- Email: [email protected]
AMYLOID AND HIPPOCAMPAL VOLUME ARE INDEPENDENTLY ASSOCIATED WITH MEMORY IN COGNITIVELY NORMAL ELDERLY
P1084
P3-340
Poster Presentations: Tuesday, July 18, 2017
AMYLOID AND HIPPOCAMPAL VOLUME ARE INDEPENDENTLYASSOCIATED WITH MEMORY IN COGNITIVELY NORMAL ELDERLY
Anna Svenningsson1, Philip Insel1, Erik Stomrud1, Sebastian Palmqvist1, Oskar Hansson2, 1Clinical Memory Research Unit, Lund University, Malm€o, Sweden; 2Lund University, Malm€o, Sweden. Contact e-mail: anna. [email protected] Background: Two hallmarks of Alzheimer’s disease (AD) are amy-
loid-beta deposition and neurodegeneration of specific areas of the brain, such as the hippocampus. However, the association between these biomarkers is not clear. Although amyloid pathology is thought to precede neurodegeneration, studies have shown Alzheimer-like structural brain changes independent of amyloidbeta. In this study, the relationship between amyloid pathology, hippocampal volume and memory in cognitively healthy elderly was examined. Methods: Cross-sectionally, the cohort of cognitively normal (CN; n¼303) in The Swedish Biofinder Study was studied with regards to cognitive tests, magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) markers. Automatic segmentation of MRI scans using FreeSurfer software was used to assess brain structure, specifically hippocampal volume. Amyloid pathology was defined as an abnormal CSF Ab42/Ab40 ratio (<0.10). ADAS delayed recall was used as assessment of memory impairment. Multiple linear regressions were performed to estimate the associations between Ab pathology, hippocampal volume and performance on memory test, adjusting for age, sex and education, as well as total intracranial volume in models with hippocampal volume. Results: Ab pathology and hippocampal volume were not significantly associated. Ab pathology was negatively associated with performance on memory test (p<0.01). The association remained the same when adjusting for hippocampal volume. Hippocampal volume was positively associated with performance on memory test (p<0.001), and this remained the same when adjusting for amyloid. Age was associated with memory performance (p<0.001), but this association was not significant when adjusting for hippocampal volume. Conclusions: These results suggest that amyloid and hippocampal volume independently affect memory in cognitively healthy elderly. The effect of age on memory disappeared when adjusting for hippocampal volume, suggesting that hippocampal volume mediates the effect of age on memory impairment.
P3-341
HIPPOCAMPAL INTEGRITY IN SWEDISH WOMEN WITH BILATERAL SALPINGOOOPHORECTOMY PRIOR TO NATURAL MENOPAUSE
Annie Duchesne1, Suzanne Tyson Witt2, Maria Engstr€om2, Elisabeth Classon2, Preben Kjølhede2, Asa Rydmark Kersley2, Elvar Theodorsson2, Elisabeth Avall Lundqvist2, Nina Lykke2, Margrit Shildrick2, Cecilia Asberg2, April Au1, Gillian Einstein1, 1 University of Toronto, Toronto, ON, Canada; 2Linkoping University, Linkoping, Sweden. Contact e-mail: [email protected] Background: Oophorectomy prior to natural menopause places
women at increased risk of dementia and/or Alzheimer’s disease (AD). Recent findings from our Toronto group reveal a negative association between oophorectomy prior to natural menopause and verbal memory in middle-aged women. We have also found a positive association between estrogen levels and verbal recall. Taken
together, these findings support previous work suggesting that oophorectomy, leading to reduced levels of estrogens, is detrimental to verbal memory. Estrogen withdrawal has also been correlated with reduced hippocampal volume and reduced hippocampal resting functional connectivity (FC), both early AD biomarkers. Thus, we wondered whether hippocampal volume and resting functional connectivity would be reduced in women with oophorectomy prior to natural menopause. Methods: In order to determine this, we recruited healthy, Swedish women (30 and 55 years) with the breast cancer mutation gene (BRCA1/2) who had a bilateral salpingo-oophorectomy (BSO) prior to natural menopause. Most women were between 1-7 years post-BSO and at least 6 months post-cancer treatment or had not had cancer. Using magnetic resonance imaging (3T scanner, Phillips) we measured functional resting state over 10 minutes and volume with a T1 structural scan. We collected urine in order to determine estrogen and progesterone levels. Results: We hypothesize that women with BSO will have structural and functional hippocampal changes compared to age matched controls. We predict that women with BSO will have smaller hippocampal volumes and reduced hippocampal FC. We further predict that lower levels of estrogens will correlate with these brain changes. Neuroimaging and endocrine analyses are ongoing. Conclusions: AD affects women in greater numbers and one possibility is that oophorectomy prior to natural menopause contributes to these numbers. Determining whether or not these women show the earliest biomarkers for AD will increase our understanding of estrogen withdrawal’s effects on brain health as well as its importance for healthy brain aging. Importantly, results of this study will inform us on the early brain changes in a population at greater risk of AD.
