Total Small Vessel Disease Score in Neurologically Healthy Japanese Adults in the Kashima Scan Study.

Objective We explored the association between the total small vessel disease (SVD) score obtained with magnetic resonance imaging and risk factors and outcomes in the Japanese population. Methods The presence of SVD features, including lacunes, cerebral microbleeds, white matter changes, and basal ganglia perivascular spaces on MRI, was summed to obtain a "total SVD score" (range 0-4). Ordinal and multinomial logistic regression analyses were performed to investigate the association of higher total SVD scores with vascular risk factors, the Mini-Mental State Examination (MMSE) score, and cerebral atrophy. Results We included 1,451 neurologically healthy adults (mean age, 57.1 years; 47% male). A multivariate ordinal logistic regression analysis showed that the total SVD score was associated with aging, hypertension, blood pressure (BP), diabetes mellitus, MMSE score, and deep cerebral atrophy, but the equal slopes assumption between scores did not hold. A multivariate multinomial logistic regression analysis (total SVD score 0=reference) showed that aging, hypertension, and BP were positively associated with scores of 1, 2, or ≥3. These effects, presented as odds ratios (ORs), increased as the score increased and were strongest with a score of ≥3 [aging (per 10-year increment), OR 4.00, 95% confidence interval (CI) 2.47-6.46; hypertension, OR 5.68, 95% CI 2.52-12.80; systolic BP (per standard deviation increase), OR 1.96, 95% CI 1.41-2.74, respectively]. Diabetes mellitus and deep cerebral atrophy tended to be associated with the SVD scores. The MMSE score showed no consistent associations. Conclusion The total SVD score may be a promising tool for indexing SVD, even in the Japanese population.

Norms of the Mini-Mental state Examination for Japanese subjects that underwent comprehensive brain examinations: the Kashima Scan Study.

OBJECTIVE: The distribution of the Mini-Mental State Examination (MMSE) scores by age and educational level was investigated in subjects that underwent comprehensive brain examinations. METHODS: This cross-sectional study included 1,414 adults without neurological disorders who underwent health-screening tests of the brain, referred to as the "Brain Dock," in our center. The MMSE scores were compared between age groups (40-44, 45-49, 50-54, 55-59, 60-64, 65-69, or ≥70 years) and educational levels [the low education level group (6-12 years) and the high education level group (≥13 years)]. RESULTS: The median age was 59 years, and 763 (54%) were women. There was no significant difference in the MMSE total score between women and men. The stepwise method of the multiple linear regression analysis confirmed that a higher age [ß value, -0.129; standard error (S.E.), 0.020; p<0.001], low education level (6-12 years) (ß value, -0.226; S.E., 0.075; p=0.003), and women (ß values, 0.148; S.E., 0.066; p=0.024) was significantly associated with decreased MMSE score. In general, both the percentile scores and mean scores decreased with aging and were lower in the low education level group than in the high education level group. The degree of decrement in scores with age was stronger in the low education level group than in the high education level group. CONCLUSION: The provided data for age- and education-specific reference norms will be useful for both clinicians and investigators who perform comprehensive brain examinations to assess the cognitive function of subjects.

Joint effect of hypertension and lifestyle-related risk factors on the risk of brain microbleeds in healthy individuals.

Brain microbleeds (MBs) are potential risk factors for future stroke, and hypertension is an established risk factor for MBs. However, data on other lifestyle-related risk factors and their joint effects with hypertension are limited. We enrolled 860 adults who underwent 1.5-T brain magnetic resonance imaging and had no history of stroke. Information on clinical risk factors was obtained from health-screening tests, and dietary history was assessed using a validated, brief, self-administered dietary questionnaire. Subjects were divided into three groups (no MBs, deep MBs and lobar MBs), which were compared for the potential risk factors; their joint effects with hypertension were assessed by logistic regression. Biologic interaction was estimated with the synergy index. After adjustment for possible confounders, age and systolic and diastolic blood pressures were found to be associated with the presence of MBs in a dose-dependent manner, especially in the case of deep MBs. With regard to lifestyle-related factors, current smoking status was significantly associated with deep MBs, and the odds ratio was 2.73 (95% confidence interval (CI) 1.15-6.48). We found that hypertension and current smoking status, higher alcohol consumption or lower calcium intake had joint effects on the risk of MBs and that hypertension and current smoking status had synergistic additive action (synergy index, 6.30; 95% CI 1.07-37.13). These results suggest that approaches combining lowering blood pressure and smoking cessation may greatly reduce the risk of MBs and contribute to preventing stroke.

Distributional impact of brain microbleeds on global cognitive function in adults without neurological disorder.

