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AAPM 2025 - 67th Annual Meeting & Exhibition of the American Association of Physicists in Medicine

Brain Damage Seen in Cognitively Normal People with Alzheimer's Disease Marker

By MedImaging International staff writers
Posted on 07 Apr 2009

Researchers have linked a potential indicator of Alzheimer's disease (AD) to brain damage in humans with no signs of mental impairment.

Although their cognitive and neurologic assessments were normal, study participants with lower levels of a substance known as amyloid beta 42 (A-beta 42) in their cerebrospinal fluid (CSF) had reduced whole brain volumes, suggesting that Alzheimer's alterations might already be damaging their brains. Scientists previously showed that low CSF levels of A-beta 42 mark the presence of amyloid deposition in the brain, a key diagnostic marker of the amyloid plaques that characterize AD.

Evidence is mounting that AD harms the brain for many years before physicians and family members can detect symptoms, and this has led many to conclude that effective AD treatments may only be possible if scientists find ways to identify presymptomatic sufferers. The results are an encouraging sign that this search for new indicators, known as antecedent biomarkers, may be succeeding, according to senior author David M. Holtzman, M.D., the Andrew and Gretchen Jones Professor and chair of the department of neurology at the Washington University School of Medicine in St. Louis (MO, USA) and neurologist-in-chief at Barnes-Jewish Hospital (St. Louis, MO, USA).

"We still need to confirm with long-term follow-up studies that subjects with this biomarker and brain damage go on to develop the cognitive changes characteristic of Alzheimer's," said Dr. Holtzman. "For now, the evidence we've uncovered further proves that identification and treatment prior to the start of the symptoms of Alzheimer's disease are likely going to be essential to preventing irreversible brain injury."

A-beta 42 is a protein fragment that clumps together in the brain to form the plaques that have long been the diagnostic hallmark of the disease. In an earlier study, the same Washington University researchers revealed that when A-beta 42 decreases in CSF, it begins to build up in the brain. "The new results show that something associated with amyloid deposition in the brain--either the amyloid itself or some toxic product of it--is causing brain damage in people who are still cognitively normal," noted Dr. Holtzman.

For the study, led by Anne Fagan, Ph.D., research associate professor of neurology, scientists analyzed CSF samples and brain scans of two groups of subjects at the university's Alzheimer's disease research center. The first group of 29 volunteers had very mild cognitive impairment; the remaining 69 volunteers were cognitively normal. Their ages ranged from 60 to 91. Researchers analyzed CSF samples and took magnetic resonance imaging (MRI) scans of subjects' brains. They used a computer program to analyze the MRI scans and determine whole brain volume, a measurement of the amount of space taken up by a patient's gray and white matter minus the CSF fluid circulating in the skull.

Participants with normal levels of A-beta 42 in their CSF had whole brain volumes within expected ranges. But in both the cognitively impaired subjects and in cognitively normal volunteers with decreased CSF A-beta 42, the size of the brain was smaller. In addition to A-beta 42, researchers assessed CSF levels of a family of proteins called tau proteins. These proteins are a component of structures called neurofibrillary tangles that increase as AD progresses. Scientists believe increased levels of tangles in the brain lead to increased CSF tau levels.

The researchers discovered CSF tau levels did not increase until the study participants became mentally impaired. "We've thought for some time that in Alzheimer's disease, amyloid builds up first followed by an increase in tangle accumulation," Dr. Holtzman stated. "This is some of the first evidence in living people that this idea may be right: large scale changes in amyloid seem to precede large scale changes in tau, which are then linked to the onset of clinical dementia symptoms."

Researchers will follow cognitively normal subjects with reduced CSF amyloid levels and brain volumes to see if they eventually become demented, potentially confirming A-beta 42 as an antecedent biomarker for Alzheimer's disease. They continue to try to find additional Alzheimer's biomarkers in CSF samples and MRI brain scans.

The study was published online in the journal Annals of Neurology in February 2009.

