Fall risk factors among poly-medicated older Lebanese patients in primary care settings: a secondary cross-sectional analysis of the "MGPIDP-L project".

BACKGROUND: Falling is a major concern for the health of older adults and significantly affects their quality of life. Identifying the various risk factors and the differences between older patients can be challenging. The objective of this study was to identify the risk factors for falls among polymedicated community-dwelling older Lebanese patients following a medication review. METHODS: In this analytical cross-sectional study, we examined the risk factors for falls in 850 patients aged ≥ 65 years who were taking ≥ 5 medications daily. The study involved conducting a medication review over the course of a year in primary care settings and using multivariate logistic regression analysis to analyze the data. RESULTS: Our results showed that 106 (19.5%) of the 850 included patients had fallen at least once in the three months prior to the medication review. Loss of appetite and functional dependence were identified as the most significant predictors of falls ORa = 3.020, CI [2.074-4.397] and ORa = 2.877, CI [1.787-4.632], respectively. Other risk factors for falls included drowsiness ORa = 2.172, CI [1.499-3.145], and the use of beta-blockers ORa = 1.943, CI [1.339-2.820]. CONCLUSION: Our study highlights the importance of addressing multiple risk factors for falls among Lebanese older adults and emphasizes the need for customized interventions and ongoing monitoring to prevent falls and improve health outcomes. This study sheds light on a critical issue in the Lebanese older population and provides valuable insight into the complex nature of falls among poly-medicated Lebanese community-dwelling older adults. TRIAL REGISTRATION: 2021REC-001- INSPECT -09-04.

Exploring the natural history of intrinsic capacity impairments: longitudinal patterns in the 10/66 study.

BACKGROUND: intrinsic capacity (IC) is a construct encompassing people's physical and mental abilities. There is an implicit link amongst IC domains: cognition, locomotion, nutrition, sensory and psychological. However, little is known about the integration of the domains. OBJECTIVES: to investigate patterns in the presentation and evolution of IC domain impairments in low-and-middle-income countries and if such patterns were associated with adverse outcomes. METHODS: secondary analyses of the first two waves of the 10/66 study (population-based surveys conducted in eight urban and four rural catchment areas in Cuba, Dominican Republic, Puerto Rico, Venezuela, Peru, Mexico and China). We applied latent transition analysis on IC to find latent statuses (latent clusters) of IC domain impairments. We evaluated the longitudinal association of the latent statuses with the risk of frailty, disability and mortality, and tested concurrent and predictive validity. RESULTS: amongst 14,923 participants included, the four latent statuses were: high IC (43%), low deterioration with impaired locomotion (17%), high deterioration without cognitive impairment (22%), and high deterioration with cognitive impairment (18%). A total of 61% of the participants worsened over time, 35% were stable, and 3% improved to a healthier status.Participants with deteriorated IC had a significantly higher risk of frailty, disability and dementia than people with high IC. There was strong concurrent and predictive validity. (Mortality Hazard Ratio = 4.60, 95%CI 4.16; 5.09; Harrel's C = 0.73 (95%CI 0.72;0.74)). CONCLUSIONS: half of the study population had high IC at baseline, and most participants followed a worsening trend. Four qualitatively different IC statuses or statuses were characterised by low and high levels of deterioration associated with their risk of disability and frailty. Locomotion and cognition impairments showed other trends than psychological and nutrition domains across the latent statuses.

Factors Predicting Engagement of Older Adults With a Coach-Supported eHealth Intervention Promoting Lifestyle Change and Associations Between Engagement and Changes in Cardiovascular and Dementia Risk: Secondary Analysis of an 18-Month Multinational Randomized Controlled Trial.

