Marta Baroni

Fracture prevention service to bridge the osteoporosis care gap.

Background A care gap exists between the health care needs of older persons with fragility fractures and the therapeutic answers they receive. The Fracture Prevention Service (FPS), a tailored in-hospital model of care, may effectively bridge the osteoporosis care gap for hip-fractured older persons. The purpose of this study was to evaluate the efficacy of the FPS in targeting persons at high risk of future fracture and to improve their adherence to treatment. Methods This was a prospective observational study conducted in a teaching hospital with traumatology and geriatric units, and had a pre-intervention and post-intervention phase. The records of 172 participants were evaluated in the pre-intervention phase, while data from 210 participants were gathered in the post-intervention phase. All participants underwent telephone follow-up at 12 months after hospital discharge. The participants were patients aged ≥65 years admitted to the orthopedic acute ward who underwent surgical repair of a proximal femoral fracture. A multidisciplinary integrated model of care was established. Dedicated pathways were implemented in clinical practice to optimize the identification of high-risk persons, improve their evaluation through bone mineral density testing and blood examinations, and initiate an appropriate treatment for secondary prevention of falls and fragility fractures. Results Compared with the pre-intervention phase, more hip-fractured persons received bone mineral density testing (47.62% versus 14.53%, P<0.0001), specific pharmacological treatments (48.51% versus 17.16%, P<0.0001), and an appointment for evaluation at a fall and fracture clinic (52.48% versus 2.37%, P<0.0001) in the post-intervention phase. Independent of some confounders, implementation of the FPS was positively associated with recommendations for secondary fracture prevention at discharge (P<0.0001) and with 1-year adherence to pharmacological treatment (P<0.0001). Conclusion The FPS is an effective multidisciplinary integrated model of care to optimize identification of older persons at highest risk for fragility fracture, to improve their clinical management, and to increase adherence to prescriptions.

Anticholinergic burden and functional status in older people with cognitive impairment: Results from the ReGAl project

ObjectiveThe use of drugs with intrinsic anticholinergic properties is widespread among old age persons. A growing body of evidences suggest that a high anticholinergic burden is associated with physical and cognitive impairment. However, the association between anticholinergic drug use and functional status is still poorly investigated, particularly among subjects with initial cognitive impairment.DesignCross-sectional study examining the association between drug-related anticholinergic burden and functional status in cognitively healthy (CH) (n=691), mild cognitive impairment (MCI) (n=541) or mild Alzheimer’s diseases (AD) (n=1127) subjects.SettingData were gathered from the ReGAl project (Rete Geriatrica Alzheimer-Geriatric Network on Alzheimer’s disease), a large longitudinal Italian multicentric clinical-based study, promoted by the Italian Society of Gerontology and Geriatrics (SIGG).Participants2359 outpatients, older than 65 years, admitted to memory clinics. The total sample size, estimated according to a global effect size of 25% with type I error of 0.05 and a power of 95% is 2010 subjects.MeasurementFunctional status was evaluated by the Katz Index of Independence in Activities of Daily Living (ADL) and the Lawton-Brody Instrumental Activities of Daily Living (IADL) scales. The drug-related anticholinergic burden was estimated by the Anticholinergic Risk Scale (ARS).ResultsThe 15.9 % (n=375) of total population used at least one drug with anticholinergic properties. Such a drug use was associated with partially dependence in ADL (OR:1.42, CI95%: 1.10-1.83; p=0.006), independently of gender, number of drugs, comorbidity index, presence of clinically relevant neuropsychiatric symptoms and adjusted MMSE. Anticholinergic drug use was associated with un-ability at each IADL task only in male MCI subjects, with significant impairment in shopping (p=0.011), and drug management (p=0.05).ConclusionsThe use of medications with anticholinergic properties is common among older persons cognitively health as well as with cognitive impairment. Our results suggest that the use of anticholinergic drugs is associated with functional impairment, especially in old age subjects with initial cognitive impairment. Minimizing anticholinergic burden should result in maintaining daily functioning, especially in a vulnerable population, such as MCI and mild AD.

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.

Five-class differential diagnostics of neurodegenerative diseases using random undersampling boosting

Differentiating between different types of neurodegenerative diseases is not only crucial in clinical practice when treatment decisions have to be made, but also has a significant potential for the enrichment of clinical trials. The purpose of this study is to develop a classification framework for distinguishing the four most common neurodegenerative diseases, including Alzheimers disease, frontotemporal lobe degeneration, Dementia with Lewy bodies and vascular dementia, as well as patients with subjective memory complaints. Different biomarkers including features from images (volume features, region-wise grading features) and non-imaging features (CSF measures) were extracted for each subject. In clinical practice, the prevalence of different dementia types is imbalanced, posing challenges for learning an effective classification model. Therefore, we propose the use of the RUSBoost algorithm in order to train classifiers and to handle the class imbalance training problem. Furthermore, a multi-class feature selection method based on sparsity is integrated into the proposed framework to improve the classification performance. It also provides a way for investigating the importance of different features and regions. Using a dataset of 500 subjects, the proposed framework achieved a high accuracy of 75.2% with a balanced accuracy of 69.3% for the five-class classification using ten-fold cross validation, which is significantly better than the results using support vector machine or random forest, demonstrating the feasibility of the proposed framework to support clinical decision making.

