Management of potentially inappropriate medication use among older adult's patients in primary care settings: description of an interventional prospective non-randomized study.

BACKGROUND: The management of inappropriate medication use in older patients suffering from multimorbidity and polymedication is a major healthcare challenge. In a primary care setting, a medication review is an effective tool through which a pharmacist can collaborate with a practitioner to detect inappropriate drug use. AIM: This project described the implementation of a systematic process for the management of potentially inappropriate medication use among Lebanese older adults. Its aim was to involve pharmacists in geriatric care and to suggest treatment optimization through the analysis of prescriptions using explicit and implicit criteria. METHOD: This study evaluated the medications of patients over 65 years taking a minimum of five chronic medications a day in different regions of Lebanon. Descriptive statistics for all the included variables using mean and standard deviation (Mean (SD)) for continuous variables and frequency and percentage (n, (%)) for multinomial variables were then performed. RESULTS: A total of 850 patients (50.7% women, 28.6% frail, 75.7 (8.01) mean age (SD)) were included in this study. The mean number of drugs per prescription was 7.10 (2.45). Roughly 88% of patients (n = 748) had at least one potentially inappropriate drug prescription: 66.4% and 64.4% of the patients had at least 1 drug with an unfavorable benefit-to-risk ratio according to Beers and EU(7)-PIM respectively. Nearly 50.4% of patients took at least one medication with no indication. The pharmacists recommended discontinuing medication for 76.5% of the cases of drug related problems. 26.6% of the overall proposed interventions were implemented. DISCUSSION: The rate of potentially inappropriate drug prescribing (PIDP) (88%) was higher than the rates previously reported in Europe, US, and Canada. It was also higher than studies conducted in Lebanon where it varied from 22.4 to 80% depending on the explicit criteria used, the settings, and the medical conditions of the patients. We used both implicit and explicit criteria with five different lists to improve the detection of all types of inappropriate medication use since Lebanon obtains drugs from many different sources. Another potential source for variation is the lack of a standardized process for the assessment of outpatient medication use in the elderly. CONCLUSION: The prevalence PIDP detected in the sample was higher than the percentages reported in previous literature. Systematic review of prescriptions has the capacity to identify and resolve pharmaceutical care issues thus improving geriatric care.

Integrating a multimodal lifestyle intervention with medical food in prodromal Alzheimer's disease: the MIND-ADmini randomized controlled trial.

BACKGROUND: The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) showed cognitive benefits from a multidomain lifestyle intervention in at-risk older people. The LipiDiDiet trial highlighted benefits of medical food in prodromal Alzheimer's disease (AD). However, the feasibility and impact of multimodal interventions combining lifestyle with medical food in prodromal AD is unclear. METHODS: MIND-ADmini was a 6-month multinational (Sweden, Finland, Germany, France) proof-of-concept randomized controlled trial (RCT). Participants were 60-85 years old, had prodromal AD (International Working Group-1 criteria), and vascular/lifestyle risk factors. The parallel-group RCT had three arms: multimodal lifestyle intervention (nutritional guidance, exercise, cognitive training, vascular/metabolic risk management and social stimulation); multimodal lifestyle intervention + medical food (Fortasyn Connect); and regular health advice/care (control). Participants were randomized 1:1:1 (computer-generated allocation at each site). Outcome evaluators were blinded to randomization. Primary outcome was feasibility of the multimodal intervention, evaluated by recruitment rate during a 6-month recruitment phase, overall adherence in each intervention arm, and 6-month retention rate. Successful adherence was pre-specified as attending ≥ 40% of sessions/domain in ≥ 2/4 domains (lifestyle intervention), and consuming ≥ 60% of the medical food (lifestyle intervention + medical food). The secondary outcomes included adherence/participation to each intervention component and overall adherence to healthy lifestyle changes, measured using a composite score for healthy lifestyle. Cognitive assessments were included as exploratory outcomes, e.g. Clinical Dementia Rating scale. RESULTS: During September 2017-May 2019, 93 individuals were randomized (32 lifestyle intervention, 31 lifestyle + medical food, and 30 control group). Overall recruitment rate was 76.2% (64.8% during the first 6 months). Overall 6-month retention rate was 91.4% (lifestyle intervention 87.5%; lifestyle + medical food 90.3%; control 96.7%). Domain-specific adherence in the lifestyle intervention group was 71.9% to cognitive training, 78.1% exercise, 68.8% nutritional guidance, and 81.3% vascular risk management; and in the lifestyle + medical food group, 90.3% to cognitive training, 87.1% exercise, 80.7% nutritional guidance, 87.1% vascular risk management, and 87.1% medical food. Compared with control, both intervention arms showed healthy diet improvements (ßLifestyle×Time = 1.11, P = 0.038; ßLifestyle+medical food×Time = 1.43, P = 0.007); the lifestyle + medical food group also showed vascular risk reduction (P = 0.043) and less cognitive-functional decline (P < 0.05, exploratory analysis). There were 5 serious adverse events (control group: 1; lifestyle intervention: 3; lifestyle + medical food: 1) unrelated to interventions. CONCLUSIONS: The multidomain lifestyle intervention, alone or combined with medical food, had good feasibility and adherence in prodromal AD. Longer-term cognitive and other health benefits should be further investigated in a larger-scale trial. TRIAL REGISTRATION: ClinicalTrials.gov NCT03249688.

