Cognitive Decline and Neuroanatomical Changes in Parkinson's Disease

Parkinson’s disease (PD) is well characterised by its motor symptoms, yet cognitive decline has emerged as a critical non-motor dimension that profoundly affects quality of life and disease prognosis. Cognitive impairment in PD spans a spectrum from subtle executive-attentional deficits and visuospatial dysfunction in mild cognitive impairment (MCI) to frank dementia, often accompanied by cholinergic and dopaminergic losses. Neuroanatomical substrates underpinning these changes encompass both cortical and subcortical structures. Cortical thinning is most pronounced in temporal, parietal and frontal association areas, reflecting synaptic loss and neuronal apoptosis. Subcortical regions including the hippocampus, thalamus, caudate and putamen undergo volumetric reduction, while white matter tracts may show altered diffusivity long before grey matter atrophy becomes overt. Pathophysiological mechanisms include propagation of α-synuclein pathology, neuroinflammation, mitochondrial dysfunction and synaptic dysregulation. Advances in multimodal imaging—combining structural MRI, diffusion-weighted imaging and functional PET—have enabled the detection of early microstructural changes and hypometabolism that correlate with cognitive trajectories. Genetic and transcriptomic studies further suggest that individual susceptibility to cortical and subcortical degeneration may be influenced by common variants affecting neurodevelopmental and autophagic pathways. Understanding the interplay between evolving neuroanatomical alterations and clinical phenotype is essential for stratifying risk, refining prognostic models and guiding therapeutic interventions aimed at halting or slowing cognitive decline in PD.

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Cognitive Decline and Neuroanatomical Changes in Parkinson's Disease publication trend

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Technical terms

Mild cognitive impairment (MCI): Transitional stage between normal cognition and dementia, characterised by measurable cognitive deficits that do not yet impair daily function.

Cortical thickness: Measure of the distance between the white matter and pial surfaces of the cerebral cortex, used to assess regional atrophy.

Voxel-based morphometry (VBM): Automated neuroimaging technique that compares local concentrations of grey matter across brain scans.

Diffusion-weighted MRI (dMRI): Imaging modality that quantifies the diffusion of water molecules to infer microstructural integrity of white matter.

Morphometric similarity network: Graph-based approach that quantifies structural resemblance between brain regions based on multiple anatomical indices.

References

1. Shared molecular genetic factors influence subcortical brain morphometry and Parkinson’s disease risk. npj Parkinson's Disease (2023).
2. Imaging biomarkers of cortical neurodegeneration underlying cognitive impairment in Parkinson’s disease. European Journal of Nuclear Medicine and Molecular Imaging (2025).
3. Morphometric similarity differences in drug‐naive Parkinson's disease correlate with transcriptomic signatures. CNS Neuroscience & Therapeutics (2024).
4. White matter alterations in Parkinson’s disease with normal cognition precede grey matter atrophy. PLOS ONE (2018).
5. Subcortical Atrophy Is Associated with Cognitive Impairment in Mild Parkinson Disease: A Combined Investigation of Volumetric Changes, Cortical Thickness, and Vertex-Based Shape Analysis. American Journal of Neuroradiology (2014).
6. Patterns of cortical thinning in nondemented Parkinson's disease patients. Movement Disorders (2016).