- Email: [email protected]
SLEEP QUALITY IN YOUNG AND MIDDLE AGE-PERIOD IS ASSOCIATED WITH CEREBRAL AMYLOID BURDEN IN COGNITIVELY NORMAL ELDERLY PEOPLE
Podium Presentations: Sunday, July 24, 2016 Background: Several investigations have provided clues into resilient brain aging. These investigations included reserve/lifestyle approaches, the study of older people with outstanding cognitive abilities or of those that show normal cognition in the setting of Alzheimer’s Disease (AD) pathology. The goal of the present study was to further our understanding of brain resilience by exploring the cognitive, lifestyle, psychoaffective and neuroimaging features of older adults showing normal cognition despite very high risk for AD: i) older age, ii) predisposing genetic backgrounds and iii) amyloid (Ab) positivity. Methods: Thirteen percent (n¼23) of the participants from the Berkeley Aging Cohort with available neuroimaging and genetic information met the criteria (i.e., >70 yrs, APOE+ and/or Family history of AD and Ab+) (age 75.763.9, 18 females, education 16.163.3). First, we assessed the demographic, lifestyle/reserve and psychoaffective characteristics of these high risk (HR) individuals as compared to participants >70 years, without these risk factors (low risk group, LR) (n¼ 63). Second, we evaluated baseline cognitive and metabolic characteristics (FDG-PET) as compared to a LR sex, age, education-matched sample (LRmatched) (n¼23). Finally, in a repeated measures ANOVA, we evaluated the group (HR vs LR-matched) by time (18.466.4 months) interaction on memory performance. Results: The HR group did not differ in demographic, lifestyle and psychoaffective variables from the LR group. However, the HR group showed significantly higher memory performance as compared to the matched-LR group (Fig1A). Voxel-wise FDG-PET analyses revealed increased metabolism in medial prefrontal and medial parietal regions in the HR group as compared to the LR-matched group (Fig 2). Finally, we observed a group*time interaction such that only the HR group showed decrease memory performance over time (Fig1 B). Conclusions: In cognitively
Fig 1. (A) Baseline differences between the high (blue) and low (green) risk groups in the different cognitive domains (adjusted by age, sex and education). Note that for speed processing and inhibition composites higher scores reflect poorer performances. (B) Plot of the estimated marginal means from the repeated measures ANOVA (adjusted by age, sex and education), showing a time*group interaction on memory performance (p¼0,04).The two groups were comparable in terms of time between visits (HR group: 18,4 6 6,6 months, LR group: 18.4 6 6,3 months). *p<0,05; ns: no significant; t: trend.
normal, high risk adults, greater memory ability and metabolism might counter the effects of multiple risk factors on cognition. They may have started with higher levels of memory and metabolism and/or may be showing functional compensation. Regardless of the exact mechanism, these data suggest that over time they become more susceptible and may begin to progress towards AD. O1-01-04
INCREASES IN PIB RETENTION ARE ASSOCIATED WITH INCREASED CEREBRAL GLUCOSE METABOLISM IN COGNITIVELY NORMAL ELDERLY: ROLE FOR COMPENSATORY HYPERMETABOLISM?
