Multidomain Alzheimer Preventive Trial Study Research Articles

Longitudinal Associations Between ATPase Inhibitory Factor 1, Growth Differentiation Factor-15, and Nutritional Status in Older Adults From the MAPT Study.

Weight and appetite regulation have been associated with the expression and secretion of ATPase inhibitory factor 1 (IF1) and growth differentiation factor-15 (GDF-15), 2 potential biomarkers for age-related mitochondrial dysfunction. The aim was to explore the associations between these biomarkers and nutritional variables in the Multidomain Alzheimer Preventive Trial study. IF1 and GDF-15 plasma levels were quantified at 1-year follow-up. The nutritional status was measured using the Mini Nutritional Assessment (MNA) score variation between baseline and 1- and 2-year visits; appetite loss was extracted from the MNA. Bodyweight was measured every 6 months until the third year and then yearly until the fifth year of follow-up, and weight loss was established if the loss was greater than 5% or 10% within the past 6 or 12 months, respectively. Bidirectional associations of IF1 and GDF-15 levels with malnutrition, appetite, and weight loss were examined. The interactions between individual IF1 and GDF-15 with sex were explored. Four hundred and forty-eight participants had MNA data and 1 045 had weight loss data. All the associations between IF1 levels and the MNA score, appetite loss, and weight loss were nonsignificant. Higher GDF-15 levels were cross-sectionally associated with appetite loss at the first year of follow-up, and the GDF-15 highest quartile was associated with nearly 80% higher risks of weight loss over 4 years. Interactions between IF1 and GDF-15 levels, and between these 2 markers and sex were not significantly associated with the outcomes. GDF-15 plasma levels were related to key malnutrition criteria.

TNFR-1 and GDF-15 Are Associated With Plasma Neurofilament Light Chain and Progranulin Among Community-Dwelling Older Adults: A Secondary Analysis of the MAPT Study.

There is growing evidence that cognitive decline can be affected by both nutritional aspects and inflammation. Plasma neurodegenerative biomarkers stand out as minimally invasive useful measures to monitor the potential risk of cognitive decline. This study aimed to investigate the associations between biomarkers of neurodegeneration, nutrition, and inflammation among community-dwelling older adults, and to verify if associations differed according to apolipoprotein E (APOE) ε4 status. This cross-sectional analysis included 475 participants ≥70 years old from the Multidomain Alzheimer Preventive Trial (MAPT), mean age 76.8 years (SD = 4.5), 59.4% women. Biomarkers of neurodegeneration (plasma amyloid-β 42/40-Aβ 42/40, neurofilament light chain-NfL, progranulin), nutrition (erythrocyte docosahexaenoic acid, eicosapentaenoic acid, omega-3 index; plasma homocysteine-Hcy, 25 hydroxyvitamin D), inflammation (plasma tumor necrosis factor receptor 1-TNFR-1, monocyte chemoattractant protein 1-MCP-1, interleukin 6-IL-6), and cellular stress (plasma growth differentiation factor 15-GDF-15) were assessed. Linear regression analyses were performed to investigate the associations between nutritional and inflammatory biomarkers (independent variables) and neurodegenerative biomarkers (dependent variables), with adjustments for age, sex, education, body mass index, physical activity, allocation to MAPT groups, and APOE ε4 status. After adjusting for confounders, Aβ 42/40 was not associated with nutritional or inflammatory markers. NfL was positively associated with GDF-15, TNFR-1, IL-6, and Hcy. Progranulin was positively associated with GDF-15, TNFR-1, and MCP-1. Analyses restricted to APOE ε4 carriers (n = 116; 26.9%) or noncarriers were mostly similar. Our cross-sectional study with community-dwelling older adults corroborates previous evidence that inflammatory pathways are associated to plasma markers of neurodegeneration. Clinical Trials Registration Number: NCT00672685.