Predictive Capacity of the Integrated Care for Older People Screening Tool for Intrinsic Capacity Impairments: Results From the INSPIRE-T Cohort.

BACKGROUND: The Integrated Care for Older People (ICOPE) approach was developed by the World Health Organization (WHO) aiming to shift the traditional focus of care based on diseases to a function- and person-centered approach, focused on maintaining and monitoring intrinsic capacity (IC). This study aimed to investigate the ability of the ICOPE screening tool to identify older people with clinically meaningful impairments in IC domains. METHODS: This cross-sectional analysis included 603 older adults, participants (mean age 74.7 [SD = 8.8] years, women 59.0%) of the INSPIRE Translational (INSPIRE-T) cohort. Responses at screening were compared to results of the subsequent in-depth assessment (ie, Mini-Mental State Examination, Mini Nutritional Assessment, Short Physical Performance Battery, Patient Health Questionnaire-9, and clinical investigation of vision problems) to determine its predictive capacity for impairments at the IC domains (ie, cognition, psychological, sensory (vision), vitality, and locomotion). RESULTS: The ICOPE screening items provided very high sensitivity for identifying abnormality in vision (97.2%) and varied from 42.0% to 69.6% for the other domains. High specificity (>70%) was observed for all the IC domains, except for vision (2.7%). CONCLUSIONS: The ICOPE screening tool can be a useful instrument enabling the identification of older people with impairments in IC domains, but studies with different populations are needed. It should be considered as a low-cost and simple screening tool in clinical care.

Prognostication algorithm for non-cirrhotic non-B non-C hepatocellular carcinoma-a multicenter study under the aegis of the French Association of Hepato-Biliary Surgery and liver Transplantation.

Background: Liver resection and local ablation are the only curative treatment for non-cirrhotic hepatocellular carcinoma (HCC). Few data exist concerning the prognosis of patients resected for non-cirrhotic HCC. The objectives of this study were to determine the prognostic factors of recurrence-free survival (RFS) and overall survival (OS) and to develop a prognostication algorithm for non-cirrhotic HCC. Methods: French multicenter retrospective study including HCC patients with non-cirrhotic liver without underlying viral hepatitis: F0, F1 or F2 fibrosis. Results: A total of 467 patients were included in 11 centers from 2010 to 2018. Non-cirrhotic liver had a fibrosis score of F0 (n=237, 50.7%), F1 (n=127, 27.2%) or F2 (n=103, 22.1%). OS and RFS at 5 years were 59.2% and 34.5%, respectively. In multivariate analysis, microvascular invasion and HCC differentiation were prognostic factors of OS and RFS and the number and size were prognostic factors of RFS (P<0.005). Stratification based on RFS provided an algorithm based on size (P=0.013) and number (P<0.001): 2 HCC with the largest nodule ≤10 cm (n=271, Group 1); 2 HCC with a nodule >10 cm (n=176, Group 2); >2 HCC regardless of size (n=20, Group 3). The 5-year RFS rates were 52.7% (Group 1), 30.1% (Group 2) and 5% (Group 3). Conclusions: We developed a prognostication algorithm based on the number (≤ or >2) and size (≤ or >10 cm), which could be used as a treatment decision support concerning the need for perioperative therapy. In case of bifocal HCC, surgery should not be a contraindication.

Biomarkers of mitochondrial dysfunction and inflammaging in older adults and blood pressure variability.

Most physiopathological mechanisms underlying blood pressure variability (BPV) are implicated in aging. Vascular aging is associated with chronic low-grade inflammation occurring in late life, known as "inflammaging" and the hallmark "mitochondrial dysfunction" due to age-related stress. We aimed to determine whether plasma levels of the pleiotropic stress-related mitokine growth/differentiation factor 15 (GDF-15) and two inflammatory biomarkers, interleukin 6 (IL-6) and tumor necrosis factor receptor 1 (TNFR-1), are associated with visit-to-visit BPV in a population of community-dwelling older adults. The study population consisted of 1096 community-dwelling participants [median age 75 (72-78) years; 699 females, 63.7%] aged ≥ 70 years from the MAPT study. Plasma blood sample was collected 12 months after enrolment and BP was assessed up to seven times over a 4-year period. Systolic (SBPV) and diastolic BPV (DBPV) were determined through several indicators taking into account BP change over time, the order of measurements and formulas independent of mean BP levels. Higher values of GDF-15 were significantly associated with increased SBPV (all indicators) after adjustment for relevant covariates [adjusted 1-SD increase in GDF-15: ß (SE) = 0.07 (0.04), p < 0.044, for coefficient of variation%]. GDF-15 levels were not associated with DBPV. No significant associations were found between IL-6 and BPV, whereas TNFR1 was only partially related to DBPV. Unlike inflammation biomarkers, higher GDF-15 levels were associated with greater SBPV. Our findings support the age-related process of mitochondrial dysfunction underlying BP instability, suggesting that BPV might be a potential marker of aging.

