Cognitive status correlates with white matter alteration in Parkinson's disease

Abstract

Patients with Parkinson's disease (PD) can develop mild cognitive impairment (PD-MCI), frequently progressing to dementia (PDD). Here, we aimed to elucidate the relationship between white matter alteration and cognitive status in PD and dementia with Lewy bodies (DLB) by using diffusion tensor imaging. We also compared the progression patterns of white and gray matter and the cerebral perfusion. We enrolled patients with PD cognitively normal (PD-CogNL, n = 32), PD-MCI (n = 28), PDD (n = 25), DLB (n = 29), and age- and sex-matched healthy control subjects (n = 40). Fractional anisotropy (FA) map of a patient group was compared with that of control subjects by using tract-based spatial statistics. For the patient cohort, intersubject voxel-wise correlation was performed between FA values and Mini-Mental Status Examination (MMSE) scores. We also evaluated the gray matter and the cerebral perfusion by conducting a voxel-based analysis. There were significantly decreased FA values in many major tracts in patients with PD-MCI, PDD, and DLB, but not in PD-CogNL, compared with control subjects. FA values in the certain white matter areas, particularly the bilateral parietal white matter, were significantly correlated with MMSE scores in patients with PD. Patients with PDD and DLB had diffuse gray matter atrophy. All patient groups had occipital and posterior parietal hypoperfusion when compared with control subjects. Our results suggest that white matter damage underlies cognitive impairment in PD, and cognitive impairment in PD progresses with functional alteration (hypoperfusion) followed by structural alterations in which white matter alteration precedes gray matter atrophy.

Figure 1

TBSS analysis of FA map in Lewy body disease. All images are displayed in Montreal Neurological Institute (MNI) space. The mean FA skeleton is shown in green. (A) White matter atlas. The representative mean FA skeleton was superimposed on the atlas. Copper, superior longitudinal fascicle; red, inferior longitudinal fasciculus; yellow, inferior fronto‐occipital fasciculus; dark blue, uncinate fasciculus; light blue, cingulum; purple, corticospinal tract. (B–E) Areas of significantly decreased FA values. Areas of significantly decreased FA values in patients with PD‐MCI (B), PDD (C), and DLB (D) compared with control subjects, and in patients with PDD compared with patients with PD‐CogNL (E) are shown by colors ranging from red to yellow (P < 0.05, corrected for multiple comparison by using TFCE). All images are oriented according to radiological convention (i.e., the left hemisphere of the brain corresponds to the right side of the image).

Figure 2

TBSS analysis of FA map in the corpus callosum in Lewy body disease. The mean FA skeleton is shown in green. Areas with significantly decreased FA values in patients with PD‐MCI (A), PDD (B), and DLB (C), compared with control subjects, and in patients with PDD compared with patients with PD‐CogNL (D) are shown by colors ranging from red to yellow (P < 0.05, corrected for multiple comparisons).

Figure 3

The white matter areas where FA values correlated with MMSE scores in patients with PD. (A) The mean FA skeleton is shown in green. The white matter areas where FA values were significantly correlated with Mini‐Mental State Examination (MMSE) scores in patients with PD are shown by color ranging from red to yellow (P < 0.05, corrected for multiple comparisons). All images are oriented according to radiological convention (i.e., the left hemisphere of the brain corresponds to the right side of the image). (B) Rendered version of (A).

Figure 4

Gray matter atrophy in PDD or DLB. Areas with significant gray matter atrophy in patients with PDD (A) and DLB (B), compared with control subjects, are shown by colors ranging from red to yellow (P < 0.05, corrected for multiple comparisons). All images are oriented according to radiological convention (i.e., the left hemisphere of the brain corresponds to the right side of the image).

Figure 5

Cerebral hypoperfusion in Lewy body disease. Areas with hypoperfusion are shown in patients with PD‐CogNL (A), PD‐MCI (B), PDD (C), and DLB (D) compared with control subjects, and in patients with DLB compared with patients with PDD (E). A Z‐score of > 3.00 (P < 0.001, uncorrected for multiple comparisons) was considered to indicate statistical significance.