Clinical features and prognosis in Vascular Cognitive Impairment

The general objective of this thesis was to investigate the clinical features and prognosis of patients with vascular cognitive impairment (VCI) in a memory clinic setting. To this end, the TRACE-VCI study was initiated, resulting in a large, unique cohort of 860 patients from three Dutch outpatient clinics at two university hospitals. The first part of this thesis focused on the clinical features and cognitive profile of the patients included in the TRACE-VCI cohort. Chapter 2 described the design and clinical features of the TRACE-VCI cohort regarding type of vascular brain injury, severity of cognitive impairment and combination with other neurodegenerative etiologies. In this memory clinic population with VCI, the main types of vascular brain injury were moderate/severe WMH (46%), microbleed(s) (43%) and lacunar infarct(s) (11%). In total, 52% of patients showed dementia, in which 86% had a neurodegenerative etiology, mostly Alzheimer’s disease (79%). Chapter 3 showed that type and severity of vascular brain injury explained little of the variation in cognitive profile. The cognitive profile was remarkably similar across all types of vascular brain injury. Chapter 4 showed no different cognitive profile among sexes. Type of vascular brain injury did show differences between sexes; female patients showed larger WMH volumes, while males showed more non-lacunar and lacunar infarct(s). The most important difference was made by the presence of a positive CSF biomarker Alzheimer profile. A positive CSF biomarker Alzheimer profile by itself markedly affected cognitive performance on all domains showing worse performance on all cognitive domains, especially memory. This finding provides support for the theory that vascular brain injury lowers the threshold for symptoms of cognitive impairment in co-occurring Alzheimer pathology. Chapter 5 demonstrated that memory clinic patients with VCI and different types of vascular brain injury on MRI showed little differences in cognitive trajectories depending on type of vascular brain injury. Across the TRACE-VCI study population performance declined over time on all tests. The data provided some suggestion that lacunar and non-lacunar infarct(s) were associated with minor differences in tests evaluating attention and executive functioning. These subtle associations were mainly attributable to patients with dementia. Chapter 6 described the creation and external validation of a risk score to predict poor clinical outcome. In 688 patients, follow-up collection was performed after a mean of 2.1 years, in which 170 patients showed poor clinical outcome. We defined a composite primary outcome measure that was robust and clinically relevant including (1) substantial cognitive decline, (2) occurrence of a major cardiovascular event (MACE), (3) death and/or (4) institutionalization due to other reasons than cognitive decline. Age, clinical syndrome diagnosis, Disability Assessment for Dementia, Neuropsychiatric Inventory, medial temporal lobe atrophy most strongly predicted poor outcome and constituted the risk score. None of the vascular risk factors or types of vascular brain injury were predictive for poor clinical outcome. Validation of the prediction score in an independent cohort showed comparable predictive ability. Chapter 4 described no statistically significant differences in poor clinical outcome between sexes. In conclusion, the overall aim of the TRACE-VCI study was to investigate the clinical features and prognosis of patients with possible VCI in a memory clinic setting. This thesis showed that type of vascular brain injury in a memory clinic population explained little of the variance in cognitive profile and trajectory. The presence of co-existing Alzheimer pathology by itself markedly affected cognitive performance on all domains. Prediction of poor clinical outcome in the TRACE-VCI study was mainly influenced by age, type of cognitive impairment, MTA score, neuropsychiatric symptoms and disability in daily living on baseline visit. Also here, no vascular predictors were retained in this model.