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).

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.

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.

Assessing Alzheimer's disease patients' quality of life: Discrepancies between patient and caregiver perspectives.

INTRODUCTION: Quality of life (QOL) is an important dimension to consider in Alzheimer's disease (AD), but few large-scale studies have analyzed self and caregiver reports of patient QOL. METHODS: Patient QOL was evaluated in a cohort of 574 AD patients with the QOL-AD scale over 2 years. RESULTS: Caregiver reports of patient QOL were lower at baseline than self reports. Older patient age was associated with overestimation of QOL by caregivers, whereas neuropsychiatric inventory score and caregiver burden were associated with underestimation. Activities of daily living limitation, depressive symptoms, and caregiver burden were systematically associated with poorer QOL, whereas caregiver relationship and apathy were associated with poorer QOL only for self reports or caregiver reports, respectively. Cognitive function and professional care were not associated with QOL. Self-rated patient QOL did not change over time, whereas disease severity markers and caregiver-rated patient QOL declined. DISCUSSION: It is important to assess both self and caregiver ratings when assessing patient QOL.

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.

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.

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.

Potentially inappropriate medication use among patients with Alzheimer disease in the REAL.FR cohort: be aware of atropinic and benzodiazepine drugs!

OBJECTIVE: Few studies have investigated potentially inappropriate medication (PIM) use in patients with Alzheimer's disease (AD). The aim of our study was to assess the prevalence of PIM in community-dwelling patients diagnosed with mild-to-moderate AD and identify the clinical factors associated with PIM prescriptions. METHODS: REAL.FR is a 4-year, prospective, multicenter French cohort of AD patients recruited in centers of expertise. We analyzed patient baseline data at entry into the study. PIMs were assessed using the Laroche list. A multivariate logistic regression was conducted to assess factors associated with PIMs. RESULTS: A total of 684 AD patients were enrolled in the study [mean age 77.9 ± 6.8 years, 486 (71.0 %) females]. According to the Laroche list, 46.8 % [95 % confidence interval (CI) 43.0-50.5 %] of the patients had at least one PIM. "Cerebral vasodilators" were the most widely used class of PIM, accounting for 24.0 % (95 % CI 20.9-27.3 %) of all prescriptions, followed by atropinic drugs (17.0 %, 95 % CI 14.1-19.8 %) and long half-life benzodiazepines (8.5 %, 95 % CI 6.4-10.6 %). Atropinic drugs were associated with cholinesterase inhibitors in 16 % of patients. In the multivariate analysis, only two factors, namely, female gender [odds ratio (OR) 1.5, 95 % CI 1.1-2.2] and polypharmacy (≥5 drugs; OR 3.6, 95 % CI 2.6-4.5) were associated with prescriptions for PIMs. CONCLUSIONS: These results reveal that approximately one out of two community-dwelling patients with mild-to-moderate AD treated by AD specialists use PIMs. They also indicate that the characteristics of the disease and the pharmacodynamic/pharmacokinetic profile of the drugs prescribed are not sufficiently taken into account by physicians when prescribing for AD patients.

Weight changes in Alzheimer's disease patients with increased aberrant motor behavior.

OBJECTIVE: Weight loss and behavioral disturbances are frequent over the course of Alzheimer's disease (AD) and are risk factors for poor outcome. We investigated the impact of aberrant motor behavior (AMB) on weight changes in older adults with AD. The hypothesis that patients with AMB are more likely to lose weight than patients without AMB was assessed. METHODS: A prospective study of 686 patients with moderate AD from the REAL.FR cohort was assessed. The AMB at baseline was defined by the item 10 from the Neuropsychiatric Inventory scale (NPI-10). Patients were classified as "no or light AMB" (NPI-10 < 4), and "significant AMB" (NPI-10 ≥ 4). Weight changes were determined over the 4-year follow-up. RESULTS: The mean weight change over the 4 years was +2.2 ± 0.9 kg in patients with "significant AMB," whereas weight remained stable in patients with "no or light AMB" (p = 0.02). CONCLUSION: Older adults with moderate AD and "significant AMB" do gain weight.

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 .

Exploring the relationship between Alzheimer's disease severity and longitudinal costs.

OBJECTIVE: The joint impact of cognitive, functional, and behavioral statuses must be measured when exploring the impact of new drugs on Alzheimer's disease (AD) costs. There are very few recent studies of AD costs by all dimensions of disease severity. Our objective was to improve estimation of the relationship between AD severity and costs of AD care by using more comprehensive AD data severity and a large sample size. METHODS: Participants were community-dwelling AD patients recruited between 2003 and 2005 and followed annually during a 2-year period in 50 French memory clinics. We used the Resource Use in Dementia questionnaire to estimate costs from a societal perspective. We explored the presence of potential endogeneity bias by using instrumental variable regressions. RESULTS: Cognitive declines impacted informal costs more than medical and nonmedical costs, while functional declines impacted nonmedical costs more than medical and informal costs. Both cognitive and function declines increased the total costs of care. We found that the endogeneity of these variables led to a large underestimation of their impact of AD severity on costs. CONCLUSION: Potential endogeneity should be controlled for to prevent biased estimations of the impact of AD severity measures on costs.

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.

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.

Long-term progression of Alzheimer's disease in patients under antidementia drugs.

