Prevalence and etiology of dementia in a Japanese community.

BACKGROUND AND PURPOSE: We sought to determine the type-specific prevalence of dementia and its risk factors in elderly persons from the Japanese community of Hisayama. METHODS: We studied the prevalence of dementia in 887 Hisayama residents (353 men and 534 women) aged 65 years or older (screening rate, 94.6%) using various items of clinical information, neurological examination, and dementia scales. We also studied brain morphology in 50 of 59 determined to have dementia by computed tomography or autopsy during the subsequent 54-month period. Factors relevant to dementia were compared between 27 patients with vascular dementia and 789 control subjects without dementia in a retrospective fashion. RESULTS: The prevalence rate of dementia among Hisayama residents aged 65 or older was estimated at 6.7%, with a females to males ratio of 1:2. Among 50 cases of dementia in which brain morphology was examined, the frequency of vascular dementia was 56%; this rate was 2.2 times higher than that for senile dementia of the Alzheimer type. Aging, hypertension, electrocardiographic abnormalities, and high hematocrit were significantly (p less than 0.05) and independently associated with the occurrence of vascular dementia. CONCLUSIONS: Prevalence of dementia among the Hisayama residents was relatively identical to that previously reported, but vascular dementia was more predominant. Risk factors for vascular dementia were similar to those for lacunar infarcts. Control of hypertension may be a key to reducing dementia among the Japanese population.     

Trends in autopsy‐verified dementia prevalence over 29 years of the Hisayama study

We investigated the trends in dementia over the past 29 years in the town of Hisayama, Japan using 1266 autopsy specimens. The Hisayama study is a prospective cohort study of lifestyle‐related diseases that was started in 1961. Clinical examination of dementia was started in 1985 with five detailed cross‐sectional assessments conducted in 1985, 1992, 1998, 2005 and 2012. To examine the trends in dementia, we divided the 1266 autopsy samples into five groups according to the year of death: I (1986–1991, 257 cases), II (1992–1997, 268 cases), III (1998–2004, 318 cases), IV (2005–2011, 296 cases) and V (2012–2014, 127 cases). The prevalence of all‐cause dementia significantly increased over time (28.4% in group I, 22.4% in group II, 32.1% in group III, 30.1% in group IV, 51.2% in group V; P for trend <0.001). A similar trend was observed for Alzheimer's disease (AD) (15.2%, 11.9%, 17.3%, 20.6% and 33.1%, respectively; P for trend <0.001). A significant increasing trend was observed in both men and women. A rapid increase in senile dementia of the NFT type (SD‐NFT) in recent years was notable. Vascular dementia was the most common type of dementia in men prior to 2004; however, its prevalence decreased over time. Our study revealed that tauopathies, including AD and SD‐NFT, significantly increased in the aged Japanese population over the course of this study. The neuritic plaque pathology of AD was associated with metabolic disorders such as insulin resistance and abnormal lipid metabolism, whereas the risk factors for tau pathology remain unclear. Although aging is considered one of the important risk factors accelerating tau pathology, there could be other risk factors associated with lifestyle diseases.     

Trends in prevalence of Alzheimer’s disease and vascular dementia in a Japanese community: the Hisayama Study

Sekita A, Ninomiya T, Tanizaki Y, Doi Y, Hata J, Yonemoto K, Arima H, Sasaki K, Iida M, Iwaki T, Kanba S, Kiyohara Y. Trends in prevalence of Alzheimer’s disease and vascular dementia in a Japanese community: the Hisayama Study. Objective: To examine secular trends in the prevalence of Alzheimer’s disease (AD) and vascular dementia (VD) in a general Japanese population. Method: Four cross‐sectional examinations were conducted among residents of a Japanese community aged ≥65 in 1985, 1992, 1998 and 2005. Results: The age‐ and sex‐adjusted prevalence of all‐cause dementia significantly increased with time (6.0% in 1985, 4.4% in 1992, 5.3% in 1998 and 8.3% in 2005; P for trend = 0.002). A similar trend was observed for AD (1.1%, 1.3%, 2.3% and 3.8% respectively; P for trend < 0.001), while the age‐ and sex‐adjusted prevalence of VD and other/unclassified dementia showed J‐shaped patterns (for VD: 2.3%, 1.5%, 1.5% and 2.5%, respectively, P for trend = 0.82; for other/unclassified dementia: 2.6%, 1.7%, 1.5% and 2.0%, P for trend = 0.26). The prevalence of AD was likely to increase with time from 1985 to 2005 among subjects aged 75 or older. The ratio of the prevalence of VD to that of AD decreased with time (2.1 in 1985, 1.2 in 1992, 0.7 in 1998 and 0.7 in 2005). Conclusion: Our findings suggest that the prevalence of all‐cause dementia and AD significantly increased over the past two decades in the general Japanese population.     