P3-342
RELATIONSHIP OF PHYSICAL ACTIVITIES DURING YOUNG ADULTHOOD AND MIDLIFE WITH BRAIN AMYLOID DEPOSITION, GLUCOSE METABOLISM, AND CORTICAL THICKNESS IN LATE-LIFE
Bo Kyung Sohn1, Dahyun Yi2, Min Soo Byun3, Young Min Choe4, Jee Wook Kim5, Hyo Jung Choi2, Hyewon Baek6, Jun Ho Lee2, Hyun Jung Kim7, Shin Gyeom Kim8, Eun Hyun Seo9, Ji Young Han2, Jong Inn Woo10, Dong Young Lee2,3, 1SMG-SNU Boramae Medical Center, Seoul, Republic of South Korea; 2Seoul National University Hospital, Seoul, Republic of South Korea; 3Seoul National University College of Medicine, Seoul, Republic of South Korea; 4Ulsan University Hospital, Ulsan, Republic of South Korea; 5Hallym University Dongtan Sacred Hospital, Seoul, Republic of South Korea; 6Kyunggi Provincial Hospital for the Elderly, Yongin, Republic of South Korea; 7Changsan Convalescent Hospital, Changwon, Republic of South Korea; 8Soon Chun Hyang University Bucheon Hospital, Bucheon, Republic of South Korea; 9College of Health Science, Chosun University, Gwangju, Republic of South Korea; 10 Medical Research Center Seoul National University, Seoul, Republic of South Korea. Contact e-mail: [email protected] Background: Epidemiological studies suggested that lifetime phys-
ical activities (PA) are related with the reduced risk of Alzheimer’s disease (AD) dementia. However, very limited information is available for the association between PA during earlier lifetime and in vivo cerebral AD pathologies in late-life. This study aimed to investigate the relationship of PA in young adulthood and midlife with beta-amyloid (Ab) accumulation and neurodegeneration in cognitive normal (CN) elderly individuals. Methods: One-hundred sixty five CN elderly subjects aged 61 years or over who participated in the Korean Brain Aging Study for Early Diagnosis and
P3-340
Poster Presentations: Tuesday, July 18, 2017
AMYLOID AND HIPPOCAMPAL VOLUME ARE INDEPENDENTLYASSOCIATED WITH MEMORY IN COGNITIVELY NORMAL ELDERLY
Anna Svenningsson1, Philip Insel1, Erik Stomrud1, Sebastian Palmqvist1, Oskar Hansson2, 1Clinical Memory Research Unit, Lund University, Malm€o, Sweden; 2Lund University, Malm€o, Sweden. Contact e-mail: anna. [email protected] Background: Two hallmarks of Alzheimer’s disease (AD) are amy-
loid-beta deposition and neurodegeneration of specific areas of the brain, such as the hippocampus. However, the association between these biomarkers is not clear. Although amyloid pathology is thought to precede neurodegeneration, studies have shown Alzheimer-like structural brain changes independent of amyloidbeta. In this study, the relationship between amyloid pathology, hippocampal volume and memory in cognitively healthy elderly was examined. Methods: Cross-sectionally, the cohort of cognitively normal (CN; n¼303) in The Swedish Biofinder Study was studied with regards to cognitive tests, magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) markers. Automatic segmentation of MRI scans using FreeSurfer software was used to assess brain structure, specifically hippocampal volume. Amyloid pathology was defined as an abnormal CSF Ab42/Ab40 ratio (<0.10). ADAS delayed recall was used as assessment of memory impairment. Multiple linear regressions were performed to estimate the associations between Ab pathology, hippocampal volume and performance on memory test, adjusting for age, sex and education, as well as total intracranial volume in models with hippocampal volume. Results: Ab pathology and hippocampal volume were not significantly associated. Ab pathology was negatively associated with performance on memory test (p<0.01). The association remained the same when adjusting for hippocampal volume. Hippocampal volume was positively associated with performance on memory test (p<0.001), and this remained the same when adjusting for amyloid. Age was associated with memory performance (p<0.001), but this association was not significant when adjusting for hippocampal volume. Conclusions: These results suggest that amyloid and hippocampal volume independently affect memory in cognitively healthy elderly. The effect of age on memory disappeared when adjusting for hippocampal volume, suggesting that hippocampal volume mediates the effect of age on memory impairment.
