Effectiveness and Satisfaction with Telemedicine in Geriatric Patients at High Risk of Fragility Fractures.

Background: Telemedicine has increasingly widespread to improve the monitoring of patients with chronic diseases. Secondary prevention of fragility fractures is an urgent matter to be addressed by means of available technology, although supported by little evidence so far. We investigated the feasibility, efficacy, and satisfaction of managing older adults at high risk of fragility fractures during the COVID-19 lockdown. Methods: During the period January to July 2021, a prospective observational study for safety and adherence purposes was conducted among older adults (n = 407) with ongoing treatments for secondary prevention of fragility fractures. The study procedures comply with national and regional resolutions related to telemedicine service (TS), including equipment, staff behaviors, and patient reports. Results: A majority (86.48% [n = 352]) of the eligible patients joined the remote visits, mainly women (88.2%), 81.4 ± 8.8 years of age, 49.6% independent in 5 out of 6 BADL, despite high comorbidity (4.9 ± 1.5), and polypharmacy (4.9 ± 3.1). Almost all were on second-line antifracture treatments (95.58%) due to previous major (84.03%) and minor (42.5%) fragility fractures. About 58% reported good and very good reliability of the internet network, allowing easy access to the TS platform, and 54% declared the degree of satisfaction with TS as good and very good. About 75% of clinicians acknowledged the efficacy of TS and expressed willingness to recommend the use of TS to colleagues. Ultimately, 68% of specialists defined the time allocated for patients' remote visits as acceptable. Conclusion: TS may be an opportunity to improve the availability of appropriate health care services to satisfy patients' needs and optimize health care resource allocation.

The correlates of post-surgical haematoma in older adults with proximal femoral fractures.

BACKGROUND: Little is known about the incidence of haematoma, and clinical correlates among orthogeriatric patients. AIMS: This study aims to describe the incidence of haematoma after surgical repair of hip fracture and to identify the clinical correlates of haematoma among orthogeriatric patients. METHODS: Two orthopaedic surgeons and a dedicated operator using ultrasound technique, each other in blindness, evaluated 154 orthogeriatric patients during their hospital stay. All patients received a comprehensive geriatric assessment. We investigated the concordance between clinical diagnosis and ultrasound detection of haematoma, and then we explored the clinical correlates of the onset of post-surgical haematoma. RESULTS: Blood effusion at the surgical site was detected in 77 (50%) patients using ultrasound technique; orthopaedic surgeons reached a clinical agreement about post-surgical haematoma in 18 (23%) patients. The sensitivity of clinical evaluation was 0.66, and the specificity was 0.70. Independent of age, clinical, pharmacological, and surgical confounders, proton pump inhibitors (PPIs) were associated with post-surgical haematoma (OR 2.28; 95% CI 1.15-4.49). A tendency towards association was observed between selective serotonin reuptake inhibitors and post-surgical haematoma (OR 2.10; 95% CI 0.97-4.54), CONCLUSIONS: Half of older patients undergoing surgical repair of proximal femoral fracture develop a post-surgical haematoma. Clinical assessment, even if made by senior orthopaedic surgeons, underestimates the actual occurrence of post-surgical haematoma compared to ultrasound detection. Ultrasound technique may help to detect haematoma larger than 15 mm better than clinical assessment. PPIs's use is a risk factor for post-surgical haematoma independent of several medical and surgical confounders.

Bone Health Care Pathway for Non-metastatic Prostate Cancer Patients on Radiation and Androgen Deprivation Therapy.

