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Neuroimaging Reveal Brain Changes in Individuals at Genetic Risk for Alzheimer's

By MedImaging International staff writers
Posted on 13 Jan 2011

People with a known, high risk for Alzheimer's disease (AD) develop abnormal brain function even before the appearance of characteristic amyloid plaques that are characteristic of the disease, according to a new study.

Researchers from the Washington University School of Medicine in St. Louis (MO, USA) reported in the December 15, 2010, issue of the Journal of Neuroscience that these patients had a particular form of the apolipoprotein E (APOE) gene called APOE4. The study's findings suggest that the gene variant affects brain function long before the brain begins accumulating the amyloid that will eventually lead to dementia.

Researchers identified functional differences in the brains of APOE4-positive and APOE4-negative individuals. Red indicates increased connectivity among regions at rest while blue shows decreased connectivity. "We looked at a group of structures in the brain that make up what's called the default mode network,” said lead author Yvette I. Sheline, MD. "In particular, we are interested in a part of the brain called the precuneus, which may be important in Alzheimer's disease and in pre-Alzheimer's because it is one of the first regions to develop amyloid deposits. Another factor is that when you look at all of the structural and functional connections in the brain, the most connected structure is the precuneus. It links many other key brain structures together.”

The research team conducted functional MRI scans on 100 people whose average age was 62. Just under half of them carried the APOE4 variant, which is a genetic risk factor for late-onset AD. Earlier PET scans of the study subjects had demonstrated that they did not have amyloid deposits in the brain.

Participants in the study also underwent spinal puncture tests that revealed they had normal amyloid levels in their cerebrospinal fluid. "Their brains were ‘clean as a whistle,'” noted Dr. Sheline, a professor of psychiatry, radiology, and of neurology and director of Washington University's Center for Depression, Stress, and Neuroimaging. "As far as their brain amyloid burden and their cerebrospinal fluid levels, these individuals were completely normal. But the people who had the APOE4 variant had significant differences in the way various brain regions connected with one another.”

Dr. Sheline's team focused on the brain's default mode network. Typically, the default network is active when the mind rests. Its activity slows down when an individual concentrates. Subjects do not need to perform anyspecific tasks for researchers to study the default mode network. They simply relax in the MRI scanner and reflect or daydream while the system measures oxygen levels and blood flow in the brain. "We make sure they don't go to sleep,” Dr. Sheline stated. "But other than not sleeping, study participants had no instructions. They were just lying there at rest, and we looked at what their brains were doing.”

This is the latest in a series of studies in which Dr. Sheline and her colleagues have looked at brain function in people at risk for AD. At first, her team compared the default mode networks in the brains of people with mild AD to the same structures in the brains of those who were cognitively normal. In that study, her team found significant differences in how the network functioned. Then, using positron emission tomography (PET) imaging to identify cognitively health individuals who had amyloid deposits in their brains in a second study, they compared those cognitively normal people whose PET scans revealed that their brains contained amyloid to others whose PET scans showed no evidence of amyloid. Again, the default mode network performed differently in those with amyloid deposits.

In the current study, there was no evidence of dementia or amyloid deposits. However, in those with the APOE4 variant, there was irregular functioning in the default mode network. APOE4 is the major genetic risk factor for sporadic cases of Alzheimer's disease. Other genes that pass on inherited, early-onset forms of the disease have been identified, but APOE4 is the most important genetic marker of the disease identified so far, according to Dr. Sheline.

The study participants, all of whom participate in studies through the university's Charles F. and Joanne Knight Alzheimer's Disease Research Center, will be followed to see whether they eventually develop amyloid deposits. The goal is to identify those with the highest risk of AD and to develop treatments that interfere with the progression of the disease, keeping it from advancing to the stage when amyloid begins to build up in the brain and, eventually, dementia sets in. "The current belief is that from the time excess amyloid begins to collect in the brain, it takes about 10 years for a person to develop dementia,” Dr. Sheline concluded. "But this new study would suggest we might be able to intervene even before amyloid plaques begin to form. That could give us an even longer time window to intervene once an effective treatment can be developed.”

