<?xml version="1.0" encoding="utf-8"?>
<recommendedContent xmlns="http://api.mspoke.com">
    <recommendedItem id="20090101_19_2236"
                     title="ICAD: Alzheimer&apos;s Drug Mechanism Defies Animal Studies"
                     score="-0.005"
                     href="http://www.medpagetoday.com/MeetingCoverage/ICAD/tb/15103?impressionId=1265792452967"
                     
      VIENNA, July 15 -- An independent study aimed at understanding the mechanism of dimebolin (Dimebon), a controversial, yet potentially beneficial investigational anti-Alzheimer&apos;s drug, was long on questions and short on answers, researchers here said.
              &lt;p&gt;  
              &lt;p&gt;For example when the drug was examined in a mouse model, short-term administration resulted in a rapid increase in levels of A-beta amyloid. Beta amyloid is a putative cause of Alzheimer&apos;s disease and reducing levels of the compound in the brain is a frequent goal of drug therapy for Alzheimer&apos;s.
              &lt;p&gt; 
              &lt;p&gt;The rise in amyloid levels was surprising in light of published Phase II clinical data indicating that dimebolin -- long used as an antihistamine in Russia -- not only delayed deterioration in Alzheimer&apos;s patients, but also appeared to improve cognition in some patients. (See &lt;a href=&quot;http://www.medpagetoday.com/Geriatrics/AlzheimersDisease/10174&quot; target=&quot;blank&quot;&gt;Old Antihistamine Pops Up as Potential Alzheimer&apos;s Therapy&lt;/a&gt;)
              &lt;p&gt;  
              &lt;p&gt;&quot;Our study raises more questions than we have answered,&quot; said Samuel Gandy, MD, PhD, professor of neurology and psychiatry at the Mt. Sinai School of Medicine, New York, at the Alzheimer&apos;s Association 2009 International Conference on Alzheimer&apos;s Disease here.
              &lt;p&gt;  
              &lt;p&gt;&quot;This result is highly unexpected in what may prove to be a clinically beneficial Alzheimer&apos;s drug,&quot; Dr. Gandy said.
              &lt;p&gt; 
              &lt;p&gt;Dr. Gandy studied the drug in brain cells from transgenic mice as a model of what happens in human cells. The studies indicated that dimebolin increased the amount of amyloid in the cells up to two times.
              &lt;p&gt; 
              &lt;p&gt;Asked to explain the increase in amyloid, he said, &quot;It may turn out that the drug works by getting toxic amyloid out of brain nerve cells. Or, the effects of dimebolin on other brain systems may override its effect on increasing beta amyloid. Finally, the drug&apos;s beneficial actions might have nothing to do with amyloid, which, if true, indicates the existence of important therapeutic targets independent of beta amyloid.&quot;
              &lt;p&gt; 
              &lt;p&gt;Dr. Gandy, however, was not ready to abandon the amyloid hypothesis as a cause of Alzheimer&apos;s disease. &quot;I know of no pharmaceutical company that is preparing medications that increase levels of beta amyloid in the brain,&quot; he said.
              &lt;p&gt; 
              &lt;p&gt;He noted that the increase in beta amyloid in his experiments occurred within the first few hours after administration and does not indicate what long-term conditions would be. He also said that the doubling of beta amyloid observed in his model was a relatively modest increase -- one that could be offset by other effects of the drug.
              &lt;p&gt; 
              &lt;p&gt;Lynn Seely, MD, chief medical officer for Medivation, the San Francisco-based company that is developing dimebolin, said the company believes that dimebolin exerts its influence on outcomes by strengthening cell mitochondrion, which, in turn, helps in cell survival.
              &lt;p&gt; 
              &lt;p&gt; &quot;We really don&apos;t know what to make of Dr. Gandy&apos;s studies,&quot; Dr. Seely said.
