Investigating the relationships between motor skills, cognitive status, and area deprivation index in Arizona: a pilot study.

Introduction: Previous studies highlight the negative impact of adverse socioeconomic conditions throughout life on motor skills and cognitive health. Factors such as cognitive activity, physical activity, lifestyle, and socioeconomic position significantly affect general health status and brain health. This pilot study investigates the relationships among the Area Deprivation Index (ADI)-a measure of neighborhood-level socioeconomic deprivation, brain structure (cortical volume and thickness), and cognitive status in adults in Arizona. Identifying measures sensitive to ADI could elucidate mechanisms driving cognitive decline. Methods: The study included 22 adults(mean age = 56.2 ± 15.2) in Arizona, residing in the area for over 10 years(mean = 42.7 ± 15.8). We assessed specific cognitive domains using the NeuroTrax™ cognitive screening test, which evaluates memory, executive function, visual-spatial processing, attention, information processing speed, and motor function. We also measured cortical thickness and volume in 10 cortical regions using FreeSurfer 7.2. Linear regression tests were conducted to examine the relationships between ADI metrics, cognitive status, and brain health measures. Results: Results indicated a significant inverse relationship between ADI metrics and memory scores, explaining 25% of the variance. Both national and state ADI metrics negatively correlated with motor skills and global cognition (r's < -0.40, p's < 0.05). In contrast, ADI metrics generally positively correlated with motor-related volumetric and cortical thickness measures (r's > 0.40, p's < 0.05). Conclusion: The findings suggest that neighborhood-level social deprivation might influence memory and motor status, primarily through its impact on motor brain health.

A State-of-the-Art Review on the Role of Cognitive and Motor Reserve on Quality of Life: A Focus on Cardiovascular Patients in a Lifespan Perspective.

Cardiovascular diseases (CVDs) reflect a huge and diversified condition that influences patient quality of life (QoL) both in the physical and mental aspects, especially in older adults who often present comorbidities and may be affected by cognitive decline. The concept of cognitive reserve (CR), which is built through life course experiences, has widely been considered a protective factor against cognitive decline, while the results of QoL in the field of CVDs are still controversial. In particular, there is a lack of evidence that explicitly explores the effects of CR on the QoL in CVD cases since studies have considered only single CR proxies (e.g., education) or specific cardiovascular conditions. Moreover, none of them have considered the motor reserve (MR), another recent concept that considers the amount of physical activity carried out during a lifespan. Its potential role in preventing age-related diseases has been observed, but more clarification is needed given the importance of the physical component in CVDs. The present state-of-the-art review aims to (i) examine how the literature conceives CR and its proxies in CVDs relating to QoL and (ii) integrate the concept of MR in this framework. Implications for clinical practice will also be discussed.

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.

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.

Tau accumulation is associated with dopamine deficiency in vivo in four-repeat tauopathies.

PURPOSE: We hypothesized that severe tau burden in brain regions involved in direct or indirect pathways of the basal ganglia correlate with more severe striatal dopamine deficiency in four-repeat (4R) tauopathies. Therefore, we correlated [18F]PI-2620 tau-positron-emission-tomography (PET) imaging with [123I]-Ioflupane single-photon-emission-computed tomography (SPECT) for dopamine transporter (DaT) availability. METHODS: Thirty-eight patients with clinically diagnosed 4R-tauopathies (21 male; 69.0 ± 8.5 years) and 15 patients with clinically diagnosed α-synucleinopathies (8 male; 66.1 ± 10.3 years) who underwent [18F]PI-2620 tau-PET and DaT-SPECT imaging with a time gap of 3 ± 5 months were evaluated. Regional Tau-PET signals and DaT availability as well as their principal components were correlated in patients with 4R-tauopathies and α-synucleinopathies. Both biomarkers and the residuals of their association were correlated with clinical severity scores in 4R-tauopathies. RESULTS: In patients with 4R-tauopathies, [18F]PI-2620 binding in basal ganglia and midbrain regions was negatively associated with striatal DaT availability (i.e. globus pallidus internus and putamen (ß = - 0.464, p = 0.006, Durbin-Watson statistics = 1.824) in a multiple regression model. Contrarily, [18F]PI-2620 binding in the dentate nucleus showed no significant regression factor with DaT availability in the striatum (ß = 0.078, p = 0.662, Durbin-Watson statistics = 1.686). Patients with α-synucleinopathies did not indicate any regional associations between [18F]PI-2620-binding and DaT availability. Higher DaT-SPECT binding relative to tau burden was associated with better clinical performance (ß = - 0.522, p = 0.011, Durbin-Watson statistics = 2.663) in patients with 4R-tauopathies. CONCLUSION: Tau burden in brain regions involved in dopaminergic pathways is associated with aggravated dopaminergic dysfunction in patients with clinically diagnosed primary tauopathies. The ability to sustain dopamine transmission despite tau accumulation may preserve motor function.

