Cerebral Metabolic Rate of Oxygen and Accelerometry-Based Fatigability in Community-Dwelling Older Adults.

Alterations in energy metabolism may drive fatigue in older age, but prior research primarily focused on skeletal muscle energetics without assessing other systems, and utilized self-reported measures of fatigue. We tested the association between energy metabolism in the brain and an objective measure of fatigability in the Study of Muscle, Mobility and Aging (N=119, age 76.8±4.

Regional cerebral cholinergic vesicular transporter correlates of visual contrast sensitivity in Parkinson's disease: Implications for visual and cognitive function.

Visual and visual processing deficits are implicated in freezing, falling, and cognitive impairments in Parkinson's disease (PD). In particular, contrast sensitivity deficits are common and may be related to cognitive impairment in PD. While dopaminergic deficits play a role in PD-related visual dysfunction, brain cholinergic systems also modulate many aspects of visual processing.

Post-Physical Therapy 4-Month In-Home Dynamic Standing Protocol Maintains Physical Therapy Gains and Improves Mobility, Balance Confidence, Fear of Falling and Quality of Life in Parkinson's Disease: A Randomized Controlled Examiner-Blinded Feasibility Clinical Trial.

Objective: Parkinson's patients will experience mobility disturbances with disease progression. Beneficial effects of physical therapy are short-lasting. Novel interventions are needed to maintain these benefits.

Impaired mitochondrial function in bipolar disorder and alcohol use disorder: a case study using F-BCPP-EF PET imaging of mitochondrial Complex I.

Background: With bipolar disorder (BD) having a lifetime prevalence of 4.4% and a significant portion of patients being chronically burdened by symptoms, there has been an increased focus on uncovering new targets for intervention in BD. One area that has shown early promise is the mitochondrial hypothesis.

Topography of Cholinergic Nerve Terminal Vulnerability and Balance Self-Efficacy in Parkinson's Disease.

Background: Postural instability and gait disturbances (PIGD) represent a significant cause of disability in Parkinson's disease (PD). Cholinergic system dysfunction has been implicated in falls in PD. The occurrence of falls typically results in fear of falling (FoF) that in turn may lead to poorer balance self-efficacy.

Dynamic balance and gait impairments in Parkinson's disease: novel cholinergic patterns.

The cholinergic system has been implicated in postural deficits, in particular falls, in Parkinson's disease (PD). Falls and freezing of gait typically occur during dynamic and challenging balance and gait conditions, such as when initiating gait, experiencing postural perturbations, or making turns. However, the precise cholinergic neural substrate underlying dynamic postural and gait changes remains poorly understood.

The Middle Managers: Thalamic and Cholinergic Contributions To Coordinating Top-Down And Bottom-Up Processing.

Methodological advances have facilitated extensive revision of traditional views of thalamic and cholinergic contributions to cognition and behavior. Increasing attention to the integrative capabilities of the thalamus highlights its role beyond a simple sensory relay, recognizing its complex connectivity and role in orchestrating different phases of attention. Correspondingly, modern conceptualizations position the cholinergic system as key in integrating sensory information with attention and goals.

Higher Striatal Dopamine is Related With Lower Physical Performance Fatigability in Community-Dwelling Older Adults.

Background: Fatigability in community-dwelling older adults is highly prevalent and disabling, but lacks a treatment. Greater nigrostriatal dopaminergic signaling can ameliorate performance fatigability in healthy young adults, but its role in community-dwelling older adults is not known. We hypothesized that higher nigrostriatal dopaminergic integrity would be associated with lower performance fatigability, independent of cardiopulmonary and musculoskeletal energetics and other health conditions.

Body Composition, Falls, and Freezing of Gait in Parkinson's Disease: Gender-Specific Effects.

Background: Postural instability and gait difficulties (PIGD) are a significant cause of mobility loss and lower quality of life in Parkinson's disease (PD). When PD progresses, patients may experience falls and freezing of gait (FoG) resulting in fear of falling and increasing sedentariness. Sedentary behavior results in sarcopenia associated with other changes in body composition, especially in older patients becoming frail.

Cognitive and Cholinergic Systems Trajectories in Parkinson Disease.

Objective: Cognitive decline in Parkinson disease (PD) is a disabling and highly variable non-motor feature. While cholinergic systems degeneration is linked to cognitive impairments in PD, most prior research reported cross-sectional associations. We aimed to fill this gap by investigating whether baseline regional cerebral vesicular acetylcholine transporter ligand [ F]-fluoroethoxybenzovesamicol ([ F]-FEOBV) binding predicts longitudinal cognitive changes in mild to moderate, non-demented PD subjects.

Golexanolone reduces glial activation in the striatum and improves non-motor and some motor alterations in a rat model of Parkinson's disease.

Background: Parkinson's disease (PD) affects more than 6 million people worldwide. Along with motor impairments, patients and animal models exhibiting PD symptoms also experience cognitive impairment, fatigue, anxiety, and depression. Currently, there are no drugs available for PD that alter the progression of the disease.

