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Late-life depression (LLD) increases risk for dementia and brain pathology, but possibly this is only true for one or more symptom profiles of LLD. In 4354 participants (76±5 years; 58% female) from the Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study, we identified five LLD symptom profiles, based on the Geriatric Depression Scale-15 (no LLD(57%); apathy(31%); apathy with emptiness(2%), mild LLD(8%) and severe LLD(2%)). Cox regression analyses showed that severe LLD, mild LLD and apathy increased risk of dementia up to 12 years, compared to no LLD. Additionally, hippocampal volume loss and white matter lesion increase, were assessed on 1.5 T MR images, at baseline and after 5 years follow-up. Only severe LLD showed increased WML volume over time, but not on hippocampal volume loss. WML increase over time mediated partially the relation between mild LLD and dementia but not for the other symptom profiles. It appears that hippocampal atrophy and LLD are independent predictors for dementia incidence, whereas for mild LLD the risk for dementia is partially mediated by WML changes.

BACKGROUND: Frailty is often associated with multimorbidity and disability. OBJECTIVES: We investigated heterogeneity in the frail older population by characterizing five subpopulations according to quantitative biological markers, multimorbidity and disability, and examined their association with mortality and nursing home admission. DESIGN: Observational study. PARTICIPANTS: Participants (n=4,414) were from the population-based Age Gene/Environment Susceptibility Reykjavik Study. MEASUREMENTS: Frailty was defined by ≥ 3 of five characteristics: weight loss, weakness, reduced energy levels, slowness and physical inactivity. Multimorbidity was assessed using a simple disease count, based on 13 prevalent conditions. Disability was assessed by five activities of daily living; participants who had difficulty with one or more tasks were considered disabled. Differences among frail subpopulations were based on the co-presence of multimorbidity and disability. Differences among the following subpopulations were examined: 1) Non-frail (reference group); 2) Frail only; 3) Frail with disability; 4) Frailty with multimorbidity; 5) Frail with disability and multimorbidity. RESULTS: Frailty was present in 10.7% (n=473). Frailty was associated with increased risk for mortality (OR 1.40; 95% CI 1.15-1.69) and nursing home admission (OR 1.50; 95% CI 1.16-1.93); risks differed by subpopulations. Compared to the non-frail, the frail only group had poorer cognition and increased inflammation levels but did not have increased risk for mortality (OR 1.40; 95% CI 0.84-2.33) or nursing home admission (OR 1.01; 95% CI 0.46-2.21). Compared to the non-frail, the other frail subpopulations had significantly poorer cognition, increased inflammation levels, more white matter lesions, higher levels of calcium, glucose and red cell distribution width and increased risk for mortality and nursing home admission. CONCLUSIONS: The adverse health risks associated with frailty in the general older adult population may primarily be driven by increased disease burden and disability.

Objectives: Reimbursement decisions are conventionally based on evidence from randomised controlled trials (RCTs) which often have high internal validity but low external validity. Real-world data (RWD) may provide complimentary evidence for relative effectiveness assessments (REAs) and cost-effectiveness assessments (CEAs). This study examines whether RWD is incorporated in Health Technology Assessment (HTA) of melanoma drugs by European HTA agencies, differences in RWD use between agencies and across time. Methods: HTA reports published between 01.01.2011 and 31.12.2016 were retrieved from websites of agencies representing 5 jurisdictions: England (NICE), Scotland (SMC), France (HAS), Germany (IQWiG) and the Netherlands (ZIN). A standardized data-extraction form was used to extract information on RWD inclusion for both REAs and CEAs. A panel of senior HTA assessors representing the 5 agencies was consulted to check the robustness of data extracted and interpretation. Results: Fifty-two reports were retrieved. All 52 reports contained REAs; CEAs were present in 25. RWD was included in 28 of 52 REAs (54%); mainly to estimate melanoma prevalence. RWD was included in 22 of 25 (88%) of CEAs; mainly to extrapolate long-term effectiveness and/or identify drug-related costs drugs. Differences emerged between agencies regarding RWD use in REAs; ZIN and IQWiG cited RWD for evidence on prevalence whereas NICE, SMC and HAS additionally cited RWD use for drug effectiveness. No visible trend for RWD use in REAs and CEAs over time was observed. Conclusions: In general, RWD inclusion was higher in CEAs than REAs. It was mostly used to estimate melanoma prevalence in REAs or to predict long-term effectiveness in CEAs. Differences emerged between agencies' use of RWD. However, no visible trends for RWD use over time were observed. Future research should explore the use of RWD in HTA of drugs in other disease indications and in conditional reimbursement schemes.

Contains fulltext : 97597.pdf (Publisher’s version ) (Open Access) A previous genome-wide association (GWA) meta-analysis of 12,386 PD cases and 21,026 controls conducted by the International Parkinson's Disease Genomics Consortium (IPDGC) discovered or confirmed 11 Parkinson's disease (PD) loci. This first analysis of the two-stage IPDGC study focused on the set of loci that passed genome-wide significance in the first stage GWA scan. However, the second stage genotyping array, the ImmunoChip, included a larger set of 1,920 SNPs selected on the basis of the GWA analysis. Here, we analyzed this set of 1,920 SNPs, and we identified five additional PD risk loci (combined p