Data-driven sequence of cognitive decline in people with Parkinson's disease.

Background: Understanding the sequential progression of cognitive impairments in Parkinson's disease (PD) is crucial for elucidating neuropathological underpinnings, refining the assessment of PD-related cognitive decline stages and enhancing early identification for targeted interventions. The first aim of this study was to use an innovative event-based modeling (EBM) analytic approach to estimate the sequence of cognitive declines in PD. The second aim was to validate the EBM by examining associations with EBM-derived individual-specific estimates of cognitive decline severity and performance on independent cognitive screening measures.

A naturally occurring variant of SHLP2 is a protective factor in Parkinson's disease.

Mitochondrial DNA single nucleotide polymorphisms (mtSNPs) have been associated with a reduced risk of developing Parkinson's disease (PD), yet the underlying mechanisms remain elusive. In this study, we investigate the functional role of a PD-associated mtSNP that impacts the mitochondrial-derived peptide (MDP) Small Humanin-like Peptide 2 (SHLP2). We identify m.

Increased perivascular space volume in white matter and basal ganglia is associated with cognition in Parkinson's Disease.

Perivascular spaces (PVS), fluid-filled compartments surrounding brain vasculature, are an essential component of the glymphatic system responsible for transport of waste and nutrients. Glymphatic system impairment may underlie cognitive deficits in Parkinson's disease (PD). Studies have focused on the role of basal ganglia PVS with cognition in PD, but the role of white matter PVS is unknown.

Exercise alters cortico-basal ganglia network metabolic connectivity: a mesoscopic level analysis informed by anatomic parcellation defined in the mouse brain connectome.

The basal ganglia are important modulators of the cognitive and motor benefits of exercise. However, the neural networks underlying these benefits remain poorly understood. Our study systematically analyzed exercise-associated changes in metabolic connectivity in the cortico-basal ganglia-thalamic network during the performance of a new motor task, with regions-of-interest defined based on mesoscopic domains recently defined in the mouse brain structural connectome.

A mind in motion: Exercise improves cognitive flexibility, impulsivity and alters dopamine receptor gene expression in a Parkinsonian rat model.

Cognitive impairment, particularly deficits in executive function (EF) is common in Parkinson's disease (PD) and may lead to dementia. There are currently no effective treatments for cognitive impairment. Work from our lab and others has shown that physical exercise may improve motor performance in PD but its role in cognitive function remains poorly eludicated.

Physical activity intensity is associated with cognition and functional connectivity in Parkinson's disease.

Background: Cognitive impairment is common in Parkinson's disease (PD) and often leads to dementia, with no effective treatment. Aging studies suggest that physical activity (PA) intensity has a positive impact on cognition and enhanced functional connectivity may underlie these benefits. However, less is known in PD.

Magnetic resonance spectroscopy shows associations between neurometabolite levels and perivascular space volume in Parkinson's disease: a pilot and feasibility study.

Objective: Higher volume fraction of perivascular space (PVS) has recently been reported in Parkinson's disease (PD) and related disorders. Both elevated PVS and altered levels of neurometabolites, assayed by proton magnetic resonance spectroscopy (MRS), are suspected indicators of neuroinflammation, but no published reports have concurrently examined PVS and MRS neurometabolites.

Methods: In an exploratory pilot study, we acquired multivoxel 3-T MRS using a semi-Localization by Adiabatic SElective Refocusing (sLASER) pulse-sequence (repetition time/echo time = 2810/60 ms, voxels 10 × 10 × 10 mm3) from a 2D slab sampling bilateral frontal white matter (FWM) and anterior middle cingulate cortex (aMCC).

Promoting Physical Activity in a Spanish-Speaking Latina Population of Low Socioeconomic Status With Chronic Neurological Disorders: Proof-of-Concept Study.

Background: Physical activity (PA) is known to improve quality of life (QoL) as well as reduce mortality and disease progression in individuals with chronic neurological disorders. However, Latina women are less likely to participate in recommended levels of PA due to common socioeconomic barriers, including limited resources and access to exercise programs. Therefore, we developed a community-based intervention with activity monitoring and behavioral coaching to target these barriers and facilitate sustained participation in an exercise program promoting PA.