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Washington University School of Medicine in St. Louis

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56 (!!!!! 1657.0091247559): 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=294732958 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1

57 (!!!!! 11415.958404541): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294732958 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294732958 AND published='1' LIMIT 1

58 (!!!!! 12003.898620605): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294732958 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294732958 AND published='1' LIMIT 1

59 (!!!!! 10708.093643188): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294732958 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294732958 AND published='1' LIMIT 1

60 (!!!!! 7924.7951507568): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294732958 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294732958 AND published='1' LIMIT 1

61 (!!!!! 1111.0305786133): select cover from jos_number where journalid in (5) and cover is not null order by left(issue,2)+right(issue,2)*12 desc limit 1

62 (987.05291748047): SELECT fid FROM jos_deeppockets WHERE id=294732958 AND published='1' union SELECT fid FROM jos_deeppockets_archive WHERE id=294732958 AND published='1' LIMIT 1

63 (!!!!! 1195.1923370361): SELECT id,name,sponsor_text FROM jos_deeppockets dp left outer join jos_channel_sponsor cs on dp.id=cs.fid WHERE cat=10 AND TYPE='file_folder' AND published=1 AND id=212 ORDER BY `ordering`

64 (!!!!! 2017.9748535156): select jos_twitters.link from jos_twitters where cat=10

65 (77.962875366211): select jos_facebook.link from jos_facebook where cat=10

66 (714.06364440918): select jos_google_plus.link from jos_google_plus where cat=10

67 (82.969665527344): select jos_linkedin.link from jos_linkedin where cat=10

68 (102.99682617188): SELECT fid FROM jos_deeppockets WHERE id=294732958 AND published='1' union SELECT fid FROM jos_deeppockets_archive WHERE id=294732958 AND published='1' LIMIT 1

69 (68.187713623047): SELECT id,name,sponsor_text FROM jos_deeppockets dp left outer join jos_channel_sponsor cs on dp.id=cs.fid WHERE cat=10 AND TYPE='file_folder' AND published=1 AND id=212 ORDER BY `ordering`

70 (!!!!! 2372.0264434814): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294732958 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

71 (440.12069702148): SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294732958 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

72 (!!!!! 7488.0123138428): 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`

73 (!!!!! 3246.0689544678): SELECT show_live FROM jos_com_show_setting LIMIT 1

74 (130.89179992676): SELECT show_live FROM jos_com_show_setting LIMIT 1

75 (!!!!! 3755.0926208496): SELECT show_live FROM jos_com_show_setting LIMIT 1

76 (133.03756713867): SELECT show_live FROM jos_com_show_setting LIMIT 1

77 (61.03515625): SELECT show_live FROM jos_com_show_setting LIMIT 1

78 (43.153762817383): SELECT show_live FROM jos_com_show_setting LIMIT 1

79 (45.061111450195): SELECT show_live FROM jos_com_show_setting LIMIT 1

80 (41.007995605469): SELECT show_live FROM jos_com_show_setting LIMIT 1

81 (41.007995605469): SELECT show_live FROM jos_com_show_setting LIMIT 1

82 (41.961669921875): SELECT show_live FROM jos_com_show_setting LIMIT 1

83 (42.915344238281): SELECT show_live FROM jos_com_show_setting LIMIT 1

84 (41.007995605469): SELECT show_live FROM jos_com_show_setting LIMIT 1

85 (43.869018554688): SELECT show_live FROM jos_com_show_setting LIMIT 1

86 (41.007995605469): SELECT show_live FROM jos_com_show_setting LIMIT 1

87 (92.029571533203): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294732958 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

88 (52.928924560547): SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294732958 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

89 (54.121017456055): 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`

90 (113.01040649414): SELECT show_live FROM jos_com_show_setting LIMIT 1

91 (49.829483032227): SELECT show_live FROM jos_com_show_setting LIMIT 1

92 (46.968460083008): SELECT show_live FROM jos_com_show_setting LIMIT 1

93 (42.915344238281): SELECT show_live FROM jos_com_show_setting LIMIT 1

94 (54.836273193359): SELECT show_live FROM jos_com_show_setting LIMIT 1

95 (45.061111450195): SELECT show_live FROM jos_com_show_setting LIMIT 1

96 (50.067901611328): SELECT show_live FROM jos_com_show_setting LIMIT 1

97 (45.061111450195): SELECT show_live FROM jos_com_show_setting LIMIT 1

98 (41.007995605469): SELECT show_live FROM jos_com_show_setting LIMIT 1

99 (40.054321289062): SELECT show_live FROM jos_com_show_setting LIMIT 1

100 (42.200088500977): SELECT show_live FROM jos_com_show_setting LIMIT 1

101 (38.862228393555): SELECT show_live FROM jos_com_show_setting LIMIT 1

102 (46.968460083008): SELECT show_live FROM jos_com_show_setting LIMIT 1

103 (41.007995605469): SELECT show_live FROM jos_com_show_setting LIMIT 1

104 (!!!!! 5012.035369873): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294732958 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294732958 AND published='1' LIMIT 1