BACKGROUND: Digital health interventions could help to prevent age-related diseases, but little is known about how older adults engage with such interventions, especially in the long term, or whether engagement is associated with changes in clinical, behavioral, or biological outcomes in this population. Disparities in engagement levels with digital health interventions may exist among older people and be associated with health inequalities. OBJECTIVE: This study aimed to describe older adults' engagement with an eHealth intervention, identify factors associated with engagement, and examine associations between engagement and changes in cardiovascular and dementia risk factors (blood pressure, cholesterol, BMI, physical activity, diet, and cardiovascular and dementia risk scores). METHODS: This was a secondary analysis of the 18-month randomized controlled Healthy Ageing Through Internet Counselling in the Elderly trial of a tailored internet-based intervention encouraging behavior changes, with remote support from a lifestyle coach, to reduce cardiovascular and cognitive decline risk in 2724 individuals aged ≥65 years, recruited offline in the Netherlands, Finland, and France. Engagement was assessed via log-in frequency, number of lifestyle goals set, measurements entered and messages sent to coaches, and percentage of education materials read. Clinical and biological data were collected during in-person visits at baseline and 18 months. Lifestyle data were self-reported on a web-based platform. RESULTS: Of the 1389 intervention group participants, 1194 (85.96%) sent at least one message. They logged in a median of 29 times, and set a median of 1 goal. Higher engagement was associated with significantly greater improvement in biological and behavioral risk factors, with evidence of a dose-response effect. Compared with the control group, the adjusted mean difference (95% CI) in 18-month change in the primary outcome, a composite z-score comprising blood pressure, BMI, and cholesterol, was -0.08 (-0.12 to -0.03), -0.04 (-0.08 to 0.00), and 0.00 (-0.08 to 0.08) in the high, moderate, and low engagement groups, respectively. Low engagers showed no improvement in any outcome measures compared with the control group. Participants not using a computer regularly before the study engaged much less with the intervention than those using a computer up to 7 (adjusted odds ratio 5.39, 95% CI 2.66-10.95) or ≥7 hours per week (adjusted odds ratio 6.58, 95% CI 3.21-13.49). Those already working on or with short-term plans for lifestyle improvement at baseline, and with better cognition, engaged more. CONCLUSIONS: Greater engagement with an eHealth lifestyle intervention was associated with greater improvement in risk factors in older adults. However, those with limited computer experience, who tended to have a lower level of education, or who had poorer cognition engaged less. Additional support or forms of intervention delivery for such individuals could help minimize potential health inequalities associated with the use of digital health interventions in older people.

Is more always better? Dose effect in a multidomain intervention in older adults at risk of dementia.

BACKGROUND: Little is known regarding the dose-response function in multidomain interventions for dementia prevention. METHOD: The Multidomain Alzheimer Preventive Trial is a 3-year randomized controlled trial comprising cognitive training, physical activity, nutrition, and omega-3 polyunsaturated fatty acids for at-risk older adults. The dose delivered (number of sessions attended) was modeled against global cognition, memory, and fluency in 749 participants. Interaction effects were assessed for age, sex, education, dementia score (CAIDE), frailty score, and apolipoprotein E (APOE) ε4 status. RESULTS: The dose-response models were non-linear functions indicating benefits up to about 12 to 14 training hours or 15 to 20 multidomain sessions followed by a plateau. Participants who benefited from a higher dose included women, younger participants, frail individuals, and those with lower education or lower risk of dementia. DISCUSSION: The non-linear function indicates that a higher dose is not necessarily better in multidomain interventions. The optimal dose was about half of the potentially available sessions.

Cognitive decline as an outcome and marker of progression toward dementia, in early preventive trials.

INTRODUCTION: Recent Food and Drug Administration guidance endorses cognitive assessment as a possible primary endpoint for early trials for Alzheimer's disease but emphasizes the need for certainty regarding the relationship with progression to dementia. METHODS: We compared the validity of the 2-year change (Y0-Y2) of 11 markers of neuropsychological and functional abilities for the prediction of incident dementia over the following 3 years (Y2-Y5), in 860 subjects aged 70 years or older, who consulted for memory loss and were included in the "GuidAge" prevention trial. RESULTS: The Free and Cued Selective Reminding Test-Free Recall (FCSRT-FR) score showed the most predictive 2-year change (area under the curve = 0.72 95% confidence interval = 0.64;0.81). Changes in other subscores of the FCSRT, verbal fluencies tasks, and composite cognitive score were also significantly predictive. Conversely, 2-year change of Mini-Mental State Examination, Trail Making test (TMT)-A, TMT-B, Clinical Dementia Rating Sum of Boxes, and Instrumental Activities of Daily Living scores did not significantly predict occurrence of dementia. CONCLUSION: The FCSRT, the Fluency Task, and the composite cognitive score appear to be good cognitive markers of progression toward dementia in early prevention trials.

