Different patterns of N-acetylaspartate loss in subcortical ischemic vascular dementia and AD

Abstract

Objectives: 1) To determine the regional pattern of reduced N-acetylaspartate (NAA) in subcortical ischemic vascular dementia (SIVD); 2) to explore the relationship between NAA reduction and subcortical vascular disease; and 3) to test if MR spectroscopic imaging (MRSI) in combination with structural MRI improves differentiation between SIVD and Alzheimer disease (AD).

Methods: Thirteen patients with SIVD (71 +/- 8 years old) and 43 patients with AD of comparable age and dementia severity were studied using MRSI and MRI. Patients were compared to 52 cognitively normal subjects with and without lacunes.

Results: Compared to controls, patients with SIVD had lower NAA by 18% (p < 0.001) in frontal cortex and by 27% (p < 0.003) in parietal cortex, but no significant NAA reduction in white matter and medial temporal lobe. Compared to patients with AD, patients with SIVD had lower NAA by 13% (p < 0.02) in frontal cortex and by 20% (p < 0.002) in left parietal cortex. Cortical NAA decreased in SIVD with increasing white matter lesions (r = 0.54, p < 0.02) and number of lacunes (r = 0.59, p < 0.02). Thalamic lacunes were associated with greater NAA reduction in frontal cortex than were lacunes outside the thalamus (p < 0.02) across groups, after adjusting for cognitive impairments. Adding parietal NAA to MRI-derived hippocampal atrophy improved separation between SIVD and AD (p = 0.02) from 79 to 89%.

Conclusions: These results emphasize the importance of cortical dysfunction as a factor in SIVD and indicate a characteristic pattern of metabolite change that might serve as a basis for improved diagnosis.

Figure 1

Relationship between cortical [NAA] and subcortical vascular disease, assessed by white matter hyperintensities (WMH) and number of lacunes in patients with subcortical ischemic vascular disease (●) and cognitively normal subjects (○). WMH volume was indexed to percent of normal white matter and [NAA] is represented in arbitrary units (au).

Figure 2

Cortical [NAA] of frontal and parietal lobe as a function of presence (+Thal) or absence (−Thal) of thalamic lacunes in subjects with subcortical infarctions. Also indicated are mean values and 1.0 standard deviations for each subgroup. Data from patients with subcortical ischemic vascular disease (▼), patients with Alzheimer disease (▲), and cognitively normal subjects (●) with lacunes are pooled.

Figure 3

Discrimination between patients with subcortical ischemic vascular disease (●) and Alzheimer disease (○) by MRI-derived hippocampal volume and magnetic resonance spectroscopic imaging–derived cortical [NAA] of parietal lobe.