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      Cerebrovascular Reactivity in Degenerative and Vascular Dementia: A Transcranial Doppler Study

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          Abstract

          Background: An impairment of cerebral microvessels is reported both in normal ageing and in senescence-associated processes, as well as in Alzheimer’s disease (AD) and vascular dementia (VaD). The aim of this study was to explore cerebral hemodynamics by transcranial Doppler in VaD and AD, compared with age-matched control subjects. Methods: Transcranial Doppler was investigated in all patients in the basal condition. Cerebral vasoreactivity to hyper- and hypocapnia was evaluated with CO<sub>2</sub> mixture inhalation followed by hyperventilation. Results: We studied 60 AD and 58 VaD patients and 62 nondemented controls. Both AD and VaD subjects showed lower flow velocities (FV) and higher pulsatility indices (PI) as compared with controls. Lower total vasomotor reactivity and lower response to hypercapnia were observed in the AD and VaD groups as compared with controls. AD and VaD patients did not show significant differences in FV, PI values or cerebral vasoreactivity. Conclusions: Reduced FV and increased PI with a significant vasoreactivity reduction in VaD and AD patients are indicators of impairment of cerebral microvasculature circulation in both diseases. The identification of vascular function impairment in all kinds of dementia could be of help in identifying patients who would thus benefit more from specific therapeutic approaches.

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          Serum lipoprotein levels, statin use, and cognitive function in older women.

          Few strategies are available for the prevention of cognitive impairment in elderly persons. Serum lipoprotein levels may be important predictors of cognitive function, and drugs that lower cholesterol may be effective for the prevention of cognitive impairment. To determine whether serum lipoprotein levels, the 4-year change in serum lipoprotein levels, and the use of statin drugs are associated with cognition in older women without dementia. An observational study of 1037 postmenopausal women with coronary heart disease enrolled in the Heart and Estrogen/progestin Replacement Study (participants at 10 of 20 centers). The Modified Mini-Mental State Examination was administered at the end of the study after 4 years of follow-up. Women whose score was less than 84 points (>1.5 SDs below the mean) were classified as having cognitive impairment. Lipoprotein levels (total, high-density lipoprotein, and low-density lipoprotein [LDL] cholesterol and triglycerides) were measured at baseline and at the end of the study; statin use was documented at each visit. Compared with women in the lower quartiles, women in the highest LDL cholesterol quartile at cognitive testing had worse mean plus minus SD Modified Mini-Mental State Examination scores (93.7 plus minus 6.0 vs 91.9 plus minus 7.6; P =.002) and an increased likelihood of cognitive impairment (adjusted odds ratio, 1.76; 95% confidence interval, 1.04-2.97). A reduction in the LDL cholesterol level during the 4 years tended to be associated with a lower odds of impairment (adjusted odds ratio, 0.61; 95% confidence interval, 0.36-1.03) compared with women whose levels increased. Higher total and LDL cholesterol levels, corrected for lipoprotein(a) levels, were also associated with a worse Modified Mini-Mental State Examination score and a higher likelihood of impairment, whereas high-density lipoprotein cholesterol and triglyceride levels were not associated with cognition. Compared with nonusers, statin users had higher mean plus minus SD Modified Mini-Mental State Examination scores (92.7 plus minus 7.1 vs 93.7 plus minus 6.1; P =.02) and a trend for a lower likelihood of cognitive impairment (odds ratio, 0.67; 95% confidence interval, 0.42-1.05), findings that seemed to be independent of lipid levels. High LDL and total cholesterol levels are associated with cognitive impairment, and lowering these lipoprotein levels may be a strategy for preventing impairment. The association between statin use and better cognitive function in women without dementia requires further study.
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            Cerebrovascular reactivity and cognitive decline in patients with Alzheimer disease.

