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Poster Session III, December 6, 2017 Neuropsychopharmacology (2017) 42, S476–S652 © 2017 American College of Neuropsychopharmacology. All rights reserved 0893-133X/17 www.neuropsychopharmacology.org Poster Session III a high-resolution research tomograph (HRRT), and struc- Palm Springs, California, December 3–7, 2017 tural (T1) MRI using a 3-Tesla scanner. PET data analyses were carried out using the validated 2-tissue compartment Sponsorship Statement: Publication of this supplement is model to determine the total volume of distribution (VT) of sponsored by the ACNP. [18F]FEPPA. Individual contributor disclosures may be found within the Results: Results show significant inverse associations (con- abstracts. Part 1: All Financial Involvement with a pharma- trolling for rs6971 genotype) between neuroinflammation ceutical or biotechnology company, a company providing (VTs) and cortical thickness in the right medial prefrontal clinical assessment, scientific, or medical products or compa- cortex [r = -.562, p = .029] and the left dorsolateral nies doing business with or proposing to do business with prefrontal cortex [r = -.629, p = .012](p values are not ACNP over past 2 years (Calendar Years 2014–Present); Part 2: corrected for multiple comparisons). No significant associa- Income Sources & Equity of $10,000 per year or greater tions were found with surface area. (Calendar Years 2014 - Present): List those financial relation- Conclusions: These results, while preliminary, suggest links ships which are listed in part one and have a value greater than between the microglial activation/neuroinflammation and $10,000 per year, OR financial holdings that are listed in part cortical thickness in the dorsolateral prefrontal cortex and one and have a value of $10,000 or greater as of the date of medial prefrontal cortex in AD patients. disclosure; Part 3: Financial Involvement with a pharmaceu- Keywords: Positron Emission Tomography Imaging, Alzhei- tical or biotechnology company, a company providing clinical mer's Disease, Structural MRI assessment, scientific, or medical products or companies doing Disclosure: Nothing to Disclose. business with or proposing to do business with ACNP which constitutes more than 5% of personal income (Calendar Years 2014 - Present); Part 4: Grants from pharmaceutical or W2. Impact of BDNF and Sex on Maintaining Intact biotechnology company, a company providing clinical assess- Memory Function in Early Midlife ment, scientific, or medical products directly, or indirectly through a foundation, university, or any other organization Kyoko Konishi*, Emily Jacobs, Sara Cherkerzian, (Calendar Years 2014 - Present); Part 5: My primary employer Blair Scribner-Weiss, Dorene Rentz, Anne Remington, is a pharmaceutical/biotech/medical device company. Harlyn Aizley, Anne Klibanksi, Philip De Jager, Asterisks in the author lists indicate presenter of the abstract Jill Goldstein at the annual meeting. Harvard Medical School, Brigham & Women's Hospital, Boston, Massachusetts, United States Background: The population is rapidly aging, thus under- W1. Association Between Neuroinflammation and standing how to maintain intact memory function in midlife is Cortical Thickness in Alzheimer’sDisease:APET-MRI a major public health concern. The hippocampus (HIPP), a Study key region in the memory circuitry, is one of the few Sina Hafizi*, Anne Wheeler, Ivonne Suridjan, brain structures that continue to undergo neurogenesis with Nicolaas Verhoeff, Pablo M. Rusjan, Sylvain Houle, aging, albeit at a reduced rate. Sex steroid hormones and Romina Mizrahi growth factors, such as brain-derived neurotrophic factor (BDNF), play a significant neuroprotective role in memory Centre for Addiction and Mental Health, Toronto, circuitry aging through mechanisms of neurogenesis, cellular Canada survival, axonal growth, dendritic growth, and synaptic plasticity. We and others have shown in some women Background: Increased translocator protein 18kDa (TSPO) across the menopausal transition, there are decreased memory expression is a reliable marker of (micro)glial activation and performance and altered brain function and connectivity in neuroinflammation in-vivo, which was shown to be in- memory circuitry regions. We hypothesize that the abrupt creased in Alzheimer’s disease (AD). Moreover, structural depletion of sex steroid hormones may require a higher imaging studies on AD patients showed widespread production of growth hormones for maintaining intact abnormal brain structural changes, such as reduced cortical memory function in the face of reproductive aging. Here, we thickness and decreased cortical surface area, in several brain present new findings characterizing the impact of BDNF on regions, particularly in the prefrontal cortex (i.e. dorsolateral