Implementation of the WHO integrated care for older people (ICOPE) programme in clinical practice: a prospective study.

BACKGROUND: The INSPIRE integrated care for older people (ICOPE)-CARE programme is a public health programme implementing the ICOPE health-care pathway in clinical practice. The primary objective of this study was to describe the large-scale implementation and feasibility of the INSPIRE ICOPE-CARE guidelines in clinical practice. The secondary aims were to describe the characteristics of patients who were identified as positive for abnormalities in intrinsic capacity (ie, locomotion, cognition, psychology, vitality, hearing, and vision) during step 1, and to describe the prevalence of these positive screenings. METHODS: In this prospective study, we evaluated a real-life population of users of primary care services in the Occitania region (France). Participants who were aged 60 years and older and lived in a community were eligible for inclusion in our study. Individuals aged ≥60 years were screened (step 1) by health-care providers or through self-assessments using digital tools (the ICOPE MONITOR app and the ICOPEBOT conversational robot). Our implementation strategy involved raising awareness among health-care professionals about the WHO ICOPE programme, training professionals in the ICOPE-CARE guidelines, and developing a digital infrastructure (ie, digital tools, a database, and a remote ICOPE monitoring platform). The feasibility of implementing the INSPIRE ICOPE-CARE guidelines was determined by the anticipated inclusion of ≥10 000 participants, and having a follow-up rate of over 50%. FINDINGS: Between Jan 1, 2020, and November 18, 2021, 10 903 older people (mean age 76·0, SD 10·5 years; 6627 [60·8%] of whom were women) had a baseline step 1 screening done, and 5185 (70·4%) of 7367 eligible participants had a 6-month follow-up of step 1 screening. 10 285 (94·3%) participants had a positive intrinsic capacity result during screening at baseline. 958 (9·3%) participants were evaluated with step 2 (in-depth assessments). Positive intrinsic capacity was confirmed in 865 (90·3%) participants. Most recommendations in step 3 (care plan) were related to locomotion, vitality, and cognition. INTERPRETATION: The high number of participants included in our study, as well as the high rates of follow-up, provides evidence to suggest that the large-scale implementation of ICOPE in clinical practice is feasible. The very high prevalence of positive screening for impaired intrinsic capacity during step 1, as well as the high rates of confirmed deficits in intrinsic capacity during step 2, suggest that the INSPIRE ICOPE-CARE programme is able to target individuals who are at increased risk for functional loss and disability. FUNDING: Occitania Regional Health Agency, Region Occitanie and Pyrénées-Méditerranée, European Regional Development Fund, and The Interreg Program V-A Spain-France-Andorra.

Clinically meaningful change for the chair stand test: monitoring mobility in integrated care for older people.

BACKGROUND: Clinically meaningful changes in the five-repetition chair stand test are essential for monitoring mobility in integrated care for older people. Recommendations for the clinically meaningful change of the chair stand test are not well known. Our study aimed to estimate the absolute and relative clinically meaningful changes for older adults' five-repetition chair stand test. METHODS: We applied distribution-based and anchor-based methods in addition to receiver operator characteristics analyses to a population-based study of community-dwelling adults (SAGE Mexico study, n = 897) to derive the clinically meaningful change in the chair stand test. We used three self-reported clinical anchors: moving around, vigorous activities, and walking 1 km. Our primary outcome was the incidence of disability for basic activities of daily living (ADL). Secondly, we examined our estimates of clinically meaningful change in a clinical trial population of healthy volunteers (MAPT, France, study n = 1575) concerning the risk of incident ADL disability. RESULTS: The age of SAGE Mexico participants ranged from 60 to 96 years; mean (SD) = 69.0 (6.2); 54.4% were female. Their baseline chair stand time averaged 12.1 s (SD = 3 s). Forty-eight participants (5.6%) showed incident disability over 3 years. The absolute and relative clinically meaningful change cut points found over 3 years of follow-up were 2.6 s and 27.7%, respectively. Absolute clinically meaningful change ranged from 0.5 to 4.7 s, depending on the estimation method. Relative clinically meaningful change ranged from 9.6 to 46.2%. SAGE Mexico participants with absolute and relative clinically meaningful declines (increasing 2.6 s and 27.7% from baseline time, respectively) showed an increased risk of ADL disability [aRR = 1.93; P = 0.0381; 95% CI (1.05, 3.46) and aRR = 2.27; P = 0.0157; 95% CI (1.22, 4.10)], respectively, compared with those without a clinically meaningful decline. MAPT participants [age range = 70-94; mean (SD) = 75.3 (4.4); 64.8% female; incident ADL disability over 5 years = 145(14.8%)] with a relative clinically meaningful decline (≥27.7% from baseline over 3 years) had a 74% higher risk of incident ADL disability than their counterparts [aHR = 1.74; P = 0.016; CI95% (1.11, 2.72); mean follow-up of 58 months]. CONCLUSIONS: Community-dwelling older adults with an increase of 3 s or 28% in chair stand test performance over 3 years (approximately 1 s or 10% per year) could be the target of interventions to enhance mobility and prevent incident disability.

