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Neuroimaging Shows Women Experience Higher Rates of Decline in Alzheimer’s Disease and Aging

By MedImaging International staff writers
Posted on 08 Aug 2013
The rates of regional brain loss and cognitive decline caused by aging and the early stages of Alzheimer’s disease (AD) are higher for women and for individuals with a major genetic risk factor for AD, according to recent research.

The scientists, from the University of California, San Diego (UCSD) School of Medicine (USA), published their findings online July 4, 2013, in the American Journal of Neuroradiology. The linkage between APOE ε4, which codes for a protein involved in binding lipids in the lymphatic and circulatory systems, was already documented as the strongest known genetic risk factor for sporadic AD, the most typical form of the disease. But the correlation between the sex of an individual and AD has been less-well documented, according to the UC San Diego scientists.

“APOE ε4 has been known to lower the age of onset and increase the risk of getting the disease,” said the study’s first author Dominic Holland, PhD, a researcher in the department of neurosciences at UC San Diego School of Medicine. “Previously we showed that the lower the age, the higher the rates of decline in AD. So it was important to examine the differential effects of age and APOE ε4 on rates of decline, and to do this across the diagnostic spectrum for multiple clinical measures and brain regions, which had not been done before.”

The researchers assessed 688 men and women over the age of 65 participating in the Alzheimer’s Disease Neuroimaging Initiative (La Jolla, CA, USA; www.adni-info.org), a longitudinal, multi-institution study to monitor the progression of AD and its effects upon the structures and functions of the brain. They discovered that women with mild cognitive impairment (a disorder precursory to AD diagnosis) suffered higher rates of cognitive decline than men; and that all women, regardless of whether or not they showed signs of dementia, experienced greater regional brain loss over time than did men. The magnitude of the sex effect was as large as that of the APOE ε4 allele.

“Assuming larger population-based samples reflect the higher rates of decline for women than men, the question becomes what is so different about women,” said Dr. Holland. Hormonal variances or change seems a clear place to start, however, Dr. Holland reported that this is mostly unknown territory—at least regarding AD.

“Another important finding of this study is that men and women did not differ in the level of biomarkers of Alzheimer’s disease pathology,” said co-author Linda McEvoy, PhD, an associate professor in the UCSD department of radiology. “This suggests that brain volume loss in women may also be caused by factors other than Alzheimer’s disease, or that in women, these pathologies are more toxic. We clearly need more research on how an individual’s sex affects AD pathogenesis.”

Dr. Holland recognized that the study may raise more questions than it answers. “There are many factors that may affect the sex differences we observed, such as whether the women in this study may have had higher rates of diabetes or insulin resistance than the men. We also do not know how the use of hormone replacement therapy, reproductive history, or years since menopause may have affected these differences. All these issues need to be examined. There is no prevailing theory.”

However, Dr. Holland noted that just as APOE ε4 status identifies individuals at greater risk of AD, the sex of an individual might prove an significant element in future treatment as well. Currently, there is no cure for AD or any existing therapies that slow or stop disease progression. “The biggest impact might be down the road when disease-modifying therapies become available,” said Dr. Holland. “What works best for men might not work best for women. The same may be true for ε4 carriers versus noncarriers.”

Dr. Holland added that the findings also feed back into clinical trial design. The sex-composition of the sample will affect the rates of decline for both natural progression (the placebo component), and in all probability, the level of disease modification in participants receiving therapy. Therefore, a sex-based sub-analysis might be applicable. “Additionally, in clinical practice it may be important to expect higher rates of decline for women patients, to help anticipate when stages of decline that significantly alter quality of life would be reached,” Dr. Holland noted.

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University of California, San Diego School of Medicine





