Whole-Brain Atrophy Rate and Cognitive Decline: Longitudinal MR Study of Memory Clinic Patients

PURPOSE: To prospectively determine whole-brain atrophy rate in mild cognitive impairment (MCI) and Alzheimer disease (AD) and its association with cognitive decline, and investigate the risk of progression to dementia in initially nondemented patients given baseline brain volume and whole-brain atrophy rate. MATERIALS AND METHODS: This study was IRB approved; written informed consent was obtained; and included 65 AD patients (38 women, 27 men; age, 52-81 years), 45 MCI patients (22 women, 23 men; age, 56-80 years), 27 patients with subjective complaints (12 women, 15 men; age, 50-87 years), and 10 healthy controls (six women, four men; age, 53-80 years). Two magnetic resonance (MR) images were acquired at average interval of 1.8 years +/- 0.7 (standard deviation). Baseline brain volume and whole-brain atrophy rates were measured on three-dimensional T1-weighted MR images (1.0 T; single slab, 168 sections; matrix size, 256 x 256; field of view, 250 mm; voxel size, 1 x 1 x 1.5 mm; repetition time msec/echo time msec/inversion time msec, 15/7/300; and flip angle, 15 degrees ). Associations were assessed by using partial-correlations. Cox proportional hazards models were used to estimate risk of developing dementia. RESULTS: Baseline brain volume was lowest in AD but did not differ significantly between MCI, subjective complaints, and control groups (P > .38). Whole-brain atrophy rates were higher in AD (-1.9% per year +/- 0.9) than MCI (-1.2% per year +/- 0.9, P = .003) patients, who had higher whole-brain atrophy rates than patients with subjective complaints (-0.7% per year +/- 0.7, P = .03) and controls (-0.5% per year +/- 0.5, P = .05). Whole-brain atrophy rate correlated with annualized Mini-Mental State Examination (MMSE) change (r = 0.48, P < .001), while baseline volume did not (r = 0.11, P = .22). Cox models showed that-after correction for age, sex, and baseline MMSE-a higher whole-brain atrophy rate was associated with an increased risk of progression to dementia (highest vs lowest tertile hazard ratio, 3.6; 95% confidence interval: 1.2, 11.4). CONCLUSION: Whole-brain atrophy rate was strongly associated with cognitive decline. In nondemented participants, a high whole-brain atrophy rate was associated with an increased risk of progression to dementia.