Cerebral infarction in Alzheimer's disease is associated with severe amyloid angiopathy and hypertension
J. M. Olichney, L. A. Hansen, C. R. Hofstetter, M. Grundman, R. Katzman and L. J. Thal
Alzheimer's Disease Research Center, University of California-San Diego, La Jolla, USA.
OBJECTIVE: To determine if severe cerebral amyloid angiopathy (AA) in
patients with Alzheimer's disease (AD) is associated with an increased
prevalence of cerebral infarction diagnosed at autopsy. Amyloid angiopathy
is increasingly recognized as a cause of ischemic infarcts, as well as
cerebral hemorrhages. However, the relationship of AA to cerebral
infarction in patients with AD is uncertain. DESIGN: Retrospective
clinicopathological study of autopsy-confirmed cases of AD. PATIENTS: One
hundred forty-five deceased patients with AD confirmed at autopsy. MAIN
OUTCOME MEASURES: Semiquantitative scores of AA severity were done in four
brain regions: midfrontal, inferior parietal, superior temporal, and
hippocampal. The finding of cerebral infarction at autopsy was modeled as a
function of AA severity, hypertension, age at death, AD severity, and sex
in chi 2 and multiple logistic regression analyses. RESULTS: Severe AA was
significantly associated with cerebral infarction at autopsy in patients
with AD (odds ratio [OR], 3.5; 95% confidence interval [CI], 1.4 to 8.9).
None of the other independent variables in the multiple logistic regression
analysis were significant predictors. While hypertension was equally common
in the severe and mild AA subgroups, the combination of both severe AA and
hypertension interacted to increase the risk of infarction (OR, 14.2; 95%
CI, 3.2 to 63.4) beyond that observed with hypertension (OR, 1.1; 95% CI,
0.4 to 3.2) or severe AA (OR, 1.3; 95% CI, 0.3 to 5.3) alone. CONCLUSIONS:
Severe AA is associated with an increased frequency of cerebral infarction
in patients with AD. This appears to be largely due to an interaction
between severe AA and hypertension that may produce multiplicative injuries
on the vasculature. Further study with regard as to how AA may cause
ischemia and its role in the neuropathologic and clinical progression of AD
is needed.