Prodromal Parkinsonian Features in GBA1 Mutation Carriers

Carriers of a variant in the GBA1 gene (GBA carriers) are at the highest risk of developing Parkinson disease (PD). A screening study for prodromal PD features in a cohort of obligatory GBA carriers between 40-75 years was initiated to identify candidates for a PD prevention trial. We added healthy controls and GD patients in order to determine the incidence of prodromal PD and for analyzing the differences between the two groups helping to build a model for identifying at risk PD at the prodromal stage.

Participants preform 15 pre-defined non-invasive tests for prodromal PD and assessment of risk factors. Risk factors for PD included age, sex, type of GBA1 variant, coffee and tea caffeine consumption, smoking habits, exposure to solvents and pesticides, and family history of PD (1st and/or 2nd degree relatives with PD).

Transcranial sonography (TCS) is a useful noninvasive diagnostic tool to detect hyperechogenicity (SN+) of the substantia nigra area in the brain. The hyperechogenicity happens due to increased amounts of iron, reflecting a functional impairment.

Color discrimination was analyzed using The Farnsworth-Munsell 100 hue test. The test includes four boxes with a fixed number of color shade caps with slight shade differences needed to be ordered correctly. The result of each box was entered into a computerized system and automated the total error score (TES)

The shorter version of the UPSIT smell test (The University of Pennsylvania Smell Identification Test) was used to evaluate hyposmia using twelve cards, each with a different smell.

defined as a fall of at least 20 mmHg systolic or at least ten mmHg diastolic blood pressure by 3 min of active standing or head-up tilt

evaluate the cognitive and mental aspects associated with PD. A Montreal Cognitive Assessment (MoCA) score of 26 and above was considered normal

The NeuroTrax computerized battery (www.neurotrax.com) includes seven sections: memory, executive function, attention, information processing speed, visual-spatial, verbal function, and motor skills

self-administered questioner including 21 questions used to screen, diagnose, and measure the severity of depression.

evaluates executive dysfunction

Idiopathic rapid eye movement sleep behavior disorder is an important risk factor in the diagnosis of PD. The REM questionnaire was completed by the participant.

assessing daytime sleepiness includes an eight-question questionnaire scoring between 0 and 24; the higher the score, the higher the chances of dosing off

Perdue pegboard measures the movement of fingers, hands, and arms in 4 different tasks, testing motor abilities and coordination by placing as many pegs and discs on a board in three 30 seconds trials for each subset and three 60 second trials for the assembly subset

measures gross motor function. A score above 6, not including postural and action tremor, was considered abnormal

The Timed Up and Go (iTUG) (EncephaLogTM) is a platform that utilizes smartphones' internal motion sensors for conducting motor evaluation including general walking score, step to step persistency, hand sway and rotation time.

Spontaneous bowel movement frequency was used to define constipation. Urinary and erectile dysfunction were assessed according to the MDS criteria