L. Mosconi, J. Murray, W. Tsui, Yi Li, M. Davies, Schantel Williams, E. Pirraglia, N. Spector, R. Osorio, Lidia Glodzik, P. McHugh, M. J. Leon
{"title":"Mediterranean Diet and Magnetic Resonance Imaging-Assessed Brain Atrophy in Cognitively Normal Individuals at Risk for Alzheimer's Disease.","authors":"L. Mosconi, J. Murray, W. Tsui, Yi Li, M. Davies, Schantel Williams, E. Pirraglia, N. Spector, R. Osorio, Lidia Glodzik, P. McHugh, M. J. Leon","doi":"10.14283/jpad.2014.17","DOIUrl":"https://doi.org/10.14283/jpad.2014.17","url":null,"abstract":"OBJECTIVES\u0000Epidemiological evidence linking diet, one of the most important modifiable environmental factors, and risk of Alzheimer's disease (AD) is rapidly increasing. Several studies have shown that higher adherence to a Mediterranean diet (MeDi) is associated with reduced risk of AD. This study examines the associations between high vs. lower adherence to a MeDi and structural MRI-based brain atrophy in key regions for AD in cognitively normal (NL) individuals with and without risk factors for AD.\u0000\u0000\u0000DESIGN\u0000Cross-sectional study.\u0000\u0000\u0000SETTING\u0000Manhattan (broader area).\u0000\u0000\u0000PARTICIPANTS\u0000Fifty-two NL individuals (age 54+12 y, 70% women) with complete dietary information and cross-sectional, 3D T1-weighted MRI scans were examined.\u0000\u0000\u0000MEASUREMENTS\u0000Subjects were dichotomized into those showing higher vs. lower adherences to the MeDi using published protocols. Estimates of cortical thickness for entorhinal cortex (EC), inferior parietal lobe, middle temporal gyrus, orbitofrontal cortex (OFC) and posterior cingulate cortex (PCC) were obtained by use of automated segmentation tools (FreeSurfer). Multivariate general linear models and linear regressions assessed the associations of MeDi with MRI measures.\u0000\u0000\u0000RESULTS\u0000Of the 52 participants, 20 (39%) showed higher MeDi adherence (MeDi+) and 32 (61%) showed lower adherence (MeDi-). Groups were comparable for clinical, neuropsychological measures, presence of a family history of AD (FH), and frequency of Apolipoprotein E (APOE) ε4 genotype. With and without controlling for age and total intracranial volume, MeDi+ subjects showed greater thickness of AD-vulnerable ROIs as compared to MeDi- subjects (Wilk's Lambda p=0.026). Group differences were most pronounced in OFC (p=0.001), EC (p=0.03) and PCC (p=0.04) of the left hemisphere. Adjusting for gender, education, FH, APOE status, BMI, insulin resistance scores and presence of hypertension did not attenuate the relationship.\u0000\u0000\u0000CONCLUSION\u0000NL individuals showing lower adherence to the MeDi had cortical thinning in the same brain regions as clinical AD patients compared to those showing higher adherence. These data indicate that the MeDi may have a protective effect against tissue loss, and suggest that dietary interventions may play a role in the prevention of AD.","PeriodicalId":48606,"journal":{"name":"Jpad-Journal of Prevention of Alzheimers Disease","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2014-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66892414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
B. Vellas, I. Carrié, S. Gillette‐Guyonnet, J. Touchon, T. Dantoine, J. Dartigues, M. Cuffi, S. Bordes, Y. Gasnier, P. Robert, L. Bories, O. Rouaud, F. Desclaux, K. Sudres, M. Bonnefoy, A. Pesce, C. Dufouil, S. Lehéricy, M. Chupin, J. F. Mangin, P. Payoux, D. Adel, P. Legrand, D. Catheline, C. Kanony, M. Zaim, L. Molinier, N. Costa, J. Delrieu, T. Voisin, C. Faisant, F. Lala, F. Nourhashemi, Y. Rolland, G. A. van Kan, C. Dupuy, C. Cantet, P. Cestac, S. Belleville, S. Willis, M. Cesari, M. Weiner, M. Soto, P. Ousset, S. Andrieu
