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Neuroimaging Study May Pave Way for Effective Alzheimer's Treatments

By MedImaging International staff writers
Posted on 11 Mar 2010
Scientists have determined that a new imaging technology known as Pittsburgh Compound-B (PIB)-positron emission tomography (PET) is effective in detecting deposits of amyloid-beta protein plaques in the brains of living people, and that these deposits are predictive of who will develop Alzheimer's disease (AD).

The findings, the result of a survey of more than 100 studies involving the methodology, including those by the scientists, validates the sensitivity of the technique, not yet commercially available. In clinical practice, amyloid deposits are detected only on autopsy.

The study also provides strong evidence supporting the so-called "amyloid hypothesis”-- the theory that accumulation of amyloid-beta protein plaques in the brain is key to the development of the disease. Whereas significant evidence has supported this hypothesis, it has been questioned for two main reasons. First, amyloid deposits do not correlate with the severity of the disease, and are, in fact, found at autopsy in people who did not have clinical symptoms; and second, drugs targeting the plaques have shown disappointing results, even when the drugs were successful at substantially lowering plaque burden. Thus, the question of amyloid's role in the illness has remained.

"Our survey of PIB-PET studies, which looked cross-sectionally and longitudinally at people with normal cognitive performance, mild cognitive impairment and full-fledged Alzheimer's disease, showed that amyloid deposits can be detected in a significant proportion of cognitively normal older adults, and that their presence is associated with Alzheimer's-like brain atrophy and changes in brain activity,” said coauthor Gil Rabinovici, M.D., assistant professor of neurology in the University of California, San Francisco (UCSF) Memory and Aging Center (USA).

The study also revealed that older individuals with amyloid deposits were much more likely to show cognitive decline over time than their amyloid-negative counterparts, according to Dr. Rabinovici.

The results of the survey, released online in December 2009 in the journal Behavioral Neurology, may clarify why patients with AD have not responded to promising experimental drugs that target amyloid, and suggest that these drugs may be effective if administered earlier.

"Amyloid deposits appear to reach a plateau early in the disease course, when patients experience very mild symptoms or no symptoms at all,” stated Dr. Rabinovici, a recipient of new investigator awards from the Alzheimer's Association and the U.S. National Institute on Aging (Bethesda, MD, USA). "By the time patients have developed the symptoms of Alzheimer's disease, clinical decline and brain changes are occurring independently of further amyloid accumulation. This suggests that we have been starting treatment too late, and that amyloid-based therapies are most likely to work very early in the disease process.”

Existing drugs, such as Aricept, Exelon, and Razadyne, treat symptoms but do not modify the biological progression of the disease, he says. Many treatments under development, however, target amyloid deposits in an attempt to arrest further decline. Thus far, these treatments have failed to produce a benefit in two phase-III clinical trials in mild-to-moderate AD.

PIB-PET involves injecting a tracer material into the brain via the bloodstream, and imaging the brain with positron emission tomography (PET). PIB binds to amyloid-beta protein plaques, a hallmark of Alzheimer's disease, and sends a signal that is then detected by the PET scanner and translated into an image reflecting the quantity and distribution of amyloid in the brain. In the studies surveyed, scientists complemented the PIB-PET research by using additional neuroimaging techniques such as magnetic resonance imaging (MRI) or fluorodeoxyglucose (FDG)-PET, which allowed them to measure the size of different brain structures, network connections or brain metabolism.

While PIB-PET is used for research purposes only, due to its limited "half life,” or amount of time it takes for the radioactive signal of the compound to decay, other amyloid imaging agents are being developed for commercial use. However, Dr. Rabinovici "strongly discourages” uses of the technology in cognitively normal individuals until effective and safe antiamyloid therapies are available and the benefit of preventive treatment is demonstrated in clinical trials.

Eventually, Dr. Rabinovici predicts, the technology might be used for screening those genetically at risk for Alzheimer's, as well as those who are minimally symptomatic. Antiamyloid treatments would then be prescribed to prevent the onset of the disease.