P3-341
HIPPOCAMPAL INTEGRITY IN SWEDISH WOMEN WITH BILATERAL SALPINGOOOPHORECTOMY PRIOR TO NATURAL MENOPAUSE
Annie Duchesne1, Suzanne Tyson Witt2, Maria Engstr€om2, Elisabeth Classon2, Preben Kjølhede2, Asa Rydmark Kersley2, Elvar Theodorsson2, Elisabeth Avall Lundqvist2, Nina Lykke2, Margrit Shildrick2, Cecilia Asberg2, April Au1, Gillian Einstein1, 1 University of Toronto, Toronto, ON, Canada; 2Linkoping University, Linkoping, Sweden. Contact e-mail: [email protected] Background: Oophorectomy prior to natural menopause places
women at increased risk of dementia and/or Alzheimer’s disease (AD). Recent findings from our Toronto group reveal a negative association between oophorectomy prior to natural menopause and verbal memory in middle-aged women. We have also found a positive association between estrogen levels and verbal recall. Taken
together, these findings support previous work suggesting that oophorectomy, leading to reduced levels of estrogens, is detrimental to verbal memory. Estrogen withdrawal has also been correlated with reduced hippocampal volume and reduced hippocampal resting functional connectivity (FC), both early AD biomarkers. Thus, we wondered whether hippocampal volume and resting functional connectivity would be reduced in women with oophorectomy prior to natural menopause. Methods: In order to determine this, we recruited healthy, Swedish women (30 and 55 years) with the breast cancer mutation gene (BRCA1/2) who had a bilateral salpingo-oophorectomy (BSO) prior to natural menopause. Most women were between 1-7 years post-BSO and at least 6 months post-cancer treatment or had not had cancer. Using magnetic resonance imaging (3T scanner, Phillips) we measured functional resting state over 10 minutes and volume with a T1 structural scan. We collected urine in order to determine estrogen and progesterone levels. Results: We hypothesize that women with BSO will have structural and functional hippocampal changes compared to age matched controls. We predict that women with BSO will have smaller hippocampal volumes and reduced hippocampal FC. We further predict that lower levels of estrogens will correlate with these brain changes. Neuroimaging and endocrine analyses are ongoing. Conclusions: AD affects women in greater numbers and one possibility is that oophorectomy prior to natural menopause contributes to these numbers. Determining whether or not these women show the earliest biomarkers for AD will increase our understanding of estrogen withdrawal’s effects on brain health as well as its importance for healthy brain aging. Importantly, results of this study will inform us on the early brain changes in a population at greater risk of AD.
P3-342
RELATIONSHIP OF PHYSICAL ACTIVITIES DURING YOUNG ADULTHOOD AND MIDLIFE WITH BRAIN AMYLOID DEPOSITION, GLUCOSE METABOLISM, AND CORTICAL THICKNESS IN LATE-LIFE
Bo Kyung Sohn1, Dahyun Yi2, Min Soo Byun3, Young Min Choe4, Jee Wook Kim5, Hyo Jung Choi2, Hyewon Baek6, Jun Ho Lee2, Hyun Jung Kim7, Shin Gyeom Kim8, Eun Hyun Seo9, Ji Young Han2, Jong Inn Woo10, Dong Young Lee2,3, 1SMG-SNU Boramae Medical Center, Seoul, Republic of South Korea; 2Seoul National University Hospital, Seoul, Republic of South Korea; 3Seoul National University College of Medicine, Seoul, Republic of South Korea; 4Ulsan University Hospital, Ulsan, Republic of South Korea; 5Hallym University Dongtan Sacred Hospital, Seoul, Republic of South Korea; 6Kyunggi Provincial Hospital for the Elderly, Yongin, Republic of South Korea; 7Changsan Convalescent Hospital, Changwon, Republic of South Korea; 8Soon Chun Hyang University Bucheon Hospital, Bucheon, Republic of South Korea; 9College of Health Science, Chosun University, Gwangju, Republic of South Korea; 10 Medical Research Center Seoul National University, Seoul, Republic of South Korea. Contact e-mail: [email protected] Background: Epidemiological studies suggested that lifetime phys-
ical activities (PA) are related with the reduced risk of Alzheimer’s disease (AD) dementia. However, very limited information is available for the association between PA during earlier lifetime and in vivo cerebral AD pathologies in late-life. This study aimed to investigate the relationship of PA in young adulthood and midlife with beta-amyloid (Ab) accumulation and neurodegeneration in cognitive normal (CN) elderly individuals. Methods: One-hundred sixty five CN elderly subjects aged 61 years or over who participated in the Korean Brain Aging Study for Early Diagnosis and