Application of LLM Care and Related Affective Computing Systems on People With Parkinson's Disease (pdLLM)

Application of Cognitive and Physical Training (LLM Care) and Related Affective Computing Systems on People With Parkinson's Disease (Movement Disorders)

The study is an adaptation of the Long Lasting Memories (LLM) (NCT02267499) and the subsequent LLM Care (NCT02313935) projects in patients with Parkinson's Disease (PD). The study aims to examine the viability and any potential benefits of cognitive and physical training, as offered via the ICT-based (non-pharmacological) intervention of LLM Care, on people with PD. It is worth investigating whether this intervention can offer a better quality of life in patients with PD and counterbalance the often associated with the PD disease neurodegeneration. To evaluate any physical, cognitive, behavioral, and neuroplastic changes and measure the influence (affective status of participant) of the training on the pathological population, the study utilizes somatometric and neuropsychological assessments and neuroscientific (electroencephalographic, EEG-related) indices, as well as affective computing systems.

Parkinson's Disease (PD) is a highly prevalent chronic neurodegenerative disease of the central nervous system, with both motor and non-motor symptoms, having a high impact on the quality of life of the patients. There is still no cure available for individuals with PD but only pharmaceutical treatments that manage the symptoms, thus non-pharmaceutical treatments such as physical and cognitive training are of great importance. This study aims to evaluate the benefits of the LLM Care (NCT02313935) Integrated Healthcare System (https://www.llmcare.gr/en/home/), which is a successful example of commercializing the LLM (NCT02267499) research program (http://www.longlastingmemories.eu/), in patients with PD. The LLM Care (non-pharmaceutical) intervention is an integrated training system that targets nondemented and demented aging population and adopts an approach of cognitive and physical training to improve the quality of life and prolong the functionality of the elders. The physical training (PT) component of the LLM, WebFitForAll, was developed by the research team of the Medical Physics Laboratory, Department of Medicine, Aristotle University of Thessaloniki. WebFitForAll is an effective physical platform that strengthens the body and enhances aerobic capacity, flexibility, and balance. The cognitive training (CT) component of the LLM is a Greek adaptation of the BrainHQ online interactive environment, and comprises six categories with 29 brain exercises with hundred levels of difficulty. The exercises focus on attention, memory, brain speed, people skills, navigation, and intelligence. The target population is PD patients which were classified according to their cognitive state as PD-cognitively normal (PD-CN) and PD-mild cognitive impairment (PD-MCI). Both PD-CN and PD-MCI followed similar training schemes of the intervention, two times per week for one hour for a total of 10 weeks (aiming at 20 sessions/individual). Specifically, the patients were categorized as follows: (i) LLM training group, where participants attended a training protocol consisting of pseudo-randomized physical and cognitive exercises (30 minutes of cognitive and 30 minutes of physical training), (ii) physical training group, whereas participants underwent only physical training (one hour of physical training), and (iii) cognitive training group, in which participants performed cognitive tasks (one hour of cognitive training). The main goal of this study is to quantify the effects of implementing the LLM Care intervention on patients with PD, determine any benefits in physical status, cognition, behavior, and brain function, and eventually assess if adopting a cognitively and physically stimulating lifestyle can offer a better quality of life in this pathological group. All of the patients were evaluated at baseline (pre) and exit (post) via EEG measures and a battery of routinely used clinical and neuropsychological tests. Additionally, the training platform utilizes affective computing systems to evaluate the affective status of all participants throughout the training and to establish a pleasant learning environment for all participants.

LLM Care training Participants use the webFitForAll exergaming computer platform as the physical training component (PT); Participants use the language adapted version of the BrainHQ Program as the cognitive training component (CT)

Physical training only. Participants use the webFitForAll exergaming computer platform as the physical training component (PT).

Cognitive training only. Participants use the language adapted Version of the BrainHQ Program as the cognitive training component (CT).

PT training participants use the webFitForAll exergaming computer platform as the physical training component (PT)

CT training participants use the language adapted version of the BrainHQ program as the cognitive training component (CT)

Change is defined as statistical significance in the t-test comparison of the current density strength as reconstructed via Low Resolution Electromagnetic Tomography (LORETA) algorithm on the basis of high-density EEG recordings before compared to after the training.

Changes in the cortical connectivity caused via the training. Change is defined as statistical significance in the t-test comparison of the Phase Transfer Entropy (PTE) estimated from the cortical activity, as reconstructed via Low Resolution Electromagnetic Tomography (LORETA) algorithm on the basis of high-density EEG recordings, before compared to after the training.

Changes in the global and local graph theoretical indexes of the brain networks caused via the training. Change is defined as statistically significance in the t-test comparison of the graph theory indexes, before compared to after the training.

Change in walking speed as measured via the 10 Meter Walk test (Walking Speed m/s; Household Ambulator: <0.40 m/s; Limited Community Ambulator: 0.40 to <0.80 m/s; Community Ambulator: ≥0.80 m/s)

Change in gait and balance, and fall risk as measured via the Tinetti POMA (scale: 0-28; gait is scored over 12; balance is scored over 16; perfect: 28; the lower the score on the Tinetti test, the higher the risk of falling; High risk of fall: ≤ 18; Moderate risk of fall: 19-23; Low risk of fall≥ 24)

Change in Fitness. Change in aerobic fitness, strength, and flexibility as measured via the Fullerton Senior Fitness Test (SFT)

PDQ-8: activities of daily living, attention and working memory, communication, depression, quality of life, and social relationships in persons with Parkinson's Disease, scale: 0-100 (0: good health, 100: poor health)

GDS: depressive symptoms, scale: 0-15 (normal: 0-5; mild depression: 5-8; moderate depression: 9-11; severe depression: 12-15)

Change in physical function as measured via the Short Physical Performance Battery (SPPB, scale from 0 to 12, perfect 12)

Change in cognitive function as measured via the Montreal Cognitive Assessment (MOCA, scale: 0-30; perfect: 30; normal: ≥26)

Inclusion Criteria: Age 50 years and older Native level speakers of the Greek language Able to commit for the required intervention time No significant mobility problems (upper or lower limbs) Normal or corrected to normal visual and auditory acuity In case of any chronic diseases, such as hypertension, diabetes, etc., there should be advice from the competent doctor No serious cardiovascular problems Mild physical activity supervised by a physician Stable medication so as not to affect the patient's functionality from Parkinson's motor symptoms (e.g., stiffness, dyskinesia, restlessness, gait disorder and instability, etc.) Exclusion Criteria: History of serious neurological diseases or psychiatric illness Recent (within 6 months) history of stroke, transient ischemic stroke episode, traumatic brain injury, ALS, multiple sclerosis Substance abuse Use of acetylcholinesterase inhibitor is not excluded, as long as its use has started 4 months before joining the study, and is stable during its course study remains constant Significant communication disorders Simultaneous enrolment in other studies Patients suspected of not being able or willing to cooperate or comply with study protocol requirements Statin users may be excluded unless during the study the use is constant Patients diagnosed in stages 4 and 5 of the disease, or have undergone surgical treatment

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