Clinical and Cognitive Features of Idiopathic Normal Pressure Hydrocephalus

Introduction: Idiopathic normal pressure hydrocephalus (iNPH) is characterized by dilated cerebral ventricles with progressive impaired gait, cognition, and urinary control. Firstly described in 1965 by Hakim and Adam, it remains largely under-diagnosed. The diagnosis is based on clinical and imaging (CT or MRI) investigations; a timely diagnosis and cerebrospinal fluid (CSF) shunt surgery has reported to be beneficial in 60 up to 80% of the cases

Computer-based cognitive rehabilitation: the CoRe system

This work aims at providing a tool for supporting cognitive rehabilitation. This is a wide field, that includes a variety of diseases and related clinical pictures; for this reason the need arises to have a tool available that overcomes the difficulties entailed by what currently is the most common approach, that is, the so-called pen and paper rehabilitation. Methods: We first organized a big number of stimuli in an ontology that represents concepts, attributes and a set of relationships among concepts. Stimuli may be words, sounds, 2D and 3D images. Then, we developed an engine that automatically generates exercises by exploiting that ontology. The design of exercises has been carried on in synergy with neuropsychologists and speech therapists. Solutions have been devised aimed at personalizing the exercises according to both patients’ preferences and performance. Results: Exercises addressed to rehabilitation of executive functions and aphasia-related diseases have been implemented. The system has been tested on both healthy volunteers (n 1/4 38) and patients (n 1/4 9), obtaining a favourable rating and suggestions for improvements. Conclusions: We created a tool able to automate the execution of cognitive rehabilitation tasks. We hope the variety and personalization of exercises will allow to increase compliance, particularly from elderly people, usually neither familiar with technology nor particularly willing to rely on it. The next step involves the creation of a telerehabilitation tool, to allow therapy sessions to be undergone from home, thus guaranteeing continuity of care and advantages in terms of time and costs for the patients and the National Healthcare System (NHS).Postprint (published version

Smart aging platform for evaluating cognitive functions in aging: A comparison with the MoCA in a normal population

Postprint (author's final draft

The Multidisciplinary Approach to Alzheimer's Disease and Dementia. A Narrative Review of Non-Pharmacological Treatment

Background: Alzheimer's disease (AD) and dementia are chronic diseases with progressive deterioration of cognition, function, and behavior leading to severe disability and death. The prevalence of AD and dementia is constantly increasing because of the progressive aging of the population. These conditions represent a considerable challenge to patients, their family and caregivers, and the health system, because of the considerable need for resources allocation. There is no disease modifying intervention for AD and dementia, and the symptomatic pharmacological treatments has limited efficacy and considerable side effects. Non-pharmacological treatment (NPT), which includes a wide range of approaches and techniques, may play a role in the treatment of AD and dementia.Aim: To review, with a narrative approach, current evidence on main NPTs for AD and dementia.Methods: PubMed and the Cochrane database of systematic reviews were searched for studies written in English and published from 2000 to 2018. The bibliography of the main articles was checked to detect other relevant papers.Results: The role of NPT has been largely explored in AD and dementia. The main NPT types, which were reviewed here, include exercise and motor rehabilitation, cognitive rehabilitation, NPT for behavioral and psychological symptoms of dementia, occupational therapy, psychological therapy, complementary and alternative medicine, and new technologies, including information and communication technologies, assistive technology and domotics, virtual reality, gaming, and telemedicine. We also summarized the role of NPT to address caregivers' burden.Conclusions: Although NPT is often applied in the multidisciplinary approach to AD and dementia, supporting evidence for their use is still preliminary. Some studies showed statistically significant effect of NPT on some outcomes, but their clinical significance is uncertain. Well-designed randomized controlled trials with innovative designs are needed to explore the efficacy of NPT in AD and dementia. Further studies are required to offer robust neurobiological grounds for the effect of NPT, and to examine its cost-efficacy profile in patients with dementia

