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Background: With no effective treatments for cognitive decline or dementia, improving the evidence base for modifiable risk factors is a research priority. This study investigated associations between risk factors and late-life cognitive decline on a global scale, including comparisons between ethno-regional groups., Methods and Findings: We harmonized longitudinal data from 20 population-based cohorts from 15 countries over 5 continents, including 48,522 individuals (58.4% women) aged 54-105 (mean = 72.7) years and without dementia at baseline. Studies had 2-15 years of follow-up. The risk factors investigated were age, sex, education, alcohol consumption, anxiety, apolipoprotein E ε4 allele (APOE*4) status, atrial fibrillation, blood pressure and pulse pressure, body mass index, cardiovascular disease, depression, diabetes, self-rated health, high cholesterol, hypertension, peripheral vascular disease, physical activity, smoking, and history of stroke. Associations with risk factors were determined for a global cognitive composite outcome (memory, language, processing speed, and executive functioning tests) and Mini-Mental State Examination score. Individual participant data meta-analyses of multivariable linear mixed model results pooled across cohorts revealed that for at least 1 cognitive outcome, age (B = -0.1, SE = 0.01), APOE*4 carriage (B = -0.31, SE = 0.11), depression (B = -0.11, SE = 0.06), diabetes (B = -0.23, SE = 0.10), current smoking (B = -0.20, SE = 0.08), and history of stroke (B = -0.22, SE = 0.09) were independently associated with poorer cognitive performance (p < 0.05 for all), and higher levels of education (B = 0.12, SE = 0.02) and vigorous physical activity (B = 0.17, SE = 0.06) were associated with better performance (p < 0.01 for both). Age (B = -0.07, SE = 0.01), APOE*4 carriage (B = -0.41, SE = 0.18), and diabetes (B = -0.18, SE = 0.10) were independently associated with faster cognitive decline (p < 0.05 for all). Different effects between Asian people and white people included stronger associations for Asian people between ever smoking and poorer cognition (group by risk factor interaction: B = -0.24, SE = 0.12), and between diabetes and cognitive decline (B = -0.66, SE = 0.27; p < 0.05 for both). Limitations of our study include a loss or distortion of risk factor data with harmonization, and not investigating factors at midlife., Conclusions: These results suggest that education, smoking, physical activity, diabetes, and stroke are all modifiable factors associated with cognitive decline. If these factors are determined to be causal, controlling them could minimize worldwide levels of cognitive decline. However, any global prevention strategy may need to consider ethno-regional differences., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: AEA is a consultant for Kinsa Inc. and has received an unrestricted gift from Gojo Inc. CB is a member of the Editorial Board of PLOS Medicine. HB is on the Advisory Board of Nutricia Australia. MG was on Biogen Inc’s “Patient Journey Advisory Group” in 2016 and 2017. NS reports personal fees from Merck Consumer Health and the NIH outside the submitted work. RBL is the Edwin S. Lowe Professor of Neurology at the Albert Einstein College of Medicine in New York. He receives research support from the NIH: 2PO1 AG003949 (mPI), 5U10 NS077308 (PI), RO1 NS082432 (Investigator), 1RF1 AG057531 (Site PI), RF1 AG054548 (Investigator), 1RO1 AG048642 (Investigator), R56 AG057548 (Investigator), K23 NS09610 (Mentor), K23AG049466 (Mentor), 1K01AG054700 (Mentor). He also receives support from the Migraine Research Foundation and the National Headache Foundation. He serves on the editorial board of Neurology, senior advisor to Headache, and associate editor to Cephalalgia. He has reviewed for the NIA and NINDS, holds stock options in eNeura Therapeutics and Biohaven Holdings; serves as consultant, advisory board member, or has received honoraria from: American Academy of Neurology, Alder, Allergan, American Headache Society, Amgen, Autonomic Technologies, Avanir, Biohaven, Biovision, Boston Scientific, Dr. Reddy’s, Electrocore, Eli Lilly, eNeura Therapeutics, GlaxoSmithKline, Merck, Pernix, Pfizer, Supernus, Teva, Trigemina, Vector, Vedanta. He receives royalties from Wolff’s Headache 7th and 8th Edition, Oxford Press University, 2009, Wiley and Informa. PSS received grant funding from the NIH/NIA (USA) and the NHMRC (Australia), as well as philanthropic funding through The Dementia Momentum. He is on the Australian Advisory Board of Biogen Pharmaceuticals. All other authors have declared that no competing interests exist.