Brett Curtis, Beth E. Snitz, Dana L. Tudorascu, Julie Price, Chester Mathis, Howard J. Aizenstein, William E. Klunk, Ann D. Cohen, University of Pittsburgh, Pittsburgh, PA, USA. Contact e-mail: [email protected] Background: Inverse correlations between amyloid-beta (Ab)
measured by PiB-PET and cerebral metabolism using FDG-PET in Alzheimer’s disease (AD) suggests local Ab-induced metabolic insults. In mild cognitive impairment (MCI), we have previously observed no significant negative correlations between PiB and FDG, but frequent positive correlations, particularly in frontal brain regions, suggesting that in MCI, higher basal metabolism (i.e., higher brain reserve) could be increasing the threshold of Ab necessary for expressing cognitive impairment. In the current study we explored FDG metabolism in cognitively normal elderly subjects (NC) with and without increasing PiB retention over a 24-month period. Methods: PiB PET and FDG PET was performed in 50 NC (7665 years; MMSE: 2862; 68% female) at baseline and 24months. Tissue ratios were calculated for cortical regions-of-interest for both tracers, using cerebellum as reference (SUVR). Subjects were divided into two groups depending on whether PiB retention increased >20% over 24-months (PiB-increaser), or was stable (increased <10%; PiB-stable) and differences in FDG metabolism was examined on an ROI and voxel-wise basis using a 2-sample t-test. Results: At baseline, there were no significant differences in FDG or PiB SUVR between groups. However, the PiB-increaser group showed significantly higher FDG-SUVR values in anterior cingulate and frontal cortices at 24 months compared to PiB-stable subjects (p<0.01). This relationship was magnified among those without an ApoeE4 allele (p<0.001). Additionally, PiB-increasers also demonstrated a significant increase in FDG-SUVR in the anterior cingulate (p<0.05). A significant relationship was also observed between the degree of change in PiB SUVR from 0-24 months and FDG SUVR at 24 months only in frontal brain regions [anterior cingulate and frontal cortex (r¼0.46-0.51; p<0.01)]. Conclusions: NC subjects with increased PiB retention show an increase in FDG metabolism over a 24-month period in frontal cortical regions compared to subjects with stable PiB retention. These data suggest that a reactive hypermetabolism occurs in frontal regions of NC subjects as Ab-load increases in the brain. O1-01-05
Fig 2. Sagittal views of the voxel-wise analyses showing increased FDGPET uptake in the high risk as compared to the low risk group (HR>LR). No significant results were found using the opposite contrast (HR
P171
SLEEP QUALITY IN YOUNG AND MIDDLE AGE-PERIOD IS ASSOCIATED WITH CEREBRAL AMYLOID BURDEN IN COGNITIVELY NORMAL ELDERLY PEOPLE
Young Min Choe1, Min Soo Byun2, Dahyun Yi2, Hyo Jung Choi2, Hyewon Baek2, Jun Ho Lee2, Hyun Jung Kim2, Bo Kyung Sohn3, Jee Wook Kim4, Younghwa Lee2, Hyunwoong Ko2, Na Young Han2, Seung Hoon Lee2, Kang Ko2, Jong Inn Woo2, Dong Young Lee2, 1Ulsan
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Podium Presentations: Sunday, July 24, 2016
Table Correlation between sleep variables and Pittsburgh Compound B (PiB) retention
<20y sleep quality <20y sleep duration 20-39y sleep quality 20-39y sleep duration 40-59y sleep quality 40-59y sleep duration Total PSQI
Unadjusted
Mutivariable Adjusted*
Correlation Coefficient
P Value
Partial Correlation Coefficient
P Value
0.246 -0.050 0.175 -0.002 0.203 -0.058 0.010
0.006 0.582 0.055 0.984 0.025 0.526 0.912
0.224 -0.030 0.174 -0.013 0.198 -0.085 0.044
0.015 0.748 0.060 0.889 0.032 0.360 0.637
