Peripheral Oxidative Stress Markers in Individuals with Alzheimer's Disease with or without Cerebrovascular Disease

Abstract

To the Editor: Growing evidence suggests that oxidative stress plays an important role in the pathogenesis of Alzheimer's disease (AD).1, 2 A previous meta-analysis reported that a number of studies showed high lipid peroxidation marker, protein oxidation marker, and deoxyribonucleic acid and ribonucleic acid oxidation marker levels and low antioxidant levels in individuals with AD.3 Extensive lines of evidence support the role of oxidative injury in the pathogenesis of stroke and other vascular disease.4 Cerebrovascular disease (CVD), such as lacunes and white matter lesions, are common in elderly adults with AD. Although there may be some differences in oxidative damage between individuals with AD with and without CVD, there is a lack of studies examining biomarkers of oxidative damage in these individuals. In the present study, differences in peripheral oxidative stress markers between individuals with CVD with and without AD were determined, and correlations between biomarkers of oxidative damage and cognitive impairment were investigated. Sixty-nine individuals with AD without CVD (AD group) and 36 individuals with AD and CVD (AD + CVD group) were enrolled from a memory clinic. Individuals with AD had to meet the National Institute of Neurological and Communicative Disorders and Stroke and Alzheimer's Disease and Related Disorders Association criteria5 for a diagnosis of probable AD. AD with CVD was defined as typical AD associated with clinical and radiological evidence of CVD in the deep gray and white matter.6 In addition, 40 elderly individuals with no signs of cognitive impairment or CVD in the clinic were randomly chosen and used as a control group. Individuals with malignancies, severe cardiac or pulmonary disease, liver cirrhosis, renal failure, infectious disease, or disease requiring immunosuppressive therapy; current smokers; and individuals taking antioxidant supplements or vitamins were excluded. Cognitive function was assessed using the Mini-Mental State Examination (MMSE).7 Diacron reactive oxygen metabolite (dROM) levels, reflecting the amount of organic hydroperoxide, and biological antioxidant potential (BAP), measuring the ferric reducing ability of blood plasma, were measured using a free radical analyzer system (FRAS 4, Wismerll Company Ltd., Tokyo, Japan).8, 9 All analyses were performed within 48 hours of venous blood collection. Statistical analysis was conducted using Student t-tests, the chi-square test, analysis of covariance (ANCOVA), and the Spearman rank correlation test. Table 1 show participant characteristics and peripheral oxidative stress markers. The group with AD was significantly younger than the control group and had significantly more women than the control and AD + CVD groups. No significant differences in education and comorbidities such as hypertension, diabetes mellitus, dyslipidemia, and heart disease were found between the three groups. The AD and AD + CVD groups had significantly lower MMSE scores than the control group, but no significant differences in MMSE score and dementia duration were found between the AD and AD + CVD groups. ANCOVA, taking into account age and sex as covariates, showed that dROM levels were significantly higher in the AD group than in the control group and that BAP levels were significantly lower in the AD + CVD group than in the control and AD groups. As a result, BAP/dROM ratios were significantly lower in the AD and AD + CVD groups than in the control group and significantly lower in the AD + CVD group than in the AD group. MMSE scores significantly and negatively correlated with dROM levels (correlation coefficient (r) = −0.231, P = .02) and significantly and positively correlated with BAP/dROM ratios (r = 0.224, P = .02) but did not correlate significantly with BAP levels in participants with AD and AD + CVD. Oxidative damage was involved in the pathophysiology of the AD and AD + CVD groups and correlated with cognitive impairment. In particular, the AD + CVD group had greater abnormalities of oxidative stress markers, including the antioxidant defense system, than the AD group. These results suggest that intervention for oxidative stress may be appropriate for the inhibition of progression and prevention of cognitive impairment in individuals with AD, particularly for those who also have CVD. Although there may be some differences in oxidative damage between the central nervous system and peripheral tissue, measurements of peripheral oxidative stress markers may be useful for the assessment of disease progression. Conflict of Interest: The authors have no financial disclosures to declare. There are no conflicts of interest regarding this letter. Author Contributions: Hanyu, Iwamoto: study concept and design, acquisition of participants and data, data analysis and interpretation, preparation of manuscript. Hatanaka, Hirose, Fukasawa, Namioka: acquisition of patients, data analysis. Sponsor's Role: None.