BACKGROUND/AIM: Survival rates of prostate cancer (PCa) patients have improved considerably as a result of earlier diagnosis and therapies, including radiotherapy (RT) and androgen deprivation therapy (ADT). Patients on ADT develop cancer treatment-induced bone loss (CTIBL) and a high risk of fragility fractures. Bone health (BH) assessment is strongly recommended, together with timely initiation of treatments, to counteract CTIBL and preserve bone strength. Therefore, we decided to develop an interdisciplinary pathway of care (IPC) dedicated to non-metastatic PCa patients on long-term ADT and RT. PATIENTS AND METHODS: An interdisciplinary team allocated resources to support an IPC to manage patients' CTIBL and prevent fragility fractures. The team provided a diagnostic and therapeutic workflow according to patients' and professional perspectives, consistent with recommendations and healthcare policies. The hospital's quality department certified the IPC, the Ethical Committee approved procedures over the workflow. The Fracture Liaison Service (FLS) standards inspired services and professionals' activities and interactions. RESULTS: Preliminary data support the feasibility of the IPC from professionals' and patients' perspectives. Median age of the enrolled patients was 75 years, more than a half (58.9%) had low grade osteopenia or normal BMD (T-score ≥-1.5 standard deviation, SD), while 23.5% and 17.6% had osteoporosis and osteopenia, respectively. The IPC meets the requirements of a FLS concerning crucial indicators. CONCLUSION: Our IPC was a suitable approach to assure timely identification, assessment, initiation, and monitoring of adherence to anti-fracture treatments among non-metastatic PCa patients on long-term ADT and RT. Further data are required to show its effectiveness on fragility fracture prevention.

The interdisciplinary fracture liaison service improves health-related outcomes and survival of older adults after hip fracture surgical repair.

Due to the high burden of fragility fractures, we developed an interdisciplinary FLS care pathway for early management and monitoring of older adults discharged from a high-volume trauma center after hip fracture repair. Interdisciplinary FLS effectively improves up to 1-year adherence to treatments for secondary prevention of fragility fractures, reduces health facility admission, and improves long-term survival. PURPOSE: To compare adherence to secondary fragility fracture prevention, falls, healthcare facility admissions, and mortality between hip fracture older adults who entered the fracture liaison services pathway of care (FLS-CP) and those managed according to the usual traumatologist model of care (U-CP). METHODS: Prospective observational study enrolling subjects aged ≥ 65 years discharged by high-volume trauma center after hip fracture repair from February 2016 to February 2017, who consecutively entered FLS-CP or U-CP according to their preference and goals. RESULTS: Compared to U-CP, those in FLS-CP had higher initiation rate and up to 1-year adherence to secondary prevention of fragility fracture, including vitamin D and calcium (87.7% vs 36.9%; p < 0.0001), specific anti-osteoporosis drugs (75.1% vs 8.0%; p < 0.0001), and complete anti-fracture therapy (72.3% vs 5.7%; p < 0.0001). Older adults belonging to FLS-CP showed a lower likelihood of healthcare facility admission (RR 0.597; 95% CI 0.398-0.895; p = 0.0125), with a longer re-hospitalization-free survival (176.4 vs 88.7 days; p = 0.0152) than those in U-CP. One-year incidence of falls and fractures was similar between groups, with a lower tendency of the subjects in the FLS-CP to be multiple fallers (19% vs 34.8%; OR 0.057; 95% CI 0.004-0.876; p = 0.0690). The FLS-CP group experienced a lower 1-year (87.2% vs 74.3%; p = 0.001) and 3-year mortality (67.9% vs 55.6%; p = 0.0245) and a lower adjusted 5-year mortality hazard ratio (50.2% vs 58%; HR = 0.76; 95% CI 0.60; 0.96). CONCLUSION: The FLS-CP may improve initiation and adherence to secondary prevention of fragility fractures, reduces healthcare facility admission, and improves long-term survival.

Metabolic Score for Insulin Resistance (METS-IR) and Circulating Cytokines in Older Persons: The Role of Gender and Body Mass Index.

