The Mini Nutritional Assessment-Short Form and mortality in nursing home residents — Results from the INCUR study

**Objectives** To examine whether the Mini Nutritional Assessment-Short Form (MNA-SF) score and its individual items are predictors of mortality in a nursing home population. **Design** Prospective, secondary analysis from the Incidence of pNeumonia and related ConseqUences in nursing home Residents (INCUR) study with 1-year follow-up. **Participants** A total of 773 older persons (women 74.4%) living in 13 French nursing homes. **Measurements** At baseline, nutritional status was assessed with the MNA-SF. Overall mortality rate was measured over a 12-month follow-up period after the baseline assessment visit. Cox proportional hazard models were performed to test the predictive capacity of the MNA-SF score and its single components for mortality. **Results** Mean age of participants was 86.2 (standard deviation, SD 7.5) years. Mean MNA-SF score was 9.8 (SD 2.4). Among participants, 198 (25.6%) presented a normal nutritional status (12–14 points), 454 (58.7%) were at risk of malnutrition (8–11 points), and 121 (15.7%) were malnourished. After one year of follow-up, 135 (17.5%) participants had died. Age, female gender, baseline weight, BMI and MNA-SF were significant predictors of mortality whereas no specific chronic disease was. The total MNA-SF score was a significant predictor of mortality (Hazard Ratio=0.83; 95% CI 0.75–0.91; p<0.001), even after adjustment for potential confounders. Four individual items: weight loss, decrease in food intake, recent stress and BMI were independent predictors of mortality. **Conclusion** The MNA-SF appears to be an accurate predictor of one-year mortality in nursing home residents. Thus, this tool may be regarded not only as a nutritional screening tool, but also as an instrument for identifying the most-at-risk individuals in this population

Validation of the Mini Nutritional Assessment-Short Form in a population of frail elders without disability. Analysis of the Toulouse Frailty Platform population in 2013

**Objective** To assess the validity of the Mini Nutritional Assessment-Short Form (MNA-SF) in elderly patients from the Toulouse Frailty Platform. **Participants** Overall, 267 patients aged 65 and over, without severe cognitive impairment (i.e. Mini Mental Status Examination > 20 and CDR<1), no physical disability (i.e. Activities of Daily Living ≥ 5) and no active cancer history (over the past 12 months) were included in 2013. **Measurements** Receiver operating characteristic (ROC) analyses were used to assess the predictive validity of the French version of the MNA-SF for good nutritional status (defined as a full MNA score≥24/30). Analyses were conducted in the overall sample and then in subgroups of frail and pre-frail subjects according to the frailty phenotype. Optimal cut-off points were determined to obtain the best sensitivity/specificity ratio and the highest number of correctly classified subjects. **Results** Among 267 patients, mean age=81.5±5.8; women=67.0%; 138 (51.7%) were frail, 98 (36.7%) were pre-frail and 31 (11.6%) were robust. Given their MNA-SF scores, 201 (75.3%) had a good nutritional status, 61 (22.8%) were at risk of malnutrition and 5 (1.9%) were malnourished. In the overall sample, but also in subgroups of pre-frail or frail elders, the areas under ROC curves were 0.954, 0.948 and 0.958 respectively. The 11 points cut-off provided the best correct classification ratio (91.4%); sensitivity=94.0%, specificity=83.3%. **Conclusion** The MNA-SF appeared to be a validated and effective tool for malnutrition screening in frail elders. Implementing this tool in clinical routine should contribute to improving the screening of malnourished frail individuals

A Pragmatic, Data-Driven Method to Determine Cutoffs for CSF Biomarkers of Alzheimer Disease Based on Validation Against PET Imaging