Biomarkers of Age-Related Frailty and Frailty Related to Diseases: An Exploratory, Cross-Sectional Analysis from the MAPT Study

BackgroundFrailty may in most cases result from two main causes: the aging process (age-related frailty) and diseases (evolving chronic conditions or acute medical illnesses — disease-related frailty). The biological determinants characterizing these two main causes of frailty may be different.ObjectivesThe aim of this study is to compare the biological and neuroimaging profile of people without frailty, those with age-related frailty, and subjects with disease-related frailty in community-dwelling older adults.Material and MethodsWe performed a secondary, cross-sectional analysis from the Multidomain Alzheimer Preventive Trial (MAPT). We included 1199 subjects without frailty throughout the 5-year follow-up, 82 subjects with incident age-related frailty, and 53 with incident disease-related frailty. Available blood biomarkers involved nutritional (eg, vitamin D, omega-3 fatty acids), inflammatory-related (IL-6, TNFR1, GDF15), neurodegenerative (eg, beta-amyloid, neurofilament light chain) and neuroimaging markers (MRI, Amyloid-PET).ResultsAlthough not statistically significant, the results of the unadjusted model showed increasing gradients for inflammatory markers (GDF15, TNFR1) and decreasing gradients for nutritional and neuroimaging markers (omega 3 index, hippocampal volume) from age-related frailty participants to individuals with disease-related frailty. Considering the linear models we observed higher GDF15 values in disease-related frailty group compared to age-related frailty individuals [β = 242.8 (49.5, 436.2)]. We did not find any significant difference between subjects without frailty and those with age-related frailty. Subjects with disease-related frailty compared to subjects without frailty had lower values of DHA [β = −2.42 (−4.76, −0.08)], Omega 3 Index [β = −0.50 (−0.95, −0.06)] and hippocampal volume [β = −0.22 (−0.42,−0.02)]. They also had higher values of GDF15 [β = 246.1 (88.9, 403.4)] and TNFR1 [β = 157.5 (7.8, 307.2)].ConclusionAge-related frailty and disease-related frailty may represent different degrees of frailty severity on a biological level. Further research is needed to identify biomarkers potentially able to distinguish these classifications of frailty.

Physical Activity, Body Mass Index, and Blood Progranulin in Older Adults: Cross-Sectional Associations in the MAPT Study.

Physical activity (PA) has been shown to moderate the negative effects of obesity on pro-inflammatory cytokines but its relationship with the adipokine progranulin (PGRN) remains poorly investigated. This study aimed to examine the cross-sectional main and interactive associations of body mass index (BMI) and PA level with circulating PGRN in older adults. Five-hundred and twelve participants aged 70 years and older involved in the Multidomain Alzheimer Preventive Trial (MAPT) study who underwent plasma PGRN measurements (ng/mL) were included. Self-reported PA levels were assessed using questionnaires. People were classified into 3 BMI categories: normal weight, overweight, or obesity. Further categorization using PA tertiles was used to define highly active, moderately active, and low active individuals. Multiple linear regressions were performed in order to test the associations of BMI, PA level, and their interaction with PGRN levels. Multiple linear regressions adjusted by age, sex, diabetes mellitus status, total cholesterol, creatinine level, and MAPT group demonstrated significant interactive associations of BMI status and continuous PA such that in people without obesity, higher PA levels were associated with lower PGRN concentrations, while an opposite pattern was found in individuals with obesity. In addition, continuous BMI was positively associated with circulating PGRN in highly active individuals but not in their less active peers. This cross-sectional study demonstrated reverse patterns in older adults with obesity compared to those without obesity regarding the relationships between PA and PGRN levels. Longitudinal and experimental investigations are required to understand the mechanisms that underlie the present findings. Clinical Trials Registration Number: NCT00672685.

Potentially Inappropriate Medication Prescribing Detected by Computer Algorithm among Older Patients: Results from the MAPT Study.

(1) Background: Some medications may be dangerous for older patients. Potentially inappropriate medication prescribing (PIP) among older patients represents a significant cause of morbidity. The aim of this study was to create an algorithm to detect PIP in a geriatric database (Multidomain Alzheimer Preventive Trial (MAPT) study), and then to assess the algorithm construct validity by comparing the prevalence of PIP and associated factors with literature data. (2) Methods: An algorithm was constructed to detect PIP and was based on different explicit criteria among which the European list of potentially inappropriate medications (EU(7)-PIM), the STOPP and START version 2 tools. For construct validity assessment, logistic mixed-effects model repeated measures analyses were used to identify factors associated with PIP. (3) Results: Prevalence of PIP was 59.0% with the EU(7)-PIM list criteria, 43.2% with the STOPP criteria and 51.3% with the START criteria. Age, polypharmacy, and higher Charlson comorbidity index were associated with PIP. (4) Conclusions: Prevalence of PIP and associated factors are consistent with literature data, supporting the construct validity of our algorithm. This algorithm opens up interesting perspectives both in terms of analysis of very large databases and integration into e-prescribing or pharmaceutical validation software.