BACKGROUND: Patients with Alzheimer's disease (AD), even in the presence of symptomatic relief from medical intervention, face a persistent worsening of cognitive decline and performance in activities of daily living. Data regarding the long-term disease progression outside of therapeutic trials are lacking. We examined the effects of standard of care for AD patients on the prognosis of the disease in a real-life study over a 4-year period. METHODS: A total of 686 patients with mild-moderate AD were enrolled in 16 memory clinics (REseau sur la maladie d' Alzheimer FRançais [REAL.FR] cohort) and followed up twice annually with tools used in therapeutic trials (Mini-Mental Status Examination, Alzheimer Disease Assessment Scale-cognitive subscale [ADAS-cog]: cognitive function, Clinical Dementia Rating: dementia severity, Activity of Daily Living [ADL]: incapacities, NeuroPsychiatric Inventory: neuropsychiatric symptom). RESULTS: More than 90% of the patients used AD-specific medication over 4 years. Patients lost on average 2.4 points per year on the Mini-Mental Status Examination and gained 4.5 points on the ADAS-cog. ADL and NeuroPsychiatric Inventory scores became significantly worse over time. Incidence of incapacities for ADL and worsening of neuropsychiatric symptoms were 52.5 (95% confidence interval [CI]: 47.7-57.4) and 51.1 (95% CI: 46.2-56.1), respectively. Rates of mortality and institutionalization were 7.4 (95% CI: 6.2-8.5) and 13.4 (95% CI: 11.7-15.1). In all, 17% of patients in mild stage at baseline (Clinical Dementia Rating = 0.5) did not experience a major event (functional disabilities, neuropsychiatric symptoms, or death) over a 4-year period. CONCLUSIONS: As compared with previous surveys, the current study shows slower rates of decline in AD patients. The present data also underline the high level of variability of disease progression among AD patients. Outcome measures commonly used in clinical trials will need to take into account the recent changes in the prognosis of the disease.

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.

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.

Gait and balance impairments in Alzheimer disease patients.

OBJECTIVE: To describe the characteristics and associated factors of Alzheimer disease (AD) patients with balance and gait impairments. METHODS: Balance and gait impairments were assessed in 380 AD patients using the Tinetti test. RESULTS: A total of 120 (31.5%) patients had an abnormal Tinetti test, 96 (25.2%) had balance impairments, and 72 (18.9%) patients presented gait impairments. Global Tinetti score was associated with age [odds ratio (OR), 1.09; 95% confidence interval (CI), 1.05-1.14], Mini-Mental State Examination (MMSE) score (OR, 0.94; 95% CI, 0.90-0.99), activities of daily living (ADL) score (OR, 0.62; 95% CI, 0.47-0.83), and being man (OR, 0.44; 95% CI, 0.25-0.78). Balance impairment was associated with age (OR, 1.11; 95% CI, 1.05-1.17), ADL score (OR, 0.60; 95% CI, 0.43-0.84), and being female (OR, 0.19; 95% CI, 0.08-0.49). Gait impairment was associated with age (OR, 1.09; 95% CI, 1.03-1.15), MMSE score (OR, 0.92; 95% CI, 0.87-0.98), ADL score (OR, 0.63; 95% CI, 0.46-0.87), body mass index (OR, 1.10; 95% CI, 1.01-1.18), presence of comorbidities (OR, 2.13; 95% CI, 1.14-3.96), and the Cornell score (OR, 2.97; 95% CI, 1.12-7.89). CONCLUSIONS: AD patients are frequently concerned with balance and gait impairments. These impairments were associated to factors related to the severity of the disease (low MMSE and low ADL); nonmodifiable factors such as age or sex; and modifiable factors such as depression, obesity, and presence of comorbidities.

Antidepressant use in Alzheimer's disease patients: results of the REAL.FR cohort.

BACKGROUND: Psychotropic medication is widely prescribed in clinical practice for the management of behavioral and psychological symptoms of dementia (BPSD) in Alzheimer's disease (AD). However, there have been few pharmaco-epidemiological studies or studies conducted in a natural setting on the real use of antidepressants in AD. The aim of this survey was to assess the prevalence of antidepressant use in AD and to identify the clinical factors associated with antidepressant prescription. METHODS: REAL.FR is a four-year, prospective, multi-center study. Baseline data including demographic characteristics, clinical variables and drug intake were obtained. Depressive symptoms were determined using the Neuropsychiatric Inventory (NPI). RESULTS: A total of 686 AD patients were included. Antidepressant treatment was prescribed for 34.8% of patients. Clinically significant depressive symptoms (NPI >or= 4) were observed in 20.5% of the total population. Although depressed subjects were significantly more likely to be treated with antidepressants than non-depressed subjects (p<0.0001), only 60% of depressed subjects overall were prescribed an antidepressant. In multivariate analysis, clinically significant depressive symptoms were associated with antidepressant prescription although this result was only observed in subjects without a previous history of depression. CONCLUSIONS: The available data on antidepressant efficacy in BPSD other than depression (in particular, agitation, aggression and, occasionally, psychotic symptoms) do not influence prescription choices. Depressive symptoms may be taken more seriously in the absence of a previous history of depression, leading to increased antidepressant prescription rates in individuals presenting with depression for the first time.

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 .