OBJECTIVE: To elaborate a new algorithm to establish a standardized method to define cuff-offs for CSF biomarkers of Alzheimer's disease (AD) by validating the algorithm against CSF classification derived from PET imaging. METHODS: Low and high levels of CSF phosphorylated tau were first identified to establish optimal cut-offs for CSF amyloid-β peptide (Aβ) biomarkers. These Aβ cut-offs were then used to determine cut-offs for CSF tau and phosphorylated tau markers. We compared this algorithm to a reference method, based on tau and amyloid PET imaging status (ADNI study), and then applied the algorithm to 10 large clinical cohorts of patients. RESULTS: A total of 6,922 subjects with CSF biomarkers data were included (mean (SD) age: 70.6 (8.5) years, 51.0% women). In the ADNI study population (n=497), the agreement between classification based on our algorithm and one based on amyloid/tau PET imaging was high with Cohen's kappa coefficient between 0.87 and 0.99. Applying the algorithm to 10 large cohorts of patients (n=6,425), the proportion of persons with AD ranged from 25.9% to 43.5%. DISCUSSION: The proposed novel, pragmatic method to determine CSF biomarkers cut-offs for AD does not require assessment of other biomarkers or assumptions concerning the clinical diagnosis of patients. Use of this standardized algorithm is likely to reduce heterogeneity in AD classification

Plos Med

Background The ε4 allele of apolipoprotein E (APOE) gene and increasing age are two of the most important known risk factors for developing Alzheimer disease (AD). The diagnosis of AD based on clinical symptoms alone is known to have poor specificity; recently developed diagnostic criteria based on biomarkers that reflect underlying AD neuropathology allow better assessment of the strength of the associations of risk factors with AD. Accordingly, we examined the global and age-specific association between APOE genotype and AD by using the A/T/N classification, relying on the cerebrospinal fluid (CSF) levels of β-amyloid peptide (A, β-amyloid deposition), phosphorylated tau (T, pathologic tau), and total tau (N, neurodegeneration) to identify patients with AD. Methods and findings This case–control study included 1,593 white AD cases (55.4% women; mean age 72.8 [range = 44–96] years) with abnormal values of CSF biomarkers from nine European memory clinics and the American Alzheimer’s Disease Neuroimaging Initiative (ADNI) study. A total of 11,723 dementia-free controls (47.1% women; mean age 65.6 [range = 44–94] years) were drawn from two longitudinal cohort studies (Whitehall II and Three-City), in which incident cases of dementia over the follow-up were excluded from the control population. Odds ratio (OR) and population attributable fraction (PAF) for AD associated with APOE genotypes were determined, overall and by 5-year age categories. In total, 63.4% of patients with AD and 22.6% of population controls carried at least one APOE ε4 allele. Compared with non-ε4 carriers, heterozygous ε4 carriers had a 4.6 (95% confidence interval 4.1–5.2; p < 0.001) and ε4/ε4 homozygotes a 25.4 (20.4–31.2; p < 0.001) higher OR of AD in unadjusted analysis. This association was modified by age (p for interaction < 0.001). The PAF associated with carrying at least one ε4 allele was greatest in the 65–70 age group (69.7%) and weaker before 55 years (14.2%) and after 85 years (22.6%). The protective effect of APOE ε2 allele for AD was unaffected by age. Main study limitations are that analyses were based on white individuals and AD cases were drawn from memory centers, which may not be representative of the general population of patients with AD. Conclusions In this study, we found that AD diagnosis based on biomarkers was associated with APOE ε4 carrier status, with a higher OR than previously reported from studies based on only clinical AD criteria. This association differs according to age, with the strongest effect at 65–70 years. These findings highlight the need for early interventions for dementia prevention to mitigate the effect of APOE ε4 at the population level

Contribution of amyloid biomarkers for characterizing memory complaints in older adults