Curcumin and Novel Synthetic Analogs in Cell-Based Studies of Alzheimer’s Disease

Alzheimer’s disease (AD) is a chronic neurodegenerative disorder that is associated with the most common type of dementia and is characterized by the presence of deposits of the protein fragment amyloid beta (Aβ) in the brain. The natural product mixture of curcuminoids that improves certain defects in innate immune cells of AD patients may selectively enhance Aβ phagocytosis by alteration of gene transcription. In this work, we evaluated the protective effects of curcuminoids in cells from AD patients by investigating the effect on NF-κB and BACE1 signaling pathways. These results were compared to the gene expression profile of the clearance of Aβ. The minor curcumin constituent, bisdemethoxycurcumin (BDC) showed the most potent protective action to decrease levels of NF-κB and BACE1, decrease the inflammatory cascade and diminish Aβ aggregates in cells from AD patients. Moreover, mannosyl-glycoprotein 4-beta-N-acetylglucosaminyltransferase (MGAT3) and vitamin D receptor (VDR) gene mRNAs were up-regulated in peripheral blood mononuclear cells from AD patients treated with BDC. BDC treatment impacts both gene expression including Mannosyl (Beta-1,4-)-Glycoprotein Beta-1,4-N-Acetylglucosaminyltransferase, Vitamin D and Toll like receptor mRNA and Aβ phagocytosis. The observation of down-regulation of BACE1 and NF-κB following administration of BDC to cells from AD patients as a model system may have utility in the treatment of asymptomatic AD patients

The association of indwelling urinary catheter with delirium in hospitalized patients and nursing home residents: an explorative analysis from the "Delirium Day 2015"

Backround: Use of indwelling urinary catheter (IUC) in older adults has negative consequences, including delirium. Aim: This analysis, from the "Delirium Day 2015", a nationwide multicenter prevalence study, aim to evaluate the association of IUC with delirium in hospitalized and Nursing Homes (NHs) patients. Methods: Patients underwent a comprehensive geriatric assessment, including the presence of IUC; inclusion criteria were age > 65 years, being Italian speaker and providing informed consent; exclusion criteria were coma, aphasia, end-of-life status. Delirium was assessed using the 4AT test (score ≥ 4: possible delirium; scores 1-3: possible cognitive impairment). Results: Among 1867 hospitalized patients (mean age 82.0 ± 7.5 years, 58% female), 539 (28.9%) had IUC, 429 (22.9%) delirium and 675 (36.1%) cognitive impairment. IUC was significantly associated with cognitive impairment (OR 1.60, 95% CI 1.19-2.16) and delirium (2.45, 95% CI 1.73-3.47), this latter being significant also in the subset of patients without dementia (OR 2.28, 95% CI 1.52-3.43). Inattention and impaired alertness were also independently associated with IUC. Among 1454 NHs residents (mean age 84.4 ± 7.4 years, 70.% female), 63 (4.3%) had IUC, 535 (36.8%) a 4AT score ≥ 4, and 653 (44.9%) a 4AT score 1-3. The multivariate logistic regression analysis did not show a significant association between 4AT test or its specific items with IUC, neither in the subset of patients without dementia. Discussion: We confirmed a significant association between IUC and delirium in hospitalized patients but not in NHs residents. Conclusion: Environmental and clinical factors of acute setting might contribute to IUC-associated delirium occurrence

"Delirium Day": A nationwide point prevalence study of delirium in older hospitalized patients using an easy standardized diagnostic tool