Can We Distinguish Age-Related Frailty from Frailty Related to Diseases? Data from the MAPT Study

BackgroundNo study has tried to distinguish subjects that become frail due to diseases (frailty related to diseases) or in the absence of specific medical events; in this latter case, it is possible that aging process would act as the main frailty driver (age-related frailty).ObjectivesTo classify subjects according to the origin of physical frailty: age-related frailty, frailty related to diseases, frailty of uncertain origin, and to compare their clinical characteristics.Materials and methodsWe performed a secondary analysis of the Multidomain Alzheimer Preventive Trial (MAPT), including 195 subjects ≥70 years non-frail at baseline who became frail during a 5-year follow-up (mean age 77.8 years ± 4.7; 70% female). Physical frailty was defined as presenting ≥3 of the 5 Fried criteria: weight loss, exhaustion, weakness, slowness, low physical activity. Clinical files were independently reviewed by two different clinicians using a standardized assessment method in order to classify subjects as: “age-related frailty”, “frailty related to diseases” or “frailty of uncertain origin”. Inconsistencies among the two raters and cases of uncertain frailty were further assessed by two other experienced clinicians.ResultsFrom the 195 included subjects, 82 (42%) were classified as age-related frailty, 53 (27%) as frailty related to diseases, and 60 (31%) as frailty of uncertain origin. Patients who became frail due to diseases did not differ from the others groups in terms of functional, cognitive, psychological status and age at baseline, however they presented a higher burden of comorbidity as measured by the Cumulative Illness Rating Scale (CIRS) (8.20 ± 2.69; vs 6.22 ± 2.02 frailty of uncertain origin; vs. 3.25 ± 1.65 age-related frailty). Time to incident frailty (23.4 months ± 12.1 vs. 39.2 ± 19.3 months) and time spent in a pre-frailty condition (17.1 ± 11.4 vs 26.6 ± 16.6 months) were shorter in the group of frailty related to diseases compared to age-related frailty. Orthopedic diseases (n=14, 26%) were the most common pathologies leading to frailty related to diseases, followed by cardiovascular diseases (n=9, 17%) and neurological diseases (n = 8, 15%).ConclusionPeople classified as age-related frailty and frailty related to diseases presented different frailty-associated indicators. Future research should target the underlying biological cascades leading to these two frailty classifications, since they could ask for distinct strategies of prevention and management.

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

BackgroundThe 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.MethodsMAPT-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.ResultsThe 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.ConclusionsMI 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 registrationClinicalTrials.gov Identifier, NCT01513252.

Effect of long-term omega-3 supplementation and a lifestyle multidomain intervention on intrinsic capacity among community-dwelling older adults: Secondary analysis of a randomized, placebo-controlled trial (MAPT study)

ObjectivesTo investigate the effect of omega-3 (ω-3) polyunsaturated fatty acid supplementation and a multidomain intervention (MI) (physical activity counselling, cognitive training and nutritional advice) among community-dwelling older adults on levels of intrinsic capacity (IC), a construct recently proposed by the World Health Organization. Study designSecondary analysis from the factorial-design 3-year Multidomain Alzheimer Preventive Trial (MAPT) with 1445 subjects (64.2 % female, mean age 75.3 years, SD = 4.4) randomized to one group of MI plus ω-3 (800 mg docosahexaenoic acid and 225 mg eicosapentaenoic acid/day); MI plus placebo; ω-3 supplementation alone; or placebo alone. Data collection was held between 2008 and 2014. Main outcome measuresIC domains were examined with the Geriatric Depression Scale (psychological); Short Physical Performance Battery (mobility); Z-score combining four tests (cognitive function); and handgrip strength (vitality). All domains were combined into a composite IC Z-score. ResultsAfter 3 years, IC Z-score decreased among all groups when time was considered continuous (MI plus ω-3: -0.16, 95 %CI: -0.22 to -0.10; MI alone: -0.13, 95 %CI: -0.19 to -0.07; ω-3 alone: -0.19, 95 %CI: -0.25 to -0.10; placebo: -0.20, 95 %CI: -0.26 to -0.14; all p < 0.0001). There were no significant differences between groups. In a sensitivity analysis with categorical time, significant within-group declines were first identified at 24 months for all groups. ConclusionsThis trial designed to improve cognitive function was unable to find effects of the intervention on the composite IC Z-score. Further investigations are needed, especially trials providing stronger interventions (such as exercise training and a controlled diet) and also embracing the sensorial domain of IC.