Les biomarqueurs de la maladie d’Alzheimer (MA) permettraient d’identifier les processus pathologiques de la maladie plusieurs années avant l’apparition des premiers signes cliniques. Ainsi, la tomographie par émission de positons (TEP) reposant sur les radio-traceurs liant les plaques amyloïdes, a ouvert de nouvelles perspectives en matière d’identification précoce de la maladie, in vivo, très en amont des premiers symptômes. Cependant, l’utilisation de ces biomarqueurs est restée limitée à de faibles effectifs de sujets, rarement suivis au-delà de quelques mois et le coût important de ces outils nous autorise à étudier leurs performances au regard des batteries de tests cognitifs et fonctionnels dont nous disposons. L’objectif général de ce travail était d’évaluer l’intérêt de l’utilisation du TEP scanner amyloïde au sein d’une population parfaitement phénotypée de sujets âgés présentant une plainte mnésique associée ou non à des signes cliniques objectifs. Notre population d’étude était constituée de 271 participants de l’essai MAPT âgés de 70 ans et plus, sans troubles cognitifs majeurs, ayant réalisé un TEP scanner amyloïde. Dans un premier travail, nous avons comparé les caractéristiques socio-démographiques et cliniques des sujets selon la présence ou non de plaques amyloïdes et d’une atteinte de la mémoire épisodique. Dans un second travail, nous avons analysé l’association transversale entre la charge amyloïde cérébrale et les performances pour les activités instrumentales de la vie quotidienne (IADL). Enfin, dans un troisième travail, nous avons comparé l’évolution des performances pour les IADL au cours des trois années de suivi en fonction de la charge amyloïde cérébrale.Les sujets avec une charge amyloïde positive au TEP présentaient de moins bonnes performances pour les IADL que ceux ayant un scanner négatif, en dépit d’un fonctionnement cognitif comparable. La présence de plaques amyloïdes cérébrales était associée à une évolution défavorable des performances pour les IADL, malgré la prise en compte de l’âge, du groupe d’intervention dans l’essai MAPT et du génotype ApoE. Notre travail montre que la présence de plaques amyloïdes cérébrales chez des sujets ayant une plainte mnésique est systématiquement associée à une moindre capacité à réaliser les activités complexes du quotidien malgré l’absence de troubles cognitifs avérés. Néanmoins, l’absence de traitement curatif de la MA et l’incertitude quant à l’évolution à long terme des sujets asymptomatiques présentant une anomalie isolée d’un biomarqueur motivent la réalisation d’autres études longitudinales, ciblées sur les sujets les plus âgés.The biomarkers of Alzheimer’s disease (AD) have enabled the identification of its pathological features, many years before the onset of clinical symptoms. Positon Emission Tomography (PET) using radiotracers binding the amyloid plaques has, indeed, paved the way for new perspectives. However, these biomarkers have only been studies in small populations so far, with limited follow-up. Moreover, their high costs allow us to question their performances in view of their relationship to physical and cognitive assessment instruments. The main goal of our work was to assess the interest of amyloid PET in a well-phenotyped population of elderly subjects reporting memory complaints, associated with objective cognitive impairment or not. Our studied population comprised 271 participants from the MAPT trial aged 70 and over, without major cognitive impairment, who performed amyloid PET examination. The first analysis studied the socio-demographical and clinical characteristics of individuals depending on the presence of brain amyloid deposition or episodic memory impairment. A second study examined the cross-sectional association between brain amyloid load and Instrumental Activities of Daily Living (IADL) performance. The last analysis focused of the longitudinal change in IADL abilities between amyloid positive and amyloid negative participants over the 3-year follow-up.Amyloid positive subjects showed poorer abilities in IADL compared to their amyloid negative counterparts, despite similar cognitive performance. Brain amyloid load also impacted the daily functioning of individuals over time, taking in consideration confounding factors such as age, randomization group and ApoE genotyping. These findings confirmed the relationship of brain amyloid deposition to subtle changes in IADL abilities, even in the absence of cognitive impairment. Yet, the absence of disease modifying agents as well as uncertainties regarding the long-term evolution of asymptomatic individuals showing a positive biomarker are still to be determined. Further longitudinal studies including older old participants are warranted to address these concerns

Evaluation de l'efficacité d'un outil destiné aux médecins généralistes pour la prise en charge des personnes âgées dénutries au décours d'une hospitalisation en gériatrie aiguë

PARIS6-Bibl. St Antoine CHU (751122104) / SudocSudocFranceF

RETRACTED: Association Between Frailty and Cognitive Impairment: Cross-Sectional Data From Toulouse Frailty Day Hospital

