Journal of Alzheimer's Disease - Volume 56, issue 2

Authors: Carotenuto, Anna | Rea, Raffaele | Traini, Enea | Fasanaro, Angiola Maria | Ricci, Giovanna | Manzo, Valentino | Amenta, Francesco

Article Type: Research Article

Abstract: Background : Behavioral and psychological symptoms of dementia (BPSD) are a group of psychological reactions, psychiatric symptoms, and behaviors commonly found in Alzheimer’s disease (AD). Four clusters of BPSD have been described: mood disorders (depression, anxiety, and apathy), psychotic symptoms (delusions and hallucinations), aberrant motor behaviors (pacing, wandering, and other purposeless behaviors), and inappropriate behaviors (agitation, disinhibition, and euphoria). Most of them are attributed to acetylcholine deficiency. Objective: To evaluate if a higher amount of acetylcholine obtained by associating donepezil and choline alphoscerate might have a favorable effect on BPSD. Methods: BPSD were measured at baseline …and after 24 months in 113 mild/moderate AD patients, included in the double-blind randomized trial ASCOMALVA, by the Neuropsychiatric Inventory (NPI). Two matched groups were compared: group A treated with donepezil (10 mg/day) plus choline alphoscerate (1200 mg/day), and group B treated with donepezil (10 mg/day) plus placebo. Results: Data of NPI revealed a significant decrease of BPSD severity and distress of the caregiver in patients of group A compared with group B. Mood disorders (depression, anxiety and apathy) were significantly decreased in subjects treated with donepezil and choline alphoscerate, while their severity and frequency was increased in the other group. Conclusions: Patients treated with donepezil plus choline alphoscerate showed a lower level of behavioral disturbances than subjects treated with donepezil only, suggesting that the association can have beneficial effects. Show more

Keywords: Alzheimer’s disease, behavioral and psychological symptoms of dementia, choline alphoscerate, donepezil, neuropsychiatric symptoms

DOI: 10.3233/JAD-160675

Citation: Journal of Alzheimer's Disease, vol. 56, no. 2, pp. 805-815, 2017

Authors: Nakanishi, Miharu | Niimura, Junko | Yamasaki, Syudo | Nishida, Atsushi

Article Type: Research Article

Abstract: Background: Japan designates psychiatric inpatient care for behavior management of individuals with dementia and for helping dementia patients discharge to home. However, there has been no examination of the effectiveness of this strategy. Objective: The present study investigated the association between dementia and the discharge destination of patients in psychiatric hospitals. Methods: Data from the National Patient Survey, which is a nationally representative cross-sectional survey of inpatient care, were used. The 96,420 patients with dementia or other mental illness who were discharged from psychiatric hospitals in September of every 3 years from 1996 to 2014 …were included in analyses. Results: Of the 96,420 discharged patients, 13,823 had dementia as the primary disease. Of the 13,823 dementia patients, 3,865 (28.0%) were discharged to home, 3,870 (28.0%) were admitted to a facility or other care settings, 3,574 (25.9%) were admitted to another hospital, and 2,514 (18.2%) died. Patients were more likely to die in psychiatric hospital if their primary disease was dementia, and they had resided in a region that provided fewer home visits for psychiatric nursing care or had available a larger number of psychiatric hospital beds per capita. Conclusion: Psychiatric inpatient care may be ineffective as a treatment for the challenging behaviors of dementia. A community mental health system for behavior management should be constructed in parallel with a reduction in the number of hospital beds allotted for psychiatric care. Show more

Keywords: Behavioral symptoms, community mental health services, dementia, health services research, psychiatric hospitals

DOI: 10.3233/JAD-160935

Citation: Journal of Alzheimer's Disease, vol. 56, no. 2, pp. 817-824, 2017

Authors: Benussi, Luisa | Ghidoni, Roberta | Dal Piaz, Fabrizio | Binetti, Giuliano | Di Iorio, Giuseppe | Abrescia, Paolo

