 0.0001). Language is influenced by early education and occupation, and the effects of occupation are also observed in PD patients with the GG genotype (q = 0.0040) and in healthy adults carrying the T genotype (q = 0.0040). CONCLUSIONS: CR, established at different life stages, can be influenced by the GBA rs9628662 genotype, impacting later-life cognition. Validating genotypes and incorporating genotype information when assessing cognitive reserve effects is crucial and can enhance targeted cognitive training.

The Role of Cognitive Reserve in Protecting Cerebellar Volumes of Older Adults with mild Cognitive Impairment.

The present study aims to investigate the relationship between cerebellar volumes and cognitive reserve in individuals with Mild Cognitive Impairment (MCI). A description of proxies of cerebellar cognitive reserve in terms of different volumes across lobules is also provided. 36 individuals with MCI underwent neuropsychological (MoCA, MMSE, Clock test, CRIq) assessment and neuroimaging acquisition with magnetic resonance imaging at 3 T. Simple linear correlations were applied between cerebellar volumes and cognitive measures. Multiple linear regression models were then used to estimate standardized regression coefficients and 95% confidence intervals. Simple linear correlations between cerebellar lobules volumes and cognitive features highlighted a significant association between CRIq_Working activity and specific motor cerebellar volumes: Left_V (ρ = 0.40, p = 0.02), Right_V (r = 0.42, p = 0.002), Vermis_VIIIb (ρ = 0.47, p = 0.003), Left_X (ρ = -0.46, p = 0.002) and Vermis_X (r = 0.35, p = 0.03). Furthermore, CRIq_Working activity scores correlated with certain cerebellar lobules implicated in cognition: Left_Crus_II, Vermis VIIb, Left_IX. MMSE was associated only with the Right_VIIB volume (r = 0.35, p = 0.02), while Clock Drawing Test scores correlated with both Left_Crus_I and Right_Crus_I (r = -0.42 and r = 0.42, p = 0.02, respectively). This study suggests that a higher cognitive reserve is associated with specific cerebellar lobule volumes and that Working activity may play a predominant role in this association. These findings contribute to the understanding of the relationship between cerebellar volumes and cognitive reserve, highlighting the potential modulatory role of Working activity on cerebellum response to cognitive decline.

Disentangling sex-dependent effects of APOE on diverse trajectories of cognitive decline in Alzheimer's disease.

Current diagnostic systems for Alzheimer's disease (AD) rely upon clinical signs and symptoms, despite the fact that the multiplicity of clinical symptoms renders various neuropsychological assessments inadequate to reflect the underlying pathophysiological mechanisms. Since putative neuroimaging biomarkers play a crucial role in understanding the etiology of AD, we sought to stratify the diverse relationships between AD biomarkers and cognitive decline in the aging population and uncover risk factors contributing to the diversities in AD. To do so, we capitalized on a large amount of neuroimaging data from the ADNI study to examine the inflection points along the dynamic relationship between cognitive decline trajectories and whole-brain neuroimaging biomarkers, using a state-of-the-art statistical model of change point detection. Our findings indicated that the temporal relationship between AD biomarkers and cognitive decline may differ depending on the synergistic effect of genetic risk and biological sex. Specifically, tauopathy-PET biomarkers exhibit a more dynamic and age-dependent association with Mini-Mental State Examination scores (p<0.05), with inflection points at 72, 78, and 83 years old, compared with amyloid-PET and neurodegeneration (cortical thickness from MRI) biomarkers. In the landscape of health disparities in AD, our analysis indicated that biological sex moderates the rate of cognitive decline associated with APOE4 genotype. Meanwhile, we found that higher education levels may moderate the effect of APOE4, acting as a marker of cognitive reserve.

Cognitive reserve in ALS: the role of occupational skills and requirements.

