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May 06, 2008; 70 (19 Part 2) Articles

Whole-brain atrophy rate in Alzheimer disease

Identifying fast progressors

J. D. Sluimer, H. Vrenken, M. A. Blankenstein, N. C. Fox, P. Scheltens, F. Barkhof, W. M. van der Flier
First published May 5, 2008, DOI: https://doi.org/10.1212/01.wnl.0000311446.61861.e3
J. D. Sluimer
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H. Vrenken
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M. A. Blankenstein
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N. C. Fox
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P. Scheltens
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F. Barkhof
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W. M. van der Flier
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Citation
Whole-brain atrophy rate in Alzheimer disease
Identifying fast progressors
J. D. Sluimer, H. Vrenken, M. A. Blankenstein, N. C. Fox, P. Scheltens, F. Barkhof, W. M. van der Flier
Neurology May 2008, 70 (19 Part 2) 1836-1841; DOI: 10.1212/01.wnl.0000311446.61861.e3

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Abstract

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 ε4 (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 ε4 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 ε4 positive, and have pronounced hippocampal atrophy.

Glossary

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