Connectome-based brain fingerprints predict early cognitive decline in Parkinson’s patients with minor hallucinations

Individual variability in connectome organization offers a unique framework for capturing patient-specific alterations and advancing personalized models in medicine. Minor hallucinations (MH) affect up to 40% of Parkinson’s disease (PD) patients and are early indicators of cognitive decline and dementia, hence crucial for early intervention. While previous studies focused on group-level differences, connectome-based brain fingerprinting enables deeper, individualized analysis of neural change. Applying this approach to PD patients with and without MH using resting-state fMRI, we show that each patient exhibited unique brain fingerprint, revealing rich quantifiable personalized features with medical relevance. MH-patients showed a loss of subject-specific features in brain networks linked to cognitive health, while somatosensory regions – typically less distinctive – became more prominent, emphasizing their role in MH pathogenesis. These differences enabled to identify – in an entirely data driven manner – patient-specific networks linked to early subclinical cognitive alterations, as well differential spatial fingerprinting organization linked to cortical densities of neurotransmitters. These findings reveal a distinct, patient-specific connectomic signature that differentiates PD patients with MH, uncovering early neural markers for precision medicine in PD.