Journal of Alzheimer's Disease - Volume 50, issue 4

Authors: Mohseni, Hedieh K. | Chettle, David R.

Article Type: Review Article

Abstract: Aluminum, as an abundant metal, has gained widespread use in human life, entering the body predominantly as an additive to various foods and drinking water. Other major sources of exposure to aluminum include medical, cosmetic, and occupational routes. As a common environmental toxin, with well-known roles in several medical conditions such as dialysis encephalopathy, aluminum is considered a potential candidate in the causality of Alzheimer’s disease. Aluminum mostly accumulates in the bone, which makes bone an indicator of the body burden of aluminum and an ideal organ as a proxy for the brain. Most of the techniques developed for measuring …aluminum include bone biopsy, which requires invasive measures, causing inconvenience for the patients. There has been a considerable effort in developing non-invasive approaches, which allow for monitoring aluminum levels for medical and occupational purposes in larger populations. In vivo neutron activation analysis, a method based on nuclear activation of isotopes of elements in the body and their subsequent detection, has proven to be an invaluable tool for this purpose. There are definite challenges in developing in vivo non-invasive techniques capable of detecting low levels of aluminum in healthy individuals and aluminum-exposed populations. The following review examines the method of in vivo neutron activation analysis in the context of aluminum measurement in humans focusing on different neutron sources, interference from other activation products, and the improvements made in minimum detectable limits and patient dose over the past few decades. Show more

Keywords: Aluminum, Alzheimer’s disease, bone, dementia, gamma spectroscopy, in vivo neutron activation analysis

DOI: 10.3233/JAD-150595

Citation: Journal of Alzheimer's Disease, vol. 50, no. 4, pp. 913-926, 2016

Authors: Wang, Jun | Tan, Lan | Yu, Jin-tai

Article Type: Review Article

Abstract: Alzheimer’s disease (AD) is the most common form of dementia in the elderly. Over the past 20 years, both pharmacological and lifestyle interventions have been studied for AD prevention, but the overall results have been disappointing. The majority of disappointing results have raised questions and great challenges for the future of AD prevention trials. Ongoing advances in the knowledge of pathogenesis, in the identification of novel targets, in improved outcome measures, and in identification and validation of biomarkers may lead to effective strategies for AD prevention. In this paper, we review the selection of participants and interventions, trial design, outcome …assessments, and promising biomarkers in prevention trials, and summarize the lessons learned from completed trials and perspectives from ongoing trials in AD prevention. Selection of optimal participants and interventions, coupled with more refined outcomes and more efficient trial design, may have the capacity to deliver a new era of preventive discovery in this challenging area. Show more

Keywords: Alzheimer’s disease, lifestyle, pharmacology, prevention, trial

DOI: 10.3233/JAD-150826

Citation: Journal of Alzheimer's Disease, vol. 50, no. 4, pp. 927-945, 2016

Authors: Boccardi, Virginia | Ruggiero, Carmelinda | Patriti, Alberto | Marano, Luigi

Article Type: Review Article

Abstract: A growing concern in patients affected by Alzheimer’s disease (AD) is dysphagia, or swallowing impairment, which leads to malnutrition, dehydration, weight loss, functional decline and fear of eating and drinking, as well as a decrease in the quality of life. Thus the diagnostic assessment of dysphagia in patients with AD is imperative to ensure that they receive effective management, avoiding complications, and reducing comorbidity and mortality in such a growing population. Dysphagia management requires a multidisciplinary approach considering that no single strategy is appropriate for all patients. However, evidence for clinical diagnostic assessment, interventions, and medical management of dysphagia in …these patients are still limited: few studies are reporting the evaluation and the management among this group of patients. Here we analyzed the most recent findings in diagnostic assessment and management of swallowing impairment in patients affected by AD. Show more

