Clinical associations of T2-weighted lesion load and lesion location in small vessel disease: Insights from a large prospective cohort study.

BACKGROUND: Subcortical T2-weighted (T2w) lesions are very common in older adults and have been associated with dementia. However, little is known about the strategic lesion distribution and how lesion patterns relate to vascular risk factors and cognitive impairment. AIM: The aim of this study was to analyze the association between T2w lesion load and location, vascular risk factors, and cognitive impairment in a large cohort of older adults. METHODS: 1017 patients participating in a large prospective cohort study (INtervention project on cerebroVAscular disease and Dementia in the district of Ebersberg, INVADE II) were analyzed. Cerebral T2w white matter and deep grey matter lesions, the so-called white matter hyperintensities (WMHs), were outlined semi-automatically on fluid attenuated inversion recovery images and normalized to standard stereotaxic space (MNI152) by non-linear registration. Patients were assigned to either a low-risk or a high-risk group. The risk assessment considered ankle brachial index, intima media thickness, carotid artery stenosis, atrial fibrillation, previous cerebro-/cardiovascular events and peripheral artery disease as well as a score based on cholesterol levels, blood pressure and smoking. Separate lesion distributions were obtained for the two risk groups and compared using voxel-based lesion-symptom mapping. Moreover, we assessed the relation between lesion location and cognitive impairment (demographically adjusted z-scores of the Consortium to Establish a Registry for Alzheimer's Disease Neuropsychological Assessment Battery Plus, CERAD-NAB Plus) using voxel-based statistics (α = 0.05). RESULTS: A total of 878 out of 1017 subjects (86%) had evaluable MRI data and were included in the analyses (mean age: 68.2 ±â€¯7.6 years, female: 515). Patients in the high-risk group were characterized by a significantly higher age, a higher proportion of men, a higher lesion load (p < 0.001), and a worse performance in some of the cognitive subdomain scores (p < 0.05). Voxels with significant associations to the subjects' cerebrovascular risk profiles were mainly found at locations of the corpus callosum, superior corona radiata, superior longitudinal fasciculus, internal and external capsule, and putamen. While several cognitive domains have shown significant associations with the participants' total lesion burden (p < 0.05), no focal WMH locations were found to be associated with cognitive impairment. CONCLUSION: Age, gender, several cognitive scores, and WMH lesion load were shown to be significantly associated with vascular risk factors in a population of older, but cognitively preserved adults. Vascular risk factors seem to promote lesion formation most severely at well-defined locations. While lesion load showed weak associations to some cognitive scores, no focal locations causing specific cognitive disturbances were identified in this large cohort of older adults.

Reduction of Long-Term Care Dependence After an 8-Year Primary Care Prevention Program for Stroke and Dementia: The INVADE Trial.

BACKGROUND: Stroke and dementia are the major causes for long-term care (LTC) dependence in old age. This intervention trial compared a multidomain prevention program for stroke and dementia with usual medical care in reducing the need for LTC. METHODS AND RESULTS: The Intervention Project on Cerebrovascular Disease and Dementia in the District of Ebersberg (INVADE) was a general practice-based 8-year trial in 2 defined catchment areas in Upper Bavaria, Germany. All 11 317 insurants of a statutory health insurance plan who were ≥55 years of age and lived in the intervention district were offered the opportunity to participate in a prevention program; 3908 enrolled. The 13 301 insurants in the reference district received usual medical care. The intervention consisted of the systematic identification and evidence-based treatment of vascular risk factors. The primary clinical end point was incidence of LTC dependence according to external assessment by a special medical service in the framework of the statutory German LTC insurance. Age- and sex-specific incidence rates from the reference district were used to calculate the expected number of cases of LTC dependence under usual medical care. The expected number was compared with the observed number of cases in the intervention district. Analysis was by intention to treat. During the 5 years after completion of the recruitment period, significantly fewer incident cases of LTC dependence arose in the intervention district than expected (χ(2)=13.25; P<0.001). In women, the incidence was reduced by 10% (P<0.01). In men, the incidence was reduced by 9.6% (P<0.05). CONCLUSIONS: Our results support the feasibility and effectiveness of a primary care prevention program for stroke and dementia to reduce the risk of developing LTC dependence. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01107548. (J Am Heart Assoc. 2012;1:e000786 doi: 10.1161/JAHA.112.000786.).