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University of California, San Francisco Memory and Aging Center

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87 (40.054321289062): SELECT show_live FROM jos_com_show_setting LIMIT 1
88 (36.954879760742): SELECT show_live FROM jos_com_show_setting LIMIT 1
89 (76.055526733398): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294728410 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
90 (41.961669921875): SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294728410 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
91 (46.014785766602): SELECT id,name,title FROM jos_deeppockets WHERE cat=10 AND TYPE='file_folder' AND published=1 AND id != 294743300 AND id != 294743301 AND id != 294743302 AND id != 294743303 AND id != 294743304 AND id != 294743305 AND id != 294743306 AND id != 294743307 AND id != 294743308 AND id != 294743309 AND id != 294743310 AND metakey != 'aacc' ORDER BY `ordering`
92 (627.04086303711): SELECT show_live FROM jos_com_show_setting LIMIT 1
93 (48.160552978516): SELECT show_live FROM jos_com_show_setting LIMIT 1
94 (225.06713867188): SELECT show_live FROM jos_com_show_setting LIMIT 1
95 (41.961669921875): SELECT show_live FROM jos_com_show_setting LIMIT 1
96 (111.81831359863): SELECT show_live FROM jos_com_show_setting LIMIT 1
97 (36.954879760742): SELECT show_live FROM jos_com_show_setting LIMIT 1
98 (47.922134399414): SELECT show_live FROM jos_com_show_setting LIMIT 1
99 (35.04753112793): SELECT show_live FROM jos_com_show_setting LIMIT 1
100 (174.99923706055): SELECT show_live FROM jos_com_show_setting LIMIT 1
101 (37.908554077148): SELECT show_live FROM jos_com_show_setting LIMIT 1
102 (183.8207244873): SELECT show_live FROM jos_com_show_setting LIMIT 1
103 (41.007995605469): SELECT show_live FROM jos_com_show_setting LIMIT 1
104 (283.95652770996): SELECT show_live FROM jos_com_show_setting LIMIT 1
105 (56.028366088867): SELECT show_live FROM jos_com_show_setting LIMIT 1
106 (!!!!! 3541.9464111328): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294728410 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294728410 AND published='1' LIMIT 1
107 (!!!!! 3965.1393890381): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294728410 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294728410 AND published='1' LIMIT 1
108 (355.95893859863): SELECT dp.*, ch.title as channel, exp.name as author_name, exp.specialization as author_specialization, exp.images as author_photo FROM jos_deeppockets as dp LEFT JOIN jos_experts as exp ON exp.id = dp.author LEFT JOIN jos_deeppockets as ch ON dp.fid = ch.id WHERE 1=1 AND dp.cat=10 AND dp.id=294728410 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
109 (753.87954711914): SELECT dp.*, ch.title as channel, exp.name as author_name, exp.specialization as author_specialization, exp.images as author_photo FROM jos_deeppockets_archive as dp LEFT JOIN jos_experts as exp ON exp.id = dp.author LEFT JOIN jos_deeppockets as ch ON dp.fid = ch.id WHERE 1=1 AND dp.cat=10 AND dp.id=294728410 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
110 (!!!!! 3340.9595489502): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294728410 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294728410 AND published='1' LIMIT 1
111 (175.95291137695): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294728410 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294728410 AND published='1' LIMIT 1
112 (78.916549682617): SELECT dp.*, ch.title as channel, exp.name as author_name, exp.specialization as author_specialization, exp.images as author_photo FROM jos_deeppockets as dp LEFT JOIN jos_experts as exp ON exp.id = dp.author LEFT JOIN jos_deeppockets as ch ON dp.fid = ch.id WHERE 1=1 AND dp.id=294728410 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
113 (782.01293945312): SELECT dp.*, ch.title as channel, exp.name as author_name, exp.specialization as author_specialization, exp.images as author_photo FROM jos_deeppockets_archive as dp LEFT JOIN jos_experts as exp ON exp.id = dp.author LEFT JOIN jos_deeppockets as ch ON dp.fid = ch.id WHERE 1=1 AND dp.id=294728410 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
114 (!!!!! 1318.9315795898): SELECT dp.name, dp.id, dp2.name as channel, ex.name as author_name, ex.specialization, ex.images FROM jos_deeppockets as dp LEFT JOIN jos_experts as ex ON ex.id = dp.author LEFT JOIN jos_deeppockets as dp2 ON dp2.id = dp.fid WHERE dp.author != 0 AND dp.cat = 10 AND dp.published = 1 AND ( (dp.fid = 294743300) OR (dp.fid = 294743301) OR (dp.fid = 294743302) OR (dp.fid = 294743303) OR (dp.fid = 294743304) OR (dp.fid = 294743305) OR (dp.fid = 294743306) OR (dp.fid = 294743307) OR (dp.fid = 294743308) OR (dp.fid = 294743309) OR (dp.fid = 294743310) ) ORDER BY RAND() LIMIT 1
