Fatigue Linked to Specific Patterns of Brain Degeneration in Parkinson’s Patients, Study Reports

fatigue, brain degeneration

In Parkinson’s disease patients, fatigue is linked to specific patterns of brain degeneration that are not present in individuals of the same age who do not have the condition, a study reports.

Findings of the study, “Structural brain correlates of fatigue in older adults with and without Parkinson’s disease,” were published in the journal NeuroImage: Clinical.

Previous research has shown that more than half of patients with Parkinson’s disease are affected by fatigue, which is one of the most common non-motor symptoms of the disorder and is also frequently found among older individuals without the disease. However, the reason why fatigue is so prevalent among older adults and whether it is linked to Parkinson’s is still unclear.

Because Parkinson’s disease is associated with structural changes in the brain, a group of researchers from the University of Colorado School of Medicine and collaborators set out to investigate if fatigue could be linked to alterations in the brains of Parkinson’s patients, compared with older individuals without the disease.

To study this, the team used a combination of magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) — a technique that measures the diffusion of water molecules in the brain to evaluate white matter integrity — to assess gray and white matter integrity.

Gray matter refers to areas of the central nervous system (brain, brainstem, and cerebellum) made up of neuron cell bodies, whereas white matter refers to areas of the central nervous system made up of myelinated nerve segments (axons) responsible for the transmission of nerve signals and that connect various gray matter areas.

The study involved a total of 60 patients with Parkinson’s — 17 women and 43 men with an average age of 67.58 years and mean disease duration of 5.67 years — and 41 age- and sex-matched healthy individuals used as controls.

Brain imaging data showed that Parkinson’s patients had a significant loss of gray matter volume in the brain’s striatum, a region involved in motor control, and the insula, a region involved in consciousness, emotion and motor control. The reduction in gray matter volume in the brain’s striatum was even more pronounced among patients who were also affected by fatigue.

No significant differences in brain structure were found between healthy controls with and without fatigue. Likewise, no significant differences were found on fractional anisotropy between those with or without fatigue from both groups. Fractional anisotropy reflects the diffusion of a liquid within white matter nerve tracts that connect gray matter areas.

“Fatigue in PD [Parkinson’s disease] is associated with unique [brain] structural changes, … suggesting fatigue in PD is primarily related to PD pathology [disease development], particularly in the dorsal striatum, and not simply a consequence of aging,” the researchers wrote.

“These results suggest that PD-related fatigue is a neurobiologically distinct syndrome and that further research is merited to better understand its phenomenology and pathophysiology with the goal of developing better treatments for this common and debilitating symptom,” they added.

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Genetic Variant Predetermines Risk of Cognitive Decline in Parkinson’s, Research Suggests

genetic variant

Researchers have found that Parkinson’s patients whose cognitive ability is intact, but who have a specific genetic variant, have significantly less gray matter in the regions of their brain that are related to dementia.

The study with that finding, “Reduced gray matter volume in cognitively preserved COMT 158Val/Val Parkinson’s disease patients and its association with cognitive decline,” was published in Brain Imaging and Behavior.

Several mutations in the COMT gene have been associated with the risk of developing Parkinson’s disease. This gene provides instructions for making catechol-O-methyltransferase (COMT), an enzyme that helps break down certain chemical messengers like dopamine.

The most common alteration in the DNA sequence that makes up the COMT gene is the Val158Met mutation in which a valine (Val) is replaced by a methionine (Met) at position 158. Val and Met are both amino acids, also known as the protein’s building blocks.

Every individual has two copies of each gene, one inherited from each parent. Therefore, a person can have two Val’s in the same position at both COMT gene copies (also known as the Val/Val genotype), a Val in one gene and a Met in the other (Val/Met genotype), or two Met’s (Met/Met genotype). Scientists use the word “genotype” to describe a person’s genetic constitution.

Changes in COMT’s molecular structure, lead to high (Val/Val), intermediate (Val/Met) and low (Met/Met) enzymatic activity.

The Val158Met mutation in the COMT gene has been associated with an increased risk of cognitive decline in Parkinson’s disease, particularly in people with greater COMT activity. When this happens, there is too much neurotransmitter degradation, thus leading to reduced levels of dopamine and affecting basic brain functions such as motor coordination and memory.

Evidence suggests a correlation between cognitive impairment, one of Parkinson’s non-motor features, and reduced gray matter volume.

The brain is composed of gray and white matter. The first consists of cell bodies — the control center of neurons — while the latter is made up of nerve cell projections, known as axons or fibers, connecting distinct parts of gray matter.

A Spanish team of researchers used magnetic resonance imaging (MRI), a non-invasive imaging technology, to investigate a possible structural brain compromise in Parkinson’s patients with highly active COMT activity that could explain their increased risk for subsequent cognitive impairment.

The study included 120 newly diagnosed Parkinson’s patients with normal cognition (who were not previously treated for the disease) and 48 healthy controls from the Parkinson’s Progression Markers Initiative database.

Results showed that there was a widespread, significant reduction in cerebral gray matter volume in patients with the Val/Val genotype. They observed alterations in the fronto-subcortical and posterior-cortical brain regions, where motor and cognitive functions originate.

Gray matter volume at some of the identified regions was associated with cognitive decline in a four-year follow-up period, suggesting that gray matter volume reduction during the early stages of disease predisposes Val/Val patients to cognitive impairment.

Nonetheless, gray matter volume analysis at one-year follow-up was not increased in Val/Val subjects, in comparison to Val/Met and Met/Met participants, indicating a somewhat stable atrophy in the Val/Val subset and that those brain changes might already be present prior to diagnosis.

The team believes their research “sparks the need to further characterize the association between a modified COMT enzymatic effect and a structural brain compromise in the early stages of [Parkinson’s disease].”

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