Asymmetry and Cognitive Function in Parkinson's Disease

Parkinson’s disease typically begins with asymmetric degeneration of dopaminergic neurons, leading to a persistent imbalance in motor symptoms between the left and right sides of the body. This lateralisation extends beyond movement to influence cognitive performance, mood and daily functioning. Patients whose symptoms emerge predominantly on the left side often exhibit greater impairments in executive functions, working memory and anxiety, whereas right-onset cases may demonstrate preserved executive resources but altered motivational or visuospatial processing. Neuroimaging studies reveal that interhemispheric functional connectivity becomes disrupted in regions such as the frontal cortex, basal ganglia and cerebellum, mirroring the pattern of motor asymmetry and correlating with disease severity. Biological factors including sex, uric acid levels and genetic variants further modulate cognitive outcomes, interacting with motor laterality to shape individual trajectories. A deeper understanding of asymmetry in Parkinson’s disease has immediate clinical implications: it enables personalised prognostic counselling, guides targeted cognitive rehabilitation and informs the development of therapies tailored to the more vulnerable hemisphere.

Research from Nature Portfolio

Imbalanced motivated behaviours according to motor sign asymmetry in drug-naïve Parkinson’s disease A cross-sectional study of newly diagnosed, untreated patients examined how the side of motor onset correlates with patterns of motivated behaviour. Using a validated behavioural scale, researchers found that individuals with right-dominant motor signs displayed significantly lower frequencies of approach behaviours—such as nocturnal activity, creative pursuits and excess motivation—than those with left-dominant signs. Avoidance behaviours, including apathy and anxiety, did not differ by side of onset. These findings highlight that motor asymmetry is not only a hallmark of movement dysfunction but also shapes motivational dimensions that may presage cognitive and psychiatric outcomes.

Asymmetry and Cognitive Function in Parkinson's Disease publication trend

The graph below shows the total number of articles in asymmetry and cognitive function in parkinson's disease across all publications each year (not limited to Nature Index journals).

Technical terms

Motor symptom asymmetry: Unequal severity of tremor, rigidity or bradykinesia between the left and right sides of the body.

Hemibody: One lateral half of the body, used to describe side-specific symptom presentation.

Voxel-mirrored homotopic connectivity (VMHC): A neuroimaging measure of synchronous activity between corresponding regions in opposite hemispheres.

Executive function: Higher-order cognitive processes such as working memory, planning and cognitive flexibility.

Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS): A clinical tool for assessing motor and non-motor symptom severity in Parkinson’s disease.

Nigrostriatal pathway: The dopaminergic neural tract linking the substantia nigra to the striatum, critical for motor control and impacted asymmetrically in Parkinson’s disease.

References

1. Imbalanced motivated behaviors according to motor sign asymmetry in drug-naïve Parkinson’s disease. Scientific Reports (2023).
2. Moderating effects of uric acid and sex on cognition and psychiatric symptoms in asymmetric Parkinson’s disease. Biology of Sex Differences (2023).
3. Exploring brain asymmetry in early‐stage Parkinson's disease through functional and structural MRI. CNS Neuroscience & Therapeutics (2024).
4. Side‐of‐onset of Parkinson's disease in relation to neuropsychological measures. Brain and Behavior (2016).