BACKGROUND: Inflammation, along with aging processes, contributes to the development of insulin resistance (IR), but the roles of different inflammatory and other cytokines in this process remain unclear. Thus, we aimed to analyze the association between several plasma cytokines with IR as evaluated by the metabolic score for insulin resistance, METS-IR. METHODS: We measured the plasma concentrations of thirty cytokines from a cohort of older persons and analyzed their role as independent factors for IR. We used regression analyses adjusted for known IR-associated factors (including age, gender, cholesterol levels, and BMI) to find the determinants of IR. RESULTS: The study evaluated 132 subjects, mostly women (82F/50M), slightly overweight, and with a mean age of 78.5 ± 6.5 years. In the overall population, IL-15 significantly and negatively correlates with METS-IR (r = -0.183, p = 0.036). A regression model showed that the association between IL-15 and METS-IR was significantly modulated by gender and BMI (R2: 0.831). Only in women, EGF, Eotaxin and MCP-1 significantly correlated with METS-IR even after controlling by age (EGF, r = 0.250 p = 0.025; Eotaxin, r = 0.276 p = 0.13; MCP-1, r = 0.237, p = 0.033). Furthermore, regression models showed that these molecules were associated with METS-IR and were strongly mediated by BMI. CONCLUSIONS: Our results indicate the association between cytokines and IR has to be interpreted in a gender-specific manner. In women, EGF, Eotaxin, and MCP-1 circulating levels are associated with METS-IR being BMI a significant mediator. Understanding the role of gender in the relationship between cytokines and IR will help to define individualized preventive and treatment interventions to reduce the risk of age-related metabolic disorders.

cCOG: A web-based cognitive test tool for detecting neurodegenerative disorders.

INTRODUCTION: Web-based cognitive tests have potential for standardized screening in neurodegenerative disorders. We examined accuracy and consistency of cCOG, a computerized cognitive tool, in detecting mild cognitive impairment (MCI) and dementia. METHODS: Clinical data of 306 cognitively normal, 120 mild cognitive impairment (MCI), and 69 dementia subjects from three European cohorts were analyzed. Global cognitive score was defined from standard neuropsychological tests and compared to the corresponding estimated score from the cCOG tool containing seven subtasks. The consistency of cCOG was assessed comparing measurements administered in clinical settings and in the home environment. RESULTS: cCOG produced accuracies (receiver operating characteristic-area under the curve [ROC-AUC]) between 0.71 and 0.84 in detecting MCI and 0.86 and 0.94 in detecting dementia when administered at the clinic and at home. The accuracy was comparable to the results of standard neuropsychological tests (AUC 0.69-0.77 MCI/0.91-0.92 dementia). DISCUSSION: cCOG provides a promising tool for detecting MCI and dementia with potential for a cost-effective approach including home-based cognitive assessments.

Evaluating 2-[18F]FDG-PET in differential diagnosis of dementia using a data-driven decision model.

2-[18F]fluoro-2-deoxy-d-glucose positron emission tomography (2-[18F]FDG-PET) has an emerging supportive role in dementia diagnostic as distinctive metabolic patterns are specific for Alzheimer's disease (AD), dementia with Lewy bodies (DLB) and frontotemporal dementia (FTD). Previous studies have demonstrated that a data-driven decision model based on the disease state index (DSI) classifier supports clinicians in the differential diagnosis of dementia by using different combinations of diagnostic tests and biomarkers. Until now, this model has not included 2-[18F]FDG-PET data. The objective of the study was to evaluate 2-[18F]FDG-PET biomarkers combined with commonly used diagnostic tests in the differential diagnosis of dementia using the DSI classifier. We included data from 259 subjects diagnosed with AD, DLB, FTD, vascular dementia (VaD), and subjective cognitive decline from two independent study cohorts. We also evaluated three 2-[18F]FDG-PET biomarkers (anterior vs. posterior index (API-PET), occipital vs. temporal index, and cingulate island sign) to improve the classification accuracy for both FTD and DLB. We found that the addition of 2-[18F]FDG-PET biomarkers to cognitive tests, CSF and MRI biomarkers considerably improved the classification accuracy for all pairwise comparisons of DLB (balanced accuracies: DLB vs. AD from 64% to 77%; DLB vs. FTD from 71% to 92%; and DLB vs. VaD from 71% to 84%). The two 2-[18F]FDG-PET biomarkers, API-PET and occipital vs. temporal index, improved the accuracy for FTD and DLB, especially as compared to AD. Moreover, different combinations of diagnostic tests were valuable to differentiate specific subtypes of dementia. In conclusion, this study demonstrated that the addition of 2-[18F]FDG-PET to commonly used diagnostic tests provided complementary information that may help clinicians in diagnosing patients, particularly for differentiating between patients with FTD, DLB, and AD.

