Narrative Review of Body-First Versus Brain-First Prodromal Neuropsychiatric Symptoms in Parkinson's Disease.

Research overview

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Parkinson's disease (PD) is a multisystem neurodegenerative disorder in which nonmotor symptoms often precede classical motor manifestations by years. Neuropsychiatric symptoms such as REM sleep behavior disorder (RBD), depression, anxiety, apathy, and mild cognitive impairment are increasingly recognized as clinically meaningful prodromal features, yet they remain underrecognized in routine practice. This narrative review summarizes literature identified through PubMed, Scopus, and Google Scholar between 2003 and 2025 using terms related to PD, prodromal symptoms, neuropsychiatric symptoms, alpha-synuclein, and body-first versus brain-first disease. Priority was given to review articles, original studies, clinical trials, Movement Disorder Society prodromal criteria, and foundational neuropathological models. Current evidence supports a dual pathway model of PD progression. In the body-first phenotype, pathology may begin in the peripheral autonomic or enteric nervous system and ascend through the brainstem, where RBD and autonomic dysfunction are prominent early markers. In the brain-first phenotype, pathology is proposed to arise in olfactory or limbic regions, where hyposmia, anxiety, and depression may precede motor disease. Prodromal neuropsychiatric symptoms are among the earliest clinically detectable features of PD. Interpreting these symptoms within the body first versus brain first framework may improve risk stratification, earlier recognition, and selection of candidates for biomarker-driven and disease-modifying studies.

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