              &lt;p&gt; 
              &lt;p&gt;She said a second pivotal study -- the Phase II trial has been accepted by the Food and Drug Administration as one of two trials needed for new drug approval -- has completed enrollment and the Phase III results of the six-month trial are expected to be reported in 2010.
              &lt;p&gt; 
              &lt;p&gt;Another study is also underway, she said, that looks at outcomes when dimebolin is used with donepezil (Aricept). A preliminary safety and tolerability trial of the combination showed no major problems, she said.
              &lt;p&gt; 
              &lt;p&gt;&quot;If the clinical benefits of dimebolin are confirmed by the ongoing clinical trials, it may give us pause in our belief that amyloid is the major cause of Alzheimer&apos;s disease and whether we need to be looking at additional mechanisms,&quot; said Ralph Nixon, MD, PhD, professor of psychiatry and cell biology at New York University School of Medicine.
              &lt;p&gt; 
              &lt;p&gt;&quot;Should there be a positive result in these new clinical trials that would confirm the findings in the original trials, it would suggest a plausible link to mitochondria,&quot; he said. Dr. Nixon moderated a press briefing at which Dr. Gandy&apos;s work was reviewed.
              &lt;p&gt; 
              &lt;p&gt;&lt;table cellspacing=&quot;0&quot; hspace=&quot;1&quot; style=&quot;border-style:solid; border-width:1px; border-color:#8dabbc; font-family:arial; font-size:12px; background-color:#DBE9F2; padding:5px 5px 5px 5px;&quot;&gt;
&lt;tr&gt;&lt;td&gt;The study was supported by Cure Alzheimer&apos;s Fund and National Institute on Aging.
              &lt;p&gt; 
              &lt;p&gt;Dr. Gandy disclosed possible financial conflicts of interest with Forest, Wyeth, Elan, Amicus, Diagenic and Epix. Dr. Seely is an employee of Medivation. Dr. Nixon said he had no disclosures.&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;
             
    </recommendedItem>
    <recommendedItem id="20090101_19_4082"
                     title="Imaging Test May Predict Alzheimer&apos;s (CME/CE)"
                     score="-0.005"
                     href="http://www.medpagetoday.com/Neurology/AlzheimersDisease/tb/17518?impressionId=1265792452967"
                     
      &lt;p&gt;An imaging technique used to visualize the brains of patients already diagnosed with Alzheimer&apos;s disease may also predict who will develop the disease in the future, a new study found.&lt;/p&gt;
&lt;p&gt;Patients who tested higher on positron emission tomography (PET) scans for Pittsburgh Compound B (PiB), a compound that binds to the plaque in the brains of Alzheimer&apos;s disease patients, were nearly four times more likely to suffer cognitive declines and loss of brain tissue associated with Alzheimer&apos;s disease (95% CI 1.22 to 19.01; &lt;em&gt;P&lt;/em&gt;=0.02), according to an online report in the Dec. 14 &lt;em&gt;Archives of Neurology&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;&quot;Many more individuals, studied for longer intervals and ideally through autopsy, will be needed to confirm or refute our observations,&quot; John C. Morris, MD, of Washington University in St. Louis, and colleagues wrote.&lt;/p&gt;
&lt;p&gt;&quot;Nonetheless, this study provides support for the premise that preclinical Alzheimer&apos;s disease, detected either by the cerebrospinal fluid signature for Alzheimer&apos;s disease or here by elevated PiB retention, predicts symptomatic Alzheimer&apos;s disease.&quot;&lt;/p&gt;
&lt;p&gt;Pittsburgh Compound B binds to beta-amyloids, amino acids that form plaques in the brains of Alzheimer&apos;s patients. The compound has been used in combination with PET scans to detect the plaques in patients diagnosed with the disease.&lt;/p&gt;