Noradrenergic cardiac denervation is associated with gait velocity in Parkinson disease: a dual ligand PET study.

Purpose: Preliminary data suggest that gait abnormalities in Parkinson disease (PD) may be associated with sympathetic cardiac denervation. No kinematic gait studies were performed to confirm this observation. We aimed to correlate spatiotemporal kinematic gait parameters with cardiac sympathetic denervation as determined by cardiac [C]HED PET in PD.

Association of Specific Leg Muscle Strength and Motor Features in Parkinson's Disease.

Background: Postural instability and gait difficulties (PIGD) are a significant cause of falls, mobility loss, and lower quality of life in Parkinson's disease (PD). The connection between PD progression and diminished strength in the lower limbs has been acknowledged. However, the identification of specific muscle groups linked to PIGD and non-PIGD motor features is still unknown.

Sensitivity to and Control of Distraction: Distractor-Entrained Oscillation and Frontoparietal EEG Gamma Synchronization.

While recent advancements have been made towards a better understanding of the involvement of the prefrontal cortex (PFC) in the context of cognitive control, the exact mechanism is still not fully understood. Successful behavior requires the correct detection of goal-relevant cues and resisting irrelevant distractions. Frontal parietal networks have been implicated as important for maintaining cognitive control in the face of distraction.

Multisensory mechanisms of gait and balance in Parkinson's disease: an integrative review.

Understanding the neural underpinning of human gait and balance is one of the most pertinent challenges for 21st-century translational neuroscience due to the profound impact that falls and mobility disturbances have on our aging population. Posture and gait control does not happen automatically, as previously believed, but rather requires continuous involvement of central nervous mechanisms. To effectively exert control over the body, the brain must integrate multiple streams of sensory information, including visual, vestibular, and somatosensory signals.

Serotonin transporter density in isolated rapid eye movement sleep behavioral disorder.

Background/objective: The serotoninergic nervous system is known to play a role in the maintenance of rapid eye movement (REM) sleep. Serotoninergic projections are known to be vulnerable in synucleinopathies. To date, positron emission tomography (PET) studies using serotonin-specific tracers have not been reported in isolated REM sleep behavior disorder (iRBD).

Cardiac sympathetic denervation and anxiety in Parkinson disease.

Background: Anxiety in Parkinson disease (PD) negatively impacts quality of life. While research predominantly focuses on central nervous system changes, some evidence suggests a connection between peripheral autonomic dysfunctions and PD-related anxiety. The role of the peripheral autonomic nervous system in this context may be overlooked.

Beta-Gamma Phase-Amplitude Coupling as a Non-Invasive Biomarker for Parkinson's Disease: Insights from Electroencephalography Studies.

Phase-amplitude coupling (PAC) describes the interaction of two separate frequencies in which the lower frequency phase acts as a carrier frequency of the higher frequency amplitude. It is a means of carrying integrated streams of information between micro- and macroscale systems in the brain, allowing for coordinated activity of separate brain regions. A beta-gamma PAC increase over the sensorimotor cortex has been observed consistently in people with Parkinson's disease (PD).

Cholinergic changes in Lewy body disease: implications for presentation, progression and subtypes.

Cholinergic degeneration is significant in Lewy body disease, including Parkinson's disease, dementia with Lewy bodies, and isolated REM sleep behaviour disorder. Extensive research has demonstrated cholinergic alterations in the CNS of these disorders. More recently, studies have revealed cholinergic denervation in organs that receive parasympathetic denervation.

Transitioning from Subtyping to Precision Medicine in Parkinson's Disease: A Purpose-Driven Approach.

The International Parkinson and Movement Disorder Society (MDS) created a task force (TF) to provide a critical overview of the Parkinson's disease (PD) subtyping field and develop a guidance on future research in PD subtypes. Based on a literature review, we previously concluded that PD subtyping requires an ultimate alignment with principles of precision medicine, and consequently novel approaches were needed to describe heterogeneity at the individual patient level. In this manuscript, we present a novel purpose-driven framework for subtype research as a guidance to clinicians and researchers when proposing to develop, evaluate, or use PD subtypes.

GABA Receptor Benzodiazepine Binding Sites and Motor Impairments in Parkinson's Disease.

Flumazenil is an allosteric modulator of the γ-aminobutyric acid-A receptor (GABAR) benzodiazepine binding site that could normalize neuronal signaling and improve motor impairments in Parkinson's disease (PD). Little is known about how regional GABAR availability affects motor symptoms. We investigated the relationship between regional availability of GABAR benzodiazepine binding sites and motor impairments in PD.

Basal forebrain integrity, cholinergic innervation and cognition in idiopathic Parkinson's disease.

Most individuals with Parkinson's disease experience cognitive decline. Mounting evidence suggests this is partially caused by cholinergic denervation due to α-synuclein pathology in the cholinergic basal forebrain. Alpha-synuclein deposition causes inflammation, which can be measured with free water fraction, a diffusion MRI-derived metric of extracellular water.