- Email: [email protected]
Brain white-matter hyperintensity volume is related to lower cognitive function in older community-dwelling individuals without cognitive impairment
P398
Poster Presentations: P2
(p¼0.03), such that hippocampal volume was associated with CDR progression only in low reserve subjects. Conclusions: Markers of amyloid and neurodegeneration may predict subsequent global functional impairment within CN subjects. Furthermore, the association between neurodegeneration and progression may be modified by both amyloid and cognitive reserve. Future analyses will examine relationships to objective measures of cognitive performance. P2-143
EXERCISE, TNFa AND VOLUME OF THE AGING BRAIN
Meredith Braskie1, Christina Boyle1, Priya Rajagopalan2, Boris Gutman2, Arthur Toga2, Cyrus Raji2, Lewis Kuller3, James Becker3, Oscar Lopez3, Paul Thompson2, 1University of California, Los Angeles, Los Angeles, California, United States; 2UCLA, Los Angeles, California, United States; 3 University of Pittsburgh, Pittsburgh, Pennsylvania, United States. Contact e-mail: [email protected] Background: Exercise, insulin-like growth factor 1 (IGF1), and inflammation moderate each other and relate to structural brain integrity. We hypothesized that in older adults, more exercise and higher serum IGF1 levels would correlate with greater brain volume while higher levels of the inflammatory marker tumor necrosis factor a (TNFa) would relate to smaller brain volumes. We further hypothesized that IGF1 and TNFa would partly mediate the exercise effect on brain volume. Methods: We examined 43 controls (79.3 6 4.8 years) and 39 Alzheimer’s disease (AD) patients (81.9 6 5.1 years) from the Cardiovascular Health Study. Subjects had reported exercise intensity at year 1 of the study, blood serum TNF a and IGF1 measures at year 5, and volumetric MRI scans at year 9. We automatically segmented skull-stripped images into brain and cerebrospinal fluid. We evaluated how brain as a percentage of intracranial volume (brain %) related to exercise, TNF a, and IGF1 individually, while controlling for age, sex, education, diagnosis, apolipoprotein E genotype, scan location, body mass index, and depression rating. We refined significant results by including the same variables in a voxelwise tensor based morphometry (TBM) analysis. The false discovery rate (FDR; q¼0.05) controlled for multiple voxelwise comparisons. Results: Baseline exercise intensity (overall p ¼ 3.95 x 10 -9; exercise partial p ¼ 0.03) and TNF a (overall p ¼ 4.99 x 10 -9; TNF a partial p ¼ 0.006) (but not IGF1) were significantly associated with brain % individually and together (overall p ¼ 4.68 x 10 -9; TNF a partial p ¼ 0.007; exercise partial p ¼ 0.018). Exercise intensity and TNF a were not significantly associated with each other (overall model p ¼ 0.19). Using TBM, TNF a, but not exercise, was significantly associated with brain structure in the left supramarginal gyrus (FDR critical p value ¼ 3.2 x10 -5). Conclusions: Exercise and TNF a may independently influence brain structure in seniors. The TNF a effect is strongest in the left supramarginal gyrus, a region implicated in cognitive reserve and in predicting conversion to AD. IGF-1 levels were not significantly correlated with brain %, suggesting that IGF1 brain effects, if they exist, may be more focused anatomically.
