Brain age as a biomarker for pathological versus healthy ageing - a REMEMBER study.

OBJECTIVES: This study aimed to evaluate the potential clinical value of a new brain age prediction model as a single interpretable variable representing the condition of our brain. Among many clinical use cases, brain age could be a novel outcome measure to assess the preventive effect of life-style interventions. METHODS: The REMEMBER study population (N = 742) consisted of cognitively healthy (HC,N = 91), subjective cognitive decline (SCD,N = 65), mild cognitive impairment (MCI,N = 319) and AD dementia (ADD,N = 267) subjects. Automated brain volumetry of global, cortical, and subcortical brain structures computed by the CE-labeled and FDA-cleared software icobrain dm (dementia) was retrospectively extracted from T1-weighted MRI sequences that were acquired during clinical routine at participating memory clinics from the Belgian Dementia Council. The volumetric features, along with sex, were combined into a weighted sum using a linear model, and were used to predict 'brain age' and 'brain predicted age difference' (BPAD = brain age-chronological age) for every subject. RESULTS: MCI and ADD patients showed an increased brain age compared to their chronological age. Overall, brain age outperformed BPAD and chronological age in terms of classification accuracy across the AD spectrum. There was a weak-to-moderate correlation between total MMSE score and both brain age (r = -0.38,p < .001) and BPAD (r = -0.26,p < .001). Noticeable trends, but no significant correlations, were found between BPAD and incidence of conversion from MCI to ADD, nor between BPAD and conversion time from MCI to ADD. BPAD was increased in heavy alcohol drinkers compared to non-/sporadic (p = .014) and moderate (p = .040) drinkers. CONCLUSIONS: Brain age and associated BPAD have the potential to serve as indicators for, and to evaluate the impact of lifestyle modifications or interventions on, brain health.

Evaluation of the Geriatric Nutritional Risk Index in predicting mortality in older patients with COVID-19 in the AgeBru cohort.

OBJECTIVE: To determine whether the Geriatric Nutritional Risk Index (GNRI) on hospital admission was associated to an increased 14-day and 12-month mortality-risk in older inpatients with COVID-19. METHODS: Cohort study of consecutive inpatients admitted with COVID-19 in a university hospital (20/03/2020-11/05/2021). INCLUSION CRITERIA: age over 65 years and positive polymerase chain reaction test. EXCLUSION CRITERIA: missing data for weight, height, and/or albumin, hospital-acquired COVID-19, or patients transferred to other health facilities. OUTCOME: all-cause mortality at 14-day and 12-month follow-up. GNRI [1.489 × albumin (g/L)] + [41.7 (weight/ideal body weight)] was assessed at admission; scores ≤98 indicated risk of malnutrition. Cox-proportional hazards models assessed the association between the admission GNRI and 14-day and 12-month mortality-risk, after adjusting by demographic and clinical variables, including inflammation (C-reactive protein). RESULTS: Of the 570 eligible patients, 224 (mean age 78 years; 52.2% women) met inclusion criteria and 151 (67.4%) were classified at risk of malnutrition. Twenty patients died during the 14-day and 42 during the 12-month follow-up. The risk of 14-day mortality was nearly 10 times higher in patients with GNRI scores ≤98 (HR = 9.6 [95%CI 1.3-71.6], P = 0.028); this association was marginally significant in the adjusted model (HR = 6.73 [95%CI 0.89-51.11], P = 0.065)]. No association between GNRI and the 12-month mortality-risk was found. CONCLUSIONS: The GNRI may play a role in the short-term prognosis of older inpatients with COVID-19. Further studies are required to confirm the short-term predictive validity of the GNRI within this population (Clinicaltrials.gov_NCT05276752).

Association between Malnutrition Assessed by the Global Leadership Initiative on Malnutrition Criteria and Mortality in Older People: A Scoping Review.