PIH46 COSTS AND OUTCOMES ASSOCIATED TO POTENTIALLY INAPPROPRIATE DRUG PRESCRIBING DETECTED BY ALGORITHM: PRELIMINARY RESULTS FROM THE MAPT STUDY

Drug prescribing is an essential component in the management of pathologies and functional capacity of older patients. However, some medicines may be dangerous for patients. The potentially inappropriate drug prescribing (PIDP) among older patients represents a significant cause of morbidity. The aim of this study was to compare the clinical characteristics and the healthcare costs of elderly patients according to potentially inappropriate drug prescribing. Analyses were conducted using data from the MAPT (Multidomain Alzheimer Preventive Trial) study. An algorithm was constructed to detect potentially inappropriate drug prescribing and was based on different explicit criteria: the European List of potentially inappropriate medications, the STOPP and START tools version 2, Alert and Mastering of Iatrogenesis indicators (AMI) of the French High Authority for Health (HAS), the market withdrawals and the Summary of Product Characteristics (SPC) for contraindications. We performed the cost analysis from the French national health insurance perspective. The costs are reported as means and bootstrap 95% confidence intervals. At baseline, the algorithm analysed prescriptions from included patients (N=1525 aged 75.3±4.4 years; 64% women (N=978)). Among the included patients, 80.4% had PIDP (N=1226). The patients with PIDP (versus without PIDP) didn’t differ regarding sex, education levels, Fried frailty phenotype, intrinsic capacity domains (cognitive, psychological, locomotion and vitality). The patients with PIDP were slightly older (75.3 vs 74.8, p=0.028), had more prescribed drugs (5.4 vs 2.0, p<0.001), and more comorbidities (p= 0.029) (Charlson index) than those without PIDP. The average healthcare costs per patient over 6 months were 723€ [636€; 831€] for patients with PIDP and 658€ [540€; 788€] for patients without PIDP. Participants did not differ, as a function of PIDP, in terms of functional capacity and frailty, but differed regarding co-morbidities. These results have to be confirmed by a multivariate analysis on longitudinal data.

Prospective Associations Between Diffusion Tensor Imaging Parameters and Frailty in Older Adults.

Cross-sectional associations have been found between frail individuals and worse white matter (WM) integrity. However, the prospective association between WM integrity and frailty is still unclear. Our objectives were to measure associations between WM integrity using diffusion tensor imaging (DTI) and the 5-year worsening of frailty in community-dwelling older adults. Secondary analysis of the randomized controlled Multidomain Alzheimer Preventive Trial (MAPT). Thirteen memory centers in France and Monaco between 2008 and 2011. Participants (mean age = 74.7 ± 3.9 years) with no dementia at baseline who had functional magnetic resonance imaging performed as part of the MAPT study (n = 227). Fractional anisotropy and mean diffusivity (MD), axial diffusivity (AxD), and radial diffusivity (RD) were acquired for 10 different brain regions. Frailty was assessed by the Fried frailty phenotype (score from 0 to 5, higher is worse) at up to seven time points for 5 years. Mixed effect ordinal logistic regression model was used to assess the prospective association between DTI parameters (independent variables) and frailty (dependent variable). All the analyses were adjusted for age, sex, baseline total intracranial volume, and the presence of one of the following cardiovascular risk factors (hypertension, diabetes, and/or hypercholesterolemia). A statistically significant association was found between the RD, AxD, and MD for different brain regions (anterior limb of internal capsule, external capsule, posterior corona radiata, posterior thalamic radiation, superior corona radiata, superior frontal occipital fasciculus, and superior longitudinal fasciculus) and worsening of frailty over 5 years after adjusting for multiple comparisons. This is the first study to show that WM integrity is associated with frailty in older adults. The mechanisms related to these results require further investigation. J Am Geriatr Soc 68:1050-1055, 2020.