{"title":"MAPT STUDY: A MULTIDOMAIN APPROACH FOR PREVENTING ALZHEIMER'S DISEASE: DESIGN AND BASELINE DATA.","authors":"B. Vellas, I. Carrié, S. Gillette‐Guyonnet, J. Touchon, T. Dantoine, J. Dartigues, M. Cuffi, S. Bordes, Y. Gasnier, P. Robert, L. Bories, O. Rouaud, F. Desclaux, K. Sudres, M. Bonnefoy, A. Pesce, C. Dufouil, S. Lehéricy, M. Chupin, J. F. Mangin, P. Payoux, D. Adel, P. Legrand, D. Catheline, C. Kanony, M. Zaim, L. Molinier, N. Costa, J. Delrieu, T. Voisin, C. Faisant, F. Lala, F. Nourhashemi, Y. Rolland, G. A. van Kan, C. Dupuy, C. Cantet, P. Cestac, S. Belleville, S. Willis, M. Cesari, M. Weiner, M. Soto, P. Ousset, S. Andrieu","doi":"10.14283/jpad.2014.34","DOIUrl":"https://doi.org/10.14283/jpad.2014.34","url":null,"abstract":"OBJECTIVE\u0000The Multidomain Alzheimer Preventive Trial (MAPT study) was designed to assess the efficacy of isolated supplementation with omega-3 fatty acid, an isolated multidomain intervention (consisting of nutritional counseling, physical exercise, cognitive stimulation) or a combination of the two interventions on the change of cognitive functions in frail subjects aged 70 years and older for a period of 3 years. Ancillary neuroimaging studies were additionally implemented to evaluate the impact of interventions on cerebral metabolism (FDG PET scans) and atrophy rate (MRIs), as well as brain amyloïd deposit (AV45 PET scans).\u0000\u0000\u0000DESIGN PATIENTS\u00001680 subjects (mean age: 75.3 years; female: 64.8 %), enrolled by 13 memory clinics, were randomized into one of the following four groups: omega-3 supplementation alone, multidomain intervention alone, omega-3 plus multidomain intervention, or placebo. Participants underwent cognitive, functional and biological assessments at M6, M12, M24 and M36 visits. The primary endpoint is a change of memory function at 3 years, as assessed by the Free and Cued Selective Reminding test. All participants will be followed for 2 additional years after the 3-years intervention (MAPT PLUS extension study).\u0000\u0000\u0000INTERVENTIONS\u00001/Omega-3 supplementation: two soft capsules daily as a single dose, containing a total of 400 mg docosahexaenoic acid (DHA), i.e., 800 mg docosahexaenoic acid per day, for 3 years. 2/ Multidomain intervention: collective training sessions conducted in small groups (6-8 participants) in twelve 120-minute sessions over the first 2 months (two sessions a week for the first month, and one session a week the second month) then a 60-minute session per month in the following three areas: nutrition, physical activity, and cognition until the end of the 3 years. In addition to the collective sessions, individualized preventive outpatient visits exploring possible risk factors for cognitive decline are performed at baseline, M12 and M24.\u0000\u0000\u0000BASELINE POPULATION\u0000For cognition, the mean MMSE at baseline was 28.1 (± 1.6). About 58% and 42% of participants had a CDR score equal to 0 and 0.5, respectively. Regarding mobility status, 200 (11.9%) had a 4-m gait speed lower or equal to 0.8 m/s. According to the Fried criteria, 673 (42.1%) participants were considered pre frail, and 51 (3.2%) frail. The red blood cell DHA content was 26.1 ± 8.1 µg/g. Five hundred and three participants underwent baseline MRI. AV45 PET scans were performed in 271 individuals and preliminary results showed that 38.0% had a cortical SUVR > 1.17, which gave an indication of significant brain amyloïd deposit. DISCUSSION: The MAPT trial is presently the first largest and longest multidomain preventive trial relevant to cognitive decline in older adults with subjective memory complaints. The multidomain intervention designed for the MAPT trial is likely to be easily implemented within the general population.","PeriodicalId":48606,"journal":{"name":"Jpad-Journal of Prevention of Alzheimers Disease","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2014-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66892629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
P. Dacks, S. Andrieu, D. Blacker, A. Carman, Allan M. Green, F. Grodstein, V. Henderson, B. James, R. Lane, J. Lau, P. Lin, B. Reeves, R. Shah, B. Vellas, K. Yaffe, K. Yurko-Mauro, D. Shineman, D. Bennett, H. Fillit