Screening for intrinsic capacity impairments as markers of increased risk of frailty and disability in the context of integrated care for older people: Secondary analysis of MAPT.

AIM: This longitudinal secondary analysis of the Multidomain Alzheimer Preventive Trial (MAPT) aimed to test whether the Integrated Care for Older People (ICOPE) Step 1 screening tool is able to identify people at risk of developing frailty and disability in basic (ADL) and instrumental (IADL) activities of daily living among community-dwelling older adults. PARTICIPANTS AND SETTING: Seven hundred and fifty-nine (n = 759) non-demented participants of the MAPT aged 70-89 years were assessed in memory clinics in France between 2008 and 2013. METHODS: We measured six intrinsic capacity (IC) impairments, adapted from the ICOPE screening tool. We used Cox models to estimate the adjusted hazard ratios of incident frailty and IADL/ADL disability. Incident frailty was defined by Fried's phenotype, and incident disability was measured according to Lawton and Katz for IADLs and ADLs. RESULTS: Limited mobility (HR= 2.97, 95%CI= 1.85-4.76), depressive symptoms (HR= 2.07, 95%CI= 1.03-4.19), and visual impairment (HR= 1.70, 95%CI 1.01-2.86) were associated with a higher incidence of frailty over 5 years. Each additional IC condition demonstrated a positive association with a higher risk of incident frailty, IADL, ADL disability, with risk increased by 47%, 27%, and 23% over 5 years, respectively. CONCLUSION: Screening for IC impairments identifies older adults at higher risk of incident frailty and incident IADL/ADL disability. It is relevant to screen for these impairments together because the risk of frailty and disability increases with each additional one. ClinicalTrials.gov identifier: NCT00672685.

Prevention of dementia using mobile phone applications (PRODEMOS): protocol for an international randomised controlled trial.

INTRODUCTION: Profiles of high risk for future dementia are well understood and are likely to concern mostly those in low-income and middle-income countries and people at greater disadvantage in high-income countries. Approximately 30%-40% of dementia cases have been estimated to be attributed to modifiable risk factors, including hypertension, smoking and sedentary lifestyle. Tailored interventions targeting these risk factors can potentially prevent or delay the onset of dementia. Mobile health (mHealth) improves accessibility of such prevention strategies in hard-to-reach populations while at the same time tailoring such approaches. In the current study, we will investigate the effectiveness and implementation of a coach-supported mHealth intervention, targeting dementia risk factors, to reduce dementia risk. METHODS AND ANALYSIS: The prevention of dementia using mobile phone applications (PRODEMOS) randomised controlled trial will follow an effectiveness-implementation hybrid design, taking place in the UK and China. People are eligible if they are 55-75 years old, of low socioeconomic status (UK) or from the general population (China); have ≥2 dementia risk factors; and own a smartphone. 2400 participants will be randomised to either a coach-supported, interactive mHealth platform, facilitating self-management of dementia risk factors, or a static control platform. The intervention and follow-up period will be 18 months. The primary effectiveness outcome is change in the previously validated Cardiovascular Risk Factors, Ageing and Incidence of Dementia dementia risk score. The main secondary outcomes include improvement of individual risk factors and cost-effectiveness. Implementation outcomes include acceptability, adoption, feasibility and sustainability of the intervention. ETHICS AND DISSEMINATION: The PRODEMOS trial is sponsored in the UK by the University of Cambridge and is granted ethical approval by the London-Brighton and Sussex Research Ethics Committee (reference: 20/LO/01440). In China, the trial is approved by the medical ethics committees of Capital Medical University, Beijing Tiantan Hospital, Beijing Geriatric Hospital, Chinese People's Liberation Army General Hospital, Taishan Medical University and Xuanwu Hospital. Results will be published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ISRCTN15986016.

Evidence-based prevention of Alzheimer's disease: systematic review and meta-analysis of 243 observational prospective studies and 153 randomised controlled trials.