Education,occupation, and prevalence of dementia: findings from the Conselice study

Information about the epidemiology of dementia in Italy is still limited, although this cognitive disorder represents a serious public health concern. We estimated the prevalence of dementia and dementia subtypes in the elderly population of a Northern Italian municipality, Conselice, in the Emilia Romagna region (n = 1,016 subjects aged 65-97 years). The associations of dementia with two modifiable risk factors, education and occupation, were also evaluated. Overall dementia prevalence was 5.9% (95% confidence interval 4.3-7.8), exponentially increased with age, and was higher among women. Of the dementia cases, 50% were Alzheimer's disease (AD), but an unusually high prevalence (45%) was found for vascular dementia (VD). After adjustment for age and gender, education but not occupation was associated with both AD and VD. This association could not be explained by occupation, life habits, and previous history of hypertension or cardiovascular disease.     

Vascular risk factors in demented elderly: analysis of Alzheimer Clinic materials]

In recent years evidence is increasing that vascular disease is associated with cognitive impairment and dementia. Moreover, presence of cerebrovascular disease may intensify the clinical symptoms of Alzheimer's disease (AD). The aim of the study was to determine the prevalence of vascular risk factors in age and sex matched patients with dementia. We studied 109 patients with AD and 37 patients vascular dementia (VD). DSM-III-R test for dementia, NINCDS-ADRDA guidelines for AD and NINDS-ARIEN for VD were applied. RESULTS: Mean age of dementia onset in AD and VD was 65.8 SD 7.8 and 67.4 SD 7.0 years (p > 0.05), the duration of dementia, MMS and GDS for patients with AD and VD was not significantly different. Arterial hypertension was associated in 51.3% VD and 30.3% AD (p < 0.05), hypotension in 11.1 and 23.6% respectively (p > 0.05), atrial fibrillation was similar in AD and VD, coronary artery disease was presents 64.8% AD and 46.8 VD (p > 0.05) and type 2 diabetes in 21.6% and 10.1% (p > 0.05) respectively. No significant differences in serum lipid profile were found in both groups, except two times higher incidence of normal HDL-cholesterol concentration in AD compare to VD. The relation between alcohol consumption, cigarette smoking and head trauma was similar in both types of dementia. CONCLUSION: Vascular disease and AD have to some extent a shared aetiology, and risk factors that they have in common increase the risk of both disorders independently and vascular disease is perhaps involved in the aetiology of AD.     

Gender differences in the incidence of AD and vascular dementia: The EURODEM Studies. EURODEM Incidence Research Group

OBJECTIVE: To study the difference in risk for dementing diseases between men and women. BACKGROUND: Previous studies suggest women have a higher risk for dementia than men. However, these studies include small sample sizes, particularly in the older age groups, when the incidence of dementia is highest. METHODS: Pooled analysis of four population-based prospective cohort studies was performed. The sample included persons 65 years and older, 528 incident cases of dementia, and 28,768 person-years of follow-up. Incident cases were identified in a two-stage procedure in which the total cohort was screened for cognitive impairment, and screen positives underwent detailed diagnostic assessment. Dementia and main subtypes of AD and vascular dementia were diagnosed according to internationally accepted guidelines. Sex- and age-specific incidence rates, and relative and cumulative risks for total dementia, AD, and vascular dementia were calculated using log linear analysis and Poisson regression. RESULTS: There were significant gender differences in the incidence of AD after age 85 years. At 90 years of age, the rate was 81.7 (95% CI, 63.8 to 104.7) in women and 24.0 (95% CI, 10.3 to 55.6) in men. There were no gender differences in rates or risk for vascular dementia. The cumulative risk for 65-year-old women to develop AD at the age of 95 years was 0.22 compared with 0.09 for men. The cumulative risk for developing vascular dementia at the age of 95 years was similar for men and women (0.04). CONCLUSION: Compared with men, women have an increased risk for AD. There are no gender differences in risk for vascular dementia.     

