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.

Plasma p-tau181 as an outcome and predictor of multidomain intervention effects: a secondary analysis of a randomised, controlled, dementia prevention trial.

BACKGROUND: It is unknown whether multidomain interventions, which might preserve late-life cognition, affect Alzheimer's disease pathology. Previous studies measured cerebrospinal fluid and imaging Alzheimer's disease biomarkers in small subsamples of multidomain trial participants. Newly developed assays enable the measurement of blood-based Alzheimer's disease biomarkers in larger samples. We aimed to assess whether plasma tau phosphorylated at threonine 181 (p-tau181) was able to detect or predict 3-year multidomain intervention effects. METHODS: This is a secondary analysis of the randomised, controlled, Multidomain Alzheimer Prevention Trial (MAPT) testing a 3-year multidomain intervention, omega-3 fatty acid supplementation, or both versus placebo, in individuals aged 70 years and older in 13 memory centres in France and Monaco. Plasma p-tau181 was measured in stored blood samples in a subsample of 527 participants on an intention-to-treat basis. Changes in cognitive score were calculated as a composite measure using the average of Z scores for the following tests: Mini Mental State Examination orientation items, Free and Cued Selective Reminding Test (sum of free and total recall scores), category fluency, and Digit Symbol Substitution Test. Intervention effects on 3-year change in p-tau181 concentration were estimated by use of a linear mixed model with centre-specific random intercepts. FINDINGS: Recruitment took place between May 30, 2008, and Feb 24, 2011. Median baseline plasma p-tau181 was 8·8 pg/mL (IQR 6·7-11·9) in the total sample, and significantly higher in older individuals, men, APOE ε4 carriers, and participants with renal dysfunction or a positive PET amyloid scan. During 3-year follow-up, individuals with raised baseline p-tau181 underwent greater cognitive decline (eg, mean difference in 3-year change on the composite cognitive score between control group participants with normal and abnormal baseline levels of p-tau was -0·34 [effect size -0·52; 95% CI -0·61 to 0·07] in the fully adjusted model using a 12·4 pg/mL cutoff for abnormal baseline p-tau181), but there were no intervention effects on change in p-tau181 either in this subgroup or the total population, and no effect on cognitive change in individuals with raised baseline p-tau181 (eg, in the fully adjusted model using the 12·4 pg/mL cutoff for p-tau181 abnormality, the mean difference [95% CI] in this subgroup in 3-year decline on the composite cognitive score between the control group and the multidomain + omega-3 group, the omega-3 group, and the multidomain intervention group, was, respectively: 0·13 [-0·21 to 0·47], 0·03 [-0·30 to 0·36], and 0·10 [-0·26 to 0·46]). Surprisingly, individuals with raised baseline p-tau181 showed a decrease in p-tau181 during follow-up (eg, unadjusted mean [95% CI] 3-year change was -3·01 pg/mL (-4·45 to -1·56) in control group subjects with abnormal baseline p-tau181 [using the 12·4 pg/mL abnormal p-tau cutoff]). INTERPRETATION: Our results support the utility of p-tau181 as a prognostic biomarker, but it did not predict or detect intervention effects in this study. Further investigation of its usefulness as a prevention trial outcome measure is required. FUNDING: Toulouse Gérontopôle, French Ministry of Health and Pierre Fabre Research Institute.

Exploring Predictive Factors for Potentially Avoidable Emergency Department Transfers: Findings From the FINE Study.

