Hippocampal volumes, proton magnetic resonance spectroscopy metabolites, and cerebrovascular disease in mild cognitive impairment subtypes

Abstract

Background: Although a majority of patients with amnestic mild cognitive impairment (aMCI) progress to Alzheimer disease, the natural history of nonamnestic MCI (naMCI) is less clear. Noninvasive imaging surrogates for underlying pathological findings in MCI would be clinically useful for identifying patients who may benefit from disease-specific treatments at the prodromal stage of dementia.

Objective: To determine the characteristic magnetic resonance imaging (MRI) and proton MR spectroscopy (1H MRS) profiles of MCI subtypes.

Design: Case-control study.

Setting: Community-based sample at a tertiary referral center.

Patients: Ninety-one patients with single-domain aMCI, 32 patients with multiple-domain aMCI, 20 patients with single- or multiple-domain naMCI, and 100 cognitively normal elderly subjects frequency-matched by age and sex.

Main outcome measures: Posterior cingulate gyrus 1H MRS metabolite ratios, hippocampal volumes, and cerebrovascular disease on MRI.

Results: Patients with single-domain aMCI were characterized by small hippocampal volumes and elevated ratios of myo-inositol to creatine levels. Patients with naMCI on average had normal hippocampal volumes and 1H MRS metabolite ratios, but a greater proportion (3 of 20 patients [15%]) had cortical infarctions compared with patients with single-domain aMCI (6 of 91 [7%]). For characterization of MCI subtypes, 1H MRS and structural MRI findings were complementary.

Conclusions: The MRI and 1H MRS findings in single-domain aMCI are consistent with a pattern similar to that of Alzheimer disease. Absence of this pattern on average in patients with naMCI suggests that cerebrovascular disease and other neurodegenerative diseases may be contributing to the cognitive impairment in many individuals with naMCI.

Figure 1

Estimated relative probability of group membership as a function of 4 imaging measures. The relative probabilities shown are the estimated probability of group membership obtained from the multinomial model divided by the estimated probability at the median of the imaging measure. The gray reference lines intersect at the median for the measure on the x-axis and 1.0 on the y-axis. For all estimates we assumed a 77-year-old man with 14 years of education. Cho indicates choline; CN, cognitively normal; Cr, creatine; MD-aMCI, multiple-domain amnestic mild cognitive impairment (MCI); mI, myo-inositol; naMCI, nonamnestic MCI; SD-aMCI, single-domain aMCI; and WMH, white matter hyperintensity.