The accuracy of early diagnosis and predictors of death in Alzheimer's disease and vascular dementia--a follow-up study

A total of 87 patients with mild or moderate degree of dementia of the Alzheimer type (AD) or vascular dementia (VD) was identified (DSM-III criteria), and their cognitive capacity was evaluated by means of rating scales and psychometric tests. Three years later 30 patients (34%) were dead. Significantly more VD than AD patients died. Eight of the survivors declined to participate in a follow-up study, and 1 patient was excluded by mistake. Of the survivors, 17 had indisputably suffered cognitive decline during the follow-up period (4 VD and 13 AD, 35%). In the case of 11 patients (2 VD and 9 AD) cognitive decline remained doubtful, and 20 patients (9 VD and 11 AD, 42%) underwent no intellectual deterioration during the follow-up period. The results underline the problems of early diagnosis of dementia according to DSM-III criteria. For both sexes a high ischemia score and a low body mass index predicted death. A low score on a verbal fluency test predicted death for men but not for women, and a high difference between systolic and diastolic blood pressure increased the risk of death for men but not for women.     

Further evidence of westernization of dementia prevalence in Nagasaki, Japan, and family recognition

The present study examined the prevalence of dementia in the Nagasaki Prefecture. The purposes of our investigation were (a) to study the relationship between aging and the prevalence of dementia and the ratio of Alzheimer's disease (AD) to vascular dementia (VD), (b) to understand the features of early-onset dementia as seen in patients from 60 to 65 years, and (c) to examine the recognition of dementia by family members. The subjects of the study, a total of 4,368, were all 60 years old and over and were residing in the three areas of Nagasaki Prefecture at the time of the investigation, August 1995. We adopted a two-stage design. The first-stage questionnaire that we developed was delivered to subjects, and we selected for the second stage those subjects who met the criteria outlined in the Methods section. The second-stage investigation was an interview by community nurses and psychiatrists. The prevalence of dementia in subjects 60 years and over was 6.2% (men: 5.9%; women: 6.8%). The prevalence increased with age. The AD/VD ratio was 1.4, and was similar to the recent trend in Japan in that the ratio has reversed to resemble the western pattern. In regard to the family members' recognition of illness, the higher the severity of dementia, the higher the recognition ratio of family members became. Only half of these subjects were recognized as having dementia by their family members. In conclusion, the westernization of the AD/VD ratio in Japan was proved. There was little study about family recognition of dementia. In this study, it was remarkable that only half of the subjects were recognized as having dementia by their family members.     

Seizures in patients with Alzheimer’s disease or vascular dementia: A population‐based nested case–control analysis

Purpose: Patients with Alzheimer’s disease (AD) have an increased risk of developing seizures or epilepsy. Little is known about the role of risk factors and about the risk of developing seizures/epilepsy in patients with vascular dementia (VD). The aim of this study was to assess incidence rates (IRs) of seizures/epilepsy in patients with AD, VD, or without dementia, and to identify potential risk factors of seizures or epilepsy. Methods: We conducted a follow‐up study with a nested case–control analysis using the United Kingdom–based General Practice Research Database (GPRD). We identified patients aged ≥65 years with an incident diagnosis of AD or VD between 1998 and 2008 and a matched comparison group of dementia‐free patients. Conditional logistic regression was used to estimate the odds ratio (OR) with a 95% confidence interval (CI) of developing seizures/epilepsy in patients with AD or VD, stratified by age at onset and duration of dementia as well as by use of antidementia drugs. Key Findings: Among 7,086 cases with AD, 4,438 with VD, and 11,524 matched dementia‐free patients, we identified 180 cases with an incident diagnosis of seizures/epilepsy. The IRs of epilepsy/seizures for patients with AD or VD were 5.6/1,000 person‐years (py) (95% CI 4.6–6.9) and 7.5/1,000 py (95% CI 5.7–9.7), respectively, and 0.8/1,000 py (95% CI 0.6–1.1) in the dementia‐free group. In the nested case–control analysis, patients with longer standing (≥3 years) AD had a slightly higher risk of developing seizures or epilepsy than those with a shorter disease duration, whereas in patients with VD the contrary was observed. Significance: Seizures or epilepsy were substantially more common in patients with AD and VD than in dementia‐free patients. The role of disease duration as a risk factor for seizures/epilepsy seems to differ between AD and VD.     

