Nicolaus Copernicus University in Torun Collegium Medicum in Bydgoszcz Poland

1. Nicolaus CopernicusUniversityinTorun Collegium Medicumin Bydgoszcz Poland Oliwia McFarlane, PhDinMedicine Bloodbiomarkers of an earlycognitivedecline

2. Dementia • Dementia affects about 46 million people globally; about 10% develop the disorder at some point in life • The most prevalent dementia cause - Alzheimer’s Disease - is characterized by nearly 20-year clinically silent course • Due to brain plasticity, the process of neuronal cell loss remains unnoticed • First symptoms occur when the loss of neurons exceeds 50% • There is no known cure for dementia

3. Together with development of new pharmaceutical interventions, as well as introducing the concept of the initial phase of dementia, the demand for early diagnosis has been growing • Biological markers, which allow a diagnosis establishment at the early stages of the disease, especially ones that can be assayed in blood, are much needed • Research on potential plasma biomarkers have provided ambiguous results thoughout

4. Aim of the study Finding and describing the correlations between candidate plasma biomarkers of an early neurodegeneration: 24(S)-hydroxycholesterol, amyloid beta 42, and ubiquitin with cognitive functioning of the elderly

5. Material and methods Retrospective use of data and biological material (plasma) derived from the Polish national study on the elderly, implemented in Poland from 2007 to 2011: „PolSenior: Medical, psychological, sociological and economical aspects of aging in Poland”.

6. Study sample • The study sample consisted of 230 participants, 109 women, and 121 men aged 65 plus The analysis was conducted in 3 age groups: • 65 – 74; • 75 – 84; • 85 + The analysis was conducted in 3 groups of cognitive performance, divided with the Mini-Mental State Examination (MMSE). • cognitively normal, • mild cognitive impairment(MCI), • milddementia

7. Study sample Exclusion criteria: • Intake of statins, • Depression, • Moderate and severe dementia, • Brain stroke, • Acute illness, • Other conditions that can impact cognitive performance

8. Methods Three candidate plasma biomarkers: 24(S)-hydroxycholesterol, amyloid beta 42, andubiquitin were assayed and assessedaccording to cognitive performance level, gender, and age

9. Results: Candidate plasma biomarkers and cognitive functioning No statistically significant differences between concentrations of 24(S)-hydroxycholesterol, amyloid-β 42, andubiquitin and cognitive functioning

11. Results: Candidate plasma biomarkers and age/gender No statistically significant correlations between concentrations of 24(S)-hydroxycholesterol, amyloid-β 42, ubiquitin and age were found. No statistically significant differences between concentrations of 24(S)-hydroxycholesterol, amyloid β 42 and gender were found. Statistically significant higher level of ubiquitin in women than in men (p=0,032) were identified.

12. Results: Correlations between candidate plasma biomarkers Weak negative correlations between plasma levels of ubiquitin and 24(S)-hydroxycholesterol (r=-0,18; p=0,011) and between plasma levels of ubiquitin and amyloid-β 42 (r=-0,19; p=0,007) were found. No significant correlations between concentrations of 24(S)-hydroxycholesterol and amyloid-β 42 were identified.

13. Conclusions • No statisticallysignificantdifferencesinlevels of candidateplasmabiomarkers of an earlyneurodegenerationaccording to cognitivefunctioning and agewerefound. • In accordance with the criteria for potential plasma biomarkers of an early neurodegeneration, it can be assumed that none of the analyzed parameters can qualify for the plasma biomarker of an early neurodegeneration. • In order to fullyassesspotential of assayingchosenbiochemicalparametresinthecontext of an earlycognitivedecline, prospectivestudiesareneeded.

14. Thank you for your attention