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Whole-brain atrophy rate in Alzheimer disease

Identifying fast progressors

From the Alzheimer Centre and Department of Diagnostic Radiology (J.D.S., F.B.), Image Analysis Centre (J.D.S., F.B.), Physics and Medical Technology (H.V.), Clinical Chemistry (M.A.B.), and Department of Neurology (N.C.F., P.S., W.M.v.d.F.), VU University Medical Center, Amsterdam, the Netherlands; and Dementia Research Centre (N.C.F.), National Hospital for Neurology and Neurosurgery, London, England.

Address correspondence and reprint requests to Dr Sluimer, Department of Radiology and Alzheimer Centre, Vrije Universiteit Medical Centre, PO Box 7057, 1007 MB Amsterdam, The Netherlands jd.sluimer{at}vumc.nl

Objective: To assess which baseline clinical and MRI measures influence whole-brain atrophy rates, measured from serial MR imaging.

Methods: We recruited 65 patients with Alzheimer disease (mean ± SD age 70 ± 8 y, 58% women, Mini-Mental State Examination [MMSE] 22 ± 5), scanned with an average interval of 1.7 ± 0.6 years. Whole-brain atrophy rates were used as outcome measure. Baseline normalized brain volume, hippocampal volume, and whole-brain atrophy rates were measured using three-dimensional T1-weighted imaging. The influence of age, sex, apolipoprotein E genotype (APOE), baseline MMSE, baseline hippocampal volume, and baseline normalized brain volume on whole-brain atrophy rates was assessed using linear regression.

Results: The mean whole-brain atrophy rate was –1.9 ± 0.9% per year. In the multivariate model, younger age (β [SE] = 0.03 [0.01]; p = 0.04), absence of APOE 4 (β [SE] = 0.61 [0.28]; p = 0.03), and a low MMSE (β [SE] = 0.11 [0.03]; p < 0.001) were associated with a higher whole-brain atrophy rate. Furthermore, a relatively spared hippocampus predicted faster decline for patients with a smaller baseline brain volume (p = 0.09), and with a lower MMSE (p = 0.07). Finally, a smaller brain volume was associated with a higher rate of atrophy in younger patients (p = 0.03).

Conclusions: Our results suggest it is possible to characterize a subgroup of patients with Alzheimer disease (AD) who are at risk of faster loss of brain volume. Patients with more generalized, rather than focal hippocampal atrophy, who often have an onset before the age of 65, and are APOE 4 negative, seem to be at risk of faster whole-brain atrophy rates than the more commonly seen patients with AD, who are older, are APOE 4 positive, and have pronounced hippocampal atrophy.

Abbreviations: AD = Alzheimer disease; MMSE = Mini-Mental State Examination; NBV = normalized baseline brain volume; PBVC = percentage brain volume change.

J.D. Sluimer is recipient of grant 03514 from the ISAO (Internationale Stichting Alzheimer Onderzoek) and supported by the Image Analysis Center (IAC). N.C. Fox holds an MRC (UK) senior clinical fellowship and holds an honorary position as professor at the VUMC. The Alzheimer Centre VUMC is supported by Alzheimer Nederland and Stichting VUMC fonds. The clinical database structure was developed with funding from Stichting Dioraphte.

Disclosure: The authors report no conflicts of interest.

Received June 18, 2007. Accepted in final form October 4, 2007.