Vascular risk factors and Alzheimer's disease: are these risk factors for plaques and tangles or for concomitant vascular pathology that increases the likelihood of dementia? An evidence-based review
1 Department of Neurology, University of Southern California, 1520 San Pablo Street, Los Angeles, CA 90033, USA
2 Department of Neurology, University of Southern California, 2020 Zonal Ave, IRD930, Los Angeles, CA 90033, USA
3 University of California Davis, Alzheimer Disease Center, Department of Neurology, 150 Muir Road (127a), Martinez, CA 94553, USA
4 Department of Pathology and Laboratory Medicine, UCLA Medical Center, Los Angeles, CA 90095, USA
5 Department of Preventive Medicine, University of Southern California, 2001 Soto St., SSB 202Y, Los Angeles, CA 90033, USA
Alzheimer's Research & Therapy 2011, 4:1 doi:10.1186/alzrt98Published: 4 January 2012
Recent epidemiologic studies have noted that risk factors for atherosclerosis (for example, diabetes mellitus, hypertension, and hyperlipidemia) are associated with increased risk of incident Alzheimer's disease (AD). In this evidence-based review, we frame the proposition as a question: are vascular risk factors also risk factors for plaques and tangles or just for concomitant vascular pathology that increases the likelihood of dementia? To date, no representative, prospective studies with autopsy (evidence level A) show significant positive associations between diabetes mellitus, hypertension, or intracranial atherosclerosis and plaques or tangles. Some prospective, representative, epidemiologic studies (evidence level B) show associations between diabetes, hypertension, hyperlipidemia, and aggregated risk factors with clinically diagnosed incident AD. However, the strength of association diminishes in the following order: vascular dementia (VaD) > AD + VaD > AD. This pattern is arguably more consistent with the hypothesis that atherosclerosis promotes subclinical vascular brain injury, thereby increasing the likelihood of dementia and in some cases making symptoms present earlier. Several autopsy studies from AD brain banks (evidence level C) have observed positive associations between intracranial atherosclerosis and severity of plaques and tangles. However, these studies may reflect selection bias; these associations are not confirmed when cases are drawn from non-dementia settings. We conclude that, at the present time, there is no consistent body of evidence to show that vascular risk factors increase AD pathology.