BACKGROUND AND PURPOSE: Brain microbleeds (MBs) are considered to be associated with cognitive decline and can be pathologically and topographically classified as cerebral amyloid angiopathy-related (located in lobar regions) and hypertensive microangiopathy-related (located in deep regions). We examined whether different effects on global cognitive function might be seen with different distributions of MBs. METHODS: A total of 1279 adults without neurological disorders were studied prospectively. Subjects were divided into 4 groups: without-MBs group; lobar group; deep group; and with in both areas (diffuse group). The Mini-Mental State Examination was administered to determine global cognitive functions, with scores<27 regarded as subnormal. RESULTS: MBs were detected in 98 subjects (8%): 36 subjects (3%) classified as lobar group, 48 subjects (4%) as deep group, and 14 subjects (1%) as diffuse group. Subnormal scores were found in 76 subjects (5.9%), associated with age, education, hypertension, severe white matter hyperintensities, and distribution and number of MBs. In the final model of logistic regression analysis, the deep group (OR, 2.79; 95% CI, 1.14-6.79) was associated with subnormal scores, whereas the lobar group (OR, 0.77; 95% CI, 0.17-3.44) was not. Trend for the diffuse group did not reach the level of significance (OR, 5.01; 95% CI, 0.88-28.41). These trends were also seen in analysis using another cut-off point for subnormal score. Scores for total Mini-Mental State Examination and attention and calculation were significantly lower in the deep group and the diffuse groups compared with the without-MBs group. CONCLUSIONS: This Japanese cross-sectional study demonstrated that MB-related global cognitive dysfunction seems to occur based on hypertensive pathogenesis rather than on cerebral amyloid angiopathy.

Marked cerebral atrophy is correlated with kidney dysfunction in nondisabled adults.

The relationship between kidney dysfunction, such as chronic kidney disease (CKD), and brain morphology has attracted increasing attention, but the association between kidney dysfunction and cerebral atrophy has yet to be determined. The purpose of this study was to clarify the relationship between kidney function and a substantial degree of cerebral atrophy. A total of 610 consecutive Japanese adults without neurological disorders who had undergone health screening tests of the brain were studied prospectively. Magnetic resonance imaging was performed using a 1.5-T scanner. Using a computer-assisted processing system, the percentage of cerebrum atrophy (%Cerebrum atrophy) was calculated as an index of cerebral atrophy. Atrophy was defined as >2 s.d.s below the mean %Cerebrum atrophy. The glomerular filtration rate (GFR) was estimated using the revised equations for estimated GFR from serum creatinine in Japan. Kidney function variables included the GFR value and the prevalence of subjects with GFR <60 ml min⁻¹ per 1.73 m². Cerebral atrophy was found in 25 (4.1%) cases. Univariate analysis showed that age, male sex, hypertension, each kidney function variable, white matter hyperintensities and lacunae were associated with cerebral atrophy. On logistic regression analysis, GFR (odds ratio (OR), 0.64; 95% confidence interval (CI), 0.42-0.98) and GFR <60 ml min⁻¹ per 1.73 m² (OR, 5.93; 95% CI, 1.82-19.27) were significantly associated with cerebral atrophy. On sub-analysis, GFR <60 ml min⁻¹ per 1.73 m² was significantly associated with cortical atrophy (OR, 3.23; 95% CI, 1.15-9.11). Decreased GFR was significantly associated with cerebral atrophy, indicating that treatment of CKD may control age-related degenerative processes of the brain.

Brain microbleeds and global cognitive function in adults without neurological disorder.

BACKGROUND AND PURPOSE: Increasing attention has been paid to associations between cognitive dysfunction and brain microbleeds (MBs). Because all previous studies have investigated patients with neurological disorders, we examined subjects without neurological disorder in order to clarify pathogenic relationships. METHODS: A total of 518 consecutive adults without neurological disorder who had undergone health-screening tests of the brain were studied prospectively. Gradient-echo T2*-weighted MRI using a 1.5-T system was used to detect MBs. The Mini-Mental State Examination (MMSE) was administered to determine cognitive functions. MMSE scores <27 or >1.5 SDs below the age-related mean were regarded as subnormal. RESULTS: MBs were found in 35 subjects (6.8%). MMSE score <27 was found in 25 subjects (4.8%), with MMSE score >1.5 SDs below the age-related mean in 34 subjects (6.6%). Univariate analysis showed presence and number of MBs, short duration of education, and severe white matter hyperintensities as significantly associated with subnormal scores. In logistic regression analysis, presence of MBs (odds ratio [OR], 5.44; 95% CI, 1.83 to 16.19) and number of MBs (OR, 1.32; 95% CI, 1.04 to 1.68) still displayed significant associations with MMSE score <27. Logistic regression analysis revealed a significant relationship between presence (OR, 3.93; 95% CI, 1.44 to 10.74) and number (OR, 1.26; 95% CI, 1.01 to 1.59) of MBs and MMSE score >1.5 SDs below the age-related mean. Among MMSE subscores, "attention and calculation" was significantly lower in MB-positive subjects (P=0.017). CONCLUSIONS: MBs appear to be primarily associated with global cognitive dysfunction.