Lower serum levels of IL-13 is associated with increased carotid intima-media thickness in old age subjects.

BACKGROUND: Cardiovascular diseases due to atherosclerosis represent the major cause of disability and mortality in old age subjects. The atherosclerotic process is linked to a low grade of systemic inflammation with the involvement of many cytokines and inflammatory proteins. Among them, evidence from animal studies suggests that IL-13 has a protective property. However, the role of IL-13 in the pathogenesis of atherosclerosis in humans is still unknown. AIMS: With this study, we aim to investigate a potential association between IL-13 and carotid intima-media thickness (IMT) in old age subjects. METHODS: This is a retrospective study conducted among 79 old age subjects (over 75 years old). All subjects underwent IMT assessment by high-resolution B-mode ultrasonography and IL-13 measurement in serum by ELISA. RESULTS: Subjects (41 M/38F) had a mean age of 81.0 ± 4.5 years and were mostly overweight. Stratifying the whole cohort by IMT thickness (IMT ≤ 0.9, n = 17; IMT ≥ 1 and ≤ 1.3, n = 50; IMT ≥ 1.4, n = 12) among the main variables explored, only BMI and triglycerides differed among groups, having subjects with higher IMT significantly higher BMI and lower triglycerides. Serum IL-13 levels significantly differed among groups having subjects with IMT ≥ 1.4 lower levels as compared to other groups (p < 0.0001). In all sample population, IMT values significantly correlate with IL-13 levels (r = - 0.454, p < 0.0001). Indeed, a linear regression analysis showed that independent of age, gender, body mass index, triglycerides, systolic blood pressure, statin use and smoking habit, lower IL-13 serum levels were associated with higher IMT values. CONCLUSIONS: IL-13, an anti-inflammatory cytokine, may have a protective role in the human atherosclerotic process. It could be used as an effective and promising novel therapeutic target development.

Effects of Weekly Supplementation of Cholecalciferol and Calcifediol Among the Oldest-Old People: Findings From a Randomized Pragmatic Clinical Trial.

Vitamin D inadequacy is pervasive in the oldest-old. Many vitamin D metabolites are available for supplementation, their effects on the recovery of adequate serum levels remain unknown. We investigate the effects of supplementation with cholecalciferol (D3) and calcifediol (25D3) on serum levels of 25(OH)D, 1-25(OH)D, bone and inflammatory markers, ultimately identifying clinical predictors of successful treatment. Sixty-seven oldest-old individuals were randomized to weekly administration of 150 mcg of 25D3 or D3, from hospital admission to 7 months after discharge. Supplementation of 25D3 and D3 were associated with increasing serum levels of 25(OH)D (p < 0.001) and 1-25(OH)D (p = 0.01). Participants on 25D3 experienced a steeper rise than those on D3 (group*time interaction p = 0.01), after adjustment for intact parathyroid hormone (iPTH) levels the differences disappeared (intervention*iPTH interaction p = 0.04). Vitamin D supplementation was associated with a decreasing trend of iPTH and C-reactive protein (CRP) (p < 0.001). Polypharmacy and low handgrip strength were predictors of failure of intervention, independent of vitamin D metabolites. In conclusion, D3 and 25D3 supplementation significantly increase vitamin D serum levels in the oldest-old individuals, with a tendency of 25D3 to show a faster recovery of acceptable iPTH levels than D3. Polypharmacy and low muscle strength weaken the recovery of adequate vitamin D serum levels.

Impact of a clinical decision support tool on prediction of progression in early-stage dementia: a prospective validation study.