OBJECTIVE: Amyotrophic Lateral Sclerosis (ALS) is a heterogeneous neurodegenerative condition featuring variable degrees of motor and cognitive impairment. We assessed the impact of specific, empirically derived occupational skills and requirements on cognitive and motor functioning in ALS. METHODS: Individuals with ALS (n = 150) were recruited from the University of Pennsylvania's Comprehensive ALS Clinic. The Edinburgh Cognitive and Behavioral ALS Screen (ECAS) measured cognition, and the Penn Upper Motor Neuron (PUMNS) and ALS Functional Rating Scales (ALSFRS-R) measured motor symptoms. We derived 17 factors representing distinct occupational skills and requirements from the Occupational Information Network (O*NET), which were related to cognitive and motor scores using multiple linear regression. RESULTS: Occupational roles involving greater reasoning ability (ß = 2.12, p < .05), social ability (ß = 1.73, p < .05), analytic skills, (ß = 3.12, p < .01) and humanities knowledge (ß = 1.83, p<.01) were associated with better performance on the ECAS, while jobs involving more exposure to environmental hazards (ß=-2.57, p < .01) and technical skills (ß=-2.16, p<.01) were associated with lower ECAS scores. Jobs requiring more precision skills (ß = 1.91, p < .05) were associated with greater motor dysfunction on the PUMNS. CONCLUSIONS: Occupational histories involving more cognitively complex skills and activities were related to preserved cognitive functioning in ALS consistent with the cognitive reserve hypothesis, while jobs with greater exposure to environmental hazards and technical demands were linked to poorer cognitive functioning. Jobs involving more repetitive movements were associated with worse motor functioning, possibly due to overuse. Occupational history provides insight into protective and risk factors for variable degrees of cognitive and motor dysfunction in ALS.

Correlates of SuperAging in Two Population-Based Samples of Hispanic Older Adults.

OBJECTIVES: 'SuperAgers' are generally defined as people 80+ years old with episodic memory performance comparable to those 20 years younger. Limited knowledge exists to describe characteristics of SuperAgers, with even less known about Hispanic SuperAgers. METHODS: We examined indicators of cognitive, physical, and psychological resilience in relation to the likelihood of being a SuperAger using data from two population-based studies of Hispanic older adults [Puerto Rican Elder: Health Conditions (PREHCO) study; Health and Retirement Study (HRS)]. SuperAgers were defined as 1) ≥80 years old, 2) recall scores ≥ the median for Hispanic respondents aged 55-64, and 3) no cognitive impairment during the observation period. Overall, 640 PREHCO participants and 180 HRS participants were eligible, of whom 45 (7%) and 31 (17%) met SuperAging criteria. RESULTS: Logistic regressions controlling for age and sex demonstrated that higher education (PREHCO: odds ratio[OR]=1.20, p<.001; HRS: OR=1.14, p=.044) and fewer instrumental activities of daily living (IADL) limitations (PREHCO: OR=0.79, p=.019; HRS: OR=0.58, p=.077) (cognitive resilience), fewer activities of daily living (ADL) limitations (PREHCO: OR=0.72, p=.031; HRS: OR=0.67, p=.068) (physical resilience), and fewer depressive symptoms (PREHCO: OR=0.84, p=.015; HRS: OR=0.69, p=.007) (psychological resilience) were associated with SuperAging, although not all results reached threshold for statistical significance, presumably due to low statistical power. Additionally, known indicators of physical health (e.g., chronic conditions, self-rated health) did not relate to SuperAging. DISCUSSION: Increasing access to education and recognizing/treating depressive symptoms represent potential pathways to preserve episodic memory among older Hispanic adults.

Associations of cardiac function and arterial stiffness with cerebrovascular disease.

BACKGROUND: White matter hyperintensities (WMHs) represent diffuse small vessel disease implicating the cardiac, systemic, and cerebral vasculatures. As the brain may be the end-organ of cumulative vascular disease, and higher education is protective of both cardiovascular and brain health, we aim to clarify their intertwining relationships. METHODS: We evaluated participants (mean age = 64) from the UK Biobank with neuroimaging measures of WMHs, left ventricular ejection fraction (LVEF) quantified using cardiovascular MRI, and arterial stiffness index (ASI) quantified using finger photoplethysmography. We used multiple regression to evaluate the basic, independent, and interactive relationships of LVEF status (n = 27,512) and ASI (n = 33,584) with WMHs. Moderated mediation analysis was used to determine whether the relationship between LVEF status and WMH was mediated by ASI and moderated by education. RESULTS: Abnormal LVEF (ß = -0.082, p < 0.001) and higher ASI (ß = 0.02, p < 0.001) were associated with greater WMHs separately and independently, but not interactively. Moderated mediation analyses revealed that the relationship between abnormal LVEF and WMH was mediated by ASI, for individuals with lower education (ß = -0.004, p < 0.001). Abnormal LVEF was associated with lower cortical thickness in 16 predominantly frontotemporal and select parietal regions (FDR, q < 0.05). CONCLUSIONS: Cardiovascular dysfunction is associated with regional cerebral atrophy and may precipitate cerebrovascular disease via stiffening of systemic vasculatures, particularly for individuals with lower education. Integrative approaches to study biophysiological vascular systems can elucidate the complex interplay between biological and social determinants of brain and cerebrovascular health.