Keywords: Alzheimer’s disease, dysphagia, elderly, nutrition

DOI: 10.3233/JAD-150931

Citation: Journal of Alzheimer's Disease, vol. 50, no. 4, pp. 947-955, 2016

Authors: Balietti, Marta | Giuli, Cinzia | Fattoretti, Patrizia | Fabbietti, Paolo | Postacchini, Demetrio | Conti, Fiorenzo

Article Type: Short Communication

Abstract: We evaluated the effect of cognitive stimulation (CS) on platelet total phospholipases A2 activity (tPLA2 A) in patients with mild cognitive impairment (MCI_P). At baseline, tPLA2 A negatively correlated with Mini-Mental State Examination score (MMSE_s): patients with MMSE_s <26 (Subgroup 1) had significantly higher activity than those with MMSE_s ≥26 (Subgroup 2), who had values similar to the healthy elderly. Regarding CS effect, Subgroup 1 had a significant tPLA2 A reduction, whereas Subgroup 2 did not significantly changes after training. Our results showed for the first time that tPLA2 A correlates with the cognitive conditions of MCI_P, and that …CS acts selectively on subjects with a dysregulated tPLA2 A. Show more

Keywords: Blood platelets, cognitive stimulation, mild cognitive impairment, phospholipases A2

DOI: 10.3233/JAD-150714

Citation: Journal of Alzheimer's Disease, vol. 50, no. 4, pp. 957-962, 2016

Authors: Rodriguez-Perdigon, Manuel | Solas, Maite | Ramirez, Maria Javier

Article Type: Short Communication

Abstract: In the present work, the involvement of JNK in insulin signaling alterations and its role in glutamatergic deficits in Alzheimer’s disease (AD) has been studied. In postmortem cortical tissues, pJNK levels were increased, while insulin signaling and the expression of VGLUT1 were decreased. A significant correlation was found between reduced expression of insulin receptor and VGLUT1. The administration of a JNK inhibitor reversed the decrease in VGLUT1 expression found in a mice model of insulin resistance. It is suggested that activation of JNK in AD inhibits insulin signaling which could lead to a decreased expression of VGLUT1, therefore contributing to …the glutamatergic deficit in AD. Show more

Keywords: Glutamate, insulin, JNK, Mini-Mental State Examination, pAkt, postmortem human tissue

DOI: 10.3233/JAD-150659

Citation: Journal of Alzheimer's Disease, vol. 50, no. 4, pp. 963-967, 2016

Authors: Gallucci, Maurizio | Spagnolo, Pierpaolo | Aricò, Maria | Grossi, Enzo

Article Type: Research Article

Abstract: Background: The pharmacological treatment of Alzheimer’s disease (AD) is based largely on cholinesterase inhibitors (ChEI). Objective: To investigate whether or not some non-pharmacological and contextual factors measured prior to starting treatment such as past occupation, lifestyles, marital status, degree of autonomy and cognitive impairment, living alone or with others, and the degree of brain atrophy are associated with a better response to ChEI treatment. Methods: Eighty-four AD and six AD with cerebrovascular disease (AD + CVD) outpatients of Treviso Dementia (TREDEM) Registry, with an average cholinesterase inhibitors treatment length of four years, were considered. The outpatients had …undergone a complete evaluation and some non-pharmacological and contextual factors were collected. We defined responder a patient with a delta score T0 – T1 equal or inferior to 2.0 points per year of MMSE and a non-responder a patient with a delta score T0 – T1 superior to 2.0 points per year. In order to identify hidden relationships between variables related to response and non-response, we use a special kind of artificial neural network called Auto-CM, able to create a semantic connectivity map of the variables considered in the study. Results: A higher cognitive profile, a previous intellectual occupation, healthier lifestyles, being married and not living alone, a higher degree of autonomy, and lower degree of brain atrophy at baseline resulted in affecting the response to long-term ChEI therapy. Conclusion: Non-pharmacological and contextual factors appear to influence the effectiveness of treatment with ChEI in the long term. Show more

Keywords: Alzheimer’s disease, Auto-CM system, brain and cognitive reserve, brain atrophy, cholinesterase inhibitors, environmental enrichment, TREDEM

