MRI and neuropsychological correlates of white matter hyperintensities in asymptomatic subjects aged 50 to 65 years

Abstract

Hachinski, Potter and Merskey introduced the term “leukoaraiosis” (from the Greek “leuko” = “white”, and “araiosis” = “rarefaction”) to designate bilateral and symmetrical areas in the white matter (WM) of the periventricular region and centrum semiovale that appeared hypodense on computerized tomography (CT). Over the past three decades, the amount of data on the clinical and pathological correlates of these incidental WM findings has vastly increased. Nowadays, white matter hyperintensities (WMHs) are currently thought to be a consequence of cerebral small-vessel disease (SVD). They are usually divided into two groups depending on their anatomical position: periventricular hyperintensities (PVHs) and deep white matter hyperintensities (DWMHs). Most research about WMHs has involved participants who are older than 65 years. However, these radiological abnormalities are also seen commonly in middle-aged individuals in their 50s and early 60s.

The general aim of this thesis was to study the association between WMHs, their related magnetic resonance imaging (MRI) structural correlates, and cognitive function in a community sample of stroke- and dementia-free individuals aged 50 to 65 years old. To that end, participants were recruited from an ongoing population-based study, different MRI techniques were applied, and a comprehensive neuropsychological assessment was implemented, following vascular cognitive impairment (VCI) harmonization standards.

Our data suggest that DWMHs have a predominant role in cognitive function of community middle-aged individuals without symptomatic CVD and overt cognitive impairment. High grade DWMHs are specifically associated with an extensive cognitive profile, whereas high grade PVHs are not associated with cognitive function. It would be desirable that neuroradiologists characterize separately PVHs and DWMHs in their reports, which should be available for neuropsychologists. Given that the role of DWMHs may be attributed to underlying ischemic processes, primary prevention and treatment of modifiable vascular risk factors may be crucial to maintain cognitive function and prevent future cognitive decline during biological aging of the brain.

The use of a voxel-based approach allows the identification of MRI correlates of WMHs in conventional MRI and novel neuroimaging techniques such as DTI. Individuals with high grade

DWMHs show reduced gray matter (GM) volume in different areas, whereas participants with high grade PVHs do not. Participants with high grade PVHs and participants with high grade DWMHs show lower fractional anisotropy (FA) in different areas of specific WM tracts. Therefore, DTI could serve as an additional tool to conventional MRI to investigate extension of WM damage.

Only MRI correlates of DWMHs are predictive of cognitive function, which reinforces a predominant role of these lesions in this group of age. The predictive value to cognition of lower FA within specific WM tracts supports the involvement of cerebral circuits in cognitive deficits related to WMHs. The combination of conventional MRI and DTI may be useful to predict cognitive function in SVD.

En las últimas tres décadas, la evidencia científica sobre las repercusiones clínicas de las hiperintensidades de sustancia blanca cerebral (HSBC) ha sido numerosa. En la actualidad, están consideradas como una consecuencia de la patología de pequeño vaso cerebral. La mayor parte de la investigación se ha centrado en personas mayores de 65 años, aunque las HSBC también se hallan en personas de mediana edad entre 50 y 65 años.

El objetivo general de esta tesis doctoral es el estudio de la asociación entre las HSBC, sus correlatos estructurales de resonancia magnética (RM), y la función cognitiva en una muestra poblacional entre 50 y 65 años sin antecedentes de ictus ni demencia.

Nuestros resultados sugieren que las HSBC localizadas en la sustancia blanca profunda tienen un papel predominante en la función cognitiva de este grupo de edad. Asimismo, el análisis vóxel a vóxel permite la identificación de los correlatos estructurales de RM de dichas lesiones. Sólo los correlatos estructurales relacionados con las HSBC localizadas en la sustancia blanca profunda predicen el rendimiento cognitivo. El uso multimodal de RM convencional y de imagen por tensión de difusión (DTI) podría ser útil para predecir el funcionamiento cognitivo y para entender los mecanismos subyacentes y las consecuencias clínicas de las HSBC.