BACKGROUND: Evidence on preventing Alzheimer's disease (AD) is challenging to interpret due to varying study designs with heterogeneous endpoints and credibility. We completed a systematic review and meta-analysis of current evidence with prospective designs to propose evidence-based suggestions on AD prevention. METHODS: Electronic databases and relevant websites were searched from inception to 1 March 2019. Both observational prospective studies (OPSs) and randomised controlled trials (RCTs) were included. The multivariable-adjusted effect estimates were pooled by random-effects models, with credibility assessment according to its risk of bias, inconsistency and imprecision. Levels of evidence and classes of suggestions were summarised. RESULTS: A total of 44 676 reports were identified, and 243 OPSs and 153 RCTs were eligible for analysis after exclusion based on pre-decided criteria, from which 104 modifiable factors and 11 interventions were included in the meta-analyses. Twenty-one suggestions are proposed based on the consolidated evidence, with Class I suggestions targeting 19 factors: 10 with Level A strong evidence (education, cognitive activity, high body mass index in latelife, hyperhomocysteinaemia, depression, stress, diabetes, head trauma, hypertension in midlife and orthostatic hypotension) and 9 with Level B weaker evidence (obesity in midlife, weight loss in late life, physical exercise, smoking, sleep, cerebrovascular disease, frailty, atrial fibrillation and vitamin C). In contrast, two interventions are not recommended: oestrogen replacement therapy (Level A2) and acetylcholinesterase inhibitors (Level B). INTERPRETATION: Evidence-based suggestions are proposed, offering clinicians and stakeholders current guidance for the prevention of AD.

Meal-related difficulties and weight loss in older people: Longitudinal data from MAPT study.

BACKGROUND: Difficulties with meal-related activities (preparing meals and food shopping) may influence food intake, and contribute to nutritional risk among elderly people. All known studies on this topic had a cross-sectional design, thereby no causal relationships could be derived. We aim to investigate if difficulties with meal-related activities can contribute to subsequent weight loss in community-dwelling older people. METHODS: We used data of older subjects from the MAPT Study (n = 1531, median age = 74 years, 64% women), who provided prospective data on weight every 6 months and cognitive, physical condition, and functional capacities every year during a 3-year period. Difficulties preparing meals and shopping were evaluated each year with the Alzheimer's Disease Cooperative Study-Activities of Daily Living Prevention Instrument (ADCS ADL-PI) Scale. The risk of losing weight (≥5% or ≥ 3 kg in the following year) was estimated using a time-dependent Cox regression model. RESULTS: During the 3-year follow-up, a total of 851 subjects experienced at least a 5% or 3 kg weight loss. Two hundred thirty-seven subjects declared having difficulties with meal preparation at least once, and 133 declared having difficulties shopping. Subjects reporting any meal-related difficulties were older (p < 0.001), had more depressive symptoms (p < 0.001), and a lower physical function (p < 0.001) compared to those without difficulties. They also had a lower cognitive score (preparing meals: p < 0.001; shopping: p = 0.005) and a lower body mass index (preparing meals: p = 0.005; shopping: p = 0.023) at the end of the study. Meal-related activities were not associated with weight loss in unadjusted analysis and after adjustment for sex, age, depression, physical and cognitive status. CONCLUSION: Difficulties preparing meals and shopping had no effect on weight loss in community-dwelling older people, despite their association with advanced age, functional decline, and depressive symptoms.

Systematic Dementia Screening by Multidisciplinary Team Meetings in Nursing Homes for Reducing Emergency Department Transfers: The IDEM Cluster Randomized Clinical Trial.

Importance: Dementia is often underdiagnosed in nursing homes (NHs). This potentially results in inappropriate care, and high rates of emergency department (ED) transfers in particular. Objective: To assess whether systematic dementia screening of NH residents combined with multidisciplinary team meetings resulted in a lower rate of ED transfer at 12 months compared with usual care. Design, Setting, and Participants: Multicenter, cluster randomized trial with NHs as the unit of randomization. The IDEM (Impact of Systematic Tracking of Dementia Cases on the Rate of Hospitalization in Emergency Care Units) trial took place at 64 public and private NHs in France. Recruitment started on May 1, 2010, and was completed on March 31, 2012. Residents who were aged 60 years or older, had no diagnosed or documented dementia, were not bedridden, had lived in the NH for at least 1 month at inclusion, and had a life expectancy greater than 12 months were included. The residents were followed up for 18 months. The main study analyses were completed on October 14, 2016. Intervention: Two parallel groups were compared: an intervention group consisting of NHs that set up 2 multidisciplinary team meetings to identify residents with dementia and to discuss an appropriate care plan, and a control group consisting of NHs that continued their usual practice. During the inclusion period of 23 months, all residents of participating NHs who met eligibility criteria were included in the study. Main Outcomes and Measures: The primary end point (ED transfer) was analyzed at 12 months, but the residents included were followed up for 18 months. Results: A total of 64 NHs participated in the study and enrolled 1428 residents (mean [SD] age, 84.7 [8.1] years; 1019 [71.3%] female): 599 in the intervention group (32 NHs) and 829 in the control group (32 NHs). The final study visit was completed by 1042 residents (73.0%). The main reason for early discontinuation was death (318 residents [22.7%]). The intervention did not reduce the risk of ED transfers during the 12-month follow-up: the proportion of residents transferred at least once to an ED during the 12-month follow-up was 16.2% in the intervention group vs 12.8% in the control group (odds ratio, 1.32; 95% CI, 0.83-2.09; P = .24). Conclusions and Relevance: This study failed to demonstrate that systematic screening for dementia in NHs resulted in fewer ED transfers. The findings do not support implementation of multidisciplinary team meetings for systematic dementia screening of all NH residents, beyond the national recommendations for dementia diagnosis, to reduce ED transfers. Trial Registration: ClinicalTrials.gov Identifier: NCT01569997.

