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From the Departments of Epidemiology and Biostatistics (Drs. Den Heijer, Prins, Van Dijk, Vermeer, Hofman, and Breteler) and Neurology (Drs. Den Heijer, Prins, Van Dijk, Vermeer, and Koudstaal), Erasmus Medical Center, Rotterdam, the Netherlands; and Neuroepidemiology Section (Dr. Launer), National Institute on Aging, Bethesda, MD.
Address correspondence and reprint requests to Dr. M.M.B. Breteler, Department of Epidemiology and Biostatistics, Erasmus MC, 3000 DR Rotterdam, the Netherlands; e-mail: m.breteler{at}erasmusmc.nl
Background: Blood pressure level is associated with the risk of clinical Alzheimer disease (AD), yet the underlying mechanisms are unclear. High blood pressure levels may cause cerebral small-vessel pathology, which contributes to cognitive decline in patients with AD. Alternatively, in persons with high blood pressure, increased numbers of neurofibrillary tangles and amyloid plaques at autopsy have also been observed, suggesting direct links between blood pressure and AD.
Objective: To investigate the association of blood pressure and markers of small-vessel disease (white matter lesions [WMLs] on MRI) with hippocampal and amygdalar atrophy on MRI—potential in vivo indicators of Alzheimer pathology.
Methods: In 1995 to 1996, 511 nondemented elderly subjects (age 60 to 90) underwent MRI. The extent of WMLs was assessed, and volumes of the hippocampus and amygdala were measured. Blood pressure levels were assessed at the time of MRI and 5 years before the MRI.
Results: Higher diastolic blood pressure 5 years before MRI predicted more hippocampal atrophy in persons untreated for hypertension (per SD increase –0.10 mL [95% CI –0.19 to –0.02, p = 0.02]). Conversely, in persons treated for hypertension, a low diastolic blood pressure was associated with more severe atrophy. Persons with more WMLs on MRI more often had severe atrophy of the hippocampus and amygdala.
Conclusion: Blood pressure and indicators of small-vessel disease in the brain may be associated with atrophy of structures affected by Alzheimer pathology.
Supported by the Netherlands Organisation for Scientific Research (NWO) and the Health Research and Development Council (ZON-MW).
Received July 8, 2004. Accepted in final form October 7, 2004.
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