P2-144
AGE-RELATED FRONTAL LOBE COMPENSATION DURING NOVELTY DETECTION
Catherine Chong1, Jiong Shi2, Marwan Sabbagh3, Kewei Chen4, Richard Caselli5, Leslie Baxter2, 1Barrow Neurological Institutute, Phoenix, Arizona, United States; 2Barrow Neurological Institute, Phoenix, Arizona, United States; 3BSHRI, Sun City, Arizona, United States; 4Banner Alzheimer’s Institute, Phoenix, Arizona, United States; 5Mayo Clinic, Scottsdale, Arizona, United States. Contact e-mail: cavecreekcutter@ yahoo.com Background: Episodic memory declines with advancing age, but some adults compensate better than others. A number of functional MRI (fMRI) encoding studies have indicated an age-related ’over-recruitment’ of bilateral frontal regions, perhaps reflecting compensatory mechanisms for maintaining task performance as memory abilities decline. Many fMRI tasks employ complex paradigms to assess age-related encoding differences, which may confound performance-related changes with age-related differences. Methods: In order to minimize task demands, we designed a loweffort novelty face-encoding paradigm that enabled older and younger adults to perform with over 80% accuracy. Using the general linear model, we investigated regions of shared activation as well as regions that were differentially activated in older adults. Subsequently, we extracted contrast estimate means of selected regions-of-interest in order to correlate frontal activation patterns to memory abilities using the Rey-Auditory-Verbal Learning test. Results: Both young (n ¼ 23) and older (n ¼ 42) subjects activated temporal (hippocampal, fusiform, amygdala) and inferior right frontal regions. The older adults showed reduction in temporal activation but increased right middle frontal activation relative to younger adults. Testing frontal compensation models of memory in the elderly revealed that left middle frontal activation was greatest in those with weakest memory abilities (r ¼ .42, p<0.006) as measured by the Rey Auditory Verbal Learning Test. Conclusions: Our findings demonstrate that on a fMRI encodings task with limited task demands, older adults with lower memory abilitites showed more contralateral frontal activation than those with better memory resources. This supports the hypothesis that frontal recruitment can be a compensatory strategy for declining memory resources in cognitively healthy older adults.
Left frontal activation showed a strong negative correlation (r ¼ -.42, p < .0006) with long delay recall age-adjusted AVLT-z scores indicating that this frontal region was engaged when the subject’s memory performance was weaker.
P2-145
BRAIN WHITE-MATTER HYPERINTENSITY VOLUME IS RELATED TO LOWER COGNITIVE FUNCTION IN OLDER COMMUNITY-DWELLING INDIVIDUALS WITHOUT COGNITIVE IMPAIRMENT
Zoe Arvanitakis1, Debra Fleischman1, Konstantinos Arfanakis2, Sue Leurgans1, David Bennett3, 1Rush Alzheimer’s Disease Center,
Poster Presentations: P2 Chicago, Illinois, United States; 2Illinois Institute of Technology, Chicago, Illinois, United States; 3Rush University Medical Center, Chicago, Illinois, United States. Contact e-mail: [email protected] Background: White matter hyperintensities (WMH) on brain magnetic resonance imaging (MRI) are common in aging, yet their relation to cognition in individuals without overt cognitive impairment is unclear. The aim of this study was to examine the relation of total WMH volume to function in different cognitive systems in older community-dwelling individuals without dementia or mild cognitive impairment. Methods: We used data from women and men enrolled in an epidemiologic study of aging, the Memory and Aging Project. Cognitive data included composite measures of five different cognitive systems and global cognition, based on 19 individual tests. Brain MRI data were available in 285 subjects without dementia or mild cognitive impairment (mean age ¼81 years and education ¼15 years; 75% women). WMH were automatically segmented based on both T 2 weighted FLAIR and T 1 -weighted MPRAGE data. Total WMH volume was measured for each participant. Linear regression analyses, adjusted for demographic and other variables, were used to examine the relation of logarithmically-transformed total WMH volume, normalized by intracranial volume, to global cognition and to cognition in five different cognitive domains. Results: Most individuals had some WMH and WMH volume was associated with age (r s ¼0.41; p <0.001). In a linear regression model adjusted for age, sex, and education, larger WMH volumes were associated with lower levels of global cognitive function (estimate ¼ -0.170, SE ¼0.057; p ¼0.003). In a series of adjusted analyses of different cognitive systems, larger WMH volumes were associated with lower perceptual speed (estimate ¼ -0.470, SE ¼0.094; p <0.001) and semantic memory (estimate ¼ -0.153, SE ¼0.076; p ¼ 0.046), but not with episodic memory, working memory, or visuospatial abilities (all p >0.14). There was no evidence for effect modification by age, ApoEε4, or vascular disease. Conclusions: This study of older community-dwelling individuals without overt cognitive impairment suggests that total WMH volume is related to lower cognition, especially perceptual speed. Findings appear to be independent of age and vascular disease. Future work will need to examine mechanisms linking WMH to cognition. P2-146