BACKGROUND: In clinical practice, it is often difficult to predict which patients with cognitive complaints or impairment will progress or remain stable. We assessed the impact of using a clinical decision support system, the PredictND tool, to predict progression in patients with subjective cognitive decline (SCD) and mild cognitive impairment (MCI) in memory clinics. METHODS: In this prospective multicenter study, we included 429 patients with SCD (n = 230) and MCI (n = 199) (female 54%, age 67 ± 9, MMSE 28 ± 2) and followed them for at least 12 months. Based on all available patient baseline data (demographics, cognitive tests, cerebrospinal fluid biomarkers, and MRI), the PredictND tool provides a comprehensive overview of the data and a classification defining the likelihood of progression. At baseline, a clinician defined an expected follow-up diagnosis and estimated the level of confidence in their prediction using a visual analogue scale (VAS, 0-100%), first without and subsequently with the PredictND tool. As outcome measure, we defined clinical progression as progression from SCD to MCI or dementia, and from MCI to dementia. Correspondence between the expected and the actual clinical progression at follow-up defined the prognostic accuracy. RESULTS: After a mean follow-up time of 1.7 ± 0.4 years, 21 (9%) SCD and 63 (32%) MCI had progressed. When using the PredictND tool, the overall prognostic accuracy was unaffected (0.4%, 95%CI - 3.0%; + 3.9%; p = 0.79). However, restricting the analysis to patients with more certain classifications (n = 203), we found an increase of 3% in the accuracy (95%CI - 0.6%; + 6.5%; p = 0.11). Furthermore, for this subgroup, the tool alone showed a statistically significant increase in the prognostic accuracy compared to the evaluation without tool (6.4%, 95%CI 2.1%; 10.7%; p = 0.004). Specifically, the negative predictive value was high. Moreover, confidence in the prediction increased significantly (∆VAS = 4%, p < .0001). CONCLUSIONS: Adding the PredictND tool to the clinical evaluation increased clinicians' confidence. Furthermore, the results indicate that the tool has the potential to improve prediction of progression for patients with more certain classifications.

Detecting frontotemporal dementia syndromes using MRI biomarkers.

BACKGROUND: Diagnosing frontotemporal dementia may be challenging. New methods for analysis of regional brain atrophy patterns on magnetic resonance imaging (MRI) could add to the diagnostic assessment. Therefore, we aimed to develop automated imaging biomarkers for differentiating frontotemporal dementia subtypes from other diagnostic groups, and from one another. METHODS: In this retrospective multicenter cohort study, we included 1213 patients (age 67 ±â€¯9, 48% females) from two memory clinic cohorts: 116 frontotemporal dementia, 341 Alzheimer's disease, 66 Dementia with Lewy bodies, 40 vascular dementia, 104 other dementias, 229 mild cognitive impairment, and 317 subjective cognitive decline. Three MRI atrophy biomarkers were derived from the normalized volumes of automatically segmented cortical regions: 1) the anterior vs. posterior index, 2) the asymmetry index, and 3) the temporal pole left index. We used the following performance metrics: area under the receiver operating characteristic curve (AUC), sensitivity, and specificity. To account for the low prevalence of frontotemporal dementia we pursued a high specificity of 95%. Cross-validation was used in assessing the performance. The generalizability was assessed in an independent cohort (n = 200). RESULTS: The anterior vs. posterior index performed with an AUC of 83% for differentiation of frontotemporal dementia from all other diagnostic groups (Sensitivity = 59%, Specificity = 95%, positive likelihood ratio = 11.8, negative likelihood ratio = 0.4). The asymmetry index showed highest performance for separation of primary progressive aphasia and behavioral variant frontotemporal dementia (AUC = 85%, Sensitivity = 79%, Specificity = 92%, positive likelihood ratio = 9.9, negative likelihood ratio = 0.2), whereas the temporal pole left index was specific for detection of semantic variant primary progressive aphasia (AUC = 85%, Sensitivity = 82%, Specificity = 80%, positive likelihood ratio = 4.1, negative likelihood ratio = 0.2). The validation cohort provided corresponding results for the anterior vs. posterior index and temporal pole left index. CONCLUSION: This study presents three quantitative MRI biomarkers, which could provide additional information to the diagnostic assessment and assist clinicians in diagnosing frontotemporal dementia.

Automatically computed rating scales from MRI for patients with cognitive disorders.

