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Effects of Nilvadipine on Cerebral Blood Flow in Patients With Alzheimer Disease.
de Jong, DLK, de Heus, RAA, Rijpma, A, Donders, R, Olde Rikkert, MGM, Günther, M, Lawlor, BA, van Osch, MJP, Claassen, JAHR
Hypertension (Dallas, Tex. : 1979). 2019;(2):413-420
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Abstract
Cerebrovascular changes, including reduced cerebral blood flow (CBF), occur early in the development of Alzheimer disease and may accelerate disease progression. This randomized, double-blind, placebo-controlled study investigated how 6 months of treatment with the calcium antagonist nilvadipine would affect CBF in patients with mild-to-moderate Alzheimer disease. CBF was measured with magnetic resonance arterial spin labeling in whole-brain gray matter and in a priori defined regions of interest including the hippocampus. Fifty-eight patients were randomly assigned (29 in each group), of whom 22 in both groups had no magnetic resonance exclusion criteria and were medication compliant over 6 months. Mean age was 72.8±6.2 years, mean mini-mental state examination was 20.4±3.4. Nilvadipine treatment lowered systolic blood pressure (Δ=-11.5 [95% CI, -19.7 to -3.2] mm Hg; P<0.01), while whole-brain gray-matter CBF remained stable (Δ=5.4 [95% CI, -6.4 to 17.2] mL/100 g per minute; P=0.36). CBF in the hippocampus increased (left: Δ=24.4 [95% CI, 4.3-44.5] mL/100 g per minute; P=0.02; right: Δ=20.1 [95% CI, -0.6 to 40.8] mL/100 g per minute; P=0.06). There was no significant change in CBF in the posterior cingulate cortex (Δ=5.2 [95% CI, -16.5 to 27.0] mL/100 g per minute; P=0.63) or other regions of interest. In conclusion, nilvadipine reduced blood pressure and increased CBF in the hippocampus, whereas other regions showed stable or small nonsignificant increases in CBF. These findings not only indicate preserved cerebral autoregulation in Alzheimer disease but also point toward beneficial cerebrovascular effects of antihypertensive treatment. Clinical Trial Registration- URL: http://www.clinicaltrials.gov . Unique identifier: NCT02017340.
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Long Term Effect of Intensive Lifestyle Intervention on Cerebral Blood Flow.
Espeland, MA, Luchsinger, JA, Neiberg, RH, Carmichael, O, Laurienti, PJ, Pi-Sunyer, X, Wing, RR, Cook, D, Horton, E, Casanova, R, et al
Journal of the American Geriatrics Society. 2018;(1):120-126
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OBJECTIVES To determine whether long-term behavioral intervention targeting weight loss through increased physical activity and reduced caloric intake would alter cerebral blood flow (CBF) in individuals with type 2 diabetes mellitus. DESIGN Postrandomization assessment of CBF. SETTING Action for Health in Diabetes multicenter randomized controlled clinical trial. PARTICIPANTS Individuals with type 2 diabetes mellitus who were overweight or obese and aged 45 to 76 (N = 310). INTERVENTIONS A multidomain intensive lifestyle intervention (ILI) to induce weight loss and increase physical activity for 8 to 11 years or diabetes support and education (DSE), a control condition. MEASUREMENTS Participants underwent cognitive assessment and standardized brain magnetic resonance imaging (MRI) (3.0 Tesla) to assess CBF an average of 10.4 years after randomization. RESULTS Weight changes from baseline to time of MRI averaged -6.2% for ILI and -2.8% for DSE (P < .001), and increases in self-reported moderate or intense physical activity averaged 444.3 kcal/wk for ILI and 114.8 kcal/wk for DSE (P = .03). Overall mean CBF was 6% greater for ILI than DSE (P = .04), with the largest mean differences between ILI and DSE in the limbic region (3.39 mL/100 g per minute, 95% confidence interval (CI) = 0.07-6.70 mL/100 g per minute) and occipital lobes (3.52 mL/100 g per minute, 95% CI = 0.20-6.84 mL/100 g per minute). In ILI, greater CBF was associated with greater decreases in weight and greater increases in physical activity. The relationship between CBF and scores on a composite measure of cognitive function varied between intervention groups (P = .02). CONCLUSIONS Long-term weight loss intervention in overweight and obese adults with type 2 diabetes mellitus is associated with greater CBF.
