Dementia: Alzheimer pathology and vascular factors: From mutually exclusive to interaction

Alzheimer's disease (AD) is the most common type of dementia. Both its incidence and prevalence are expected to increase exponentially as populations' age worldwide. Despite impressive efforts of research worldwide, neither cure nor effective preventive strategy is available for this devastating disease. Currently there are several hypotheses on what causes AD, with the amyloid hypothesis being the most investigated and accepted hypothesis over the past 20 years. However the exact role of amyloid-β in the onset and progression of AD is not yet fully understood, and even the validity of the amyloid hypothesis itself is still being discussed. This debate is fuelled by the vascular hypothesis, as increasing epidemiological, neuroimaging, pathological, pharmacotherapeutic and clinical studies suggest that vascular pathology plays a key role in the onset and progression of AD. We here will discuss arguments in favor and limitations of both hypotheses within the framework of available literature, but also provide arguments for convergence of both hypotheses.Finally we propose approaches that may aid in unraveling the etiology and treatment of AD. This article is part of a Special Issue entitled: Imaging Brain Aging and Neurodegenerative disease.

► Alzheimer's disease is caused by a mixture of interacting risk factors.
► Amyloid-β accumulation and vascular damage are the most frequent risk factors.
► The interaction of Aβ and vascular damage is a double hit on cognitive function.
► Etiological research needs a large, well-defined study population with long follow up.
► Influence of risk factors varies over time with potential therapeutic consequences.