Narrative review synthesizing animal and clinical evidence to map molecular mechanisms of memory impairment in Parkinson's disease, emphasizing dopamine depletion, alpha-synuclein pathology, neuroinflammation, oxidative stress, cholinergic dysfunction, impaired synaptic plasticity, cortical…

Useful for therapeutic discovery because it consolidates multiple actionable target areas (inflammation, alpha‑synuclein, cholinergic and synaptic mechanisms, gut–brain interactions) to guide prioritization and repurposing, though its narrative review format and lack of novel data limit immediate…

BACKGROUND AND AIM: Parkinson's disease (PD) is primarily known for its motor symptoms but is increasingly recognized for its substantial cognitive effects, particularly on memory. This narrative review aims to clarify the complex molecular mechanisms contributing to memory impairment in PD by integrating findings from both animal and clinical research. METHODS: This study is a narrative review synthesizing data from existing literature. It begins by addressing the prevalence of cognitive deficits among PD patients. It then explores animal studies investigating pathophysiological changes associated with PD, focusing on the impact of dopaminergic depletion on neural circuitry. These findings are integrated with clinical research to identify specific molecular changes closely associated with memory impairment independent of motor dysfunction. RESULTS: The review systematically examines key molecular mechanisms contributing to memory deficits in PD. These mechanisms include disruptions in neural circuits, dopamine depletion, neuroinflammation, oxidative stress, and alpha-synuclein pathology. Additional contributing factors identified include cholinergic system dysfunction, cortical thinning and atrophy, disrupted neural oscillations, gut-brain axis dysfunction, impaired synaptic plasticity, and alterations in neurotransmitter systems. The analysis illustrates how these factors collectively undermine cognitive function. CONCLUSION: By synthesizing insights from various studies, this narrative review offers a comprehensive perspective on the intricate molecular pathogenesis of memory impairment in PD. It underscores the necessity of addressing both motor and non-motor symptoms in managing PD effectively and advocates for a holistic treatment approach that considers cognitive decline alongside traditional motor symptom management.