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Effects of Yangxue Qingnao Granules on chronic cerebral circulation insufficiency: a randomized, double-blind, double-dummy, controlled multicentre trial.
Wu, C, Liao, L, Yan, X, Li, M, Wu, S, Wang, J, Lin, J, Li, S, Gao, L, DU, J, et al
Psychogeriatrics : the official journal of the Japanese Psychogeriatric Society. 2013;(1):29-34
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BACKGROUND There is a great deal of interest in traditional Chinese medicine as a treatment for chronic cerebral circulation insufficiency (CCCI). In the present study, we evaluated the efficacy and safety of Yangxue Qingnao Granules (YXQNG) as a monotherapy in patients with CCCI. METHODS From July 2007 to May 2010, 273 patients with CCCI at nine centres in China were randomly assigned to receive either YXQNG with nimodipine placebo (n= 140, 12 g/day) or nimodipine with YXQNG placebo (n= 133, 30 mg/day) for 8 weeks. The primary end points after 8 weeks of treatment were changes from baseline in severity of headache, heavy-headed feeling, dizziness and sleep disorder. RESULTS The mean baseline levels of headache, heavy-headed feeling, dizziness and sleep disorder were comparable between the two groups. Both therapies significantly improved these symptoms after 8 weeks of treatment (P < 0.001). Compared with nimodipine therapy, YXQNG resulted in similar reductions in these symptoms. No adverse effects were observed in the YXQNG group. CONCLUSIONS These data demonstrate that YXQNG as a monotherapy were as effective as nimodipine monotherapy in improving the symptoms of CCCI. It is well-tolerated and may have an important place in the management of this condition. Whether a combination of these two medicines will increase therapeutic efficacy deserves further clinical investigation.
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Cerebral blood flow and glucose metabolism in appetite-related brain regions in type 1 diabetic patients after treatment with insulin detemir and NPH insulin: a randomized controlled crossover trial.
van Golen, LW, IJzerman, RG, Huisman, MC, Hensbergen, JF, Hoogma, RP, Drent, ML, Lammertsma, AA, Diamant, M
Diabetes care. 2013;(12):4050-6
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OBJECTIVE To test the hypothesis that insulin detemir, which is associated with less weight gain than other basal insulin formulations, exerts its weight-modulating effects by acting on brain regions involved in appetite regulation, as represented by altered cerebral blood flow (CBF) or cerebral glucose metabolism (CMRglu). RESEARCH DESIGN AND METHODS Twenty-eight male type 1 diabetic patients (age 36.9 ± 9.7 years, BMI 24.9 ± 2.7 kg/m(2), A1C 7.5 ± 0.6%) successfully completed a randomized crossover study, consisting of two periods of 12-week treatment with either insulin detemir or NPH insulin, both in combination with prandial insulin aspart. After each treatment period, patients underwent positron emission tomography scans to measure regional CBF and CMRglu. RESULTS After 12 weeks, A1C, daily insulin doses, fasting insulin, and blood glucose levels were similar between treatments. Insulin detemir resulted in body weight loss, whereas NPH insulin induced weight gain (between-treatment difference 1.3 kg; P = 0.02). After treatment with insulin detemir relative to NPH insulin, CBF was higher in brain regions involved in appetite regulation, whereas no significant difference in CMRglu was observed. CONCLUSIONS Treatment with insulin detemir versus NPH insulin resulted in weight loss, paralleled by increased CBF in appetite-related brain regions in the resting state, in men with well-controlled type 1 diabetes. These findings lend support to the hypothesis that a differential effect on the brain may contribute to the consistently observed weight-sparing effect of insulin detemir.