Frequency of Conditions Associated with Declines in Intrinsic Capacity According to a Screening Tool in the Context of Integrated Care for Older People.

The screening tool of the Integrated Care for Older People (ICOPE Step 1), designed to detect declines in the domains of intrinsic capacity, has been incipiently investigated in older adult populations. To retrospectively estimate the frequency of priority conditions associated with declines in intrinsic capacity according to an adaptation of the screening tool ICOPE Step 1 among participants of the Multidomain Alzheimer Preventive Trial (MAPT). A cross-sectional retrospective analysis from the baseline assessment of the MAPT. The data was gathered during a preventive consultation for cardiovascular risk factors in memory clinics in France. Seven hundred fifty-nine older adults aged 70-89 years with memory complaints, allocated to the multidomain groups of the MAPT study. Five domains of intrinsic capacity (cognition, locomotion, nutrition, sensorial, and psychological) were assessed using a screening tool similar to the ICOPE Step 1 (MAPT Step 1). The frequency of six conditions associated with declines in intrinsic capacity (cognitive decline, limited mobility, malnutrition, visual impairment, hearing loss, and depressive symptoms) was obtained for older adults with memory complaints participating in the MAPT study. Overall, 89.3% of the participants had one or more conditions associated with declines in intrinsic capacity. The overall frequency of each condition was: 52.2% for cognitive decline, 20.2% for limited mobility, 6.6% for malnutrition, 18.1% for visual impairment, 56.2% for hearing loss, and 39% for depressive symptoms. After being screened with an adaptation of the ICOPE step 1 (MAPT step 1) tool, 9/10 older adults had one or more conditions associated with declines in intrinsic capacity. The relative frequency differs across conditions and could probably be lower in a population without memory complaints. The frequency of screened conditions associated with declines in IC highlights how relevant it is to develop function-centered care modalities to promote healthy aging.

Associations of C-reactive protein and homocysteine concentrations with the impairment of intrinsic capacity domains over a 5-year follow-up among community-dwelling older adults at risk of cognitive decline (MAPT Study).

The World Health Organization (WHO) recently proposed an innovative model of care focusing on functional rather than disease-based perspectives, based on a construct of intrinsic capacity (IC). This study aimed to analyze if low-grade inflammation (LGI) (chronically raised C-reactive protein - CRP) and hyperhomocysteinemia (HHcy) were associated with variation in IC domains (mobility, cognition, psychological and vitality) and in a combined IC Z-score over a 5-year follow-up among non-demented, community-dwelling older adults at risk of cognitive decline. This observational study included 1516 subjects ≥70 years (64.5% female, mean age 75.4 years, SD = 4.5), volunteers from the interventional study Multidomain Alzheimer Preventive Trial (MAPT). Plasma CRP (at baseline, 6 and 12 months) and homocysteine (at baseline) concentrations were measured. LGI was defined as having ≥2 consecutively CRP readings >3 to 10 mg/L between baseline and 12 months, and HHcy was defined as homocysteine >15 μM/L. IC domains were operationalized as follows: Psychological. Depressive symptoms evaluated by the Geriatric Depression Scale (GDS); Mobility. Assessed by the Short Physical Performance Battery (SPPB); Cognitive function. Examined by a Z-score combining four tests; Vitality. Based on hand grip strength. Outcomes were combined into a composite IC Z-score. IC Z-score decreased among groups with no inflammation and LGI after 5 years, but this decrease was more pronounced among the LGI group (unadjusted mean group difference: 0.09, 95%CI: 0.01 to 0.16; p = 0.032). Participants with HHcy also presented IC Z-score decreases over time. Combined conditions provided more pronounced declines, even after adjusting for potential confounders. LGI and HHcy were both related with impairment on the combined IC levels among older adults after a 5-year follow-up. Identifying biomarkers that strongly associate with IC may help to settle strategies aiming to prevent the incidence and slow down the evolution of age-related functional decline and care dependency.