The Effects of Cardiorespiratory and Motor Skill Fitness on Intrinsic Functional Connectivity of Neural Networks in Individuals with Parkinson's Disease.

Background: Studies in aging older adults have shown the positive association between cognition and exercise related fitness, particularly cardiorespiratory fitness. These reports have also demonstrated the association of high cardiorespiratory fitness, as well as other types of fitness, on the reversal of age-related decline in neural network connectivity, highlighting the potential role of fitness on age- and disease-related brain changes. While the clinical benefits of exercise are well-documented in Parkinson's disease (PD), the extent to which cardiorespiratory fitness (assessed by estimated VO testing) or motor skill fitness (assessed by the Physical Performance Test (PPT)) affects neural network connectivity in PD remains to be investigated.

Knockdown of Astrocytic Monocarboxylate Transporter 4 in the Motor Cortex Leads to Loss of Dendritic Spines and a Deficit in Motor Learning.

Monocarboxylate transporters (MCTs) shuttle molecules, including L-lactate, involved in metabolism and cell signaling of the central nervous system. Astrocyte-specific MCT4 is a key component of the astrocyte-neuron lactate shuttle (ANLS) and is important for neuroplasticity and learning of the hippocampus. However, the importance of astrocyte-specific MCT4 in neuroplasticity of the M1 primary motor cortex remains unknown.

Cognition and motor learning in a Parkinson's disease cohort: importance of recall in episodic memory.

Impaired motor learning in individuals with Parkinson's disease is often attributed to deficits in executive function, which serves as an important cognitive process supporting motor learning. However, less is known about the role of other cognitive domains and its association with motor learning in Parkinson's disease. The objective of this study was to investigate the associations between motor learning and multiple domains of cognitive performance in individuals with Parkinson's disease.

Thalamic volume mediates associations between cardiorespiratory fitness (VOmax) and cognition in Parkinson's disease.

Introduction: Cognitive deficits occur in Parkinson's disease (PD). Cardiorespiratory fitness (CRF) is associated with better cognitive performance in aging especially in executive function (EF) and memory. The association between CRF and cognitive performance is understudied in people with PD.

Exogenous l-lactate promotes astrocyte plasticity but is not sufficient for enhancing striatal synaptogenesis or motor behavior in mice.

l-Lactate is an energetic and signaling molecule that may be produced through astrocyte-specific aerobic glycolysis and is elevated in striatal muscle during intensive exercise. l-Lactate has been shown to promote neurotrophic gene expression through astrocytes within the hippocampus, however, its role in neuroplasticity within the striatum remains unknown. This study sought to investigate the role of peripheral sources of l-lactate in promoting astrocyte-specific gene expression and morphology as well as its role in neuroplasticity within the striatum of healthy animals.

Global and Regional Changes in Perivascular Space in Idiopathic and Familial Parkinson's Disease.

Background: The glymphatic system, including the perivascular space (PVS), plays a critical role in brain homeostasis. Although mounting evidence from Alzheimer's disease has supported the potential role of PVS in neurodegenerative disorders, its contribution in Parkinson's disease (PD) has not been fully elucidated. Although idiopathic (IPD) and familial PD (FPD) share similar pathophysiology in terms of protein aggregation, the differential impact of PVS on PD subtypes remains unknown.

Cognitive flexibility deficits in rats with dorsomedial striatal 6-hydroxydopamine lesions tested using a three-choice serial reaction time task with reversal learning.

Lesions of the dorsomedial striatum elicit deficits in cognitive flexibility that are an early feature of Parkinson's disease (PD), and presumably reflect alterations in frontostriatal processing. The current study aimed to examine deficits in cognitive flexibility in rats with bilateral 6-hydroxydopamine lesions in the dorsomedial striatum. While deficits in cognitive flexibility have previously been examined in rodent PD models using the cross-maze, T-maze, and a food-digging task, the current study is the first to examine such deficits using a 3-choice serial reaction time task (3-CSRT) with reversal learning (3-CSRT-R).

Mild cognitive impairment, psychiatric symptoms, and executive functioning in patients with Parkinson's disease.

Objective: Mild cognitive impairment (MCI) and psychiatric symptoms (anxiety, depression, and apathy) are common in Parkinson's disease (PD). While studies have supported the association between psychiatric symptoms and cognitive performance in PD, it is unclear if the magnitude of link between psychiatric symptoms and cognitive health is stronger by MCI status. The purpose of this study was to examine the association between cognitive performance and psychiatric symptoms in PD and whether MCI status moderates this association.

