Today there is consensus that Alzheimer’s disease is a complex condition resulting from a variety of factors and characterized by different types of damage to the brain contributing to the development of dementia and cognitive impairments.
One of the most common features that is often concurrent with the classical Alzheimer’s disease amyloid and tau toxic protein deposits is the presence of damage to the brain vessels, aka vascular pathology.
The vascular contributions to cognitive impairments and dementia are conditions arising from stroke and other vascular brain injuries that cause significant changes to memory, thinking and behavior. The impact on these cognitive functions in general depends on the size, location, and number of these vascular brain injuries.
Vascular dementia arises because of risk factors that similarly increase the risk for cerebrovascular disease (stroke), including atrial fibrillation (a problem with the rhythm of the heartbeat), high blood pressure and diabetes.
Mixed pathology dementia account for more than half of dementia cases, with brain amyloid plaques and vascular disease being the most frequent combination.
Cerebral amyloid angiopathy, the accumulation of amyloid beta in an around the brain vessels, is often an underappreciated lesion present in about 80 % of all Alzheimer’s cases. It is responsible for what is called microvascular degeneration which progressively restricts nutrients to the functional areas of the brain and by promoting injury processes such as inflammation, oxidative stress and leakage ultimately leads to nerve cell death and dementia.
It has been recognized that patients with mixed vascular and Alzheimer’s pathologies have nearly twice the risk of dementia compared with patients with only Alzheimer’s-type lesions.
Current work in our and other labs is trying to identify how vascular risk factors such as high blood pressure, or low brain perfusion potentiate the toxic effects of the amyloid beta and tau on the brain vasculature and nerve cells.
Clarifying the causes of the vascular contributions to cognitive impairment of Alzheimer’s disease will have an enormous impact on public health and clinical practice and increase the possibility to find effective treatments and preventative strategies against it.
Domenico Praticò, MD, holds the position of the Scott Richards North Star Charitable Foundation Chair for Alzheimer’s Research and serves as a Professor and the Director at the Alzheimer’s Center at Temple, as well as a Professor of Pharmacology at Lewis Katz School of Medicine at Temple University.
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