OBJECTIVES: To assess the prevalence of potentially avoidable transfers (PAT) and identify factors associated with these transfers to emergency departments (EDs) among nursing home (NH) residents. DESIGN: This is a secondary outcome analysis of the FINE study, a multicenter observational study collecting data on NH residents, NH settings, and contextual factors of ED transfers. SETTINGS AND PARTICIPANTS: NHs in the former Midi-Pyrénées region of the southwest of France (n = 312); a total of 1037 NH residents who experienced ED transfers (n = 1017) between January 2016 and December 2016. METHODS: The analysis included resident baseline characteristics and NH and transfer decision-making characteristics. An expert group categorized the transfer status as either PAT or unavoidable. Multivariable analysis using a mixed logistic model, accounting for intra-NH correlation, was conducted to assess factors independently associated with PAT. RESULTS: Among 1017 included transfers, 87.02% (n = 885) were identified as PAT and 12.98% (n = 132) unavoidable transfers. Multivariable analysis revealed that the following patient-related factors were associated with a likely high rate of PAT: usual behavior disturbances before transfer, including productive trouble (OR 2.04, 95% CI 1.25-3.33; P = .0044) and unusual symptom of falling during the week preceding the transfer (OR 4.55, 95% CI 1.76-11.82; P = .0019). On the other hand, distance between ED and NH (OR 0.98, 95% CI 0.97-0.998; P = .0231), NH staff trained in palliative care in the last 3 years (OR 0.52, 95% CI 0.29-0.95; P = .0324), the impossibility of direct hospitalization to an appropriate unit (OR 0.54, 95% CI 0.34-0.87; P = .0117), and the resident Charlson Comorbidity Index (OR 0.90, 95% CI 0.82-0.99; P = .0369) were associated with a lower probability of PAT. CONCLUSION AND IMPLICATIONS: Transfers from NHs to hospital EDs were frequently potentially avoidable, meaning that there are still significant opportunities to reduce PAT. Our findings may help to specifically identify interventions that should be targeted at both NH and resident levels.

Cognitive impact of multidomain intervention and omega 3 according to blood Aß42/40 ratio: a subgroup analysis from the randomized MAPT trial.

BACKGROUND: In MAPT (Multidomain Alzheimer Preventive Trial), a cognitive effect of multidomain intervention (MI) was showed in non-demented subjects with positive amyloid PET. However, screening eligible patients for multidomain intervention by PET is difficult to generalize in real-world settings. METHODS: MAPT study was a 3-year, randomized, placebo-controlled trial followed by a 2-year observational and optional extension. All participants were non-demented and randomly assigned (1:1:1:1) to the MI plus omega 3, MI plus placebo, omega 3 alone, or placebo alone group. The objectives were to assess the cognitive effect of MAPT interventions (omega 3 supplementation, MI, combined intervention) in non-demented subjects according to amyloid blood status at 12, 36, and 60 months. In this subgroup analysis (n = 483), amyloid status was defined by plasma Aß42/40 ratio (cutoff ≤ 0.0107). The primary outcome measure was the change in cognitive composite score after a 1, 3, and 5-year clinical follow-up. RESULTS: The intention-to-treat (ITT) population included 483 subjects (161 positive and 322 negative amyloid participants based on plasma Aß42/40 ratio). In the positive amyloid ITT population, we showed a positive effect of MI plus omega 3 on the change in composite cognitive score in 12 (raw p = .0350, 0.01917, 95% CI = [0.0136 to 0.3699]) and 36 months (raw p = .0357, 0.2818, 95% CI = [0.0190 to 0.5446]). After correction of multiple comparisons and adjustments, these differences were not significant (adjusted p = .1144 and .0690). In the per-protocol positive amyloid group (n = 154), we observed a significant difference between the combined intervention and placebo groups at 12 (p = .0313, 0.2424, 0.0571 to 0.4276) and 36 months (p = .0195, 0.3747, 0.1055 to 0.6439) persisting after adjustment. In the ITT and per-protocol analyses, no cognitive effect was observed in the positive and negative amyloid group at 60-month visit. CONCLUSIONS: These findings suggest a benefit of MI plus omega 3 in positive blood amyloid subjects. This promising trend needs to be confirmed before using blood biomarkers for screening in preventive trials. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01513252 .

A 1-year randomized controlled trial of a nutritional blend to improve nutritional biomarkers and prevent cognitive decline among community-dwelling older adults: The Nolan Study.