Treadmill exercise rescues mitochondrial function and motor behavior in the CAG knock-in mouse model of Huntington's disease.

Background: Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by polyglutamine (CAG) expansion in the Huntingtin (HTT) gene. The CAG knock-in (KI) mouse model recapitulates the progression of motor symptoms emerging at 12 months of age.

Objective: This study was aimed at assessing the effects of exercise, in the form of treadmill running, and examining its impact on motor behavior and markers of metabolism in the CAG KI mouse model of HD after motor symptoms have emerged.

Exercise induces region-specific remodeling of astrocyte morphology and reactive astrocyte gene expression patterns in male mice.

Astrocytes are essential mediators of many aspects of synaptic transmission and neuroplasticity. Exercise has been demonstrated to induce neuroplasticity and synaptic remodeling, such as through mediating neurorehabilitation in animal models of neurodegeneration. However, the effects of exercise on astrocytic function, and how such changes may be relevant to neuroplasticity remain unclear.

Intensive treadmill exercise increases expression of hypoxia-inducible factor 1α and its downstream transcript targets: a potential role in neuroplasticity.

Exercise and other forms of physical activity lead to the activation of specific motor and cognitive circuits within the mammalian brain. These activated neuronal circuits are subjected to increased metabolic demand and must respond to transient but significant reduction in available oxygen. The transcription factor hypoxia-inducible factor 1α (HIF-1α) is a regulatory mediator of a wide spectrum of genes involved in metabolism, synaptogenesis, and blood flow.

Worse cognitive performance predicts increased anxiety and depressive symptoms in patients with Parkinson's disease: A bidirectional analysis.

Objective: Symptoms of anxiety, depression commonly co-occur with cognitive decline in patients with Parkinson's disease (PD). The directionality of this association is unclear, however, in that poor cognitive performance may lead to increased symptoms of anxiety and depression or higher anxiety and depressive symptoms may lead to cognitive decline. The purpose of this study was to elucidate the directionality of the association between symptoms of anxiety and depression with cognitive performance in newly diagnosed patients with PD.

Basal ganglia and beyond: The interplay between motor and cognitive aspects in Parkinson's disease rehabilitation.

Parkinson's disease (PD) is characterized by motor and cognitive dysfunctions, affecting the motor behaviour. We summarize evidence that the interplay between motor and cognitive approaches is crucial in PD rehabilitation. Rehabilitation is complementary to pharmacological therapy and effective in reducing the PD disturbances, probably acting by inducing neuroplastic effects.

The Oxygen Paradox, the French Paradox, and age-related diseases.

A paradox is a seemingly absurd or impossible concept, proposition, or theory that is often difficult to understand or explain, sometimes apparently self-contradictory, and yet ultimately correct or true. How is it possible, for example, that oxygen "a toxic environmental poison" could be also indispensable for life (Beckman and Ames Physiol Rev 78(2):547-81, 1998; Stadtman and Berlett Chem Res Toxicol 10(5):485-94, 1997)?: the so-called Oxygen Paradox (Davies and Ursini 1995; Davies Biochem Soc Symp 61:1-31, 1995). How can French people apparently disregard the rule that high dietary intakes of cholesterol and saturated fats (e.

Treadmill exercise modifies dopamine receptor expression in the prefrontal cortex of the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned mouse model of Parkinson's disease.

Parkinson's disease (PD) is the second most common neurodegenerative disorder for which there is no cure. PD is a dopamine (DA)-deficit disorder marked by progressive motor and nonmotor disturbances, including cognitive impairment. Executive function (EF) is the most common subtype of cognitive impairment in PD and consists of deficits in number of processes including behavioral flexibility.

Engaging cognitive circuits to promote motor recovery in degenerative disorders. exercise as a learning modality.

Exercise and physical activity are fundamental components of a lifestyle essential in maintaining a healthy brain. This is primarily due to the fact that the adult brain maintains a high degree of plasticity and activity is essential for homeostasis throughout life. Plasticity is not lost even in the context of a neurodegenerative disorder, but could be maladaptive thus promoting disease onset and progression.