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PET Technique Sees Brain Aging Before Symptoms Appear

By MedImaging International staff writers
Posted on 09 Feb 2009
Scientists are using innovative brain-scan technology combined with patient-specific information on Alzheimer's disease risk, to help diagnose brain aging, often before symptoms appear.

Published in the January 2008 issue of the journal Archives of General Psychiatry, the investigators' study may offer a more effective method for tracking brain aging. The technology, developed at the University of California, Los Angeles (UCLA; USA) researchers, used positron emission tomography (PET) imaging, which allows "a window into the brain” of living people and specifically reveals plaques and tangles, the hallmarks of neurodegeneration. The PET scans were complemented by information on patients' age, cognitive status, and a genetic profile.

"Combining key patient information with a brain scan may give us better predictive power in targeting those who may benefit from early interventions, as well as help test how well treatments are working,” said study author Dr. Gary Small, a professor at the Semel Institute for Neuroscience and Human Behavior at UCLA.

Scientists captured PET brain scans of 76 non-demented volunteers after they had been intravenously injected with a new chemical marker called FDDNP (2-(1-{6-[(2-[F-18] fluoroethyl) (methyl)amino]-2-naphthyl}ethylidene)malononitrile), which binds to plaque and tangle deposits in the brain. Researchers were then able to target where these abnormal protein deposits were accumulating. They reported that older age correlated with higher concentrations of FDDNP in the medial and lateral temporal regions of the brain, areas involved with memory, where plaques and tangles typically gather. The average age of study volunteers was 67.

Thirty-four of the 76 volunteers carried the APOE-4 gene allele, which increases the risk for developing Alzheimer's disease. This group demonstrated higher FDDNP levels in the frontal region of the brain (also involved in memory) than study participants without the allele.

"We found that for many volunteers, the imaging scans reflected subtle brain changes, which take place before symptoms manifest,” said Dr. Small, who is also director of the UCLA Center on Aging. Dr. Small noted that the brain would try to compensate for any problems, which is why cognitive symptoms may not become apparent until much later. "This type of scan offers an opportunity to see what is really going on in the brain,” he said.

Another subset of the participants had mild cognitive impairment (MCI), a condition that increases the risk of developing Alzheimer's disease. These 36 participants had higher measures of FDDNP in the medial temporal brain regions than normal volunteers. Those who had both MCI and the APOE-4 gene had higher concentrations of FDDNP in the medial temporal brain regions than volunteers who had MCI but not APOE-4.

"We could see more advancing disease in those with mild cognitive impairment, who are already demonstrating some minimal symptoms,” Dr. Small said. "Eventually, this imaging method, together with patient information like age, cognitive status, and genetics, may help us better manage brain aging.”

According to Dr. Small, in the future, brain aging may be controlled similarly to high cholesterol or high blood pressure. Patients would receive a brain scan and perhaps a genetic test to predict their risk. Medications and other interventions could be prescribed, if necessary, to prevent or delay future neurodegeneration, allowing physicians to protect a healthy brain before extensive damage occurs. The PET brain scans may also prove helpful in tracking the effectiveness of treatments.

PET, combined with the FDDNP probe, is the only imaging technology that provides a full profile of neurodegeneration that includes measures of both plaques and tangles--the physical evidence of Alzheimer's disease in the brain. "The fact that we can see tau tangles as well as amyloid plaques is critically important in early detection of brain aging, since the tangles are the first abnormal proteins that appear in the brain, long before dementia is clinically obvious to the physician,” said Dr. Jorge R. Barrio, a study author and professor of molecular and medical pharmacology at the David Geffen School of Medicine at UCLA.

Such subtleties allow more insight into how the plaques and tangles spread and ultimately how Alzheimer's disease may develop, according to the investigators. Currently, the new FDDNP-PET scans are used in a research setting, but clinical trials are in development to bring the technology to wider patient use.

