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      Multidimensional Apathy in Behavioral Variant Frontotemporal Dementia, Primary Progressive Aphasia, and Alzheimer Disease

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          Abstract

          Apathy is prevalent in dementia, such as behavioral variant frontotemporal dementia (bvFTD), primary progressive aphasia (PPA), and Alzheimer disease (AD). As a multidimensional construct, it can be assessed and subsumed under a Dimensional Apathy Framework. A consistent apathy profile in bvFTD and PPA has yet to be established. The aim was to explore apathy profiles and awareness in bvFTD, PPA, and AD. A total of 12 patients with bvFTD, 12 patients with PPA, 28 patients with AD, and 20 matched controls, as well as their informants/carers, were recruited. All participants completed the Dimensional Apathy Scale (DAS), assessing executive, emotional, and initiation apathy subtypes, a 1-dimensional apathy measure, depression measure, and functional and cognitive screens. Apathy subtype awareness was determined through DAS informant/carer and self-rating discrepancy. Apathy profile comparison showed patients with bvFTD had significantly higher emotional apathy than patients with AD ( P < .01) and significantly higher apathy over all subtypes than patients with PPA ( Ps < .05). Additionally, patients with bvFTD had significantly lower awareness for emotional apathy ( P < .01) when compared to patients with AD and PPA. All patient groups had significant global apathy over all subtypes compared to controls. The emergent apathy profile for bvFTD seems to be emotional apathy (indifference or emotional/affective neutrality), with lower self-awareness in this subtype. Further, lower self-awareness for executive apathy (lack of motivation for planning, organization, or attention) differentiates bvFTD from PPA. Future research should investigate the cognitive and neural correlates as well as the practical impact of apathy subtypes.

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          Most cited references51

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          The diagnosis of dementia due to Alzheimer's disease: Recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease

          The National Institute on Aging and the Alzheimer's Association charged a workgroup with the task of revising the 1984 criteria for Alzheimer's disease (AD) dementia. The workgroup sought to ensure that the revised criteria would be flexible enough to be used by both general healthcare providers without access to neuropsychological testing, advanced imaging, and cerebrospinal fluid measures, and specialized investigators involved in research or in clinical trial studies who would have these tools available. We present criteria for all-cause dementia and for AD dementia. We retained the general framework of probable AD dementia from the 1984 criteria. On the basis of the past 27 years of experience, we made several changes in the clinical criteria for the diagnosis. We also retained the term possible AD dementia, but redefined it in a manner more focused than before. Biomarker evidence was also integrated into the diagnostic formulations for probable and possible AD dementia for use in research settings. The core clinical criteria for AD dementia will continue to be the cornerstone of the diagnosis in clinical practice, but biomarker evidence is expected to enhance the pathophysiological specificity of the diagnosis of AD dementia. Much work lies ahead for validating the biomarker diagnosis of AD dementia. Copyright © 2011. Published by Elsevier Inc.
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            Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia.

            Based on the recent literature and collective experience, an international consortium developed revised guidelines for the diagnosis of behavioural variant frontotemporal dementia. The validation process retrospectively reviewed clinical records and compared the sensitivity of proposed and earlier criteria in a multi-site sample of patients with pathologically verified frontotemporal lobar degeneration. According to the revised criteria, 'possible' behavioural variant frontotemporal dementia requires three of six clinically discriminating features (disinhibition, apathy/inertia, loss of sympathy/empathy, perseverative/compulsive behaviours, hyperorality and dysexecutive neuropsychological profile). 'Probable' behavioural variant frontotemporal dementia adds functional disability and characteristic neuroimaging, while behavioural variant frontotemporal dementia 'with definite frontotemporal lobar degeneration' requires histopathological confirmation or a pathogenic mutation. Sixteen brain banks contributed cases meeting histopathological criteria for frontotemporal lobar degeneration and a clinical diagnosis of behavioural variant frontotemporal dementia, Alzheimer's disease, dementia with Lewy bodies or vascular dementia at presentation. Cases with predominant primary progressive aphasia or extra-pyramidal syndromes were excluded. In these autopsy-confirmed cases, an experienced neurologist or psychiatrist ascertained clinical features necessary for making a diagnosis according to previous and proposed criteria at presentation. Of 137 cases where features were available for both proposed and previously established criteria, 118 (86%) met 'possible' criteria, and 104 (76%) met criteria for 'probable' behavioural variant frontotemporal dementia. In contrast, 72 cases (53%) met previously established criteria for the syndrome (P < 0.001 for comparison with 'possible' and 'probable' criteria). Patients who failed to meet revised criteria were significantly older and most had atypical presentations with marked memory impairment. In conclusion, the revised criteria for behavioural variant frontotemporal dementia improve diagnostic accuracy compared with previously established criteria in a sample with known frontotemporal lobar degeneration. Greater sensitivity of the proposed criteria may reflect the optimized diagnostic features, less restrictive exclusion features and a flexible structure that accommodates different initial clinical presentations. Future studies will be needed to establish the reliability and specificity of these revised diagnostic guidelines.
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              Classification of primary progressive aphasia and its variants

