Visual dysfunction and its underlying brain changes can identify Parkinson’s disease patients at higher risk of cognitive decline, who might benefit most from future clinical trials, according to two new studies.
The studies, “Organisational and neuromodulatory underpinnings of structural-functional connectivity decoupling in patients with Parkinson’s disease” and “Visual Dysfunction Predicts Cognitive Impairment and White Matter Degeneration in Parkinson’s Disease,” were published in the journals Communications Biology and Movement Disorders, respectively.
Parkinson’s features both visual dysfunction and cognitive decline, but the relationship between those two aspects has been poorly understood, as they affect individuals differently.
In a pair of studies, scientists from University College London, in the U.K., found that visual dysfunction predicts which Parkinson’s patients will more likely experience cognitive decline and how changes in the brain’s wiring relate to this decline.
In one study, the researchers performed magnetic resonance imaging (MRI) and clinical assessments in 77 Parkinson’s patients and 25 healthy individuals used as controls. Among Parkinson’s patients, 22 were classified as having low visual function and 55 as having intact vision, while 13 were classified as having mild cognitive impairment and 51 as having normal cognition.
Parkinson’s patients who were classified as having visual dysfunction showed worse cognitive performance and were more likely to develop mild cognitive impairment than those with normal vision.
Poor visual function accompanied the loss of white matter over time, suggesting that a simple vision test might indicate which individuals are at higher risk for cognitive decline. White matter is the brain tissue composed mainly of nerve fibers that coordinates communication between different regions of the brain.
In their next study, the team investigated the structural and functional brain changes underlying visual impairment, using cutting-edge neuroimaging techniques.
They identified 88 Parkinson’s patients, classifying 33 of them as low visual performers and 55 as high visual performers, based on computerized tests that correlate visual tasks with cognitive decline. Low visual performers in these tests tended to have a higher risk of dementia.
Strong physical — or structural — connections between brain regions normally correlate with functional connections in the healthy brain. Essentially, the more neural connections there are between two regions, the more those regions work together.
The study found that an increasing loss of these connections led to the regions decoupling, becoming less functionally related to each other. This decoupling appeared to associate with worse outcomes.
While the overall brain connectivity pattern showed more decoupling in Parkinson’s brains, relative to those of controls, low and high visual performers also showed key differences.
Low visual performers showed more focal — less widespread — decoupling than high visual performers, particularly in regions related to memory and in the temporal lobe, which supports memory, information processing, and aspects of visual perceptions, among others.
Another major difference between low and high performers occurred in the activity of receptors for certain neurotransmitters — chemicals used by neurons to relay information.
Dopamine is the neurotransmitter most associated with Parkinson’s, as the loss of dopamine-producing neurons is one of the disorder’s defining features.
In addition to dopamine receptors, the investigators observed changes in certain receptors for serotonin, acetylcholine, and noradrenaline, with noticeably different activity in low versus high visual performers.
Decoupling in low visual performers appeared particularly pronounced in regions with less of a noradrenaline receptor called ADRA2. Slight changes in the DNA sequence of the ADRA2 gene has been identified in a study linking genetic changes to Parkinson’s, according to the researchers.
The combined results of the studies suggest that a vision test might identify those Parkinson’s patients most at risk for imminent cognitive decline and provide a set of potential therapeutic targets — the neurotransmitter receptors — for future clinical trials.
“Our findings could be valuable for clinical trials, by showing that vision tests can help us identify who we should be targeting for trials of new drugs that might be able to slow Parkinson’s,” Rimona Weil, MD, the senior author of both studies, said in a university press release. “And ultimately if effective treatments are found, then these simple tests may help us identify who will benefit from which treatments.”
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