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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
SCREENING
Masking
NONE
Enrollment
82
Simultaneous cognitive-motor training and strength training
Empa
Sankt Gallen, Canton of St. Gallen, Switzerland
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 30 minutes
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).
Time frame: 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.
Time frame: 16 hours
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