Introduction: This study aimed to test the efficacy of a nutritional blend (NB) in improving nutritional biomarkers and preventing cognitive decline among older adults. Methods: A 1-year randomized, double-blind, multicenter, placebo-controlled trial with 362 adults (58.6% female, mean 78.3 years, SD = 4.8) receiving an NB or placebo. Erythrocyte ω-3 index and homocysteine concentrations were primary outcomes. Other outcomes included Patient-Reported Outcomes Measurement Information System (PROMIS) Applied Cognition-Abilities, composite cognitive score (CCS), Cognitive Function Instrument (CFI) self-assessment and study partner, hippocampal volume (HV), and Alzheimer's disease signature cortical thickness (CT). Results: A total of 305 subjects completed the follow-up. Supplementation increased ω-3 index and decreased homocysteine, but did not affect CCS, CFI self-assessment, HV, and CT. Placebo improved and treatment did not change PROMIS at 1 month. Intervention showed a positive effect on CFI study partner. Discussion: Although improving nutritional biomarkers, this 1-year trial with a multi-nutrient novel approach was not able to show effects on cognitive outcomes among older adults.

Associations of erythrocyte omega-3 fatty acids with cognition, brain imaging and biomarkers in the Alzheimer's disease neuroimaging initiative: cross-sectional and longitudinal retrospective analyses.

BACKGROUND: The association between omega-3 (ω-3) PUFAs and cognition, brain imaging and biomarkers is still not fully established. OBJECTIVES: The aim was to analyze the cross-sectional and retrospective longitudinal associations between erythrocyte ω-3 index and cognition, brain imaging, and biomarkers among older adults. METHODS: A total of 832 Alzheimer's Disease Neuroimaging Initiative 3 (ADNI-3) participants, with a mean (SD) age of 74.0 (7.9) y, 50.8% female, 55.9% cognitively normal, 32.7% with mild cognitive impairment, and 11.4% with Alzheimer disease (AD) were included. A low ω-3 index (%EPA + %DHA) was defined as the lowest quartile (≤3.70%). Cognitive tests [composite score, AD Assessment Scale Cognitive (ADAS-Cog), Wechsler Memory Scale (WMS), Trail Making Test, Category Fluency, Mini-Mental State Examination, Montreal Cognitive Assessment] and brain variables [hippocampal volume, white matter hyperintensities (WMHs), positron emission tomography (PET) amyloid-ß (Aß) and tau] were considered as outcomes in regression models. RESULTS: Low ω-3 index was not associated with cognition, hippocampal, and WMH volume or brain Aß and tau after adjustment for demographics, ApoEε4, cardiovascular disease, BMI, and total intracranial volume in the cross-sectional analysis. In the retrospective analysis, low ω-3 index was associated with greater Aß accumulation (adjusted ß = 0.02; 95% CI: 0.01, 0.03; P = 0.003). The composite cognitive score did not differ between groups; however, low ω-3 index was significantly associated with greater WMS-delayed recall cognitive decline (adjusted ß = -1.18; 95% CI: -2.16, -0.19; P = 0.019), but unexpectedly lower total ADAS-Cog cognitive decline. Low ω-3 index was cross-sectionally associated with lower WMS performance (adjusted ß = -1.81, SE = 0.73, P = 0.014) and higher tau accumulation among ApoE ε4 carriers. CONCLUSIONS: Longitudinally, low ω-3 index was associated with greater Aß accumulation and WMS cognitive decline but unexpectedly with lower total ADAS-Cog cognitive decline. Although no associations were cross-sectionally found in the whole population, low ω-3 index was associated with lower WMS cognition and higher tau accumulation among ApoE ε4 carriers. The Alzheimer's Disease Neuroimaging Initiative (ADNI) is registered at clinicaltrials.gov as NCT00106899.

Association between urate-lowering therapies and cognitive decline in community-dwelling older adults.