Longitudinal validation of cognitive reserve proxy measures: a cohort study in a rural Chinese community.

BACKGROUND: While evidence supports cognitive reserve (CR) in preserving cognitive function, longitudinal validation of CR proxies, including later-life factors, remains scarce. This study aims to validate CR's stability over time and its relation to cognitive function in rural Chinese older adults. METHODS: Within the project on the health status of rural older adults (HSRO), the survey included baseline assessment (2019) and follow-up assessment (2022). 792 older adults (mean age: 70.23 years) were followed up. The confirmatory factor analysis (CFA) was constructed using cognitive reserve proxies that included years of formal education, social support, hobbies, and exercise. We examined the longitudinal validity of the CR factor using confirmatory factor analyses and measurement invariance and explored the association of CR with cognition using Spearman's correlation and Generalized Estimating Equations (GEE). RESULTS: The results showed that CR's CFA structure was stable over time (T0, χ2/df: 3.21/2; RMSEA: 0.02, and T1, χ2/df: 7.47/2; RMSEA: 0.05) and that it accepted both configural and metric invariance (Δχ2/df = 2.28/3, P = 0.52). In addition, it was found that CR had a stable positive relationship with cognitive function across time (T0, r = 0.54; T1, r = 0.49). Furthermore, longitudinal CR were associated with MMSE (ß = 2.25; 95%CI = 2.01 ~ 2.49). CONCLUSIONS: This study provided valuable evidence on the stability and validity of cognitive reserve proxy measures in rural Chinese older adults. Our findings suggested that cognitive reserve is associated with cognitive function over time and highlighted the importance of accumulating cognitive reserve in later life.

Occupational differences in a Dutch sample of patients with primary progressive aphasia, behavioral variant frontotemporal dementia, and Alzheimer's dementia.

BACKGROUND: Cognitive reserve is a potential mechanism to cope with brain damage as a result of dementia, which can be defined by indirect proxies, including education level, leisure time activities, and occupational attainment. In this study we explored the association between dementia diagnosis and type of occupation in a retrospective Dutch outpatient memory clinic sample of patients with primary progressive aphasia (PPA), behavioral variant frontotemporal dementia (bvFTD), and Alzheimer's Dementia (AD). METHODS: We included data from 427 patients (bvFTD n = 87, PPA n = 148, AD n = 192) and compared the frequency of occupations (11 categories) between patients and data from the Dutch census using Pearson Χ2 tests and we calculated odds ratios (OR) by means of multinomial logistic regression analyses. We also investigated patient group differences in age, sex, education, disease duration, and global cognition. RESULTS: The frequency of teachers in patients with PPA was significantly higher than the frequency of teachers in patients with bvFTD [OR = 4.79, p = .007] and AD [OR = 2.04, p = .041]. The frequency of teachers in patients with PPA (16%) was also significantly higher than the frequency of teachers in the Dutch census [5.3%; OR = 3.27, p < .001]. The frequency of teachers in both bvFTD and AD groups were not significantly different from the frequency of teachers in the Dutch census (p = .078 and p = .513, respectively). CONCLUSIONS: A potential explanation for our results is the so called "wear and tear" hypothesis, suggesting that teachers have a communication-wise demanding occupation - and therefore are at higher risk to develop PPA. Alternatively, teaching requires continuous communication, hence teachers are more sensitive to subtle changes in their speech and language abilities. Our findings broaden our understanding of the relationship between occupational activity and cognitive reserve in the development of dementia.

Influence of cognitive reserve on cognitive and motor function in α-synucleinopathies: A systematic review and multilevel meta-analysis.