Related Links:
Washington University School of Medicine in St. Louis

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58 (138.99803161621): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294722699 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294722699 AND published='1' LIMIT 1

59 (154.01840209961): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294722699 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294722699 AND published='1' LIMIT 1

60 (66.995620727539): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294722699 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294722699 AND published='1' LIMIT 1

61 (123.02398681641): 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 (576.01928710938): SELECT fid FROM jos_deeppockets WHERE id=294722699 AND published='1' union SELECT fid FROM jos_deeppockets_archive WHERE id=294722699 AND published='1' LIMIT 1

63 (56.028366088867): 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 (66.995620727539): select jos_twitters.link from jos_twitters where cat=10

65 (39.100646972656): select jos_facebook.link from jos_facebook where cat=10

66 (33.140182495117): select jos_google_plus.link from jos_google_plus where cat=10

67 (30.994415283203): select jos_linkedin.link from jos_linkedin where cat=10

68 (38.862228393555): SELECT fid FROM jos_deeppockets WHERE id=294722699 AND published='1' union SELECT fid FROM jos_deeppockets_archive WHERE id=294722699 AND published='1' LIMIT 1

69 (34.809112548828): 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 (550.0316619873): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294722699 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

71 (344.03800964355): SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294722699 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

72 (58.889389038086): 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 (47.922134399414): SELECT show_live FROM jos_com_show_setting LIMIT 1

74 (30.040740966797): SELECT show_live FROM jos_com_show_setting LIMIT 1

75 (27.894973754883): SELECT show_live FROM jos_com_show_setting LIMIT 1

76 (30.040740966797): SELECT show_live FROM jos_com_show_setting LIMIT 1

77 (27.894973754883): SELECT show_live FROM jos_com_show_setting LIMIT 1

78 (27.894973754883): SELECT show_live FROM jos_com_show_setting LIMIT 1

79 (26.941299438477): SELECT show_live FROM jos_com_show_setting LIMIT 1

80 (27.894973754883): SELECT show_live FROM jos_com_show_setting LIMIT 1

81 (26.941299438477): SELECT show_live FROM jos_com_show_setting LIMIT 1

82 (27.894973754883): SELECT show_live FROM jos_com_show_setting LIMIT 1

83 (27.179718017578): SELECT show_live FROM jos_com_show_setting LIMIT 1

84 (28.133392333984): SELECT show_live FROM jos_com_show_setting LIMIT 1

85 (27.894973754883): SELECT show_live FROM jos_com_show_setting LIMIT 1

86 (28.848648071289): SELECT show_live FROM jos_com_show_setting LIMIT 1

87 (41.961669921875): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294722699 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

88 (29.087066650391): SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294722699 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

89 (33.855438232422): 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 (52.928924560547): SELECT show_live FROM jos_com_show_setting LIMIT 1

91 (30.994415283203): SELECT show_live FROM jos_com_show_setting LIMIT 1

92 (46.968460083008): SELECT show_live FROM jos_com_show_setting LIMIT 1

93 (28.848648071289): SELECT show_live FROM jos_com_show_setting LIMIT 1

94 (28.133392333984): SELECT show_live FROM jos_com_show_setting LIMIT 1

95 (28.133392333984): SELECT show_live FROM jos_com_show_setting LIMIT 1

96 (27.894973754883): SELECT show_live FROM jos_com_show_setting LIMIT 1

97 (27.894973754883): SELECT show_live FROM jos_com_show_setting LIMIT 1

98 (26.941299438477): SELECT show_live FROM jos_com_show_setting LIMIT 1

99 (27.894973754883): SELECT show_live FROM jos_com_show_setting LIMIT 1

100 (40.054321289062): SELECT show_live FROM jos_com_show_setting LIMIT 1

101 (36.001205444336): SELECT show_live FROM jos_com_show_setting LIMIT 1

102 (27.894973754883): SELECT show_live FROM jos_com_show_setting LIMIT 1

103 (28.133392333984): SELECT show_live FROM jos_com_show_setting LIMIT 1

104 (86.069107055664): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294722699 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294722699 AND published='1' LIMIT 1

105 (46.968460083008): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294722699 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294722699 AND published='1' LIMIT 1

106 (55.789947509766): 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=294722699 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1

107 (46.014785766602): 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=294722699 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1