&lt;p&gt;However, to detect early cases of Alzheimer&apos;s where patients have yet to show clinical symptoms, doctors have relied on screening an individual&apos;s cerebrospinal fluid for biomarkers of the condition.&lt;/p&gt;
&lt;p&gt;In their study, Morris and colleagues explored whether PET PiB might also be used to detect preclinical Alzheimer&apos;s.&lt;/p&gt;
&lt;p&gt;&quot;The concept of preclinical Alzheimer&apos;s disease holds that the Alzheimer&apos;s pathologic process operates for many years before producing a clinically detectable impairment,&quot; they wrote.&lt;/p&gt;
&lt;p&gt;&quot;A key corollary of this concept is that preclinical Alzheimer&apos;s disease is not benign and will eventually produce sufficient synaptic and neuronal damage to cause cognitive decline and other symptoms of Alzheimer&apos;s disease.&quot;&lt;/p&gt;
&lt;p&gt;The researchers studied the use of PET PiB to predict the disease in 159 participants (mean age 71.5 years) at the Alzheimer&apos;s Disease Research Center at Washington University.&lt;/p&gt;
&lt;p&gt;They followed the participants, who initially showed no signs of dementia and had Clinical Dementia Ratings (CDR) of 0 based on a PET PiB, for periods ranging between 10 months and 5.5 years after the scans.&lt;/p&gt;
&lt;p&gt;Over the course of the study, twenty-three participants progressed to CDR 0.5 at follow-up assessment.&lt;/p&gt;
&lt;p&gt;Nine of these 23 patients were diagnosed with dementia of the Alzheimer&apos;s type (DAT) and showed declines in episodic memory, semantic memory, and visuospatial performance, along with shrinkage of the parahippocampal gyrus portion of the brain.&lt;/p&gt;
&lt;p&gt;Older patients and those with initial higher mean values of PiB binding (indicating more beta-amyloid plaques) were more likely to progress to the CDR 0.5/DAT group. The test did not predict which patients would develop dementia from causes other than Alzheimer&apos;s.&lt;/p&gt;
&lt;p&gt;In addition to cautioning that their results need to be confirmed by larger studies, the authors noted that the study was limited by short follow-up times and only one autopsy-confirmed case of dementia of Alzheimer&apos;s type (patients with the other eight cases were still alive).&lt;/p&gt;
&lt;p&gt;They also noted that the psychometric battery used in the study was developed in 1979 and may have lacked more sensitive measures developed since then.&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;The study was funded by the National Institute on Aging, the Charles and Joanne Knight Alzheimer&apos;s Research Initiative and an anonymous foundation.&lt;/p&gt;&lt;p&gt;Co-investigator Dr. Mark A. Mintun reported receiving consulting fees from Avid RP.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20090101_19_4104"
                     title="Beta-Amyloid Inhibitor Fails in Alzheimer&apos;s Trial (CME/CE)"
                     score="-0.005"
                     href="http://www.medpagetoday.com/Neurology/AlzheimersDisease/tb/17560?impressionId=1265792452967"
                     
      An investigational drug to reduce beta-amyloid protein deposition failed to prevent Alzheimer&apos;s disease progression in a Phase III study, after the drug had shown promise in an earlier trial.&lt;br&gt;
&lt;br&gt;Declines in cognitive function and ability to perform daily tasks were the same in patients who received tarenflurbil or a placebo in a 1,684-patient randomized trial, reported Robert C. Green, MD, MPH, of Boston University, and colleagues.&lt;br&gt;
&lt;br&gt;&quot;Tarenflurbil did not slow cognitive decline or the loss of activities of daily living in patients with mild Alzheimer&apos;s disease,&quot; the researchers concluded in their report, published in the Dec. 16 &lt;em&gt;Journal of the American Medical Association&lt;/em&gt;.&lt;br&gt;
