Prospective Randomized Trial to Assess Effects of Continuing Hormone Therapy on Cerebral Function in Postmenopausal Women at Risk for Dementia

<div><p></p><p>The objective of this study was to examine the effects of estrogen-based hormone therapy (HT) on regional cerebral metabolism in postmenopausal women (mean age = 58, SD = 5) at risk for development of dementia. The prospective clinical trial design included pre- and post-intervention neuroimaging of women randomized to continue (HT+) or discontinue (HT−) therapy following an average of 10 years of use. The primary outcome measure was change in brain metabolism during the subsequent two years, as assessed with fluorodeoxyglucose-18 positron emission tomography (FDG-PET). Longitudinal FDG-PET data were available for 45 study completers. Results showed that women randomized to continue HT experienced relative preservation of frontal and parietal cortical metabolism, compared with women randomized to discontinue HT. Women who discontinued 17-β estradiol (17βE)-based HT, as well as women who continued conjugated equine estrogen (CEE)-based HT, exhibited significant decline in metabolism of the precuneus/posterior cingulate cortical (PCC) area. Significant decline in PCC metabolism was additionally seen in women taking concurrent progestins (with either 17βE or CEE). Together, these findings suggest that among postmenopausal subjects at risk for developing dementia, regional cerebral cortical metabolism is relatively preserved for at least two years in women randomized to continue HT, compared with women randomized to discontinue HT. In addition, continuing unopposed 17βE therapy is associated specifically with preservation of metabolism in PCC, known to undergo the most significant decline in the earliest stages of Alzheimer's disease.</p><p>Trial Registration</p><p><a href="http://ClinicalTrials.gov" target="_blank">ClinicalTrials.gov</a><a href="http://clinicaltrials.gov/ct2/show/NCT00097058" target="_blank">NCT00097058</a></p></div

Bilateral medial frontal metabolism (first row) and left temporo-occipital metabolism (second row) were significantly preserved in HT+ women who were ApoE-ε4 negative, compared to HT− women who were ApoE-ε4 negative.

<p>Color voxels shown above have significance of p<0.001.</p

Study Sample Demographics and Clinical Characteristics (N = 45).

<p>Study Sample Demographics and Clinical Characteristics (N = 45).</p

Study Subject Flow.

<p>Study Subject Flow.</p

Alterations in the Salivary Proteome and <i>N</i>‑Glycome of Sjögren’s Syndrome Patients

We used isobaric mass tagging (iTRAQ) and lectin affinity capture mass spectrometry (MS)-based workflows for global analyses of parotid saliva (PS) and whole saliva (WS) samples obtained from patients diagnosed with primary Sjögren’s Syndrome (pSS) who were enrolled in the Sjögren’s International Collaborative Clinical Alliance (SICCA) as compared with two control groups. The iTRAQ analyses revealed up- and down-regulation of numerous proteins that could be involved in the disease process (e.g., histones) or attempts to mitigate the ensuing damage (e.g., bactericidal/permeability increasing fold containing family (BPIF) members). An immunoblot approach applied to independent sample sets confirmed the pSS associated up-regulation of β2-microglobulin (in PS) and down-regulation of carbonic anhydrase VI (in WS) and BPIFB2 (in PS). Beyond the proteome, we profiled the <i>N</i>-glycosites of pSS and control samples. They were enriched for glycopeptides using lectins <i>Aleuria aurantia</i> and wheat germ agglutinin, which recognize fucose and sialic acid/<i>N</i>-acetyl glucosamine, respectively. MS analyses showed that pSS is associated with increased <i>N</i>-glycosylation of numerous salivary glycoproteins in PS and WS. The observed alterations of the salivary proteome and <i>N</i>-glycome could be used as pSS biomarkers enabling easier and earlier detection of this syndrome while lending potential new insights into the disease process