The Global Leadership Initiative on Malnutrition (GLIM) criteria were introduced in 2018 for the diagnosis of malnutrition in adults. This review was aimed at gathering the evidence about the association between malnutrition according to the GLIM criteria and mortality in older people, an emerging and clinically meaningful topic in the implementation of the GLIM criteria in geriatric healthcare settings. This scoping review considered meta-analyses, systematic reviews, cohort studies, and cross-sectional studies published in PubMed, Scopus, and the Cochrane Database for Systematic Reviews from the development of the GLIM criteria in 2018 to January 2023. Seventeen articles (15 cohort and 2 cross-sectional studies) were included. The association between GLIM criteria and mortality had been assessed in hospitalized (11 over the 17 articles) and community-dwelling older populations, and those in nursing homes. The review found a strong association between malnutrition according to GLIM criteria and mortality in hospitalized (1.2-fold to 7-fold higher mortality) and community-dwelling older people (1.6-fold to 4-fold higher mortality). These findings highlight the prognostic value of the GLIM criteria and support strategies towards the implementation of malnutrition evaluation according to the GLIM, in order to optimize comprehensive geriatric assessment and provide older people with the highest quality of nutritional care. Studies in nursing home populations were very scarce and may be urgently required.

A short and simple bedside test to detect cognitive fluctuations in patients with dementia with Lewy bodies.

BACKGROUND AND PURPOSE: The establishment of cognitive fluctuations is important when dementia with Lewy bodies (DLB) is suspected but can be especially difficult in the absence of a caregiver who lives with the patient. We examined the possibility of using fluctuating scores on a forward (FDS) and a backward digit span (BDS) test as a marker for cognitive fluctuation. METHODS: Patients with DLB (21), other forms of dementia (14 with Alzheimer's disease, 8 with vascular dementia) and 20 controls were asked to perform an FDS and BDS twice, with an interval of 20 min. RESULTS: Seventy percent of patients with DLB showed evidence of cognitive fluctuations for at least one test, while less than 10% of controls and patients with other dementias did. Evidence of cognitive fluctuations on at least one of both tests classified 83% of patients correctly (i.e. DLB or not), with a sensitivity of 70% and a specificity of 90%. CONCLUSIONS: Repeated forward and backward digit span tests seem a valid, short, easy and inexpensive bedside tool to detect cognitive fluctuations in the diagnostic work-up of DLB, even in the absence of a caregiver, which limits the use of questionnaires.

External validation of FRISBEE 5-year fracture prediction models: a registry-based cohort study.

Five-year fracture risk prediction from the Fracture Risk Brussels Epidemiological Enquiry (FRISBEE) models was externally tested in 9716 Canadian women and demonstrated good discrimination but consistently overestimated risk. INTRODUCTION: Five-year risk prediction models for all fractures, major osteoporotic fractures (MOFs) and central fractures (proximal to forearm and ankle) from the FRISBEE cohort demonstrated good performance in the original derivation cohort. Our aim was to externally validate the FRISBEE-based 5-year prediction models in routine practice. METHODS: Using the population-based Manitoba Bone Mineral Density (BMD) registry, we identified women aged 60-85 years undergoing baseline BMD assessment from September 1, 2012 to March 31, 2018. Five-year probabilities of all fractures, MOFs and central fractures were calculated using the FRISBEE prediction models. We identified incident non-traumatic fractures up to 5 years from population-based healthcare data sources. Performance characteristics included area under the receiver operating characteristic curve (AUROC), gradient of risk (hazard ratio [HR] per SD increase and across risk tertiles) from Cox regression analysis, and calibration (ratio 5-year observed cumulative incidence to predicted fracture probability). RESULTS: We included 9716 women (mean age 70.7 + / - SD 5.3 years). During a mean observation time of 2.5 years, all fractures, MOFs and central fractures were identified in 377 (3.9%), 264 (2.7%) and 259 (2.7%) of the women. AUROC showed significant fracture risk stratification with the FRISBEE models (all fractures 0.69 [95%CI 0.67-0.72], MOFs 0.71 [95%CI 0.68-0.74], central fractures 0.72 [95%CI 0.69-0.75]). There was a strong gradient of risk for predicting fracture outcomes per SD increase (HRs from 1.98 to 2.26) and across risk tertiles (HRs for middle vs lowest from 2.25 to 2.41, HRs for highest vs lowest from 4.70 to 6.50). However, risk was overestimated for all fractures (calibration-in-the-large 0.63, calibration slope 0.63), MOF (calibration-in-the-large 0.51, calibration slope 0.57) and central fractures (calibration-in-the-large 0.55, calibration slope 0.60). CONCLUSIONS: FRISBEE 5-year prediction models were externally validated to stratify fracture risk similar to the derivation cohort, but would need recalibration for Canada as risk was overestimated.