Cognitive reserve has shown promise as a justification for neuropathologically unexplainable clinical outcomes in Alzheimer's disease. Recent evidence suggests this effect may be replicated in conditions like Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy. However, the relationships between cognitive reserve and different cognitive abilities, as well as motor outcomes, are still poorly understood in these conditions. Additionally, it is unclear whether the reported effects are confounded by medication. This review analysed studies investigating the relationship between cognitive reserve and clinical outcomes in these α-synucleinopathy cohorts, identified from MEDLINE, Scopus, psycINFO, CINAHL, and Web of Science. 85 records, containing 176 cognition and 31 motor function effect sizes, were pooled using multilevel meta-analysis. There was a significant, positive association between higher cognitive reserve and both better cognition and motor function. Cognition effect sizes differed by disease subtype, cognitive reserve measure, and outcome type; however, no moderators significantly impacted motor function. Review findings highlight the clinical implications of cognitive reserve and importance of engaging in reserve-building behaviours.

Protective effects of physical activity on episodic memory during aging are explained by executive functioning.

Aging is marked by a memory decline related to an executive function decline. Physical activity (PA) has beneficial effects on both executive functions and memory, especially in aging. The protective effects of PA on these two cognitive abilities have always been studied separately, despite the well-established relationship between memory and executive functions. Our objective was to explore whether the benefits of PA on memory could be explained by reduced age-related changes in executive functions.Nineteen young adults (27.16 years old) and 25 older adults (69.64 years old) performed a resource-dependent memory task, three executive tasks and completed a PA questionnaire (measuring sports and leisure PA). Age group and PA effects on memory and executive performance were analyzed with generalized linear models. Mediation analyses were calculated using method of causal steps approach with a non-parametric bootstrapping procedure.The results confirmed the effects of age and PA on memory and executive performance. A significant interaction confirmed the protective effect of PA on age-related cognitive performance. PA was positively correlated with performance in both memory and executive tasks, but only in the older adults. Although each predictor alone (age, executive functions and PA) significantly explained memory performance in older adults, only the effect of PA on memory performance remained significant when all the predictors were introduced in the analyses.PA mediates the effects of age and executive functions on memory performance. This suggests that PA protects older adults against memory decline by reducing the decline in executive functioning.

Cognitive rehabilitation program in patients with multiple sclerosis: A pilot study.

INTRODUCTION: In recent years, there has been an increase of studies dedicated to cognitive rehabilitation in patients with multiple sclerosis (MS); however, few of these analyze the impact on such variables as cognitive reserve. The study aims to explore the effects of a cognitive rehabilitation program comprising a combination of cognitive and physical exercises, as well as group sessions to improve cognitive performance, emotional state, and cognitive reserve index. METHOD: Fifty patients with MS were subdivided into 2 groups: the control group, which performed aerobic exercise (n=25), and the experimental group (n=25), which participated in the integrated cognitive rehabilitation program (ICRP). All participants were evaluated 3 times (baseline, post-treatment, and long-term) with the Brief Repeatable Battery of Neuropsychological Tests, Cognitive Reserve Scale, Beck Depression Inventory, and a scale evaluating trait and state anxiety. RESULTS: Compared with the control group, patients in the experimental group showed improvements in cognitive function, with significant changes in measures of information processing speed, attention, memory, cognitive reserve index, and long-term mood. CONCLUSIONS: The ICRP was effective in improving cognitive and emotional function in MS, and increased the cognitive reserve index.

Lower cognitive reserve is related to worse working memory performance in older adults after mTBI. An ERP study.

OBJECTIVE: Older adults (OA) after mild traumatic brain injury (mTBI) have a high risk of developing persistent post-injury cognitive impairments. Lower pre-morbid cognitive reserve (CR) is increasingly investigated as a risk factor for cognitive dysfunction in OA. However, how CR protects against effects of mTBI at the brain level remains largely understudied. METHODS: We examined 22 OA who sustained mTBI (mean 67.69 years, SD 5.11) in the sub-acute phase and 15 age- and CR-matched healthy OA (mean 68 years, SD 5.55) performing a three-level visual N-back task using electroencephalography. We calculated inverse efficiency scores of performance from accuracy and reaction times. Event-related potentials served as neurocognitive correlates of attentional (P2) and working memory (P3) processing. RESULTS: Overall, mTBI OA performed worse than healthy OA (p = 0.031). Lower CR generally decreased performance (p < 0.001). Furthermore, with increasing task difficulty, task performance was more affected by CR (p = 0.004). At the brain level, P2 amplitude was lower in mTBI OA than in healthy OA (p = 0.05). There was no clear effect of CR on P2 or P3 measures. CONCLUSION: As mTBI OA with lower CR performed worse on a working-memory task, lower CR may be a risk factor for worse recovery after mTBI in this group.

