Non-invasive, Wearable Multi-parameter System for the Early Prediction of Cognitive Decline and Dementia in Older Adults

Study Overview
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Brief Summary
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This project develops an innovative screening system and prediction model to detect preclinical symptoms of cognitive impairment and predict the potential development of mild cognitive impairments and dementia in older adults. The earliest possible detection of preclinical symptoms is prerequisite to improve the efficacy of subsequent preventative non-pharmacological, life-style and exercise related, personalized treatment interventions.

Detailed Description
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BACKGROUND: Early detection of preclinical symptoms and prediction of potential development of mild cognitive impairment (MCI) and Alzheimer's disease (AD) could improve non-pharmacologic, life-style and exercise related preventative interventions' efficacy and slow-down disease progression. To achieve this goal, discriminating the earliest preclinical stage of MCI/AD from healthy state would be necessary. However, this is still challenging and current clinical methods are not feasible for preventative screening in larger populations of older adults, as they involve invasive sampling of molecular blood or cerebrospinal fluid biomarkers, as well as expensive brain imaging and extensive neuropsychological testing. Recently, several non-invasive alternative measures, including electroencephalography (EEG), gait analysis, heart rate variability (HRV), and core body temperature (Tc), were shown to be associated with preclinical symptoms of MCI/AD and to predict disease progression. AIM: The investigators aim to combine these measures in a novel non-invasive multi-parameter prediction model, which better reflects multimodal symptomatology compared to currently used methods and, therefore, allows discriminating healthy persons from MCI state with adequate sensitivity (i.e. >80%). METHODS: A cohort of 85 older adults, ≥65 years of age, including healthy persons and patients with MCI, will be recruited. Assessments will be performed at baseline, after 2 months (within these two 2 months one group will follow a cognitive-motor training intervention, while the other serves as passive control), and at 12-month follow-up. Assessments include EEG, gait analysis, HRV, and Tc at rest and during walking, and will be compared to reference measures of MCI status, including neuropsychological tests, to develop the prediction model and evaluate its sensitivity.

Official Title
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Development of an Innovative, Non-invasive, Wearable Multi-parameter System for the Early Prediction of Cognitive Decline and Dementia in Older Adults

Conditions
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Mild Cognitive Impairment, Healthy Aging

Intervention / Treatment
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* Other: Cognitive-motor training


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: participants have to be older than 65 years of age cognitively healthy or diagnosed with MCI able to walk at least 8 minutes for gait analysis, with or without walking aids live independently or in a retirement home (classified 0, 1, or 2 within the Swiss classification system for health-care requirements BESA-levels [German abbreviation for: Bewohner-Einstufungs- und Abrechnungs-System; level 0 meaning the person does not need care or treatment; level 1 to 2 meaning, the person only needs little care or treatment]) sign informed consent Exclusion Criteria: previously diagnosed dementia, e.g. Alzheimer's disease recent head injury judgment by the participant's primary care physician will be required in the case of acute or instable chronic diseases (e.g. stroke, diabetes) and rapidly progressing or terminal illnesses Additional exclusion criteria for the subgroup of 15 participants who would agree to take the telemetric gastrointestinal temperature pill: history of operations and/or disease related to the gastrointestinal tract within last 5 years implanted medical device planned MRI examination nausea, vomiting, constipation or abdominal pain within 1 months prior to the day of planned measurement

Ages Eligible for Study
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Minimum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Screening
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cognitive-motor training<br>Simultaneous cognitive-motor training (i.e. exergame) and strength training | Other: Cognitive-motor training<br>* Simultaneous cognitive-motor training and strength training<br>* Other names: Step Mania;|
| No Intervention: Control<br>Passive control group | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Electroencephalography (EEG) | EEG frequency bands (Hz) will be assessed during 10 minutes at rest in a seated position (5 min eyes closed, 5 min eyes open) and will be recorded using a wearable system covering the frontal, parietal, temporal, and occipital cortex and integrating 20 gel-pad electrode channels. The assessment will be continued during the subsequent gait protocol which consists of 8 minutes of walking back and forth at preferred speed on a 20 m track. | 30 minutes | 
| Gait speed analysis with inertial sensors | The gait protocol consists of 8 minutes of walking back and forth at preferred speed on a 20 m track. Thereby, walking speed (m/s) will be assessed using inertial sensors attached to the feet. | 15 minutes | 
| Gait variability analysis with inertial sensors | The gait protocol consists of 8 minutes of walking back and forth at preferred speed on a 20 m track. Thereby, step length variability (%) and step time variability (%) will be assessed using inertial sensors attached to the feet. | 15 minutes | 
| Heart rate variability (HRV) indices SDNN and RMSSD with two-lead electrocardiogram chest belt | The HRV indices SDNN (ms) and RMSSD (ms) will be assessed during 10 minutes in a seated position, using a two-lead electrocardiogram chest belt. | 10 minutes | 
| Heart rate variability (HRV) index HF power with two-lead electrocardiogram chest belt | The HRV index HF power (ms^2) will be assessed during 10 minutes in a seated position, using a two-lead electrocardiogram chest belt. | 10 minutes | 
| Body temperature (T) with temperature sensors (thermistors) | T will be assessed under controlled climatic conditions (22°C/40% relative humidity) measuring skin T (°C) at the scapula and the the ribs (lateral) using temperature sensors (thermistors) during 10 minutes sitting and 8 minutes walking as described above. | 30 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cognitive performance with neuropsychological tests | Neuropsychological tests will be performed to assess general cognitive performance (Quick Mild Cognitive Impairment screen), episodic memory (associative memory, Face-Name Associative Memory Exam, FNAME-12 test), semantic verbal fluency (category and letter fluency test), and executive functions (Trail Making Tests A/B, Stroop Test). The score of each test will be standardized and added up into a combined score of cognitive performance (z-score). | 1 hour | 
| Core body temperature (Tc) with telemetric gastrointestinal temperature pill | In a subgroup of 15 participants, Tc (°C) will be recorded with a telemetric gastrointestinal temperature pill over a period of 16 hours. | 16 hours |