Fragility Fractures in Postmenopausal Women: Development of 5-Year Prediction Models Using the FRISBEE Study.

CONTEXT: Individualized fracture risk may help to select patients requiring a pharmacological treatment for osteoporosis. FRAX and the Garvan fracture risk calculators are the most used tools, although their external validation has shown significant differences in their risk prediction ability. OBJECTIVE AND METHODS: Using data from the Fracture Risk Brussels Epidemiological Enquiry study, a cohort of 3560 postmenopausal women aged 60 to 85 years, we aimed to construct original 5-year fracture risk prediction models using validated clinical risk factors (CRFs). Three models of competing risk analysis were developed to predict major osteoporotic fractures (MOFs), all fractures, and central fractures (femoral neck, shoulder, clinical spine, pelvis, ribs, scapula, clavicle, sternum). RESULTS: Age, a history of fracture, and hip or spine BMD were predictors common to the 3 models. Excessive alcohol intake and the presence of comorbidities were specific additional CRFs for MOFs, a history of fall for all fractures, and rheumatoid arthritis for central fractures. Our models predicted the fracture probability at 5 years with an acceptable accuracy (Brier scores ≤ 0.1) and had a good discrimination power (area under the receiver operating curve of 0.73 for MOFs and 0.72 for central fractures) when internally validated by bootstrap. Three simple nomograms, integrating significant CRFs and the mortality risk, were constructed for different fracture sites. In conclusion, we derived 3 models predicting fractures with an acceptable accuracy, particularly for MOFs and central fractures. The models are based on a limited number of CRFs, and we constructed nomograms for use in clinical practice.

Prediction of an Imminent Fracture After an Index Fracture - Models Derived From the Frisbee Cohort.

Patients who sustain a fracture are at greatest risk of recurrent fracture during the next 2 years. We propose three models to identify subjects most at risk of an imminent fracture, according to fracture site (any fracture, major osteoporotic fracture [MOF] or central). They were constructed using data of the prospective Frisbee cohort, which includes 3560 postmenopausal women aged 60 to 85 years who were followed for at least 5 years. A total of 881 subjects had a first incident validated fragility fracture before December 2018. Among these, we validated 130 imminent fractures occurring within the next 2 years; 79 were MOFs, and 88 were central fractures. Clinical risk factors were re-evaluated at the time of the index fracture. Fine and Gray proportional hazard models were derived separately for each group of fractures. The following risk factors were significantly associated with the risk of any imminent fracture: total hip bone mineral density (BMD) (p < 0.001), a fall history (p < 0.001), and comorbidities (p = 0.03). Age (p = 0.05 and p = 0.03, respectively) and a central fracture as the index fracture (p = 0.04 and p = 0.005, respectively) were additional predictors of MOFs and central fractures. The three prediction models are presented as nomograms. The calibration curves and the Brier scores based on bootstrap resampling showed calibration scores of 0.089 for MOF, 0.094 for central fractures, and 0.132 for any fractures. The predictive accuracy of the models expressed as area under the receiver operating characteristic (AUROC) curve (AUC) were 0.74 for central fractures, 0.72 for MOFs, and 0.66 for all fractures, respectively. These AUCs compare well with those of FRAX and Garvan to predict the 5- or 10-year fracture probability. In summary, five predictors (BMD, age, comorbidities, falls, and central fracture as the incident fracture) allow the calculation with a reasonable accuracy of the imminent risk of fracture at different sites (MOF, central fracture, and any fracture) after a recent sentinel fracture. © 2021 American Society for Bone and Mineral Research (ASBMR).

Independent External Validation of FRAX and Garvan Fracture Risk Calculators: A Sub-Study of the FRISBEE Cohort.