OBJECTIVES: The aims of this study were to examine whether visual MRI rating scales used in diagnostics of cognitive disorders can be estimated computationally and to compare the visual rating scales with their computed counterparts in differential diagnostics. METHODS: A set of volumetry and voxel-based morphometry imaging biomarkers was extracted from T1-weighted and FLAIR images. A regression model was developed for estimating visual rating scale values from a combination of imaging biomarkers. We studied three visual rating scales: medial temporal lobe atrophy (MTA), global cortical atrophy (GCA), and white matter hyperintensities (WMHs) measured by the Fazekas scale. Images and visual ratings from the Amsterdam Dementia Cohort (ADC) (N = 513) were used to develop the models and cross-validate them. The PredictND (N = 672) and ADNI (N = 752) cohorts were used for independent validation to test generalizability. RESULTS: The correlation coefficients between visual and computed rating scale values were 0.83/0.78 (MTA-left), 0.83/0.79 (MTA-right), 0.64/0.64 (GCA), and 0.76/0.75 (Fazekas) in ADC/PredictND cohorts. When performance in differential diagnostics was studied for the main types of dementia, the highest balanced accuracy, 0.75-0.86, was observed for separating different dementias from cognitively normal subjects using computed GCA. The lowest accuracy of about 0.5 for all the visual and computed scales was observed for the differentiation between Alzheimer's disease and frontotemporal lobar degeneration. Computed scales produced higher balanced accuracies than visual scales for MTA and GCA (statistically significant). CONCLUSIONS: MTA, GCA, and WMHs can be reliably estimated automatically helping to provide consistent imaging biomarkers for diagnosing cognitive disorders, even among less experienced readers. KEY POINTS: • Visual rating scales used in diagnostics of cognitive disorders can be estimated computationally from MRI images with intraclass correlations ranging from 0.64 (GCA) to 0.84 (MTA). • Computed scales provided high diagnostic accuracy with single-subject data (area under the receiver operating curve range, 0.84-0.94).

Impact of a Clinical Decision Support Tool on Dementia Diagnostics in Memory Clinics: The PredictND Validation Study.

BACKGROUND: Determining the underlying etiology of dementia can be challenging. Computer- based Clinical Decision Support Systems (CDSS) have the potential to provide an objective comparison of data and assist clinicians. OBJECTIVES: To assess the diagnostic impact of a CDSS, the PredictND tool, for differential diagnosis of dementia in memory clinics. METHODS: In this prospective multicenter study, we recruited 779 patients with either subjective cognitive decline (n=252), mild cognitive impairment (n=219) or any type of dementia (n=274) and followed them for minimum 12 months. Based on all available patient baseline data (demographics, neuropsychological tests, cerebrospinal fluid biomarkers, and MRI visual and computed ratings), the PredictND tool provides a comprehensive overview and analysis of the data with a likelihood index for five diagnostic groups; Alzheimer´s disease, vascular dementia, dementia with Lewy bodies, frontotemporal dementia and subjective cognitive decline. At baseline, a clinician defined an etiological diagnosis and confidence in the diagnosis, first without and subsequently with the PredictND tool. The follow-up diagnosis was used as the reference diagnosis. RESULTS: In total, 747 patients completed the follow-up visits (53% female, 69±10 years). The etiological diagnosis changed in 13% of all cases when using the PredictND tool, but the diagnostic accuracy did not change significantly. Confidence in the diagnosis, measured by a visual analogue scale (VAS, 0-100%) increased (ΔVAS=3.0%, p<0.0001), especially in correctly changed diagnoses (ΔVAS=7.2%, p=0.0011). CONCLUSION: Adding the PredictND tool to the diagnostic evaluation affected the diagnosis and increased clinicians' confidence in the diagnosis indicating that CDSSs could aid clinicians in the differential diagnosis of dementia.

Hypovitaminosis D: A Disease Marker in Hospitalized Very Old Persons at Risk of Malnutrition.

