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Abstract
Objective: Since Alzheimer disease (AD) is a slowly progressive disorder and its pathologic features are likely to be present for many years before symptoms become manifest, we investigated whether microstructural white matter changes similar to those identified in patients with AD can be detected in cognitively normal individuals without dementia destined to develop amnestic mild cognitive impairment (aMCI).
Methods: We studied 193 cognitively normal individuals, of whom 173 remained cognitively stable (CN-stable) and 20 were diagnosed with aMCI (CN-aMCI converter) 2 years later. Structural MRI and diffusion tensor imaging were acquired at baseline to assess gray matter atrophy and microstructural white matter changes, respectively.
Results: At baseline, compared with CN-stable, CN-aMCI converters had substantial reductions in white matter integrity in the precuneus, parahippocampal cingulum, parahippocampal gyrus white matter, and fornix. Other diffuse white matter changes were observed in the frontal, parietal, and subcortical regions, whereas gray matter structures were relatively intact. The fractional anisotropy (FA) values of the precuneus were found to be a predictor of conversion from cognitively normal to aMCI. In addition, the FA values of the left parahippocampal gyrus white matter were predictive of subsequent episodic memory decline.
Conclusions: Microstructural white matter changes are present in cognitively normal individuals in the pre-aMCI stage, and may serve as a potential imaging marker of early AD-related brain changes.
GLOSSARY
- AD=
- Alzheimer disease;
- aMCI=
- amnestic mild cognitive impairment;
- ANCOVA=
- analysis of covariance;
- ANOVA=
- analysis of variance;
- CN=
- cognitively normal;
- DSM-IV=
- Diagnostic and Statistical Manual of Mental Disorders, 4th edition;
- DARTEL=
- diffeomorphic anatomic registration using exponentiated lie algebra;
- DTI=
- diffusion tensor imaging;
- FA=
- fractional anisotropy;
- FLAIR=
- fluid-attenuated inversion recovery;
- FWE=
- family-wise error;
- GM=
- gray matter;
- GMD=
- gray matter density;
- LM=
- Logical Memory;
- MMSE=
- Mini-Mental State Examination;
- MNI=
- Montreal Neurological Institute;
- RAVLT=
- Rey Auditory Verbal Learning Test;
- RAVLT6=
- Rey Auditory Verbal Learning Test short-term delayed recall trial 6;
- RAVLT7=
- Rey Auditory Verbal Learning Test long-term delayed recall trial 7;
- RAVLTtotr=
- Rey Auditory Verbal Learning Test total learning sum of trials 1–5;
- TBSS=
- tract-based spatial statistics;
- VBM=
- voxel-based morphometry;
- WM=
- white matter;
- WMH=
- white matter hyperintensity.
Footnotes
Study funding: Supported by Australian National Health and Medical Research Council (NHMRC) Program Grant ID 350833, NHMRC Project Grant ID 510175, and Australian Research Council Discovery Grant ID ARC DP-0774213.
Editorial, page 726.
Supplemental data at www.neurology.org
- Received November 17, 2011.
- Accepted February 8, 2012.
- Copyright © 2012 by AAN Enterprises, Inc.
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