Impact of pharmacist-led interventions on patient care in ambulatory care settings: A systematic review.

BACKGROUND: In an era of rapid evolution in healthcare delivery, major changes have occurred within the profession of pharmacist. Because the impact of pharmacist-led interventions in the hospital setting has been well-studied and showed mixed findings on drug-related readmissions, all-cause emergency department visits and mortality, this systematic review focused on services provided by pharmacists in the community or ambulatory care setting without being limited to a specific intervention or outcome. OBJECTIVE: To investigate the impact of pharmacist-led interventions, categorised into clinical medication review (CMR), adherence review (AR), and prescription review (PR) on various aspects of patient care (clinical, behavioural, economic and humanistic outcomes in ambulatory care setting) and understand which particular intervention makes the greatest contribution. METHODS: A literature search was conducted using MEDLINE, Embase and the Cochrane Library for publications from 2000 onwards. FINDINGS AND INTERPRETATION: A total of 31 relevant publications corresponding to 27 controlled trials (CTs) and 4 observational studies were selected. CMR was the most studied pharmacist-led intervention (n = 19, 61.29%), followed by AR (n = 6, 19.3%). CMR demonstrated a favourable effect on different clinical outcomes mainly the management of drug-related problems and adverse events, and it also contributed the most to the reduction of healthcare costs. AR was the most effective intervention to improve patient's adherence. CMR alone or combined with AR both raised equally the patient's satisfaction. CONCLUSION: Our results showed that CMR can play a major role in the management of drug-related problems and economic issues. AR can significantly improve patient compliance. Larger, standardised and rigorously designed intervention studies are needed to help decision-makers to select appropriate interventions leading to meaningful improvements in patient care.

What day is today? Cognitive capacity and the risk of incident dementia in the context of integrated care for older people (ICOPE Step 1).

Based on clinical observations, our objective was to test if the older adults who failed to recall the name of the weekday, or had a higher number of mistakes in the word recall were at higher risk of mild cognitive impairment (MCI) or dementia. Longitudinal data of the Multidomain Alzheimer Preventive Trial (MAPT) was used to retrospectively measure the cognitive capacity according to the ICOPE Step 1 tool. Incident dementia was assessed by two multidisciplinary committees independent from each other. MCI was defined as Clinical Dementia Rating scale CDR = 0.5. Failure to recall the name of the weekday had a three-fold risk of incident dementia in the next 5 years (HRa = 3.11, 95%CI: 1.18-8.17). Having two or three mistakes in the word recall carried a higher risk of incident dementia, (HRa for two mistakes = 3.50, 95% CI: 1.49-8.26; HRa for three mistakes = 4.28, 95% CI: 1.60-11.46), but not MCI. People with impaired cognitive capacity according to the ICOPE Step 1 tool deserve further assessment and a closer follow-up.

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.

Experiences of dementia and attitude towards prevention: a qualitative study among older adults participating in a prevention trial.

BACKGROUND: A better insight into older adults' understanding of and attitude towards cognitive disorders and their prevention, as well as expectations and reasons for participation in prevention trials, would help design, conduct, and implement effective preventive interventions. This qualitative study aimed at exploring the knowledge and perceptions of cognitive disorders and their prevention among participants in a prevention trial. METHODS: Semi-structured interviews were conducted among the participants of a multinational randomised controlled trial testing the efficacy of a lifestyle-based eHealth intervention in preventing cardiovascular disease or cognitive decline in community dwellers aged 65+. Participants were probed on their reasons for participation in the trial and their views on general health, cardiovascular disease, ageing, and prevention. The subset of data focusing on cognitive disorders (15 interviewees; all in Finland) was considered for this study. Data were analysed using content analysis. RESULTS: Participants' knowledge of the cause and risk factors of cognitive disorders and prevention was limited and superficial, and a need for up-to-date, reliable, and practical information and advice was expressed. Cognitive disorders evoked fear and concern, and feelings of hopelessness and misery were frequently expressed, indicating a stigma. Strong heredity of cognitive disorders was a commonly held belief, and opinions on the possibility of prevention were doubtful, particularly in relation to primary prevention. Family history and/or indirect experiences of cognitive disorders was a recurrent theme and it showed to be linked to both the knowledge of and feelings associated with cognitive disorders, as well as attitude towards prevention. Indirect experiences were linked to increased awareness and knowledge, but also uncertainty about risk factors and possibility of prevention. Distinct fear and concerns, particularly over one's own cognition/risk, and high motivation towards engaging in prevention and participating in a prevention trial were also identified in connection to this theme. CONCLUSIONS: Family history and/or indirect experiences of cognitive disorders were linked to sensitivity and receptiveness to brain health and prevention potential. Our findings may be helpful in addressing older adults' expectations in future prevention trials to improve recruitment, maximise adherence, and facilitate the successful implementation of interventions.