Absence of Relationship Between Self-Reported Sleep Measures and Amyloid Load in Elderly Subjects.

Objective: To determine the relationships between self-reported sleep profile and cortical amyloid load in elderly subjects without dementia. Methods: This cross-sectional study included 143 community-dwelling participants aged ≥70 years (median: 73 years [70-85]; 87 females) with spontaneous memory complaints but dementia-free. Sociodemographic characteristics, health status, neuropsychological tests, sleep, and 18F-florbetapir (amyloid) PET data were collected. The clinical sleep interview evaluated nighttime sleep duration, but also daytime sleep duration, presence of naps, and restless leg syndrome (RLS) at time of study. Validated questionnaires assessed daytime sleepiness, insomnia, and risk of sleep apnea. The cortical standardized uptake value ratio (SUVr) was computed across six cortical regions. The relationship between sleep parameters and SUVr (cut-off ratio>1.17 and tertiles) was analyzed using logistic regression models. Results: Amyloid-PET was positive in 40.6% of participants. Almost 40% were at risk for apnea, 13.5% had RLS, 35.5% insomnia symptoms, 22.1% daytime sleepiness, and 18.8% took sleep drugs. No significant relationship was found between positive amyloid PET and nighttime sleep duration (as a continuous variable, or categorized into <6; 6-7; ≥7 h per night). Logistic regression models did not show any association between SUVr and daytime sleep duration, 24-h sleep duration, naps, RLS, daytime sleepiness, insomnia symptoms, and sleep apnea risk (before and after adjustment for APOEε4 and depressive symptoms). Conclusion: Our study did not confirm the association between amyloid-PET burden, poor sleep quantity/quality in elderly population, suggesting that the interplay between sleep, and amyloid is more complex than described.

Effect of Long-Term Omega 3 Polyunsaturated Fatty Acid Supplementation with or without Multidomain Lifestyle Intervention on Muscle Strength in Older Adults: Secondary Analysis of the Multidomain Alzheimer Preventive Trial (MAPT).

BACKGROUND: The benefits of long-term omega 3 polyunsaturated fatty acid (ω3-PUFA) supplementation on muscle strength in older adults remains to be investigated. OBJECTIVES: We assessed the effect of ω3-PUFA supplementation and a multidomain (physical activity, cognitive training, and nutritional advice), alone or in combination, compared with placebo, on muscle strength. We also hypothesized that ω3-PUFA supplementation resulted in additional benefit in participants with a low docosahexaenoic acid (DHA)/eicosapentaenoic acid (EPA) erythrocyte level at baseline and high adherence to the multidomain intervention sessions. DESIGN: We performed secondary analyses of the Multidomain Alzheimer Preventive Trial (MAPT), a 3-year, multicenter, randomized, placebo-controlled trial with four parallel groups. Participants were non-demented, aged 70 years or older. They were recruited in 13 memory clinics in France and Monaco between 30 May 2008 and 24 February 2011. Participants were randomly assigned to either ω3-PUFA alone (two capsules a day providing a total daily dose of 800 mg DHA and 225 mg EPA), ω3-PUFA plus the multidomain intervention (43 group sessions integrating advice for physical activity (PA), and nutrition, cognitive training, and three preventive consultations), the multidomain intervention plus placebo, or placebo alone. Our primary outcome was the change from baseline to 36 months of the muscle strength assessed with the repeated chair stand test and handgrip strength. RESULTS: A total of 1680 participants (75.34 years ± 4.42) were randomized. In the modified intention-to-treat population (n = 1679), no significant differences at 3-year follow-up were observed in the repeated chair stand test score between any of the three intervention groups and the placebo group. The between-group differences compared with placebo were -0.05388 (-0.6800 to 0.5723; Standard Error, SE = 0.3192; p = 0.8660) for the ω3-PUFA group, -0.3936 (-1.0217 to 0.2345; SE = 0.3180; p = 0.2192) for the multidomain intervention plus placebo group, and -0.6017 (-1.2255 to 0.02222; SE = 0.2092; p = 0.3202) for the combined intervention group. No significant effect was also found for the handgrip strength. Sensitivity analyses performed among participants with low (DHA+EPA) erythrocyte level at baseline (first quartile vs. others) or highly adherent participants (≥75% of the multidomain intervention sessions) revealed similar results. CONCLUSION: Low dose ω3-PUFA supplementation, either alone or in combination with a multidomain lifestyle intervention comprising physical activity counselling, had no significant effects on muscle strength over 3 years in elderly people.