EVALUATION OF COMMON CHANGES IN THE AGING BRAIN: COMPARING HIGH- AND LOW-FIELD MRI
Xiaowei Song1, Hui Guo2, Yunting Zhang3, Kenneth Rockwood1, Dalhousie University, Halifax, Nova Scotia, Canada; 2Tianjin Medical University, Tianjin, China; 3Tianjin Medical University, Tianjin, Massachusetts, China. Contact e-mail: [email protected] 1
Background: Multiple brain structural changes occur during aging, including atrophy, white matter lesions, and small vessel damage. These changes typically are more common and more severe in Alzheimer’s disease (AD). Recently, a Brain Atrophy and Lesion Index (BALI) has been established using high-field MRI (e.g., 3.0T) exploiting its higher signal to noise ratio. The BALI can be used to evaluate such brain structural changes in relation to their combined effect on cognition. Given how much existing data on AD and aging used conventional MRI (e.g., 1.5T), we examined the validity of using the BALI with low-field MRI data. Methods: Data were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Subjects who had MRI scans with T1 and T2-weighted images (T1WI and T2WI) at both 1.5T and 3.0T on the same day were retrieved (AD¼37, MCI¼45, HC¼45). Clinical assessments included the Mini-Mental State Examination (MMSE) and the Alzheimer’s disease Assessment Scale-cognitive subscale (ADAS-cog), completed within 14 days of neuroimaging. All images were evaluated applying the same BALI rating schema, to assess lesions in the deep white matter, periventricular, basal ganglia and the infratentorial regions, deficits in the cortical gray matter, the extent of dilated small vessels, and global atrophy. Maximum possible BALI¼25; higher scores indicate greater damage. Results: The inter-rater agreement rate was consistently high, ranging from 0.96 to 0.98. Under each field-strength and image-type condition, the BALI scores differed significantly between diagnosis (p<0.05): people in the AD group had the greatest BALI on average
P399
(12.763.0), whereas those in the healthy control group had the lowest (10.562.6). Under each condition, the BALI score was significantly correlated with age (r>0.35, p<0.001), MMSE (r>0.40, p<0.001), and ADAScog (r>0.36, p<0.001). The BALI score at 3.0T was slightly greater than that at 1.5T (F>3.90, p<0.06), so as with T2WI comparing to T1WI (F>3.99, p<0.05) without interaction (F<0.06, p>0.80). The BALI scores at 1.5T and 3.0T were significantly correlated, for both T1WI (r¼0.94, p<0.001) and T2WI (r>0.95, p<0.001). Conclusions: T1WI and T2WI based BALI scores at 1.5T can be used to capture global brain structural changes and their relations to cognition. P2-147
DECREASED GRAY MATTER VOLUME IN POSTMENOPAUSAL WOMEN WHO REPORT COGNITIVE COMPLAINTS
Lilia Zurkovsky1, Julie Dumas2, Christine Valiquette1, Brenna McDonald3, Andrew Saykin4, Warren Taylor1, Magdalena Naylor2, Paul Newhouse1, 1 Vanderbilt University Medical Center, Nashville, Tennessee, United States; 2 University of Vermont, Burlington, Vermont, United States; 3Indiana University School of Medicine, Indianapolis, Indiana, United States; 4 Indiana University School of Medicine, Indianapolis, Indiana, United States. Contact e-mail: [email protected] Background: In middle-age, subjective complaints about memory without objective declines in cognitive performance are associated with smaller hippocampal volume and lower gray matter density in the medial temporal lobe. As women are at greater risk for late-life dementia, such cognitive complaints may represent a risk marker. We found previously that cognitive complainers show increased activation during attention and working memory tasks in the medial temporal lobe and dorsolateral prefrontal cortex, respectively (Dumas et al., Neurobiol Aging, 34:1145-1147, 2013). For this project, we sought to better understand the relevance of cognitive complaints following menopause on regional brain volume. Methods: This study examined 40 healthy, post-menopausal women aged 50-60 as part of a larger, treatment study examining 17b-estradiol effects on cholinergic-mediated cognitive function. Participants were categorized as complainers or non-complainers based on endorsing at least 20% of items across 5 cognitive symptom questionnaires, but were shown to have equivalent baseline cognitive performance. T1-weighted anatomical images were collected using magnetic resonance imaging. Analyses of baseline pre-treatment scans were performed