            The aim of this study was to explore the possible contribution of alterations in cerebral hemodynamics to the evolution of cognitive impairment in patients with Alzheimer disease (AD). Fifty-three patients with AD were investigated. The evolution of cognitive decline over 12 months was evaluated by means of changes in Mini Mental State Examination (MMSE) and AD Assessment Scale for Cognition (ADAS-Cog) scores. Demographic characteristics, vascular risk profile, pharmacological treatment, and presence of white matter lesions were assessed at entry. Further, a basal evaluation of cerebrovascular reactivity to hypercapnia was measured with transcranial Doppler ultrasonography using the breath-holding index (BHI). Of all the variables considered, both MMSE and ADAS-Cog changes had the highest correlation with BHI, followed by age and diabetes. After subdividing both cognitive measures reductions into bigger and smaller-than-average decline (2 points for MMSE; 5 points for ADAS-Cog), multiple logistic regression indicated BHI as the sole significant predictor of cognitive decline. These results show an association between impaired cerebral microvessels functionality and unfavorable evolution of cognitive function in patients with AD. Further research is needed to fully establish whether altered cerebral hemodynamics may be considered an independent factor in sustaining cognitive decline progression or an effect of pathological processes involved in AD.
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              Mixed dementia: emerging concepts and therapeutic implications.

              The prevalence of mixed dementia, defined as the coexistence of Alzheimer disease (AD) and vascular dementia (VaD), is likely to increase as the population ages. To provide an overview of the diagnosis, pathophysiology, and interaction of AD and VaD in mixed dementia, and to provide a systematic literature review of the current evidence for the pharmacologic therapy of mixed dementia. The Cochrane Database of Systematic Reviews was searched using the keyword dementia. MEDLINE was searched for English-language articles published within the last 10 years using the keywords mixed dementia, the combination of keywords Alzheimer disease, cerebrovascular disorders, and drug therapy, and the combination of keywords vascular dementia and drug therapy. Dementia is more likely to be present when vascular and AD lesions coexist, a situation that is especially common with increasing age. The measured benefits in clinical trials for the treatment of mixed dementia are best described as statistically significant differences in cognitive test scores and clinician and caregiver impressions of change. In these studies, the control groups' scores typically decline while the treatment groups improve slightly or decline to a lesser degree over the study period. Nevertheless, even the patients who experience treatment benefits eventually decline. Cholinesterase inhibitor (ChI) therapy for mixed dementia shows modest clinical benefits that are similar to those found for ChI treatment of AD. The N-methyl-D-aspartate (NMDA) antagonist memantine also shows modest clinical benefits for the treatment of moderate to severe AD and mild to moderate VaD, but it has not been studied specifically in mixed dementia. The treatment of cardiovascular risk factors, especially hypertension, may be a more effective way to protect brain function as primary, secondary, and tertiary prevention for mixed dementia. Currently available medications provide only modest clinical benefits once a patient has developed mixed dementia. Cardiovascular risk factor control, especially for hypertension and hyperlipidemia, as well as other interventions to prevent recurrent stroke, likely represent important strategies for preventing or slowing the progression of mixed dementia. Additional research is needed to define better what individuals and families hope to achieve from dementia treatment and to determine the most appropriate use of medication to achieve these goals.
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                Author and article information

                Journal
                ENE
                Eur Neurol
                10.1159/issn.0014-3022
                European Neurology
                S. Karger AG
                0014-3022
                1421-9913
                2007
                August 2007
                12 June 2007
                : 58
                : 2
                : 84-89
                Affiliations
                Department of Neurological Sciences, University of Rome, La Sapienza, Rome, Italy
                Article
                103642 Eur Neurol 2007;58:84–89
                10.1159/000103642
                17565221
                c7f7f955-8ad6-41dd-b59c-c5b414ef3946
                © 2007 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                : 06 September 2006
                : 28 January 2007
                Page count
                Tables: 3, References: 41, Pages: 6
                Categories
                Original Paper

                Geriatric medicine,Neurology,Cardiovascular Medicine,Neurosciences,Clinical Psychology & Psychiatry,Public health
                Transcranial Doppler,Alzheimer’s disease,Cerebral vasoreactivity,Vascular dementia

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