Age-specific incidence rates of Alzheimer's disease: the Baltimore Longitudinal Study of Aging

OBJECTIVE: To estimate age-specific incidence rates of AD in the Baltimore Longitudinal Study of Aging (BLSA). BACKGROUND: The BLSA is a volunteer cohort of normal subjects followed longitudinally with biennial evaluations at the Gerontology Research Center of the National Institute on Aging. METHODS: Subjects are 1236 participants (802 men, 434 women) in the BLSA with longitudinal follow-up between January 1985 and May 1998. The average length of follow-up was 7.5 years, with participants evaluated every 2 years by physical, neurologic, and neuropsychological examinations. Using Diagnostic and Statistical Manual of Mental Disorders, 3rd ed., revised and National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria, the authors diagnosed dementia and AD. RESULTS: The authors diagnosed 155 cases of dementia, of which 114 (74%) were AD. Incidence rates of AD increased with age from an estimated 0.08% per year (95% CI 0.00 to 0.43) in the 60 to 65 age group to an estimated 6.48% per year (95% CI 5.01 to 8.38) in the 85+ age group for men and women combined. The doubling time of incidence rates was estimated to be approximately 4.4 years and the median time of conversion from mild cognitive impairment to diagnosis of AD was estimated to be 4.4 years. There was a trend for women to have higher incidence rates than men and for fewer years of education to be associated with higher incidence rates; however, these effects were not significant. CONCLUSION: Incidence rates for AD in the BLSA are consistent with published rates in other studies. The longitudinally followed subjects of the BLSA offer a unique opportunity to prospectively investigate the antecedents of AD.     

Dementia associated with lacunar infarction.

BACKGROUND AND PURPOSE: The purpose of this study was to assess the number of patients with lacunar lesions who develop dementia and to evaluate in patients with and without dementia the relevance of risk factors for cerebrovascular disease, the occurrence of leukoaraiosis, the volume and location of vascular lesions, the size of ventricular and subarachnoid spaces, and stroke recurrence. METHODS: One hundred eight patients in whom computed tomograms revealed lacunar lesions that could account for their clinical neurological pictures were followed up for an average of 4 years after their first lacunar stroke. RESULTS: Twenty-five patients (23.1%) developed dementia. The prognosis regarding occurrence of dementia during the follow-up period, evaluated by the Kaplan-Meier method, was significantly worse in subjects with the greatest evidence of cerebral atrophy (p less than 0.009) and in subjects who underwent new focal cerebrovascular episodes (p less than 0.000001). No differences were seen in the frequency of vascular risk factors or the site or volume of lesions between the demented and nondemented groups. CONCLUSIONS: Patients with lacunar infarcts suffer from dementia 4-12 times more frequently than the normal population. Cerebral atrophy and recurrent stroke, as well as other as-yet unclarified factors, are involved in producing dementia.     

广州市城乡65岁及其以上人群痴呆患病率调查

目的调查广州市城乡≥65岁人群痴呆的患病率。方法采用分层随机整群抽样方法对广州市城乡人群进行抽样，用筛查和确诊两阶段法进行调查，实查14个居委会、2个村委会中≥65岁人群共3780人。按美国精神障碍诊断与统计手册第4版的标准诊断痴呆，阿尔茨海默病（AD）诊断采用美国神经病学、语言障碍和卒中研究所及阿尔茨海默病与相关障碍协会的标准。结果（1）查出痴呆患者182例，粗患病率为4．81％；其中AD128例（3．39％），血管性痴呆（VD）44例（1．16％）；经2000年广州市人口年龄构成进行标化，痴呆、AD和VD患病率分别为4．54％、3．17％和1．11％。（2）女性痴呆患者134例，粗患病率（5．98％）高于男性（48例，3．12％；P〈0．001），经年龄标化患病率分别为6．03％和2．74％。（3）痴呆患病率随年龄增长急剧上升。结论广州地区年龄≥65岁老人的痴呆患病率为4．81％，AD患病率高于VD。老年期痴呆患病率随年龄的增长而急剧升高。     