How long have you exercised in your life? The effect of motor reserve and current physical activity on cognitive performance.

OBJECTIVES: Aging of the population encourages research on how to preserve cognition and quality of life. Many studies have shown that Physical Activity (PA) positively affects cognition in older adults. However, PA carried out throughout the individual's lifespan may also have an impact on cognition in old age. We hypothesize the existence of Motor Reserve (MR), a flexible and dynamic construct that increases over time and compensates for age-related motor and cognitive loss. METHODS: Two questionnaires were developed and validated to estimate MR (Physical Activity carried out throughout the individual's lifespan) and Current Physical Activity (CPA, PA carried out in the previous 12 months). They were administered to 75 healthy individuals over 50 to verify the relation with cognition. MR and CPA include physical exercise (i.e., structured activities to improve or maintain physical fitness) and incidental PA, which we consider as any movement that leads to a metabolic cost above baseline (e.g., housekeeping, walking). In addition, the Cognitive Reserve Index questionnaire (CRI), a reliable predictor of cognitive performance, was used to measure each participant's Cognitive Reserve. RESULTS: The factors that most influenced performance are Age and Cognitive Reserve, but also MR and CPA together and MR when it is the only factor. CONCLUSIONS: Cognitive variability in adult and elderly populations is explained by both MR and CPA. PA training could profitably be included in new preventive and existing interventions.

Extra-Basal Ganglia Brain Structures Are Related to Motor Reserve in Parkinson's Disease.

BACKGROUND: The "motor reserve" is an emerging concept based on the discrepancy between the severity of parkinsonism and dopaminergic degeneration; however, the related brain structures have not yet been elucidated. OBJECTIVE: We investigated brain structures relevant to the motor reserve in Parkinson's disease (PD) in this study. METHODS: Patients with drug-naïve, early PD were enrolled, who then underwent dopamine transporter (DAT) scan and diffusion tensor imaging (DTI). The severity of motor symptoms was evaluated with the Unified Parkinson's Disease Rating Scale score of bradykinesia and rigidity on the more affected side and dopaminergic degeneration of DAT uptake of the more affected putamen. Individual motor reserve estimate (MRE) was evaluated based on the discrepancy between the severity of motor symptoms and dopaminergic degeneration. Using DTI and the Brainnetome atlas, brain structures correlated with MRE were identified. RESULTS: We enrolled 193 patients with drug-naïve PD (mean disease duration of 15.6±13.2 months), and the MRE successfully predicted the increase of levodopa equivalent dose after two years. In the DTI analysis, fractional anisotropy values of medial, inferior frontal, and temporal lobes, limbic structures, nucleus accumbens, and thalamus were positively correlated with the MRE, while no brain structures were correlated with mean diffusivity. Additionally, degree centrality derived from the structural connectivity of the frontal and temporal lobes and limbic structures was positively correlated with the MRE. CONCLUSION: Our results show empirical evidence for MR in PD and brain structures relevant to MR, particularly, the extra-basal ganglia system including the limbic and frontal structures.

Potential Link Between Cognition and Motor Reserve in Patients With Parkinson's Disease.

OBJECTIVE: To investigate whether there is a link between cognitive function and motor reserve (i.e., individual capacity to cope with nigrostriatal dopamine depletion) in patients with newly diagnosed Parkinson's disease (PD). METHODS: A total of 163 patients with drug-naïve PD who underwent 18F-FP-CIT PET, brain MRI, and a detailed neuropsychological test were enrolled. We estimated individual motor reserve based on initial motor deficits and striatal dopamine depletion using a residual model. We performed correlation analyses between motor reserve estimates and cognitive composite scores. Diffusion connectometry analysis was performed to map the white matter fiber tracts, of which fractional anisotropy (FA) values were well correlated with motor reserve estimates. Additionally, Cox regression analysis was used to assess the effect of initial motor reserve on the risk of dementia conversion. RESULTS: The motor reserve estimate was positively correlated with the composite score of the verbal memory function domain (γ = 0.246) and with the years of education (γ = 0.251). Connectometry analysis showed that FA values in the left fornix were positively correlated with the motor reserve estimate, while no fiber tracts were negatively correlated with the motor reserve estimate. Cox regression analysis demonstrated that higher motor reserve estimates tended to be associated with a lower risk of dementia conversion (hazard ratio, 0.781; 95% confidence interval, 0.576-1.058). CONCLUSION: The present study demonstrated that the motor reserve estimate was well correlated with verbal memory function and with white matter integrity in the left fornix, suggesting a possible link between cognition and motor reserve in patients with PD.

