Helsinki, Finland; 9 University of Helsinki, Helsinki, Finland; 10 Kuopio University Hospital, Kuopio, Finland. Contact e-mail: miia.kivipelto@ki.se Background: Observational studies have identified multiple modifiable risk factors associated with increased risk of late-life cognitive impairment and Alzheimer’s disease (AD). However, previous smaller and shorter term pre- vention trials with single-factor interventions have had disappointing or at best modest results. The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) investigated the effects of a 2-year multidomain intervention targeting several lifestyle and vascular risk factors simultaneously. Methods: FINGER is a 2-year multicenter ran- domized controlled trial with 1260 participants aged 60-77 years recruited from previous population-based survey cohorts. Inclusion criteria were: CAIDE Dementia Risk Score > 6 points, indicating the presence of modifi- able risk factors; and cognitive performance at the mean level or slightly lower than expected for age. Participants were randomized (1:1) into either the multidomain intervention group or the control group. The intervention included nutritional guidance, physical exercise, cognitive training and so- cial activities, and management of vascular risk factors. The control group received regular health advice. Primary outcome after 2 years is cognitive performance measured by a comprehensive neuropsychological test battery (NTB) composite Z score. An extended follow-up (7 years) with a suste- nance intervention is planned to evaluate longer-term effects on dementia/ AD incidence, and secondary and exploratory outcomes including bio- markers and neuroimaging with MRI and PET. The 2-year intervention was finalized in February 2014. Here we report the main intention-to-treat (ITT) results on cognition after 2 years of intervention. Linear mixed-model statistical analyses were used. Results: We found a significant beneficial intervention effect on overall cognitive performance (NTB) (p < 0.001 for time*group interaction). The beneficial effect was seen on each cogni- tive domain: memory (p < 0.05); executive function (p < 0.05), and psycho- motor speed (p < 0.05). Drop-out rate was only 11%, and participants’ experiences were very positive. Conclusions: This is the first large RCT showing that it is possible to prevent cognitive decline using a multidomain intervention among older at-risk individuals. These results highlight the value of the feasible and novel multidomain approach that is effective for several cognitive domains. O1-05-05 ASSESSING CLINICAL PROGRESSION FOR DEMENTIA PREVENTION TRIAL: RESULTS FROM THE HBA TRIAL Mary Sano 1 , Susan Egelko 2 , Michael C. Donohue 3 , Jeffrey Kaye 4 , James Mundt 5 , Chung-Kai Sun 6 , Steven Ferris 7 , Paul S. Aisen 8 , 1 Mount Sinai School of Medicine & James J Peters VAMC, New York, New York, United States; 2 Mt. Sinai School of Medicine/James J Peters VA, New York, New York, United States; 3 University of California, San Diego, La Jolla, California, United States; 4 Oregon Health & Science University, Portland, Oregon, United States; 5 Center for Psychological Research, Training & Consultation, Madison, Wisconsin, United States; 6 UC San Diego, La Jolla, California, United States; 7 New York University Langone Medical Center, New York, New York, United States; 8 University of California at San Diego, La Jolla, California, United States. Contact e-mail: mary.sano@mssm.edu Background: The Home Based Assessment trial, designed to develop methods for studies of dementia prevention, consented, randomized, and base lined 581 non-demented participants at 27 sites, and compared three methods of test administration and data collection over a 4-year period. Assessment methods were: 1) mail-in questionnaire with live telephone in- terviews (MIP); 2) automated telephone with interactive voice response (IVR); and 3) Internet-based computer kiosk (KIO). Test domains (i.e., cognitive performance, self-rated cognitive complaint, functioning in daily life, affective symptoms, global change, quality of life and resource use) were captured with each method at each assessment. Methods: Enrolled participants had an in-person (standard) assessment prior to baseline. Based on existing data, predefined scores on specific cognitive and functional