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Comparative Study
. 2013 Aug;70(8):1039-45.
doi: 10.1001/jamaneurol.2013.1878.

Dissociable effects of Alzheimer disease and white matter hyperintensities on brain metabolism

Thaddeus J Haight  1 , Susan M Landau, Owen Carmichael, Christopher Schwarz, Charles DeCarli, William J Jagust; Alzheimer's Disease Neuroimaging Initiative
Affiliations
Comparative Study

Dissociable effects of Alzheimer disease and white matter hyperintensities on brain metabolism

Thaddeus J Haight et al. JAMA Neurol. 2013 Aug.

Abstract

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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Conflict of interest statement

Conflict of Interest Disclosures: Dr Landau has served on a scientific advisory board for Janssen Alzheimer Immunotherapy and as a neuroimaging scientist at Avid Radiopharmaceuticals Inc. Dr Carmichael has received funding from the Dana Foundation and the Hiblom Foundation, and his research has been supported by grant IIS-1117663 from the National Science Foundation, by sponsor award 201016148-01 from the Department of Defense, and by grants AG030514, AG010129, AG024904, AG20098, and AG012435 from the National Institutes of Health. Dr DeCarli’s research is supported by grant AG 024904 from the National Institutes of Health. Dr Jagust has served as a consultant to Genentech Inc, GE Healthcare, Bayer HealthCare, Synarc, Janssen Alzheimer Immunotherapy, TauRx, Merck & Co, and Siemens, and his research has been supported by grants AG027859, AG027984, and AG 024904 from the National Institutes of Health.

Figures

Figure 1
Figure 1
Model results. 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.
Figure 2
Figure 2
Model results. The same plots as those in Figure 1 are shown for nonconverters. WMH indicates white matter hyperintensity; CSF-Aβ, cerebrospinal fluid β-amyloid.
See this image and copyright information in PMC

Comment in

References

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