Identifying the white matter structural network of motor reserve in early Parkinson's disease.

INTRODUCTION: Motor reserve refers to the individual capacity to cope with nigrostriatal dopamine depletion in Parkinson's disease (PD). This study aimed to explore the white matter structural network associated with motor reserve in patients with newly diagnosed PD. METHODS: A total of 238 patients with early-stage drug-naïve PD who underwent 18F-FP-CIT PET and brain MRI scans at initial assessment were enrolled. We estimated individual motor reserve based on the Unified Parkinson's Disease Rating Scale Part III (UPDRS-III) scores and dopamine transporter availability in the posterior putamen using a residual model. Then, we performed threshold-free network-based statistics (TFNBS) analysis to identify the structural brain network associated with the estimated motor reserve. We also assessed the effect of the network connectivity strength on the longitudinal increase in levodopa-equivalent dose (LED). RESULTS: The mean age at PD symptom onset was 69.10 ± 9.03 years and the mean UPDRS-III score at the time of PD diagnosis was 22.44 ± 9.72. TFNBS analysis identified a motor reserve-associated structural network whose nodes were mainly in the frontal region and cerebellum. Higher network strength (i.e., greater motor reserve) was associated with a slower longitudinal increase in LED during a 3-year follow-up period. CONCLUSION: The structural brain network is associated with motor reserve in patients with PD. Connectivity strength within the identified network indicates the individual's capacity to tolerate PD-related pathologies, which is maintained with disease progression and affects the long-term motor prognosis of PD.

Motor reserve: How to build neuronal resilience against ageing and neurodegeneration?

With the percentage of the population above age 65 expected to double by 2030, the healthcare costs across neurodegenerative diseases will in all likelihood significantly increase. As such, disease-modifying, preventive strategies are urgently needed. However, despite major technological advances and massive concerted efforts, we still fall short of disease prevention, delayed progression or reversal when it comes to neurodegenerative diseases. An increasing wealth of information has come to formally demonstrate that exercise serves as one of the best strategies for coping with neurodegeneration. Herein, we review the available evidence on how and to which extent physical activity can expand one's motor reserve in the settings of neuropathology and ageing. Individuals who attain higher levels of functionality via lifelong experience develop a higher motor reserve throughout life and clinically relevant symptoms only later in life. The higher the motor reserve, the higher the degree of resilience and the better individuals can cope with a given level of neuropathology. Physical exercise is an efficacious and efficient way of strengthening one's motor reserve, allowing for an increased ability to cope with neuropathology throughout life and resulting in delayed disease onset and progression. Motor learning, and not necessarily motor performance, seems to be the key when aiming at maximizing the benefits of physical exercise in the context of motor reserve. As a result, a variety of challenging activities are to be recommended and maintained throughout life.

Glucocerebrosidase Mutations and Motor Reserve in Parkinson's Disease.

BACKGROUND: The concept of motor reserve explains the individual differences in motor deficits despite similar degrees of nigrostriatal dopamine depletion in Parkinson's disease (PD). OBJECTIVE: To investigate glucocerebrosidase (GBA) variants as potential determinants of motor reserve for exploratory purposes. METHODS: A total of 408 patients with drug-naïve PD were enrolled from the Parkinson's Progression Markers Initiative cohort database. All patients underwent SPECT dopamine transporter (DAT) scans and had results for Sanger sequencing of GBA. Parkinsonian motor deficits were assessed using the Movement Disorders Society Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS-III). We compared MDS-UPDRS-III scores while adjusting for DAT availability in the putamen (i.e., motor reserve) between the PD groups according to the presence of GBA mutations. RESULTS: Fifty-four (13.2%) patients carried GBA mutations. PD patients with GBA mutations were younger than those without mutations. There were no significant differences in sex, disease duration, years of education, and striatal DAT availability between the PD groups. PD patients with GBA mutations had higher MDS-UPDRS-III scores for the less affected side than those without mutations, despite similar levels of DAT availability in the contralateral putamen. The MDS-UPDRS-III sub-scores of the more affected side did not differ between the two PD groups. CONCLUSION: The results of this study demonstrated the detrimental effect of GBA variants on individual capacity to cope with PD-related pathologies, with different impacts depending on the motor laterality.

