Cardiac and vascular pathology in Lewy body disease and Alzheimer's disease: exploring neurocognitive disorder beyond the brain

This project focuses on three major challenges concerning dementia / neurocognitive disorders (NCD):

1 - Clinical diagnostic tools to determine a NCD are not as accurate as the diagnosis based on neuropathological examination of the brain. Thus, the percentage of misdiagnosis or failing to detect mixed pathologies are presumably high. This is considered both a clinical problem and a limitation within clinical research where the wrong or not accurate diagnosis might be studied.
2 - Established risk factors for Alzheimer's disease (AD), the most prevalent NCD, are a high age, family history, and genetic factors. Recently, cardiovascular disease, hypertension, and diabetes mellitus type II have been proposed as potential preventable and treatable risk factors for AD. This of interest as we still lack curative or disease-modifying treatment for the disease. AD is characterized by protein depositions in the brain, accumulation of pathological amyloid and tau, which is believed to be the cause of the disease. The risk factors above contribute to atherosclerosis and an impaired oxygen flow to the brain which are proposed to stimulate the accumulation of these pathological protein depositions, although the exact mechanisms are unknown. These risk factors are known and established for vascular dementia (VaD), the second most common NCD, a disease where affected oxygen supply to the brain is responsible for the symptoms.
3 – NCD is considered the seventh leading cause of death and a higher mortality has been reported among individuals suffering from an NCD. Of special interest is alpha-synucleinopathies (AS). A disease group that includes Lewy body disease (LBD) and multiple system atrophy. LBD connotes the disorders Parkinson’s disease / Parkinson’s disease dementia and dementia with Lewy bodies. AS are defined as neurodegenerative disorders where pathological aggregations of the protein alpha-synuclein is believed to cause the disease. However, recent findings suggest that the protein pathology in AS is not only limited to the brain and the central nervous system but widespread in nerves in several different organs, including the heart. Additionally, the disease group is suggested to have a higher mortality rate than other NCDs and reports of sudden death have been made in Parkinson’s disease.

This project will only include cases who have undergone a full body autopsy and a complete neuropathological examination of the brain. Thus, the existing brain pathology of each study subject will be confirmed.

Aims:
1 – To investigate the prevalence of cardiovascular disease, hypertension, and diabetes mellitus type II in AD, LBD, VaD, and mixed AD-VaD.
2 – To explore the prevalence of alpha-synuclein in cardiac nerves in AS.
3 – To investigate the cause of death and prevalence of cardiovascular disease and risk factors in AS positive for cardiac alpha-synuclein.