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