*Adjusted for age, gender, apolipoprotein E e4 status, and Hamilton Depression Rating Scale score. University Hospital, Ulsan, Republic of Korea; 2Seoul National University Hospital, Seoul, Republic of Korea; 3SMG-SNU Boramae Medical Center, Seoul, Republic of Korea; 4Hallym University Dongtan Sacred Hospital, Seoul, Republic of Korea. Contact e-mail: [email protected] Background: Very little is known for the association between lifetime sleep experience and cerebral beta-amyloid protein (Ab) deposition, which is the core pathological change related to Alzheimer’s disease process. This study aimed to investigate the relationship of hours of sleep and sleep quality in young and middle age-period with cerebral Ab burden in elderly individuals with normal cognition. Methods: One hundred and twenty-two cognitively normal old adults (age range: 60-87 years), who participated in the Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer’s Disease (KBASE), were included. All subjects underwent comprehensive clinical and neuropsychological assessment, 11C labelled Pittsburgh Compound B (PiB) positron emission tomography (PET). Through structured clinical interview for each participant, mean hours of sleep and sleep quality were assessed for the following age-periods: before 20 years, in their 20-30s, and 40-50s. Current sleep quality was also assessed by using the Pittsburgh Sleep Quality Index (PSQI). Global cerebral Ab deposition was defined as mean cortical PiB retention of the cortical regions including the frontal, lateral temporal, lateral parietal and precuneus/posterior cingulate cortices. Results: The poorer sleep quality in all the three younger age-periods was associated with higher mean cortical PiB retention even after controlling for age, gender, apolipoprotein E e4 status, and Hamilton Depression Rating Scale score. In contrast, mean hours of sleep in any young or middle age-period or current sleep quality measured by the PSQI were not related to mean cortical PiB retention. Conclusions: These findings suggest that poorer sleep quality, but not hours of sleep, in young and middle age-period may contribute to increased cerebral amyloid burden in old age. O1-01-06
DIFFERENTIAL INFLUENCE OF SEX HORMONES, GONADOTROPINS, AND SEX HORMONE BINDING GLOBULIN ON BRAIN AMYLOID BURDEN BETWEEN MALE AND FEMALE IN A COGNITIVELY NORMAL ELDERLY POPULATION
Jun Ho Lee1, Min Soo Byun1, Dahyun Yi2, Young Min Choe3, Hyo Jung Choi1,4, Hyewon Baek1, Bo Kyung Sohn5, Hyun Jung Kim1, Jee Wook Kim6, Younghwa Lee1, Jong Inn Woo2, Dong Young Lee1,4,
1 Seoul National University Hospital, Seoul, Republic of Korea; 2Medical Research Center Seoul National University, Seoul, Republic of Korea; 3 Ulsan University Hospital, Ulsan, Republic of Korea; 4Seoul National University College of Medicine, Seoul, South Korea; 5SMG-SNU Boramae Medical Center, Seoul, Republic of Korea; 6Hallym University Dongtan Sacred Hospital, Seoul, Republic of Korea. Contact e-mail: kukulolv@ naver.com
Background: Although previous studies reported that sex hor-
mones are associated with cognitive decline and increased risk for Alzheimer’s disease in elderly population, few studies investigated the association between sex hormones and brain beta amyloid protein (Ab) deposition. In this study, we investigated the association between sex hormones and cerebral Ab deposition in cognitively normal elderly population. Methods: Through the Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer’s Disease (KBASE), 117 cognitively normal elderly subjects (female 61, male 56) were included in this study. All the subjects underwent comprehensive clinical and neuropsychological assessment, 11C-labelled Pittsburgh Compound B (PiB) positron emission tomography (PET), and blood sampling. Global cerebral Ab deposition was defined as mean cortical PiB retention of the cortical regions including the frontal, lateral temporal, lateral parietal
Table 1 Pearson’s correlation between hormones. gona dotropins, sex hormone binding globulin (SHBG)1 and Pittsburgh compound B (PiB) retention.
LN cFE2 LN+ FTI LN SHBG LN LH LN FSH
Overall
Female
Male
0.012 -0.054 0.165 0.004 -0.043
-0.131 -0.329** -0.145 -0.049 -0.306**
-0.023 -0.260 0.351** 0.181 0.160
Values presented are the Pearson’s correlation coefficients between PiB retention and each measures of hormones and SHBG. Significance is marked at the 0.05* and 0.01** level (two- tailed). Variables darting from a normal distribution underwent LN transformation unless marked LN+, then LN(x+l). Abbreviations: cFE2. calculated free estradiol; FTI. free testosterone index; LH, luteinizing hormone; FSH, follicle stimulating hormone.
