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    <recommendedItem id="20100101_19_358"
                     title="Poststroke Antidepressant Boosts Mental Agility (CME/CE)"
                     score="0.01"
                     href="http://www.medpagetoday.com/Cardiology/Strokes/tb/18240?impressionId=1265756396128"
                     
      &lt;p&gt;Antidepressants in the first months after a stroke may aid cognitive recovery for patients without depression, according to a randomized trial analysis.&lt;/p&gt;
&lt;p&gt;Global cognitive function scores improved significantly more with escitalopram (Lexapro) than with problem-solving therapy or placebo (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.01), according to Ricardo E. Jorge, MD, of the University of Iowa in Iowa City, and colleagues.&lt;/p&gt;
&lt;p&gt;Memory scores rose significantly higher with the antidepressant as well (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.01), with both effects independent of those on depression, they reported in the February &lt;em&gt;Archives of General Psychiatry&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;&quot;Adjunctive restorative therapies administered during the first few months after stroke, the period with the greatest degree of spontaneous recovery, reduce the number of stroke patients with significant disability,&quot; the researchers concluded.&lt;/p&gt;
&lt;p&gt;The &lt;a href=&quot;http://www.medpagetoday.com/Cardiology/Strokes/9621&quot; mce_href=&quot;http://www.medpagetoday.com/Cardiology/Strokes/9621&quot; target=&quot;_blank&quot;&gt;primary analysis&lt;/a&gt; of the trial, reported in the &lt;em&gt;Journal of the American Medical Association on&lt;/em&gt; May 28, 2008, showed that prophylactic escitalopram treatment would prevent poststroke depression in one patient for every 7.2 treated &lt;em&gt;(P&lt;/em&gt;&amp;lt;0.001 compared with placebo). That article ultimately raised a controversy over an undisclosed conflict of interest.&lt;/p&gt;
&lt;p&gt;Escitalopram is a selective serotonin reuptake inhibitor (SSRI). Since serotonin plays a role in neuroplastic changes in the developing brain as well as in depression, Jorge&apos;s group analyzed whether there might be such an effect after a stroke.&lt;/p&gt;
&lt;p&gt;The study randomized patients to double-blind treatment with escitalopram (10 mg/d under age 65 or 5 mg/day age 65 and older) or placebo or unblinded problem-solving therapy (12 sessions of going through steps to arrive at a course of action for a patient-selected problem).&lt;/p&gt;
&lt;p&gt;The intent-to-treat analysis included 129 patients treated starting within the first three months after their mild to moderate severity stroke and who did not meet criteria for major or minor depression.&lt;/p&gt;
&lt;p&gt;Overall, global cognitive functioning was significantly changed between groups as measured on the Repeatable Battery for the Assessment of Neuropsychological Status (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.01).&lt;/p&gt;
&lt;p&gt;After controlling for change in depression score and type of stroke, escitalopram was associated with the best cognitive recovery, an adjusted mean change of 9.9 points compared with 1.9 for problem-solving therapy (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.01) and 4.0 for placebo (&lt;em&gt;P&lt;/em&gt;=0.02).&lt;/p&gt;
&lt;p&gt;Similarly, for delayed memory scores on the same test battery, escitalopram came out on top (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.01).&lt;/p&gt;
&lt;p&gt;After adjustment for depression score change and stroke mechanism, the antidepressant was associated with an 11.2 point improvement in delayed memory, compared with a change of -0.7 with problem-solving therapy (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.001) and 3.9 with placebo (&lt;em&gt;P&lt;/em&gt;=0.02).&lt;/p&gt;
&lt;p&gt;On test of immediate memory, escitalopram again yielded the best recovery.&lt;/p&gt;
&lt;p&gt;The researchers found mean improvement of 13.4 points with the antidepressant compared with 2.0 with problem-solving therapy (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.001) and 7.2 with placebo (&lt;em&gt;P&lt;/em&gt;=0.04), after adjustment for time between stroke and treatment, depression score change, and stroke type.&lt;/p&gt;
&lt;p&gt;These mental benefits appeared to have an impact on functional status as well.&lt;/p&gt;
&lt;p&gt;Cognitive domain scores on the Functional Independence Measure were better for escitalopram-treated patients than those who didn&apos;t get the drug (&lt;em&gt;P&lt;/em&gt;=0.05), as were memory domain scores on the same measure (&lt;em&gt;P&lt;/em&gt;=0.03).&lt;/p&gt;
&lt;p&gt;At baseline, the global cognitive functioning and delayed and immediate memory scores were nonsignificantly lower in the antidepressant group than in the other two groups, which could have biased the results.&lt;/p&gt;