memory circuitry aging across the menopausal transition. prefrontal and medial prefrontal cortices). However, no Methods: Two hundred and twelve middle-aged adults study has assessed the link between neuroinflammation and (age range 45–55) recruited from the New England Family structural brain changes in AD. Study (NEFS) cohort underwent neuropsychological assess- Methods: Using a novel second-generation PET radiotracer ment and fMRI scanning. A multiplex immunoassay analysis for TSPO, [18F]FEPPA, we evaluated the association and genome-wide association study (GWAS) were con- between neuroinflammation and brain structural deficits in ducted to assess BDNF plasma levels and BDNF genotype, dorsolateral prefrontal and medial prefrontal cortices in AD. respectively. The sample consisted of 106 women (mean Sixteen patients with AD underwent [18F]FEPPA PET, using age = 49.82 ± 1.99) and 106 men (mean age = 50.09 ± 2.28). ACNP 56th Annual Meeting Abstracts S477 Following the STRAW-10 criteria, reproductive history and maintaining intact memory function across the menopausal serologic evaluation (FSH, LH, estradiol, progesterone) were transition, thus providing evidence for potential sex- used to determine women’s reproductive stage. Women were dependent avenues for attenuating risk of memory decline categorized as late reproductive (“pre-menopause”), meno- in early midlife. pausal transition (“peri-menopause”), or early post- Keywords: Aging, Memory, Hippocampus, Sex Differences, menopausal (“post-menopause”). Participants performed a Menopause verbal working memory task (N-Back) during fMRI scan- Disclosure: Nothing to Disclose. ning and data were analyzed in SPM8. Under normal testing conditions, usually overall deactivation of HIPP is observed. As such, an ROI analysis was conducted with an W3. Persistent Cancer-Related Cognitive Impairment anatomically defined mask of HIPP. Mean β weights from Following Cancer Chemotherapy: Comparison to Post the HIPP were extracted for each participant as a function of Menopausal Subjective Cognitive Decline 4 working memory load (2-back 0-back) and were used for Jennifer Vega, Julie Dumas, Kimberly Albert, subsequent analyses. Neuropsychological assessments of Paul Newhouse* verbal and associative memory were conducted with the 6- Trial Selective Reminding Test (SRT) and the Face-Name Vanderbilt University Medical Center, Nashville, Associative Memory Exam (FNAME). Tennessee, United States Results: The menopausal transition was associated with decreased memory performance with post-menopausal wo- Background: Cancer-related cognitive impairment (CRCI) is men performing worse than pre- and peri-menopausal commonly reported following the administration of cancer women. In the current study, this effect was attenuated in treatment. Current longitudinal studies, primarily in women post-menopausal women with high-BDNF plasma levels with breast cancer suggest that up 35%–60% exhibit (FNAME: F = 4.14, p = 0.008, η2 = 0.12; SRT Total recall: persistent cognitive complaints following completion of F = 1.78, p = 0.16, η2 = 0.06). Post-menopausal women with chemotherapy. Additionally, there is evidence that in non- high-BDNF plasma levels did not differ on FNAME and SRT cancer patients, subjective cognitive decline (SCD) may be from pre- (FNAME: p = 0.39; SRT Total recall: p = 0.42) and predictive of later cognitive dysfunction and we and others peri-menopausal women (FNAME: p = 0.80; SRT Total recall: have shown that SCD may begin in mid-life in women p = 0.53) and performed significantly better than men during or after the menopause transition. For example, (FNAME: p = 0.05). In contrast, post-menopausal women approximately 42% of postmenopausal women reported a with low-BDNF plasma levels performed significantly worse negative change in cognition in the Study of Women Across than pre- (FNAME: p = 0.02; SRT Total recall: p = 0.06) and the Nation. We have previously shown functional connec- peri-menopausal women (FNAME: p = 0.006; SRT Total tivity differences in women who endorse menopause- recall: p = 0.05) and performed similar to men (FNAME: associated subjective cognitive decline (maSCD), and that p = 0.47; SRT Total recall: p = 0.92) on the same tests cancer chemotherapy alters task-related brain activity even (FNAME: F = 4.96, p = 0.003, η2 = 0.14; SRT Total recall: after chemotherapy is completed. These findings suggest that F = 4.30, p = 0.007, η2 = 0.12). Plasma BDNF levels also cortical connectivity changes or compensation may be impacted functional changes in working memory circuitry responsible for the symptoms of maSCD and pCRCI. Given observed across reproductive aging. Across the menopausal that SCD may be a risk factor for late-life cognitive decline transition, regional deactivation of
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