Defining Vitality: Associations of Three Operational Definitions of Vitality with Disability in Instrumental Activities of Daily Living and Frailty among Elderly Over a 3-Year Follow-Up (MAPT Study).

This study aimed to examine the associations of three operational definitions of vitality with variation in instrumental activities of daily living (IADL) and frailty over a 3-year follow-up among non-demented, community-dwelling elderly. Observational study. 1,679 elderly >70y (64.7% female) participants of the Multidomain Alzheimer Preventive Trial (MAPT). Vitality was defined as a psychological concept using three items from the Geriatric Depression Scale; as a physical construct using the highest quartile for hand grip strength; and as global physiological reservoir using a combination of good physical and cognitive functions. Variables were assessed at baseline, 6, 12, 24 and 36 months of follow-up. Prevalence of high vitality at baseline was 57.1%, 28.5% and 21.6% for psychological, physical, and physiological reservoir, respectively. People with high vitality presented higher IADL scores compared to people with low vitality for all definitions. Analysis from the mixed-effect model found no differences between vitality groups for IADL performance across all definitions. IADL scores improved among subjects with high vitality over time, independent on the definition; while no significant variation was observed among those with low vitality. Participants with low vitality presented 2.0 to 6.1 higher odds of having more frailty components over time (p<0.0001). High vitality defined as a concept related to psychological, physical, or physiological reservoir constructs were positively associated with better IADL performance and with reduced likelihood of frailty worsening over time.

Shifting from Declines to Improvements: Associations between a Meaningful Walking Speed Change and Cognitive Evolution over Three Years in Older Adults.

Although the close relationship between mobility and cognitive declines is well-known, literature has very little questioned whether improvement in walking speed over time could be associated with improvements in cognitive functions. The objective of this study was to examine the associations between a clinically meaningful improvement in walking speed and global and specific cognitive changes in older adults. Prospective cohort study. Multidomain Alzheimer Preventive Trial (MAPT) study. Three-hundred participants from the control group of the MAPT study (mean age 74.8 ± 4.2; 57% women). The 4-m usual walking speed, global cognition, memory, executive functions, and processing speed measures were collected at baseline, and at 6, 12, 24 and 36 months. Participants were categorized into three groups according to their walking speed change over the three-year study: 1/ Non-Improvers (participants not presenting an increase ≥0.05m/sec on walking speed; n=138); 2/ Improvers (increase ≥0.05m/sec; n=40); Cyclic (≥0.05m/sec improvement at some time points without maintaining it through the whole period; n=122). Adjusted mixed-effect linear regressions revealed that walking speed improvers did not significantly differ from participants who never or temporarily improved their walking speed on all of global and specific cognitive functions over three years. Nevertheless, a sensitivity analysis (excluding participants with a non-clinical walking speed improvement) indicated specific cognitive trajectories per group associated with better episodic memory scores for Improvers compared to non-improvers (β=2.41, 95% CI=.12 - 4.71; p=.039). This study found that the overtime trajectories of cognitive functions did not differ as a function of clinically meaningful walking speed changes in older adults. Nevertheless, secondary analyses provided new insights on the relationship between walking speed and specific cognitive functions. The novelty of this approach (switching from declines to improvements) should be considered in future large-scale, observational longitudinal studies.

Effect of Multidomain Intervention, Omega-3 Polyunsaturated Fatty Acids Supplementation or their Combinaison on Cognitive Function in Non-Demented Older Adults According to Frail Status: Results from the MAPT Study.