Vitamin E family: Role in the pathogenesis and treatment of Alzheimer's disease

Vitamin E family, composed by tocopherols and tocotrienols, is a group of compounds with neuroprotective properties. The exact role in the pathogenesis and the benefit of vitamin E as treatment for Alzheimers disease (AD) are still under debate.

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.

Of Energy and Entropy: The Ineluctable Impact of Aging in Old Age Dementia

Alzheimer’s disease (AD) represents the most common form of dementia among older age subjects, and despite decades of studies, the underlying mechanisms remain unresolved. The definition of AD has changed over the past 100 years, and while early-onset AD is commonly related to genetic mutations, late-onset AD is more likely due to a gradual accumulation of age-related modifications. “Normal brain aging” and AD may represent different pathways of successful or failed capability to adapt brain structures and cerebral functions. Cellular senescence and age-related changes (ARCs) affecting the brain may be considered as biologic manifestations of increasing entropy, a measure of disorder. Late-onset AD may be regarded as the final effect of a reduced energy production, due to exhausted mitochondria, and an increased entropy in the brain. This unique trajectory enables a bioenergetics-centered strategy targeting disease-stage specific profile of brain metabolism for disease prevention and treatment.

DIFFERENT COMBINATIONS OF DIAGNOSTIC TESTS DISCRIMINATE SPECIFIC SUBTYPES OF DEMENTIA

TDP-43), ii) covarying with CSF biomarkers (Ab42, total tau, ptau) and iii) covarying with episodic memory scores (FCSRT, Landscape Test and CERAD Constructional Praxis recall). Results:Amyloid/Tau pathology affected mainly posterior HC while anterior left HC was more atrophied in TDP-43pathies. We also observed a significant correlation between posterior hippocampal atrophy and AD CSF biomarkers levels. In addition, visual memory scores correlated with posterior HC atrophy, whereas verbal memory correlated with both anterior and posterior hippocampal atrophy. Conclusions:These findings fit well with the hypothesis that HC is involved in two different cortical systems that harbor different cognitive functions, which could have distinct vulnerability to different proteinopathies. Taken together, these data suggest that there is a potential differentiation along the hippocampal longitudinal axis based on the underlying pathology, which could be used as a potential biomarker to identify the underlying pathology in different neurodegenerative diseases.

CONSISTENCY OF MUISTIKKO WEB-BASED COGNITIVE TEST WHILE PERFORMED AT CLINIC AND AT HOME

P1-328 CONSISTENCY OF MUISTIKKOWEBBASED COGNITIVE TEST WHILE PERFORMED AT CLINIC AND AT HOME Jyrki Lotjonen, Teemu Paajanen, Shadi Mahdiani, Marie Bruun, Marta Baroni, Hanneke F. M. RhodiusMeester, Afina W. Lemstra, Sanna-Kaisa Herukka, Maria Pikkarainen, Tuomo H€anninen, Mark van Gils, Sten Gregers Hasselbalch, Patrizia Mecocci, Anne Remes, Wiesje M. Van der Flier, Hilkka Soininen, Combinostics Ltd, Tampere, Finland; Finnish Institute of Occupational Health, Helsinki, Finland; VTT Technical Research Centre of Finland, Tampere, Finland; Danish Dementia Research Centre, Rigshospitalet, Copenhagen, Denmark; Institute of Gerontology and Geriatrics, Department of Medicine, University of Perugia, Perugia, Italy; Alzheimer Center, Department of Neurology, VU University Medical Center, Amsterdam, Netherlands; Alzheimer Center and Department of Neurology, Amsterdam Neuroscience, VU University Medical Center, Amsterdam, Netherlands; Neurocenter, Neurology, Kuopio University Hospital, Kuopio, Finland; University of Eastern Finland, Kuopio, Finland; Department of Neurology, Kuopio University Hospital, Kuopio, Finland; VTT Technical Research Centre of Finland Ltd, Tampere, Finland; Institute of Clinical Medicine/Neurology, University of Eastern Finland, Kuopio, Finland; VU University Medical Center, Amsterdam, Netherlands. Contact e-mail: jyrki.lotjonen@combinostics.com

DETECTING FRONTOTEMPORAL DEMENTIA USING A NOVEL MRI IMAGING BIOMARKER: THE ANTERIOR VERSUS POSTERIOR INDEX

Abbreviations: VBM: Voxel based morphometry. TMT: Trail making test. MMSE: Mini mental state examination. AB42: Amyloid beta 1-42. NOTE: The table shows the combinations of determinants which achieve the highest balanced accuracy in pairwise comparison of diagnostic groups. by different combinations of biomarkers. Overviews obtained by data-driven approaches like this could contribute to improved use of biomarkers in clinical practice.