Abstract
Frontotemporal dementia, a heterogeneous neurodegenerative disorder, is a common cause of young onset dementia (i.e. dementia developing in midlife or earlier). The estimated point ...prevalence is 15-22/100,000, and incidence 2.7-4.1/100,000. Some 25% are late-life onset cases. Population studies show nearly equal distribution by gender, which contrasts with myriad clinical and neuropathology reports. FTD is frequently familial and hereditary; five genetic loci for causal mutations have been identified, all showing 100% penetrance. Non-genetic risk factors are yet to be identified. FTD shows poor life expectancy but with survival comparable to that of Alzheimer's disease. Recent progress includes the formulation of up-to-date diagnostic criteria for the behavioural and language variants, and the development of new and urgently needed instruments for monitoring and staging the illness. There is still need for descriptive population studies to fill gaps in our knowledge about minority groups and developing regions. More pressing, however, is the need for reliable physiological markers for disease. There is a present imperative to develop a translational science to form the conduit for transferring neurobiological discoveries and insights from bench to bedside.
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The human cerebellum plays an essential role in motor control, is involved in cognitive function (i.e., attention, working memory, and language), and helps to regulate emotional responses. ...Quantitative in-vivo assessment of the cerebellum is important in the study of several neurological diseases including cerebellar ataxia, autism, and schizophrenia. Different structural subdivisions of the cerebellum have been shown to correlate with differing pathologies. To further understand these pathologies, it is helpful to automatically parcellate the cerebellum at the highest fidelity possible. In this paper, we coordinated with colleagues around the world to evaluate automated cerebellum parcellation algorithms on two clinical cohorts showing that the cerebellum can be parcellated to a high accuracy by newer methods. We characterize these various methods at four hierarchical levels: coarse (i.e., whole cerebellum and gross structures), lobe, subdivisions of the vermis, and the lobules. Due to the number of labels, the hierarchy of labels, the number of algorithms, and the two cohorts, we have restricted our analyses to the Dice measure of overlap. Under these conditions, machine learning based methods provide a collection of strategies that are efficient and deliver parcellations of a high standard across both cohorts, surpassing previous work in the area. In conjunction with the rank-sum computation, we identified an overall winning method.
•First paper to evaluate the state-of-the-art in cerebellum parcellation.•Presenting results on both Adult and Pediatric Cohorts.•Adult Cohort contains healthy controls, and patients with either symptoms of cerebellar dysfunction or SCA 6.•Pediatric Cohort contains healthy controls, and patients with ADHD or Autism.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Mild behavioral impairment (MBI) is a construct that describes the emergence at ≥50 years of age of sustained and impactful neuropsychiatric symptoms (NPS), as a precursor to cognitive decline and ...dementia. MBI describes NPS of any severity, which are not captured by traditional psychiatric nosology, persist for at least 6 months, and occur in advance of or in concert with mild cognitive impairment. While the detection and description of MBI has been operationalized in the International Society to Advance Alzheimer's Research and Treatment - Alzheimer's Association (ISTAART-AA) research diagnostic criteria, there is no instrument that accurately reflects MBI as described.
To develop an instrument based on ISTAART-AA MBI criteria.
Eighteen subject matter experts participated in development using a modified Delphi process. An iterative process ensured items reflected the five MBI domains of 1) decreased motivation; 2) emotional dysregulation; 3) impulse dyscontrol; 4) social inappropriateness; and 5) abnormal perception or thought content. Instrument language was developed a priori to pertain to non-demented functionally independent older adults.
We present the Mild Behavioral Impairment Checklist (MBI-C), a 34-item instrument, which can easily be completed by a patient, close informant, or clinician.
The MBI-C provides the first measure specifically developed to assess the MBI construct as explicitly described in the criteria. Its utility lies in MBI case detection, and monitoring the emergence of MBI symptoms and domains over time. Studies are required to determine the prognostic value of MBI for dementia development, and for predicting different dementia subtypes.
See King et al. (doi:10.1093/aww348) for a scientific commentary on this article.Detailed mapping of clinical dysfunctions to the cerebellar lobules in disease populations is necessary to establish ...the functional significance of lobules implicated in cognitive and motor functions in normal subjects. This study constitutes the first quantitative examination of the lobular correlates of a broad range of cognitive and motor phenomena in cerebellar disease. We analysed cross-sectional data from 72 cases with cerebellar disease and 36 controls without cerebellar disease. Cerebellar lobule volumes were derived from a graph-cut based segmentation algorithm. Sparse partial least squares, a variable selection approach, was used to identify lobules associated with motor function, language, executive function, memory, verbal learning, perceptual organization and visuomotor coordination. Motor dysfunctions were chiefly associated with the anterior lobe and posterior lobule HVI. Confrontation naming, noun fluency, recognition, and perceptual organization did not have cerebellar associations. Verb and phonemic fluency, working memory, cognitive flexibility, immediate and delayed recall, verbal learning, and visuomotor coordination were variably associated with HVI, Crus I, Crus II, HVII B and/or HIX. Immediate and delayed recall also showed associations with the anterior lobe. These findings provide preliminary anatomical evidence for a functional topography of the cerebellum first defined in task-based functional magnetic resonance imaging studies of normal subjects and support the hypotheses that (i) cerebellar efferents target frontal lobe neurons involved in forming action representations and new search strategies; (ii) there is greater involvement of the cerebellum when immediate recall tasks involve more complex verbal stimuli (e.g. longer words versus digits); and (iii) it is involved in spontaneous retrieval of long-term memory. More generally, they provide an anatomical background for studies that seek the mechanisms by which cognitive and motor dysfunctions arise from cerebellar degeneration. Beyond replicating these findings, future research should employ experimental tasks to probe the integrity of specific functions in cerebellar disease, and new imaging methods to quantitatively map atrophy across the cerebellum.