Aim: The aim of this study was to explore whether multidomain intervention (MI) and Omega-3 Polyunsaturated Fatty Acids supplementation can modify the cognitive function on elderly according to frail status. Data are from a secondary exploratory analysis of the Multidomain Alzheimer Preventive Trial (MAPT), a French community-dwellers aged 70 or over reporting subjective memory complaints, but free from clinical dementia. The multidomain intervention consisted of 2 hours group sessions focusing on three domains (cognitive stimulation, physical activity, and nutrition) and a preventive consultation (at baseline, 12 months, and 24 months). For Omega-3 Polyunsaturated Fatty Acids supplementation, participants took two capsules of either placebo or polyunsaturated fatty acids daily. Linear mixed-model repeated-measures analyses were used including baseline, 6, 12, 24 and 36-month follow-up data to assess between-group differences in the change in cognitive tests over 36 months. The overall mean age of the MAPT study population was 75.25(±4.38). A tend toward significant differences in TMT-A were found for the effect of the multidomain intervention on the prefrail group compared to non-frail group. The MI and n3 PUFA program could not significantly have reduced cognitive function in a sample of pre-frailty elders. This population-based study in community-dwellers aged 70 years or over suggested that multidomain intervention and n3 PUFA supplementation have not significant effects on cognitive function change in frail older adults with memory complaints. The beneficial effect of multidomain intervention and n3 PUFA supplementation on cognitive function did not differ between frail and nonfrail participants.

Brain Amyloid Deposition Is Associated With Lower Instrumental Activities of Daily Living Abilities in Older Adults. Results From the MAPT Study.

Brain amyloid deposition is one of the key pathological hallmarks underlying the cognitive changes associated with Alzheimer's disease. Growing interest has been given to the earliest clinical manifestations of amyloid plaques. However, the relationship between amyloid status and activities of everyday function remains largely unknown. In the present study, we examined the relationship between instrumental activities of daily living performance (using the ADL-PI score) and amyloid status in older adults. Cross-sectional analyses of data from the Multidomain Alzheimer Preventive Trial (MAPT) were performed. Volunteers underwent a brain 18F-AV45 positron emission tomography examination. Bivariate analysis and regression models were conducted to study the relationships between brain amyloid deposition and the total ADL-PI score. We included 271 participants (women = 60%; age = 76±4 years). Amyloid positron emission tomography was positive (standard uptake value ≥1.17) for 103 participants (38%). The ADL-PI score was lower in amyloid positive participants than in their amyloid negative counterparts (38.8 vs 40.3, p = .007). This association was also confirmed in regression models adjusted for age, gender, and familial history of Alzheimer's disease (odds ratio = 0.94; 95% confidence interval 0.89-0.99; p = .02). This finding was consistent in cognitively normal individuals and in those with mild cognitive impairment, using the clinical dementia rating scale. This study highlighted an association between early functional limitations and brain amyloid deposition in elderly subjects. These symptoms could be the clinical manifestations of amyloid plaques even in the absence of overt dementia. Further prospective studies are warranted for examining the evolution of ADL-PI score over the course of Alzheimer's disease.

The multi-domain Alzheimer preventive trial (MAPT): A new approach for the prevention of Alzheimer's disease- characteristics of the study population

Because no effective curative approaches are available yet, preventive approaches in the field of Alzheimer disease (AD) are needed. In the past, several studies have suggested that many factors may be involved in the occurrence of AD in the late ages. Because of the probable multifactorial nature of AD, it would seem logical to initiate multidomain interventions designed to examine their potential synergistic effects. The aim of the MAPT study is to evaluate the efficacy of a multidomain intervention (nutritional, physical and cognitive training) and omega 3 treatment in the prevention of cognitive decline in frail elderly persons aged 70 years or over. This study also aimed to collect imaging and biological data which could be used for future AD prevention and treatment trials. MAPT is a 3-year randomized controlled trial conducted by university hospital practitioners specializing in memory disorders in 7 French cities (Bordeaux, Dijon, Limoges, Lyon, Montpellier, Nice, and Toulouse). This study plans to enrol 1200 frail elderly subjects with at least one the following criteria: subjective memory complaint spontaneously expressed to their general practitioner, limitation in one instrumental activity of daily living (IADL), and slow walking speed. Subjects are randomized in one of the following 4 groups: omega 3 alone, multidomain intervention alone, omega 3 plus multidomain intervention, or placebo group (n = 300 each). The principal outcome measure is the change in cognitive function at 3 years determined by the Grober and Buschke Test. The multidomain intervention includes training/information sessions and preventive consultations. The training/information sessions are based on recommendations relative to nutrition, physical exercise, cognitive stimulation (reasoning and memory training) and social activities. They are dispensed with the following frequency: twice a week for 1 month, then once a week for 1 month, then once a month for the rest of the follow-up period. The preventive consultations are standardised and designed to detect any hearing or visual disorders, mood disorders, anxiety, malnutrition, walking and balance problems, fear of falling and poor oral and dental health in collaboration with general practitioner. Recruitment in the MAPT study will be completed by June 2010. We will present baseline data of the recruited population.

