Neurodegeneration and microvascular dysfunction: causes and consequences

There is an imperative for a better understanding of the early pathobiology of major clinical diseases of a neuronal and microvascular origin, such as dementia, late-life depression, and diabetic retinopathy. A better understanding may lead to the identification of novel strategies to in an early-stage prevent major clinical disease, e.g., via the early-stage modification of risk factors for neurodegeneration and microvascular dysfunction. Hence, this thesis investigated how neurodegeneration and microvascular dysfunction were associated with symptoms of major clinical disease (i.e., cognitive dysfunction and depressive symptoms); and whether potentially modifiable cardiovascular and lifestyle factors were associated with neurodegeneration and microvascular dysfunction. This thesis found the following. First, neurodegeneration was associated with a higher incidence of depressive symptoms and neurodegeneration and microvascular dysfunction were associated with lower cognitive performance. Second, potentially modifiable cardiovascular and lifestyle factors were associated with neurodegeneration and microvascular dysfunction. Of the investigated factors type 2 diabetes was the most strongly associated with neurodegeneration and microvascular dysfunction. Hence, there may be a new horizon for the early prevention of major clinical disease of neuronal and microvascular origin, including dementia, late-life depression, and diabetic retinopathy.