Probabilistic models including clinical risk factors with or without bone mineral density (BMD) have been developed to estimate the 5- or 10-year absolute fracture risk. We investigated the performance of the FRAX and Garvan tools in a well-characterized population-based cohort of 3560 postmenopausal, volunteer women, aged 60 to 85 years at baseline, included in the Fracture Risk Brussels Epidemiological Enquiry (FRISBEE) cohort, during 5 years of follow-up. Baseline data were used to calculate the estimated 10-year risk of hip and major osteoporotic fractures (MOFs) for each participant using FRAX (Belgium). We computed the 5-year risk according to the Garvan model with BMD. For calibration, the predicted risk of fracture was compared with fracture incidence across a large range of estimated fracture risks. The accuracy of the calculators to predict fractures was assessed using the area under the receiver operating characteristic curves (AUC). The FRAX tool was well calibrated for hip fractures (slope 1.09, p < 0.001; intercept -0.001, p = 0.46), but it consistently underestimated the incidence of major osteoporotic fractures (MOFs) (slope 2.12, p < 0.001; intercept -0.02, p = 0.06). The Garvan tool was well calibrated for "any Garvan" fractures (slope 1.05, p < 0.001; intercept 0.01, p = 0.37) but largely overestimated the observed hip fracture rate (slope 0.32, p < 0.001; intercept 0.006, p = 0.05). The predictive value for hip fractures was better for FRAX (AUC: 0.841, 95% confidence interval [CI] 0.795-0.887) than for Garvan (AUC: 0.769, 95% CI 0.702-0.836, p = 0.01). The Garvan AUC for "any Garvan" fractures was 0.721 (95% CI 0.693-0.749) and FRAX AUC for MOFs was 0.708 (95% CI 0.675-0.741). In conclusion, in our Belgian cohort, FRAX estimated quite well hip fractures but underestimated MOFs, while Garvan overestimated hip fracture risk but showed a good estimation of "any Garvan" fractures. Both models had a good discriminatory value for hip fractures but only a moderate discriminatory ability for MOFs or "any Garvan" fractures. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Acute sarcopenia changes following hospitalization: influence of pre-admission care dependency level.

INTRODUCTION: Hospitalization is associated with acute changes in sarcopenia status in older people, but the influencing factors are not fully understood. Pre-admission care dependency level as a risk factor has not yet been investigated. OBJECTIVE: Evaluate if pre-admission care dependency level is an independent predictor of sarcopenia changes following hospitalization. SETTING AND SUBJECTS: Data came from the Sarcopenia 9+ EAMA Project, a European prospective multi-centre study. For this study, 227 hospitalised older people were included from four different hospitals in Belgium, Spain and Poland, between 18 February 2019 and 5 September 2020. METHODS: Sarcopenia status at admission and discharge were calculated using a combined score (desirability value) based on muscle mass (calf circumference), strength (grip) and function (walking speed). Ratio of admission to discharge status was the outcome (desirability ratio; 1.00 meaning no difference). Predictor variable was the pre-admission care dependency level, classified into three groups: independent older people living at home, dependent older people living at home and older people living in a care home. Linear regression models were applied, considering potential confounders. RESULTS: Mean desirability ratio for dependent older people living at home ('middle dependent group') was lower (0.89) compared to independent older people (0.98; regression coefficient -0.09 [95% CI -0.16, -0.02]) and care home patients (1.05; -0.16 [95% CI -0.01, -0.31]). Adjusting for potential confounders or using another statistical approach did not affect the main results. CONCLUSION: Dependent older people living at home were at higher risk of deterioration in sarcopenia status following hospitalization. In-depth studies investigating causes and potential interventions of these findings are needed.

Diagnostic Performance of Automated MRI Volumetry by icobrain dm for Alzheimer's Disease in a Clinical Setting: A REMEMBER Study.