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88 (39.100646972656): SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294747607 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
89 (36.001205444336): 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 (30.040740966797): SELECT show_live FROM jos_com_show_setting LIMIT 1
92 (25.98762512207): SELECT show_live FROM jos_com_show_setting LIMIT 1
93 (28.848648071289): SELECT show_live FROM jos_com_show_setting LIMIT 1
94 (968.21784973145): SELECT show_live FROM jos_com_show_setting LIMIT 1
95 (50.067901611328): SELECT show_live FROM jos_com_show_setting LIMIT 1
96 (30.040740966797): SELECT show_live FROM jos_com_show_setting LIMIT 1
97 (30.994415283203): SELECT show_live FROM jos_com_show_setting LIMIT 1
98 (35.04753112793): SELECT show_live FROM jos_com_show_setting LIMIT 1
99 (26.941299438477): SELECT show_live FROM jos_com_show_setting LIMIT 1
100 (25.98762512207): SELECT show_live FROM jos_com_show_setting LIMIT 1
101 (27.894973754883): SELECT show_live FROM jos_com_show_setting LIMIT 1
102 (28.848648071289): SELECT show_live FROM jos_com_show_setting LIMIT 1
103 (26.941299438477): SELECT show_live FROM jos_com_show_setting LIMIT 1
104 (265.12145996094): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294747607 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294747607 AND published='1' LIMIT 1
105 (244.140625): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294747607 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294747607 AND published='1' LIMIT 1
106 (215.05355834961): 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=294747607 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
107 (401.97372436523): 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=294747607 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
108 (!!!!! 5872.9648590088): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294747607 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294747607 AND published='1' LIMIT 1
109 (!!!!! 3906.0115814209): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294747607 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294747607 AND published='1' LIMIT 1
110 (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.id=294747607 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
111 (416.04042053223): 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=294747607 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
112 (!!!!! 1061.9163513184): 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 (!!!!! 1209.9742889404): 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 (822.78251647949): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294747607 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294747607 AND published='1' LIMIT 1
115 (232.93495178223): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294747607 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294747607 AND published='1' LIMIT 1
116 (357.86628723145): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294747607 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294747607 AND published='1' LIMIT 1
117 (!!!!! 1579.0462493896): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294747607 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294747607 AND published='1' LIMIT 1
118 (277.04238891602): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294747607 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294747607 AND published='1' LIMIT 1
119 (61.988830566406): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294747607 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294747607 AND published='1' LIMIT 1
120 (267.98248291016): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294747607 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294747607 AND published='1' LIMIT 1
121 (142.09747314453): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294747607 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294747607 AND published='1' LIMIT 1
122 (353.09791564941): SELECT * FROM trending_articles WHERE `journal_id` = 10 AND `timestamp` <= NOW() + INTERVAL 7 DAY ORDER BY `order`
123 (!!!!! 104847.90802002): 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 (!!!!! 1543.0450439453): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294747607 AND type='deeppockets_item' AND published='1' union SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294747607 AND type='deeppockets_item' AND published='1' LIMIT 1
125 (769.85359191895): ( 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 (51.021575927734): ( 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 (34.809112548828): 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 (30.994415283203): 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 (238.18016052246): 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 (43.869018554688): 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 (30.994415283203): 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 (30.040740966797): 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 (442.9817199707): 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 (39.100646972656): 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 (437.02125549316): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294747607 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
136 (388.86070251465): SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294747607 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
137 (168.0850982666): SELECT name FROM jos_deeppockets WHERE id=212
138 (34.093856811523): SELECT name FROM jos_deeppockets WHERE id=212
139 (578.88031005859): 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((;)|($))' AND catid IN (0,110) ORDER BY publish_up ASC LIMIT 3
140 (470.87669372559): SELECT *, DATE_FORMAT(publish_up,'%d %b %Y') AS date_publish_up, DATE_FORMAT(publish_down,'%d %b %Y') AS date_publish_down FROM jos_events WHERE state=1 AND publish_up > NOW() and extra_info REGEXP '((;)|(^))212((;)|($))' AND catid IN (0,110) ORDER BY publish_up ASC LIMIT 3
141 (87.976455688477): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294747607 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294747607 AND published='1' LIMIT 1
142 (46.968460083008): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294747607 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294747607 AND published='1' LIMIT 1
143 (!!!!! 17138.004302979): TRUNCATE TABLE jos_trademed_module
144 (92.983245849609): 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=294747607 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
145 (55.074691772461): 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=294747607 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
146 (972.03254699707): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294747607 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
147 (55.074691772461): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294747607 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
148 (58.889389038086): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294747607 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294747607 AND published='1' LIMIT 1
149 (44.107437133789): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294747607 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294747607 AND published='1' LIMIT 1
150 (!!!!! 1207.1132659912): 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 (92.983245849609): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294747607 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294747607 AND published='1' LIMIT 1
152 (59.127807617188): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294747607 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294747607 AND published='1' LIMIT 1
153 (64.849853515625): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294747607 AND type='deeppockets_item' AND published='1' union SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294747607 AND type='deeppockets_item' AND published='1' LIMIT 1
154 (529.05082702637): 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 (55.074691772461): 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 (44.107437133789): SELECT livesite FROM jos_dp_categories WHERE id=10 AND published='1' LIMIT 1
157 (171.89979553223): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294747607 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294747607 AND published='1' LIMIT 1
158 (92.029571533203): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294747607 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294747607 AND published='1' LIMIT 1
159 (72.002410888672): select jos_twitters.link from jos_twitters where cat=10
160 (44.107437133789): select jos_facebook.link from jos_facebook where cat=10
161 (66.995620727539): select jos_google_plus.link from jos_google_plus where cat=10
162 (32.901763916016): select jos_linkedin.link from jos_linkedin where cat=10
163 (279.90341186523): update jos_bannersmanager_banner set impmade=impmade+1 where id in(14615,14202,14203)
164 (993.96705627441): insert into jos_banners_delta values (14615,'2025-06-25 09:22:06','216.73.216.120','view'),(14202,'2025-06-25 09:22:06','216.73.216.120','view'),(14203,'2025-06-25 09:22:06','216.73.216.120','view')