&lt;br&gt;The finding raises more questions about the pathological role of beta-amyloid plaques in the disease  --  suggesting, perhaps, that such plaques are not responsible themselves for the death of brain cells or the clinical symptoms of Alzheimer&apos;s disease.&lt;p&gt;&lt;/p&gt;
&lt;p&gt;But it is also possible that the drug did not effectively inhibit plaque formation, since only clinical symptoms were evaluated in the study.&lt;/p&gt;
&lt;p&gt;Tarenflurbil is the R-enantiomer of the nonsteroidal anti-inflammatory drug flurbiprofen (Ansaid). In vitro studies have shown that it inhibits the gamma-secretase enzyme that cleaves the 42-amino acid version of beta-amyloid protein from a precursor molecule.&lt;/p&gt;
&lt;p&gt;This form of beta-amyloid is believed to be the primary component of the sticky, insoluble plaques that infest the brains of Alzheimer&apos;s patients.&lt;/p&gt;
&lt;p&gt;Studies in animals have suggested that such plaques are neurotoxic, but researchers have argued for years as to their contribution to the neurological and clinical features of human Alzheimer&apos;s disease.&lt;/p&gt;
&lt;p&gt;A Phase II trial of tarenflurbil reported last year indicated that the drug blocked clinical progression in patients with mild disease. (See &lt;a href=&quot;http://www.medpagetoday.com/Geriatrics/AlzheimersDisease/9277&quot; mce_href=&quot;http://www.medpagetoday.com/Geriatrics/AlzheimersDisease/9277&quot; target=&quot;_blank&quot;&gt;Investigational Drug Slows Functional Decline in Early Alzheimer&apos;s&lt;/a&gt;)&lt;/p&gt;
&lt;p&gt;That finding prompted the drug&apos;s manufacturer, Myriad Pharmaceuticals, to sponsor a Phase III study, also in patients with early-stage symptoms.&lt;/p&gt;
&lt;p&gt;The primary outcomes were changes in the 80-point cognitive subscale of the Alzheimer Disease Assessment Scale (ADAS-Cog) and in functional ability as assessed by the Alzheimer Disease Cooperative Study&apos;s Activities of Daily Living index (ADCS-ADL), after 18 months of treatment.&lt;/p&gt;
&lt;p&gt;Patients receiving tarenflurbil showed a mean increase of 7.27 points on the ADAS-Cog scale during the study, compared with rise of 7.08 points in the placebo group.&lt;/p&gt;
&lt;p&gt;On the ADCS-ADL scale, scores declined by a mean 7.12 points with tarenflurbil versus 7.08 points in the placebo group.&lt;/p&gt;
&lt;p&gt;There were also no significant differences in a host of secondary outcomes, including scores on two other neuropsychiatric instruments (Mini-Mental State Exam and Neuropsychiatric Inventory) as well as assessments of patient and caregiver quality of life and caregiver burden.&lt;/p&gt;
&lt;p&gt;Discontinuations because of adverse events were substantially more common with tarenflurbil (18.4% versus 11.6% with placebo, &lt;em&gt;P&lt;/em&gt;&amp;lt;0.001).&lt;/p&gt;
&lt;p&gt;However, adverse event rates overall did not differ between treatments, nor did the particular types of events reported. Dizziness was slightly more common, but still affected less than 10% of patients in the tarenflurbil group.&lt;/p&gt;
&lt;p&gt;Green and colleagues offered a possible explanation for the lack of efficacy. &quot;Data from earlier studies in healthy older individuals had indicated a dose-dependent penetration of drug from plasma to cerebrospinal fluid of only 0.5% to 1%,&quot; they wrote, although CSF concentrations weren&apos;t measured in the current study.&lt;/p&gt;
&lt;p&gt;&quot;It is possible that the 800-mg dose [used in the study] may have been too low for a therapeutically relevant gamma-secretase modulatory effect in humans,&quot; they wrote.&lt;/p&gt;
&lt;p&gt;On the other hand, Green and colleagues pointed out, patients with the highest plasma levels of tarenflurbil in the study  --  who might be assumed to have had the highest CSF concentrations as well  --  did not have noticeably better clinical outcomes.&lt;/p&gt;