International audienc

Cerebrospinal Fluid Alpha-Synuclein Improves the Differentiation between Dementia with Lewy Bodies and Alzheimer&rsquo;s Disease in Clinical Practice

Background: Alpha-synuclein, abnormally aggregated in Dementia with Lewy Bodies (DLB), could represent a potential biomarker to improve the differentiation between DLB and Alzheimer&rsquo;s disease (AD). Our main objective was to compare Cerebrospinal Fluid (CSF) alpha-synuclein levels between patients with DLB, AD and Neurological Control (NC) individuals. Methods: In a monocentric retrospective study, we assessed CSF alpha-synuclein concentration with a validated ELISA kit (ADx EUROIMMUN) in patients with DLB, AD and NC from a tertiary memory clinic. Between-group comparisons were performed, and Receiver Operating Characteristic analysis was used to identify the best CSF alpha-synuclein threshold. We examined the associations between CSF alpha-synuclein, other core AD CSF biomarkers and brain MRI characteristics. Results: We included 127 participants (mean age: 69.3 &plusmn; 8.1, Men: 41.7%). CSF alpha-synuclein levels were significantly lower in DLB than in AD (1.28 &plusmn; 0.52 ng/mL vs. 2.26 &plusmn; 0.91 ng/mL, respectively, p &lt; 0.001) without differences due to the stage of cognitive impairment. The best alpha-synuclein threshold was characterized by an Area Under the Curve = 0.85, Sensitivity = 82.0% and Specificity = 76.0%. CSF alpha-synuclein was associated with CSF AT(N) biomarkers positivity (p &lt; 0.01) but not with hippocampal atrophy or white matter lesions. Conclusion: CSF Alpha-synuclein evaluation could help to early differentiate patients with DLB and AD in association with existing biomarkers

Plasma neurofilament light chain in memory clinic practice: Evidence from a real-life study

Objective: To explore the accuracy of plasma neurofilament light chain (NfL) as a biomarker for diagnosis and staging of cognitive impairment, in a large cohort with of previously diagnosed patients in clinical practice. Methods: Retrospective, cross-sectional, monocentric study, from a tertiary memory clinic. Patients underwent cerebrospinal fluid core Alzheimer's disease (AD) biomarker evaluation using ELISA or Elecsys methods, and plasma NfL analysis using the single molecule array technology. The patients' biomarker data were examined for associations with: i/cognitive status ii/presence of neurodegenerative disease and iii/diagnostic groups. Associations between core CSF biomarkers and plasma NfL were determined. Results: Participants (N = 558, mean age = 69.2 ± 8.8, 56.5% women) were diagnosed with AD (n = 274, considering dementia and MCI stages), frontotemporal dementia (FTD, n = 55), Lewy body disease (LBD, n = 40, considering MCI and dementia stages), other neurodegenerative diseases, n = 57 (e.g Supranuclear Palsy, Corticobasal syndrome), non-neurodegenerative cognitive impairment (NND, n = 79, e.g. vascular lesions, epilepsy or psychiatric disorders) or subjective cognitive impairment (SCI, n = 53). Mean plasma NfL (log, pg/mL) levels were higher in neurodegenerative than non-neurodegenerative disorders (1.35 ± 0.2 vs 1.16 ± 0.23, p < 0.001), higher in all diagnostic groups than in SCI (1.06 ± 0.23) p < 0.001), and associated with the stage of cognitive impairment (p < 0.001). The addition of plasma NfL to a clinical model (age, MMSE and APOE ε4 carriership) marginally improved the discrimination of degenerative from non-degenerative disorders in ROC analysis (AUC clinical model: 0.81, 95% CI = [0.77;0.85] AUC clinical model + plasma NfL: AUC = 0.83 95% CI = [0.78;0.87], delta Akaike information criterion = −11.7). Discussion: Plasma NfL could help discrimination between degenerative and non-degenerative cognitive disorders, albeit not better than comprehensive clinical evaluation