DOI: 10.3233/JAD-150747

Citation: Journal of Alzheimer's Disease, vol. 50, no. 4, pp. 969-979, 2016

Authors: Belkacemi, Abdenour | Ramassamy, Charles

Article Type: Research Article

Abstract: In Alzheimer’s disease (AD) and in mild cognitive impairment (MCI) patients, by-products of lipid peroxidation such as acrolein accumulated in vulnerable regions of the brain. We have previously shown that acrolein is a highly reactive and neurotoxic aldehyde and its toxicity involves the alteration of several redox-sensitive pathways. Recently, protein-conjugated acrolein in cerebrospinal fluid has been proposed as a biomarker to distinguish between MCI and AD. With growing evidence of the early involvement of oxidative stress in AD etiology, one would expect that a successful therapy should prevent brain oxidative damage. In this regard, several studies have demonstrated that polyphenol-rich …extracts exert beneficial effect on cognitive impairment and oxidative stress. We have recently demonstrated the efficacy of an anthocyanin formulation (MAF14001) against amyloid-β-induced oxidative stress. The aim of this study is to investigate the neuroprotective effect of MAF14001 as a mixture of anthocyanins, a particular class of polyphenols, against acrolein-induced oxidative damage in SK-N-SH neuronal cells. Our results demonstrated that MAF14001, from 5μ M, was able to efficiently protect SK-N-SH cells against acrolein-induced cell death. MAF14001 was able to lower reactive oxygen species and protein carbonyl levels induced by acrolein. Moreover, MAF1401 prevented glutathione depletion and positively modulated, in the presence of acrolein, some oxidative stress-sensitive pathways including the transcription factors NF-κ B and Nrf2, the proteins γ -GCS and GSK3β, and the protein adaptator p66Shc. Along with its proven protective effect against amyloid-β toxicity, these results demonstrate that MAF14001 could target multiple mechanisms and could be a promising agent for AD prevention. Show more

Keywords: Acrolein, Alzheimer’s disease, anthocyanins, antioxidant, glutathione, oxidative stress, polyphenols

DOI: 10.3233/JAD-150770

Citation: Journal of Alzheimer's Disease, vol. 50, no. 4, pp. 981-998, 2016

Authors: Gramunt, Nina | Sánchez-Benavides, Gonzalo | Buschke, Herman | Lipton, Richard B. | Masramon, Xavier | Gispert, Juan D. | Peña-Casanova, Jordi | Fauria, Karine | Molinuevo, José L.

Article Type: Research Article

Abstract: Background: Episodic memory testing is fundamental for the diagnosis of Alzheimer’s disease (AD). Although the Free and Cued Selective Reminding Test (FCSRT) is widely used for this purpose, it may not be sensitive enough for early detection of subtle decline in preclinical AD. The Memory Binding Test (MBT) intends to overcome this limitation. Objectives: To analyze the test-retest reliability of the MBT and its convergent validity with the FCRST. Methods: 36 cognitively healthy participants of the ALFA Study, aged 45 to 65, were included for the test-retest study and 69 for the convergent analysis. They were …visited twice in a period of 6 ± 2 weeks. Test-retest reliability was determined by the calculation of the intra-class correlation coefficient (ICC). Score differences were studied by computing the mean percentage of score variation between visits and visualized by Bland-Altman plots. Convergent validity was determined by Pearson’s correlations. Results: ICC values in the test-retest reliability analysis of the MBT direct scores ranged from 0.64 to 0.76. Subjects showed consistent practice effects, with mean amounts of score increasing between 10% and 26%. Pearson correlation between MBT and FCSRT direct scores showed r values between 0.40 and 0.53. The FCSRT displayed ceiling effects not observed in the MBT. Conclusions: The MBT shows adequate test-retest reliability and overall moderate convergent validity with the FCSRT. Unlike the FCSRT, the MBT does not have ceiling effects and it may therefore be especially useful in longitudinal studies, facilitating the measurement of subtle memory performance decline and the detection of very early AD. Show more