115 (941.03813171387): SELECT dp.name, dp.id, dp2.name as channel, ex.name as author_name, ex.specialization, ex.images FROM jos_deeppockets as dp LEFT JOIN jos_experts as ex ON ex.id = dp.author LEFT JOIN jos_deeppockets as dp2 ON dp2.id = dp.fid WHERE dp.author != 0 AND dp.cat = 10 AND dp.published = 1 AND ( (dp.fid = 294743300) OR (dp.fid = 294743301) OR (dp.fid = 294743302) OR (dp.fid = 294743303) OR (dp.fid = 294743304) OR (dp.fid = 294743305) OR (dp.fid = 294743306) OR (dp.fid = 294743307) OR (dp.fid = 294743308) OR (dp.fid = 294743309) OR (dp.fid = 294743310) ) ORDER BY RAND() LIMIT 1
116 (411.03363037109): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294728410 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294728410 AND published='1' LIMIT 1
117 (441.07437133789): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294728410 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294728410 AND published='1' LIMIT 1
118 (468.96934509277): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294728410 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294728410 AND published='1' LIMIT 1
119 (233.17337036133): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294728410 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294728410 AND published='1' LIMIT 1
120 (88.930130004883): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294728410 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294728410 AND published='1' LIMIT 1
121 (61.988830566406): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294728410 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294728410 AND published='1' LIMIT 1
122 (448.94218444824): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294728410 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294728410 AND published='1' LIMIT 1
123 (71.048736572266): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294728410 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294728410 AND published='1' LIMIT 1
124 (!!!!! 1161.8137359619): SELECT * FROM trending_articles WHERE `journal_id` = 10 AND `timestamp` <= NOW() + INTERVAL 7 DAY ORDER BY `order`
125 (!!!!! 73245.048522949): SELECT * FROM jos_deeppockets WHERE jos_deeppockets.cat = 10 AND jos_deeppockets.type = 'deeppockets_item' AND jos_deeppockets.published = 1 AND jos_deeppockets.created + INTERVAL 14 DAY >= NOW() ORDER BY jos_deeppockets.hits DESC LIMIT 7
126 (!!!!! 2296.9245910645): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294728410 AND type='deeppockets_item' AND published='1' union SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294728410 AND type='deeppockets_item' AND published='1' LIMIT 1
127 (310.89782714844): ( SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.video != '' AND dp.video_source != '' AND dp.cat = 10 AND dp.published = 1 AND dp.type != 'deeppockets_item_link' ORDER BY created DESC LIMIT 3 ) UNION ( SELECT dpa.id, dpa.name, dpa.title, dpa.video, dpa.video_source, dpa.created FROM jos_deeppockets_archive AS dpa WHERE dpa.video != '' AND dpa.video_source != '' AND dpa.cat = 10 AND dpa.published = 1 AND dpa.type != 'deeppockets_item_link' ORDER BY created DESC LIMIT 3 ) ORDER BY created DESC LIMIT 3
128 (57.93571472168): ( SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.video != '' AND dp.video_source != '' AND dp.cat = 10 AND dp.published = 1 AND dp.type != 'deeppockets_item_link' ORDER BY created DESC LIMIT 3 ) UNION ( SELECT dpa.id, dpa.name, dpa.title, dpa.video, dpa.video_source, dpa.created FROM jos_deeppockets_archive AS dpa WHERE dpa.video != '' AND dpa.video_source != '' AND dpa.cat = 10 AND dpa.published = 1 AND dpa.type != 'deeppockets_item_link' ORDER BY created DESC LIMIT 3 ) ORDER BY created DESC LIMIT 3
129 (68.902969360352): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294803337 LIMIT 1
130 (49.829483032227): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294803337 LIMIT 1
131 (69.856643676758): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294803276 LIMIT 1
132 (44.822692871094): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294803276 LIMIT 1
133 (42.915344238281): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets_archive AS dp WHERE dp.id = 294803276 LIMIT 1
134 (46.014785766602): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets_archive AS dp WHERE dp.id = 294803276 LIMIT 1
135 (49.829483032227): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294802958 LIMIT 1
136 (43.153762817383): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294802958 LIMIT 1
137 (463.96255493164): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294728410 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
138 (369.78721618652): SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294728410 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
139 (59.127807617188): SELECT name FROM jos_deeppockets WHERE id=213
