neuroSHARE

The neuroSHARE project in the 10th wave of SHARE

The tenth wave of the SHARE project will focus on collecting neuromarkers in the neuroSHARE project, consisting of a smell test, speech test, and questionnaire on REM sleep quality, in collaboration with the First Faculty of Medicine of Charles University and the Czech Technical University in Prague.

Three short tests will be conducted immediately after the main questionnaire is completed. Speech, smell, and sleep disorders are important early markers for Parkinson’s and Alzheimer’s diseases, as well as depression. This is a unique project being tested for the first time on a large population sample. The aim of the project is the early diagnosis of these diseases, their timely treatment, and the prolongation of quality of life.

In the eleventh wave, we plan to collect even more comprehensive objective data, known as biomarkers. This project will be carried out in collaboration with the large RECETOX research infrastructure at Masaryk University in Brno.

neuroSHARE - Measurement of Neurodegenerative Diseases in SHARE Survey

Speech, olfactory (smell) and sleep dysfunctions belong among the earliest and most important signs of neurodegenerative diseases and depression. In Parkinson’s and Alzheimer’s disease, decreased sense of smell precedes the occurrence of motor and cognitive symptoms by years or even decades. Similarly, prosodic changes of speech are evident already in the prodromal stages of both diseases. Finally, the strongest risk factor for dementia or later development of Parkinson’s disease is REM Sleep Behavior Disorder.

This project will implement the olfactory and speech tests on the sample of Czech respondents in the SHARE (Survey of Health, Ageing, and Retirement in Europe) project, the largest representative panel study of the population aged 50+. The measurements will take place in wave 10 (2024-2025) in the Czech Republic (4,000 respondents). The sleep disorder will be captured by a short validated questionnaire. Respondents with abnormal test results will be invited for medical examination.

The project is financed by the LM and LX grants from the Ministry of Education, Youth and Sports of the Czech Republic. The finances are allocated for years 2024-2025 corresponding to wave 10 of the SHARE project. These finances are grant and project specific and cannot be used for other purposes and cannot be transferred to subsequent years.

Together, these tests will provide very robust biomarkers of neurodegeneration scalable to larger populations. All tests are inexpensive, noninvasive, and can be performed and assessed repeatedly. The project will be their first implementation on a large, representative sample of respondents and will provide unique insights and opportunities for early diagnosis and treatment in the ageing European population. The output will be open-access data available to all registered users of SHARE. The methodology will be piloted in wave 10 in the Czech Republic and later used in other countries in Wave 11 in the SHARE HCAP2 project.

Novel Biomarkers for Early Detection of Neurodegenerative Diseases

Introduction

Speech, olfactory (smell) and sleep dysfunctions belong among the earliest and most important signs of neurodegenerative diseases. In Parkinson’s disease (PD) and Alzheimer’s disease (AD), decreased sense of smell precedes the occurrence of motor and cognitive symptoms by years or even decades. Similarly, prosodic and/or linguistic changes of speech are evident already in the prodromal stages of both diseases. Finally, the strongest risk factor for the development of PD and dementia with Lewy bodies is rapid eye movement (REM) Sleep Behavior Disorder (RBD). Thus, patients with isolated RBD represent a special case of prodromal alpha-synucleinopathy with a very high rate of conversion to a manifest neurodegenerative disorder. However, while sensitive screening tests for speech, olfactory, and sleep dysfunction are available, they often lack specificity when administered individually.

An intriguing novel approach for early, accessible detection of neurodegeneration involves analyzing altered speech and smell patterns in combination. These methods are non-invasive, inexpensive and easy to administer, even from subject’s home, making them practical for screening large populations for early signs of neurodegeneration. Speech is highly susceptible to neurodegeneration, providing a window into brain health. It reflects cognitive-linguistic and motor-execution performance but also mood and emotions via facial expression, which are all affected by neurodegeneration. Olfactory dysfunction, such as impaired odor identification and detection, often appears years before other symptoms. The brain areas responsible for processing smell, including the olfactory bulb, entorhinal cortex and hippocampus, are also some of the first regions affected by alpha-synuclein-related and Alzheimer’s-related pathology, respectively. Studies have shown that people with reduced olfactory abilities are at a higher risk of developing cognitive impairment, AD, and PD.