BACKGROUND: Magnetic resonance imaging (MRI) has become important in the diagnostic work-up of neurodegenerative diseases. icobrain dm, a CE-labeled and FDA-cleared automated brain volumetry software, has shown potential in differentiating cognitively healthy controls (HC) from Alzheimer's disease (AD) dementia (ADD) patients in selected research cohorts. OBJECTIVE: This study examines the diagnostic value of icobrain dm for AD in routine clinical practice, including a comparison to the widely used FreeSurfer software, and investigates if combined brain volumes contribute to establish an AD diagnosis. METHODS: The study population included HC (n = 90), subjective cognitive decline (SCD, n = 93), mild cognitive impairment (MCI, n = 357), and ADD (n = 280) patients. Through automated volumetric analyses of global, cortical, and subcortical brain structures on clinical brain MRI T1w (n = 820) images from a retrospective, multi-center study (REMEMBER), icobrain dm's (v.4.4.0) ability to differentiate disease stages via ROC analysis was compared to FreeSurfer (v.6.0). Stepwise backward regression models were constructed to investigate if combined brain volumes can differentiate between AD stages. RESULTS: icobrain dm outperformed FreeSurfer in processing time (15-30 min versus 9-32 h), robustness (0 versus 67 failures), and diagnostic performance for whole brain, hippocampal volumes, and lateral ventricles between HC and ADD patients. Stepwise backward regression showed improved diagnostic accuracy for pairwise group differentiations, with highest performance obtained for distinguishing HC from ADD (AUC = 0.914; Specificity 83.0%; Sensitivity 86.3%). CONCLUSION: Automated volumetry has a diagnostic value for ADD diagnosis in routine clinical practice. Our findings indicate that combined brain volumes improve diagnostic accuracy, using real-world imaging data from a clinical setting.

Dementia with Lewy bodies in first-generation immigrants in a European memory clinic.

We wanted to explore possible differences in disease presentation, frequency, and age of onset of dementia with Lewy bodies (DLB) between first-generation immigrants (FGI) and patients born in Belgium (PBIB). We conducted a retrospective study on all patients of our Memory Clinic between June 1, 2010 and January 31, 2020. A synucleinopathy was diagnosed in 150 of 2702 patients (5.5%): 91 received a diagnosis of DLB (3.4%). FGI were two times more likely to receive a diagnosis of DLB, due to a higher prevalence in North-Africans and Latin-Americans. Visual hallucinations were less frequent in North-Africans than in other immigrants. FGI were younger than PBIB and reported more often parasomnia. Our data suggest a higher risk for DLB in certain immigrant groups. Especially for North-African patients, a genetic factor can be suspected, namely mutations in Leucine-rich repeat kinase 2 (LRRK2). Memory clinics with a high rate of FGI may provide interesting data and insights into the prevalence of DLB, genetic and environmental differences.

Silica-clay nanocomposites for the removal of antibiotics in the water usage cycle.

The increasingly frequent detection of resistant organic micropollutants in waters calls for better treatment of these molecules that are recognized to be dangerous for human health and the environment. As an alternative to conventional adsorbent material such as activated carbon, silica-clay nanocomposites were synthesized for the removal of pharmaceuticals in contaminated water. Their efficiency with respect to carbamazepine, ciprofloxacin, danofloxacin, doxycycline, and sulfamethoxazole was assessed in model water and real groundwater spiked with the five contaminants. Results showed that the efficacy of contaminant removal depends on the chemical properties of the micropollutants. Among the adsorbents tested, the nanocomposite made of 95% clay and 5% SiO2 NPs was the most efficient and was easily recovered from solution after treatment compared with pure clay, for example. The composite is thus a good candidate in terms of operating costs and environmental sustainability for the removal of organic contaminants.

Pregabalin as a Treatment for Anxiety in Patients With Dementia With Lewy Bodies: A Case Series.

BACKGROUND: Anxiety is a common and invalidating symptom of dementia with Lewy bodies (DLB). METHODS: To evaluate the efficacy of pregabalin as a treatment for anxiety in DLB, we screened all medical files of our patients with DLB for the use of pregabalin in this context. FINDINGS: Overall, pregabalin was well tolerated. Ten (62.5%) of 16 patients showed an improvement of anxiety, whereas in 3 of them, anxiety disappeared completely, at respectively 3, 11, and 22 months of follow-up, with total daily doses ranging from 75 to 150 mg. Positive response to pregabalin was associated with a significant reduction in benzodiazepine use. CONCLUSIONS: Pregabalin seems a useful and safe tool for treating anxiety in patients with DLB.

Anxiety symptoms are quantitatively and qualitatively different in dementia with Lewy bodies than in Alzheimer's disease in the years preceding clinical diagnosis.

