Novel ways of preventing age-related cognitive decline: Identifying the role of speech processing deficits in Alzheimer’s disease

Responsible: Dr. Nathalie Giroud
Duration of the project: September 1st 2020 – August 31st 2025

Project Description:

The Alzheimer’s dementia (AD) prevalence in Switzerland is expected to double in the next 20 years. A novel and promising way to approach this problem is to identify modifiable risk factors which may delay the onset of AD for individuals at-risk such as those with mild cognitive impairment (MCI) and subjective cognitive impairment (SCI) or delay the progression in already affected older adults. Hearing loss (HL) has been estimated to be the modifiable risk factor with the highest potential impact on risk reduction, if treated properly. However, current approaches to assess and treat HL mainly target peripheral HL (pHL), an age-related decline of the inner ear functions, while next to nothing is known about how to characterize and treat central HL (cHL), an age-related decline of auditory circuits of the brain leading to speech perception deficits. Yet, speech perception deficits have been shown to lead to communication problems, social isolation, and higher rates of depressive symptoms among others, all risk factors for cognitive decline in aging. Furthermore, traditional screening tools for pHL and cHL often require the tested individuals to have intact cognitive functioning (e.g. behavioral tasks are used to assess speech-in-noise perception performance) and may therefore not be appropriate for individuals at-risk of cognitive decline or individuals affected by AD because of the potential confound by their impaired cognitive functioning.


This research project will fill these gaps and will be the first to address the following research questions: 1) To what extent is cHL (i.e. speech perception deficits) prevalent in SCI, MCI and AD and which hierarchical stages of neural speech perception (from early auditory brainstem processes to speech perception in cortical auditory circuits to different stages of higher-level linguistic integration) are impaired in these groups? 2) How can we assess these different stages of speech perception using neuroimaging without relying on behavioral performance of the tested individuals, which is likely to be confounded by their cognitive abilities? 3) To what extent is treated and untreated pHL interacting with cHL in these individuals and how does pHL-treatment, cognitive capacity, proper or disrupted speech signals (bottom-up) and different levels of linguistic predictability (top-down) influence speech processing at different hierarchical stages? To address these questions optimally this project will develop novel neuroimaging protocols based on the powerful approach of concurrent hierarchical tracking (CHT) disentangling neural responses evoked specifically by distinct acoustic/linguistic processing levels along the auditory and language pathways in the brain. In a large sample of older individuals (65-80 years) with varying degree of pHL who are healthy, at-risk of cognitive decline (i.e. SCI, MCI), or affected by AD, magnetoencephalography (MEG), electroencephalography (EEG) and auditory brainstem responses (ABR) will be recorded while participants are presented with (un)predictable, (un)chopped, foreign, and proper continuous speech allowing to systematically characterize the interplay between pHL, cHL, cognitive decline, and bottom-up and top-down driven speech perception mechanisms at different hierarchical stages. Furthermore, all participants will undergo comprehensive demographic, neuropsychological, and audiological screening as well as cognitive and speech perception testing in order to assess their cognitive capacities as well as speech perception abilities. Moreover, the in-depth analysis of neuroimaging data of an existing large longitudinal dataset will be included into this research program to address specific questions about the impact of HL on brain structural integrity in SCI, MCI, and dementia patients.


In sum, this research will be the first to comprehensively describe the neural link between speech perception deficits and cognitive decline in older adults by applying novel neuroimaging techniques. The results of this research will provide the basis to outline new ways for improved, early, and efficient AD-risk screening and consequently delay the onset or progression of the disease in SCI and MCI patients by avoiding increasing risks. Moreover, it will contribute to basic science and advancement in a number of academic and clinical disciplines such as Alzheimer’s research, audiology, neuroimaging, and cognitive aging, and brain and language.

Partners:

Funding source(s): Swiss National Science Foundation, PRIMA grant, Nr. PR00P1_185715

Within CL: Prof. Dr. Volker Dellwo. Dr. Sandra Schwab, Dr. Elisa Pellegrino;

Outside CL: Clinic for Geriatric Psychiatry at Psychiatric University Hospital Zurich, Department of Psychology at the University of Zurich, Zurich Center for Linguistics at University of Zurich, Center for the Interdisciplinary Study of Language Evolution (ISLE) at University of Zurich, Department of Auditory Neuroscience Institute of Experimental Medicine of the CAS (Czech Republic), Department of Psychology at Concordia University & Canadian Consortium on Neurodegeneration in Aging (Canada), Gonda Multidisciplinary Brain Research Center at Bar Ilan University (Israel) and Industrial partners (Dr. Ulrike Lemke from Sonova and Edith Egloff from Pro Audito)