Microvascular Dysfunction and Cognitive Impairment

Abstract

The impact of vascular risk factors on cognitive function has garnered much interest in recent years. The appropriate distribution of oxygen, glucose, and other nutrients by the cerebral vasculature is critical for proper cognitive performance. The cerebral microvasculature is a key site of vascular resistance and a preferential target for small vessel disease. While deleterious effects of vascular risk factors on microvascular function are known, the contribution of this dysfunction to cognitive deficits is less clear. In this review, we summarize current evidence for microvascular dysfunction in brain. We highlight effects of select vascular risk factors (hypertension, diabetes, and hyperhomocysteinemia) on the pial and parenchymal circulation. Lastly, we discuss potential links between microvascular disease and cognitive function, highlighting current gaps in our understanding.

Keywords: Cerebral circulation; Diabetes; Endothelium; Hypertension; Microcirculation; Vascular remodeling.

Fig. 1

Array of effects, and altered endpoints, that occur in the face of risk factors for vascular disease

Fig. 2

Levels of arteriolar pressure, expressed as a percent of systemic arterial pressure, in multiple species. Data are redrawn from the following references. (Baumbach et al. ; Baumbach and Heistad ; Baumbach et al. , ; Beyer et al. ; Chillon et al. ; Faraci et al. ; Harper and Bohlen ; Harper et al. ; Hurn et al. ; Kadel et al. ; Mayhan and Faraci ; Shima et al. ; Tamaki et al. 1986, 1992)

Fig. 3

Vascular remodeling expressed as differences in internal diameter of maximally dilated cerebral arterioles (versus controls) in several models of hypertension. Data are shown for hypertensive mice (Baumbach et al. 2003) (R⁺A⁺ and BPH2) and rats (Baumbach and Hajdu 1993) (SHR and renal hypertension) along with data from mice infused chronically with a pressor dose of angiotensin II (Ang II) (Chan and Baumbach 2013a). Data from parenchymal arterioles in mice treated with DOCA-salt (De Silva et al. a) (unpublished observations) are included for comparison

Fig. 4

Schematic illustration showing the temporal progression of vascular disease and its effect on CBF and cognition with normal aging as well as aging in the presence of vascular risk factors. Both chronic hypoperfusion and loss of acute vasodilator responses [neurovascular coupling (NVC) in this example] are illustrated