&lt;p&gt;The researchers asserted that faulty trial design was not responsible for the negative findings, and an accompanying editorial by two independent neurobiologists concurred.&lt;/p&gt;
&lt;p&gt;&quot;With 18 months of follow-up, it was adequately powered and designed to detect delayed progression of disease,&quot; wrote Thomas Montine, MD, PhD, of the University of Washington, and Eric Larson, MD, MPH, of Group Health Research Institute, both in Seattle.&lt;/p&gt;
&lt;p&gt;Montine and Larson also noted that the study was &quot;the largest treatment trial for [Alzheimer&apos;s disease] to date.&quot;&lt;/p&gt;
&lt;p&gt;The study authors said in their report that the study serves as &quot;a reminder that interventions affecting amyloid have not yet been shown to alter the course of Alzheimer&apos;s disease.&quot;&lt;/p&gt;
&lt;p&gt;But in an interview, Green said it was far too early to close the door on treatments targeting beta-amyloid.&lt;/p&gt;
&lt;p&gt;&quot;I think the amyloid story still has many chapters to be written,&quot; he told &lt;em&gt;MedPage Today&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;&quot;This was one gamma-secretase modulator, which may not have worked because not enough of it got into the brain . . . or because it was not a robust enough modulator. It may not have worked because, even in mild Alzheimer&apos;s disease, the cascade of events may have already been set in motion, such that it&apos;s hard to slow it down at that stage,&quot; he continued, adding that the answers won&apos;t be clear &quot;until a number of agents have been tried.&quot;&lt;/p&gt;
&lt;p&gt;Green said that, despite the negative finding, the trial had much to tell designers of future trials about the sample sizes, duration, and measurements needed to adequately test Alzheimer&apos;s drugs.&lt;/p&gt;
&lt;p&gt;Montine and Larson, in their editorial, cautioned that most patients with Alzheimer&apos;s disease also have other pathologies, such as vascular insufficiency and Lewy body disease, that contribute to dementia symptoms to varying degrees.&lt;/p&gt;
&lt;p&gt;&quot;A &apos;comorbidity problem&apos; confounds studies that rely on clinical criteria that are excellent at detecting Alzheimer disease but do not adequately discern actual or concomitant vascular brain injury or Lewy body disease as the cause of dementia,&quot; they wrote.&lt;/p&gt;
&lt;p&gt;The editorialists said effective treatments will likely &quot;focus [not] on a single pathophysiologic process but rather target multiple processes that affect or influence disease progression.&quot;&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;The study was funded by Myriad Pharmaceuticals. Individual researchers also had support from other entities including the National Institutes of Health and the U.K. Department of Health.&lt;/p&gt;&lt;p&gt;Green reported relationships with Myriad, Elan, and Eli Lilly. Other study authors reported relationships with these firms and others including AstraZeneca, Baxter, Forest Laboratories, Johnson &amp;amp; Johnson, Novartis, Pfizer, Takeda, Wyeth, Abbott Laboratories, Allergan, Allon, Alzheimer Drug Discovery Foundation, Bristol-Myers Squibb, GlaxoSmithKline, Institute IPSEN, Lundbeck, Medivation, Merck, Novartis, Roche, sanofi-aventis, Servier, Schering-Plough, Schwabe, Teva, Toyama, Transition Therapeutics, Voyager, Eisai, Evotec, Marix Drug Development, Neuropharm, and Shire Pharmaceuticals. Several authors were employees of Myriad.&lt;/p&gt;&lt;p&gt;Montine and Larson reported they had no potential conflicts of interest.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_130"
                     title="Dementia, Hypertension Linked Again (CME/CE)"
                     score="-0.005"