Depressive symptoms, sex, and risk for Alzheimer's disease

Depression associates with increased risk for dementia and Alzheimer's disease (AD), although it is unclear whether it represents an actual risk factor or a prodrome. To determine the relative hazard of premorbid depressive symptomatology for development of dementia and AD, we studied risk for incident dementia and AD over a 14-year period in 1,357 community-dwelling men and women participating in the 40-year prospective Baltimore Longitudinal Study of Aging. Screening for depressive symptoms, comprehensive medical and neuropsychological evaluations were prospectively collected every 2 years. Time-dependent proportional hazards of development of AD or dementia were calculated separately for men and women, with symptoms of depression detected at 2-, 4-, and 6-year intervals before onset of dementia symptoms. Vascular risk factors were analyzed as covariates. Premorbid depressive symptoms significantly increased risk for dementia, particularly AD in men but not in women. Hazard ratios were approximately two times greater than for individuals without history of depressive symptoms, an effect independent of vascular disease. We conclude that the impact of depressive symptoms on risk for dementia and AD may vary with sex. Further studies assessing separately the role of depression as a risk factor in men and women are necessary.     

Hypertension, cigarette smoking, and the decline in stroke incidence in eastern Finland

Finland has high rates of both cardiovascular disease and cardiovascular disease risk factors. We studied random samples of the population 30-59 years of age for risk factors in two provinces of eastern Finland in 1972 and 1977. We then followed both cohorts until 1985 through linkage with national hospital discharge and death certificate registers. The prevalence of hypertension and smoking in both provinces declined between 1972 and 1977, as did the stroke incidence in the 8-year period of follow-up of each cohort. We observed no differences in stroke incidence between the two provinces. The relative risk of stroke in the later period (1977-1985) was 0.71 and 0.58 for men and women, respectively, when compared with the earlier period (1972-1980). Overall, 28% of all stroke events could be attributed to hypertension, 17% to smoking, and 43% to these two factors jointly. The decrease in the prevalence of hypertension and smoking accounted for about 29% of the decline.     

Prevalence, resource utilization and costs of vascular dementia compared to Alzheimer's dementia in a population setting

OBJECTIVES: To determine the prevalence of dementia and to measure the monetary impact and health resources utilization of vascular dementia (VD) compared to Alzheimer's dementia (AD) in persons aged over 64 years in a population setting. METHODS: Retrospective, cross-sectional study. In the initial phase, information was obtained on specific clinical characteristics from the subjects with an active diagnosis of dementia. The second phase consisted of a clinical evaluation and validation of the cases. Mini-Mental State Examination was used to assess cognitive impairment. Dementia and its subtypes were determined using established diagnostic criteria. Information was obtained on the use of health care resources (direct costs) and the number of hours devoted by the primary caregiver (indirect costs) for patients with a documented diagnosis of AD or VD within the last 6 months prior to the interview. A multiple logistic regression analysis was performed to correct the model. RESULTS: A total of 6,004 subjects were analyzed, 258 with diagnosis of dementia (overall prevalence: 4.3%). An evaluation was made of 224 patients, and gross prevalence of AD and VD was 2.4 and 1.0%, respectively. Cost per patient per semester was EUR 8,086 for AD and EUR 11,039 for VD (p = 0.016). 85.5% of the cost was attributable to primary caregiver time in AD and 84.4% in VD. CONCLUSIONS: The prevalence of AD and VD increases with age. No sociodemographic differences were seen between AD and VD. Costs associated with health care resource and primary caregiver utilization were high, being higher in VD than in AD.     

