White matter microstructure and cognitive decline in metabolic syndrome: a review of diffusion tensor imaging

Abstract

Metabolic syndrome is a cluster of cardiovascular risk factors defined by the presence of abdominal obesity, glucose intolerance, hypertension and/or dyslipidemia. It is a major public health epidemic worldwide, and a known risk factor for the development of cognitive dysfunction and dementia. Several studies have demonstrated a positive association between the presence of metabolic syndrome and worse cognitive outcomes, however, evidence of brain structure pathology is limited. Diffusion tensor imaging has offered new opportunities to detect microstructural white matter changes in metabolic syndrome, and a possibility to detect associations between functional and structural abnormalities. This review analyzes the impact of metabolic syndrome on white matter microstructural integrity, brain structure abnormalities and their relationship to cognitive function. Each of the metabolic syndrome components exerts a specific signature of white matter microstructural abnormalities. Metabolic syndrome and its components exert both additive/synergistic, as well as, independent effects on brain microstructure thus accelerating brain aging and cognitive decline.

Keywords: Brain; Cognitive decline; Diffusion tensor imaging; Metabolic syndrome; White matter mictrostructure.

Figure 1

Conceptual model that describes the main mechanisms by which metabolic syndrome and its components lead to structural and functional brain abnormalities, accelerate brain aging and cognitive decline. Cellular, vascular and genetic factors as well as inflammation and oxidative stress are the main contributors to this complicated process. Abbreviations: neuronal growth regulator 1 (NEDR1); apolipoprotein E4 (ApoE4); reactive oxygen species (ROS); blood brain barrier (BBB); small vessel disease (SVD); macrovascular disease (MVD); gray matter (GM); white matter (WM); white matterhyperintensities (WMH); fractiona anisotropy (FA); mean diffusivity (MD); axial diffusivity (AD); radial diffusivity (RD)