Objectives: Amyloid-beta (Aβ) and tau pathologies are commonly observed among clinically normal older individuals at postmortem and can now be detected with in vivo neuroimaging. The association and interaction of these proteinopathies with prospective cognitive decline in normal aging and preclinical Alzheimer's disease (AD) remains to be fully elucidated. Methods: One hundred thirty-seven older individuals (age = 76.3 AE 6.22 years) participating in the Harvard Aging Brain Study underwent Aβ ( 11 C-Pittsburgh compound B) and tau ( 18 F-flortaucipir) positron emission tomography (PET) with prospective neuropsychological assessments following PET imaging (mean number of cognitive visits = 2.8 AE 1.1). Tau and Aβ PET measures were assessed in regions of interest (ROIs) as well as vertex-wise map analyses. Cognitive change was evaluated with Memory and Executive Function composites. Results: Higher levels of Aβ and tau were both associated with greater memory decline, but not with change in executive function. Higher cortical Aβ was associated with higher tau levels in all ROIs, independent of age, and very elevated levels of tau were observed primarily in clinically normal with elevated Aβ. A significant interaction between tau and Aβ was observed in both ROI and map-level analyses, such that rapid prospective memory decline was observed in participants who had high levels of both pathologies. Interpretation: Our results are consistent with the supposition that both Aβ and tau are necessary for memory decline in the preclinical stages of AD. These findings may be relevant for disambiguating aging and early cognitive manifestations of AD, and to inform secondary prevention trials in preclinical AD.

R ecent meta-analyses have shown a possible increased risk of cancer associated with angiotensin-receptor blockers used alone or combined with angiotensin-convertingenzyme (ACE) inhibitors.1,2 Despite the strong internal validity of randomized controlled trials (RCTs) used in prior meta-analyses, it is difficult to interpret these results because of the short duration of follow-up for cancer detection.3 A previous retrospective cohort study with a mean follow-up of 6.6 years showed that the use of ACE inhibitors was associated with a significantly de creased risk of overall cancer, and cancer of the lung, breast and female reproductive organs and smoking-related cancers. 4 Despite the inconsistent results reported by previous observational studies regarding this issue, 4−35 we conducted a meta-analysis of cohort and casecontrol studies to assess the association between use of these medications and the risk of cancer. Methods Literature searchWe searched MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library up to January 2011 using common keywords related to ACE inhibitors, angiotensin-receptor blockers and cancer. The search terms were as follows: "angiotensin-converting enzyme inhibitor" or "angiotensin receptor blocker" or trade names of the medications AND "cancer" or "carcinoma" or "neoplasm" or "malignancy" or names of specific types of cancer. (For details about the search strategy, see Appendix 1, at www.cmaj.ca /lookup /suppl/doi:10.1503 /cmaj .101497 /-/DC1.) We also reviewed the bibliographies of relevant articles to identify additional publications. Studies were restricted to those involving humans. We performed a meta-analysis of observational studies to assess the association.

This study suggests a possible relationship between obesity at early adulthood and higher mortality among patients with ovarian cancer. Further studies are needed to elucidate the harmful effect of obesity on the survival of patients with ovarian cancer.