Article Type: Research Article

Abstract: Cholesterol (C) brain accumulation seems to play a role in the Alzheimer’s disease (AD) pathogenesis. 24(S)-hydroxycholesterol (24OH-C) is the predominant metabolite of brain C and its synthesis is believed to represent a way to remove excess C from neurons. Previous studies showed that 24OH-C level is altered in patients with neurodegenerative diseases, including AD. Only one study demonstrated that 24OH-C esterification is altered in neurodegenerative diseases, i.e., amyotrophic lateral sclerosis. Herein we analyzed the level of 24OH-C esters (% 24OH-CE) in i) cerebrospinal fluid (CSF) and homologous serum of AD (n  = 13) and controls (n  = 8); ii) plasma from AD …(n  = 30), controls (n  = 30), mild cognitive impairment (MCI) converting to AD (n  = 34), and stable MCI (n  = 40). The % 24OH-CE in CSF positively correlated with that in homologous serum and was lower in both CSF and blood from AD patients as compared to controls; moreover, the plasma value of % 24OH-CE was lower in MCI conv-AD than in non-converters. Kaplan Meier Survival curves revealed a significant anticipation of the disease onset in AD and MCI conv-AD subjects with the lowest % 24OH-CE values. In conclusion, the reduction of % 24OH-CE in AD and MCI conv-AD, as well as the anticipation of the disease in patients with the lowest % 24OH-CE, support a role of the cholesterol/lecithin-cholesterol acyltransferase axis in AD onset/progression. Thus, targeting brain cholesterol metabolism could be a valuable strategy to prevent AD associated cognitive decline. Show more

Keywords: Alzheimer’s disease, biomarker, case control studies, cholesterol esterification, cohort studies, mild cognitive impairment

DOI: 10.3233/JAD-160930

Citation: Journal of Alzheimer's Disease, vol. 56, no. 2, pp. 825-833, 2017

Authors: Dashinimaev, Erdem B. | Artyuhov, Alexander S. | Bolshakov, Alexey P. | Vorotelyak, Ekaterina A. | Vasiliev, Andrey V.

Article Type: Research Article

Abstract: People with Down syndrome (DS) are at high risk of developing pathology similar to Alzheimer’s disease (AD). Modeling of this pathology in vitro may be useful for studying this phenomenon. In this study, we analyzed three different cultures of neural cells carrying trisomy of chromosome 21, which were generated by directed differentiation from induced pluripotent stem cells (iPS cells). We report here that in vitro generated DS neural cells have abnormal metabolism of amyloid-β (Aβ) manifested by increased secretion and accumulation of Aβ granules of Aβ42 pathological isoform with upregulated expression of the APP gene. Additionally, we …found increased expression levels of genes that are considered to be associated with AD (BACE2, RCAN1, ETS2, TMED10), as compared to healthy controls. Thus, the neural cells generated from induced pluripotent stem cells with DS reproduce initial cellular signs of AD-type pathology and can be useful tools for modeling and studying this variant of AD in vitro . Show more

Keywords: Alzheimer’s disease, amyloid-β, Aβ42, APP, BACE2, Down syndrome, ETS2, IPSC, RCAN1, TMED10

DOI: 10.3233/JAD-160945

Citation: Journal of Alzheimer's Disease, vol. 56, no. 2, pp. 835-847, 2017

Authors: Betrie, Ashenafi H. | Ayton, Scott | Bush, Ashley I. | Angus, James A. | Lei, Peng | Wright, Christine E.

Article Type: Research Article

Abstract: Aggregation of tau protein into intracellular deposits is a pathognomonic feature of tauopathies such as Alzheimer’s disease (AD) and lowering tau is a prominent therapeutic strategy under development. However, the physiological function of tau protein is not well known, particularly in the periphery. Lowering tau protein risks disrupting its physiological role leading to unwanted effects. In this study, the presence of tau protein in cardiac tissue is confirmed and the functional role in the cardiovascular system and the consequences of its loss were explored. Isolated right and left atria and small mesenteric arteries from wild type and tau deficient (KO) …mice of two age groups (13 and 23 months old) were used to assess cardiovascular phenotypes. Tau KO mice showed an increased systolic blood pressure and cardiac hypertrophy at 13 months, which was accompanied by a significantly lower right atrial rate and a subtle decrease in the maximum contractility to calcium, isoprenaline, and electrical sympathetic nerve stimulation. Aging tau KO mice to 23 months resulted in cardiac hypertrophy with significantly attenuated left atrial contractility, increased blood pressure, and sensitivity of isolated mesenteric arteries to angiotensin II contraction and isoprenaline relaxation compared to their younger counterparts. This study supports a functional role of tau in the heart and loss of this protein leads to a deterioration in cardiovascular performance which worsens with age. Taken together, these results provide insight into the peripheral function of tau protein, and give caution to the therapeutic strategy of lowering tau protein. Show more

Keywords: Alzheimer’s disease, cardiovascular, heart, mesenteric arteries, pharmacology, tau protein

DOI: 10.3233/JAD-161093

Citation: Journal of Alzheimer's Disease, vol. 56, no. 2, pp. 849-860, 2017