Table 2 The association between sex hormones, gona dotropins, sex hormone binding globulin and Pittsburgh compound B (PiB) retention in overall group, female and male subgroups using linear regression model. R2
Variables
b
t
P
Overall Female
0.099 0.209
Male
0.198
None LN FTI LN FSH LN SHBG ApoE ε4 positivity
-9.24 -0.13 0.187 0.152
-2.92 -2.73 2.75 2.23
0.005 0.008 0.008 0.030
Stepwise multiple linear regression analyses were carried out. Dependent variable was PiB retention and independent variables were age, ApoE ε4 positivity, LN cFE2, LN+ FTI, LN SHBG, LN LH, LN FSH, and gender as appropriate. Variables darting from a normal distribution underwent LN transformation unless marked LN+, then LN(x+l). Abbreviations: cFE2, calculated free estradiol; FTI, free testosterone index; LH, luteinizing hormone; FSH, follicle stimulating hormone.
Fig 1. (A) Baseline differences between the high (blue) and low (green) risk groups in the different cognitive domains (adjusted by age, sex and education). Note that for speed processing and inhibition composites higher scores reflect poorer performances. (B) Plot of the estimated marginal means from the repeated measures ANOVA (adjusted by age, sex and education), showing a time*group interaction on memory performance (p¼0,04).The two groups were comparable in terms of time between visits (HR group: 18,4 6 6,6 months, LR group: 18.4 6 6,3 months). *p<0,05; ns: no significant; t: trend.
normal, high risk adults, greater memory ability and metabolism might counter the effects of multiple risk factors on cognition. They may have started with higher levels of memory and metabolism and/or may be showing functional compensation. Regardless of the exact mechanism, these data suggest that over time they become more susceptible and may begin to progress towards AD. O1-01-04
INCREASES IN PIB RETENTION ARE ASSOCIATED WITH INCREASED CEREBRAL GLUCOSE METABOLISM IN COGNITIVELY NORMAL ELDERLY: ROLE FOR COMPENSATORY HYPERMETABOLISM?
Brett Curtis, Beth E. Snitz, Dana L. Tudorascu, Julie Price, Chester Mathis, Howard J. Aizenstein, William E. Klunk, Ann D. Cohen, University of Pittsburgh, Pittsburgh, PA, USA. Contact e-mail: [email protected] Background: Inverse correlations between amyloid-beta (Ab)
measured by PiB-PET and cerebral metabolism using FDG-PET in Alzheimer’s disease (AD) suggests local Ab-induced metabolic insults. In mild cognitive impairment (MCI), we have previously observed no significant negative correlations between PiB and FDG, but frequent positive correlations, particularly in frontal brain regions, suggesting that in MCI, higher basal metabolism (i.e., higher brain reserve) could be increasing the threshold of Ab necessary for expressing cognitive impairment. In the current study we explored FDG metabolism in cognitively normal elderly subjects (NC) with and without increasing PiB retention over a 24-month period. Methods: PiB PET and FDG PET was performed in 50 NC (7665 years; MMSE: 2862; 68% female) at baseline and 24months. Tissue ratios were calculated for cortical regions-of-interest for both tracers, using cerebellum as reference (SUVR). Subjects were divided into two groups depending on whether PiB retention increased >20% over 24-months (PiB-increaser), or was stable (increased <10%; PiB-stable) and differences in FDG metabolism was examined on an ROI and voxel-wise basis using a 2-sample t-test. Results: At baseline, there were no significant differences in FDG or PiB SUVR between groups. However, the PiB-increaser group showed significantly higher FDG-SUVR values in anterior cingulate and frontal cortices at 24 months compared to PiB-stable subjects (p<0.01). This relationship was magnified