AIM: Dementia with Lewy bodies (DLB) is a common but underdiagnosed type of cognitive impairment and dementia. The current diagnostic criteria for research purposes have a high specificity but lack sensitivity. Moreover, patients who live alone are not always aware that they have core clinical features such as cognitive fluctuations, visual hallucinations, and parasomnia. Anxiety is a common and early manifestation in DLB. METHODS: We matched 41 DLB patients with 41 patients with Alzheimer's disease (AD) according to gender, age, and cognitive status and retrospectively analyzed their files for the presence of anxiety, depression, constipation, and the core clinical features of DLB in the documented period before diagnosis. RESULTS: Anxiety, but not depression, occurred significantly more frequently in DLB than in AD (63.4% vs 26.8%). It appears up to 4-5 years before the diagnosis of DLB and is associated with depression and living at home. Anxiety in DLB was often described as intermittent panic attacks without reason or during states of delirium; it was also severe enough to require medical treatment and inpatient or outpatient psychiatric care. It was often mistaken for a psychiatric illness or a manifestation of other common forms of dementia. Anxiety in AD seemed much milder, was often related to the patient's coping with cognitive dysfunction, and was never cited as a specific reason for medical help. The concomitant presence of anxiety with at least one core clinical criterion of DLB enabled us to differentiate it from AD in our study, with a sensitivity of 63.4% but a specificity of 100%. CONCLUSIONS: In all patients over 50 who present with cognitive problems and anxiety, DLB should be considered. Patients and informants should be carefully questioned regarding the presence of other typical signs and symptoms of DLB.

A Retrospective Belgian Multi-Center MRI Biomarker Study in Alzheimer's Disease (REMEMBER).

BACKGROUND: Magnetic resonance imaging (MRI) acquisition/processing techniques assess brain volumes to explore neurodegeneration in Alzheimer's disease (AD). OBJECTIVE: We examined the clinical utility of MSmetrix and investigated if automated MRI volumes could discriminate between groups covering the AD continuum and could be used as a predictor for clinical progression. METHODS: The Belgian Dementia Council initiated a retrospective, multi-center study and analyzed whole brain (WB), grey matter (GM), white matter (WM), cerebrospinal fluid (CSF), cortical GM (CGM) volumes, and WM hyperintensities (WMH) using MSmetrix in the AD continuum. Baseline (n = 887) and follow-up (FU, n = 95) T1-weighted brain MRIs and time-linked neuropsychological data were available. RESULTS: The cohort consisted of cognitively healthy controls (HC, n = 93), subjective cognitive decline (n = 102), mild cognitive impairment (MCI, n = 379), and AD dementia (n = 313). Baseline WB and GM volumes could accurately discriminate between clinical diagnostic groups and were significantly decreased with increasing cognitive impairment. MCI patients had a significantly larger change in WB, GM, and CGM volumes based on two MRIs (n = 95) compared to HC (FU>24months, p = 0.020). Linear regression models showed that baseline atrophy of WB, GM, CGM, and increased CSF volumes predicted cognitive impairment. CONCLUSION: WB and GM volumes extracted by MSmetrix could be used to define the clinical spectrum of AD accurately and along with CGM, they are able to predict cognitive impairment based on (decline in) MMSE scores. Therefore, MSmetrix can support clinicians in their diagnostic decisions, is able to detect clinical disease progression, and is of help to stratify populations for clinical trials.

Pioneers in migration, pioneering in dementia: first generation immigrants in a European metropolitan memory clinic.

By reviewing the clinical files of 1,058 consecutive newly admitted outpatients of a Brussels-based memory clinic between 2005 and 2012, this study aims to document the demographic and clinical characteristics of European and non-European first generation immigrants. They accounted for 18.6% of the patients, of which 8.6% came from outside Europe (mostly from Morocco, Turkey and the Democratic Republic of Congo). Immigrants with AD tended to be younger, and there was a higher proportion of males among non-European ethnic minorities. There was a higher proportion of Parkinson-related cognitive disorders and Lewy Body disease among European immigrants, whereas non-Europeans had more often a psychiatric diagnosis. Even after correction for education, non-European immigrants had lower MMSE scores, and they did report longer delays between first symptoms and diagnosis, although this last difference was not statistically significant. These results suggest that non-European immigrants with cognitive problems consult later.