Cognitive Decline in Prodromal Alzheimer Disease and Mild Cognitive Impairment

Rush Alzheimer's Disease Center, Department of Neurological Science, Rush University Medical Center, 600 S Paulina Ave, Ste 1038, Chicago, IL 60612, USA.
Archives of neurology (Impact Factor: 7.42). 03/2011; 68(3):351-6. DOI: 10.1001/archneurol.2011.31
Source: PubMed


To characterize the course of cognitive decline during the prodromal phase of Alzheimer disease.
Longitudinal cohort study with up to 16 years of observation.
Older persons from 2 studies underwent annual clinical evaluations that included cognitive function testing and clinical classification of mild cognitive impairment, dementia, and Alzheimer disease. At baseline, there were 2071 individuals without dementia and 1511 without cognitive impairment.
During follow-up, 462 persons developed Alzheimer disease (20 with dementia solely due to another condition were excluded). Five to six years before diagnosis, the rate of global cognitive decline accelerated more than 15-fold. The acceleration in cognitive decline occurred slightly earlier for semantic memory (76 months before diagnosis) and working memory (75 months) than other cognitive functions. Mild cognitive impairment was also preceded by years of cognitive decline that began earlier (80 months before diagnosis) and proceeded more rapidly (annual loss of 0.102 unit) in the amnestic than in the nonamnestic (62 months, 0.072 unit) subtype.
Dementia due to Alzheimer disease is preceded by about 5 to 6 years of accelerated decline in multiple cognitive functions. By contrast, little decline is evident in persons who do not develop Alzheimer disease.

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    • "Due to its devastating effect on cognition and high social and economic cost [5] [6], AD has become an important subject of research and, due to its characteristics, is also a challenge. This is especially true since the neurodegenerative process may progress for many years before clear behavioral and cognitive symptoms permit diagnosis [7] [8]. "
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    • "The raw scores from each assessment were standardized according to the sample mean and standard deviation ; the standardized scores were then averaged to create a summary score of learning and memory. This method has been used previously (Wilson et al., 2011). "

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    • "However, even if this is the case, the current data would still support the notion that memory even after very brief delays, on the order of seconds, is impaired in a-MCI with the material-specific anatomic mappings described. 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). "
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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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