&lt;p&gt;However, the treatment effects appeared to be real, Jorge explained in an interview.&lt;/p&gt;
&lt;p&gt;In an unpublished regression analysis, the baseline scores were not a significant covariate. &quot;If [the results were] related only to the difference in baseline, this would be significant but it wasn&apos;t,&quot; he told &lt;em&gt;MedPage Today&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;Moreover, with an initially lower score it might have been expected that the escitalopram-treated group would have had a lower score at the end of the study than the other groups, added co-author Robert G. Robinson, MD, also of the University of Iowa.&lt;/p&gt;
&lt;p&gt;But that wasn&apos;t the case, he said in an interview. With regard to delayed memory, for example, &quot;the escitalopram-treated group went from the most impaired to the best performing.&quot;&lt;/p&gt;
&lt;p&gt;The researchers didn&apos;t compare end scores for the escitalopram, problem solving therapy, and placebo groups, but they were: &lt;ul&gt; &lt;li&gt;For global cognitive functioning 89.8, 89.1, and 91.0 points, respectively&lt;/li&gt; &lt;li&gt;For delayed memory, 96.6, 89.1, and 94.2, respectively&lt;/li&gt; &lt;li&gt;For immediate memory, 95.1, 94.9, and 98.5, respectively&lt;/li&gt; &lt;/ul&gt;&lt;/p&gt;
&lt;p&gt;The treatment showed no effect on other individual cognitive measurements, including those for attention, language, and IQ. Nor were there significant differences in changes in occupational or living conditions.&lt;/p&gt;
&lt;p&gt;Although SSRIs such as escitalopram have been associated with hospitalization for GI bleeding and falls in prior studies, these complications did not occur in Jorge&apos;s study.&lt;/p&gt;
&lt;p&gt;&quot;Long-term administration of SSRIs appears to be an effective and safe treatment option to improve cognitive outcomes among patients with cerebrovascular disease,&quot; they concluded in the &lt;em&gt;Archives&lt;/em&gt; paper.&lt;/p&gt;
&lt;p&gt;The researchers cautioned that the study was limited by lack of CT or MRI scans and the younger age of escitalopram-treated patients, compared with other groups. That may have been a source of bias, although age did not appear to be a significant factor in the trial results.&lt;/p&gt;
&lt;p&gt;In this analysis, the researchers emphasized that the trial was not financially supported in any way by any drug company  --  a declaration hinting at the controversy that brewed last year over failure of one of the authors of the original &lt;em&gt;JAMA&lt;/em&gt; article to &lt;a href=&quot;http://www.medpagetoday.com/PublicHealthPolicy/HealthPolicy/13391&quot; mce_href=&quot;http://www.medpagetoday.com/PublicHealthPolicy/HealthPolicy/13391&quot; target=&quot;_blank&quot;&gt;properly disclose ties&lt;/a&gt; to Forest Pharmaceuticals, which makes escitalopram.&lt;/p&gt;
&lt;p&gt;Another scientist who discovered that omission published the information in a competing journal, inducing &lt;em&gt;JAMA&lt;/em&gt; to issue a gag rule on reporting of undisclosed conflicts of interest. That policy encourages those who discover such conflicts to report them to &lt;em&gt;JAMA&apos;s&lt;/em&gt; editors but prohibits them from disclosing the conflicts publicly pending an investigation by the journal.&lt;/p&gt;
&lt;p&gt;In the current analysis, the disclosure statement indicated that co-author Robertson, had received honoraria and speakers&apos; bureau fees from Forest, with the caveat that &quot;none of the design, analysis, or expenses (including the cost of medications) of this study were supported by monies, materials, or any intellectual input from Forest Laboratories.&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 supported solely by a grant from the National Institute of Mental Health.&lt;/p&gt;&lt;p&gt;Jorge reported having received travel awards to participate in national meetings from the former Hamilton Pharmaceutical Company and Avanir Pharmaceutical Company.&lt;/p&gt;&lt;p&gt;Co-authors reported financial conflicts of interest with Merck, NMT Medical, Eli Lilly, Centocor, Sanofi-Bristol-Meyers-Squibb, Boerhringer-Ingelheim, Schering-Plough, AstraZeneca, and GlaxoSmithKline, the former Hamilton Pharmaceutical Company, Avanir Pharmaceutical Company, Lubeck, Forest Laboratories, and Pfizer.&lt;/p&gt;&lt;p&gt;No pharmaceutical company donated medications for or had any financial interest in the study.&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=1265756396128"
                     
      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="20090101_2_405"
                     title="Hypertension Linked to Risk of Cognitive Impairment"
                     score="-0.005"
                     href="