108 (73.19450378418): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294722699 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294722699 AND published='1' LIMIT 1

109 (43.869018554688): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294722699 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294722699 AND published='1' LIMIT 1

110 (46.968460083008): 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=294722699 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1

111 (538.11073303223): 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=294722699 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1

112 (566.95938110352): 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 (432.96813964844): 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 (80.108642578125): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294722699 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294722699 AND published='1' LIMIT 1

115 (47.206878662109): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294722699 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294722699 AND published='1' LIMIT 1

116 (48.87580871582): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294722699 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294722699 AND published='1' LIMIT 1

117 (38.14697265625): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294722699 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294722699 AND published='1' LIMIT 1

118 (51.975250244141): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294722699 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294722699 AND published='1' LIMIT 1

119 (51.975250244141): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294722699 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294722699 AND published='1' LIMIT 1

120 (72.002410888672): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294722699 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294722699 AND published='1' LIMIT 1

121 (46.968460083008): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294722699 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294722699 AND published='1' LIMIT 1

122 (291.10908508301): SELECT * FROM trending_articles WHERE `journal_id` = 10 AND `timestamp` <= NOW() + INTERVAL 7 DAY ORDER BY `order`

123 (!!!!! 21553.993225098): 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 (544.78645324707): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294722699 AND type='deeppockets_item' AND published='1' union SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294722699 AND type='deeppockets_item' AND published='1' LIMIT 1

125 (!!!!! 8993.8640594482): ( 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 (141.85905456543): ( 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 (71.048736572266): 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 (39.100646972656): 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 (78.201293945312): 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 (46.014785766602): 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 (377.17819213867): 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 (47.922134399414): 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 (111.10305786133): 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 (41.961669921875): 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 (550.98533630371): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294722699 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

136 (497.81799316406): SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294722699 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

137 (46.968460083008): SELECT name FROM jos_deeppockets WHERE id=212

138 (34.809112548828): SELECT name FROM jos_deeppockets WHERE id=212

139 (734.09080505371): 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 (678.06243896484): 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 (103.95050048828): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294722699 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294722699 AND published='1' LIMIT 1

142 (72.956085205078): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294722699 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294722699 AND published='1' LIMIT 1

143 (!!!!! 10352.849960327): TRUNCATE TABLE jos_trademed_module

144 (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 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=294722699 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1

145 (75.817108154297): 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=294722699 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1

146 (!!!!! 1084.0892791748): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294722699 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

147 (74.148178100586): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294722699 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

148 (80.82389831543): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294722699 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294722699 AND published='1' LIMIT 1

149 (243.9022064209): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294722699 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294722699 AND published='1' LIMIT 1

150 (!!!!! 1518.0110931396): 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 (77.009201049805): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294722699 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294722699 AND published='1' LIMIT 1

152 (61.988830566406): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294722699 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294722699 AND published='1' LIMIT 1

153 (55.074691772461): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294722699 AND type='deeppockets_item' AND published='1' union SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294722699 AND type='deeppockets_item' AND published='1' LIMIT 1

154 (46.968460083008): 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 (43.153762817383): 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 (51.021575927734): SELECT livesite FROM jos_dp_categories WHERE id=10 AND published='1' LIMIT 1

157 (202.89421081543): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294722699 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294722699 AND published='1' LIMIT 1

158 (71.048736572266): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294722699 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294722699 AND published='1' LIMIT 1

159 (62.942504882812): select jos_twitters.link from jos_twitters where cat=10

160 (38.14697265625): select jos_facebook.link from jos_facebook where cat=10

161 (40.054321289062): select jos_google_plus.link from jos_google_plus where cat=10

162 (37.908554077148): select jos_linkedin.link from jos_linkedin where cat=10

163 (390.05279541016): update jos_bannersmanager_banner set impmade=impmade+1 where id in(14615,14202,14203)

164 (!!!!! 1575.9468078613): insert into jos_banners_delta values (14615,'2025-06-29 10:39:18','216.73.216.249','view'),(14202,'2025-06-29 10:39:18','216.73.216.249','view'),(14203,'2025-06-29 10:39:18','216.73.216.249','view')

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