The Cortical Signature of Alzheimer's Disease: Regionally Specific Cortical Thinning Relates to Symptom Severity in Very Mild to Mild AD Dementia and is Detectable in Asymptomatic Amyloid-Positive Individuals

Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA.
Cerebral Cortex (Impact Factor: 8.67). 03/2009; 19(3):497-510. DOI: 10.1093/cercor/bhn113
Source: PubMed


Alzheimer's disease (AD) is associated with neurodegeneration in vulnerable limbic and heteromodal regions of the cerebral
cortex, detectable in vivo using magnetic resonance imaging. It is not clear whether abnormalities of cortical anatomy in
AD can be reliably measured across different subject samples, how closely they track symptoms, and whether they are detectable
prior to symptoms. An exploratory map of cortical thinning in mild AD was used to define regions of interest that were applied
in a hypothesis-driven fashion to other subject samples. Results demonstrate a reliably quantifiable in vivo signature of
abnormal cortical anatomy in AD, which parallels known regional vulnerability to AD neuropathology. Thinning in vulnerable
cortical regions relates to symptom severity even in the earliest stages of clinical symptoms. Furthermore, subtle thinning
is present in asymptomatic older controls with brain amyloid binding as detected with amyloid imaging. The reliability and
clinical validity of AD-related cortical thinning suggests potential utility as an imaging biomarker. This “disease signature”
approach to cortical morphometry, in which disease effects are mapped across the cortical mantle and then used to define ROIs
for hypothesis-driven analyses, may provide a powerful methodological framework for studies of neuropsychiatric diseases.

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    • "Every year 4.6 million cases of AD are reported, and it has been suggested that the number of patients will double every 20 years to affect 80 million people by 2040 (Ferri et al. 2005). AD is characterised by premature severe atrophy of the cerebral cortex frontal, temporal, occipital and parietal lobes due to excessive neuronal cell death (Dickerson et al. 2009). In fact a study has confirmed the association between the size of the hippocampus, a subcortical brain structure involved in memory formation, with the severity of dementia (Eckerström et al. 2010). "
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    • "and/or hypometabolic in individuals with AD (Dickerson et al., 2009; Landau et al., 2009; Schroeter and Neumann, 2011; Wirth et al., 2013a). In this opinion paper, we further suggest that they represent the point of convergence of multiple pathologies, as well as brain regions where pathologies might have a synergistic effect. "

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    • "Finally, it is worth noting that short-term and working memory may be more generally affected in prodromal AD (Gagnon and Belleville 2011; Saunders and Summers 2011; Wilson et al. 2011), particularly considering we included multi-domain MCI in the cohort, and that this more general impairment produced the uniform reduced performance observed across conditions. Indeed, fronto-parietal networks more traditionally thought to support this domain (e.g., [Xu and Chun 2006; Majerus 2013]) are regions that do display evidence of atrophy in early stages of disease (Dickerson et al. 2009). That involvement of these cortical regions may have contributed to impairment on the experimental task is, perhaps, supported by the overall poorer performance of md-MCI relative to sd-MCI group, consonant with the evidence of more extensive cortical neurodegeneration in the former (Bell-McGinty et al. 2005; Whitwell et al. 2007). "
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    ABSTRACT: Short-term memory (STM) has generally been thought to be independent of the medial temporal lobe (MTL) in contrast to long-term memory (LTM). Prodromal Alzheimer's disease (AD) is a condition in which the MTL is a major early focus of pathology and LTM is thought disproportionately affected relative to STM. However, recent studies have suggested a role for the MTL in STM, particularly hippocampus, when binding of different elements is required. Other work has suggested involvement of extrahippocampal MTL structures, particularly in STM tasks that involve item-level memory. We examined STM for individual objects, locations, and object-location conjunctions in amnestic mild cognitive impairment (MCI), often associated with prodromal AD. Relative to age-matched, cognitively normal controls, MCI patients not only displayed impairment on object-location conjunctions but were similarly impaired for non-bound objects and locations. Moreover, across all participants, these conditions displayed dissociable correlations of cortical thinning along the long axis of the MTL and associated cortical nodes of anterior and posterior MTL networks. These findings support the role of the MTL in visual STM tasks and the division of labor of MTL in support of different types of memory representations, overlapping with findings in LTM. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail:
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