among those without an ApoeE4 allele (p<0.001). Additionally, PiB-increasers also demonstrated a significant increase in FDG-SUVR in the anterior cingulate (p<0.05). A significant relationship was also observed between the degree of change in PiB SUVR from 0-24 months and FDG SUVR at 24 months only in frontal brain regions [anterior cingulate and frontal cortex (r¼0.46-0.51; p<0.01)]. Conclusions: NC subjects with increased PiB retention show an increase in FDG metabolism over a 24-month period in frontal cortical regions compared to subjects with stable PiB retention. These data suggest that a reactive hypermetabolism occurs in frontal regions of NC subjects as Ab-load increases in the brain. O1-01-05
Fig 2. Sagittal views of the voxel-wise analyses showing increased FDGPET uptake in the high risk as compared to the low risk group (HR>LR). No significant results were found using the opposite contrast (HR
P171
SLEEP QUALITY IN YOUNG AND MIDDLE AGE-PERIOD IS ASSOCIATED WITH CEREBRAL AMYLOID BURDEN IN COGNITIVELY NORMAL ELDERLY PEOPLE
Young Min Choe1, Min Soo Byun2, Dahyun Yi2, Hyo Jung Choi2, Hyewon Baek2, Jun Ho Lee2, Hyun Jung Kim2, Bo Kyung Sohn3, Jee Wook Kim4, Younghwa Lee2, Hyunwoong Ko2, Na Young Han2, Seung Hoon Lee2, Kang Ko2, Jong Inn Woo2, Dong Young Lee2, 1Ulsan
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Podium Presentations: Sunday, July 24, 2016
Table Correlation between sleep variables and Pittsburgh Compound B (PiB) retention
<20y sleep quality <20y sleep duration 20-39y sleep quality 20-39y sleep duration 40-59y sleep quality 40-59y sleep duration Total PSQI
Unadjusted
Mutivariable Adjusted*
Correlation Coefficient
P Value
Partial Correlation Coefficient
P Value
0.246 -0.050 0.175 -0.002 0.203 -0.058 0.010
0.006 0.582 0.055 0.984 0.025 0.526 0.912
0.224 -0.030 0.174 -0.013 0.198 -0.085 0.044
0.015 0.748 0.060 0.889 0.032 0.360 0.637
*Adjusted for age, gender, apolipoprotein E e4 status, and Hamilton Depression Rating Scale score. University Hospital, Ulsan, Republic of Korea; 2Seoul National University Hospital, Seoul, Republic of Korea; 3SMG-SNU Boramae Medical Center, Seoul, Republic of Korea; 4Hallym University Dongtan Sacred Hospital, Seoul, Republic of Korea. Contact e-mail: [email protected] Background: Very little is known for the association between lifetime sleep experience and cerebral beta-amyloid protein (Ab) deposition, which is the core pathological change related to Alzheimer’s disease process. This study aimed to investigate the relationship of hours of sleep and sleep quality in young and middle age-period with cerebral Ab burden in elderly individuals with normal cognition. Methods: One hundred and twenty-two cognitively normal old adults (age range: 60-87 years), who participated in the Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer’s Disease (KBASE), were included. All subjects underwent comprehensive clinical and neuropsychological assessment, 11C labelled Pittsburgh Compound B (PiB) positron emission tomography (PET). Through structured clinical interview for each participant, mean hours of sleep and sleep quality were assessed for the following age-periods: before 20 years, in their 20-30s, and 40-50s. Current sleep quality was also assessed by using the Pittsburgh Sleep Quality Index (PSQI). Global cerebral Ab deposition was defined as mean cortical PiB retention of the cortical regions including the frontal, lateral temporal, lateral parietal and precuneus/posterior cingulate cortices. Results: The poorer sleep quality in all the three younger age-periods was associated with higher mean cortical PiB retention even after controlling for age, gender, apolipoprotein E e4 status, and Hamilton Depression Rating Scale score. In contrast, mean hours of sleep in any young or middle age-period or current sleep quality measured by the PSQI were not related to mean cortical PiB retention. Conclusions: These findings suggest that poorer sleep quality, but not hours of sleep, in young and middle age-period may contribute to increased cerebral amyloid burden in old age. O1-01-06
