Yuki Takashima

Association between arterial stiffness and cerebral white matter lesions in community-dwelling elderly subjects.

The presence of cerebral white matter lesions (WMLs) on MRI is suggested to be a predictive factor for vascular dementia and stroke. To investigate the relationship between arterial stiffness and WMLs, we performed brain MRI to evaluate the presence of two subtypes of WML—periventricular hyperintensities (PVH) and deep white matter lesions (DWML)—and furthermore, determined the brachial-ankle pulse wave velocity (ba-PWV) as a marker of arterial stiffness in 132 elderly asymptomatic subjects (49 men and 83 women, 70.3±9.0 years). PVH and DWML were observed in 41 (31.0%) and 53 (40.2%) subjects, respectively. The ba-PWV values were significantly greater in subjects with PVH than in those without. DWML also tended to be associated with ba-PWV, but the correlation was not statistically significant. In multiple logistic regression analysis, age and decreased DBP were independently associated with PVH. ba-PWV was also detected as an independent factor for the appearance of PVH (adjusted odds ratio: 2.84, p=0.015) but not DWML. These results indicate that the increase in arterial stiffness contributes to the pathogenesis of PVH rather than DWML. Although further study is needed to clarify the difference between WML subtypes, our study suggests that the measurement of ba-PWV is a simple and useful tool for detecting cerebral arterial dysfunction. (Hypertens Res 2008; 31: 75−81)

Cognitive consequences of multiple lacunes and leukoaraiosis as vascular cognitive impairment in community-dwelling elderly individuals.

The aim of our study was to investigate the effects of silent brain lesions on cognitive function of community-dwelling elderly individuals. Brain magnetic resonance imaging and other medical examinations were performed on 350 nondemented elderly individuals (121 male and 229 female, average age 72.4 years) who resided in the rural community of Sefuri Village, Saga, Japan. The mini mental state examination and modified Stroop test (MST) were used to identify cognitive impairment. White matter lesions (WMLs) and cerebral atrophy on magnetic resonance imaging were measured quantitatively. Multivariate analyses were done using a logistic regression model with a software package. Cognitive impairment defined by mini mental state examination score less than 24 was present in 55 individuals (15.7%). They had a lower educational level, significantly larger quantity of WMLs, and more remarkable cerebral atrophy. Frontal lobe dysfunction was detected in 52 individuals (14.9%) through prolonged MST score (>36 seconds). Impaired frontal lobe function was related to number of silent lacunar infarcts, larger WMLs, and more prominent cerebral atrophy. MST score in individuals with two or more infarcts was significantly more prolonged compared with MST score in those without infarction. These results suggest that WMLs may cause rather diffuse cognitive decline, whereas multiple lacunar infarcts are specifically involved in frontal lobe dysfunction. Silent ischemic lesions in apparently healthy elderly individuals seem to form a distinctive group of people with vascular cognitive impairment without dementia. This group should be the primary target of prevention of vascular dementia.

Clinical correlating factors and cognitive function in community-dwelling healthy subjects with cerebral microbleeds.

We performed brain gradient-echo T2(∗)-weighted magnetic resonance imaging (GE-MRI) in community-dwelling healthy people to investigate the clinical correlates (i.e., possible risk factors) and cognitive function in subjects with cerebral microbleeds (MBs). We examined 368 healthy subjects age 39 years or older living in a Japanese rural community, performing baseline and clinical assessments and brain MRI (T2(∗)-weighted, T1-weighted, T2-weighted, and FLAIR). We assessed global cognitive function in subjects age 60 years or older using the Mini-Mental State Examination (MMSE). An MMSE score >1.5 standard deviations (SD) below the mean score for a particular age group was considered subnormal. MBs were present in 14 of 368 subjects overall (3.8%; 11 males and 3 females) and in 14 of 225 subjects age≥60 years (6.2%). In a logistic regression analysis, older age (odds ratio [OR]=2.649/10 years; 95% confidence interval [CI]=1.465-4.788) and male sex (OR=6.876; 95% CI=1.801-26.248) were significantly related to the presence of MBs. The presence of silent brain infarction and white matter lesions was correlated with MBs, suggesting that MBs were the consequence of small-vessel diseases. There was a significant association between the presence of MBs and subnormal cognition defined by MMSE (OR=5.226; 95% CI=1.463-18.662). Our data suggest that in healthy community-dwelling subjects, MBs may be a consequence of small-vessel disease, which is correlated with aging, male sex, and subnormal cognition.