                     href="http://www.medpagetoday.com/Cardiology/Hypertension/tb/17944?impressionId=1265792452967"
                     
      Another study has found that hypertension may contribute to increased risk of dementia, this time with evidence of actual brain abnormalities.&lt;br&gt;
&lt;br&gt;Data from an offshoot of the Women&apos;s Health Initiative found that participants&apos; baseline blood pressure was strongly correlated with volume of lesions in their brains&apos; white matter, according to Lewis Kuller, MD, DrPH, of the University of Pittsburgh, and colleagues.&lt;br&gt;
&lt;br&gt;Along with earlier studies linking blood pressure to clinical dementia, the evidence &quot;supports tight control of blood pressure levels, especially beginning at younger and middle age as a possible and perhaps only way to prevent dementia,&quot; Kuller and colleagues concluded online in the &lt;em&gt;Journal of Clinical Hypertension&lt;/em&gt;.&lt;br&gt;
&lt;br&gt;One study reported in 2006 found that successful hypertension control reduced the risk of dementia, while another reported the following year indicated that uncontrolled high blood pressure increased the risk. (See &lt;a href=&quot;http://www.medpagetoday.com/Cardiology/Hypertension/3037&quot; mce_href=&quot;http://www.medpagetoday.com/Cardiology/Hypertension/3037&quot; target=&quot;_blank&quot;&gt;Blood Pressure Medication May Benefit Older Brains&lt;/a&gt; and &lt;a href=&quot;http://www.medpagetoday.com/MeetingCoverage/VASCOG/6147&quot; mce_href=&quot;http://www.medpagetoday.com/MeetingCoverage/VASCOG/6147&quot; target=&quot;_blank&quot;&gt;VAS-COG: Hypertension Linked to Cognitive Decline in Older Patients&lt;/a&gt;)&lt;/p&gt;
&lt;p&gt;Kuller and colleagues analyzed data collected from 1,424 participants in the Women&apos;s Health Initiative who agreed to undergo MRI scans performed an average of eight years after starting the trial. Blood pressure was measured at baseline and annually throughout the trial.&lt;/p&gt;
&lt;p&gt;About half the women had been assigned to placebo in the trial, which primarily was designed to test two hormone replacement regimens. Some 436 received a combination of conjugated equine estrogen and medroxyprogesterone acetate, while the remainder received the equine estrogen alone.&lt;/p&gt;
&lt;p&gt;Kuller and colleagues found significant relationships between baseline systolic blood pressure and abnormal white matter lesion volumes as measured with MRI.&lt;/p&gt;
&lt;p&gt;Among participants not taking blood pressure medications, the lesion volume averaged 4.07 cm&lt;sup&gt;3&lt;/sup&gt; for those with baseline pressure of less than 100 mm Hg, compared with 5.20 cm&lt;sup&gt;3&lt;/sup&gt;among those with systolic pressure of 140 mm Hg or higher (&lt;em&gt;P&lt;/em&gt;=0.0044 for trend).&lt;/p&gt;
&lt;p&gt;A similar but weaker relationship was seen for lesion volumes according to systolic pressure at the last available measurement (&lt;em&gt;P&lt;/em&gt;=0.03) among subjects who were not on antihypertensive therapy.&lt;/p&gt;
&lt;p&gt;Baseline systolic pressure was also significantly correlated with lesion volumes in women taking blood pressure drugs, Kuller and colleagues reported.&lt;/p&gt;
&lt;p&gt;Women with baseline pressure below 100 mm Hg had lesion volumes averaging 5.56 cm&lt;sup&gt;3&lt;/sup&gt; whereas those with pressures of 140 mm Hg or higher at baseline had average lesion volume of 6.09 mm Hg (&lt;em&gt;P&lt;/em&gt;=0.002 for trend).&lt;/p&gt;
&lt;p&gt;There was a nonsignificant trend toward higher lesion volumes with increasing systolic pressure at the last measurement.&lt;/p&gt;