with FreeSurfer software. Results: Cognitive complainers showed lower overall total gray matter volume (t¼4.3, p < 0.05), as well as larger lateral ventricle volume in the right hemisphere (t¼4.4, p < 0.05). Regional differences, showed that complainers had smaller left hemisphere superior frontal (t¼4.8, p<0.04) and superior temporal (t¼6.8, p¼0.01) volumes but larger right hemisphere medial orbital frontal (t¼7.5, p<0.01) volume. Volume of the right hemisphere temporal pole was also larger in complainers (t¼9.9, p<0.01) but showed reduced thickness (t¼6.9, p¼0.01). Conclusions: Studies are ongoing to examine whether estrogen affects brain volume and cortical activity differentially in complainer versus non-complainer women. These data suggest that cognitive complaints may indicate changes in brain structural integrity and may be a potential marker for the risk of late-life cognitive dysfunction. P2-148
LONGITUDINAL HIPPOCAMPAL ATROPHY IS ASSOCIATED WITH HIPPOCAMPUS FUNCTIONAL CONNECTIVITY CHANGES IN COGNITIVELY NORMAL ELDERS
Jing He1, Baljeet Singh1, Evan Fletcher1, Oliver Martinez1, Bruce Reed2, Dan Mungas3, Charles DeCarli4, Owen Carmichael5, 1UC Davis, Davis, California, United States; 2UC Davis, Martinez, California, United States; 3 UC Davis, Sacramento, California, United States; 4University of California at Davis, Sacramento, California, United States; 5University of California, Davis, Davis, California, United States. Contact e-mail: jing. [email protected] Background: Several cross-sectional studies have reported that functional connectivity (FC) disruptions and tissue atrophy occur at similar location within large-scale brain networks in aging and neurodegenerative disease.
Poster Presentations: P2
(p¼0.03), such that hippocampal volume was associated with CDR progression only in low reserve subjects. Conclusions: Markers of amyloid and neurodegeneration may predict subsequent global functional impairment within CN subjects. Furthermore, the association between neurodegeneration and progression may be modified by both amyloid and cognitive reserve. Future analyses will examine relationships to objective measures of cognitive performance. P2-143
EXERCISE, TNFa AND VOLUME OF THE AGING BRAIN
Meredith Braskie1, Christina Boyle1, Priya Rajagopalan2, Boris Gutman2, Arthur Toga2, Cyrus Raji2, Lewis Kuller3, James Becker3, Oscar Lopez3, Paul Thompson2, 1University of California, Los Angeles, Los Angeles, California, United States; 2UCLA, Los Angeles, California, United States; 3 University of Pittsburgh, Pittsburgh, Pennsylvania, United States. Contact e-mail: [email protected] Background: Exercise, insulin-like growth factor 1 (IGF1), and inflammation moderate each other and relate to structural brain integrity. We hypothesized that in older adults, more exercise and higher serum IGF1 levels would correlate with greater brain volume while higher levels of the inflammatory marker tumor necrosis factor a (TNFa) would relate to smaller brain volumes. We further hypothesized that IGF1 and TNFa would partly mediate the exercise effect on brain volume. Methods: We examined 43 controls (79.3 6 4.8 years) and 39 Alzheimer’s disease (AD) patients (81.9 6 5.1 years) from the Cardiovascular Health Study. Subjects had reported exercise intensity at year 1 of the study, blood serum TNF a and IGF1 measures at year 5, and volumetric MRI scans at year 9. We automatically segmented skull-stripped images into brain and cerebrospinal fluid. We evaluated how brain as a percentage of intracranial volume (brain %) related to exercise, TNF a, and IGF1 individually, while controlling for age, sex, education, diagnosis, apolipoprotein E genotype, scan location, body mass index, and depression rating. We refined significant results by including the same variables in a voxelwise tensor based morphometry (TBM) analysis. The false discovery rate (FDR; q¼0.05) controlled for multiple voxelwise comparisons. Results: Baseline exercise intensity (overall p ¼ 3.95 x 10 -9; exercise partial p ¼ 0.03) and TNF a (overall p ¼ 4.99 x 10 -9; TNF a partial p ¼ 0.006) (but not IGF1) were significantly associated with brain % individually and together (overall p ¼ 4.68 x 10 -9; TNF a partial p ¼ 0.007; exercise partial p ¼ 0.018). Exercise intensity and TNF a were not significantly associated with each other (overall model p ¼ 0.19). Using TBM, TNF a, but not exercise, was significantly associated with brain structure in the left supramarginal gyrus (FDR critical p value ¼ 3.2 x10 -5). Conclusions: Exercise and TNF a may independently influence brain structure in seniors. The TNF a effect is strongest in the left supramarginal gyrus, a region implicated in cognitive reserve and in predicting conversion to AD. IGF-1 levels were not significantly correlated with brain %, suggesting that IGF1 brain effects, if they exist, may be more focused anatomically.
