VisMemoPD Protocol: an Observational Pilot Study on Spatial and Topographical Memory in Patients With Parkinson's Disease and Parkinsonism

Parkinson's disease is a chronic neurodegenerative condition characterized by both motor and non-motor symptoms. Among non-motor manifestations, cognitive decline is common and heterogeneous and may occur already in the early stages of the disease. VISMEMO-PD was developed as part of a broader research framework aimed at identifying neuropsychological markers capable of predicting disease progression and the risk of conversion to Parkinson's disease dementia through targeted clinical protocols.

The present study focuses on the assessment of visuospatial memory in reaching space and topographical memory in navigational space. The theoretical rationale underlying the protocol is based on the hypothesis that the execution of sequences in navigational space may be impaired before the execution of sequences in reaching space. This would suggest that topographical memory impairment may represent an early marker of disease progression.

The study will compare performance across four groups: patients with mild Parkinson's disease, patients with moderate-advanced Parkinson's disease, patients with Parkinsonism, and healthy participants. The Corsi Block-tapping Test will be used to assess visuospatial memory in reaching space. The Walking Corsi Test, a walking adaptation of the Corsi Block-tapping Test, will be used to assess navigational memory in extrapersonal space. During the Walking Corsi Test, participants will reproduce spatial sequences by actively moving through the testing environment.

The protocol will also investigate the association between topographical memory deficits and walking motor patterns. Gait-related parameters will be recorded using wearable inertial sensors from the MOVIT system, consisting of a triaxial accelerometer, a magnetic sensor, and a triaxial gyroscope. These measures will allow the objective recording of movement-related parameters during task execution.

In addition, visual exploration strategies during visuospatial and topographical memory tasks will be assessed using a wearable Pupil Labs eye-tracking system. Eye-tracking data will be used to quantify gaze behavior, including fixation-related parameters, saccadic exploration, gaze transitions between relevant spatial targets, and visual scanning patterns. The integration of eye-tracking measures with cognitive performance and gait-related parameters is expected to provide a more comprehensive description of the visuocognitive and visuomotor mechanisms involved in spatial and topographical memory impairment in Parkinson's disease and Parkinsonism.

The study will include baseline assessment and follow-up evaluations at 12 and 24 months. Repeated assessments will allow the investigation of temporal trajectories of cognitive decline and may contribute to the development of predictive models capable of identifying patients at greater risk of conversion to dementia. The integration of longitudinal cognitive, motor, and visual exploration data may ultimately contribute to the definition of multidimensional biomarkers of disease progression.

Inclusion criteria

• Male and female subjects aged between 35 and 80 years;
• Diagnosis of Parkinson's disease according to the United Kingdom (UK) Parkinson's Disease Society Brain Bank criteria;
• Diagnosis of primary atypical parkinsonism MSA-P, according to the Second Consensus Statement on the Diagnosis of Multiple System Atrophy;
• Diagnosis of primary atypical parkinsonism PSP-P, according to the Movement Disorder Society criteria for Progressive Supranuclear Palsy;
• Modified Hoehn and Yahr stage between 1 and 3 during the "ON" phase (Hoehn and Yahr, 1967);
• Cognitive screening with the Montreal Cognitive Assessment (MoCA) score > 17;
• Mini-Mental State Examination (MMSE) score ≥ 24 (Folstein et al., 1975);
• Ability to walk independently for 10 meters without assistive devices;
• Ability to understand and sign the informed consent form;
• Ability to comply with study procedures.

Exclusion criteria

• Diagnosis of neurological disorders other than Multiple System Atrophy (MSA) and Parkinson's disease;
• Depressive disorders or Beck Depression Inventory-II (BDI-II) score > 20;
• Musculoskeletal disorders that could impair gait performance.

The study will enroll 20 healthy subjects, matched by age and sex with patients affected by Parkinson's disease (PD) and atypical parkinsonism who will be recruited into the study.

The same inclusion criteria will be applied to both groups of patients with Multiple System Atrophy (MSA) and Parkinson's disease.

The exclusion criteria will be:

• Diagnosis of neurological disorders;
• Depressive disorders or Beck Depression Inventory-II (BDI-II) score > 20;
• Musculoskeletal disorders that could impair gait performance.