Long-term use of urate-lowering therapies (ULT) may reduce inflammaging and thus prevent cognitive decline during aging. This article examined the association between long-term use of ULT and cognitive decline among community-dwelling older adults with spontaneous memory complaints. We performed a secondary observational analysis using data of 1673 participants ≥ 70 years old from the Multidomain Alzheimer Preventive Trial (MAPT Study), a randomized controlled trial assessing the effect of a multidomain intervention, the administration of polyunsaturated fatty acids (PUFA), both, or placebo on cognitive decline. We compared cognitive decline during the 5-year follow-up between three groups according to ULT (i.e. allopurinol and febuxostat) use: participants treated with ULT during at least 75% of the study period (PT ≥ 75; n = 51), less than 75% (PT < 75; n = 31), and non-treated participants (PNT; n = 1591). Cognitive function (measured by a composite score) was assessed at baseline, 6 months and every year for 5 years. Linear mixed models were performed and results were adjusted for age, sex, body mass index (BMI), diagnosis of arterial hypertension or diabetes, baseline composite cognitive score, and MAPT intervention groups. After the 5-year follow-up, only non-treated participants presented a significant decline in the cognitive composite score (mean change - 0.173, 95%CI - 0.212 to - 0.135; p < 0.0001). However, there were no differences in change of the composite cognitive score between groups (adjusted between-group difference for PT ≥ 75 vs. PNT: 0.144, 95%CI - 0.075 to 0.363, p = 0.196; PT < 75 vs. PNT: 0.103, 95%CI - 0.148 to 0.353, p = 0.421). Use of ULT was not associated with reduced cognitive decline over a 5-year follow-up among community-dwelling older adults at risk of dementia.

Predictors of nursing home placement at 2 years in Alzheimer's disease: A follow-up survey from the THERAD study.

OBJECTIVES: Nursing Home Placement (NHP) can prove to be the only solution to some dead-end situations in Alzheimer's disease (AD). The predictors of NHP are known and can be related to either the person with dementia or his/her caregiver. We aimed to identify predictors of NHP among people with AD over a 2-year follow-up period, with a particular interest in the modifiable predictors, notably those involving caregivers. METHODS: We studied data from the THERAD study, a French monocentric randomized controlled trial, involving 196 community-dwelling dyads, primarily assessing an educational intervention in AD. We performed a bivariate analysis followed by a multivariate Cox model, with a backward stepwise procedure. RESULTS: The mean age of the patients was 82 years old, 67.7% were women and 56.9% were living with a partner. The mean age of the caregivers was 65.8 years old, 64.6% were women and half were spouses of the patients with a moderate burden. During the follow-up, 23 patients died and 49 were institutionalized. The majority of NHPs occurred during the first year (35 NHP). The mean time to NHP was 27.77 months after the diagnosis. Five independent predictors of NHP were found: a higher patient education level (aHR 6.31; CI95% = 1.88-21.22), a high caregiver Burden (aHR 3.97; CI95% = 1.33-11.85), the caregiver being the offspring of the patient (aHR 2.92; CI95% = 1.43-5.95), loss of autonomy (aHR 2.75; CI95% = 1.13-6.65) and disinhibition as a behavioural and psychological symptoms of dementia (BPSD) (aHR 2.38; CI95% = 1.26-4.47). CONCLUSIONS: Our data are in accordance with the literature in identifying loss of autonomy, burden and BPSD (disinhibition) as risk factors of NHP. We also found high patient education level and status of offspring caregiver as additional factors. It is essential to take into account the caregiver status when designing psychoeducational trials aiming to delay NHP. Further studies need to take into account both the modifiable risk factors related to the patient (productive BPSD) and the needs of offspring caregivers (work-life balance, mental load).

Impact of an educational programme on Alzheimer's disease patients' quality of life: results of the randomized controlled trial THERAD.

