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Neurodegenerative dementias, such as Alzheimer's disease, and vascular cognitive impairment were once considered unrelated processes. Emerging evidence, however, shows that both conditions often coexist and that vascular risk factors in midlife predispose to the development of cognitive decline later in older adults. In addition, recent advanced in basic science research have elucidated key underpinnings of this association. In this chapter, we review the clinical and basic science data that explain the relationship between vascular risk factors, heart disease, and cognitive decline.

Approximately one-third of strokes are cryptogenic in origin. These patients have a higher prevalence of patent foramen ovale (PFO) compared to individuals with stroke of known origin. It has been proposed that some cryptogenic strokes (CSs) can be caused by paradoxical embolism across a PFO. PFOs can be treated medically with antithrombotic agents and percutaneously with occluder devices. Large randomized clinical trials have found transcatheter PFO closure to be superior to medical treatment for the prevention of recurrent stroke in young patients with CS. However, the superiority of PFO closure over medical treatment in unselected populations has not been demonstrated. In this chapter, we review the evidence supporting PFO closure and the selection of patients for such intervention.

Fabry disease (FD), also known as angiokeratoma corporis diffusum , is an X-linked lysosomal storage disorder caused by deficiency of α-galactosidase A. This defect causes the accumulation of glycosphingolipids in cells, including endothelial and vascular smooth muscle cells of small arterioles. These vessels become dysfunctional and undergo progressive stenosis resulting in ischemia and end-organ damage. Stroke constitutes one of the most devastating complications of FD.

Cerebrovascular diseases are a leading cause of death and disability worldwide. While modifiable and nonmodifiable vascular risk factors have been identified in patients with cerebrovascular disease, these account for only a portion of the risk. It is becoming increasingly evident that genetics play a significant role in determining stroke risk with both single gene mutations and polygenic diseases contributing to stroke predisposition. Single gene mutations causing mitochondrial and metabolic dysfunction, connective tissue instability, and vascular damage and polygenic syndromes linked to hemostasis and metabolic disorders have all been associated with increased risk of stroke. Evidence from linkage analysis, twin studies, candidate gene approaches, and genome-wide association studies have drastically improved our understanding of the genetic basis for cerebrovascular disease and continue to provide valuable insight about the genetic link to stroke and related disorders. In this chapter we review uncommon genetic causes of stroke, including mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), hereditary endotheliopathy with retinopathy, nephropathy, and stroke (HERNS), homocystinuria, inherited connective tissue disorders, and moyamoya disease.

Age constitutes one of the most important nonmodifiable risk factors for cerebral infarction. About 15% of all the ischemic strokes occur in young adults. Since stroke predominately affects the elderly, most of the data gathered in pivotal clinical trials and population-based studies were obtained using cohorts of older patients with coexisting cardiac disease and atherosclerosis. In comparison to older individuals, however, patients aged 15–50 years have a lower prevalence of traditional vascular risk factors and a higher representation of uncommon causes of stroke; these differences necessitate a particularized, thoughtful approach and cause-specific treatments. This chapter hence focuses on the epidemiology, pathogenesis, and diagnostic investigations of ischemic stroke in the young.