P2-144
AGE-RELATED FRONTAL LOBE COMPENSATION DURING NOVELTY DETECTION
Catherine Chong1, Jiong Shi2, Marwan Sabbagh3, Kewei Chen4, Richard Caselli5, Leslie Baxter2, 1Barrow Neurological Institutute, Phoenix, Arizona, United States; 2Barrow Neurological Institute, Phoenix, Arizona, United States; 3BSHRI, Sun City, Arizona, United States; 4Banner Alzheimer’s Institute, Phoenix, Arizona, United States; 5Mayo Clinic, Scottsdale, Arizona, United States. Contact e-mail: cavecreekcutter@ yahoo.com Background: Episodic memory declines with advancing age, but some adults compensate better than others. A number of functional MRI (fMRI) encoding studies have indicated an age-related ’over-recruitment’ of bilateral frontal regions, perhaps reflecting compensatory mechanisms for maintaining task performance as memory abilities decline. Many fMRI tasks employ complex paradigms to assess age-related encoding differences, which may confound performance-related changes with age-related differences. Methods: In order to minimize task demands, we designed a loweffort novelty face-encoding paradigm that enabled older and younger adults to perform with over 80% accuracy. Using the general linear model, we investigated regions of shared activation as well as regions that were differentially activated in older adults. Subsequently, we extracted contrast estimate means of selected regions-of-interest in order to correlate frontal activation patterns to memory abilities using the Rey-Auditory-Verbal Learning test. Results: Both young (n ¼ 23) and older (n ¼ 42) subjects activated temporal (hippocampal, fusiform, amygdala) and inferior right frontal regions. The older adults showed reduction in temporal activation but increased right middle frontal activation relative to younger adults. Testing frontal compensation models of memory in the elderly revealed that left middle frontal activation was greatest in those with weakest memory abilities (r ¼ .42, p<0.006) as measured by the Rey Auditory Verbal Learning Test. Conclusions: Our findings demonstrate that on a fMRI encodings task with limited task demands, older adults with lower memory abilitites showed more contralateral frontal activation than those with better memory resources. This supports the hypothesis that frontal recruitment can be a compensatory strategy for declining memory resources in cognitively healthy older adults.
Left frontal activation showed a strong negative correlation (r ¼ -.42, p < .0006) with long delay recall age-adjusted AVLT-z scores indicating that this frontal region was engaged when the subject’s memory performance was weaker.