It is predictable that syndromes of frontotemporal dementia (FTD) may have a worldwide distribution; however, data available on their incidence and prevalence are variable. This variability most ...likely reflects disparities across regions in the distribution of the expertise, technology, and resources available for FTD research and care. Important discoveries have been made regarding FTD's phenotypes, genetics, and cultural influences on the expression of symptoms; however, in many countries, there are barriers posed by a dearth of resources. There are pressing needs to further develop research on FTD: including first, population studies designed to fill the gaps in our knowledge about FTD's frequency and risk factors in developing regions and among minority groups in developed countries. It is also necessary to facilitate the psychometric characterization of contemporary diagnostic criteria and their translation to different languages and cultural contexts. Furthermore, much needed is the analysis of differences in the genetic risk factors for FTD, particularly non-Mendelian susceptibility factors. It is hoped that reflections on FTD from an international perspective will spur an extension of the vibrant multicenter collaborations, that exist in North America and Europe, toward new centers to be established and supported in the developing regions of the world.
Abstract Introduction A classification framework for posterior cortical atrophy (PCA) is proposed to improve the uniformity of definition of the syndrome in a variety of research settings. Methods ...Consensus statements about PCA were developed through a detailed literature review, the formation of an international multidisciplinary working party which convened on four occasions, and a Web-based quantitative survey regarding symptom frequency and the conceptualization of PCA. Results A three-level classification framework for PCA is described comprising both syndrome- and disease-level descriptions. Classification level 1 (PCA) defines the core clinical, cognitive, and neuroimaging features and exclusion criteria of the clinico-radiological syndrome. Classification level 2 (PCA-pure, PCA-plus) establishes whether, in addition to the core PCA syndrome, the core features of any other neurodegenerative syndromes are present. Classification level 3 (PCA attributable to AD PCA-AD, Lewy body disease PCA-LBD, corticobasal degeneration PCA-CBD, prion disease PCA-prion) provides a more formal determination of the underlying cause of the PCA syndrome, based on available pathophysiological biomarker evidence. The issue of additional syndrome-level descriptors is discussed in relation to the challenges of defining stages of syndrome severity and characterizing phenotypic heterogeneity within the PCA spectrum. Discussion There was strong agreement regarding the definition of the core clinico-radiological syndrome, meaning that the current consensus statement should be regarded as a refinement, development, and extension of previous single-center PCA criteria rather than any wholesale alteration or redescription of the syndrome. The framework and terminology may facilitate the interpretation of research data across studies, be applicable across a broad range of research scenarios (e.g., behavioral interventions, pharmacological trials), and provide a foundation for future collaborative work.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Psychiatric Aspects of Dementia Onyike, Chiadi U
Continuum,
2016-April, 2016-Apr, 2016-04-00, 20160401, Volume:
22, Issue:
2, Dementia
Journal Article
Open access
PURPOSE OF REVIEW:The psychiatric aspects of dementia are increasingly recognized as significant contributors to distress, disability, and care burden, and, thus, are of increasing interest to ...practicing neurologists. This article examines how psychiatric disorders are entwined with dementia and describes the predictive, diagnostic, and therapeutic implications of the psychiatric symptoms of dementia.
RECENT FINDINGS:Psychiatric disorders, particularly depression and schizophrenia, are associated with higher risk for late-life dementia. Psychiatric phenomena also define phenotypes such as frontotemporal dementia and dementia with Lewy bodies, cause distress, and amplify dementia-related disabilities. Management requires a multidisciplinary team, a problem-solving stance, programs of care, and pharmacologic management. Recent innovations include model programs that provide structured problem-solving interventions and tailored in-home care.
SUMMARY:There is new appreciation of the complexity of the relationship between psychiatric disorders and dementia as well as the significance of this relationship for treatment, community services, and research.
Abnormalities of eating behavior, of which there are a variety, are signal features of frontotemporal dementia (FTD), as exemplified by their stipulation in contemporary diagnostic criteria. The ...study by Ahmed et al.1 examines physiologic correlates of eating disorder in behavior-variant FTD (bvFTD) and semantic-variant primary progressive aphasia (svPPA) by analyzing linkages among body mass index (BMI), peptide hormones, and hypothalamic volumes.1 The contrasts with Alzheimer disease (AD) are informative, but more might have been learned from comparisons with counterparts who did not have an eating disorder.
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.
The aims of this study are to describe the chronology of functional disabilities in primary progressive aphasia (PPA), and to examine associations between psychiatric comorbidities and functional ...disabilities.
We conducted a retrospective data analysis using subjects enrolled at Alzheimer's Disease Research Centers between 2005 and 2019. Data were obtained from the National Alzheimer's Coordinating Center database. We included subjects whose primary diagnosis was PPA. Functional status was coded as a binary variable for the following functions: ambulation, transaction skills, verbal communication, meal preparation, and self-care. Behavioral data derived from the Neuropsychiatric Inventory Questionnaire. Descriptive statistics and cox proportional hazard analyses were used to characterize the emergence of disabilities and their association with psychiatric comorbidities.
Data included 91 subjects with a clinical dementia rating scale of zero at baseline. At the initial visit, no individuals had impairments in self-care, while 7% had impairments in transactions, 3% in ambulation, and 2% in meal preparation. Ninety-three percent had language impairments at the onset of the study, and all by visit 4. By visit 5, 41% of patients had impairments in ambulation and in self-care, 49% were impaired in meal preparation and 70% had impairment in transactions. The presence of anxiety, depression, sleep disturbance and psychosis were all significantly associated with an increased risk for multiple functional disabilities.
These findings provide clinicians with guidance for forecasting disabilities and targeting interventions in PPA.
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