Cognitive, functional, physical, and nutritional status of the oldest old encountered in primary care: a systematic review.

BACKGROUND: The oldest old (individuals over 90 years) are a fast-growing population. Characterizing their specificity would be helpful to adapt health care. This study aimed to characterize the cognitive, functional, nutritional, and physical status of individuals over 90. METHODS: We conducted a systematic review of cross-sectional or cohort studies of individuals aged 90 years old or more, living at home or in a nursing home, in April 2018. Two reviewers selected eligible articles, extracted data, and evaluated the risk of bias (assessed by the Newcastle-Ottawa Scale). RESULTS: The search strategy identified 3086 references; 35 articles were included referring to 8 cross-sectional and 27 longitudinal studies. Dementia was diagnosed in 30-42.9% of study participants, cognitive impairment in 12-50%, and 31-65% had no cognitive impairment. In terms of activities of daily living, 14-72.6% of individuals had no difficulty, 35.6-38% had difficulty, and 14.4-55.5% were dependent. For instrumental activities of daily living, 20-67.9% needed help. Regarding nutritional status, the Mini Nutritional Assessment Short Form mean score ranged from 10.3 (SD: 1.8) to 11.1 (SD: 2.4). Eight to 32% of individuals could not stand up from a chair, 19-47% could stand without the use of their arms; and 12.9-15% were not able to walk 4 m. CONCLUSIONS: These results suggest a heterogeneous population with a certain proportion of oldest old with a low level of disability. These findings suggest that a specific approach in the care of the oldest old could help prevent disability.

Dementia risk scores as surrogate outcomes for lifestyle-based multidomain prevention trials-rationale, preliminary evidence and challenges.

INTRODUCTION: Although not designed as such, dementia risk scores might be useful surrogate outcomes for dementia prevention trials. Their suitability may be improved by using continuous scoring systems, taking into account all changes in risk factors, not only those crossing cut-off values. METHODS: In three large multidomain dementia prevention trials with 1.5 to 2 years of follow-up (Multidomain Alzheimer Preventive Trial, Prevention of Dementia by Intensive Vascular Care and Healthy Ageing Through Internet Counselling in the Elderly) we assessed (1) responsiveness (sensitivity to change) and (2) actual and simulated intervention effects of the original and crude/weighted z-score versions of the cardiovascular risk factors, aging and incidence of dementia, and Lifestyle for Brain Health scores. RESULTS: All versions of the risk scores were generally responsive, and able to detect small though statistically significant between-group differences after multidomain interventions. Simulated intervention effects were well detected in z-score versions as well as in the original scores. DISCUSSION: Dementia risk scores and their z-score versions show potential as surrogate outcomes. How changes in risk scores affect dementia remains to be determined.

World-Wide FINGERS Network: A global approach to risk reduction and prevention of dementia.

Reducing the risk of dementia can halt the worldwide increase of affected people. The multifactorial and heterogeneous nature of late-onset dementia, including Alzheimer's disease (AD), indicates a potential impact of multidomain lifestyle interventions on risk reduction. The positive results of the landmark multidomain Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) support such an approach. The World-Wide FINGERS (WW-FINGERS), launched in 2017 and including over 25 countries, is the first global network of multidomain lifestyle intervention trials for dementia risk reduction and prevention. WW-FINGERS aims to adapt, test, and optimize the FINGER model to reduce risk across the spectrum of cognitive decline-from at-risk asymptomatic states to early symptomatic stages-in different geographical, cultural, and economic settings. WW-FINGERS aims to harmonize and adapt multidomain interventions across various countries and settings, to facilitate data sharing and analysis across studies, and to promote international joint initiatives to identify globally implementable and effective preventive strategies.

