Prediction of AD with MRI-based hippocampal volume in mild cognitive impairment

Abstract

Objective: To test the hypothesis that MRI-based measurements of hippocampal volume are related to the risk of future conversion to Alzheimer's disease (AD) in older patients with a mild cognitive impairment (MCI).

Background: Patients who develop AD pass through a transitional state, which can be characterized as MCI. In some patients, however, MCI is a more benign condition, which may not progress to AD or may do so slowly.

Patients: Eighty consecutive patients who met criteria for the diagnosis of MCI were recruited from the Mayo Clinic Alzheimer's Disease Center/Alzheimer's Disease Patient Registry.

Methods: At entry into the study, each patient received an MRI examination of the head, from which the volumes of both hippocampi were measured. Patients were followed longitudinally with approximately annual clinical/cognitive assessments. The primary endpoint was the crossover of individual MCI patients to the clinical diagnosis of AD during longitudinal clinical follow-up.

Results: During the period of longitudinal observation, which averaged 32.6 months, 27 of the 80 MCI patients became demented. Hippocampal atrophy at baseline was associated with crossover from MCI to AD (relative risk [RR], 0.69, p = 0.015). When hippocampal volume was entered into bivariate models-using age, postmenopausal estrogen replacement, standard neuropsychological tests, apolipoprotein E (APOE) genotype, history of ischemic heart disease, and hypertension-the RRs were not substantially different from that found univariately, and the associations between hippocampal volume and crossover remained significant.

Conclusion: In older patients with MCI, hippocampal atrophy determined by premorbid MRI-based volume measurements is predictive of subsequent conversion to AD.

Figure 1. Neuroanatomic Boundaries

The column of images on the left are cropped oblique coronal MR images through the temporal lobes of a 75-year-old woman. The upper image is through the body of the hippocampus and lower image is through the head of the hippocampus. This MCI patient remained stable over 49 months of clinical followup. At baseline her hippocampal W score was 0.21. On the right are matched imaging sections of a 70-year-old woman, who was initially categorized as MCI, but become demented after 43.5 months of followup. Her hippocampal W score was −2.48 at entry into the study. The hippocampi of the patient who became demented (right) are visibly atrophic relative to the stable patient (left) despite the fact that the crossover patient was 5 years younger. The anatomic outlines of the left hippocampus are indicated.

Figure 2. Hippocampal W Score and Crossover

Kaplan-Meyer curves of patients whose hippocampal W score at baseline was ≥ 0 (n=13), 0 > W > −2.5 (n = 54), and ≤ −2.5 (n = 13).