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Cognitive and PET studies of postmenopausal women
644
Abstracts
mot, PSYCHI"TitY 1996;39:500-666
night (22.00-07.00h) and the sleep EEG was recorded from 23.0007.00 h. While there was no signiflcant effect of the NPY treatment compared to placebo on plasma levels of ACTIi. cortisol and prolactin. we found :l significant decrease in the plasma GH concentration during the first Imlf of the night (24.00-02.00 h, area under the curve: 454.3:t258.7 ng/ml x min after NPY vs 866.0:!:497 nglntl x min after placebo, p
490. GONADAL STEROID LEVELS AND MEMORY FUNCTION IN INFERTILE WOMEN
sivity) have been described in Alzheimer's disease (AD).The purposeof this study was 10 examine HPA axis function lcnghudlnally in patients with carefully charncterizcd AD. Twenty-live patients (16 females, 9 males; mean age 73.0 :t 5_8 years; mean MMSE 19.J ± S.l) meeting NINCDS criteria for probable AD were entered into the study. Basal cortisol nnd posrdexamethasone cortisol were measured on each subject on an outpatient basis at 9 monthly intervals. All patients were free of medications known to affect the DST. Results: At baseline. both basal and posrdexamcthasonc cortisol levels were significantly higher in AD subjects compared to healthy controls (n» 10) (t=2.1. df=33. p=O.04S and t=2.1. df=33. p=O.04I. respectively). Four AD subjects were DST non-suppressors (postdexumcthasone cortisol> 5 meg/dl)at baseline. At 9 months follow-up. 3 of these subjects remained. non-suppressors. one was lost to follow-up and 4 additional subjects became non-suppressors. At the 18 month assessment point. 10 more subjects were lost to follow-up. However. of the 7 subjects who were non-suppressors at 9 months. only 2 remained non-suppressors, one was a basal hypcrsecrctor, and IWO had reverted to non-suppressor status. A further 2 subjects had become non-suppressors at 18 months. It was concluded that, while the proportion of dexamethasone non-suppressors within the sample increased with disease progression. HPA axis dysfunction did not remain stable over time for the majority of AD subjects.
R.M. Soleymani J. P.A. Keenan I, & K.A. Glnsburgf IWayne State Univct!lity School of Medicine. Department of Psychiatry and Behuvlornl Neurosclcnces; ~WaYlle Slate Universlty School of Medicine. Department of Reproductive Endocrinology. Detroit, MI 48201 The hippocampus plays a critical role in explicit memory. which is memory for facts and events. This type of memory is dissocinble from implicit memory. which includes memory abilities expressed through unconscious changes in performance. The hippocampal formation is particularly sensitive [0 gomulal steroids, us changes in estradiol levels influence hippocampal physiology and morphology. Numerous studies hnve invcsrie:lh'c1 the df,·r.I<: of
s,,~roi('
hormones on m~I11~~t
492. COGNITIVE AND PET STUDIES OF
POSTMENOPAUSAL WOMEN S.G. Chakravorty I. A. Lockwood", &
U. Halbreich 1.3
::!.'n~!lg~l
menopausal, naturally cycling, and pregnant women. These studies have yielded inconsistent findings, We conducted the present study to determine if acute fluctuations in estrndlol impair explicit memory. Twentytwo infertile women undergoing hormon..! manipulation prior to ill vitro fcrtilizution (IVP) and twenty-two ugc and education-mntched normal controls partielpnted, Memory was assessed lIt baseline. during a GNRH artnlog-induccd hypoestrogenlc state. lind during a gonadctropiu-Induccd hypercstrogenic state, Both hlppocampal-dcpcndcnt explicit and nonhippocumpnl-deperulcnt implicit memory were assessed. mood samples were obtained at each testingsession,With the exception of a main effect for time on paragraph recall lind word stem completion priming (p < 0.05). both uuributable to practice effects, there were 110 significant differences between groups on nny of the memory measures, Spcclflcutly, repeated measures ANOV A indicated that explicit memory scores at the hypoestrogenlc state for the IVF women (I1.76~ J.65) were not significantly dilferent from controls (10.71:t 2.76), These data suggest thllt short term, ONRH analog-induced gonadal suppression docs not result in impairedexptlclt memory.
