Risk of dementia in MCI: combined effect of cerebrovascular disease, volumetric MRI, and 1H MRS

Abstract

Objective: To investigate the combined ability of hippocampal volumes, 1H magnetic resonance spectroscopy (MRS) metabolites, and cerebrovascular disease to predict the risk of progression to dementia in mild cognitive impairment (MCI).

Methods: We identified 151 consecutively recruited subjects with MCI from the Mayo Clinic Alzheimer's Disease Research Center and Patient Registry who underwent MRI and 1H MRS studies at baseline and were followed up with approximately annual clinical examinations. A multivariable proportional hazards model that considered all imaging predictors simultaneously was used to determine whether hippocampal volumes, posterior cingulate gyrus 1H MRS metabolites, white matter hyperintensity load, and presence of cortical and subcortical infarctions are complementary in predicting the risk of progression from MCI to dementia.

Results: Seventy-five subjects with MCI progressed to dementia by last follow-up. The model that best predicted progression to dementia included age, sex, hippocampal volumes, N-acetylaspartate (NAA)/creatine (Cr) on 1H MRS, and cortical infarctions. Based on age- and sex-adjusted Kaplan-Meier plots, we estimated that by 3 years, 26% of the MCI patients with normal hippocampal volumes, NAA/Cr ratios >1 SD, and no cortical infarctions will progress to dementia, compared with 78% of the MCI patients with hippocampal atrophy, low NAA/Cr (< or =1 SD), and cortical infarction.

Conclusions: Multiple magnetic resonance (MR) markers of underlying dementia pathologies improve the ability to identify patients with prodromal dementia over a single MR marker, supporting the concept that individuals with multiple brain pathologies have increased odds of dementia compared with individuals with a single pathology.

Figure 1 Flowchart indicating the steps involved in defining the study cohort and the number of individuals involved in each step Subjects who did not undergo MRI and magnetic resonance spectroscopy (MRS) examinations were either not willing to participate or could not undergo magnetic resonance scanning because of safety (e.g., having a pacemaker, claustrophobia). *Medical exclusions were related to alcohol addiction (n = 2), cerebral contusion (n = 1), epilepsy (n = 1), Parkinson disease (n = 1), or amyotrophic lateral sclerosis (n = 1). MCI = mild cognitive impairment; ADPR = Alzheimer’s Disease Patient Registry; ADRC = Alzheimer’s Disease Research Center.

Figure 2 Estimates of the probability of remaining free of dementia over time based on age-, sex-, and education-adjusted Cox models having a single imaging predictor Estimates assume a 76-year-old patient with 14.6 years of education and represent a weighted average of the curves for men and women where the weights are the proportion of men and women in our sample. NAA/Cr = N-acetylaspartate/creatine.

Figure 3 Estimates of the probability of remaining free of dementia for four patient groups with increasingly negative prognoses Group A has adjusted hippocampal volume and N-acetylaspartate/creatine (NAA/Cr) 1 SD above mild cognitive impairment (MCI) average and no cortical infarctions. Group B has adjusted hippocampal volume 1 SD below MCI average with NAA/Cr 1 SD above MCI average and no cortical infarctions. Group C has adjusted hippocampal volume and NAA/Cr both 1 SD below MCI average and no cortical infarctions. Group D has adjusted hippocampal volume and NAA/Cr both 1 SD below MCI average and cortical infarctions. Estimates shown represent a weighted average of the curves for men and women where the weights are the proportion of men and women in our sample.