&lt;p&gt;After adjusting for age, race, treatment assignment, total cranial volume, clinical site, and time from study termination to MRI scan, the researchers found that women with normal blood pressure (&amp;lt;140/90 mm Hg) had lower lesion volumes, not only in their white matter but also in the basal ganglia, than participants with high blood pressure.&lt;/p&gt;
&lt;p&gt;The finding held both for baseline blood pressure measurements and for pressure at the last available evaluation (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.0001 for all comparisons).&lt;/p&gt;
&lt;p&gt;High baseline blood pressure, though not later measurements, was also significantly correlated with the number of brain regions containing abnormal white matter lesions (&lt;em&gt;P&lt;/em&gt;=0.035).&lt;/p&gt;
&lt;p&gt;Regions in which high blood pressure seemed to promote abnormal lesions most strongly included frontal, parietal, and temporal lobes in both hemispheres. The frontal lobes in particular have been associated with vascular dementia and abnormal performance on cognition tests.&lt;/p&gt;
&lt;p&gt;Occipital lobes and the corpus callosum did not appear significantly affected, the MRI data indicated.&lt;/p&gt;
&lt;p&gt;&quot;The association of blood pressure levels with white matter abnormalities years before the MRI is consistent with a long incubation period for the development of the white matter abnormalities,&quot; Kuller and colleagues wrote.&lt;/p&gt;
&lt;p&gt;They said their findings are also consistent with earlier observations that midlife blood pressure is more strongly related to dementia later on than is blood pressure measured at older ages.&lt;/p&gt;
&lt;p&gt;Kuller and colleagues cautioned that it remained uncertain whether blood pressure treatment can prevent development of white matter abnormalities. Nor is it clear what the most appropriate blood pressure targets should be, or what type of treatment may be best.&lt;/p&gt;
&lt;p&gt;&quot;We have only suggestive evidence that the progression of white matter lesions can be slowed by blood pressure-lowering therapy,&quot; they wrote, calling for more clinical trials to clear up these issues.&lt;/p&gt;
&lt;p&gt;Nevertheless, they concluded, &quot;a prudent clinical approach at present would encourage maintaining as low a blood pressure as possible, especially beginning in young and middle ages, in order to possibly prevent dementia as well as stroke. There are no other potentially effective preventive therapies.&quot;&lt;/p&gt;
&lt;p&gt;Study limitations included a lack of MRI data on brain infarcts, no corroborating clinical data on cognitive performance, and, of course, the trial&apos;s restriction to women.&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;Wyeth funded the data analysis in this study. The Women&apos;s Health Initiative was sponsored by the National Heart, Lung, and Blood Institute.&lt;/p&gt;&lt;p&gt;No potential conflicts of interest were reported.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_117"
                     title="ARBs Linked to Lower Dementia Risk (CME/CE)"
                     score="-0.006"
                     href="http://www.medpagetoday.com/Neurology/AlzheimersDisease/tb/17928?impressionId=1265792452967"
                     
      Older patients treated with an angiotensin receptor blocker (ARB) had a significantly lower risk of dementia and nursing home admission than patients treated with other cardiovascular drugs, data from a large prospective cohort study showed.&lt;br&gt;
&lt;br&gt;The incidence of dementia was 20% to 24% lower, and nursing-home admissions were reduced by half among patients on ARBs, Benjamin Wolozin, MD, PhD, of Boston University, and colleagues reported online in &lt;em&gt;BMJ&lt;/em&gt;.&lt;br&gt;
&lt;br&gt;Results were similar when patients were categorized by dementia or the more specific diagnosis of Alzheimer&apos;s disease, suggesting the ARBs&apos; benefits involved more than cardiovascular effects.&lt;br&gt;