105 (!!!!! 7995.8438873291): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294732958 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294732958 AND published='1' LIMIT 1

106 (98.943710327148): 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=294732958 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1

107 (650.16746520996): 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=294732958 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1

108 (176.90658569336): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294732958 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294732958 AND published='1' LIMIT 1

109 (97.990036010742): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294732958 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294732958 AND published='1' LIMIT 1

110 (137.0906829834): 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=294732958 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1

111 (634.90867614746): 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=294732958 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1

112 (708.10317993164): 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

113 (475.16822814941): 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

114 (128.98445129395): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294732958 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294732958 AND published='1' LIMIT 1

115 (73.909759521484): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294732958 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294732958 AND published='1' LIMIT 1

116 (97.036361694336): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294732958 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294732958 AND published='1' LIMIT 1

117 (66.041946411133): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294732958 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294732958 AND published='1' LIMIT 1

118 (65.088272094727): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294732958 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294732958 AND published='1' LIMIT 1

119 (77.962875366211): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294732958 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294732958 AND published='1' LIMIT 1

120 (74.863433837891): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294732958 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294732958 AND published='1' LIMIT 1

121 (58.889389038086): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294732958 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294732958 AND published='1' LIMIT 1

122 (369.07196044922): SELECT * FROM trending_articles WHERE `journal_id` = 10 AND `timestamp` <= NOW() + INTERVAL 7 DAY ORDER BY `order`

123 (!!!!! 50629.854202271): 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

124 (974.89356994629): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294732958 AND type='deeppockets_item' AND published='1' union SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294732958 AND type='deeppockets_item' AND published='1' LIMIT 1

125 (!!!!! 20109.891891479): ( 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

126 (101.80473327637): ( 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

127 (47.922134399414): 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

128 (35.04753112793): 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

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 = 294803276 LIMIT 1

130 (36.001205444336): 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

131 (296.83113098145): 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

132 (60.081481933594): 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

133 (72.956085205078): 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

134 (51.975250244141): 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

135 (631.09397888184): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294732958 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

136 (561.95259094238): SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294732958 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

137 (73.909759521484): SELECT name FROM jos_deeppockets WHERE id=212

138 (46.014785766602): SELECT name FROM jos_deeppockets WHERE id=212

139 (732.1834564209): 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 '((;)|(^))212((;)|($))' AND catid IN (0,110) ORDER BY publish_up ASC LIMIT 3

140 (604.86793518066): 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 '((;)|(^))212((;)|($))' AND catid IN (0,110) ORDER BY publish_up ASC LIMIT 3

141 (107.0499420166): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294732958 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294732958 AND published='1' LIMIT 1

142 (68.187713623047): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294732958 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294732958 AND published='1' LIMIT 1

143 (!!!!! 19632.10105896): TRUNCATE TABLE jos_trademed_module

144 (!!!!! 1786.9472503662): 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=294732958 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1

145 (127.07710266113): 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=294732958 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1

146 (!!!!! 4194.974899292): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294732958 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

147 (137.0906829834): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294732958 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

148 (!!!!! 2562.0460510254): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294732958 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294732958 AND published='1' LIMIT 1

149 (127.07710266113): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294732958 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294732958 AND published='1' LIMIT 1

150 (!!!!! 1881.1225891113): 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

151 (112.05673217773): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294732958 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294732958 AND published='1' LIMIT 1

152 (92.983245849609): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294732958 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294732958 AND published='1' LIMIT 1

153 (76.055526733398): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294732958 AND type='deeppockets_item' AND published='1' union SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294732958 AND type='deeppockets_item' AND published='1' LIMIT 1

154 (!!!!! 2558.9466094971): 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=212 or channel_id is null)

155 (868.08204650879): 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=212 or channel_id is null)

156 (117.06352233887): SELECT livesite FROM jos_dp_categories WHERE id=10 AND published='1' LIMIT 1

157 (!!!!! 10666.847229004): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294732958 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294732958 AND published='1' LIMIT 1

158 (200.98686218262): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294732958 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294732958 AND published='1' LIMIT 1

159 (!!!!! 2331.018447876): select jos_twitters.link from jos_twitters where cat=10

160 (72.956085205078): select jos_facebook.link from jos_facebook where cat=10

161 (34.093856811523): select jos_google_plus.link from jos_google_plus where cat=10

162 (30.994415283203): select jos_linkedin.link from jos_linkedin where cat=10

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