Etiology and prognosis of cognitive disorders: With a focus on intracranial arterial calcifications

Abstract

This thesis describes our studies on two major topics: the etiology and prognosis of cognitive disorders with a focus on intracranial arterial calcifications. There are differences in risk factors between intimal and medial calcifications. Calcifications in the tunica intima were associated with the more traditional cardiovascular risk factors as male gender, smoking and hypertension. Also, predominantly intimal calcifications were associated with myocardial infarction and stroke. Risk factors for calcifications in the tunica media, including BGC, were female gender and diabetes mellitus and were associated with stroke. In our selected populations, we found no evidence that intracranial arterial calcifications are associated with cognitive decline or depressive symptoms. A possible explanation for this might be that basal ganglia are important for specific cognitive domains like attention, executive functioning and mental speed. In our studies, we measured overall cognitive functioning, while these specific cognitive domains were insufficiently measured. Patients with PFBC demonstrate the importance of (severe) intracranial calcifications on cognition and neuropsychiatric symptoms and the association between the amount of calcifications and symptoms. Mortality risks in patients with dementia are high, also in specific settings as psychiatric and inpatient care. Risk factors for mortality were higher age, male gender, more somatic comorbidities and inpatient (psychiatric) care. We calculated absolute mortality risks to support clinicians in daily practice in assessing the life expectancy in patients with dementia. These results can assist in advance care planning in these patients. We used a novel way to investigate vascular disease by focusing on arterial calcifications and specifically on the distinction between intimal and medial calcifications. Arterial calcifications are common in older adults. There are different risk factors associated with intimal and medial calcifications. From our perspective there is more evidence necessary to further determine the pathophysiology of arterial calcifications, with distinction between intimal and medial calcifications. If we are able to find specific therapeutical targets, studies should be performed to assess if treatment of arterial calcifications also reduce calcifications and reduce cardiovascular events and cognitive decline. We did not show an association between intracranial arterial calcifications and cognitive impairment. This might have resulted from methodological limitations regarding the cognitive assessment in our studies. Therefore, we would recommend to perform a study that assesses mental speed and executive function more thoroughly to identify the possible effect of intracranial arterial calcifications on these cognitive domains. Diagnostic methods to differentiate between “physiological” intracranial calcifications and PFBC are also provided in this thesis. Yet, there are still many other research questions to be answered about this rare, genetic disease. Lastly, mortality in patients with dementia is high, but also varies significantly between individual patients. Therefore, we provided prognostic models to determine the individual mortality risks of patients with dementia in a hospital-based cohort. We focused on one- and three year mortality, in-hospital mortality and mortality in psychiatric care. These models will help patients, caregivers and health care providers in advance care planning. It is important to validate these prognostic models, and also implement these models in general practice.