491. A LONGITUDINAL STUDY OF HPA AXIS DYSFUNCTION IN ALZHEIMER'S DISEASE B,A. Lawlor, G. Swanwlck, R. Coen, B.J. Walsh, & D. Coakley Department of Psychiatry lind Mercer's Institute for Research on Ageing. St. James's Hospital. Dublin 8, Ireland Hypothalamlc-pltuhury-udrenul (HPA) axis abnormalities (basal hyperconlsollsm, dexamethasone: nonsuppresslon and udrcnnl hyper-respon-
I Blobehavlorul
Program; ~Depl.of Neurology & AUdiology: JDcpt.ODI
0rn-SUNY Buffalo
Preliminary reports have shownpossible beneficial effects of estrogenon mood and cognition of POSI menopausal women. in addltlon to it's role in the prevention of cardiovascular disorders and osteoporosis. We conducted u preliminary study to assess the effects of the mixedestrogen antegonisr tumoxifen and to determine if improvement in cognitive functions is associatedwith improved cerebralblood now. Six postmenopausal women have been studied. The scan sequence was: I) resting, 2) visual task. 3) symbol digit substitution. 4) Wisconsin Card Son; repeat 2. 3. and 4. Data were analyzed with the SPM activation paradigm anti responses 10 the WCS Were recorded and tabulated. At the Bonferroni 0.05 levelof significance. the meanof the 2 wes trials, compared to rest. activated 3868 pixels with an average Z score of 4.629 (only pixels exceeding threshold of 3.584 were Included): the distribution of these pixels Was restricted to primary and assoclatlve visual areas and the cerebellum. Somewhat surprisingly, no frontal actlvaticn was seen, Frontal regions. particularly the anterior cingulatc, were included in the SPM at the omnibus 0.05 level. The absence of frontal activity at the more rigorous thresholdis consistent with the poor performance of these subjects on the WCS, An analysis of CBF duta III the Bonferroni 0.05 level comparing tlte eye movement-speech control task to the symbol digit task produced I1n SPM containing 3706 pixels with n mean Z score of 4.896. All significant pixels were in either the cerebellum or primllry and associative visual cortex,suggesting thar these brain regions mediate the spatial logic required to perform this task, Post treatment with tamoxifen, averageacrivatlon in response 10 the wes was Z=2,64S over 13,850 pixels. the omnibus was 0.05. The signincant pixels were in the Irontal lobes, Average activationin response symbol digit test Increased with an average Z score of 2.114 oyer 3730 pixels with the omnibus of 0.05. This increase was mostly in left temporal and pnrletnl areas,
Abstracts
mot, PSYCHI"TitY 1996;39:500-666
night (22.00-07.00h) and the sleep EEG was recorded from 23.0007.00 h. While there was no signiflcant effect of the NPY treatment compared to placebo on plasma levels of ACTIi. cortisol and prolactin. we found :l significant decrease in the plasma GH concentration during the first Imlf of the night (24.00-02.00 h, area under the curve: 454.3:t258.7 ng/ml x min after NPY vs 866.0:!:497 nglntl x min after placebo, p
490. GONADAL STEROID LEVELS AND MEMORY FUNCTION IN INFERTILE WOMEN
sivity) have been described in Alzheimer's disease (AD).The purposeof this study was 10 examine HPA axis function lcnghudlnally in patients with carefully charncterizcd AD. Twenty-live patients (16 females, 9 males; mean age 73.0 :t 5_8 years; mean MMSE 19.J ± S.l) meeting NINCDS criteria for probable AD were entered into the study. Basal cortisol nnd posrdexamethasone cortisol were measured on each subject on an outpatient basis at 9 monthly intervals. All patients were free of medications known to affect the DST. Results: At baseline. both basal and posrdexamcthasonc cortisol levels were significantly higher in AD subjects compared to healthy controls (n» 10) (t=2.1. df=33. p=O.04S and t=2.1. df=33. p=O.04I. respectively). Four AD subjects were DST non-suppressors (postdexumcthasone cortisol> 5 meg/dl)at baseline. At 9 months follow-up. 3 of these subjects remained. non-suppressors. one was lost to follow-up and 4 additional subjects became non-suppressors. At the 18 month assessment point. 10 more subjects were lost to follow-up. However. of the 7 subjects who were non-suppressors at 9 months. only 2 remained non-suppressors, one was a basal hypcrsecrctor, and IWO had reverted to non-suppressor status. A further 2 subjects had become non-suppressors at 18 months. It was concluded that, while the proportion of dexamethasone non-suppressors within the sample increased with disease progression. HPA axis dysfunction did not remain stable over time for the majority of AD subjects.