Adherence to multidomain interventions for dementia prevention: Data from the FINGER and MAPT trials.

INTRODUCTION: Multidomain interventions, targeting multiple risk factors simultaneously, could be effective dementia prevention strategies, but may be burdensome and not universally acceptable. METHODS: We studied adherence rates and predictors in the Finnish Geriatric Intervevntion Study to Prevent Cognitive Impairment and Disability and Multidomain Alzheimer Preventive Trial prevention trials, for all intervention components (separately and simultaneously). Finnish Geriatric Intervevntion Study to Prevent Cognitive Impairment and Disability participants received a 2-year multidomain lifestyle intervention (physical training, cognitive training, nutritional counseling, and cardiovascular monitoring). Multidomain Alzheimer Preventive Trial participants received a 3-year multidomain lifestyle intervention (cognitive training, physical activity counseling, and nutritional counseling) with either an omega-3 supplement or placebo. RESULTS: Adherence decreased with increasing intervention complexity and intensity: it was highest for cardiovascular monitoring, nutritional counseling, and the omega-3 supplement, and lowest for unsupervised computer-based cognitive training. The most consistent baseline predictors of adherence were smoking and depressive symptoms. DISCUSSION: Reducing participant burden, while ensuring that technological tools are suitable for older individuals, maintaining face-to-face contacts, and taking into account participant characteristics may increase adherence in future trials.

Factors associated with changes of the frailty status after age 70: Findings in the MAPT study.

PURPOSE: Frailty has become a major issue in the prevention of functional decline and disability in aged populations. Using repeated measurements of frailty over 3 years, this work aimed to describe transitions between frailty states and associated factors. METHODS: This study used the data from the Multidomain Alzheimer Preventive Trial and included the 842 participants aged 70 and over who did not receive the multidomain intervention. Frailty was assessed using the phenotype proposed by Fried et al. at baseline and at 6, 12, 24, and 36 months. Factors influencing the transitions across frailty states were examined using multistate modeling. RESULTS: The study population included 548 women and 294 men, mean age 75.4 ± 4.5 years. At baseline, 430 (53%) participants were nonfrail, 349 (43%) prefrail, and 28 (4%) frail. A total of 2271 pairs of consecutive measurements of frailty status were available over the 3 years of follow-up, with no change in frailty status in 1548 of them (68%), a worsening of frailty status in 426 of them (19%), and an improvement in frailty status in the remaining 297 (13%). Polypharmacy (i.e., ≥6 drugs) and probable depression were associated with incident prefrailty. Female gender was systematically associated with a lower probability of recovering from prefrailty and frailty. Older age, overweight, comorbidity, and abnormal C-reactive protein also reduced the probability of recovery from frailty or prefrailty. CONCLUSIONS: This study sheds light on factors that should be further investigated in future research to help the prevention and management of frailty.

Lifestyle multidomain intervention, omega-3 supplementation, or both for reducing the risk of developing clinically relevant depressive symptoms in older adults with memory complaints? Secondary analysis from the MAPT trial.

BACKGROUND: We tested the associations of a lifestyle multidomain intervention (MI), omega-3 supplementation (O3) or their combination with the change of clinically meaningful depressive symptoms in older adults. METHODS: Secondary analysis of the 3-year Multidomain Alzheimer Preventive Trial (MAPT), in which 1679 people, ≥70 years with memory complaints were randomized into: MI, O3, MI + O3, or placebo. MI was composed of nutritional and physical activity counselling and cognitive training. O3 supplementation corresponded to a daily dose of 1000 mg of omega-3. Discrete-time cox regressions were performed for each outcome. Three binary variables of incidence of depressive symptoms were created from the 15-item geriatric depression scale (GDS-15): minimum clinically meaningful depressive symptoms (≥2-point increase in GDS-15), moderate depressive symptoms (GDS-15 ≥ 5), and severe depressive symptoms (GDS-15 ≥ 10) DS. RESULTS: Discrete-time cox proportional hazards have found no associations for all of the analysis. The incidence of severe depressive symptoms across groups were, respectively: 1.1, 2.4, 2.3 and 2.5 per 100 person year for MI + O3, for O3, for MI, for placebo. There was a trend for a decreased risk of developing severe DS compared to placebo in the MI + O3 group (p = 0.085 after adjustment). CONCLUSIONS: To conclude, we did not find any association of a lifestyle multidomain intervention with the onset of clinically depressive symptoms in older adults with memory complaints. A study with a more intensive multidomain intervention might bring further insights on this topic.

