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 non-demented 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. (C) RSNA, 2008.