Cognitive resilience/reserve: Myth or reality? A review of definitions and measurement methods.

INTRODUCTION: This review examines the concept of cognitive reserve (CR) in relation to brain aging, particularly in the context of dementia and its early stages. CR refers to an individual's ability to maintain or regain cognitive function despite brain aging, damage, or disease. Various factors, including education, occupation complexity, leisure activities, and genetics are believed to influence CR. METHODS: We revised the literature in the context of CR. A total of 842 articles were identified, then we rigorously assessed the relevance of articles based on titles and abstracts, employing a systematic approach to eliminate studies that did not align with our research objectives. RESULTS: We evaluate-also in a critical way-the methods commonly used to define and measure CR, including sociobehavioral proxies, neuroimaging, and electrophysiological and genetic measures. The challenges and limitations of these measures are discussed, emphasizing the need for more targeted research to improve the understanding, definition, and measurement of CR. CONCLUSIONS: The review underscores the significance of comprehending CR in the context of both normal and pathological brain aging and emphasizes the importance of further research to identify and enhance this protective factor for cognitive preservation in both healthy and neurologically impaired older individuals. HIGHLIGHTS: This review examines the concept of cognitive reserve in brain aging, in the context of dementia and its early stages. We have evaluated the methods commonly used to define and measure cognitive reserve. Sociobehavioral proxies, neuroimaging, and electrophysiological and genetic measures are discussed. The review emphasizes the importance of further research to identify and enhance this protective factor for cognitive preservation.

Childhood engagement in cognitively stimulating activities moderates relationships between brain structure and cognitive function in adulthood.

Greater engagement in cognitively stimulating activities (CSA) during adulthood has been shown to protect against neurocognitive decline, but no studies have investigated whether CSA during childhood protects against effects of brain changes on cognition later in life. The current study tested the moderating role of childhood CSA in the relationships between brain structure and cognitive performance during adulthood. At baseline (N=250) and 5-year follow-up (N=204) healthy adults aged 20-80 underwent MRI to assess four structural brain measures and completed neuropsychological tests to measure three cognitive domains. Participants were categorized into low and high childhood CSA based on self-report questionnaires. Results of multivariable linear regressions analyzing interactions between CSA, brain structure, and cognition showed that higher childhood CSA was associated with a weaker relationship between cortical thickness and memory at baseline, and attenuated the effects of change in cortical thickness and brain volume on decline in processing speed over time. These findings suggest higher CSA during childhood may mitigate the effects of brain structure changes on cognitive function later in life.

Effects of cognitive reserve on cognitive frailty among older adults: A population-based prospective cohort study.

AIM: We investigated the effect of lifespan cognitive reserve and its components on cognitive frailty among older adults. METHODS: A total of 4922 participants aged ≥65 years were recruited in 2008 and were followed up in 2011 from the Chinese Longitudinal Healthy Longevity Survey. Cognitive frailty was determined through the simultaneous presence of physical frailty (pre-frailty or frailty) and mild cognitive impairment, excluding concurrent dementia. The assessment of physical frailty and mild cognitive impairment was based on the Fatigue, Resistence, Ambulation, Illness, Loss of weight (FRAIL) (Fatigue, Resistence, Ambulation, Illness, Loss) and Mini-Mental State Examination scale, respectively. The lifespan cognitive reserve consisted of education attainment, occupational complexity and later-life leisure activities. We used logistic regression models to estimate the risk of cognitive frailty associated with the lifespan cognitive reserve and its components. RESULTS: A higher level of lifespan cognitive reserve, higher educational attainment or leisure activities engagement, but not occupational complexity, were associated with lower risk of incident cognitive frailty. Furthermore, cognitive, social and physical activities were associated with lower risk of incident cognitive frailty. CONCLUSION: Cognitive reserve, particularly educational attainment and leisure activities, can protect from cognitive frailty. This implicates that individuals should accumulate cognitive reserve in their lifespan, and older adults should actively participate in leisure activities to prevent cognitive frailty. Geriatr Gerontol Int 2024; 24: 398-403.