DIFFERENTIAL INFLUENCE OF SEX HORMONES, GONADOTROPINS, AND SEX HORMONE BINDING GLOBULIN ON BRAIN AMYLOID BURDEN BETWEEN MALE AND FEMALE IN A COGNITIVELY NORMAL ELDERLY POPULATION
Jun Ho Lee1, Min Soo Byun1, Dahyun Yi2, Young Min Choe3, Hyo Jung Choi1,4, Hyewon Baek1, Bo Kyung Sohn5, Hyun Jung Kim1, Jee Wook Kim6, Younghwa Lee1, Jong Inn Woo2, Dong Young Lee1,4,
1 Seoul National University Hospital, Seoul, Republic of Korea; 2Medical Research Center Seoul National University, Seoul, Republic of Korea; 3 Ulsan University Hospital, Ulsan, Republic of Korea; 4Seoul National University College of Medicine, Seoul, South Korea; 5SMG-SNU Boramae Medical Center, Seoul, Republic of Korea; 6Hallym University Dongtan Sacred Hospital, Seoul, Republic of Korea. Contact e-mail: kukulolv@ naver.com
Background: Although previous studies reported that sex hor-
mones are associated with cognitive decline and increased risk for Alzheimer’s disease in elderly population, few studies investigated the association between sex hormones and brain beta amyloid protein (Ab) deposition. In this study, we investigated the association between sex hormones and cerebral Ab deposition in cognitively normal elderly population. Methods: Through the Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer’s Disease (KBASE), 117 cognitively normal elderly subjects (female 61, male 56) were included in this study. All the subjects underwent comprehensive clinical and neuropsychological assessment, 11C-labelled Pittsburgh Compound B (PiB) positron emission tomography (PET), and blood sampling. Global cerebral Ab deposition was defined as mean cortical PiB retention of the cortical regions including the frontal, lateral temporal, lateral parietal
Table 1 Pearson’s correlation between hormones. gona dotropins, sex hormone binding globulin (SHBG)1 and Pittsburgh compound B (PiB) retention.
LN cFE2 LN+ FTI LN SHBG LN LH LN FSH
Overall
Female
Male
0.012 -0.054 0.165 0.004 -0.043
-0.131 -0.329** -0.145 -0.049 -0.306**
-0.023 -0.260 0.351** 0.181 0.160
Values presented are the Pearson’s correlation coefficients between PiB retention and each measures of hormones and SHBG. Significance is marked at the 0.05* and 0.01** level (two- tailed). Variables darting from a normal distribution underwent LN transformation unless marked LN+, then LN(x+l). Abbreviations: cFE2. calculated free estradiol; FTI. free testosterone index; LH, luteinizing hormone; FSH, follicle stimulating hormone.
Table 2 The association between sex hormones, gona dotropins, sex hormone binding globulin and Pittsburgh compound B (PiB) retention in overall group, female and male subgroups using linear regression model. R2
Variables
b
t
P
Overall Female
0.099 0.209
Male
0.198
None LN FTI LN FSH LN SHBG ApoE ε4 positivity
-9.24 -0.13 0.187 0.152
-2.92 -2.73 2.75 2.23
0.005 0.008 0.008 0.030
Stepwise multiple linear regression analyses were carried out. Dependent variable was PiB retention and independent variables were age, ApoE ε4 positivity, LN cFE2, LN+ FTI, LN SHBG, LN LH, LN FSH, and gender as appropriate. Variables darting from a normal distribution underwent LN transformation unless marked LN+, then LN(x+l). Abbreviations: cFE2, calculated free estradiol; FTI, free testosterone index; LH, luteinizing hormone; FSH, follicle stimulating hormone.