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Association of Blood Pressure and Genetic Background With White Matter Lesions in Patients With Mild Cognitive Impairment

¹ LENITEM-Laboratory of Epidemiology, Neuroimaging and Telemedicine, ² Psychogeriatric Unit, and ³ NeuroBioGenLab–Memory Clinic, IRCCS San Giovanni di Dio–Fatebenefratelli, Brescia, Italy.
⁴ AFaR, Associazione Fatebenefratelli per la Ricerca, Rome, Italy.
⁵ Institute of Internal Medicine, Department of Medical Sciences, University of Brescia, Italy.
⁶ Service of Neuroradiology, Istituto Clinico Città di Brescia, Italy.

Address correspondence to Giovanni B. Frisoni, MD, IRCCS Centro San Giovanni di Dio–Fatebenefratelli, National Centre for Research and Care of Alzheimer's and Mental Diseases, via Pilastroni 4, 25125 Brescia, Italy. E-mail: gfrisoni{at}fatebenefratelli.it

Background. White matter lesions (WMLs) may contribute to cognitive deficits in patients with mild cognitive impairment (MCI), but their pathogenesis is complex. Fluctuations of blood pressure (BP) over 24 hours and genetic predisposition to develop vascular damage have been implicated.

Methods. In 63 MCI patients 65 years old or older, BP was measured both clinically and with ambulatory BP monitoring. Patients were classified in two groups: no/very mild (n = 34) and mild to severe (n = 29) WMLs, based on a visual scale on magnetic resonance (mean age 71.8 ± 4.7 vs 74.6 ± 5.1, and female gender 53% vs 66%, respectively). The volume of WMLs was measured by a semi-automatic method, separately for periventricular caps and rim, periventricular confluent, subcortical punctate, and subcortical confluent. Polymorphisms of cystatin C (CST3) and cholesterol 24-hydroxylase (CYP46) genes, putative risk factors for cerebrovascular disease, were determined.

Results. The prevalence of cerebrovascular risk factors was similar in the two MCI groups of different WML severity, as well as clinic and ambulatory BP. In patients with mild to severe, but not in those with no/very mild WMLs, the volume of periventricular confluent WMLs increased with increasing daytime systolic BP (regression coefficient.47, 95% confidence interval [CI],.13 to.71 vs.02, 95% CI, –.32 to.36, p =.003 for the difference between slopes). The volume of other WML subtypes was not associated with ambulatory BP. Participants carrying both CST3*B and CYP46*T alleles were overrepresented in the MCI group with mild to severe WMLs (43% vs 17%, p.03).

Conclusions. BP and gene putative risk factors for cerebrovascular disease are differentially associated with WMLs in two MCI groups of different WML severity. WMLs might develop for the convergence of innate with acquired factors.

Key Words: Blood pressure • White matter lesions • Mild cognitive impairment • Genotype • Cystatin c