Emerging Concepts of Motor Reserve in Parkinson's Disease.

The concept of cognitive reserve (CR) in Alzheimer's disease (AD) explains the differences between individuals in their susceptibility to AD-related pathologies. An enhanced CR may lead to less cognitive deficits despite severe pathological lesions. Parkinson's disease (PD) is also a common neurodegenerative disease and is mainly characterized by motor dysfunction related to striatal dopaminergic depletion. The degree of motor deficits in PD is closely correlated to the degree of dopamine depletion; however, significant individual variations still exist. Therefore, we hypothesized that the presence of motor reserve (MR) in PD explains the individual differences in motor deficits despite similar levels of striatal dopamine depletion. Since 2015, we have performed a series of studies investigating MR in de novo patients with PD using the data of initial clinical presentation and dopamine transporter PET scan. In this review, we summarized the results of these published studies. In particular, some premorbid experiences (i.e., physical activity and education) and modifiable factors (i.e., body mass index and white matter hyperintensity on brain image studies) could modulate an individual's capacity to tolerate PD pathology, which can be maintained throughout disease progression.

Initial motor reserve and long-term prognosis in Parkinson's disease.

There are individual differences in motor deficits, despite a similar degree of dopamine neuronal loss in Parkinson's disease (PD), called motor reserve (MR). Factors enhancing MR have been documented previously, but the influence of initial MR on the long-term prognosis remains unclear. In this longitudinal study, we enrolled 205 patients with de novo PD to estimate individual MR based on initial motor deficits and striatal dopamine depletion using the residual-based approach. We assessed the risk of developing levodopa-induced dyskinesia (LID) or freezing of gait (FOG) and longitudinal increases in levodopa-equivalent dose (LED) according to MR estimates using the Cox regression model and linear mixed model, respectively. Throughout the follow-up period (≥3 years), greater MR estimates were associated with a lower risk for LID and FOG. In addition, patients with high MR received lower LED than those with low MR. These findings suggest that the initial MR, that is, individual's capacity to cope with PD-related pathologies, can be maintained with disease progression and can modulate the risk for LID or FOG.

Identifying the Functional Brain Network of Motor Reserve in Early Parkinson's Disease.

BACKGROUND: The severity of motor symptoms in Parkinson's disease (PD) does not always correlate with the degree of nigral dopaminergic neuronal loss. Individuals with greater motor reserve may have milder motor signs than their striatal dopamine loss. In this study, we explored the functional brain network associated with motor reserve in early-stage PD. METHODS: We analyzed 134 patients with de novo PD who underwent dopamine transporter scans and resting-state functional magnetic resonance imaging. We estimated individual motor reserve based on initial motor deficits and striatal dopamine depletion using a residual model. We applied network-based statistic analysis to identify the functional brain network associated with the measure of motor reserve (ie, motor reserve network). We also assessed the effect of motor reserve network connectivity strength on the longitudinal increase in levodopa-equivalent dose during the 2-year follow-up period. RESULTS: Network-based statistic analysis identified the motor reserve network composed of the basal ganglia, inferior frontal cortex, insula, and cerebellar vermis at a primary threshold of P value 0.001. Patients with an increased degree of functional connectivity within the motor reserve network had greater motor reserve. There was a significant interaction between the motor reserve network strength and time in the linear mixed model, indicating that higher motor reserve network strength was associated with slower longitudinal increase in levodopa-equivalent dose. CONCLUSIONS: The present study revealed the functional brain network associated with motor reserve in patients with early-stage PD. Functional connections within the motor reserve network are associated with the individual's capacity to cope with PD-related pathologies. © 2020 International Parkinson and Movement Disorder Society.

Delayed Clinical Manifestation of Parkinson's Disease Among Physically Active: Do Participants in a Long-Distance Ski Race Have a Motor Reserve?