BACKGROUND: Although educational interventions are recommended in Alzheimer's disease (AD), studies assessing the impact of interventions such as "therapeutic patient education" are scarce. Indeed, the intrinsic nature of the disease is considered a barrier to patients' involvement in such approaches. We aimed to evaluate an intervention by using a "dyadic" approach (patient and caregiver) in both intervention and assessment. METHODS: THERAD is a monocentric, randomized, controlled trial assessing the effects of a 2-month educational programme in mild to moderately severe AD patients among 98 dyads (caregiver/patient) on caregiver-reported patient quality of life (QOL) at 2 months. Community-dwelling patients and their caregivers were recruited in ambulatory units of the French Toulouse University Hospital. Self-reported patient QOL, autonomy, behavioural and psychological symptoms and caregiver QOL and burden were collected at 2, 6 and 12 months. Linear mixed models were used in modified intention-to-treat populations. We also performed sensitivity analysis. RESULTS: A total of 196 dyads were included, 98 in each group. The mean age of the patients was 82 years, 67.7% were women, diagnosed with AD (+/- cerebrovascular component) (mean MMSE =17.6), and 56.9% lived with a partner. The mean age of the caregivers was 65.7 years, and 64.6% were women (52.3% offspring/42.6% spouses), with a moderate burden (mean Zarit score = 30.9). The mean caregiver-reported patient QOL was lower than the self-reported QOL (28.61 vs. 33.96). We did not identify any significant difference in caregiver-reported patients' QOL (p = 0.297) at 2 months, but there was a significant difference in self-reported patients' QOL at 2 months (p = 0.0483) or 6 months (p = 0.0154). No significant difference was found for the secondary outcomes. The results were stable in the sensitivity analyses. CONCLUSIONS: This randomized controlled trial assessing an educational intervention in 196 dyads (Alzheimer's disease affected patient/caregiver) highlights the need to better consider the patient's point of view, since only the self-reported QOL was improved. Additional studies using this dyadic approach are necessary in targeted subpopulations of caregivers (spouse vs. child, gender) and of patients (severity of cognitive impairment or behavioural disturbances) TRIAL REGISTRATION: THERAD study NCT01796314 . Registered on February 19, 2013.

Agitation in Alzheimer's disease: Novel outcome measures reflecting the International Psychogeriatric Association (IPA) agitation criteria.

INTRODUCTION: The 2017 European Union-North American Clinical Trials in Alzheimer's Disease Task Force recommended development of clinician-rated primary outcome measures for Alzheimer's disease (AD) agitation trials, incorporating International Psychogeriatric Association (IPA) criteria. METHODS: In a modified Delphi process, Cohen-Mansfield Agitation Inventory (CMAI) and Neuropsychiatric Inventory-Clinician (NPI-C) items were mapped to IPA agitation domains generating novel instruments, CMAI-IPA and NPI-C-IPA. Validation in the Agitation and Aggression AD Cohort (A3C) assessed minimal clinically important differences (MCIDs), change sensitivity, and predictive validity. RESULTS: MCID was -17 (odds ratio [OR] = 14.9, 95% confidence interval [CI] = 6.8-32.6) for CMAI; -5 (OR = 9.3, 95% CI = 4.0-21.2) for CMAI-IPA; -3 (OR = 11.9, 95% CI = 4.1-34.8) for NPI-C-A+A; and -5 (OR = 7.8, 95% CI = 3.4-17.9) for NPI-C-IPA at 3 months. Areas under the curve suggested no scale better predicted global clinician ratings. Sensitivity to change for all measures was high. CONCLUSION: Internal consistency and reliability analyses demonstrated better accuracy for the NPI-C-IPA than for the CMAI-IPA and can be used for agitation clinical trial inclusion, and for response to intervention.

Factors Associated with Potentially Inappropriate Transfer to the Emergency Department among Nursing Home Residents.

OBJECTIVES: To determine the factors associated with the potentially inappropriate transfer of nursing home (NH) residents to emergency departments (EDs) and to compare hospitalization costs before and after transfer of individuals addressed inappropriately vs those addressed appropriately. DESIGN: Multicenter, observational, case-control study. SETTING AND PARTICIPANTS: 17 hospitals in France, 1037 NH residents. MEASURES: All NH residents transferred to the 17 public hospitals' EDs in southern France were systematically included for 1 week per season. An expert panel composed of family physicians, emergency physicians, geriatricians, and pharmacists defined whether the transfer was potentially inappropriate or appropriate. Residents' and NHs' characteristics and contextual factors were entered into a mixed logistic regression to determine factors associated independently with potentially inappropriate transfers. Hospital costs were collected in the national health insurance claims database for the 6 months before and after the transfer. RESULTS: A total of 1037 NH residents (mean age 87.2 ± 7.1, 68% female) were transferred to the ED; 220 (21%) transfers were considered potentially inappropriate. After adjustment, anorexia [odds ratio (OR) 2.41, 95% confidence interval (CI) 1.57-3.71], high level of disability (OR 0.90, 95% CI 0.81-0.99), and inability to receive prompt medical advice (OR 1.67, 95% CI 1.20-2.32) were significantly associated with increased likelihood of potentially inappropriate transfers. The existence of an Alzheimer's disease special care unit in the NH (OR 0.66, 95% CI 0.48-0.92), NH staff trained on advance directives (OR 0.61, 95% CI 0.41-0.89), and calling the SAMU (mobile emergency medical unit) (OR 0.47, 95% CI 0.34-0.66) were significantly associated with a lower probability of potentially inappropriate transfer. Although the 6-month hospitalization costs prior to transfer were higher among potentially inappropriate transfers compared with appropriate transfers (€6694 and €4894, respectively), transfer appropriateness was not significantly associated with hospital costs. CONCLUSIONS AND IMPLICATIONS: Transfers from NHs to hospital EDs were frequently appropriate. Transfer appropriateness was conditioned by NH staff training, access to specialists' medical advice, and calling the SAMU before making transfer decisions. TRIAL REGISTRATION: clinicaltrials.gov, NCT02677272.