{"title":"Dementia Prevention: optimizing the use of observational data for personal, clinical, and public health decision-making.","authors":"P. Dacks, S. Andrieu, D. Blacker, A. Carman, Allan M. Green, F. Grodstein, V. Henderson, B. James, R. Lane, J. Lau, P. Lin, B. Reeves, R. Shah, B. Vellas, K. Yaffe, K. Yurko-Mauro, D. Shineman, D. Bennett, H. Fillit","doi":"10.14283/jpad.2014.35","DOIUrl":"https://doi.org/10.14283/jpad.2014.35","url":null,"abstract":"Worldwide, over 35 million people suffer from Alzheimer's disease and related dementias. This number is expected to triple over the next 40 years. How can we improve the evidence supporting strategies to reduce the rate of dementia in future generations? The risk of dementia is likely influenced by modifiable factors such as exercise, cognitive activity, and the clinical management of diabetes and hypertension. However, the quality of evidence is limited and it remains unclear whether specific interventions to reduce these modifiable risk factors can, in turn, reduce the risk of dementia. Although randomized controlled trials are the gold-standard for causality, the majority of evidence for long-term dementia prevention derives from, and will likely continue to derive from, observational studies. Although observational research has some unavoidable limitations, its utility for dementia prevention might be improved by, for example, better distinction between confirmatory and exploratory research, higher reporting standards, investment in effectiveness research enabled by increased data-pooling, and standardized exposure and outcome measures. Informed decision-making by the general public on low-risk health choices that could have broad potential benefits could be enabled by internet-based tools and decision-aids to communicate the evidence, its quality, and the estimated magnitude of effect.","PeriodicalId":48606,"journal":{"name":"Jpad-Journal of Prevention of Alzheimers Disease","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2014-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66892689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M. Berres, W. Kukull, A. Miserez, A. Monsch, Sarah E. Monsell, R. Spiegel
{"title":"A Novel Study Paradigm for Long-term Prevention Trials in Alzheimer Disease: The Placebo Group Simulation Approach (PGSA): Application to MCI data from the NACC database.","authors":"M. Berres, W. Kukull, A. Miserez, A. Monsch, Sarah E. Monsell, R. Spiegel","doi":"10.14283/jpad.2014.5","DOIUrl":"https://doi.org/10.14283/jpad.2014.5","url":null,"abstract":"INTRODUCTION The PGSA (Placebo Group Simulation Approach) aims at avoiding problems of sample representativeness and ethical issues typical of placebo-controlled secondary prevention trials with MCI patients. The PGSA uses mathematical modeling to forecast the distribution of quantified outcomes of MCI patient groups based on their own baseline data established at the outset of clinical trials. These forecasted distributions are then compared with the distribution of actual outcomes observed on candidate treatments, thus substituting for a concomitant placebo group. Here we investigate whether a PGSA algorithm that was developed from the MCI population of ADNI 1*, can reliably simulate the distribution of composite neuropsychological outcomes from a larger, independently selected MCI subject sample. METHODS Data available from the National Alzheimer's Coordinating Center (NACC) were used. We included 1523 patients with single or multiple domain amnestic mild cognitive impairment (aMCI) and at least two follow-ups after baseline. In order to strengthen the analysis and to verify whether there was a drift over time in the neuropsychological outcomes, the NACC subject sample was split into 3 subsamples of similar size. The previously described PGSA algorithm for the trajectory of a composite neuropsychological test battery (NTB) score was adapted to the test battery used in NACC. Nine demographic, clinical, biological and neuropsychological candidate predictors were included in a mixed model; this model and its error terms were used to simulate trajectories of the adapted