mea- sures were used to identify a point of significant impairment. These scores were used as cut-offs for test results of the longitudinal home-based assess- ment visits that "triggered" an in-person assessment. In addition, a random sample of non-triggered cases (25%) was selected for an in-person re- assessment during the 4 years of the protocol as a comparison for the trigger group. At the end of the 4-year study period all participants were given an in- person evaluation, which was the basis of categorizing the person as "clin- ical progression" (e.g. MCI or dementia) or "stable". Results: In the repeated measures logistic model (GEE) of clinical progression vs. trigger the overall (unadjusted) odds ratio was significant (OR¼3.22; CI ¼1.82-5.64; p < .001). For the individual arms, the MIP (OR ¼ 4.67; CI¼1.58-13.75; p ¼.002) and the KIO (OR¼4.64; CI¼1.01-21.26; p ¼.047) significantly detected clinical progression events corroborated by an in-person exam; the IVR arm was not significant (OR¼1.88; CI¼0.55-6.40; p ¼.528). The test of interaction of trigger and arm did not reach significance: c 2 ¼ 2.11 (df ¼2, p ¼ 0.348); none of the dyad compar- isons across arms was significant. Conclusions: This report demonstrates that in-home testing over a 4-year period may reliably predict a meaningful change in clinical diagnosis. Novel in-home assessment techniques may allow for a broader and more diverse population eligible for clinical trials. O1-05-06 THE FIRST DISEASE-MODIFYING DRUG TRIAL IN FRONTOTEMPORAL DEMENTIA: INITIAL EXPERIENCES Janine Diehl-Schmid 1 , Jiri Hardlund 2 , Peter Bentham 3 , Claude M. Wischik 4 , 1 TU M€ unchen, M€ unchen, Germany; 2 TauRx Therapeutics, Aberdeen, United Kingdom; 3 Queen Elizabeth Psychiatric Hospital, Birmingham, United Kingdom; 4 University of Aberdeen, Aberdeen, United Kingdom. Contact e-mail: janine.schmid@lrz.tum.de Background: The first disease modifying clinical trial in behavioural variant frontotemporal dementia (bvFTD) was initiated in 2013 as a 12-month trial of a reduced form of methylthioninium "LMTX", a tau and TDP-43 aggregation inhibitor. Methods: The trial is conducted glob- ally in 76 sites in 15 countries. Pre-screen failure data are available from 275 subjects as of January 2014. Results: Study design considerations: Clinical endpoints are the only ones acceptable to regulatory author- ities. Cognitive impairment is an important feature of bvFTD, is readily measurable and progresses with disease severity. Likewise CGIC reliably declines with severity. These have been selected as co-primary outcome measures. Assessments of behavior such as the NPI, which ought to be useful for capturing behavioural deficits, are particularly unsuitable because progression of apathy would appear as benefit. Problems with study conduct: Of the 275 subjects pre- screened, 55 progressed to formal screening and 20 were randomised. Reasons for pre-screen failure were defined in 80%. Of these, 28% were suffering from other conditions (phenocopies), 22% failed for procedural reasons (such as distance, hospitalization, other treatments not stabilized), 21% were older than 70, 12% had an MMSE < 20. 12% were unwilling to consent or lacked interest. In practice some bvFTD patients have difficulty with waiting times, become irritable, or do not tolerate the repeated MRI scans that have been mandated by the FDA. Untrained staff may have difficulty in managing behav- ioural problems. Although there is a possibility of selection bias in favour of quiet, apathetic patients, the pre-screen failure data do not appear to support this. Conclusions: Although the first disease-modi- fying trial in bvFTD has been eagerly awaited, patient recruitment in bvFTD studies has proven to be difficult, with the majority of prescreen failures accounted for by phenocopies and procedural factors. Phenocop- ies are controlled by a requirement for positive MRI evidence of fronto- temporal atrophy. The age cut-off has been raised to 80. Study sites will be requested to train staff to deal better with behavioural disturbances. The pre-screen failure log will be expanded to determine whether there is selection bias against behaviourally disturbed subjects. Oral Sessions: O1-05: Clinical Trials I: Trial Design and Outcome Measures P138 View publication stats View publication stats