Keywords: Alzheimer’s disease, early diagnosis, episodic memory, memory assessment, preclinical, psychometrics, reliability, validity

DOI: 10.3233/JAD-150776

Citation: Journal of Alzheimer's Disease, vol. 50, no. 4, pp. 999-1010, 2016

Authors: Dodich, Alessandra | Cerami, Chiara | Crespi, Chiara | Canessa, Nicola | Lettieri, Giada | Iannaccone, Sandro | Marcone, Alessandra | Cappa, Stefano F. | Cacioppo, John T.

Article Type: Research Article

Abstract: Cognitive and affective theory of mind (ToM) can be impaired in the course of neurodegenerative dementias. Experimental tests based on different task conditions and/or complexity may fail to capture disease-specific patterns of impairments. In this study, we assessed with a single task both the affective and the cognitive facets of ToM ability in a sample of 47 patients (i.e., 12 AD, 20 bvFTD, and 15 aMCI fulfilling IWG criteria for AD in predementia phase) and 65 healthy controls. Subjects were administered the Story-based Empathy task (SET), a non-verbal task measuring the ability to infer others’ intentions (IA) and emotions (EA) …compared to a control condition (causal inferences, CI). Global and single sub-condition scores were evaluated with a vectorial method, analyzing the relationship between social abilities and basic cognitive functioning by means of two indices representing the basic ability to perform the task and the balance between basic functions and ToM skills. Dementia (AD and bvFTD) patients showed impaired performances on all SET sub-conditions, whereas aMCI subjects’ performance was not different from healthy controls. Vectorial analysis revealed a specific change in the balance between EA and CI conditions only in the bvFTD group, supporting a disproportionate deficit in mental states attribution based on affective cues. The overall deficit in the task in AD appears to be more general and related to the severity of dementia. This latter finding is further supported by the normal performance of the prodromal AD group. Show more

Keywords: Alzheimer’s disease, frontotemporal dementia, mild cognitive impairment, neurodegenerative diseases, theory of mind

DOI: 10.3233/JAD-150605

Citation: Journal of Alzheimer's Disease, vol. 50, no. 4, pp. 1011-1022, 2016

Authors: Langlois, Roxane | Joubert, Sven | Benoit, Sophie | Dostie, Valérie | Rouleau, Isabelle

Article Type: Research Article

Abstract: Ribot’s law refers to the better preservation of remote memories compared with recent ones that presumably characterizes retrograde amnesia. Even if Ribot-type temporal gradient has been extensively studied in retrograde amnesia, particularly in Alzheimer’s disease (AD), this pattern has not been consistently found. One explanation for these results may be that rehearsal frequency rather than remoteness accounts for the better preservation of these memories. Thus, the aim of present study was to address this question by studying retrograde semantic memory in subjects with amnestic mild cognitive impairment (aMCI) (n  = 20), mild AD (n  = 20) and in healthy older controls (HC; …n  = 19). In order to evaluate the impact of repetition as well as the impact of remoteness, we used a test assessing memory for enduring and transient public events that occurred in the recent and remote past. Results show no clear temporal gradient across time periods (1960–1975; 1976–1990; 1991–2005; 2006–2011), but a better performance was observed in all three groups for enduring compared with transient events. Moreover, although deficits were globally found in both patients groups compared with HC, more specific analyses revealed that aMCI patients were only impaired on transient events while AD patients were impaired on both transient and enduring events. Exploratory analyses also revealed a tendency suggesting preservation of remote transient events in aMCI. These findings are discussed with regards to memory consolidation models. Show more

Keywords: Alzheimer’s disease, enduring, famous public events, mild cognitive impairment, retrograde memory, semantic memory, transient

DOI: 10.3233/JAD-150722

Citation: Journal of Alzheimer's Disease, vol. 50, no. 4, pp. 1023-1033, 2016