The Multidomain Alzheimer Preventive Trial (MAPT): A new approach for the prevention of Alzheimer's disease

Because no effective curative approaches are available yet, preventive approaches in the field of Alzheimer disease (AD) are needed. In the past, several studies have suggested that many factors may be involved in the occurrence of AD in the late ages. Because of the probable multifactorial nature of AD, it would seem logical to initiate multidomain interventions designed to examine their potential synergistic effects. The aim of the MAPT study is to evaluate the efficacy of a multidomain intervention (nutritional, physical and cognitive training) and omega 3 treatment in the prevention of cognitive decline in frail elderly persons aged 70 years or over. This study also aimed to collect imaging and biological data which could be used for future AD prevention and treatment trials. MAPT is a 3-year randomized controlled trial conducted by university hospital practitioners specializing in memory disorders in 4 French cities (Bordeaux, Limoges, Montpellier and Toulouse). This study plans to enrol 1200 frail elderly subjects with at least one the following criteria: subjective memory complaint spontaneously expressed to their general practitioner, limitation in one instrumental activity of daily living (IADL), and slow walking speed. Subjects are randomized in one of the following 4 groups: omega 3 alone, multidomain intervention alone, omega 3 plus multidomain intervention, or placebo group (n = 300 each). The principal outcome measure is the change in cognitive function at 3 years determined by the Grober and Buschke Test. The multidomain intervention includes training/information sessions and preventive consultations. The training/information sessions are based on recommendations relative to nutrition, physical exercise, cognitive stimulation (reasoning and memory training) and social activities. They are dispensed with the following frequency: twice a week for 1 month, then once a week for 1 month, then once a month for the rest of the follow-up period. The preventive consultations are standardised and designed to detect any hearing or visual disorders, mood disorders, anxiety, malnutrition, walking and balance problems, fear of falling and poor oral and dental health in collaboration with general practitioner. Recruitment in the MAPT study is still in process and will last 2 years. Final results should be available in 2013.

Commentary on “A roadmap for the prevention of dementia II. Leon Thal Symposium 2008.” The Multidomain Alzheimer Preventive Trial (MAPT): A new approach to the prevention of Alzheimer's disease

Background Because no effective curative approaches are available, preventive approaches in the field of Alzheimer's disease (AD) are needed. We present the design of the ongoing Multidomain Alzheimer Preventive Trial (MAPT) Study. Several previous studies suggested that many factors may be involved in the occurrence of AD at late ages. Because of the probable multifactorial nature of AD, it seems logical to initiate multidomain interventions to examine their potential synergistic effects. The MAPT Study aims to evaluate the efficacy of a multidomain intervention (nutritional, physical, and cognitive training) and omega 3 treatment in the prevention of cognitive decline in frail elderly persons aged 70 years or over. The study also collects imaging and biological data that could be used in future AD prevention and treatment trials. Methods The MAPT Study is a 3-year, randomized, controlled trial conducted by university hospital practitioners specializing in memory disorders in four French cities (Bordeaux, Limoges, Montpellier, and Toulouse). The study plans to enroll 1200 frail elderly subjects on the basis of at least one of the following criteria: subjective memory complaint spontaneously expressed to a general practitioner, limitation in one instrumental activity of daily living (IADL), and slow walking speed. To demonstrate the protective effect of interventions, subjects are randomized into one of the following four groups: omega 3 alone, multidomain intervention alone, omega 3 plus multidomain intervention, or placebo (n = 300 each). The principal outcome measure is a change in cognitive function at 3 years, as determined by the Grober and Buschke Test. Conclusions The MAPT Study is the first preventive trial involving multidomain interventions. Final results should be available in 2013.