title: Insulin resistance and medial prefrontal gyrus metabolism in women receiving hormone therapy.
abstract: Insulin resistance (IR) is a putative risk factor for cognitive decline and dementia, and has been shown to impede neuronal glucose metabolism in animal models. This post hoc study focused on metabolic changes in the medial prefrontal region, a brain region exhibiting decline years before documented cognitive changes, relative to high or low IR status in a cohort of postmenopausal women at risk for dementia who were randomized to continue or discontinue existing stable hormone therapy (HT) for 2 years. Subjects were dichotomized into high and low IR groups based on the homeostatic model assessment of insulin resistance, which was within clinically normal limits for the group as a whole at both baseline and 2-year follow-up. Results showed that high and low IR groups showed significant differences in metabolic decline of the medial prefrontal gyrus, regardless of HT randomization group. However, HT randomization was predictive of metabolic decline only in women with low HOMA (homeostatic assessment of insulin resistance). Performance in working memory was consistent with observed metabolic changes. These results suggest IR may be an independent moderator of regional metabolic changes, while protective metabolic effects of HT are most apparent in those at low-end range of IR. If replicated in future studies, these findings will help to better understand the interaction between putative risk and protective factors, and further delineate cohort postmenopausal women who may benefit from HT.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA. Electronic address: nrasgon@stanford.edu.
authors.forename: Natalie L
authors.initials: NL
authors.lastname: Rasgon
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Heather A
authors.initials: HA
authors.lastname: Kenna
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Tonita E
authors.initials: TE
authors.lastname: Wroolie
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Katherine E
authors.initials: KE
authors.lastname: Williams
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Bevin N
authors.initials: BN
authors.lastname: DeMuth
authors.affiliation: Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA, USA.
authors.forename: Daniel H S
authors.initials: DH
authors.lastname: Silverman
mesh_terms: D000368:Aged; D015914:Estrogen Replacement Therapy; D004967:Estrogens / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D006179:Gyrus Cinguli / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D008875:Middle Aged; D008954:Models, Biological; D009483:Neuropsychological Tests; D049268:Positron-Emission Tomography; D017698:Postmenopause; D017397:Prefrontal Cortex / Q000378:metabolism*; D011374:Progesterone / Q000009:adverse effects* / Q000627:therapeutic use; D012307:Risk Factors
chemical_list: D004967:Estrogens; D011374:Progesterone
keywords: Dementia; Hormone therapy; Insulin resistance; Medial prefrontal gyrus; Menopause