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

The first aim of this thesis was to evaluate the prevalence of cardiovascular disease (CaVD), hypertension (HT), and type 2 diabetes mellitus (T2DM) in the neurodegenerative disorders Alzheimer’s disease (AD) and Lewy body disease (LBD). These conditions are considered modifiable risk factors for vascular dementia (VaD), and recent research has proposed its association with AD. The field is considered unexplored when it comes to LBD, a prevalent form of alpha-synucleinopathies (AS). A second aim was to investigate cardiac disease and the presence of epicardial nerve alpha-synuclein (α-syn) as well as the cause of death in individuals with AS.
In summary, the objective was to investigate and assemble broad clinicopathological data on CaVD, HT, and T2DM in AD and AS as well as to confirm the presence of cardiac α-syn and to determine the cause of death in AS. All studies were based on subjects who had undergone a thorough neuropathological examination of the brain. Pathological and clinical data were assembled through autopsy reports and medical records. A majority of the research in this field has not included neuropathological verification of the neurocognitive disorder (NCD).
In Papers I and II, we investigated the prevalence of CaVD, found morphologically at autopsy, as well as clinical HT and T2DM in AD, VaD, mixed AD-VaD, and LBD. We found a low prevalence and no differences regarding CaVD between AD and LBD. This differed statistically from VaD in almost all parameters, which presented with a high prevalence of the studied parameters. The same differences were seen regarding HT and T2DM – a low prevalence in AD and LBD compared to a significantly higher prevalence in VaD.
In Paper III, we investigated the presence of cardiac α-syn in AS patients and a control group with other (non-AS) NCDs. We found α-syn in almost all cases of AS (82%) and within different stages of the disease. No cases within the control group had cardiac nerves positive for α-syn. The samples negative to α-syn in the AS group did not cover the epicardium with stainable nerves. We judged it probable that all AS have α-syn in their cardiac nerves.
In Paper IV, we investigated the immediate cause of death in AS individuals, postive for α-syn in their cardiac nerves compared to o control group with other (non-AS) NCDs. In addition, we assembled comprehensive data on pathological and clinical CaVD, HT, and T2DM. The majority of deaths within the AS group were interpreted as sudden cardiac death (SCD, 51.3%). These were judged to be of cardiac but not vascular-ischemic etiology. The prevalence of SCDs differed statistically from the control group where it was the second most common cause of death (22.6%, p < 0.001). No other differences were seen between the groups regarding clinicopathologial CaVD, HT, and T2DM.
We have demonstrated that CaVD, HT, and T2DM have a low prevalence in the neurodegenerative disorders AD and LBD. Our findings oppose the claims of a causal association between these disorders. Furthermore, our results support the association of these risk factors with VaD.
We have additionally indicated that α-syn is present in probably all cases of AS and within all stages of the disease. The high prevalence of SCD in AS indicate that the protein depositions may play a role for impaired cardiac function in these individuals.