The impact of a multi-domain intervention on cerebral glucose metabolism: analysis from the randomized ancillary FDG PET MAPT trial.

BACKGROUND: The Multidomain Alzheimer Preventive Trial (MAPT) was designed to assess the efficacy of omega-3 fatty acid supplementation, multidomain intervention (MI), or a combination of both on cognition. Although the MAPT study was negative, an effect of MI in maintaining cognitive functions compared to placebo group was showed in positive amyloid subjects. A FDG PET study (MAPT-NI) was implemented to test the impact of MI on brain glucose metabolism. METHODS: MAPT-NI was a randomized, controlled parallel-group single-center study, exploring the effect of MI on brain glucose metabolism. Participants were non-demented and had memory complaints, limitation in one instrumental activity of daily living, or slow gait. Participants were randomly assigned (1:1) to "MI group" or "No MI group." The MI consisted of group sessions focusing on 3 domains: cognitive stimulation, physical activity, nutrition, and a preventive consultation. [18F]FDG PET scans were performed at baseline, 6 months, and 12 months, and cerebral magnetic resonance imaging scans at baseline. The primary objective was to evaluate the MI effect on brain glucose metabolism assessed by [18F]FDG PET imaging at 6 months. The primary outcome was the quantification of regional metabolism rate for glucose in cerebral regions involved early in Alzheimer disease by relative semi-quantitative SUVr (FDG-based AD biomarker). An exploratory voxel-wise analysis was performed to assess the effect of MI on brain glucose metabolism without anatomical hypothesis. RESULTS: The intention-to-treat population included 67 subjects (34 in the MI group and 33 in the No MI group. No significant MI effect was observed on primary outcome at 6 months. In the exploratory voxel-wise analysis, we observed a difference in favor of MI group on the change of cerebral glucose metabolism in limbic lobe (right hippocampus, right posterior cingulate, left posterior parahippocampal gyrus) at 6 months. CONCLUSIONS: MI failed to show an effect on metabolism in FDG-based AD biomarker, but exploratory analysis suggested positive effect on limbic system metabolism. This finding could suggest a delay effect of MI on AD progression. TRIAL REGISTRATION: ClinicalTrials.gov Identifier, NCT01513252 .

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.

Multidomain intervention and/or omega-3 in nondemented elderly subjects according to amyloid status.

INTRODUCTION: The Multidomain Alzheimer Preventive Trial (MAPT) assessed the efficacy of omega-3 fatty acid supplementation, a multidomain intervention (MI), or a combination of both on cognition. Impact according to cerebral amyloid status was evaluated by PET scan. METHODS: Participants were nondemented and had memory complaints, limitation in one instrumental activity of daily living, or slow gait. The primary outcome was a change from baseline in 36 months measured with a cognitive composite Z score. RESULTS: No effect was observed on cognition in the negative amyloid group (n = 167). In the positive amyloid group (n = 102), we observed a difference of 0.708 and 0.471 in the cognitive composite score between the MI plus omega-3 fatty acid group, the MI alone group, and the placebo group, respectively. DISCUSSION: MI alone or in combination with omega-3 fatty acids was associated with improved primary cognitive outcome in subjects with positive amyloid status. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01513252.