Effect of an intensive nurse-managed medical care programme on ambulatory blood pressure in hypertensive patients.

BACKGROUND: Uncontrolled hypertension is a major primary healthcare problem. AIM: To investigate whether blood pressure (BP) control in primary care could be improved by nurses taking responsibility for managing hypertensive patients. METHODS: Randomized trial with two groups: usual or intensive care. Patients diagnosed previously as hypertensive and with a systolic office BP greater than 140mmHg were randomized to an intensive care programme managed by trained nurses or to usual care. The intensive care programme included a visit every 6 weeks to the general practitioner's office, with standardized BP measurement, self-measurement training, risk factor checks and advice on BP reduction. The intervention lasted for 1 year. The primary endpoints were systolic BP obtained by 24-hour ambulatory BP monitoring after 1 year and the change compared with baseline. RESULTS: Two hundred patients from 19 physicians were enrolled (102 in the intensive care group). Data on ambulatory BP were available from 140 patients. Systolic BP declined from 134.4+/-14.0 to 126.3+/-10.4mmHg in the intensive care group and from 132.4+/-13.5 to 128.2+/-13.0mmHg in the usual care group. There was no statistically significant difference in values after 1 year (p=0.332). The reduction in systolic BP was significantly greater in the intensive care group (7.6 vs 3.3mmHg in the usual care group; p=0.036). Similar results were observed for diastolic BP and day- and night-time measurements. CONCLUSIONS: An intensive medical care programme in the office setting managed by trained nurses can improve BP control effectively. Nurses could take more responsibility for managing hypertensive patients.

Combined effects of hemoglobin A1c and C-reactive protein on the progression of subclinical carotid atherosclerosis: the INVADE study.

BACKGROUND AND PURPOSE: Glycohemoglobin (hemoglobin A1c [HbA1c]) and high-sensitivity C-reactive protein (hsCRP) are risk indicators for atherosclerosis. Limited information exists regarding the combined effects of inflammation and hyperglycemia. We investigated the joint effects of both parameters on early carotid atherosclerosis progression and major vascular events in diabetic and nondiabetic subjects. METHODS: We analyzed the data of INVADE (Intervention Project on Cerebrovascular Diseases and Dementia in the Community of Ebersberg, Bavaria), a prospective, population-based study conducted in 3534 subjects (mean age, 69 years). In addition to common risk factors, measurements of carotid intima-media thickness (IMT), hsCRP, and HbA1c were performed at baseline and after 2 years of follow-up. RESULTS: For the entire population, IMT progression was significantly related to HbA1c (P=0.003) but not to hsCRP (P=0.06) after risk factor adjustment. The interaction hsCRPxHbA1c was highly significant (P=0.001), and the most pronounced IMT progression was seen in subjects with both parameters in the fourth quartiles compared with subjects with both parameters in the first quartiles (0.028 [0.025, 0.031] versus 0.012 mm/year [0.007, 0.019]; P=0.0013). We observed a significant joint effect of HbA1c and hsCRP on IMT progression in the diabetic (n=882) as well as the nondiabetic subgroup (n=2652). Subjects with HbA1c and hsCRP in the upper 2 quartiles had an increased risk for new vascular events (adjusted hazard ratio in diabetics: 4.3 [1.8, 7.3]; P=0.001; nondiabetics: 2.9 [1.6, 4.7]; P=0.001). CONCLUSIONS: The combination of hyperglycemia and inflammation is associated with an advanced early carotid atherosclerosis progression and an increased risk of new vascular events in diabetic as well as nondiabetic subjects.