Anticholinergic exposure and cognitive decline in older adults: effect of anticholinergic exposure definitions in a 3-year analysis of the multidomain Alzheimer preventive trial (MAPT) study.

AIM: The aim of the present study was to assess the association between anticholinergic (atropinic) burden and cognitive decline in older adults over the course of 3 years. METHODS: We used data from Multidomain Alzheimer Preventive Trial (MAPT) study participants aged ≥70 years and at risk of cognitive decline. Cognitive function was assessed with a composite score [Mini-Mental State Examination (MMSE) orientation, Free and Cued Selective Reminding Test, Category Naming Test, Digit Symbol Substitution Test] at 12, 24 and 36 months. Participants declining by more than 0.236 points on the composite score (representing the lowest quintile of 1-year cognitive change) during any 1-year period were considered to have undergone cognitive decline. Anticholinergic exposure was defined by four methods for each of four anticholinergic scales (Anticholinergic Drug Scale, Anticholinergic Cognitive Burden, Anticholinergic Risk Scale, the Durán list). The association between cognitive decline and time-varying anticholinergic exposure [primary analysis using the Durán list and maximal anticholinergic score (0, 1 or 3)] was assessed using Cox proportional hazards models. Other cognitive decline definitions were used in sensitivity analyses. RESULTS: At baseline, among 1396 patients included, 7.4-23.5% were exposed to anticholinergic agents, depending on the anticholinergic scale used. Sixty-four per cent of participants experienced cognitive decline during follow-up. Regardless of the anticholinergic scale/exposure measurement used, no significant association was observed with cognitive decline {primary analysis: compared with non-anticholinergic agent users, hazard ratio [HR] = 1.14 [95% confidence interval (CI) = 0.95, 1.38] for anticholinergic score = 1; HR = 0.92 [95% CI = 0.65, 1.30] for score = 3}. Results were stable in sensitivity analyses. CONCLUSION: We found no significant association between anticholinergic exposure and cognitive decline in older adults using anticholinergic scales and definitions of exposure.

Ready-meal consumption in older people: association with obesity and dietary intake.

OBJECTIVE: To investigate ready-meal consumption trends in older French people, its association with overall diet quality and obesity. DESIGN: Cross-sectional analysis SETTING: Multidomain Alzheimer Preventive Trial (MAPT), France SUBJECTS: 421 MAPT participants (mean age 76.8 years) who filled a food frequency questionnaire. RESULTS: The frequency of ready-meal consumption was low, with nearly 90% of participants declaring consuming ≤ 1 ready-meal per week. Compared to non- and low-consumers (≤ 1 ready-meal/week), regular consumers (≥ 2 ready-meals/week) were older (p < 0.01), more often frail and pre-frail (p 0.04), with impaired cognition (p = 0.02) and functional status (p = 0.02), with more depressive symptoms (p = 0.03) and more difficulties with preparing meals (p = 0.01). Results from multivariate analyses showed that regular ready-meal consumption was not associated with obesity (p = 0.26) and diet quality (p = 0.37). CONCLUSIONS: In our sample, few older people declared consumption of 2 or more ready-meals per week, this consumption was not associated with a higher prevalence of obesity or a lower diet quality, despite the fact that these subject were older, with a lower physical and cognitive status. These findings suggest that, for these people with difficulties in meal preparation, convenience foods consumed occasionally could help to maintain diet quality and weight status.

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.

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.

Resource Use and Cost of Alzheimer's Disease in France: 18-Month Results from the GERAS Observational Study.

BACKGROUND: There is little longitudinal data on resource use and costs associated with Alzheimer's disease (AD) in France. OBJECTIVES: To evaluate resource use and societal costs associated with AD in a French cohort of patients and their caregivers and the effect of patient cognitive decline on costs over an 18-month period. METHODS: Community-dwelling patients with mild, moderate, or moderately severe/severe AD dementia (n = 419) were followed-up for 18 months. Total societal costs were estimated by applying 2010 unit costs to resource use, including outpatient visits, hospital days, institutionalization, and caregiver hours. Cognitive function was assessed by Mini-Mental State Examination scores. RESULTS: Mean cumulative total costs over the 18-month period were €24,140 for patients with mild AD dementia, €34,287 for those with moderate AD dementia, and €44,171 for those with moderately severe/severe AD dementia (P < 0.001; ANOVA comparison between severity groups). The biggest contributor to total societal costs was caregiver informal care (>50% of total costs at all stages of AD dementia). Cognitive decline (≥3-point decrease in Mini-Mental State Examination score or institutionalization) was associated with a 12.5% increase in total costs (P = 0.02). Significant differences were observed across severity groups for caregiver time (P < 0.001); mean monthly caregiver time increased at each time point over the 18 months in each severity group. CONCLUSIONS: Increasing severity of AD dementia in France is associated with increased use of resources as well as increased total societal and patient costs; informal care was the greatest cost contributor. Clinically meaningful cognitive decline is associated with significantly increased costs.