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91 (36.954879760742): SELECT show_live FROM jos_com_show_setting LIMIT 1
92 (29.087066650391): SELECT show_live FROM jos_com_show_setting LIMIT 1
93 (27.894973754883): SELECT show_live FROM jos_com_show_setting LIMIT 1
94 (27.894973754883): SELECT show_live FROM jos_com_show_setting LIMIT 1
95 (29.087066650391): SELECT show_live FROM jos_com_show_setting LIMIT 1
96 (40.054321289062): SELECT show_live FROM jos_com_show_setting LIMIT 1
97 (28.848648071289): SELECT show_live FROM jos_com_show_setting LIMIT 1
98 (27.179718017578): SELECT show_live FROM jos_com_show_setting LIMIT 1
99 (28.133392333984): SELECT show_live FROM jos_com_show_setting LIMIT 1
100 (27.894973754883): SELECT show_live FROM jos_com_show_setting LIMIT 1
101 (28.848648071289): SELECT show_live FROM jos_com_show_setting LIMIT 1
102 (26.941299438477): SELECT show_live FROM jos_com_show_setting LIMIT 1
103 (26.941299438477): SELECT show_live FROM jos_com_show_setting LIMIT 1
104 (66.041946411133): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294721981 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294721981 AND published='1' LIMIT 1
105 (46.014785766602): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294721981 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294721981 AND published='1' LIMIT 1
106 (51.021575927734): 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=294721981 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=294721981 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
108 (85.115432739258): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294721981 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294721981 AND published='1' LIMIT 1
109 (48.160552978516): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294721981 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294721981 AND published='1' LIMIT 1
110 (51.021575927734): 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=294721981 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
111 (536.91864013672): 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=294721981 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
112 (552.17742919922): 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 (423.19297790527): 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 (103.95050048828): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294721981 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294721981 AND published='1' LIMIT 1
115 (64.13459777832): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294721981 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294721981 AND published='1' LIMIT 1
116 (62.942504882812): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294721981 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294721981 AND published='1' LIMIT 1
117 (41.007995605469): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294721981 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294721981 AND published='1' LIMIT 1
118 (41.961669921875): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294721981 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294721981 AND published='1' LIMIT 1
119 (38.14697265625): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294721981 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294721981 AND published='1' LIMIT 1
120 (46.014785766602): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294721981 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294721981 AND published='1' LIMIT 1
121 (42.915344238281): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294721981 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294721981 AND published='1' LIMIT 1
122 (309.94415283203): SELECT * FROM trending_articles WHERE `journal_id` = 10 AND `timestamp` <= NOW() + INTERVAL 7 DAY ORDER BY `order`
123 (!!!!! 21289.825439453): 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 (541.21017456055): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294721981 AND type='deeppockets_item' AND published='1' union SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294721981 AND type='deeppockets_item' AND published='1' LIMIT 1
125 (!!!!! 9412.0502471924): ( 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 (126.12342834473): ( 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 (524.04403686523): 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 (97.990036010742): 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 (379.80079650879): 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 (67.949295043945): 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 (329.01763916016): 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 (56.982040405273): 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 (303.98368835449): 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 (78.916549682617): 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 (550.0316619873): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294721981 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
136 (430.10711669922): SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294721981 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
137 (236.98806762695): SELECT name FROM jos_deeppockets WHERE id=213
138 (36.001205444336): SELECT name FROM jos_deeppockets WHERE id=213
139 (699.99694824219): 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((;)|($))' AND catid IN (0,110) ORDER BY publish_up ASC LIMIT 3
140 (652.79006958008): SELECT *, DATE_FORMAT(publish_up,'%d %b %Y') AS date_publish_up, DATE_FORMAT(publish_down,'%d %b %Y') AS date_publish_down FROM jos_events WHERE state=1 AND publish_up > NOW() and extra_info REGEXP '((;)|(^))213((;)|($))' AND catid IN (0,110) ORDER BY publish_up ASC LIMIT 3
141 (83.92333984375): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294721981 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294721981 AND published='1' LIMIT 1
142 (48.87580871582): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294721981 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294721981 AND published='1' LIMIT 1
143 (!!!!! 11387.825012207): TRUNCATE TABLE jos_trademed_module
144 (367.87986755371): 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=294721981 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
145 (83.92333984375): 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=294721981 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
146 (633.00132751465): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294721981 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
147 (80.108642578125): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294721981 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
148 (81.777572631836): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294721981 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294721981 AND published='1' LIMIT 1
149 (67.949295043945): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294721981 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294721981 AND published='1' LIMIT 1
150 (!!!!! 1646.9955444336): 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 (107.0499420166): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294721981 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294721981 AND published='1' LIMIT 1
152 (68.902969360352): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294721981 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294721981 AND published='1' LIMIT 1
153 (54.121017456055): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294721981 AND type='deeppockets_item' AND published='1' union SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294721981 AND type='deeppockets_item' AND published='1' LIMIT 1
154 (42.200088500977): 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)
155 (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)
156 (51.975250244141): SELECT livesite FROM jos_dp_categories WHERE id=10 AND published='1' LIMIT 1
157 (97.036361694336): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294721981 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294721981 AND published='1' LIMIT 1
158 (66.995620727539): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294721981 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294721981 AND published='1' LIMIT 1
159 (121.11663818359): select jos_twitters.link from jos_twitters where cat=10
160 (43.153762817383): select jos_facebook.link from jos_facebook where cat=10
161 (41.007995605469): select jos_google_plus.link from jos_google_plus where cat=10
162 (41.007995605469): select jos_linkedin.link from jos_linkedin where cat=10