R.M. Soleymani J. P.A. Keenan I, & K.A. Glnsburgf IWayne State Univct!lity School of Medicine. Department of Psychiatry and Behuvlornl Neurosclcnces; ~WaYlle Slate Universlty School of Medicine. Department of Reproductive Endocrinology. Detroit, MI 48201 The hippocampus plays a critical role in explicit memory. which is memory for facts and events. This type of memory is dissocinble from implicit memory. which includes memory abilities expressed through unconscious changes in performance. The hippocampal formation is particularly sensitive [0 gomulal steroids, us changes in estradiol levels influence hippocampal physiology and morphology. Numerous studies hnve invcsrie:lh'c1 the df,·r.I<: of
s,,~roi('
hormones on m~I11~~t
492. COGNITIVE AND PET STUDIES OF
POSTMENOPAUSAL WOMEN S.G. Chakravorty I. A. Lockwood", &
U. Halbreich 1.3
::!.'n~!lg~l
menopausal, naturally cycling, and pregnant women. These studies have yielded inconsistent findings, We conducted the present study to determine if acute fluctuations in estrndlol impair explicit memory. Twentytwo infertile women undergoing hormon..! manipulation prior to ill vitro fcrtilizution (IVP) and twenty-two ugc and education-mntched normal controls partielpnted, Memory was assessed lIt baseline. during a GNRH artnlog-induccd hypoestrogenlc state. lind during a gonadctropiu-Induccd hypercstrogenic state, Both hlppocampal-dcpcndcnt explicit and nonhippocumpnl-deperulcnt implicit memory were assessed. mood samples were obtained at each testingsession,With the exception of a main effect for time on paragraph recall lind word stem completion priming (p < 0.05). both uuributable to practice effects, there were 110 significant differences between groups on nny of the memory measures, Spcclflcutly, repeated measures ANOV A indicated that explicit memory scores at the hypoestrogenlc state for the IVF women (I1.76~ J.65) were not significantly dilferent from controls (10.71:t 2.76), These data suggest thllt short term, ONRH analog-induced gonadal suppression docs not result in impairedexptlclt memory.
491. A LONGITUDINAL STUDY OF HPA AXIS DYSFUNCTION IN ALZHEIMER'S DISEASE B,A. Lawlor, G. Swanwlck, R. Coen, B.J. Walsh, & D. Coakley Department of Psychiatry lind Mercer's Institute for Research on Ageing. St. James's Hospital. Dublin 8, Ireland Hypothalamlc-pltuhury-udrenul (HPA) axis abnormalities (basal hyperconlsollsm, dexamethasone: nonsuppresslon and udrcnnl hyper-respon-
I Blobehavlorul
Program; ~Depl.of Neurology & AUdiology: JDcpt.ODI
0rn-SUNY Buffalo
Preliminary reports have shownpossible beneficial effects of estrogenon mood and cognition of POSI menopausal women. in addltlon to it's role in the prevention of cardiovascular disorders and osteoporosis. We conducted u preliminary study to assess the effects of the mixedestrogen antegonisr tumoxifen and to determine if improvement in cognitive functions is associatedwith improved cerebralblood now. Six postmenopausal women have been studied. The scan sequence was: I) resting, 2) visual task. 3) symbol digit substitution. 4) Wisconsin Card Son; repeat 2. 3. and 4. Data were analyzed with the SPM activation paradigm anti responses 10 the WCS Were recorded and tabulated. At the Bonferroni 0.05 levelof significance. the meanof the 2 wes trials, compared to rest. activated 3868 pixels with an average Z score of 4.629 (only pixels exceeding threshold of 3.584 were Included): the distribution of these pixels Was restricted to primary and assoclatlve visual areas and the cerebellum. Somewhat surprisingly, no frontal actlvaticn was seen, Frontal regions. particularly the anterior cingulatc, were included in the SPM at the omnibus 0.05 level. The absence of frontal activity at the more rigorous thresholdis consistent with the poor performance of these subjects on the WCS, An analysis of CBF duta III the Bonferroni 0.05 level comparing tlte eye movement-speech control task to the symbol digit task produced I1n SPM containing 3706 pixels with n mean Z score of 4.896. All significant pixels were in either the cerebellum or primllry and associative visual cortex,suggesting thar these brain regions mediate the spatial logic required to perform this task, Post treatment with tamoxifen, averageacrivatlon in response 10 the wes was Z=2,64S over 13,850 pixels. the omnibus was 0.05. The signincant pixels were in the Irontal lobes, Average activationin response symbol digit test Increased with an average Z score of 2.114 oyer 3730 pixels with the omnibus of 0.05. This increase was mostly in left temporal and pnrletnl areas,