Background: To date, delirium prevalence in adult acute hospital populations has been estimated generally from pooled findings of single-center studies and/or among specific patient populations. Furthermore, the number of participants in these studies has not exceeded a few hundred. To overcome these limitations, we have determined, in a multicenter study, the prevalence of delirium over a single day among a large population of patients admitted to acute and rehabilitation hospital wards in Italy. Methods: This is a point prevalence study (called "Delirium Day") including 1867 older patients (aged 65 years or more) across 108 acute and 12 rehabilitation wards in Italian hospitals. Delirium was assessed on the same day in all patients using the 4AT, a validated and briefly administered tool which does not require training. We also collected data regarding motoric subtypes of delirium, functional and nutritional status, dementia, comorbidity, medications, feeding tubes, peripheral venous and urinary catheters, and physical restraints. Results: The mean sample age was 82.0 ± 7.5 years (58 % female). Overall, 429 patients (22.9 %) had delirium. Hypoactive was the commonest subtype (132/344 patients, 38.5 %), followed by mixed, hyperactive, and nonmotoric delirium. The prevalence was highest in Neurology (28.5 %) and Geriatrics (24.7 %), lowest in Rehabilitation (14.0 %), and intermediate in Orthopedic (20.6 %) and Internal Medicine wards (21.4 %). In a multivariable logistic regression, age (odds ratio [OR] 1.03, 95 % confidence interval [CI] 1.01-1.05), Activities of Daily Living dependence (OR 1.19, 95 % CI 1.12-1.27), dementia (OR 3.25, 95 % CI 2.41-4.38), malnutrition (OR 2.01, 95 % CI 1.29-3.14), and use of antipsychotics (OR 2.03, 95 % CI 1.45-2.82), feeding tubes (OR 2.51, 95 % CI 1.11-5.66), peripheral venous catheters (OR 1.41, 95 % CI 1.06-1.87), urinary catheters (OR 1.73, 95 % CI 1.30-2.29), and physical restraints (OR 1.84, 95 % CI 1.40-2.40) were associated with delirium. Admission to Neurology wards was also associated with delirium (OR 2.00, 95 % CI 1.29-3.14), while admission to other settings was not. Conclusions: Delirium occurred in more than one out of five patients in acute and rehabilitation hospital wards. Prevalence was highest in Neurology and lowest in Rehabilitation divisions. The "Delirium Day" project might become a useful method to assess delirium across hospital settings and a benchmarking platform for future surveys

Mitochondria morphology and DNA content upon sublethal exposure to beta-amyloid(1-42) peptide

Brains affected by Alzheimer's disease (AD) show a large spectrum of mitochondrial alterations at both morphological and genetic level. The causal link between amyloid beta peptides (AP) and mitochondrial dysfunction has been established in cellular models of AD using Abeta concentrations capable of triggering massive neuronal death. However, mitochondrial changes related to sublethal exposure to Abeta are less known. Here we show that subtoxic, 1 microM Abeta(1-42) exposure does not change the mitochondrial shape of living cells, as visualized upon the uptake of the non-potentiometric fluorescent probe Mitotracker Green and enhanced yellow fluorescent protein (EYFP)-tagged cytochrome c oxidase expression. Immunolocalization of oxidative adducts 8-hydroxy-2'-deoxyguanosine, 8-hydroxyguanine and 8-hydroxyguanosine demonstrates that one-micromolar concentration of Abeta(1-42) is also not sufficient to elicit dramatic qualitative changes in the RNA/DNA oxidative products. However, in comparison with controls, semi-quantitative analysis of the overall mitochondrial mass by integrated fluorescence intensity reveals an ongoing down-regulation in mitochondrial biosynthesis or, conversely, an enhanced autophagic demise of Abeta treated cells. Furthermore, a significant increase of the full-length mitochondrial DNA (mtDNA) from Abeta-treated versus control cells is found, as measured by long range polymerase chain reaction (PCR). Such up-regulation is accompanied by extensive fragmentation of the unamplified mtDNA, probably due to the detrimental effect of Abeta. We interpret these results as a sequence of compensatory responses induced by mtDNA damage, which are devoted to repression of oxidative burst. In conclusion, our findings suggest that early therapeutic interventions aimed at prevention of mitochondrial oxidative damage may delay AD progression and help in treating AD patients