140 (38.862228393555): SELECT name FROM jos_deeppockets WHERE id=213
141 (806.09321594238): SELECT *, DATE_FORMAT(publish_up,'%d %b %Y') AS date_publish_up, DATE_FORMAT(publish_down,'%d %b %Y') AS date_publish_down FROM jos_events WHERE state=1 AND publish_up > NOW() and extra_info REGEXP '((;)|(^))213((;)|($))' AND catid IN (0,110) ORDER BY publish_up ASC LIMIT 3
142 (787.01972961426): SELECT *, DATE_FORMAT(publish_up,'%d %b %Y') AS date_publish_up, DATE_FORMAT(publish_down,'%d %b %Y') AS date_publish_down FROM jos_events WHERE state=1 AND publish_up > NOW() and extra_info REGEXP '((;)|(^))213((;)|($))' AND catid IN (0,110) ORDER BY publish_up ASC LIMIT 3
143 (102.99682617188): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294728410 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294728410 AND published='1' LIMIT 1
144 (71.048736572266): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294728410 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294728410 AND published='1' LIMIT 1
145 (!!!!! 11612.892150879): TRUNCATE TABLE jos_trademed_module
146 (174.99923706055): SELECT dp.*, ch.title as channel, exp.name as author_name, exp.specialization as author_specialization, exp.images as author_photo FROM jos_deeppockets as dp LEFT JOIN jos_experts as exp ON exp.id = dp.author LEFT JOIN jos_deeppockets as ch ON dp.fid = ch.id WHERE 1=1 AND dp.cat=10 AND dp.id=294728410 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
147 (73.19450378418): SELECT dp.*, ch.title as channel, exp.name as author_name, exp.specialization as author_specialization, exp.images as author_photo FROM jos_deeppockets_archive as dp LEFT JOIN jos_experts as exp ON exp.id = dp.author LEFT JOIN jos_deeppockets as ch ON dp.fid = ch.id WHERE 1=1 AND dp.cat=10 AND dp.id=294728410 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
148 (723.12355041504): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294728410 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
149 (79.154968261719): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294728410 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
150 (102.99682617188): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294728410 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294728410 AND published='1' LIMIT 1
151 (69.141387939453): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294728410 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294728410 AND published='1' LIMIT 1
152 (!!!!! 1688.0035400391): SELECT jos_item.* FROM jos_item INNER JOIN jos_number ON jos_item.numberID=jos_number.id WHERE 1=1 AND (jos_item.imgMini<>'') AND jos_item.type='L' AND jos_item.numberID= ( SELECT jos_number.id FROM jos_number WHERE jos_number.journalID IN (10) and jos_number.id in (select distinct jos_number.id from jos_number join jos_item on jos_item.numberid=jos_number.id where jos_item.type='P') ORDER BY (CONVERT(SUBSTRING(issue,1,2),SIGNED) + (CONVERT(SUBSTRING(issue,3,2),SIGNED)*100)) DESC LIMIT 0,1 ) ORDER BY RAND() DESC LIMIT 6
153 (113.96408081055): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294728410 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294728410 AND published='1' LIMIT 1
154 (!!!!! 3654.956817627): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294728410 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294728410 AND published='1' LIMIT 1
155 (67.949295043945): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294728410 AND type='deeppockets_item' AND published='1' union SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294728410 AND type='deeppockets_item' AND published='1' LIMIT 1
156 (42.915344238281): select distinct links.* from jos_textlinks links join jos_textlinks_placement placement on links.id=placement.link_id where journal_id=(10) and (channel_id=213 or channel_id is null)
157 (36.001205444336): select distinct links.* from jos_textlinks links join jos_textlinks_placement placement on links.id=placement.link_id where journal_id=(10) and (channel_id=213 or channel_id is null)
158 (44.107437133789): SELECT livesite FROM jos_dp_categories WHERE id=10 AND published='1' LIMIT 1
159 (!!!!! 3952.9800415039): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294728410 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294728410 AND published='1' LIMIT 1
160 (97.990036010742): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294728410 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294728410 AND published='1' LIMIT 1
161 (80.108642578125): select jos_twitters.link from jos_twitters where cat=10
162 (50.067901611328): select jos_facebook.link from jos_facebook where cat=10
163 (37.908554077148): select jos_google_plus.link from jos_google_plus where cat=10
164 (34.809112548828): select jos_linkedin.link from jos_linkedin where cat=10