Bone mineral density and the risk of Alzheimer disease

BACKGROUND: Some, but not all, studies have suggested that estrogen replacement therapy has a beneficial effect on cognition in postmenopausal women. Bone mineral density (BMD) is a potential surrogate marker for cumulative estrogen exposure and has been associated with cognitive performance and risk of cognitive deterioration. OBJECTIVE: To examine whether low BMD in elderly individuals is associated with an increased risk of developing Alzheimer disease (AD). DESIGN, SETTING, AND PARTICIPANTS: Community-based prospective cohort study of 987 subjects (610 women) who were cognitively intact and had baseline BMD measured at the femoral neck, the trochanter, and the radial shaft between 1988 and 1989. MAIN OUTCOME MEASURES: Incidence of AD and all-cause dementia during an 8-year follow-up period. RESULTS: Women in the lowest quartile of femoral neck BMD had more than twice the incidence of AD (hazard ratio, 2.04; 95% confidence interval, 1.11-3.75) and all-cause dementia (hazard ratio, 2.01; 95% confidence interval, 1.16-3.49) compared with those in higher quartiles after adjusting for age, sex, apolipoprotein E epsilon4, baseline homocysteine level, education, estrogen use, smoking, and stroke. A similar but statistically nonsignificant relationship was observed between BMD of the femoral trochanter and AD, while no such relationship was seen between radial BMD and AD or all-cause dementia. In men, there was a trend toward an inverse relationship between BMD and the risk of AD, but the relationship was not statistically significant at any of the 3 sites. CONCLUSIONS: Low femoral neck BMD was associated with approximately 2 times the risk of AD and all-cause dementia in women but not men, suggesting the possibility that cumulative estrogen exposure may influence the risk of developing AD. Additional studies are needed to confirm this correlation.     

Prevalence of dementia in China

To obtain prevalence estimates of dementia in China, an analysis of 17 studies published in Chinese from 1990-1999 was carried out. The prevalence rates for the population aged 60 years and older were 1.26% for Alzheimer's disease (AD) and 0.74% for vascular dementia (VD). The prevalence of AD was 2.10% in women and 0.76% in men, while the prevalence of VD was 0.71 and 0.69%, respectively. The prevalence of AD among the three educational levels in our study (illiterate, primary school and high school) were 1.79, 0.45 and 0.15%, respectively, and those of VD were 0.26, 0.58 and 0.26%, respectively. Although the prevalence of AD (2.29%) was higher in urban than in rural areas (1.67%), the difference was not statistically significant. The difference between the prevalence of VD in urban (0.67%) and in rural areas (1.13%) was not significant either. The prevalence of AD increased with age, and gender was found to be associated with Alzheimer's disease. The prevalence of VD also increased with age, but there was no association between VD and gender.     

87例老年期痴呆住院患者死亡分析

目的:探讨住院老年期痴呆的生存时间和死亡原因.方法:收集1994年4月～2002年4月间住院死亡的阿尔茨海默病(AD)和血管性痴呆(VD)病例共87例.了解其发病年龄,病程,住院天数和死亡原因.结果:AD组发病年龄和死亡年龄均显著高于VD组.两组生存时间差异无显著性.但AD组中男性生存时间显著短于女性.两组住院天数差异无显著性.两组死亡原因主要均为感染和全身衰竭.结论:我国住院的AD患者发病年龄和死亡年龄均晚于VD患者.女性AD患者生存时间长于男性患者.感染和全身衰竭是老年期痴呆的主要死亡原因.     

Leukoaraiosis in relation to prognosis for patients with lacunar infarction.

BACKGROUND AND PURPOSE: Close relations between leukoaraiosis detected by computed tomography or magnetic resonance imaging and stroke, particularly lacunar infarction, have been reported. We studied whether leukoaraiosis is related to long-term prognosis for patients with lacunar infarction. METHODS: We examined monthly 215 patients with lacunar infarction after their first stroke. They comprised 95 patients with leukoaraiosis disclosed by computed tomography on admission (58 men and 37 women; mean age, 71.3 +/- 9.0 years) and 120 patients without leukoaraiosis (81 men and 39 women; mean age, 65.5 +/- 8.9 years). These patients had no previous history of either stroke or obvious dementia before their index stroke. We compared the prognosis with and without leukoaraiosis based on analysis of recurrent stroke, survival, and the prevalence of dementia and rate of dependence in activities of daily living. RESULTS: Life table analysis revealed that the recurrent stroke rate was significantly higher in the patients with leukoaraiosis than in those without it (p = 0.004). The prevalence of dementia and rate of dependence in activities of daily living both 1 month after the index stroke and at the end of the follow-up period were significantly higher in the patients with leukoaraiosis (all parameters, P less than 0.001). Their survival rate was significantly lower than in those not suffering from leukoaraiosis (p = 0.012). Significant differences in these comparisons were also observed after matching for age and sex. CONCLUSIONS: The presence of leukoaraiosis as identified by computed tomography indicates a poor prognosis for patients with lacunar infarction.