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Changes in Neuronal Communication Linked to Falls and Freezing of Gait in Parkinson’s, Study Finds

neuronal communication changes, Parkinson's motor symptoms

Parkinson’s disease-related falls and freezing of gait — when patients are unable to move their feet forward when trying to walk — are associated with changes in a specific type of neuronal communication in different brain regions, a study reports.

The study, “Cholinergic system changes of falls and freezing of gait in Parkinson disease,” was published in Annals of Neurology.

Many people with Parkinson’s disease will experience falling and freezing of gait, which tend to become more frequent as the disease progresses. In some cases, symptoms cannot be controlled with dopaminergic therapy, suggesting that non-dopamine mechanisms contribute to Parkinson’s disease motor symptoms.

Previous studies have shown that the brainstem (region that connects the brain to the spinal cord) and basal forebrain (important in the production of acetylcholine) regions with degenerated acetylcholine-releasing neurons projecting to the thalamus and cerebral cortex are associated with falls and slow gait speed in Parkinson’s patients.

Acetylcholine is a brain chemical (neurotransmitter) released by nerve cells to send signals to other cells (neurons, muscles, and glands). The thalamus is involved in several important processes, including consciousness, sleep, and sensory interpretation; the cerebral cortex plays a key role in memory, attention, perception, awareness, thought, language, and consciousness.

Scientists have also observed reduced dopaminergic nerve terminals in the striatum, reduced cholinergic (meaning “acetylcholine-releasing”) nerve terminals in the cortex, and more severe beta-amyloid accumulation in Parkinson’s disease “freezers” compared with “non-freezers.”

The striatum coordinates multiple aspects of cognition, including both motor and action planning; the cholinergic system contains nerve cells that use acetylcholine to propagate a nerve impulse, and has been associated with a number of cognitive functions, including memory, selective attention, and emotional processing.

University of Michigan researchers hypothesized that distinct patterns of cholinergic projection system changes in the brain are associated with freezing of gait and falls in Parkinson’s patients.

The team examined and performed [18F]FEOBV positron emission tomography (PET) scans on 94 Parkinson’s patients (72 men and 22 women) with a history of falling and “freezing.” Most subjects were taking dopamine agonists, carbidopa-levodopa or combinations of both.

[18F]FEOBV is a radioactive marker that selectively binds to the vesicular acetylcholine transporter (VACht) that loads acetylcholine into synaptic vesicles — sac-like structures in neurons that store chemical messengers before releasing them into the gap between nerve cells (synapse), enabling neuronal communication.

A PET scan is a non-invasive imaging technique to visualize metabolic processes in the body. Before the scan, [18F]FEOBV is administered via injection; doctors wait for the radiotracer to be distributed throughout the body, and then scan the patient to detect and quantify the patterns of its accumulation in the body.

Because the marker binds to VACht, scientists use it to quantify active cholinergic nerve terminals in the brain.

“Participants were asked about a history of falling. A fall was defined as an unexpected event during which a person falls to the ground. The presence or absence of (freezing of gait) was based on clinical examination and directly observed by the clinician examiner,” according to The Movement-Disorder Society Sponsored-Unified Parkinson’s Disease Rating Scale (MDSUPDRS), the researchers wrote.

They reported that 35 participants (37.2%) had a history of falls, and 15 (16%) had observed freezing of gait.

Compared with non-fallers, fallers had a significant decrease in VACht expression within the right thalamus, specifically in the lateral geniculate nucleus, which is the primary center for processing visual information. This suggests that the visual information processing required for walking around safely might be compromised in Parkinson’s patients with a history of falling.

On the other hand, patients with freezing of gait had significantly reduced VACht expression in the bilateral striatum and hippocampus — required for learning and memory — compared with non-freezers.

The team found that a history of falls was associated with cholinergic projection system changes that relay to the thalamus, while the neural signals behind freezing of gait transmit to the caudate nucleus — a brain region associated with motor processing.

They also found that Parkinson’s fallers had a lower density of thalamic cholinergic nerve terminals compared with non-fallers.

Freezing of gait was related to longer disease duration, more severe parkinsonian motor ratings, and higher levodopa levels.

These results suggest that changes in acetylcholine-mediated neuronal communication are linked to falls or freezing behavior, depending on the affected brain region.

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Structural Changes in Brain Predict Cognitive Decline in Parkinson’s Patients, Study Suggests

Parkinson's cognitive decline

Structural changes in a specific region of the brain can predict the onset of cognitive impairment in Parkinson’s patients who have not yet developed dementia, according to a recent British study.

The study, “Nucleus basalis of Meynert degeneration precedes and predicts cognitive impairment in Parkinson’s disease,” was published in the journal Brain.

A brain region called the nucleus basalis of Meynert has been identified as the primary source of acetylcholine — a brain chemical important for cognitive function development, including memory, learning, and concentration abilities.

Cognitive impairment is highly prevalent in Parkinson’s disease, with approximately 80 percent of patients eventually developing dementia during the course of their illness. It is one of the most clinically relevant symptoms of the disease, and causes an increased risk of mortality and significant reduction in quality of life.

Studies have demonstrated that the structure of the nucleus basalis of Meynert appears to be more damaged in Parkinson’s patients with cognitive impairment. However, so far, there are no reliable predictors of dementia in Parkinson’s, and the mechanisms behind the development of cognitive impairment remain unclear.

King’s College London researchers hypothesized that structural changes in this specific brain region could be behind cognitive impairment in patients with Parkinson’s disease, and could predict the development of cognitive impairment. To test this, the team compared magnetic resonance imaging (MRI) data from Parkinson’s patients with and without cognitive impairment.

A total of 304 Parkinson’s patients and 167 healthy people in a control group were included in the study. The participants’ cognitive status was assessed at the start and then every six months for 36 months, or until a patient developed cognitive impairment.

No brain anatomy differences were observed between Parkinson’s patients and the control group. However, cognitively impaired patients had higher rates of neuronal loss within the nucleus basalis of Meynert than non-demented patients with Parkinson’s.

Damage to this brain region “was predictive for developing cognitive impairment in cognitively intact patients with Parkinson’s disease, independent of other clinical and non-clinical markers of the disease,” the authors wrote.

The team also analyzed the anatomy of other cognitive function-related brain centers, but structural and microstructural changes to those regions did not precede clinical onset of cognitive impairment.

Researchers concluded that “degeneration of the nucleus basalis of Meynert precedes and predicts the onset of cognitive impairment, and might be used in a clinical setting as a reliable biomarker to stratify patients at higher risk of cognitive decline.”

The post Structural Changes in Brain Predict Cognitive Decline in Parkinson’s Patients, Study Suggests appeared first on Parkinson’s News Today.

Source: Parkinson's News Today