Preserved dopamine pools seen in Parkinson's patients with tremor

26 Nov 2024, 13:45 by Margarida Maia, PhD · Parkinson's News Today

While loss of dopamine is a hallmark of Parkinson’s disease, patients with tremor may actually have pools of dopamine in a specific region of the brain, a study by researchers at Champalimaud Foundation in Portugal found. The results could pave the way for targeted treatments to control shaking at rest.

The findings indicate that in the brain’s caudate nucleus, preserved dopamine is actually linked with tremor, aligning with earlier evidence for treating tremor separately from other motor symptoms.

“Paradoxically, we discovered that patients who exhibit tremor have more dopamine preserved in the caudate nucleus, a part of the brain important for movement planning and cognition,” neurologist Marcelo Mendonça, MD, a researcher at the Champalimaud Foundation and one of the study’s lead authors, said in a foundation news story.

The study, “Relative sparing of dopaminergic terminals in the caudate nucleus is a feature of rest tremor in Parkinson’s disease,” was published in the journal npj Parkinson’s Disease.

Tremor in Parkinson’s may not manifest in the same way for every patient. It can occur in different parts of the body, vary in intensity, and be influenced by stress. While loss of dopamine, a chemical messenger involved in the control of the body’s movement, is needed for tremor to occur, some patients fail to respond to levodopa or other medications that restore dopamine in the brain.

‘A bit of a puzzle’

“Tremor is a common and often debilitating symptom for [Parkinson’s] patients, but it has always been a bit of a puzzle,” Mendonça said. “We know dopamine is involved, but the way it affects tremor isn’t as direct as with other motor symptoms.”

To better understand the link between tremor and dopamine, the researchers looked at data from 432 patients in the Parkinson’s Progression Markers Initiative, along with 57 additional patients and healthy individuals (controls) from a single hospital in Portugal.

They used DaT-SPECT, an imaging technique that measures dopamine transporter activity in the brain. The caudate binding ratio, a measure of loss of dopamine in the caudate, was higher in patients with tremor. A higher caudate binding ratio also was linked to a greater likelihood of developing tremor.

“This is the first large study to clearly show a link between better-preserved dopamine levels in the caudate and the presence of rest tremor,” said Joaquim Alves da Silva, MD, PhD, head of the foundation’s Neural Circuits Dysfunction Lab and senior author of the study.

In contrast, binding ratio was low in the putamen, another region of the brain involved in Parkinson’s.

“Although patients with rest tremor have lost dopamine-releasing nerve endings in the caudate, they actually have more of these nerve endings preserved compared to patients without tremor,” Alves da Silva said.

Dopamine and Parkinson’s tremor

In the smaller group of patients and controls, the researchers used motion sensors to measure tremor. A specific tremor frequency, 4-6 Hz, was linked to how severe tremor was and could tell patients from healthy individuals. In patients, these measurements were linked to the caudate binding ratio.

“Wearable motion sensors gave us a clearer, more objective measurement of tremor,” said co-first author Pedro Ferreira, a PhD student at Alves da Silva lab. In the study, movement was tracked using wireless sensors placed on the lower back, left arm, and left knee.

“On the surface, patients with and without dopamine loss in the caudate may seem similar,” Ferreira said. “Sensors reveal subtle differences in tremor oscillations that traditional clinical rating scales might miss, and they’re relatively easy to use, allowing us to reliably connect symptoms with what’s happening in the brain.”

In a group of 86 patients from the Champalimaud Clinical Centre, the tremor frequency of 4-6 Hz also differed between those with versus without abnormal DaT-SPECT scans. Computer simulations confirmed that higher caudate binding ratio in patients with tremor could explain why its measurements were linked to dopamine transporter activity in various datasets.

“By focusing on rest tremor in isolation, we are in a better position to pinpoint the specific neural pathways involved,” Alves da Silva said. “Identifying reliable biological correlates for individual symptoms is critical, as it paves the way for more targeted therapies aimed at relieving them.”

Mendonça said, “By identifying the specific neural circuits involved, we hope to clear the mist surrounding the heterogeneity of [Parkinson’s] symptoms and contribute to more precise interventions that can improve the quality of life for those affected by this disease.”