Hypertension and white matter lesions are independently associated with apathetic behavior in healthy elderly subjects: the Sefuri brain MRI study

Apathy is defined as a syndrome of primary loss of motivation not attributable to emotional distress, intellectual impairment or consciousness disturbance. The aim of our study was to investigate the effects of vascular risk factors and silent ischemic brain lesions on apathetic behavior of community-dwelling elderly subjects. Brain MRI and other medical examinations were performed on 222 non-demented community-dwelling elderly subjects (96 men and 126 women, average age 70.1 years). The apathy group was defined as the most apathetic quintile determined by Starksteins apathy scale. Silent infarction, deep white matter lesions (DWMLs) and periventricular hyperintensities were detected in 12.2, 39.2 and 22.5%, respectively. Linear regression analysis (Pearson) revealed that the scores on the apathy scale correlated slightly but significantly with logarithmically transformed scores of the Modified Stroop Test (r=0.135, P=0.045), but not with the Mini-Mental State Examination. The apathy group tended to have more high blood pressure (141.6/82.6 vs. 136.1/79.6 mm Hg), less prevalent hyperlipidemia (18 vs. 35%) and lower serum albumin. Multivariate analysis (the forward stepwise method of logistic analysis) revealed an independent correlation between the apathy and grade of DWMLs (odds ratio 1.826, 95% confidence interval (CI) 1.129–2.953 per grade) or diastolic blood pressure (DBP) (odds ratio 1.055, 95% CI 1.014–1.098 per mm Hg) after adjusting for possible confounders. The mean apathy scale score in the DBP≧90 mm Hg group was significantly lower (more apathetic) than that in the DBP<80 group (P=0.011, analysis of covariance). This study showed that hypertension and DWMLs are independently associated with apathy in healthy elderly subjects.

Frontal lobe dysfunction caused by multiple lacunar infarction in community-dwelling elderly subjects

We examined the factors that influence frontal lobe function among 119 community-dwelling elderly subjects, based on magnetic resonance imaging (MRI) and clinical findings. We interviewed the subjects, and conducted a neurological examination, electrocardiogram, blood test, brain MRI examination, and cognitive function tests. The modified Stroop test and a personal computer version of the Wisconsin Card Sorting Test (WCST) were used to evaluate frontal lobe function. The subjects with impaired frontal lobe function defined by the modified Stroop test were significantly older, had more lacunar infarcts, and had lower HDL cholesterol values based on a logistic regression model. Among the aged who appear apparently normal, multiple lacunar infarcts are the cause of latent frontal lobe dysfunction.

Subclinical Cerebral Abnormalities in Chronic Kidney Disease

BACKGROUND AND PURPOSE Impaired kidney function or chronic kidney disease (CKD), as measured by estimated glomerular filtration rate (eGFR), is associated with incident stroke risk. However, few studies have examined the relationship between CKD and subclinical cerebral abnormalities. METHODS We examined 675 elderly subjects (mean age 69.9 years), who were living independently at home without apparent dementia, using magnetic resonance imaging. Serum creatinine values, measured by the enzymatic method, were used for the Japanese equation of eGFR. RESULTS Subclinical lacunar infarction, deep white matter lesions, and periventricular hyperintensities were detected in 88 (13.0%), 240 (35.6%) and 158 (23.4%) of the 675 participants, respectively. In the forward stepwise method of logistic analysis, age (OR 2.081/10, 95% CI 1.541-2.810), hypertension (OR 3.656, 95% CI 2.184-6.119), diabetes mellitus (OR 1.961, 95% CI 1.007-3.820), alcohol intake (OR 2.130, 95% CI 1.283-3.535), and eGFR <45 ml/min/1.73 m(2) were significant factors concerning subclinical lacunar infarction. CKD defined as eGFR <60 ml/min/1.73 m(2) was not significantly associated with subclinical lacunar infarction. Decreased eGFR was not a significant factor associated with white matter lesions (WMLs). Age (OR 2.781/10, 95% CI 2.252-3.435), hypertension (OR 1.746, 95% CI 1.231-2.477), diabetes mellitus (OR 1.854, 95% CI 1.070-3.213), but not eGFR were significant factors concerning WMLs. CONCLUSIONS The present study showed that community-dwelling elderly subjects with late stage 3 CKD were at high risk for prevalent subclinical lacunar infarction. The identification of CKD-specific modifiable risk factors for SBI and WMLs is of increased importance for prevention of subclinical brain ischemic lesions.

Chronic kidney disease and subclinical lacunar infarction are independently associated with frontal lobe dysfunction in community-dwelling elderly subjects: The Sefuri brain MRI study

Although recent studies have found that chronic kidney disease (CKD) is an independent risk factor for cognitive impairment in population-based cohorts, the mechanisms of cognitive impairment in subjects with CKD are unclear. We examined 503 elderly subjects (mean age: 72.4 years), who were living independently at home without apparent dementia, using MRI. The subject was judged as having frontal lobe dysfunction if the scores on the modified Stroop test were higher than the fifth quintile for each given decade. Serum creatinine values, measured by the enzymatic method, were used for the Japanese equation of estimated glomerular filtration rate (eGFR). Subjects in the frontal lobe dysfunction group tended to have higher blood pressure, lower eGFR and more lacunar infarcts, and were less educated. When possible confounders were entered into the multivariate logistic regression model, the independent predictors of frontal lobe dysfunction were eGFR (odds ratio 0.854; 95% confidence interval (CI) 0.743–0.983 per 10 ml min−1 per 1.73 m2) and the number of lacunar infarction (odds ratio 1.460; 95% CI 1.127–1.892). The mean of the logarithmically transformed Stroop test scores in the eGFR<60 ml min−1 per 1.73 m2 group was 1.376 (95% CI 1.301–1.451), which was significantly higher than that (1.250) for the eGFR 60–89 ml min−1 per 1.73 m2 group (95% CI 1.215–1.285) (P=0.009) and tended to be higher than that (1.264) for the eGFR ⩾90 ml min−1 per 1.73 m2 group (95% CI 1.188–1.340) (analysis of covariance, adjusted for age). The present study showed that CKD and subclinical lacunar infarction independently contributed to frontal lobe dysfunction in healthy elderly subjects.