BACKGROUND: Hypovitaminosis D is a frequent condition in elderly subjects. Vitamin D adequacy is best determined by measurement of the 25-hydroxyvitamin D-25(OH)D-concentration in the serum. An inverse association exists between 25(OH)D and cardiovascular, infectious, glucose metabolism, cognitive disorders, and all-cause mortality. Whether 25(OH)D is a marker of organ diseases is still under debate. We aimed to investigate whether comorbidities were associated with serum 25(OH)D levels in geriatric inpatients. METHODS: This is a retrospective study, including 237 subjects consecutively admitted to an acute care geriatric unit, with available data of 25(OH)D serum concentrations. 25(OH)D serum levels were defined according to the following cutoffs: 50⁻30 ng/mL (125⁻75 nmol/L): optimal range; 30⁻20 ng/mL (75⁻50 nmol/L): insufficiency; 20⁻10 ng/mL (5⁻25 nmol/L): deficiency; and <10 ng/mL (<25 nmol/L): severe deficiency. Comorbidity was assessed using the Cumulative Illness Rating Scale-Geriatric (CIRS-G). Two summary measures were obtained, the Illness Severity Index (CIRS-SI) and the Comorbidity Index (CIRS-CI). RESULTS: 177 (74.68%) women and 60 (25.32%) men with mean age of 85 ± 6 years old were enrolled. The majority of subjects (68.6%) were at risk of malnutrition. Overall, the burden of comorbidity was 1.87 ± 1.33 for CIRS-CI and 1.18 ± 0.40 for CIRS-SI. 25(OH)D serum concentrations were 10.58 ± 7.68 ng/mL, with 98.7% of subjects having vitamin D below 30 ng/mL and 56.6% with severe deficiency. An inverse correlation was found between 25(OH)D and both CIRS-SI (r: -0.312; p < 0.0001) and CIRS-CI (r: -0.306; p < 0.0001). Independent of multiple covariates an inverse association between both CIRS-SI (p < 0.0001) and CIRS-CI (p < 0.0001) and 25(OH)D was confirmed. Both CIRS-SI (r = 0.251, p < 0.0001) and CIRS-CI (r = 0.137, p = 0.016) were positively correlated with the length of hospital stay. An inverse correlation was confirmed between serum 25(OH)D concentrations and CRP (r = -0.142; p = 0.041). CRP, in turn, positively correlated with CIRS-SI (r = 0.209, p = 0.003) and CIRS-CI (r = 0.158, p = 0.023). Both CIRS-SI (r = 0.251, p < 0.0001) and CIRS-CI (r = 0.137, p = 0.016) were positively correlated with the length of hospital stay. CONCLUSIONS: In hospitalized very old subjects, a higher comorbidity burden is associated with lower 25(OH)D serum levels. Hypovitaminosis D was correlated with higher inflammatory status, which, together with the comorbidities burden, negatively influenced the length of hospital stay.

Evaluating combinations of diagnostic tests to discriminate different dementia types.

INTRODUCTION: We studied, using a data-driven approach, how different combinations of diagnostic tests contribute to the differential diagnosis of dementia. METHODS: In this multicenter study, we included 356 patients with Alzheimer's disease, 87 frontotemporal dementia, 61 dementia with Lewy bodies, 38 vascular dementia, and 302 controls. We used a classifier to assess accuracy for individual performance and combinations of cognitive tests, cerebrospinal fluid biomarkers, and automated magnetic resonance imaging features for pairwise differentiation between dementia types. RESULTS: Cognitive tests had good performance in separating any type of dementia from controls. Cerebrospinal fluid optimally contributed to identifying Alzheimer's disease, whereas magnetic resonance imaging features aided in separating vascular dementia, dementia with Lewy bodies, and frontotemporal dementia. Combining diagnostic tests increased the accuracy, with balanced accuracies ranging from 78% to 97%. DISCUSSION: Different diagnostic tests have their distinct roles in differential diagnostics of dementias. Our results indicate that combining different diagnostic tests may increase the accuracy further.

Data-Driven Differential Diagnosis of Dementia Using Multiclass Disease State Index Classifier.