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.

[Relationship between brain amyloid deposition and instrumental activities of daily living in older individuals: two analyses from the MAPT study]. / Relation entre dépôts amyloïdes cérébraux et autonomie pour les activités instrumentales de la vie quotidienne chez les sujets âgés : deux analyses à partir de l'étude MAPT.

The biomarkers of Alzheimer's disease (AD) have enabled the identification of its pathological features, many years before the onset of clinical symptoms. Positon emission tomography (PET) using radiotracers binding the amyloid plaques has, indeed, paved the way for new perspectives. However, these biomarkers have only been studies in small populations so far, with limited follow-up. The objectives of this work were to assess the interest of amyloid PET in elderly but also to study the relationship of amyloid deposition to Instrumental Activities of Daily Living (IADL) performance. METHODS: Our population included 271 participants from the MAPT trial aged 70 and over, without major cognitive impairment, who performed amyloid PET examination. In a cross-sectional study we examined the association between brain amyloid load and IADL abilities. Moreover, in a longitudinal analysis, we studied the changes in IADL performance between amyloid positive and amyloid negative participants over the 3-year follow-up without and with adjustments for confounding factors (age, randomization group, ApoE genotyping, timespan between baseline and PET examination). RESULTS: Amyloid positive subjects showed poorer abilities in IADL compared to their amyloid negative counterparts, despite similar cognitive performance. Brain amyloid load also impacted the daily functioning of individuals over time, taking in consideration confounding factors. The difference after 3 years between the amyloid positive and negative participants was not significant (p=0.08; in adjusted models p=0.06). Amyloid negative individuals also improved in memory-related instrumental activities (p<0.001) throughout the study, unlike amyloid positive participants. CONCLUSION: These findings confirmed the relationship of brain amyloid deposition with subtle changes in IADL abilities, even in the absence of cognitive impairment. Yet, the absence of disease modifying agents as well as uncertainties regarding the long-term evolution of asymptomatic individuals showing a positive biomarker are still to be determined.

Acetaminophen Safety: Risk of Mortality and Cardiovascular Events in Nursing Home Residents, a Prospective Study.

BACKGROUND: Acetaminophen is the most widely used analgesic today. A recent systematic review found increased adverse events and mortality at therapeutic dosage. Our aim was to challenge these results in a large sample of older adults living in nursing homes (NHs). DESIGN: Prospective study using data from the Impact of Educational and Professional Supportive Interventions on Nursing Home Quality Indicators project (IQUARE), a multicenter, individually tailored, nonrandomized controlled trial in NHs across southwestern France. SETTING/PARTICIPANTS: We studied data from 5429 participants living in 175 NHs (average age, 86.1 ± 8.1 years; 73.9% women). MEASUREMENTS: All prescriptions obtained at baseline were analyzed by a pharmacist for acetaminophen use as stand-alone or associated. Myocardial infarction (MI) and strokes were reported from participants' medical records at 18-month follow-up. Dates of death were obtained. Data collection was done through an online questionnaire at baseline and at 18 months by NH staff. Analyses were realized in our total population and a population matched on propensity score of acetaminophen intake. Six models were run for each outcome. RESULTS: A total of 2239 participants were taking, on average, 2352 ± 993 mg of acetaminophen daily. Results for mortality were: hazard ratio (HR) = 0.97 (95% confidence interval [CI] = 0.86-1.10). No associations between acetaminophen intake and the risk of mortality or MI were found. In one of our models, acetaminophen intake was associated with a significant increased risk of stroke in diabetic subjects (OR = 3.19; 95% CI = 1.25-8.18; P = .0157). [Correction added March 16, 2019, after first publication online. In the previous sentence, "HR" was mistakenly used instead of "OR".] CONCLUSION: Despite old age, polypharmacy, and polymorbidity, acetaminophen was found safe for most, but not all, of our NH study population. Pain management in NHs is a health priority, and acetaminophen remains a good therapeutic choice as a first-line analgesic. More studies are needed on older diabetic patients.

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.