P2-145
BRAIN WHITE-MATTER HYPERINTENSITY VOLUME IS RELATED TO LOWER COGNITIVE FUNCTION IN OLDER COMMUNITY-DWELLING INDIVIDUALS WITHOUT COGNITIVE IMPAIRMENT
Zoe Arvanitakis1, Debra Fleischman1, Konstantinos Arfanakis2, Sue Leurgans1, David Bennett3, 1Rush Alzheimer’s Disease Center,
Poster Presentations: P2 Chicago, Illinois, United States; 2Illinois Institute of Technology, Chicago, Illinois, United States; 3Rush University Medical Center, Chicago, Illinois, United States. Contact e-mail: [email protected] Background: White matter hyperintensities (WMH) on brain magnetic resonance imaging (MRI) are common in aging, yet their relation to cognition in individuals without overt cognitive impairment is unclear. The aim of this study was to examine the relation of total WMH volume to function in different cognitive systems in older community-dwelling individuals without dementia or mild cognitive impairment. Methods: We used data from women and men enrolled in an epidemiologic study of aging, the Memory and Aging Project. Cognitive data included composite measures of five different cognitive systems and global cognition, based on 19 individual tests. Brain MRI data were available in 285 subjects without dementia or mild cognitive impairment (mean age ¼81 years and education ¼15 years; 75% women). WMH were automatically segmented based on both T 2 weighted FLAIR and T 1 -weighted MPRAGE data. Total WMH volume was measured for each participant. Linear regression analyses, adjusted for demographic and other variables, were used to examine the relation of logarithmically-transformed total WMH volume, normalized by intracranial volume, to global cognition and to cognition in five different cognitive domains. Results: Most individuals had some WMH and WMH volume was associated with age (r s ¼0.41; p <0.001). In a linear regression model adjusted for age, sex, and education, larger WMH volumes were associated with lower levels of global cognitive function (estimate ¼ -0.170, SE ¼0.057; p ¼0.003). In a series of adjusted analyses of different cognitive systems, larger WMH volumes were associated with lower perceptual speed (estimate ¼ -0.470, SE ¼0.094; p <0.001) and semantic memory (estimate ¼ -0.153, SE ¼0.076; p ¼ 0.046), but not with episodic memory, working memory, or visuospatial abilities (all p >0.14). There was no evidence for effect modification by age, ApoEε4, or vascular disease. Conclusions: This study of older community-dwelling individuals without overt cognitive impairment suggests that total WMH volume is related to lower cognition, especially perceptual speed. Findings appear to be independent of age and vascular disease. Future work will need to examine mechanisms linking WMH to cognition. P2-146
EVALUATION OF COMMON CHANGES IN THE AGING BRAIN: COMPARING HIGH- AND LOW-FIELD MRI
Xiaowei Song1, Hui Guo2, Yunting Zhang3, Kenneth Rockwood1, Dalhousie University, Halifax, Nova Scotia, Canada; 2Tianjin Medical University, Tianjin, China; 3Tianjin Medical University, Tianjin, Massachusetts, China. Contact e-mail: [email protected] 1
Background: Multiple brain structural changes occur during aging, including atrophy, white matter lesions, and small vessel damage. These changes typically are more common and more severe in Alzheimer’s disease (AD). Recently, a Brain Atrophy and Lesion Index (BALI) has been established using high-field MRI (e.g., 3.0T) exploiting its higher signal to noise ratio. The BALI can be used to evaluate such brain structural changes in relation to their combined effect on cognition. Given how much existing data on AD and aging used conventional MRI (e.g., 1.5T), we examined the validity of using the BALI with low-field MRI data. Methods: Data were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Subjects who had MRI scans with T1 and T2-weighted images (T1WI and T2WI) at both 1.5T and 3.0T on the same day were retrieved (AD¼37, MCI¼45, HC¼45). Clinical assessments included the Mini-Mental State Examination (MMSE) and the Alzheimer’s disease Assessment Scale-cognitive subscale (ADAS-cog), completed within 14 days of neuroimaging. All images were evaluated applying the same BALI rating schema, to assess lesions in the deep white matter, periventricular, basal ganglia and the infratentorial regions, deficits in the cortical gray matter, the extent of dilated small vessels, and global atrophy. Maximum possible BALI¼25; higher scores indicate greater damage. Results: The inter-rater agreement rate was consistently high, ranging from 0.96 to 0.98. Under each field-strength and image-type condition, the BALI scores differed significantly between diagnosis (p<0.05): people in the AD group had the greatest BALI on average