&lt;br&gt;&quot;It&apos;s reasonable to conclude that the ARBs are acting in part by helping with stroke, but I doubt that&apos;s the only reason,&quot; Wolozin said in an interview.&lt;p&gt;&lt;/p&gt;
&lt;p&gt;&quot;We looked at blood-brain barrier penetration, and the ARBs that get into the brain seem to help a little more than the ARBs that don&apos;t. That&apos;s consistent with what some other people have seen with ACE inhibitors.&quot;&lt;/p&gt;
&lt;p&gt;Several comprehensive summaries have described the role of the renin-angiotensin system (RAS) in Alzheimer&apos;s disease and the effects of RAS inhibitors on cognitive function. Moreover, studies have shown associations between ARB therapy and preservation of cognitive function.&lt;/p&gt;
&lt;p&gt;Preclinical and clinical evidence suggests ARBs help maintain cognitive function by mechanisms unrelated to antihypertensive effects, the authors wrote.&lt;/p&gt;
&lt;p&gt;But the relative effects of ARBs and angiotensin-converting enzyme (ACE) inhibitors on dementia outcomes had not been studied carefully.&lt;/p&gt;
&lt;p&gt;To address the issue, Wolozin and colleagues analyzed a Veterans Affairs administrative database covering 2002 to 2006. The analysis included 819,419 patients ages 65 or older with cardiovascular disease.&lt;/p&gt;
&lt;p&gt;The study population was grouped by type of cardiovascular medication received: ARBs, ACE inhibitors (primarily lisinopril), and other cardiovascular drugs.&lt;/p&gt;
&lt;p&gt;The primary outcome was time to diagnosis of Alzheimer&apos;s disease or dementia. Disease progression was defined as the time to nursing home admission or death among patients with preexisting Alzheimer&apos;s disease or dementia.&lt;/p&gt;
&lt;p&gt;The mean age of the population was about 74, and 98% of the patients were men. The authors reported that 819,491 participants were evaluable for study of Alzheimer&apos;s disease and 799,069 for dementia. About 12,000 patients were treated with ARBs, 93,000 with lisinopril, and 714,000 with other cardiovascular drugs.&lt;/p&gt;
&lt;p&gt;Comparison of Alzheimer&apos;s incidence showed a 19% reduction with ARBs versus ACE inhibitors, including lisinopril, (HR 0.81, 95% CI 0.68 to 0.96, &lt;em&gt;P&lt;/em&gt;=0.016) and a 16% reduction versus other cardiovascular drugs (HR 0.84, 95% 0.71 to 1.00, &lt;em&gt;P&lt;/em&gt;=0.045).&lt;/p&gt;
&lt;p&gt;New cases of dementia were 19% lower with ARBs than with lisinopril and other ACE inhibitors (HR 0.81, 95% CI 0.73 to 0.90, &lt;em&gt;P&lt;/em&gt;&amp;lt;0.001) and 24% lower than other cardiovascular drugs (HR 0.76, 95% CI 0.69 to 0.84, &lt;em&gt;P&lt;/em&gt;&amp;lt;0.001).&lt;/p&gt;
&lt;p&gt;Among patients with preexisting Alzheimer&apos;s disease, treatment with an ARB was associated with a 49% reduction in the rate of nursing home admission (HR 0.51, 95% 0.36 to 0.72, &lt;em&gt;P&lt;/em&gt;=0.0001) and a 17% reduction in death (HR 0.83, 95% CI 0.71 to 0.97, &lt;em&gt;P&lt;/em&gt;=0.022).&lt;/p&gt;
&lt;p&gt;The authors found a dose-response effect of ARBs on dementia incidence, as higher doses were associated with lower rates of dementia. The association held true for analysis of individual drugs in the class.&lt;/p&gt;
&lt;p&gt;Analyses of combination RAS-inhibiting therapy also showed lower rates of Alzheimer&apos;s disease, dementia, and nursing home admission among patients treated with an ARB and an ACE inhibitor compared with either class of drug alone.&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;The study was funded by the Retirement Research Foundation and the Casten Foundation.&lt;/p&gt;&lt;p&gt;The authors disclosed no relationships aside from those involving the funding sources for the study.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
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