Designing an Internet-Based Multidomain Intervention for the Prevention of Cardiovascular Disease and Cognitive Impairment in Older Adults: The HATICE Trial.

BACKGROUND: Many dementia and cardiovascular disease (CVD) cases in older adults are attributable to modifiable vascular and lifestyle-related risk factors, providing opportunities for prevention. In the Healthy Aging Through Internet Counselling in the Elderly (HATICE) randomized controlled trial, an internet-based multidomain intervention is being tested to improve the cardiovascular risk (CVR) profile of older adults. OBJECTIVE: To design a multidomain intervention to improve CVR, based on the guidelines for CVR management, and administered through a coach-supported, interactive, platform to over 2500 community-dwellers aged 65+ in three European countries. METHODS: A comparative analysis of national and European guidelines for primary and secondary CVD prevention was performed. Results were used to define the content of the intervention. RESULTS: The intervention design focused on promoting awareness and self-management of hypertension, dyslipidemia, diabetes mellitus, and overweight, and supporting smoking cessation, physical activity, and healthy diet. Overall, available guidelines lacked specific recommendations for CVR management in older adults. The comparative analysis of the guidelines showed general consistency for lifestyle-related recommendations. Key differences, identified mostly in methods used to assess the overall CVR, did not hamper the intervention design. Minor country-specific adaptations were implemented to maximize the intervention feasibility in each country. CONCLUSION: Despite differences in CVR management within the countries considered, it was possible to design and implement the HATICE multidomain intervention. The study can help define preventative strategies for dementia and CVD that are applicable internationally.

Effects of multidomain lifestyle intervention, omega-3 supplementation or their combination on physical activity levels in older adults: secondary analysis of the Multidomain Alzheimer Preventive Trial (MAPT) randomised controlled trial.

Background/objectives: to investigate the effects of a 3-year multidomain lifestyle intervention, omega-3 supplementation or both on physical activity (PA) in older adults with subjective memory complaints. Design/settings/subjects: the Multidomain Alzheimer Preventive Trial was a 3-year randomised controlled trial that enroled 1,680 community-dwelling adults aged 70 years or over, with subjective memory complaints. Participants were randomised to omega-3 supplementation (total daily dose of 800 mg docosahexanoic acid and up to 225 mg eicosapentanoic acid), multidomain intervention (nutritional and exercise counselling and cognitive training), omega-3 plus multidomain intervention or placebo with usual care. Methods: PA was assessed using a self-reported questionnaire. From this, global moderate-to-vigorous PA, leisure-time PA, non-leisure-time PA and light PA were measured in metabolic equivalent tasks-minutes per week (MET-min/week). Results: in the multidomain groups, participants significantly increased their moderate-to-vigorous and leisure-time PA at 6 months (≥300 MET-min/week for both in the multidomain groups; P ≤ 0.002) before returning to baseline by the end of the trial. Activity in the placebo/usual care and omega-3/usual care groups declined overtime. Between-group differences remained significant for both multidomain groups for leisure-time physical activity at 2- and 3-year follow-ups. Compared to placebo/usual care, interventions had no significant effects on non-leisure-time PA and light PA. Omega-3 supplementation alone had no effects on PA. Conclusions: a multidomain intervention focused on cognitive training, and nutritional and PA counselling increased PA in the short-term and limited its decline in the long-term among older adults with memory complaints. ClinicalTrials.gov-Registration number: NCT0067268.

Using Poisson-gamma model to evaluate the duration of recruitment process when historical trials are available.

At the design of clinical trial operation, a question of a paramount interest is how long it takes to recruit a given number of patients. Modelling the recruitment dynamics is the necessary step to answer this question. Poisson-gamma model provides very convenient, flexible and realistic approach. This model allows predicting the trial duration using data collected at an interim time with very good accuracy. A natural question arises: how to evaluate the parameters of recruitment model before the trial begins? The question is harder to handle as there are no recruitment data available for this trial. However, if there exist similar completed trials, it is appealing to use data from these trials to investigate feasibility of the recruitment process. In this paper, the authors explore the recruitment data of two similar clinical trials (Intergroupe Francais du Myélome 2005 and 2009). It is shown that the natural idea of plugging the historical rates estimated from the completed trial in the same centres of the new trial for predicting recruitment is not a relevant strategy. In contrast, using the parameters of a gamma distribution of the rates estimated from the completed trial in the recruitment dynamic model of the new trial provides reasonable predictive properties with relevant confidence intervals. Copyright © 2017 John Wiley & Sons, Ltd.