Cerebral small vessel disease (SVD) is a very common disease among older adults and is visible on MRI as white matter lesions (WMLs), lacunar infarcts and/or microbleeds. Subjects with SVD may have acute symptoms such as transient ischemic attacks and lacunar syndromes, and/or subacute symptoms. These subacute symptoms not only include cognitive, but probably also motor disturbances, which are often a neglected, but nevertheless important problem as they are associated with increased morbidity and mortality. There is not much known on the role of WMLs, their severity and location and the surrounding white matter on motor performance.
In this thesis we describe the associations between MRI abnormalities in SVD and motor performance.
Association between cerebral small vessel disease and motor performance: a conventional MRI approach
In chapter 2 we report on the associations between WMLs, lacunar infarcts, microbleeds, cortical thickness and gait disturbances and the impact of their location. We furthermore studied the relationship between WMLs, lacunar infarcts and their location and mild parkinsonians signs (MPS). WMLs were characterized by volume and location [frontal, parietal, occipital, temporal lobes, sublobar (basal ganglia, thalamus, internal and external capsula, insula) and limbic areas (cingulate gyrus)]. The number of microbleeds and lacunar infarcts in the whole brain and in the abovementioned locations were rated and cortical thickness was calculated in each Brodmann area using a surface-based cortical thickness analysis. Gait was assessed with the GAITRite system and the Tinetti and Timed-Up-and-Go test. The presence of MPS was based on the motor section of the Unifi ed Parkinson’s Disease Rating Scale.
All subjects had some degree of WMLs. Lacunar infarct(s) were present in ±31% and microbleeds in ±11%. Of all the participants, ±12% had a gait velocity <1 m/s and ±21% had MPS. We found that WML volume, number of lacunar infarcts, number of microbleeds and cortical thickness were related to gait. Subjects with a higher load of one of these MRI markers of SVD had a lower gait velocity, especially due to a shorter stride length, than those with a lower load. Cadence (step frequency), was only associated with lacunar infarcts and cortical thickness. Subjects with severe WMLs or ≥1 lacunar infarct(s) had a higher risk of the presence of MPS than those without. We furthermore found a threshold- effect of WMLs; especially those with a WML volume >20 ml had a signifi cantly higher risk of gait disturbances and MPS than those with a lower WML load.
Summary
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The most important locations with regard to gait performance for WMLs were the frontal lobe, limbic and sublobar areas; for lacunar infarcts the frontal lobe, thalamus, and brainstem; and for microbleeds the frontal, temporal lobe and basal ganglia, including the thalamus. WMLs in the frontal and parietal lobe and lacunar infarcts in the thalamus seemed to be most associated with the presence of MPS.
Association between cerebral small vessel disease and motor performance: a diffusion tensor imaging approach
In chapter 3 we describe the associations between the microstructural integrity, assessed with diffusion tensor imaging (DTI), within the WMLs and the normal-appearing white matter (NAWM) and gait, using two different ways of analyzing DTI data: calculation of the mean fractional anisotropy (FA) and mean diffusivity (MD) in WMLs and NAWM and various other regions-of-interest and Tract-Based Spatial Statistics (TBSS), a method restricted to the white matter voxels that constitute the skeleton of the brain’s connectional architecture. The fi rst method was also used in relation to the presence of MPS.
We found that the mean MD and FA of the WMLs was associated with respectively gait disturbances and the presence of MPS. We furthermore showed that the mean FA and MD of the NAWM in subjects was related to their motor performance. Although the strength of these associations diminished after additional adjustment for the coexisting WML volume and number of lacunar infarcts, associations with some gait parameters (e.g. cadence, stride width) remained signifi cant. Moreover, TBSS revealed that tracts with the strongest associations with gait performance were situated in the NAWM. In both methods, loss of white matter integrity of numerous regions was related to gait disturbances. Using TBSS, we were able to investigate the strongest spatially localizing associations in the corpus callosum, predominantly in the genu, containing fi bers to the prefrontal lobe. Our fi nding in chapter 3.3 also pointed to the frontal lobe to play an important role in the presence of MPS.
Conventional MRI versus diffusion tensor imaging
Because our studies in chapter 3 suggested that damage to the NAWM is an important factor in the development of gait disturbances in SVD, we investigated in chapter 4 the additional variance in gait explained by DTI measures of the NAWM to that of conventional MRI abnormalities in SVD. We found that this accounted for very little additional explained variance in gait in addition to the coexisting conventional MRI markers of SVD (e.g. WMLs and lacunar infarcts).
We furthermore examined whether the mean MD of the whole white matter was a stronger predictor of variance in gait performance than one of the conventional MRI markers of
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SVD. The mean MD of the white matter was the main contributor to the explanation of variance of all gait parameters, although the explained variance due to this parameter was only ±1% more than that of WML volume. Of note, the total explained variance of all cerebral MRI markers, apart from age and sex (which explained 22% of the variance in gait velocity), was ±7%.
Summary