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.

Impact of diabetes on caregiver stress in patients with Alzheimer's disease: data from the ICTUS study.

ABSTRACTBackground:To estimate the impact of comorbid diabetes on caregiver stress in Alzheimer's disease (AD) patients from the Impact of Cholinergic Treatment Use (ICTUS) study. METHODS: Using the Data from the ICTUS study, diabetes mellitus (DM) was recorded at baseline and caregiver burden was assessed twice per year using the Zarit Burden Interview (ZBI) scale. The three-factorial model of ZBI (the effect on the social and personal life of caregivers, the psychological burden and the feelings of guilt) was adopted. Linear mixed models were used to examine the relation between DM and the scores of ZBI. RESULTS: The present analyses were conducted on 1,264 AD subjects. A total of 156 patients (12.3%) had DM with taking antidiabetic medication and/or self-report of a history. At baseline, the caregivers of patients with or without DM had similar ZBI global scores and similar scores of three different factors of ZBI. Unadjusted and adjusted models both indicated that ZBI global score increased over a 24-month follow-up without significant effect of DM. Similarly, unadjusted model showed that DM was not determining any significant difference in the score of any factor. However, adjusted model indicated that in diabetic patients, the scores of the social and personal life of caregivers and the psychological burden increased more slowly than those in non-diabetic patients (p = 0.04 and 0.01, respectively). CONCLUSIONS: DM may affect the caregivers' daily social and personal life and psychological burden in AD patients. It is necessary for further research.

Cross-sectional associations of cortical ß-amyloid with erythrocyte membrane long-chain polyunsaturated fatty acids in older adults with subjective memory complaints.

Omega-3 (n-3) and 6 (n-6) polyunsaturated fatty acids (PUFAs) have been associated with reduced cognitive decline in observational studies. Hence, we examined the cross-sectional associations between cortical ß-amyloid (Aß) and erythrocyte membrane PUFAs in 61 non-demented elderly individuals reporting subjective memory complaints from the Multidomain Alzheimer Preventive Trial placebo arm. Cortical-to-cerebellar standard uptake value ratios were obtained using [18 F] florbetapir positron emission tomography. Fatty acids were measured in erythrocyte membranes by gas chromatography. Associations were explored using adjusted multiple linear regression models and were considered significant at p ≤ 0.005 after correction for multiple testing (10 comparisons). We found no significant associations between cortical Aß and erythrocyte membrane PUFAs. The associations closest to significance after adjustment were those between Aß and erythrocyte membrane arachidonic acid (without apolipoprotein E status adjustment: B-coefficient, 0.03; CI, 0.01, 0.05; p = 0.02. Including Apolipoprotein E adjustment: B-coefficient, 0.03; CI, 0.00, 0.06; p = 0.04) and Aß and erythrocyte membrane linoleic acid (without apolipoprotein E status adjustment: B-coefficient, -0.02; CI, -0.04, 0.00; p = 0.02. Including Apolipoprotein E adjustment: B-coefficient, -0.02; CI, -0.04, 0.00; p = 0.09). Furthermore, the association between Aß and erythrocyte membrane arachidonic acid seemed to be specific to Apolipoprotein E ε4 non-carriers (B-coefficient 0.03, CI: 0.00, 0.06, p = 0.03, n = 36). In contrast, no association was found between Aß and erythrocyte membrane linoleic acid in Apolipoprotein E ε4 stratified analysis. Investigating the relationships between Aß and PUFAs longitudinally would provide further evidence as to whether fatty acids, particularly arachidonic acid and linoleic acid, might modulate cognition through Aß-dependent mechanisms.