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      Behavioral Disturbances in Dementia and Beyond: Time for a New Conceptual Frame?

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          Abstract

          Alzheimer’s disease and vascular dementia are estimated to be the most common causes of dementia, although mixed dementia could represent the most prevalent form of dementia in older adults aged more than 80 years. Behavioral disturbances are common in the natural history of dementia. However, so far, there is a paucity of studies that investigated the causal association between behavioral psychological symptoms of dementia and dementia sub-types, due to the high heterogeneity of methodology, study design and type of clinical assessment. To understand the scant evidence on such a relevant clinical issue, it could be hypothesized that a new shifting paradigm could result in a better identification of the relationship between behavioral disturbances and dementia. This narrative review provides an update of evidence on the behavioral patterns associated with different dementia sub-types and offers a potential future perspective as common ground for the development of new translational studies in the field of behavioral disturbances in dementia and the appropriateness of psychoactive treatments.

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          Most cited references64

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          Basic mechanisms of neurodegeneration: a critical update

          Abstract Neurodegenerative diseases are characterized by progressive dysfunction of specific populations of neurons, determining clinical presentation. Neuronal loss is associated with extra and intracellular accumulation of misfolded proteins, the hallmarks of many neurodegenerative proteinopathies. Major basic processes include abnormal protein dynamics due to deficiency of the ubiquitin–proteosome–autophagy system, oxidative stress and free radical formation, mitochondrial dysfunction, impaired bioenergetics, dysfunction of neurotrophins, ‘neuroinflammatory’ processes and (secondary) disruptions of neuronal Golgi apparatus and axonal transport. These interrelated mechanisms lead to programmed cell death is a long run over many years. Neurodegenerative disorders are classified according to known genetic mechanisms or to major components of protein deposits, but recent studies showed both overlap and intraindividual diversities between different phenotypes. Synergistic mechanisms between pathological proteins suggest common pathogenic mechanisms. Animal models and other studies have provided insight into the basic neurodegeneration and cell death programs, offering new ways for future prevention/treatment strategies.
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            Criteria for the diagnosis of ischemic vascular dementia proposed by the State of California Alzheimer's Disease Diagnostic and Treatment Centers.

            Accurate diagnosis of vascular dementia is important for the recognition of underlying pathophysiology and the institution of appropriate therapy. It is also important for the determination of the incidence and prevalence of not only vascular dementia but also Alzheimer's disease (AD), since differentiating between these two entities is often problematic. The State of California Alzheimer's Disease Diagnostic and Treatment Centers (ADDTC) herein propose criteria for the diagnosis of ischemic vascular dementia (IVD). These criteria broaden the conceptualization of vascular dementia, include the results of neuroimaging studies, emphasize the importance of neuropathologic confirmation, refine nosology, and identify areas that require further research. Parallel use of the proposed definitions of "possible" and "mixed" categories in the diagnosis of both AD and IVD would ensure compatibility between the National Institute of Neurological and Communicative Disorders and Stroke (NINCDS) criteria for AD and the ADDTC criteria for IVD. Uniform classification of subtypes of IVD will improve the generalizability of individual studies and aid in multicenter collaborations.
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              The American Psychiatric Association Practice Guideline on the Use of Antipsychotics to Treat Agitation or Psychosis in Patients With Dementia.

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                Author and article information

                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                25 July 2019
                August 2019
                : 20
                : 15
                : 3647
                Affiliations
                [1 ]Geriatrics Clinic, Department of Internal Medicine and Medical Specialties (DIMI), University of Genoa, 16132 Genoa, Italy
                [2 ]IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy
                Author notes
                [* ]Correspondence: fiammetta.monacelli@ 123456unige.it ; Tel.: +39-010353-51055
                Article
                ijms-20-03647
                10.3390/ijms20153647
                6695658
                31349706
                7151568a-c7b8-4e65-941e-cbf18578f745
                © 2019 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 28 May 2019
                : 23 July 2019
                Categories
                Review

                Molecular biology
                vascular dementia,alzheimer’s disease,mixed dementia,behavioral disturbances clusters,antipsychotics

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