              This article provides a classification of primary progressive aphasia (PPA) and its 3 main variants to improve the uniformity of case reporting and the reliability of research results. Criteria for the 3 variants of PPA--nonfluent/agrammatic, semantic, and logopenic--were developed by an international group of PPA investigators who convened on 3 occasions to operationalize earlier published clinical descriptions for PPA subtypes. Patients are first diagnosed with PPA and are then divided into clinical variants based on specific speech and language features characteristic of each subtype. Classification can then be further specified as "imaging-supported" if the expected pattern of atrophy is found and "with definite pathology" if pathologic or genetic data are available. The working recommendations are presented in lists of features, and suggested assessment tasks are also provided. These recommendations have been widely agreed upon by a large group of experts and should be used to ensure consistency of PPA classification in future studies. Future collaborations will collect prospective data to identify relationships between each of these syndromes and specific biomarkers for a more detailed understanding of clinicopathologic correlations.
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                Author and article information

                Journal
                J Geriatr Psychiatry Neurol
                J Geriatr Psychiatry Neurol
                JGP
                spjgp
                Journal of Geriatric Psychiatry and Neurology
                SAGE Publications (Sage CA: Los Angeles, CA )
                0891-9887
                1552-5708
                15 May 2020
                September 2021
                : 34
                : 5
                : 349-356
                Affiliations
                [1 ]Department of Psychology, Ringgold 3124, universityUniversity of Edinburgh; , Edinburgh, United Kingdom
                [2 ]Anne Rowling Regenerative Neurology Clinic, Ringgold 3124, universityUniversity of Edinburgh; , Edinburgh, United Kingdom
                [3 ]Alzheimer Scotland Dementia Research Centre, Ringgold 3124, universityUniversity of Edinburgh; , Edinburgh, United Kingdom
                [4 ]Euan MacDonald Centre for MND Research, Ringgold 3124, universityUniversity of Edinburgh; , Edinburgh, United Kingdom
                [5 ]Centre for Cognitive Ageing and Cognitive Epidemiology, Ringgold 3124, universityUniversity of Edinburgh; , Edinburgh, United Kingdom
                [6 ]Faculty of Medicine and Health Sciences, Ringgold 83726, universityUniversity of East Anglia; , Norwich, United Kingdom
                [7 ]Centre for Clinical Brain Sciences, Ringgold 3124, universityUniversity of Edinburgh; , Edinburgh, United Kingdom
                []Deceased
                Author notes
                [*]Ratko Radakovic, University of East Anglia Faculty of Medicine and Health Sciences, Norwich Research Park, Norwich NR4 7TJ, United Kingdom. Emails: r.radakovic@ 123456uea.ac.uk ; radakovic.ratko@ 123456gmail.com
                Author information
                https://orcid.org/0000-0001-9425-3639
                Article
                10.1177_0891988720924716
                10.1177/0891988720924716
                8326892
                32410488
                9dcb4784-2d63-40cd-a1d9-f4be39d9f66c
                © The Author(s) 2020

                This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ( https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

                History
                : 7 November 2019
                : 8 April 2020
                : 8 April 2020
                Funding
                Funded by: Anne Rowling Regenerative Neurology Clinic;
                Funded by: Motor Neurone Disease Scotland;
                Funded by: Alzheimer Scotland Dementia Research Centre;
                Funded by: University Of Edinburgh, FundRef https://doi.org/10.13039/501100000848;
                Categories
                Original Articles
                Custom metadata
                ts3

                alzheimer disease,behavioral variant frontotemporal dementia,primary progressive aphasia,frontotemporal dementia,apathy,awareness,insight

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