BACKGROUND: Physical activity is associated with reduced risk of Parkinson's disease (PD). The explanations for this association are not completely elucidated. We use long-term PD-incidence data from long-distance skiers to study the relationship between exercise and PD. OBJECTIVE: We aimed to investigate if physical activity is associated with long-term lower risk of PD and if this association could be explained by physically active people being able to sustain more PD neuropathology before clinical symptoms, a motor reserve. METHODS: Using a prospective observational design, we studied whether long-distance skiers of the Swedish Vasaloppet (n = 197,685), exhibited reduced incidence of PD compared to matched individuals from the general population (n = 197,684) during 21 years of follow-up (median 10, interquartile range (IQR) 5-15 years). RESULTS: Vasaloppet skiers (median age 36.0 years [IQR 29.0-46.0], 38% women) had lower incidence of PD (HR: 0.71; 95 % CI 0.56-0.90) compared to non-skiers. When reducing risk for reverse causation by excluding PD cases within the first five years from race participation, there was still a trend for lower risk of PD (HR: 0.80; 95 % CI 0.62-1.03). Further, the PD prevalence converged between skiers and non-skiers after 15 years of follow-up, which is more consistent with a motor reserve in the physically active rather than neuroprotection. CONCLUSIONS: A physical active lifestyle is associated with reduced risk for PD. This association weakens with time and might be explained by a motor reserve among the physically active.

Educational attainment and motor burden in advanced Parkinson's disease - The emerging role of education in motor reserve.

OBJECTIVE: To explore the relationship of motor burden and educational attainment in patients with advanced stage PD. MATERIALS AND METHODS: We included 102 consecutive patients who underwent a complete evaluation for DBS surgery, including detailed neuropsychological testing and UPDRSIII in a standardized Levodopa challenge. Years of education (YoE) were calculated as the highest grade attained in secondary school plus years for post-secondary training. RESULTS: The OFF medication UPDRS-III score was associated with YoE (p=0.006; t=-2.82) and age (p=0.007; t=-2.75) in our multivariable linear regression model even while including disease duration (p=0.8; t=0.21), presence of mild cognitive impairment (MCI) (p=0.9; t=0.16) or current IQ (p=0.2; t=1.25) as additional covariables. In a subgroup of 60 patients two years after DBS, the ON/ON UPDRS score was associated with YoE (p=0.01; t=-2.42) and diagnosis of PD dementia (p=0.05, t=1.95), while age (p=0.08, t=1.75), disease duration (p=0.6t=0.48) and LEDD (p=0.3; t=1.05) showed no significant association to ON/ON UPDRS score. CONCLUSIONS: We found an inverse correlation between years of education and lower (better) UPDRS -III motor score after adjusting for important covariables. Education may lead to an increased ability to compensate disturbances in basal ganglia circuits affecting not only for cognitive, but also for motor aspects of PD. Thus, educational attainment may play an important role in the concept of motor reserve.

Shape of the Central Sulcus and Disability After Subcortical Stroke: A Motor Reserve Hypothesis.

BACKGROUND AND PURPOSE: Both brain and cognitive reserves modulate the clinical impact of chronic brain diseases. Whether a motor reserve also modulates the relationships between stroke and disability is unknown. We aimed to determine whether the shape of the central sulcus, a marker of the development of underlying motor connections, is independently associated with disability in patients with a positive history of small subcortical ischemic stroke. METHODS: Shapes of central sulci were reconstructed from high-resolution magnetic resonance imaging and ordered without supervision according to a validated algorithm in 166 patients with a positive history of small subcortical ischemic stroke caused by CADASIL (Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy), a severe monogenic cerebral small vessel disease affecting young patients. Ordinal logistic regression modeling was used to test the relationships between modified Rankin scale, a disability scale strongly weighted toward motor disability, and sulcal shape. RESULTS: Modified Rankin scale was strongly associated with sulcal shape, independent of age, sex, and level of education (proportional odds ratio =1.19, 95% confidence interval =1.06-1.35; P=0.002). Results remained significant after further adjustment for brain atrophy, volume of lacunes, and volume of white matter hyperintensities of presumed vascular origin. CONCLUSIONS: The severity of disability in patients with a positive history of small subcortical ischemic stroke caused by a severe cerebral small vessel disease is related to the shape of the central sulcus, independently of the main determinants of disability. These results support the concept of a motor reserve that could modulate the clinical severity in patients with a positive history of small subcortical ischemic stroke.