Genetic and Vascular Risk Factors for Cognitive Decline and Cerebral Small-Vessel Disease

Abstract

One of the earliest known written reports on dementia is attributed to Pythagoras in the 7th century BC, who described old age as a period of decline and decay of the human body and regression of mental capacities. In 1907, Alois Alzheimer, a german psychiatrist and scientist, observed at necropsy an overload of - at that time still unknown - amyloid plaques and neurofi brillary tangles in the brain of a 51 year old woman who had suff ered during her life course from progressive cognitive decline. Nowadays, amyloid plaques and neurofi brillary tangles are considered the main neuropathological hallmarks of Alzheimer’s disease, which is regarded the most frequent subtype of dementia. Over the past two decades evidence has been accumulating that dementia is a heterogeneous and multifactorial disorder, and that besides accumulation of beta amyloid and neurofi brillary tangles, other factors, in particular vascular risk factors and cerebrovascular disease, may be involved, especially in late-onset dementia. Observational studies reported associations between several vascular risk factors and cognitive decline and dementia. In autopsy studies, about 35% of the brains of elderly persons, who had been diagnosed with dementia during their lifetime, had not only a higher burden of amyloid plaques and neurofi brillar tangles but rather a mixed pathology also consisting of signifi cant cerebrovascular disease. Stroke has been reported to considerably increase the risk of dementia, with prevalence rates of poststroke dementia of about 30%, refl ecting a 3.6 to 5.8-fold increased risk of dementia compared to stroke-free subjects. Cerebral small-vessel disease, which is defi ned as cerebral white matter lesions and asymptomatic lacunar brain infarcts and is a common fi nding on brain scans of elderly persons, has been reported to more than double the risk of dementia