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Original Investigation |

Dissociable Effects of Alzheimer Disease and White Matter Hyperintensities on Brain Metabolism

Thaddeus J. Haight, PhD1; Susan M. Landau, PhD1,2; Owen Carmichael, PhD4; Christopher Schwarz, PhD4; Charles DeCarli, MD4; William J. Jagust, MD1,2,3; Alzheimer’s Disease Neuroimaging Initiative
[+] Author Affiliations
1Helen Wills Neuroscience Institute, University of California, Berkeley
2Life Sciences Division, Lawrence Berkeley National Laboratory, University of California, Berkeley
3Division of Epidemiology, School of Public Health, University of California, Berkeley
4Department of Neurology, University of California, Davis
JAMA Neurol. 2013;70(8):1039-1045. doi:10.1001/jamaneurol.2013.1878.
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Published online

Importance  Cerebrovascular disease and Alzheimer disease (AD) frequently co-occur and seem to act through different pathways in producing dementia.

Objective  To examine cerebrovascular disease and AD markers in relation to brain glucose metabolism in patients with mild cognitive impairment.

Design and Setting  Cohort study among the Alzheimer Disease Neuroimaging Initiative clinical sites in the United States and Canada.

Participants  Two hundred three patients having amnestic mild cognitive impairment (74 of whom converted to AD) with serial imaging during a 3-year follow-up period.

Main Outcomes and Measures  Quantified white matter hyperintensities (WMHs) represented cerebrovascular disease, and cerebrospinal fluid β-amyloid represented AD pathology. Brain glucose metabolism in temporoparietal and frontal brain regions was measured using positron emission tomography with fluorodeoxyglucose F18.

Results  In converters, greater WMHs were associated with decreased frontal metabolism (−0.048; 95% CI, −0.067 to −0.029) but not temporoparietal metabolism (0.010; 95% CI, −0.010 to 0.030). Greater cerebrospinal fluid β-amyloid (per 10-pg/mL increase) was associated with increased temporoparietal metabolism (0.005; 95% CI, 0.000-0.010) but not frontal metabolism (0.002; 95% CI, −0.004 to 0.007) in the same patients. In nonconverters, similar relationships were observed except for a positive association of greater WMHs with increased temporoparietal metabolism (0.051; 95% CI, 0.027-0.076).

Conclusions and Relevance  The dissociation of WMHs and cerebrospinal fluid β-amyloid in relation to regional glucose metabolism suggests that these pathologic conditions operate through different and independent pathways in AD that reflect dysfunction in different brain systems. The positive association of greater WMHs with temporoparietal metabolism suggests that these pathologic processes do not co-occur in nonconverters.

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Figures

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Figure 1.
Model Results for Converters

In converters, plots depict fitted positron emission tomography with fluorodeoxyglucose F18 (FDG-PET) in different brain regions (ie, frontal and temporoparietal) based on models of the relationship between glucose metabolism and the following: A, White matter hyperintensities (WMHs) in the entire group. B, White matter hyperintensities in the subgroup with measured cerebrospinal fluid β-amyloid (CSF-Aβ). C, Cerebrospinal fluid β-amyloid.

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Figure 2.
Model Results for Nonconverters

The same plots as those in Figure 1 are shown for nonconverters. WMH indicates white matter hyperintensity; CSF-Aβ, cerebrospinal fluid β-amyloid.

Graphic Jump Location

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