Pseudodementia in Patients with Unipolar and Bipolar Disorders: A Case Series and Literature Review.

Even though pseudodementia has been historically linked to depression, other psychiatric conditions may cause reversible cognitive alterations. The purpose of this study is to improve our understanding of pseudodementia occurring throughout the entire bipolar spectrum. A systematic review was conducted according to PRISMA guidelines. PubMed, Scopus, and Web of Science databases were searched up to March 2023. Fifteen articles on patients with pseudodementia and bipolar disorder (BD), mania, hypomania, or mixed depression have been included. Moreover, seven female patients with mood disorders diagnosed with pseudodementia have been described. According to our research, pseudodementia in patients with BD mostly occurs during a depressive episode. However, pseudodementia has also been observed in the context of manic and mixed states. Psychomotor and psychotic symptoms were commonly associated. The most typical cognitive impairments were disorientation, inattention, and short-term memory deficits. Alterations in neuroimaging were frequently observed. Electroconvulsive therapy and lithium, either alone or in combination with antipsychotics, resulted in the most widely used therapies. Cognitive decline may occur in a substantial proportion of patients. Since pseudodementia can manifest along the entire mood spectrum, it should be taken into consideration as a possible diagnosis in BD patients showing cognitive deficits during manic, mixed, and depressive states.

Small vessel disease and cognitive reserve oppositely modulate global network redundancy and cognitive function: A study in middle-to-old aged community participants.

Cerebral small vessel disease (SVD) can disrupt the global brain network and lead to cognitive impairment. Conversely, cognitive reserve (CR) can improve one's cognitive ability to handle damaging effects like SVD, partly by optimizing the brain network's organization. Understanding how SVD and CR collectively influence brain networks could be instrumental in preventing cognitive impairment. Recently, brain redundancy has emerged as a critical network protective metric, providing a nuanced perspective of changes in network organization. However, it remains unclear how SVD and CR affect global redundancy and subsequently cognitive function. Here, we included 121 community-dwelling participants who underwent neuropsychological assessments and a multimodal MRI examination. We visually examined common SVD imaging markers and assessed lifespan CR using the Cognitive Reserve Index Questionnaire. We quantified the global redundancy index (RI) based on the dynamic functional connectome. We then conducted multiple linear regressions to explore the specific cognitive domains related to RI and the associations of RI with SVD and CR. We also conducted mediation analyses to explore whether RI mediated the relationships between SVD, CR, and cognition. We found negative correlations of RI with the presence of microbleeds (MBs) and the SVD total score, and a positive correlation of RI with leisure activity-related CR (CRI-leisure). RI was positively correlated with memory and fully mediated the relationships between the MBs, CRI-leisure, and memory. Our study highlights the potential benefits of promoting leisure activities and keeping brain redundancy for memory preservation in older adults, especially those with SVD.

Considering the response in addition to the challenge - a narrative review in appraisal of a motor reserve framework.

The remarkable increase in human life expectancy over the past century has been achieved at the expense of the risk of age-related impairment and disease. Neurodegeneration, be it part of normal aging or due to neurodegenerative disorders, is characterized by loss of specific neuronal populations, leading to increasing clinical impairment. The individual course may be described as balance between aging- or disease-related pathology and intrinsic mechanisms of adaptation. There is plenty of evidence that the human brain is provided with exhaustible resources to maintain function in the face of adverse conditions. While a reserve concept has mainly been coined in cognitive neuroscience, emerging evidence suggests similar mechanisms to underlie individual differences of adaptive capacity within the motor system. In this narrative review, we summarize what has been proposed to date about a motor reserve (mR) framework. We present current evidence from research in aging subjects and people with neurological conditions, followed by a description of what is known about potential neuronal substrates of mR so far. As there is no gold standard of mR quantification, we outline current approaches which describe various indicators of mR. We conclude by sketching out potential future directions of research. Expediting our understanding of differences in individual motor resilience towards aging and disease will eventually contribute to new, individually tailored therapeutic strategies. Provided early diagnosis, enhancing the individual mR may be suited to postpone disease onset by years and may be an efficacious contribution towards healthy aging, with an increased quality of life for the elderly.