Clinical decision support systems (CDSSs) hold potential for the differential diagnosis of neurodegenerative diseases. We developed a novel CDSS, the PredictND tool, designed for differential diagnosis of different types of dementia. It combines information obtained from multiple diagnostic tests such as neuropsychological tests, MRI and cerebrospinal fluid samples. Here we evaluated how the classifier used in it performs in differentiating between controls with subjective cognitive decline, dementia due to Alzheimer's disease, vascular dementia, frontotemporal lobar degeneration and dementia with Lewy bodies. We used the multiclass Disease State Index classifier, which is the classifier used by the PredictND tool, to differentiate between controls and patients with the four different types of dementia. The multiclass Disease State Index classifier is an extension of a previously developed two-class Disease State Index classifier. As the two-class Disease State Index classifier, the multiclass Disease State Index classifier also offers a visualization of its decision making process, which makes it especially suitable for medical decision support where interpretability of the results is highly important. A subset of the Amsterdam Dementia cohort, consisting of 504 patients (age 65 ± 8 years, 44% females) with data from neuropsychological tests, cerebrospinal fluid samples and both automatic and visual MRI quantifications, was used for the evaluation. The Disease State Index classifier was highly accurate in separating the five classes from each other (balanced accuracy 82.3%). Accuracy was highest for vascular dementia and lowest for dementia with Lewy bodies. For the 50% of patients for which the classifier was most confident on the classification the balanced accuracy was 93.6%. Data-driven CDSSs can be of aid in differential diagnosis in clinical practice. The decision support system tested in this study was highly accurate in separating the different dementias and controls from each other. In addition to the predicted class, it also provides a confidence measure for the classification.

Brain Aging and Late-Onset Alzheimer's Disease: A Matter of Increased Amyloid or Reduced Energy?

Alzheimer's disease (AD) represents the most common form of dementia in old age subjects, and despite decades of studies, the underlying etiopathogenetic mechanisms remain unsolved. The definition of AD has changed over the past years, offering an ever more detailed definition of pre-morbid and pre-clinical status, but without a similar strong emphasis on the role of aging as the main risk factor. In fact, while early-onset AD is a clear consequence of gene mutations, late-onset AD is more likely due to a gradual accumulation of age-related damages. The pathogenetic amyloid cascade hypothesis has been recently questioned due to multiple clinical failures. Furthermore, several studies reported that cognitively normal elderly have a high amyloid deposition in the brain comparable to the levels observed in old age subjects with AD. This suggests that amyloid accumulation enters into the normal process of aging and what really triggers neuronal death and clinical manifestation in late-onset AD still needs further explanation. In this context, 'normal brain aging' and AD might represent a different pathway of successful or failed capability to adapt brain structures and cerebral functions. Cellular senescence and age-related changes affecting the brain may be considered as biologic manifestations of increasing entropy. Bioenergetic deficits due to mitochondrial dysfunction may lead to progressive neuronal death and clinical expression of dementia. So, increased amyloid in the brain of old age subjects may represent the downstream event expression of a biological system that is cooling down because of its exhaustion and not the core causative factor of late-onset dementia.

A Long Journey into Aging, Brain Aging, and Alzheimer's Disease Following the Oxidative Stress Tracks.

The Editors of the Journal of Alzheimer's Disease invited Professor Patrizia Mecocci to contribute a review article focused on the importance and implications of her research on aging, brain aging, and senile dementias over the last years. This invitation was based on an assessment that she was one of the journal's top authors and a strong supporter of the concept that oxidative stress is a major contributor to several alterations observed in age-related conditions (sarcopenia, osteoporosis) and, more significantly, in brain aging suggesting a pivotal role in the pathogenesis and progression of one of the most dramatic age-related diseases, Alzheimer's disease (AD). Her first pioneering research was on the discovery of high level of 8-hydroxy-2'-deoxyguanosine (OH8dG), a marker of oxidation in nucleic acids, in mitochondrial DNA isolated from cerebral cortex. This molecule increases progressively with aging and more in AD brain, supporting the hypothesis that oxidative stress, a condition of unbalance between the production of reactive oxygen species and antioxidants, gives a strong contribution to the high incidence of AD in old age subjects. OH8dG also increases in peripheral lymphocyte from AD subjects, suggesting that AD is not only a cerebral but also a systemic disease. The role of antioxidants, particularly vitamin E and zinc, were also studied in longevity and in cognitive decline and dementia. This review shows the main findings from Mecocci's laboratory related to oxidative stress in aging, brain aging, and AD and discusses the importance and implications of some of the major achievements in this field of research.