Introduction: The prevalence of cognitive impairment with no dementia (CIND) varies between 5.1% and 35.9%, increasing between 65 and 85 years. The CIND increases the risk of dementia. Factors such as education, occupation, and social activities are associated with the risk of cognitive impairment. The main objective of this study was to analyse the association between the main occupation developed throughout life and CIND in a general population sample of over 55 years., Methods: In wave I of the ZARADEMP Project, a sample (n=4803) of people over 55 years was interviewed. CIND measurement was obtained through the Mini Mental State Examination. Occupational activity data were recoded into white collar, blue collar, homemakers, and farmers. The association between the occupation variables and CIND was estimated using the odds ratio, and 95% confidence intervals using logistic regression equations., Results: The prevalence of CIND in the sample was 28.2%. As regards white collar workers, the CIND diagnosis odds was 53% higher for blue collar workers, 77% higher for women who were homemakers and almost twice for farmers, after controlling for socio-demographic, behavioural and clinical variables. All results were statistically significant., Conclusions: CIND frequency is influenced by the previous occupation of the subjects. An occupation with higher intellectual requirements can help keep cognitive functions intact for longer., (Copyright © 2017 SEGG. Publicado por Elsevier España, S.L.U. All rights reserved.)

Objectives: To test the hypothesis that differences by gender will be observed in the association of hip fracture risk with stages of cognitive impairment; and to explore the association between Petersen's "mild cognitive impairment" (MCI) and DSM-5 "mild neurocognitive disorder" (MND)., Study Design: A community sample of 4803 individuals aged 55+ years was assessed in a two-phase case-finding enquiry in Zaragoza, Spain, and was followed up for 16 years. Medical and psychiatric history was collected with standardized instruments, including the Mini-Mental Status Examination (MMSE), Geriatric Mental State (GMS), History and Aetiology Schedule, and a Risk Factors Questionnaire. The statistical analysis included calculations of Hazard Ratios (HR) in multivariate Cox proportional hazards regression models., Main Outcome Measures: Identified cases of hip fracture, validated by blind researchers., Results: In men, hip fracture risk was increased at the "mild" (HR=4.99 (1.39-17.91)) and at the "severe" (HR=9.31 (1.35-64.06)) stages of cognitive impairment, indicated by MMSE performance. In contrast, in women no association could be documented at the "mild stage" (power=89%), and the association disappeared altogether at the "severe stage" in the final multivariate statistical model (power 100%). No association observed between hip fracture and mild cognitive impairment in both men (power=28% for P-MCI) and women (power=44% and 19% for Petersen's MCI and DSM-5 MND, respectively)., Conclusions: Increased hip fracture risk was associated with "mild" stages of cognitive impairment in men, but not in women. To explore the potential association with the construct MCI or MND, studies with greater statistical power would be required., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Retinal nerve fiber layer thickness (RNFL) measured by means of Optical Coherence Tomography (OCT) has been used as a marker not only of ophthalmologic diseases but also of neurodegenerative diseases such as Alzheimer's disease (AD) and mild cognitive impairment (MCI). The purpose of this work was to demonstrate that patients with amnestic MCI show an intermediate RNFL thickness between normality and AD, and a macular volume and thickness as well. In a cross-sectional study we consecutively recruited 18 patients with AD, 21 with MCI, and 41 healthy controls. OCT was performed in all of them to measure circumpapillary RNFL thickness in µm, as well as macular volume and thickness. In the analysis of variance we saw that RNFL was thinner in MCI patients compared with controls, and it was also thinner in AD patients compared with MCI patients and controls. With regard to the macular measurements in mm(3), MCI patients had the greatest macular volume in comparison with AD patients and controls. In turn the controls had greater macular volume than AD patients. The decreased RNFL thickness in MCI and AD patients suggests loss of retinal neurons and their axons. The increased thickness and macular volume have never been reported before in aMCI. This finding could be explained by inflammation and/or gliosis in early stages of AD. OCT could be a useful marker of AD for early detection and monitoring progression.