The largest multinational multilanguage trial performed by our team in a large sample of subjects with isolated RBD and early-stage PD showed that speech impairment severity assessed via acoustic analysis was progressive in both PD and RBD over one-year follow-up (Rusz et al. 2021). Subsequently, dysprosodic speech disorder was found in isolated RBD subjects with impaired olfactory function before the nigrostriatal dopaminergic transmission was affected (Rusz et al. 2022), indicating speech disorder as one of the earliest signs of PD occurring already in the Braak stage 2. Similar findings related to changes in prosody have been observed across variety of neuropsychiatric disorders including AD, other dementias, schizophrenia and other diseases (Rusz et al. 2024).

In addition, impaired facial expression is commonly observed in majority of neurodegenerative diseases such as AD and PD. Altered facial expression is one of the earliest distinct motor manifestations of PD (Fereshtehnejad et al. 2017). We recently showed that automatic video-based analysis of facial expression might detect PD early (Novotny et al. 2022).

The investigation of language function, a core cognitive domain in mild cognitive impairment, might provide valuable information about phenoconversion to dementia (Boschi et al. 2017). Indeed, objectively derived linguistic features of spontaneous speech were able to detect preclinical stages of dementia (Beltrami et al. 2018). The high clinical relevance of natural language and speech assessment has been recently demonstrated by our team in patients with isolated RBD. This trial showed for the first time that language screening is able to identify and distinguish patients who will later develop dementia or parkinsonism (Subert et al. 2024). In particular, language abnormalities were strong predictors of dementia with the highest hazard ratio reported in literature so far (approximately 100). These results were based only two minutes of spontaneous speech, thereby strongly supporting linguistic measures as ideal candidate markers to be employed in selecting patients for screening and future neuroprotective trials.

neuroSHARE Project Protocol

The combination of a standard olfactory test, a specially designed innovative speech test, and the REM Sleep Behavior Disorder Screening Questionnaire (RBDSQ) are currently tested in the pilot study of neuroSHARE in Wave 10 (2024-2025) in the Czech Republic with 4,000 respondents in the Survey of Health, Ageing, and Retirement in Europe, the largest representative panel study of the population aged 50+. Respondents with abnormal test results will be invited for an expert medical examination. The open-access data available to all registered SHARE users.

  • Fieldwork Procedures: The neuroSHARE project is introduced to all panel and refresher respondents immediately after the completion of the main interview. Respondents are asked to provide their consent with testing and the medical examination.

  • The speech test is administered by an application on the interviewer’s computer with attached microphone. There are five tasks in the speech test: prolonged phonation, repeated syllable, reading a text, retelling of a fairy tale, and a monologue. The test is language-independent. The recorded wav files are analyzed into several parameters representing key motor and cognitive speech abnormalities such as monopitch, monoloudness, harshness, impaired timing, content richness, vocabulary range, sentence development and others.

  • The smell test is a standard olfactory assessment, previously used in HCAP and HRS, involving Sniffin’ sticks test to measure both smell identification and olfactory threshold. The sleep test - RBDSQ - is an internationally validated self-administered questionnaire. The neuroSHARE questionnaire also contains additional questions related to factors that may influence speech, smell and sleep. The total duration is about 25-30 minutes.

  • Harmonization and data delivery: Smell test is harmonized with the HRS and ELSA smell tests. Data are delivered for merging to the SHARE panel data with full documentation. Transfer, analysis, and storage of audio files and other data materials comply with GDPR requirements.

  • Medical examination: Respondents with abnormal findings (around 5 percent of respondents) in smell and speech test and abnormal RBDSQ score will be invited for an expert medical examination and validation at the Department of Neurology, First Faculty of Medicine, Charles University.

  • The neuroSHARE project: is the first implementation of these tests on a large, representative sample of respondents and provides unique insights and opportunities for early diagnosis and treatment in the ageing European population. Based on the pilot study results, additional measurements might be investigated (potential long-term neuropsychiatric burden associated with depression and olfactory dysfunctions related to the Covid-19 pandemic).

  • Coordination and research team: SHARE-CZ (Radim Bohacek), First Faculty of Medicine at Charles University (Petr Dusek), Czech Technical University (Jan Rusz, Tereza Tejkalova, Vojtech Illner, Tomas Kouba).

  • Central coordination is administered by the SHARE-ERIC and the SHARE Berlin Institute. The neuroSHARE project has obtained all required approval from the Ethical Committee at the First Faculty of Medicine of Charles University. It has been supported by SHARE-ERIC Management Board, the SHARE-ERIC Scientific Monitoring Board and its chair Arie Kapteyn (USC), and the SHARE-ERIC Director, Prof. David Richter.

  • neuroSHARE in Switzerland: The methodology will be shared with other countries in the SHARE project, first with the Swiss team of SHARE-CH at the University of Lausanne in Wave 11.

For more details, see: