Vascular risk factors and dementia

Abstract

In recent years, accumulating evidence has suggested that vascular risk factors contribute to Alzheimer disease (AD). Vascular dementia had been traditionally considered secondary to stroke and vascular disease. It has been traditionally distinguished from AD, considered to be a purely neurodegenerative form of dementia. However, in light of this more recent literature, it appears that there is a spectrum: ranging from patients with pure vascular dementia to patients with pure AD and including a large majority of patients with contributions from both Alzheimer and vascular pathologies. In this article, we discuss the impact of vascular risk factors on AD and its consequences at the individual level and at the population level by highlighting the concept of attributable risk. We then discuss the key questions and next steps involved in designing a therapeutic trial to control vascular risk factors for the prevention of dementia. Neurology Over the past 10 years, a growing body of literature, including several large population-based clinicopathologic or clinicoradiologic studies, has highlighted the important contribution of vascular risk factors (hypertension and diabetes as primary examples) in Alzheimer disease (AD). [1][2][3][4] In the Rotterdam study, one of the first large studies that called attention to this issue, dementia was associated with the presence of atherosclerosis and this association applied to subjects clinically diagnosed with vascular-type dementia as well as those with AD.2 An association between high blood pressure and the risk of AD was also reported in other cohort studies with a 15-to 21-year follow-up.1,3 Diabetes, a high level of cholesterol, tobacco smoking, as well as other vascular risk factors have also been associated with a higher risk of AD. [5][6][7] Furthermore, atrial fibrillation, hypertension, and angina have been shown to be associated with a greater rate of decline in patients with AD. 8 Apart from the occurrence of a clinical stroke, the mechanisms by which vascular factors increase the risk of AD or accelerate cognitive deterioration among patients with AD are not yet fully elucidated. Most of these factors have been shown to be associated with subcortical lesions seen on brain MRI: white matter hyperintensities (WMH), 9-12 lacunar infarctions, [13][14][15] or cerebral microhemorrhages. 16 There is also evidence to suggest that lowering blood pressure may stop or delay the progression of WMH. 17 The extent of WMH has been clearly linked both to cognitive impairment and the risk of incident dementia in several population-based studies.11,18-20 Further, small, clinically silent brain infarctions appear to be at least as strong a risk for subsequent dementia 21 as larger, clinically evident strokes. 22,23 It is, however, likely that these lesions do not fully explain the impact of vascular factors on the brain and that there exist other more subtle structural changes that may have consequences related to cognition and dementia.

Cardiovascular risk in cognitively preserved elderlies is associated with glucose hypometabolism in the posterior cingulate cortex and precuneus regardless of brain atrophy and apolipoprotein gene variations

“…Moreover, the presence of the APOE ε4 allele is an important risk factor not only for AD but also for cardiovascular disease (Irie et al 2008;Kivipelto et al 2008). Such body of evidence has led to propositions that vascular-related mechanisms possibly play a critical role in the pathophysiology of AD (de la Torre and Mussivand 1993;de la Torre 2009;Qiu et al 2009;Viswanathan et al 2009). …”

Assessment of the Virchow-Robin Spaces in Alzheimer Disease, Mild Cognitive Impairment, and Normal Aging, Using High-Field MR Imaging

“…3,10 VRSs have been identified as a biomarker indicative of microvascular disease and are strongly related to systemic vascular disease; a possible association of VRS with vascular risk factors has been proposed. 5,[11][12][13] Many vascular risk factors are also risk factors for AD 14,15 so vascular and degenerative mechanisms are considered to have parallel effects. If the severity of VRSs could be an independent feature indicating vascular impairment with involvement of cerebral arteries, then it is arguable that increased VRS severity should also be associated with AD.…”

The link between cardiovascular risk, Alzheimer's disease, and mild cognitive impairment: support from recent functional neuroimaging studies

“…88 Based on the above epidemiological, clinical, and structural neuroimaging findings, it has been proposed recently that AD and VaD actually represent two extremes of a dementia spectrum ranging from patients with pure VaD to patients with pure AD, with a majority of patients having contributions from both neuropathological pathways. 53,74,89,90 Figure 1 (adapted from Viswanathan et al 90 ) illustrates the concept of a spectrum ranging from pure AD to pure VaD. Such lines of evidence have also provided support to a more ambitious ''vascular hypothesis'' for AD, which proposes that the neuropathological changes that characterize AD would originate primarily from microvascular abnormalities.…”