3 results
An exploration of cognitive subgroups in Alzheimer’s disease
- JULIE E. DAVIDSON, MICHAEL C. IRIZARRY, BETHANY C. BRAY, SALLY WETTEN, NICHOLAS GALWEY, RACHEL GIBSON, MICHAEL BORRIE, RICHARD DELISLE, HOWARD H. FELDMAN, GING-YUEK HSIUNG, LUIS FORNAZZARI, SERGE GAUTHIER, DANILO GUZMAN, INGE LOY-ENGLISH, RON KEREN, ANDREW KERTESZ, PETER ST. GEORGE-HYSLOP, JOHN WHERRETT, ANDREAS U. MONSCH
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- Journal:
- Journal of the International Neuropsychological Society / Volume 16 / Issue 2 / March 2010
- Published online by Cambridge University Press:
- 04 December 2009, pp. 233-243
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- Article
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Heterogeneity is observed in the patterns of cognition in Alzheimer’s disease (AD). Such heterogeneity might suggest the involvement of different etiological pathways or different host responses to pathology. A total of 627 subjects with mild/moderate AD underwent cognitive assessment with the Mini-Mental State Examination (MMSE) and the Dementia Rating Scale-2 (DRS-2). Latent class analysis (LCA) was performed on cognition subscale data to identify and characterize cognitive subgroups. Clinical, demographic, and genetic factors were explored for association with class membership. LCA suggested the existence of four subgroups; one group with mild and another with severe global impairment across the cognitive domains, one group with primary impairments in attention and construction, and another group with primary deficits in memory and orientation. Education, disease duration, age, Apolipoprotein E-ε4 (APOE ε4) status, gender, presence of grasp reflex, white matter changes, and early or prominent visuospatial impairment were all associated with class membership. Our results support the existence of heterogeneity in patterns of cognitive impairment in AD. Our observation of classes characterized by predominant deficits in attention/construction and memory respectively deserves further exploration as does the association between membership in the attention/construction class and APOE ε4 negative status. (JINS, 2010, 16, 233–243.)
4 - Morphometric methods and dementia
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- By Michael C. Irizarry, Alzheimer Disease Research Unit Massachusetts General Hospital – East, Charlestown, MA, USA
- Edited by Margaret M. Esiri, University of Oxford, Virginia M. -Y. Lee, University of Pennsylvania School of Medicine, John Q. Trojanowski, University of Pennsylvania School of Medicine
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- Book:
- The Neuropathology of Dementia
- Published online:
- 12 October 2009
- Print publication:
- 22 July 2004, pp 75-81
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Summary
Introduction
Classical neuropathology implements gross and microscopic methods to determine diagnosis and neuroanatomical localization of pathology. Diagnostic standards for dementing illnesses have been refined as semi-quantitative grading systems for dementia pathology, allowing rough clinical-pathological correlations. These staging systems include the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) and the Braak and Braak criteria for Alzheimer's disease (AD), and consensus neuropathological criteria for dementia with Lewy bodies (DLB) (Braak & Braak, 1991; Mirra et al., 1991; McKeith et al., 1996). For more detailed quantitative analysis of the neuropathology of dementia, sensitive morphometric methods have been developed. The dominant method in recent years is stereology, which applies a series of rules to overcome biases in counting objects (e.g. neurons) on a slide (Sterio, 1984; Gundersen et al., 1988a,b). Stereological approaches to the assessment of anatomical volumes, neurite length, synapse counts, neuron counts and neuron size have utilized such varied resources as gross brains, MRI scans, light microscopy, confocal microscopy, and electron microscopy (Geinisman et al., 1996; Everall et al., 1999; Peterson, 1999; Roberts et al., 2000). This chapter reviews principles of stereology as applied to anatomical volume measurements and neuron counting at the light microscope level, with a particular emphasis on AD. Other aspects of stereology, such as using the rotator or nucleator for particle volume and cycloid intercepts for surface area, can be found in recent reviews and texts (Gundersen et al., 1988a; Howard & Reed, 1998).
Profile-counting methods
Since it is inefficient to count all the neurons in a particular brain region, methods have been developed to estimate neuron number from a sampling of microscopic fields.
18 - Dementia with Lewy bodies
- from PART II - DISORDERS OF HIGHER FUNCTION
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- By Pamela J. McLean, Department of Neurology, Massachusetts General Hospital East, Charlestown, MA, USA, Estrella Gómez-Tortosa, Department of Neurology, Massachusetts General Hospital East, Charlestown, MA, USA, Michael C. Irizarry, Department of Neurology, Massachusetts General Hospital East, Charlestown, MA, USA, Bradley T. Hyman, Department of Neurology, Massachusetts General Hospital East, Charlestown, MA, USA
- Edited by Arthur K. Asbury, University of Pennsylvania School of Medicine, Guy M. McKhann, The Johns Hopkins University School of Medicine, W. Ian McDonald, University College London, Peter J. Goadsby, University College London, Justin C. McArthur, The Johns Hopkins University School of Medicine
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- Book:
- Diseases of the Nervous System
- Published online:
- 05 August 2016
- Print publication:
- 11 November 2002, pp 267-282
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Summary
History
The concept of the clinical syndrome of ‘dementia with Lewy bodies’ arose within the context of correlations with the pathological descriptions of Lewy body inclusions. These inclusions were first described by F. H. Lewy in 1912 in the dorsal motor nucleus of the vagus and substantia innominata (Lewy, 1912), and Lewy bodies in the substantia nigra were postulated to be specific for Parkinson's disease by Tretiakoff in 1919 (Tretiakoff, 1919). Cortical Lewy bodies were initially described in association with postencephalitic parkinsonism (Lipkin, 1959), in elderly with incidental nigral Lewy bodies (Forno, 1969), in severe dementia (Okazaki et al., 1961), and in institutionalized psychiatric patients (Woodward, 1962). From a clinicopathologic study of 20 cases in 1980, K. Kosaka proposed that the neuroanatomical spectrum of Lewy bodies ranged from isolated substantia nigra inclusions to widespread cortical inclusions; he coined the term ‘diffuse Lewy body disease’ to describe a clinical syndrome of parkinsonism, dementia, and/or psychosis associated pathologically with Lewy bodies in cortical and limbic regions in addition to subcortical nuclei (Kosaka et al., 1980). In more recent nomenclature, the clinicopathological syndrome has been termed ‘Dementia with Lewy bodies’ (DLB).
Epidemiology
DLB has been recognized as the second most common form of degenerative dementia, after Alzheimer's disease, occurring in 15–36% of pathological series of dementia (Hansen et al., 1990; Holmes et al., 1999; Perry et al., 1990), with an estimated prevalence of 10–25% in hospital and community elderly with dementia (Ballard et al., 1995; Shergill et al., 1994). Furthermore, cortical Lewy bodies are found in more than 25% of AD cases (Bergeron & Pollanen, 1989; Ditter & Mirra, 1987; Forno & Langston, 1993). In a review of autopsy-confirmed cases of DLB and AD, the frequency of males was greater in DLB (M:F 1.7 in DLB vs. 0.53 in AD), the average age of onset was similar (70 years old in DLB, 71 years old in AD), with a trend toward more rapidly progressive illness in DLB (duration 6.25 of years in DLB vs. 7.3 of years in AD) (McKeith & O'Brien, 1999).
Clinical features
The clinical features of DLB have been incorporated into consensus criteria for the clinical diagnosis of DLB (Table 18.1) (McKeith et al., 1996).