Alcohol intake and quantitative MRI findings among community dwelling Japanese subjects

BACKGROUND AND PURPOSE The relationship between alcohol consumption and subclinical findings on magnetic resonance imaging (MRI) remains uncertain. We examined the relationship between light to moderate alcohol intake and silent brain infarction (SBI), white matter lesions (WMLs), and cerebral atrophy. METHODS Cranial MRI was performed on subjects>or=40 years residing in a rural community in Japan (n=385; mean age, 67.2). Alcohol intake and type was determined using a detailed questionnaire; subjects were categorized into three groups: non-drinkers, light drinkers (<7 drinks per week), and moderate drinkers (>or=7 drinks per week). Former drinkers were considered non-drinkers. Periventricular WMLs, deep WMLs and cerebral atrophy were measured quantitatively using a computer-assisted processing system (%PVWML, %DWML, and %Brain, respectively). RESULTS Compared with non-drinkers, the prevalence odds ratios for SBI were significantly higher in light and moderate drinkers, after multivariate adjustment. After adjusting for age, sex, and other related factors, the geometric mean %PVWML volumes in light and moderate drinkers were 1.27% and 1.52%, respectively, significantly larger than those for non-drinkers (0.95%). The geometric mean %DWML volume in light drinkers was 0.10%, which was larger than the value for non-drinkers (0.06%); the value for moderate drinkers (0.13%) was significantly larger than that for non-drinkers. The geometric mean %Brain values for non-, light, and moderate drinkers were 92.1, 91.9 and 90.8%, respectively; a statistically significant difference was found between non-drinkers and moderate drinkers. CONCLUSIONS The present study indicates that regular drinking, including even low levels of consumption, may be a risk factor for subclinical findings detected on MRI in community-dwelling Japanese people.

Sex differences in the risk profile and male predominance in silent brain infarction in community-dwelling elderly subjects: the Sefuri brain MRI study

Although brain infarction is more common in men, the male predominance of silent brain infarction (SBI) was inconsistent in the earlier studies. This study was to examine the relationship between sex differences in the risk profile and SBI. We conducted a population-based, cross-sectional analysis of cardiovascular risk factors and SBI on MRI. We asked all the female participants about the age at natural menopause and parity. SBI was detected in 77 (11.3%) of 680 participants (266 men and 414 women) with a mean age of 64.5 (range 40–93) years. In the logistic analysis, age (odds ratio (OR)=2.760/10 years, 95% confidence interval (CI)=2.037–3.738), hypertension (OR=3.465, 95% CI=1.991–6.031), alcohol intake (OR=2.494, 95% CI=1.392–4.466) and smoking (OR=2.302, 95% CI=1.161–4.565) were significant factors concerning SBI. Although SBI was more prevalent among men, this sex difference disappeared on the multivariate model after adjustment for other confounders. In 215 women aged 60 years or older, age at natural menopause, early menopause, duration of menopause, number of children and age at the last parity were not significantly associated with SBI after adjustment for age. Hypertension and age were considered to be the major risk factors for SBI in community-dwelling people. Male predominance in SBI was largely due to higher prevalence of alcohol habit and smoking in men than in women in our population.

Leisure-Time Physical Inactivity Associated with Vascular Depression or Apathy in Community-Dwelling Elderly Subjects: The Sefuri Study

BACKGROUND Although physical inactivity is a major public health problem, the causative factors for physical inactivity per se are poorly understood. To address this issue, we investigated the relationship between deep white matter lesions (DWMLs) on magnetic resonance imaging, apathy, and physical activities using structural equation modeling (SEM). METHODS We examined 317 community-dwelling elderly subjects (137 men and 180 women with a mean age of 64.5 years) without dementia or clinically apparent depression. Physical activity was assessed with a questionnaire consisting of 3 components (leisure-time, work, and sport activities). RESULTS The mean score from the apathy scale (a visual analogue version of Starksteins apathy scale) of the Grades 2-3 DWML group was 420 (95% confidence interval [CI] 379-461), which was lower (more apathetic) than the Grade 0 DWML group score of 478 (95% CI 463-492) after adjustment for education as a covariate. SEM showed that the direct paths from DWMLs or education to apathy were significant, and the direct path from apathy to leisure-time activity was highly significant (β = .25, P < .001). The degree of apathetic behavior was negatively associated with sport activity in female subjects and positively associated with TV watching in male subjects. CONCLUSIONS The results of the study show that DWMLs are one of the major factors that cause apathetic behavior and that apathy has significant negative effects on leisure-time physical activity in community-dwelling elderly subjects. Even a minor level of apathy without major depression would have a significant impact on activities of daily living and quality of life.