P399
(12.763.0), whereas those in the healthy control group had the lowest (10.562.6). Under each condition, the BALI score was significantly correlated with age (r>0.35, p<0.001), MMSE (r>0.40, p<0.001), and ADAScog (r>0.36, p<0.001). The BALI score at 3.0T was slightly greater than that at 1.5T (F>3.90, p<0.06), so as with T2WI comparing to T1WI (F>3.99, p<0.05) without interaction (F<0.06, p>0.80). The BALI scores at 1.5T and 3.0T were significantly correlated, for both T1WI (r¼0.94, p<0.001) and T2WI (r>0.95, p<0.001). Conclusions: T1WI and T2WI based BALI scores at 1.5T can be used to capture global brain structural changes and their relations to cognition. P2-147
DECREASED GRAY MATTER VOLUME IN POSTMENOPAUSAL WOMEN WHO REPORT COGNITIVE COMPLAINTS
Lilia Zurkovsky1, Julie Dumas2, Christine Valiquette1, Brenna McDonald3, Andrew Saykin4, Warren Taylor1, Magdalena Naylor2, Paul Newhouse1, 1 Vanderbilt University Medical Center, Nashville, Tennessee, United States; 2 University of Vermont, Burlington, Vermont, United States; 3Indiana University School of Medicine, Indianapolis, Indiana, United States; 4 Indiana University School of Medicine, Indianapolis, Indiana, United States. Contact e-mail: [email protected] Background: In middle-age, subjective complaints about memory without objective declines in cognitive performance are associated with smaller hippocampal volume and lower gray matter density in the medial temporal lobe. As women are at greater risk for late-life dementia, such cognitive complaints may represent a risk marker. We found previously that cognitive complainers show increased activation during attention and working memory tasks in the medial temporal lobe and dorsolateral prefrontal cortex, respectively (Dumas et al., Neurobiol Aging, 34:1145-1147, 2013). For this project, we sought to better understand the relevance of cognitive complaints following menopause on regional brain volume. Methods: This study examined 40 healthy, post-menopausal women aged 50-60 as part of a larger, treatment study examining 17b-estradiol effects on cholinergic-mediated cognitive function. Participants were categorized as complainers or non-complainers based on endorsing at least 20% of items across 5 cognitive symptom questionnaires, but were shown to have equivalent baseline cognitive performance. T1-weighted anatomical images were collected using magnetic resonance imaging. Analyses of baseline pre-treatment scans were performed with FreeSurfer software. Results: Cognitive complainers showed lower overall total gray matter volume (t¼4.3, p < 0.05), as well as larger lateral ventricle volume in the right hemisphere (t¼4.4, p < 0.05). Regional differences, showed that complainers had smaller left hemisphere superior frontal (t¼4.8, p<0.04) and superior temporal (t¼6.8, p¼0.01) volumes but larger right hemisphere medial orbital frontal (t¼7.5, p<0.01) volume. Volume of the right hemisphere temporal pole was also larger in complainers (t¼9.9, p<0.01) but showed reduced thickness (t¼6.9, p¼0.01). Conclusions: Studies are ongoing to examine whether estrogen affects brain volume and cortical activity differentially in complainer versus non-complainer women. These data suggest that cognitive complaints may indicate changes in brain structural integrity and may be a potential marker for the risk of late-life cognitive dysfunction. P2-148
LONGITUDINAL HIPPOCAMPAL ATROPHY IS ASSOCIATED WITH HIPPOCAMPUS FUNCTIONAL CONNECTIVITY CHANGES IN COGNITIVELY NORMAL ELDERS
Jing He1, Baljeet Singh1, Evan Fletcher1, Oliver Martinez1, Bruce Reed2, Dan Mungas3, Charles DeCarli4, Owen Carmichael5, 1UC Davis, Davis, California, United States; 2UC Davis, Martinez, California, United States; 3 UC Davis, Sacramento, California, United States; 4University of California at Davis, Sacramento, California, United States; 5University of California, Davis, Davis, California, United States. Contact e-mail: jing. [email protected] Background: Several cross-sectional studies have reported that functional connectivity (FC) disruptions and tissue atrophy occur at similar location within large-scale brain networks in aging and neurodegenerative disease.