Sleep EEG and presymptomatic Lewy body pathology in Alzheimer´s disease: implications for treatment decisions

Alzheimer`s disease (AD) has different clinical and biological subtypes, which is reflected in the heterogeneity of initial symptom profiles and different trajectories of decline. This clinical heterogeneity is partly due to co-existing pathologies in the brain.

Our study is focused on the definition of non-invasive neurophysiological markers of early presymptomatic comorbidity with Lewy body (LB) pathology in AD patients with either mild cognitive impairment or early dementia and without clinical hallmarks of LB disease.

We shall use conventional and novel quantitative electroencephalography (qEEG) markers established in our previous research during waking state and explore qEEG markers of sleep stages.

It is well-known that LB pathology with an accumulation of pathological protein alpha-synuclein in the brain could cause early disturbances in sleep quality and behaviour, even before key clinical symptoms of the LB pathology are manifest.

The qEEG sleep markers of dual pathology will be validated with established cerebrospinal fluid (CSF) markers of amyloid deposition and neurodegeneration as well as a novel CSF marker of alpha-synuclein accumulation, a hallmark of LB pathology acquired by the RT-QuIC method.

This study contributes to the definition of biological subtypes of patients initially diagnosed with AD which has relevance for a disease prognosis, choice of currently available symptomatic, and selection of patients for upcoming disease-modifying treatments.