NTB. RESULTS The distributions of empirically observed and simulated data after 1, 2 and 3 years were very similar, with some over-estimation of decline in all 3 subgroups. The by far most important predictor of the NTB trajectories is the baseline NTB score. Other significant predictors are the MMSE baseline score and the interactions of time with ApoE4 and FAQ (functional abilities). These are essentially the same predictors as determined for the original NTB score. CONCLUSION An algorithm comprising a small number of baseline variables, notably cognitive performance at baseline, forecasts the group trajectory of cognitive decline in subsequent years with high accuracy. The current analysis of 3 independent subgroups of aMCI patients from the NACC database supports the validity of the PGSA longitudinal algorithm for a NTB. Use of the PGSA in long-term secondary AD prevention trials deserves consideration.","PeriodicalId":48606,"journal":{"name":"Jpad-Journal of Prevention of Alzheimers Disease","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66892588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Richard S. Isaacson, N. Haynes, A. Seifan, D. Larsen, S. Christiansen, J. C. Berger, Joseph Safdieh, A. Lunde, A. Luo, M. Kramps, M. McInnis, C. Ochner
{"title":"Alzheimer's Prevention Education: If We Build It, Will They Come? www.AlzU.org.","authors":"Richard S. Isaacson, N. Haynes, A. Seifan, D. Larsen, S. Christiansen, J. C. Berger, Joseph Safdieh, A. Lunde, A. Luo, M. Kramps, M. McInnis, C. Ochner","doi":"10.14283/jpad.2014.4","DOIUrl":"https://doi.org/10.14283/jpad.2014.4","url":null,"abstract":"BACKGROUND Internet-based educational interventions may be useful for impacting knowledge and behavioral change. However, in AD prevention, little data exists about which educational tools work best in terms of learning and interest in participating in clinical trials. OBJECTIVES Primary: Assess effectiveness of interactive webinars vs. written blog-posts on AD prevention learning. Secondary: Evaluate the effect of AD prevention education on interest in participating in clinical trials; Assess usability of, and user perceptions about, an online AD education research platform; Classify target populations (demographics, learning needs, interests). DESIGN Observational. SETTING Online. PARTICIPANTS Men/Women, aged 25+, recruited via facebook.com. INTERVENTION Alzheimer's Universe (www.AlzU.org) education research platform. MEASUREMENTS Pre/post-test performance, self-reported Likert-scale ratings, completion rates. RESULTS Over two-weeks, 4268 visits were generated. 503 signed-up for a user account (11.8% join rate), 196 participated in the lessons (39.0%) and 100 completed all beta-testing steps (19.9%). Users randomized to webinar instruction about AD prevention and the stages of AD demonstrated significant increases (p=0.01) in pre vs. post-testing scores compared to blog-post intervention. Upon joining, 42% were interested in participating in a clinical trial in AD prevention. After completing all beta-test activities, interest increased to 86%. Users were primarily women and the largest category was children of AD patients. 66.3% joined to learn more about AD prevention, 65.3% to learn more about AD treatment. CONCLUSIONS Webinar-based education led to significant improvements in learning about AD prevention and the stages of AD. AlzU.org participation more than doubled interest in AD prevention clinical trial participation. Subjects were quickly and cost-effectively recruited, and highly satisfied with the AD education research platform. Based on these data, we will further refine AlzU.org prior to public launch and aim to study the effectiveness of 25 interactive webinar-based vs. blog-post style lessons on learning and patient outcomes, in a randomized, within-subjects design trial.","PeriodicalId":48606,"journal":{"name":"Jpad-Journal of Prevention of Alzheimers Disease","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66892855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}